Article

The "Chemical Imbalance" Explanation for Depression: Origins, Lay Endorsement, and Clinical Implications

Authors:
To read the full-text of this research, you can request a copy directly from the authors.

Abstract

When a client asks whether her or his depression is caused by a chemical imbalance, how do you respond? Depression is regularly depicted in popular media as resulting from a "chemical imbalance" and this depiction raises a number of interesting questions for practicing clinicians. How accurate is the chemical imbalance explanation for depression? How widely do laypersons agree with the explanation, and how do they interpret the explanation? We discuss the origins, accuracy, and transmittal (e.g., via direct-to-consumer advertising) of the chemical imbalance explanation for depression. We next present results from a group case study examining lay endorsement and interpretation of the explanation. Finally, we discuss clinical implications and present a short script for educating clients concerning "chemical imbalances" in depression.

No full-text available

Request Full-text Paper PDF

To read the full-text of this research,
you can request a copy directly from the authors.

... The idea that depression is caused by lowered serotonin or another brain chemical imbalance has become, in the 21st century, what France et al. (2007) described as the 'dominant cultural story of depression aetiology' (France et al., 2007) (P 411). Social scientist, Nikolas Rose has reflected on how this story has changed the way people think about their moods and, by extension, their very concept of themselves. ...
... The idea that depression is caused by lowered serotonin or another brain chemical imbalance has become, in the 21st century, what France et al. (2007) described as the 'dominant cultural story of depression aetiology' (France et al., 2007) (P 411). Social scientist, Nikolas Rose has reflected on how this story has changed the way people think about their moods and, by extension, their very concept of themselves. ...
... Professional organisations, such as the American Psychiatric Association echoed drug company rhetoric, suggesting in a patient leaflet produced in 2005 that 'antidepressants may be prescribed to correct imbalances in the levels of chemicals in the brain' (American Psychiatric Association, 2005). Consequently, a large proportion of the population came to believe that depression is caused by a 'chemical imbalance', with surveys conducted in the 2000s finding that 88% of respondents in Australia and 85% in the US endorsed this idea (France et al., 2007;Pilkington et al., 2013). ...
Article
Full-text available
The theory that depression is caused by a serotonin abnormality of other chemical imbalance has become widely accepted by the public and is one prominent justification for the use of antidepressants. However, it has been increasingly questioned and there is little evidence it has empirical support. In response, leading psychiatrists suggested it was an ‘urban legend’ that was never taken seriously by the psychiatric profession. To interrogate these claims, we examined the coverage of the serotonin theory of depression in a sample of highly cited and influential academic literature from 1990 when the theory started to be popularized to 2010 when these responses were articulated. We analysed 30 highly cited reviews of the aetiology of depression in general, 30 highly cited papers on depression and serotonin specifically and a sample of influential textbooks. The majority of the aetiology reviews supported the hypothesis, including some that were entirely devoted to describing research on the serotonin system, and those that reviewed the aetiology of depression more broadly. Research papers on the serotonin system in depression were highly cited and most of them strongly supported the serotonin theory. All textbooks supported the theory, at least in some sections, and devoted substantial coverage to it, although some also acknowledged it remained provisional. The findings suggest that the serotonin theory was endorsed by the professional and academic community. The theory is compared to an exhausted Kuhnian paradigm with professional equivocation about it acting as a means of defending it against encroaching criticism. The analysis suggests that, despite protestations to the contrary, the profession bears some responsibility for the propagation of a theory that is not empirically supported and the mass antidepressant prescribing it has inspired.
... With advancing psychopharmacology and the demonstrated ability of antidepressants to reduce symptoms associated with depression (Kessler et al., 2003), conceptualization of mental disorders has partially shifted to a more biologically-based representation among medical and public populations. This notion is supported by evidence from France et al. (2007) in which they found that approximately nine in 10 individuals in their sample of American university students had heard the claim that depression results from a chemical imbalance in the brain. Participants also rank ordered what they believed to be the top five probable causes of depression, and the researchers found that chemical imbalance was most (Pilkington et al., 2013). ...
... For example, 88.6% of individuals in France and colleagues' 2007 study indicated that they were exposed to the chemical imbalance explanation through television, which was the most highly endorsed route of exposure, followed by friend/family member or other acquaintances. Direct-to-consumer (DTC) advertising of prescription medications has played a large role in informing individuals of the effectiveness of psychiatric drugs (France et al., 2007). This advertising is not always unbiased, as it is frequently presented by pharmaceutical companies that serve to gain from profiting off of sales of their prescription medications. ...
... This advertising is not always unbiased, as it is frequently presented by pharmaceutical companies that serve to gain from profiting off of sales of their prescription medications. The growing pharmaceutical industry has increased their investment in DTC advertising, with rates skyrocketing from approximately $12 million in 1989 to over $3 billion in 2003 (France et al., 2007). Considering the stakeholders is imperative when contemplating the perspectives of how mental disorders arise and how they should be treated. ...
Article
Full-text available
The world changed overnight with the coronavirus disease (COVID-19) pandemic, which resulted in the implementation of self-isolation, quarantine, and social distancing measures by government bodies to reduce further transmission of the disease and the burden on healthcare professionals. These measures had repercussions on the mental health system, most notably by making traditional in-person therapy inaccessible for many clients. Mental health providers quickly responded by adjusting and adopting online psychotherapy in order to address the demands for services. Clinicians are learning the benefits and costs of this type of service delivery—especially early career clinicians who are in the process of learning how to implement traditional in-person therapy. The current paper describes the experiences of two early career clinicians during the pandemic as they navigated the use of online therapy to serve clients, the unforeseen lessons learned, and recommendations to other clinicians who are practicing online therapy during this unprecedented time.
... It is indisputable that chemical imbalance is a contributing factor. However, single factors cannot give a detailed explanation of MDD without multifactorial interaction (France, Lysaker & Robinson 2007). ...
... The above is a confirmation of previous investigations (e.g., France, Lysaker & Robinson 2007) that a single gene cannot explain the aetiology of depression. Also, it is still catastrophic to isolate the gene as a contributing factor to MDD. ...
... Altogether, it will be disastrous to allege that chemicals in the brain and neurotransmitters have no vital function in the etiology of MDD (France, Lysaker, & Robinson, 2007). According to the monoamine, hypothesis theory, depression is contributed by the deficiency in the monoamine, dopamine, serotonin, and norepinephrine neurotransmitters (Jeon & Kim, 2016). ...
Article
Full-text available
This research work is done in fulfillment of the award of a master’s degree in psychology from the University of Liverpool. The work made some findings through a systematic review of previous investigations and predicted that multilateral factors are contributing factors in depression, and suggested that treatment should include a tripartite method such as pharmacotherapeutic (CBT, pharmacology, and Exercise). However, the outcome of this study is not a conclusive finding and is subject to review, hence further study is warranted.
... It is indisputable that chemical imbalance is a contributing factor. However, single factors cannot give a detailed explanation of MDD without multifactorial interaction (France, Lysaker & Robinson 2007). ...
... The above is a confirmation of previous investigations (e.g., France, Lysaker & Robinson 2007) that a single gene cannot explain the aetiology of depression. Also, it is still catastrophic to isolate the gene as a contributing factor to MDD. ...
... Altogether, it will be disastrous to allege that chemicals in the brain and neurotransmitters have no vital function in the etiology of MDD (France, Lysaker, & Robinson, 2007). According to the monoamine, hypothesis theory, depression is contributed by the deficiency in the monoamine, dopamine, serotonin, and norepinephrine neurotransmitters (Jeon & Kim, 2016). ...
Research
Full-text available
This research work is done in fulfillment of the award of a master’s degree in psychology from the University of Liverpool. The work made some findings through a systematic review of previous investigations and predicted that multilateral factors are contributing factors in depression, and suggested that treatment should include a tripartite method such as pharmacotherapeutic (CBT, pharmacology, and Exercise). However, the outcome of this study is not a conclusive finding and is subject to review, hence further study is warranted.
... The chemical imbalance belief is the most widely endorsed biogenetic explanation of depression. In one study of 262 undergraduate students taking a psychology course (France et al., 2007), nearly all (91.6%) participants were familiar with the chemical imbalance explanation, which was endorsed as a potential cause of depression by 84.7% of participants vs. 61.8% who endorsed the genetics/inherited belief. ...
... Median = 3, range 0-10). France et al., 2007) Participants were asked, "How likely is it that depression might be caused by the following", with four possible causes: "Recent or ongoing stressful experiences", "Difficult childhood experiences", "Chemical imbalance", and "Genetic/inherited problems". Items were rated on a 1 (Very Unlikely) to 6 (Very Likely) Likert Type scale. ...
... This study evaluated the prevalence and correlates of etiological beliefs of depression in a sample of acutely distressed psychiatric patients attending a partial hospital treatment program. Whereas previous studies have evaluated these beliefs in college (France et al., 2007;Kemp et al., 2014), community (Lebowitz et al., 2013), and outpatient (Dunlop et al., 2012;Klein et al., 2017;Tompkins et al., 2016) settings, to our knowledge, no study had evaluated these beliefs and correlates in a partial hospital treatment setting. In line with previous studies, we found that a psychosocial explanation of depression -depression caused by ongoing stressors -was the most commonly endorsed explanation. ...
... It was argued that low levels of serotonin and norepinephrine, monoamines (MOAs) that act as neurotransmitters, bring about depression and increasing these levels diminishes depressive symptoms. France, Lysaker, and Robinson (2007) provide a thorough overview of the foundation and advancement of this explanation. In particular, studies reporting a decrease in depressive symptoms among people taking antidepressant medication have been especially influential, even though clinical trials have yielded mixed findings or no significant effects of antidepressants, and other studies have shown positive responses to non-pharmacological interventions. ...
... In particular, studies reporting a decrease in depressive symptoms among people taking antidepressant medication have been especially influential, even though clinical trials have yielded mixed findings or no significant effects of antidepressants, and other studies have shown positive responses to non-pharmacological interventions. Reports of low levels of MOAs among people experiencing depression have also been persuasive, although they are based on correlational studies, and research on the role of serotonin and norepinephrine deficiencies in the etiology of depression has yielded inconclusive findings (France et al., 2007). More recently, advances in brain science and epigenetics, have affirmed the complex etiology of depression, and the limitations of a narrow biochemical explanation (Insel, 2011). ...
... According to a National Stigma Survey, 80% of the household respondents attributed the cause of depression to "chemical imbalance" (Pescosolido et al., 2010). The majority (86%) of undergraduate student survey respondents at one university indicated depression is likely caused by chemical imbalance (France et al., 2007). Similarly, the majority (75%) of respondents to a national telephone survey endorsed the belief that mental illness is usually caused by a chemical imbalance (APA, 2005). ...
Article
Social workers play an important role in helping clients understand the evidence base on which treatment options and choices are made. This study investigates social workers’ use of a biomedical perspective in their practice with clients who experience depression. A majority of licensed social workers who responded to an on-line survey (N = 77) reported using a chemical imbalance explanation of depression. Among the individual and contextual measures analyzed, only attitudes about antidepressants were significantly associated with use of a biochemical explanation. Implications are presented regarding developing social workers’ critical appraisal skills in support of clients’ right to self-determination.
... Yet there is little evidence that these medications are more efficacious for treating (or preventing relapse for) mood disorders than for several other conditions, such as anxiety-related disorders (e.g., panic disorder, obsessivecompulsive disorder; Donovan et al., 2010) or bulimia nervosa (Tortorella et al., 2014). Hence, their specificity to depression is doubtful, and their name derives more from historical precedence-the initial evidence for their efficacy stemmed from research on depression (France et al., 2007)-than from scientific evidence. Moreover, some authors argue that these medications are considerably less efficacious than commonly claimed, and are beneficial for only severe, but not mild or moderate, depression, rendering the label of "antidepressant" potentially misleading (Antonuccio and Healy, 2012; but see Kramer, 2011, for an alternative view). ...
... (7) Chemical imbalance. Thanks in part to the success of direct-to-consumer marketing campaigns by drug companies, the notion that major depression and allied disorders are caused by a "chemical imbalance" of neurotransmitters, such as serotonin and norepinephrine, has become a virtual truism in the eyes of the public (France et al., 2007;Deacon and Baird, 2009). This phrase even crops up in some academic sources; for example, one author wrote that one overarching framework for conceptualizing mental illness is a "biophysical model that posits a chemical imbalance" (Wheeler, 2011, p. 151). ...
Article
Full-text available
The goal of this article is to promote clear thinking and clear writing among students and teachers of psychological science by curbing terminological misinformation and confusion. To this end, we present a provisional list of 50 commonly used terms in psychology, psychiatry, and allied fields that should be avoided, or at most used sparingly and with explicit caveats. We provide corrective information for students, instructors, and researchers regarding these terms, which we organize for expository purposes into five categories: inaccurate or misleading terms, frequently misused terms, ambiguous terms, oxymorons, and pleonasms. For each term, we (a) explain why it is problematic, (b) delineate one or more examples of its misuse, and (c) when pertinent, offer recommendations for preferable terms. By being more judicious in their use of terminology, psychologists and psychiatrists can foster clearer thinking in their students and the field at large regarding mental phenomena.
... A large proportion of clients has made use of antidepressant medication in the past or is on medication while receiving therapy. These activities are likely to have exposed them to a 'chemical imbalance' explanation of depression that may be difficult to reconcile with therapy (France et al., 2007;Kemp et al., 2014). The sequencing of therapy and medication may follow different pathways. ...
... Można przypuszczać, że reakcja na opublikowany niedawno artykuł związana jest z podstawowym problemem: powszechnym, publicznym przekonaniem o "chemicznej nierównowadze" jako przyczynie depresji, deklarowanym przez ponad 80% ankietowanych w USA lub Australii [13,14,15]. Jeszcze do niedawna nawet na stronach tak szacownych instytucji jak Harvard University, American Psychiatric Association czy National Health Service znaleźć można było informacje o "nierównowadze chemicznej" czy "zbyt niskim poziomie serotoniny". ...
Article
Full-text available
Już sam tytuł artykułu, do którego pozwolono mi się tutaj odnieść (enfant terrible-dosłownie: okropne dziecko, wg słownika PWN: osoba nie-dyskretna, nietaktowna), sugeruje, że mamy do czy-nienia raczej z personalnym atakiem na autorkę niż z dyskusją o meritum. A przecież zgodnie z zasadami etosu naukowego, tak jak go definiuje choćby Merton [1], kluczowe powinno być to, co ktoś mówi, i na ile są to wnioski uprawnione, czyli oparte na poprawnych metodologicznie przesłankach, a nie to, jak z jakiegoś powodu oceniamy nadawcę komunikatu. Podobnych ataków personalnych pojawiło się wiele także w zachodnich mediach (np. [2]). Być może ma to związek z tym, że prof. Moncrieff naruszy-ła pewne tabu-może na to też wskazywać owa "niedyskrecja" za-warta w wyrażeniu enfant terrible. Jednak czy zadaniem nauki jest za-chowywanie dyskrecji i ukrywa-nie prawdy? Wydaje się, że wręcz przeciwnie. W krótkiej replice nie sposób odnieść się do wszystkich wątków podnoszonych przez prof. Rybakowskiego-większość z nich (choć również zasługują na od-powiedź) niewiele ma zresztą wspólnego z systema-tycznym przeglądem metaanaliz wykazujących brak dowodów na związek poziomu serotoniny z depresją, autorstwa Moncrieff i współpracowników, który uka-zał się w jednym z najważniejszych psychiatrycznych czasopism naukowych na świecie. Także co do istoty owych kontrowersji, w ograniczonej przestrzeni, wy-powiedzieć można się tylko bardzo skrótowo.
... Despite the fact that there is no evidence of an imbalance or abnormality of brain chemicals or any other biological abnormality in people with depression (Kennis et al., 2020;Moncrieff et al., 2021), the industry, aided and abetted by professional organisations such as the American Psychiatric Organisation and the UK's Royal College of Psychiatrists (APA, 2018;Royal College of Psychiat, 2009), has succeeded in persuading the general public that unhappiness and discontent arise from a faulty brain. Surveys conducted in the US and Australia in the 2000s, for example, showed that 85 and 88% of respondents respectively endorsed the idea that depression is caused by a chemical imbalance (France et al., 2007;Pilkington et al., 2013). ...
Article
Full-text available
The present paper analyses the functions of the mental health system in relation to the economic organisation of society, using concepts derived from Marx’s work on political economy and building on previous critiques. The analysis starts from the position that mental health problems are not equivalent to physical, medical conditions and are more fruitfully viewed as problems of communities or societies. Using the example of the United Kingdom, it traces how a public mental health system evolved alongside capitalism in order to manage the problems posed by people whose behaviour was too chaotic, disruptive or inefficient to participate in a labour market based on exploitation. The system provided a mixture of care and control, and under recent, Neoliberal regimes, these functions have been increasingly transferred to the private sector and provided in a capitalistic manner. Welfare payments are also part of the system and support those less seriously affected but unable to work productively enough to generate surplus value and profit. The increased intensity and precarity of work under Neoliberalism has driven up benefit claims at the same time as the Neoliberal state is trying to reduce them. These social responses are legitimised by the idea that mental disorders are medical conditions, and this idea also has a hegemonic function by construing the adverse consequences of social and economic structures as individual problems, an approach that has been particularly important during the rise of Neoliberalism. The concept of mental illness has a strategic role in modern societies, therefore, enabling certain contentious social activities by obscuring their political nature, and diverting attention from the failings of the underlying economic system. The analysis suggests the medical view is driven by political imperatives rather than science and reveals the need for a system that is more transparent and democratic. While the mental health system has some consistent functions across all modern societies, this account highlights one of the endemic contradictions of the capitalist system in the way that it marginalises large groups of people by narrowing the opportunities to make an economic contribution to society.
... Acker and Warner (2020) found that 90% of clinical social workers in an online survey (n = 77) use this explanation with their clients. More broadly, survey research demonstrates that many Americans believe that depression is due to a chemical imbalance in the brain (Pescosolido et al., 2010), and psychology students report having heard this explanation from authoritative sources (France, Lysaker, & Robinson, 2007). A more recent study found that from a sample of 39 international medical websites, 74% explained clinical depression as a chemical imbalance (Demasi & Gøtzsche, 2020). ...
Article
Full-text available
Major Depressive Disorder (MDD) is poorly understood and frequently diagnosed in mental health practice. Qualitative thematic analysis from interviews with 20 licensed clinical social workers (LCSWs) was conducted to evaluate clinicians’ perceptions, sources of information, and use of the chemical imbalance theory (CIT) during interactions with clients. Findings revealed that clinicians held nuanced and often critical perceptions of the CIT. When clinicians did incorporate CIT, they did so in highly specific and nuanced ways, often to justify antidepressant treatment. Social workers highlighted a gap in psychopharmacology education and training. Implications for social work education and practice are addressed.
... A large proportion of clients has made use of antidepressant medication in the past or is on medication while receiving therapy. These activities are likely to have exposed them to a 'chemical imbalance' explanation of depression that may be difficult to reconcile with therapy (France et al., 2007;Kemp et al., 2014). The sequencing of therapy and medication may follow different pathways. ...
Article
Full-text available
The adoption of a pluralistic perspective on research design, processes of data collection and analysis and dissemination of findings, has the potential to enable psychotherapy research to make a more effective contribution to building a just society. A review of the key features of the concept of pluralism is followed by a historical analysis of the ways in which research in counselling, psychotherapy and related disciplines has moved in the direction of a pluralistic position around knowledge creation. Core principles of a pluralistic approach to research are identified and explored in the context of a critical case study of contemporary research into psychotherapy for depression, examples of pluralistically oriented research practices, and analysis of a pluralistic conceptualisation of the nature of evidence. Implications of a pluralistic perspective for research training and practice are discussed. Pluralistic inquiry that emphasises dialogue, collaboration, epistemic justice and the co-existence of multiple truths, creates opportunities for individuals, families and communities from a wide range of backgrounds to co-produce knowledge in ways that support their capacities for active citizenship and involvement in open democratic decision-making. To fulfil these possibilities, it is necessary for psychotherapy research to be oriented towards social goals that are sufficiently relevant to both researchers and co-participants to harness their passion and work together for a common good.
... While there do not appear to be studies of doctor-patient communication concerning biological explanations of condition genesis, there is considerable qualitative evidence that such explanations are routinely offered in clinical practice (Cohen and Hughes 2011;Fosgerau and Davidsen 2014;France et al. 2007;Fullagar 2009;Lacasse and Leo 2015;Schreiber and Hartrick 2002). In recent years, as ''chemical imbalance,'' as a causal explanation for mood and other mental disorders has become the subject of controversy, some psychiatrists have insisted that this explanation has never been widely communicated to patients. ...
Article
Full-text available
The biomedical aspiration of psychiatry has fundamentally reoriented clinical practice since the DSM-III in 1980 and reverberated in the public sphere. Over time, lay public understanding of the causes of mental suffering has increasingly endorsed biological conceptions. In this paper, I explore the sources from which a neurobiological model for mental suffering reaches ordinary people, and investigate its rhetorical appeal, personal appropriation, and consequences. Drawing on interviews and other data, I show that these sources—physicians, popular media, and advertising—share common ontological and moral assumptions. These assumptions, in turn, influence how people take up neurobiological explanation to account for their suffering, and how, paradoxically, they join it to their projects of self-determination. I conclude by considering how, from a phenomenological perspective, a neurobiological account fails to enhance self-knowledge or determination but leads to a hermeneutic dead end.
... They were misled. The original catecholamine hypothesis of mood disorders was carefully qualified by its originators in the 1960s, recognized as significantly flawed and inadequate, and significantly modified to reflect more complex biological mechanisms in major mood disorders (Frances et al. 2007;Pies 2019). Besides mischaracterizing the neurochemistry associated with mood disorders, the "chemical imbalance" myth gave false hope to patients about the promise of antidepressant drugs and vastly underplayed the impact of psychological, interpersonal, and social factors and their role in preventing and treating mood disorders. ...
Chapter
This chapter reviews the history of academic psychology and psychiatry, using trauma as a focus. The history of psychology revolves around the question of consciousness, including the method of introspection, addressing the issue, “What is the subject?” The history of modern psychiatry, on the other hand, revolves around the crucial question of the experiential chasm, as Karl Jaspers defined it in his phenomenological psychiatry. Jaspers’ phenomenology is one of the two foundations of modern psychiatry along with Kraepelin’s classification. One hundred years of phenomenology and its relation to psychiatry is outlined through its key contributors in both fields. Much of it was founded on Husserl’s intentional or subjective phenomenology, while Badiou’s objective phenomenology is founded on his ontological theory of the subject and of the event. Finally, the possibility of evental psychiatry based on Badiou’s ontology is introduced.
... They were misled. The original catecholamine hypothesis of mood disorders was carefully qualified by its originators in the 1960s, recognized as significantly flawed and inadequate, and significantly modified to reflect more complex biological mechanisms in major mood disorders (Frances et al. 2007;Pies 2019). Besides mischaracterizing the neurochemistry associated with mood disorders, the "chemical imbalance" myth gave false hope to patients about the promise of antidepressant drugs and vastly underplayed the impact of psychological, interpersonal, and social factors and their role in preventing and treating mood disorders. ...
Chapter
This chapter addresses a great challenge for psychiatry as a medical discipline, namely, its hybrid disciplinary status. On one hand, it belongs to nomothetic and, on the other, explanatory domains of science although it is not properly identified with either of them – thus constituting the so-called explanatory gap. In effect, psychiatric diagnosis is characterized by a relatively high level of reliability and controversial claim to validity. In order to escape from a theoretical grounding, psychiatry has gradually adopted the neo-positivist stance of instrumental classifications. The rationale behind those systems is to operationalize conventions, guidelines, and criteria which combine in various ways a categorical approach with dimensional measures. In conclusion, prospects for the future development of psychiatric classification are discussed.
... They were misled. The original catecholamine hypothesis of mood disorders was carefully qualified by its originators in the 1960s, recognized as significantly flawed and inadequate, and significantly modified to reflect more complex biological mechanisms in major mood disorders (Frances et al. 2007;Pies 2019). Besides mischaracterizing the neurochemistry associated with mood disorders, the "chemical imbalance" myth gave false hope to patients about the promise of antidepressant drugs and vastly underplayed the impact of psychological, interpersonal, and social factors and their role in preventing and treating mood disorders. ...
Chapter
Whereas Protagoras proclaimed that, “Man is the measure of all things,” today’s science has become the all-purpose measure that Stephen Jay Gould (The mismeasure of man. New York: W.W. Norton & Co., 1996) characterized as “the mismeasure of man.” Much social science and biomedical research is marred by scientism and methodolatry. Psychiatry’s critical theoretical gaps are reviewed: (1) the lack of a consensual psychology, (2) the lack of an organizing consensual model of psychiatry, and (3) the lack of a consensual theory of change. To remedy them, three possibilities for a philosophy of psychiatry are outlined: (1) to view psychiatry’s crisis as a “pseudo-problem” (Wittgenstein), to settle for “weak thought” (Vattimo), and (3) to refound psychiatry on ontology or being (Badiou). Being is offered as the proper measure of humanity. Three types of thinkers in psychiatry are identified: systematizers (e.g., Kraepelin), anti-psychiatrists (e.g., Basaglia, Fanon, Lacan, Laing), and methodologists (e.g., the Evidence-Based Medicine group), as well as two psychiatric temperaments: the more “experiential” phenomenological temperament and the more “scientific,” technocratic temperament. The Greek ideal of sophrosyne (a wise, judicious balance) is contrasted to the asymptote (law of diminishing returns) of current paradigms.
... They were misled. The original catecholamine hypothesis of mood disorders was carefully qualified by its originators in the 1960s, recognized as significantly flawed and inadequate, and significantly modified to reflect more complex biological mechanisms in major mood disorders (Frances et al. 2007;Pies 2019). Besides mischaracterizing the neurochemistry associated with mood disorders, the "chemical imbalance" myth gave false hope to patients about the promise of antidepressant drugs and vastly underplayed the impact of psychological, interpersonal, and social factors and their role in preventing and treating mood disorders. ...
Chapter
This chapter inverts the logic of anti-psychiatry to investigate four key critical psychiatrists whose contributions represent “psychiatry against itself.” They are Italian psychiatric reformer Franco Basaglia, Martinican revolutionary psychiatrist Frantz Fanon, French psychoanalytic rebel Jacques Lacan, and Scottish radical psychiatrist R.D. Laing. What is intriguing about the psychiatrists associated with the anti-psychiatry movement and what unites them is negation. Each psychiatrist negated some aspect of contemporary psychiatric practice that made him a rebel, a radical, a reformer, or a revolutionary anti-psychiatrist. Each wielded a tool the author names Badiou’s sickle. Psychiatry and anti-psychiatry are explored using Giorgio Agamben’s philosophical archaeology. The work of two other influential figures is also reviewed: American psychiatrist Thomas Szasz on the myth of mental illness and French psychologist-philosopher Michel Foucault on reordering medical perception and psychiatric thought. A closing Envoi explores why mental health cannot be reduced to games and wordplay or fanciful notions of madness.
... They were misled. The original catecholamine hypothesis of mood disorders was carefully qualified by its originators in the 1960s, recognized as significantly flawed and inadequate, and significantly modified to reflect more complex biological mechanisms in major mood disorders (Frances et al. 2007;Pies 2019). Besides mischaracterizing the neurochemistry associated with mood disorders, the "chemical imbalance" myth gave false hope to patients about the promise of antidepressant drugs and vastly underplayed the impact of psychological, interpersonal, and social factors and their role in preventing and treating mood disorders. ...
Chapter
This chapter offers an overview of the interplay of the mind-brain problem and paradigm formation in psychiatry and the way in which it contributes to controversies and shifts in the dialogue across the disciplines that constitute mental health knowledge. Special attention is paid to implications of Cartesian dualism, eliminative materialism, and reductive physicalism in general, which outline the sometimes incommensurable conceptual frameworks in the history of psychiatry and in contemporary scientific efforts to explain mental disorders.
... In fact, one recent analysis of YouTube videos suggest that popular vloggers also endorse and disseminate biogenetic messages of depression (Devendorf, Bender, & Rottenberg, 2020). A study conducted 13 years ago (France, Lysaker, & Robinson, 2007) found most college students were exposed to the chemical imbalance message through television and other media; a recent survey of college students in 2019 indicates that most students are now exposed to the chemical imbalance theory of depression in the classroom . These data, along with an analysis of popular abnormal psychology textbooks (Hunter, 2013), suggest biogenetic beliefs and messages have become a part of the mainstream culture and accepted as fact enough to be taught to students in formal education settings. ...
Article
Beliefs about the malleability of attributes, also known as mindsets, have been studied for decades in social-personality psychology and education. Here, I review the many applications of mindset theory to clinical psychology and psychotherapy. First, I review social psychological and cognitive neuroscience evidence that mindsets and mindset-related messages are, to a large extent, focused on emotional tolerance. Specifically, the growth mindset, or the belief that attributes are malleable, encourages confronting and tolerating anxiety, frustration, and disappointment in healthy and adaptive ways that promote resilience, whereas the fixed mindset and related messages discourage the experience of these emotions and often leads to helplessness. Second, I review the emerging research on the anxiety mindset and discuss its relevance to clinical work. A model is proposed illustrating connections between mindsets, emotion regulation strategies, treatment preferences, and outcomes. Case examples are used to illustrate practical applications. I conclude that mindsets can inform psychotherapy, research, and public policy.
... They were misled. The original catecholamine hypothesis of mood disorders was carefully qualified by its originators in the 1960s, recognized as significantly flawed and inadequate, and significantly modified to reflect more complex biological mechanisms in major mood disorders (Frances et al. 2007;Pies 2019). Besides mischaracterizing the neurochemistry associated with mood disorders, the "chemical imbalance" myth gave false hope to patients about the promise of antidepressant drugs and vastly underplayed the impact of psychological, interpersonal, and social factors and their role in preventing and treating mood disorders. ...
Book
Psychiatry in Crisis: At the Crossroads of Social Sciences, the Humanities, and Neuroscience Authors: Di Nicola, Vincenzo, Stoyanov, Drozdstoj Offers a critical survey of the history of modern psychiatry Co-authors have dual training in scientific psychiatry and philosophy Written in accessible language with capsule summaries of key areas of theory, research and practice For students and specialists alike Abstract The field of academic psychiatry is in crisis, everywhere. It is not merely a health crisis of resource scarcity or distribution, competing claims and practice models, or level of development from one country to another, but a deeper, more fundamental crisis about the very definition and the theoretical basis of psychiatry. The kinds of questions that represent this crisis include whether psychiatry is a social science (like psychology or anthropology), whether it is better understood as part of the humanities (like philosophy, history, and literature), or if the future of psychiatry is best assured as a branch of medicine (based on genetics and neuroscience)? In fact, the question often debated since the beginning of modern psychiatry concerns the biomedical model so that part of psychiatry’s perpetual self-questioning is to what extent it is or is not a branch of medicine. This unique and bold volume offers a representative and critical survey of the history of modern psychiatry with deeply informed transdisciplinary readings of the literature and practices of the field by two professors of psychiatry who are active in practice and engaged in research and have dual training in scientific psychiatry and philosophy. In alternating chapters presenting contrasting arguments for the future of psychiatry, the two authors conclude with a dialogue between them to flesh out the theoretical, research, and practical implications of psychiatry’s current crisis, outlining areas of divergence, consensus, and fruitful collaborations to revision psychiatry today. The volume is scrupulously documented but written in accessible language with capsule summaries of key areas of theory, research, and practice for the student and practitioner alike in the social and human sciences and in medicine, psychiatry, and the neurosciences. About the Authors Vincenzo Di Nicola, MPhil, MD, PhD, FRCPC, DFAPA is Professor of Psychiatry, University of Montreal, Chief of Child & Adolescent Psychiatry, Montreal University Institute of Mental Health (Canada), and Clinical Professor of Psychiatry at The George Washington University (USA). Di Nicola has advanced training in psychology, psychiatry and philosophy and co-directs a graduate course on psychiatry and the humanities. He was nominated Academician, Bulgarian Academy of Sciences and Arts, and Distinguished Fellow of the American Psychiatric Association. Di Nicola is Founder & President, Canadian Association of Social Psychiatry, and President-Elect, World Association of Social Psychiatry. He has won numerous awards for research and leadership in psychiatry and is the author of A Stranger in the Family: Culture, Families, & Therapy (Norton, 1997) and the award-winning Letters to a Young Therapist (Atropos, 2011). Drozdstoy Stoyanov, MD, PhD, DSc, PgCert, IDFAPA is Professor and Head of the Department of Psychiatry and Leader of the Translational Neuroscience Division in the Research Institute at the Medical University of Plovdiv in Bulgaria. Stoyanov is a Visiting Fellow at the University of Pittsburgh, USA and project partner of the Collaborating Centre for Values-Based Practice in Health & Social Care, St. Catherine’s College, Oxford, UK. Significant activities include being Vice-President, European Society for Person-Centred Healthcare; Vice-Chair of Philosophy SIG, Royal College of Psychiatrists, London, UK; Member, Section of Philosophy and Humanities of World Psychiatric Association; and Member, Standing Committee on Training, Section of Psychiatry, European Union of Medical Specialists. Professor Stoyanov is an International Distinguished Fellow of the American Psychiatric Association. Hardcover ISBN 978-3-030-55139-1 eBook ISBN 978-3-030-55140-7
... Despite the lack of evidence, the "chemical imbalance" model was successfully disseminated by the pharmaceutical industry via direct-to-consumer advertising (Lacasse & Leo, 2005, infiltrating popular consciousness in the United States and influencing the culture of helpseeking and diagnosis (Angell, 2009;France, Lysaker, & Robinson, 2007 Similar increases in antidepressant and other treatments occurred in Canada, England, and the United States. There were also substantial increases in the use of psychological therapies. ...
Article
Full-text available
The germ theory of disease and the attendant public health initiatives, including sanitation, vaccination, and antibiotic treatment, led to dramatic increases in global life expectancy. As the prevalence of infectious disease declines, mental disorders are emerging as major contributors to the global burden of disease. Scientists understand little about the etiology of mental disorders, however, and many of the most popular psychopharmacological treatments, such as antidepressants and antipsychotics, have only moderate‐to‐weak efficacy in treating symptoms and fail to target biological systems that correspond to discrete psychiatric syndromes. Consequently, despite dramatic increases in the treatment of some mental disorders, there has been no decrease in the prevalence of most mental disorders since accurate record keeping began. Many researchers and theorists are therefore endeavoring to rethink psychiatry from the ground‐up. Anthropology, especially biological anthropology, can offer critical theoretical and empirical insights to combat mental illness globally. Biological anthropologists are unique in that we take a panhuman approach to human health and behavior and are trained to address each of Tinbergen's four levels of analysis as well as culture. The field is thus exceptionally well‐situated to help resolve the mysteries of mental illness by integrating biological, evolutionary, and sociocultural perspectives.
... This idea is present in the "hedonic treadmill" notion, which explains why in the long term, lottery winners are not any happier than paraplegic accident victims (Brickman and Campbell 1971;Brickman et al. 1978). Seligman invokes the idea in proposing a theory of happiness in which effortful practices can only marginally raise this natural level (Seligman 2004(Seligman , 2012. 1 The "chemical imbalance" paradigm of mood disorders such as depression, widely influential in lay understandings of mental illness, also implies the existence of such a natural homeostatic mechanism (France et al. 2007). Based on these disparate examples, we hypothesized that people would approve of mood enhancement to the extent that it is perceived to bring someone's happiness toward a "natural" set point. ...
Article
Full-text available
We investigate implicit principles that inform folk moral judgments about mood enhancement. We presented a series of vignettes involving mood enhancement to lay participants via Amazon’s Mechanical Turk platform. We hypothesized that in making intuitive moral determinations about the appropriateness of enhancement, participants would rely primarily on set points (specifically, how far away from “normal” a character’s mood is prior to or after intervention). Contrary to our hypotheses, set point was not strongly predictive of enhancement judgments. Instead, participants’ perception of the mood enhancement’s effect on the long-term well-being of the character in the vignette was robustly correlated with participants’ approval ratings for the enhancement. Long-term well-being predicted enhancement judgments even after controlling for perceived medical necessity (whether the character is perceived to have a medical need for mood improvement), indicating that long-term well-being does not simply serve as a proxy for medical judgments being applied to enhancement. This work highlights the centrality of well-being in folk judgments about enhancement and generates new considerations for adjudicating among competing views in the enhancement debate.
... Along with genetic polymorphism examinations, some researchers have sought to identify neurotransmitter involvement in psychopathy (Glenn & Raine, 2008;Wu & Barnes, 2013). This focus is not dissimilar to the interest in neurotransmitter activity underlying other mental disorders, based on the neurochemical imbalance hypothesis, which suggests that an imbalance in the brain chemistry of affected individuals leads to a variety of mental health problems (Deacon, 2013;France, Lysaker, & Robinson, 2007). ...
Article
Full-text available
Across a significant body of research, psychopathy has often been conceptualized as a biologically based malady. In this research, genetic and neurobiological differences have been conceptualized to underlie psychopathy, while affected individuals' life experiences only influence expressed psychopathic features and their severity. Psychopathy research has largely ignored developmental evidence demonstrating significant influences of environment on both biological and behavioral processes, resulting in several prominent criticisms (Edens & Vincent, 2008; Loeber, Byrd, & Farrington, 2015). The current review was conducted with two main aims: (a) to collect and consider etiological evidence from the extant body of research on genetic and neurobiological factors in psychopathy; and (b) to evaluate findings from genetic, neuro-transmitter, brain structure, and brain function studies in the context of relevant evidence from developmental research. Examples from research on adversity and traumatic stress, a common correlate of psychopathy, were used to highlight current research gaps and future directions to aid in the integration of developmental and neurobiological research agendas. While some promising evidence exists regarding possible underlying neurobiological processes of psycho-pathic traits, this evidence is insufficient to suggest a largely biological etiology for the disorder. Further, information from developmental and epigenetic research may suggest complex, multi-dimensional trajectories for individuals experiencing psychopathy. Based on these observations , the authors make several recommendations for future research, as well as for current clinical application and practice.
... Instead, this pattern of findings may be suggestive of differing cultural beliefs about psychosocial as opposed to biological explanations of behavior. Americans are likely more exposed to pharmaceutical marketing about mental illness, which has been considered to be controversial on several grounds, especially given that 'chemical imbalance' theories promoted by the industry have been judged to be scientifically inaccurate (e.g., France, Lysaker, & Robinson, 2007;LaCasse & Leo, 2015). ...
Article
Background: Cross-cultural studies find that culture shapes people's understanding of mental illnesses, particularly Depression and Schizophrenia. Aims: To compare individuals' beliefs and attitudes toward Depression and Schizophrenia in Russia and the United States. Method: Participants ( N=607) were presented with vignettes of two diagnostically unlabeled psychiatric case histories and then answered questions regarding mental health literacy (MHL) and attitudes toward the person and the illness. Results: Our findings indicate that Depression was most often attributed to psychosocial stress while Schizophrenia was thought to be caused by biological factors. People from both countries considered those suffering from Schizophrenia to be unpredictable and dangerous. US participants were more likely to endorse lay and professional help for both disorders than their Russian counterparts. Russian participants reported being less likely to turn to someone they trust and more likely to deal with problems on their own. Russian participants were also more likely to view those with Depression as 'weak-willed' and leading an 'immoral lifestyle'. Conclusion: Our findings further inform cultural understandings of these mental illnesses in an often neglected national group. Patterns suggest that both groups may benefit from exposure to corrective information about Depression and Schizophrenia.
... The authors revisit mental illness in this regard to observe that advertisements and disease awareness campaigns have disseminated the idea that mental disorders can be attributed to fixed biological properties within individuals, and that such disorders represent deviations from "normal" biological functioning [26,27]. Although such notions were initially applied only to severe mental illnesses, the application has been expanded in recent years. ...
... Depressive disorders are often conceptualized with reference to their presumed etiology [1], for example in the past as a "chemical imbalance" [2] or more recently as a disorder of brain circuits [3]. The expectation that an unknown neurobiological defect underpins depression is an influential one that guides both clinicians and researchers. ...
Article
Full-text available
Background Depression often occurs in association with stressful events. However, people with depressive disorders may experience episodes in response to minor stressors or “out of the blue.” Similar episodes can occur in people who do not have a disorder in response to severe events. This plurality of symptom patterns, occurring as it does in the absence of precise demarcation from normality has led to controversy over how depressive disorders should be defined, how common they are, and when treatment should be offered. Much of the controversy, however, may be illusory, arising from a tendency to view depressive disorders as defects or disease processes (the “clincian’s illusion”). Avoiding the illusion involves understanding depression as a defense rather than a defect and requires consideration of aspects of signal detection theory and the associated “smoke detector” principle. This perspective may help to understand aspects of depressive disorders that are otherwise puzzling and controversial. Methods In this paper, implications of signal detection theory and the “smoke detector principle” are explored: (1) conceptually, (2) using calculations performed in a spreadsheet and (3) using an agent-based model. Depressive episodes are conceptualized or represented as all-or-nothing phenomena activated in response to stressful life events. These events occur in an environment that also includes variable levels of baseline stress, creating a signal detection problem. The agent-based framework allows interaction with the environment as agents attempt to achieve an ideal level of adaptation. Results The smoke detector principle, if valid, may explain otherwise puzzling and controversial features of the depressive disorders, such as their lack of precise demarcation from normality, the role of life events and stressors and their patterns of prevalence. Conclusions Signal detection concepts help to avoid the “clinician’s illusion” in which aspects of functioning of the body’s defenses are mistaken for a disease entity or defect. These principles emphasize inevitable difficulties that are encountered in attempts to conceptualize depressive disorders without reference to the environment in which they occur, and without addressing possible stochastic (randomly varying) elements. Because of the “clinicians illusion”, current research priorities, as well as diagnosis and treatment strategies, may be flawed. Electronic supplementary material The online version of this article (10.1186/s12888-018-1969-3) contains supplementary material, which is available to authorized users.
... Scholars have rarely considered how the interpersonal relationship between helper and help recipient affects emotional and behavioral responses. The dominant research paradigm involves using hypothetical persons who do not have a relationship with the potential helper (e.g., Corrigan et al., 2003;France, Lysaker, & Robinson, 2007;Obonsawin, Lindsay, & Hunter, 2013). However, the current findings suggest that relationship type may differentially influence responses to people in need of assistance. ...
Article
Individuals with depression encounter stigmatization from others. Accordingly, there have been numerous calls for theory-based approaches to reduce stigma. Attribution theory is a useful framework for antistigma efforts because it provides insight into emotional and behavioral responses toward those in need of assistance. In service of improving antistigma efforts, the purpose of the current studies was to investigate the effects of perceived controllability and perceived stability of depression on responses to individuals with the illness. Moreover, as the impact of depression—particularly perceived stability—is likely to have greater implications for a loved one than an acquaintance, the current studies tested the moderating effect of interpersonal relationship on the attribution-emotion-helping sequence. Moderated mediation analyses were conducted to test whether the indirect effect of attributions (i.e., perceived controllability and perceived stability) on behavioral intentions (i.e., willingness to provide social support [WPSS]; desire for social distance [DSD]) through affect (i.e., sympathy, anger) was moderated by interpersonal relationship (i.e., close other, acquaintance). Findings revealed that regardless of interpersonal relationship, perceiving depression as controllable elicited more anger and less sympathy, which in turn reduced WPSS and increased DSD. Further, results indicated that among close others, perceived stability led to less sympathy, more anger, and consequently, less WPSS and greater DSD. For acquaintances, however, perceived stability was not associated with differences in emotional responses. These results indicate that relational aspects of help provision are important to consider and that perceived stability may have untoward effects among loved ones of individuals with depression.
... Depression can, in turn, lead to more stress and dysfunction and worsen the affected person's life situation and depression itself [10]. Depression is an interplay of imbalance between various chemicals like Stress hormones, Cytokines, Monoamines, Altered Glutamatergic and Gabaergic Neurotransmission ,Circadian Rhythm etc [11,12]. There is clinical and etiological heterogeneity of major depressive disorder, so it is difficult to elucidate its pathophysiology. ...
... However, the arguments and data supporting the monoamine hypothesis are problematic (Deacon, 2013;Delgado, 2000;France, Lysaker, & Robinson, 2007). Firstly, the response to antidepressants is not in itself a strong proof that a deficit in monoamine neurotransmitters is the cause of depression. ...
Article
Full-text available
This paper and its second part (Sanz & García-Vera, 2017) analyze the veracity of ten ideas about depression and its treatment that are defended in media widely available on the Internet or in some prestigious clinical practice guidelines or manuals of psychopathology or psychiatry. These ideas hinder patients’ access to appropriate treatment for their depression and favor the medicalization of this treatment over the use of psychotherapy. In this first paper, four ideas about the nature of depression are contrasted with the results of the scientific literature. A review of this literature indicates that, contrary to these ideas: a) depression is considered a mental disorder, not a mental illness; b) the existence of a biological cause is simply a hypothesis, not a reality proven empirically in an unequivocal manner; c) negative life events increase the risk of depression whereas extraversion and optimism diminish it, and d) there are small but not insignificant rates of malingered depression in both legal-forensic and ordinary clinical settings. The results of this review are discussed in the context of the reliability of the health information on the Internet.
... Depression can, in turn, lead to more stress and dysfunction and worsen the affected person's life situation and depression itself [10]. Depression is an interplay of imbalance between various chemicals like Stress hormones, Cytokines, Monoamines, Altered Glutamatergic and Gabaergic Neurotransmission ,Circadian Rhythm etc [11,12]. There is clinical and etiological heterogeneity of major depressive disorder, so it is difficult to elucidate its pathophysiology. ...
... The result is that the chemical imbalance explanation for depression is widely endorsed and yet scientifically distorted. For example, in a survey of undergraduate students, 24% erroneously believed that doctors can directly measure amounts of different brain chemicals to diagnose depression, and 35% believed that doctors treat depression by adding or subtracting brain chemicals to find the right balance (France, Lysaker, & Robinson, 2007). ...
Article
Full-text available
As knowledge of the neurobiological basis of psychopathology has advanced, public perceptions have shifted toward conceptualizing mental disorders as disorders of biology. However, little is known about how patients respond to biological information about their own disorders. We refer to such information as auto-biological—describing our own biological systems as a component of our identity. Drawing on research from attribution theory, we explore the potential for auto-biological information to shape how patients view themselves in relation to their disorders. We propose an attributional framework for presenting auto-biological information in a way that encourages agency, rather than destiny. We argue that this framework has the potential to change expectations and improve outcomes in the treatment of psychiatric disorders. © 2017 American Psychological Association. Published by Wiley Periodicals, Inc., on behalf of the American Psychological Association
... The cumulative, repeated episodes of depression may also contribute to developing some sort of inflammatory process in the body [4]. Depression is regarded as a multifactorial disorder with many causes [5]. Genetic, neurological, hormonal, immunological, and neuroendocrinological disorders have 2 BioMed Research International all been implicated as important depression mechanisms. ...
Article
Full-text available
The aim of this study was to determine if altered levels of selected trace elements manifest themselves during chronic depression. To identify elements strongly associated with chronic depression, relationships between the elemental contents of hair and nails and the interelement correlations were checked. Inductively coupled plasma mass spectrometry and ion chromatography were used to evaluate the contents of Zn, Cu, Co, Pb, Mn, and Fe in hair and nail samples from a total of 415 subjects (295 patients and 120 healthy volunteers). The study included logistic regression models to predict the probability of chronic depression. To investigate possible intercorrelations among the studied elements, the scaled principal component analysis was used. The research has revealed differences in TE levels in the group of depressed men and women in comparison to the healthy subjects. Statistically significant differences in both hair and nails contents of several elements were observed. Our study also provides strong evidence that the intermediary metabolism of certain elements is age- and gender-dependent. Zn, Mn, Pb, and Fe contents in hair/nails seem to be strongly associated with chronic depression. We found no statistically significant residence-related differences in the contents of studied elements in nonoccupationally exposed patients and healthy subjects.
... Some of the earliest support for this hypothesis comes from the 1950s and 1960s, when the antihypertensive drug reserpine was found to have serotonin-depleting properties and also to induce depressive symptoms, whereas the tuberculosis treatment iproniazid was found to enhance monoamine levels and possess antidepressant properties. Crucially, iproniazid was found to block the effects of reserpine (France et al., 2007;López-Muñoz and Alamo, 2009). Serotonin, in particular, has been the most extensively studied neurotransmitter linked to depression (Coppen, 1967;Bondy, 2002). ...
... 19 For example, studies show that patients who believe that their depression is wholly caused by a biochemical imbalance and who do not embrace a bio-psycho-social model of depression are more likely to regard themselves as essentially depressives. 20 Such patients are more likely to expect a worse prognosis and to consider lifestyle changes and other interventions as irrelevant to the treatment of depression. What is currently perceived to be trivial may, in fact, have fundamental repercussions for patient health behaviour and outcome. ...
Article
Full-text available
The doctor-patient relationship is built on an implicit covenant of trust, yet it was not until the post-World War Two era that respect for patient autonomy emerged as an article of mainstream medical ethics. Unlike their medical forebears, physicians today are expected to furnish patients with adequate information about diagnoses, prognoses and treatments. Against these dicta there has been ongoing debate over whether placebos pose a threat to patient autonomy. A key premise underlying medical ethics discussion is the notion that the placebo effect necessitates patient deception. Indeed, the American Medical Association guidelines imply that placebo treatment necessary entails a form of deception. As a consequence of this assumption, the fulcrum of debate on the use of placebo treatment has hinged on whether that deception is ever justified. Recently performed experiments with open-label transparently prescribed placebos have begun to challenge the notion that deception is necessary in eliciting the placebo effect and such effects necessarily involve a binary distinction between autonomy and beneficence. In this article we focus on the content of disclosures in distinctive open-label, transparently disclosed placebo studies and inquire whether they might be said to invoke deception in clinical contexts, and if so, whether the deception is unethical. We find that open placebos may be said to involve equivocation over how placebos work. However, drawing on surveys of patient attitudes we suggest that this equivocation appears to be acceptable to patients. We conclude that open placebos fulfil current American Medical Association guidelines for placebo use, and propose future research directions for harnessing the placebo effect ethically.
... While we don't know exactly how many clinicians have told their patients they were suffering from a chemical imbalance over the last 25 years, we believe that the number is significant and consequential. Among 237 psychology students , Frances, Lysaker, and Robinson (2007) found that 46% had heard the chemical imbalance explanation from a physician. Empirical studies report use of the chemical imbalance theory by prescribers , including psychiatrists (e.g., Cohen & Hughes, 2011; Schreiber & Hartrick, 2002; see also Acker, 2013). ...
... Under this model, terms like "antidepressant" and "antipsychotic" e which are in common use e are considered accurate and appropriate, and any overlap in their effects is ascribed to a possible "neurobiological overlap" between the conditions in which these drugs work. In a modified form, this model has gained some popularity with the public, and it has had a significant influence on the principles and practice of psychiatry [39,40]. However, it fails to explain the three phenomena described in the previous section e the variability of response, the non-specificity of certain psychotropics for particular disorders, and behavioural toxicity. ...
Article
Full-text available
Psychotropic medications are widely used to treat a variety of mental disorders, but a unifying explanation of their modes of action remains obscure.
Article
Etiological beliefs of depression have differing impacts on motivation, hope, and treatment expectations. However, it is unclear where people are exposed to these beliefs. Objective: This study examined beliefs about depression and their relations to symptoms, attitudes about depression, and treatment preferences. Participants: 426 undergraduates attending a large midwestern university. Methods: Participants completed an online survey asking about causes of depression, if and where they had heard about the "chemical imbalance" explanation of depression, attitudes about depression, as well as measures of their symptoms, treatment history, and hypothetical treatment preferences. Results: Sixty-two percent of the sample had hard of the chemical imbalance explanation, most commonly from the classroom. Biochemical beliefs about depression were most strongly endorsed among participants with a family history of depression and who had had personal experience with treatment. The chemical imbalance belief was uniquely related to dysfunctional beliefs about depression. Etiological beliefs were largely unrelated to treatment preferences. Conclusion: College students are exposed to models of mental health that may not be ideal for treatment and recovery.
Article
Full-text available
Depression is a psychosomatic disorder. The pharmacological treatment of depression has been based on the pathophysiology of deficiency in monoamines, mainly serotonin and noradrenaline. All approved antidepressants designed to enhance central monoaminergic tone possess many limitations such as 2 to 5 weeks delay in response, a limited clinical efficacy, and severe side effects. Since the pathophysiological aberrations associated to depression go beyond monoamines, the development of better antidepressants would depend on the identification and understanding of new cellular targets. The pharmacological studies of antidepressants, however, indicate the involvement of the blockade of neuronal uptake systems for norepinephrine and serotonin (5-hydroxytryptamine) including receptors for neurotransmitters. Many preclinical studies have suggested that hippocampus containing abundant agonists such as5-HT1A and 5-HT4 receptor subtypes in the dentate gyrus (DG) is critically involved in the mechanism of action of antidepressants. DG being a part of hippocampus possibly contributes to the brain functions such as formation of new sporadic memories. It is reported that antidepressants cause significant alterations in the structure and function of different brain regions in order to finally lead to their therapeutic effects. This review presents an overview of structural changes in the brain during depression; different neurobiological theories and novel drug development; strategy of augmentation with combinatorial therapy; receptors and targets of actions of antidepressants; and involvement of key signaling factors in the regulation of depression, pharmacology, metabolism, and the underlying principles involved in displaying how the application of antidepressants modulates the structure and function of the brain.
Article
Depression is a psychosomatic disorder. The pharmacological treatment of depression has been based on the pathophysiology of deficiency in monoamines, mainly serotonin and noradrenaline. All approved antidepressants designed to enhance central monoaminergic tone possess many limitations such as 2 to 5 weeks delay in response, a limited clinical efficacy, and severe side effects. Since the pathophysiological aberrations associated to depression go beyond monoamines, the development of better antidepressants would depend on the identification and understanding of new cellular targets. The pharmacological studies of antidepressants, however, indicate the involvement of the blockade of neuronal uptake systems for norepinephrine and serotonin (5-hydroxytryptamine) including receptors for neurotransmitters. Many preclinical studies have suggested that hippocampus containing abundant agonists such as5-HT1A and 5-HT4 receptor subtypes in the dentate gyrus (DG) is critically involved in the mechanism of action of antidepressants. DG being a part of hippocampus possibly contributes to the brain functions such as formation of new sporadic memories. It is reported that antidepressants cause significant alterations in the structure and function of different brain regions in order to finally lead to their therapeutic effects. This review presents an overview of structural changes in the brain during depression; different neurobiological theories and novel drug development; strategy of augmentation with combinatorial therapy; receptors and targets of actions of antidepressants; and involvement of key signaling factors in the regulation of depression, pharmacology, metabolism, and the underlying principles involved in displaying how the application of antidepressants modulates the structure and function of the brain.
Chapter
Psychology and psychiatry have generated multiple models with competing claims. Changes that are part of knowledge accumulation come under different names – paradigms, theories, and revolutions. Medical and social sciences are replete with binary oppositions and false dichotomies which distract real progress. A framework is outlined for breaking down different psychiatric theories and practices into “fast” and “slow psychiatry.” Another way to map these differences is to examine centrifugal (dispersion) versus centripetal (integration) impacts of psychiatric theories and practices. What eludes all such dichotomies is complexity. Contemporary culture finds subjectivity and complexity unwieldy leading to reductionism. Three examples of reductionism in medicine and psychiatry are discussed: (1) depression and the “chemical imbalance” myth, (2) schizophrenias and their reductions, and (3) “anorexia multiforme” as a cultural chameleon. These problems have led to the “bracket creep” of ever-expanding diagnostic criteria of DSM-5 contrasted to the slim promises of neuroscience-based criteria. Attempts to apply neuroscience to aesthetics and the arts reveal its limitations compared to the humanities and social science and richer narrative models in psychotherapy and psychiatry.
Thesis
Full-text available
This project proceeds from a narrow question: What, if anything, is a brain wave? Beguiling in its simplicity, this question prompts a cultural-historical investigation that spans over 150 years of science, technology, and society. Proposed in 1869, the original theory of brain waves cites etheric undulations to explain reports of apparent thought transference. Though most modern thinkers no longer believe in outright telepathy, I argue that dreams of thought transmission and other mental miracles subtly persist—not in obscure and occult circles, but at the forefront of technoscience. A hybrid of science and fiction, brain waves represent an ideal subject through which to explore the ways in which technical language shrouds spiritual dreams. Today, the phrase “brain waves” often function as shorthand for electrical changes in the brain, particularly in the context of technologies that purport to “read” some aspect of mental function, or to transmit neural data to a digital device. While such technologies appear uniquely modern, the history of brain waves reveals that they are merely the millennial incarnation of a much older hope—a hope for transmission and transcendence via the brain’s emanations.
Article
Full-text available
Este trabajo y su segunda parte (Sanz y García-Vera, 2017) analizan la veracidad de diez ideas sobre la depresión y su tratamiento que se defienden en medios de comunicación de amplia difusión en Internet o en algunas guías de práctica clínica y manuales de psicopatología o psiquiatría de prestigio. Estas ideas obstaculizan que los pacientes accedan a un tratamiento adecuado para su depresión y favorecen la medicalización del mismo en perjuicio de los tratamientos psicológicos. En este primer trabajo se contrastan cuatro ideas sobre la naturaleza de la depresión con los resultados de la literatura científica. Una revisión de esta literatura indica que, contrariamente a esas ideas: a) la depresión es considerada actualmente un trastorno mental, no una enfermedad mental; b) la existencia de una causa biológica es simplemente una hipótesis más, no una realidad constatada empíricamente de manera inequívoca; c) los acontecimientos vitales negativos aumentan el riesgo de depresión mientras que la extraversión y el optimismo lo disminuyen, y d) existen tasas de simulación de depresión pequeñas, pero nada despreciables, en contextos clínicos tanto ordinarios como legales o forenses. Los resultados se discuten en el contexto de la fiabilidad de la información sobre la salud en Internet.
Research
Full-text available
There is widespread agreement that neurobiology plays a role in psychological distress and that psychiatric diagnosis and associated psychopharmacological interventions can be helpful. However, there are also unresolved issues surrounding the limits of empirical support for current diagnostic criteria, shortcomings in neurobiological explanations of psychopathology, and unanswered questions about the mechanism, safety, and efficacy of psychiatric medications. This has implications for treatment errors which can precipitate negative socio-economic and health consequences, particularly for vulnerable groups like the Consumer/Survivor/Ex-Patient (c/s/x) population. It is for these reasons that the training psychologists receive to prescribe should, in addition to integrating the critiques of conventional thinking about the etiology and diagnosis of mental distress, discuss the c/s/x movement. Extent research on psychologist postdoctoral psychopharmacology training has focused on legitimacy, safety, feasibility, and training considerations. This study used content analysis and was the first to examine a selection of psychologist postdoctoral psychopharmacology training materials to understand the extent to which they were (a) integrating critiques of neurobiological hypotheses for depression’s etiology, (b) challenging the rigor of the Diagnostic and Statistical Manual of Mental Disorders (DSM) and, (c) informing students about the consumer/survivor/ex-patient movement. Results indicated that the examined body of materials did not consistently and comprehensively critique the majority of neurobiologically based etiological hypotheses for depression that were being disseminated. Next, challenges to the DSM’s empirical rigor within the examined materials primarily focused on construct validity versus inter-rater reliability, and without the provision of statistical analyses. Finally, the only substantial c/s/x content within the examined materials was limited to one book which students were not required to read. The limits of these findings and a variety of socio-cultural, ethical, legal, and professional advocacy considerations are discussed.
Chapter
In this chapter, we examine whether effort-reward imbalance (ERI) at work may contribute to the development of affective disorders. Affective disorders describe affective excesses, encompassing both elated and depressed affect. Excessive elated affect pertains to mania and bipolar disorders, excessive depressed affect without history of elated affect pertains to depressive disorders. Here, we mainly focus on depressive disorders. The reasons are, first, that depressive disorders are of particular public health relevance as they are regarded as one of the most important contributors to the loss of healthy life years in the world. Second, whereas ERI has been discussed as a potential risk factor for depressive disorders, we are not aware of discussions relating ERI to elevated mood and disorders in the manic or bipolar spectrum
Article
This paper analyzes how major U.S. print and broadcast news media framed depression causal and problem-solving responsibilities at individual and societal levels over the past three decades. Results from the content analysis showed that the media placed more causal and problem-solving responsibilities on individuals than the society. However, references to societal solutions increased moderately over time. Organizational differences emerged in news attribution of responsibilities, as print media presented more individual-level causes while broadcast media focused more on solutions at both individual and societal levels. Additionally, local newspapers put more problem-solving responsibilities on individuals than national newspapers, while a cable news channel allocated more time to the discussion of overall depression responsibilities than network TV. Findings are discussed in the context of cultural orientations, organizational constraints, changing practice and trends in health news reporting, and the broader political/social environment in which the news media operate. Practical implications for health journalism, mental health communication and advocacy, and public health policy-making are discussed.
Book
The individual has never been more important in society in almost every sphere of public and private life, the individual is sovereign. Yet the importance and apparent power assigned to the individual is not all that it seems. As ‘Responsible Citizens’ investigates via its UK-based case studies, this emphasis on the individual has gone hand in hand with a rise in subtle authoritarianism, which has insinuated itself into the government of the population. Whilst present throughout the public services, this authoritarianism is most conspicuous in the health and social welfare sectors, such that a kind of ‘governance through responsibility’ is today enforced upon the population.
Article
Neuroessentialism is the view that the definitive way of explaining human psychological experience is by reference to the brain and its activity. This leads to the view that psychological disorders, such as depression, are fundamentally brain disorders. Neuroessentialism has grown increasingly popular for academic and public audiences. It has also attracted critics. This article describes neuroessentialism, the reasons for its rising prominence, and the theoretical and clinical concerns it raises. It connects these concerns to evidence from empirical studies that suggest that neuroessentialistic conceptualization of depression can have negative clinical impacts that need to be considered by mental health professionals.
Article
To evaluate the existing data on aromatherapy interventions for improvement of sleep quality. Systematic literature review and meta-analysis on the effects of aromatherapy. Study Sources: Electronic databases, including the Korea Education and Research Information Service (KERIS), Korean studies Information Service System (KISS), National Assembly Library, and eight academies within the Korean Society of Nursing Science, were searched to identify studies published between 2000 and August 2013. Randomized controlled and quasi-experimental trials that included aromatherapy for the improvement of sleep quality. Of the 245 publications identified, 13 studies met the inclusion and exclusion criteria, and 12 studies were used in the meta-analysis. Meta-analysis of the 12 studies using a random-effects model revealed that the use of aromatherapy was effective in improving sleep quality (95% confidence interval [CI], 0.540-1.745; Z=3.716). Subgroup analysis revealed that inhalation aromatherapy (95% CI, 0.792-1.541; Z=6.107) was more effective than massage therapy (95% CI, 0.128-2.166; Z=2.205) in unhealthy (95% CI, 0.248-1.100; Z=3.100) and healthy (95% CI, 0.393-5.104; Z=2.287) participants, respectively. Readily available aromatherapy treatments appear to be effective and promote sleep. Thus, it is essential to develop specific guidelines for the efficient use of aromatherapy.
Article
Full-text available
This paper reports a study on university students' attributions for the causes of and cures for depression conducted in a Turkish sample. Results revealed six components for causes, which were trauma, job-related problems, loss, disposition, intimacy, and isolation. Seven components were found for cures, which were hobby, sensation seeking, avoidance, professional help, religious practices, esteem, and spiritual activities. Men rated religious practices as more useful than women did. No other differences pertaining to gender or previous contact were found. Results are discussed together with the limitations of the study.
Article
Full-text available
We present a revision of the 1978 reformulated theory of helplessness and depression and call it the hopelessness theory of depression. Although the 1978 reformulation has generated a vast amount of empirical work on depression over the past 10 years and recently has been evaluated as a model of depression, we do not think that it presents a clearly articulated theory of depression. We build on the skeletal logic of the 1978 statement and (a) propose a hypothesized subtype of depression— hopelessness depression, (b) introduce hopelessness as a proximal sufficient cause of the symptoms of hopelessness depression, (c) deemphasize causal attributions because inferred negative consequences and inferred negative characteristics about the self are also postulated to contribute to the formation of hopelessness and, in turn, the symptoms of hopelessness depression, and (d) clarify the diathesis—stress and causal mediation components implied, but not explicitly articulated, in the 1978 statement. We report promising findings for the hopelessness theory and outline the aspects that still need to be tested. (PsycINFO Database Record (c) 2012 APA, all rights reserved)
Article
Full-text available
This semiotic analysis demonstrates how pharmaceutical companies strategically frame depression within the hotly contested terrain of direct-to-consumer (DTC) advertising. The study tracks regulation of the pharmaceutical industry, relative to DTC advertising, including recent industry codes of conduct. Focusing on the antidepressant category, and its three major brands—Paxil (GlaxoSmithKline), Prozac (Eli Lilly), and Zoloft (Pfizer)—this comparative study analyzes 7 years of print advertising following deregulation in 1997. The authors glean themes from within the advertising texts, across the drug category and within individual-brand campaigns. The findings indicate that DTC advertising of antidepressants frames depression within the biochemical model of causation, privileges benefits over risks, fails to adequately educate consumers, and frames depression as a female condition. The authors close with commentary on the potential implications, with particular focus on the new codes of conduct, and offer suggestions for future research.
Article
Full-text available
The title of this review would be regarded by some psychiatrists as provocative; they would relegate the biochemical concomitants of depression and mania to a secondary position and deny that biochemical changes have any place in the aetiology of these conditions. However, in my view, the weight of evidence, although it is by no means conclusive, suggests that biochemical changes are most important in the aetiology of affective disorders. A biochemical aetiology implies that there are certain biochemical changes in the brain which need to be restored to normal before the patient's clinical condition will improve. This does not deny that psychological and environmental events may precipitate and maintain the biochemical events which in turn lead to the affective disorder. The study of these biochemical events is clearly at too early a stage for speculations about the interrelationship between environmental and endogenous elements to be fruitful; this study must wait until the biochemical aetiology is clearer than at present.
Article
Full-text available
A double-blind placebo-controlled cross-over study in which plasma tryptophan was manipulated by administration of a tryptophan-deficient amino acid mixture. In the placebo condition, all subjects received a nutritionally balanced amino acid mixture that contained tryptophan. To further standardize baseline amino acids, each subject was provided with a low-protein diet the day before amino acid challenges. Subjects were euthymic, healthy men aged 18 to 30 years with either a multigenerational family history of affective illness or no family history of psychiatric illness in the present or in the two previous generations. Each subject was screened with a structured clinical interview to rule out a personal history of psychiatric illness. Plasma tryptophan was reduced by 89% 5 hours after the administration of the tryptophan-deficient amino acid mixture. Six of 20 subjects with a family history of affective illness and none of 19 subjects without a family history of psychiatric illness showed a lowering of mood of 10 or more points on the Profile of Mood States depression scale (P = .012, Fisher's Exact Test) 5 hours after tryptophan depletion. No significant mood changes were observed following the control treatment (balanced amino acid mixture) in either group. Our data support the hypothesis that subjects with no prior depressive episodes but with a multigenerational family history of major affective disorder show a greater reduction in mood after tryptophan depletion. They are also consistent with theories that implicate deficient serotonergic function as one possible etiological factor in major depressive disorders.
Article
Full-text available
Antidepressant medication has apparently become the most popular treatment for depression in the USA. Several beliefs about the efficacy of antidepressant medications prevail among mental health professionals and the public. This paper explores relevant research data and raises questions about these beliefs. Many of the common beliefs about these medications are not adequately supported by scientific data. The following issues are raised: (1) industry-funded research studies which result in negative findings sometimes do not get published; (2) placebo washout procedures may bias results in some studies; (3) there are serious questions about the integrity of the double-blind procedure; (4) the 'true' antidepressant drug effect in adults appears to be relatively small; (5) there is minimal evidence of antidepressant efficacy in children; (6) side effects are fairly common even with the newer antidepressants; (7) combining medications raises the risk for more serious complications; (8) all antidepressants can cause withdrawal symptoms; (9) genetic influences on unipolar depression appear to be weaker than environmental influences; (10) biochemical theories of depression are as yet unproven; (11) biological markers specific for depression have been elusive; (12) dosage and plasma levels of antidepressants have been minimally related to treatment outcome; (13) preliminary evidence suggests that patients who improve with cognitive-behavioral psychotherapy show similar biological changes as those who respond to medication, and (14) the evidence suggests that psychological interventions are at least as effective as pharmacotherapy in treating depression, even if severe, especially when patient-rated measures are used and long-term follow-up is considered.
Article
Full-text available
The hippocampus is a target of stress hormones, and it is an especially plastic and vulnerable region of the brain. It also responds to gonadal, thyroid, and adrenal hormones, which modulate changes in synapse formation and dendritic structure and regulate dentate gyrus volume during development and in adult life. Two forms of structural plasticity are affected by stress: Repeated stress causes atrophy of dendrites in the CA3 region, and both acute and chronic stress suppresses neurogenesis of dentate gyrus granule neurons. Besides glucocorticoids, excitatory amino acids and N-methyl-D-aspartate (NMDA) receptors are involved in these two forms of plasticity as well as in neuronal death that is caused in pyramidal neurons by seizures and by ischemia. The two forms of hippocampal structural plasticity are relevant to the human hippocampus, which undergoes a selective atrophy in a number of disorders, accompanied by deficits in declarative episodic, spatial, and contextual memory performance. It is important, from a therapeutic standpoint, to distinguish between a permanent loss of cells and a reversible atrophy.
Article
Full-text available
The authors used nationwide survey data to characterize current public conceptions related to recognition of mental illness and perceived causes, dangerousness, and desired social distance. Data were derived from a vignette experiment included in the 1996 General Social Survey. Respondents (n = 1444) were randomly assigned to 1 of 5 vignette conditions. Four vignettes described psychiatric disorders meeting diagnostic criteria, and the fifth depicted a "troubled person" with subclinical problems and worries. Results indicate that the majority of the public identifies schizophrenia (88%) and major depression (69%) as mental illnesses and that most report multicausal explanations combining stressful circumstances with biologic and genetic factors. Results also show, however, that smaller proportions associate alcohol (49%) or drug (44%) abuse with mental illness and that symptoms of mental illness remain strongly connected with public fears about potential violence and with a desire for limited social interaction. While there is reason for optimism in the public's recognition of mental illness and causal attributions, a strong stereotype of dangerousness and desire for social distance persist. These latter conceptions are likely to negatively affect people with mental illness.
Article
Full-text available
Low levels of central serotonin (5-HT) have been related to the state of depression, and 5-HT is the major target of the newer antidepressant drugs such as selective serotonin reuptake inhibitors (SSRIs). Neurons and platelets display structural and functional similarities, so that the latter have been proposed as a peripheral model of central functions. In particular, in blood more than 99% of 5-HT is contained in platelets, so that one could consider changes in 5-HT levels in platelets as a mirror of changes in central 5-HT. Here, this hypothesis has been studied via the analysis of the influence of: (1) the forced swimming test (FST, which has been proved to be of utility to predict the clinical efficacy of antidepressants in rodents) and (2) treatment with the SSRI fluoxetine upon 5-HT levels monitored in brain regions and in peripheral platelets by means of electrochemical in vivo and ex vivo measurements. The results obtained confirm that the FST increases immobility; furthermore they show a parallel and significant decrease in cerebral (brain homogenate) and peripheral (in platelet-rich plasma, PRP) voltammetric 5-HT levels following the FST in naive rats. In addition, subchronic treatment with fluoxetine was followed by a significant increase in 5-HT levels in PRP, while the same SSRI treatment performed within the FST resulted in a decrease in the 5-HT levels in PRP. However, this decrease was inferior to that observed without SSRI treatment. These data suggest that there is an inverse relationship between immobility and the levels of 5-HT in PRP and that these peripheral 5-HT levels are sensitive to: (1) the FST, (2) the treatment with fluoxetine and (3) the combination of both treatments, i.e. SSRI + FST. It has been reported that SSRI treatment at first inhibits the 5-HT transporter in brain, resulting in increased extracellular 5-HT, while following sustained SSRI treatments decreased intracellular levels of central 5-HT were observed. Accordingly, the present data show that the initial block of 5-HT reuptake is revealed by the selective increase in 5-HT levels (extracellular content) measured in PRP (not in insulated platelets, IPs) the 1st day of fluoxetine treatment. The initial action of this SSRI upon the 5-HT transporter in brain has also been confirmed by in vivo voltammetric data showing selective increase in the serotonergic signal following local injection of fluoxetine into the brain region studied. Successively, the major effect monitored is a decrease in 5-HT levels, which is more evident in IPs than in PRP. However, it is known that following 2 weeks treatment with an SSRI, 5-HT autoreceptors are desensitized and the serotonin synthesis is restored, together with the intracellular 5-HT levels. The present data showing that the levels of 5-HT in IPs tend to return to control values 12 days after the beginning of chronic fluoxetine treatment suggest that 5-HT levels in IPs (intracellular environment) mirror the influence of SSRI treatment upon the central 5-HT system. On the other hand, at day 12 of the chronic fluoxetine treatment, 5-HT content remains low in PRP. Similarly, low levels of 5-HT have been monitored in brain homogenate of rats chronically treated with fluoxetine. This would support the similarity between PRP preparation and brain homogenate as in both cases cells are disrupted by sample preparation. In conclusion this work supports the literature in proposing platelets as a peripheral model of central functions. In particular, the present data support the idea that peripheral 5-HT platelet levels can reflect the state of the central 5-HT system in conditions of depression. Furthermore, the main outcome of this study is that PRP may mirror central extracellular 5-HT levels, whilst IPs mirror neuronal 5-HT changes.
Article
Full-text available
Acute tryptophan depletion (ATD) induces depressive symptoms in 50-60% of selective serotonin reuptake inhibitor (SSRI) treated, recovered depressed patients. However, no reliable predictors of mood response to ATD have been established. In the present study, individual subject data of six ATD studies were pooled ('mega-analysis') in order to investigate the mediating role of clinical, demographic and biochemical characteristics in the mood response to ATD. A procedure was developed to make different versions of the Hamilton scale comparable. Recurrent depressive episodes, female gender, prior exposure to SSRI antidepressant treatment and previous serious suicidal thoughts/attempts all appear to be independent predictors of mood response to ATD. Chronicity of illness is the most powerful predictor. Residual symptoms of depression were not found to predict response to ATD. ATD may be useful to study the mechanism of action of SSRI antidepressants and individual biological vulnerability of the serotonin system. Whether the effects of ATD represent a reversal of the action of SSRI antidepressants or individual vulnerability probably depends upon the timing of the procedure in the course of remission of a depressive episode.
Article
Full-text available
Uncertainties exist about prevalence and correlates of major depressive disorder (MDD). To present nationally representative data on prevalence and correlates of MDD by Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria, and on study patterns and correlates of treatment and treatment adequacy from the recently completed National Comorbidity Survey Replication (NCS-R). Face-to-face household survey conducted from February 2001 to December 2002. The 48 contiguous United States. Household residents ages 18 years or older (N = 9090) who responded to the NCS-R survey. Prevalence and correlates of MDD using the World Health Organization's (WHO) Composite International Diagnostic Interview (CIDI), 12-month severity with the Quick Inventory of Depressive Symptomatology Self-Report (QIDS-SR), the Sheehan Disability Scale (SDS), and the WHO disability assessment scale (WHO-DAS). Clinical reinterviews used the Structured Clinical Interview for DSM-IV. The prevalence of CIDI MDD for lifetime was 16.2% (95% confidence interval [CI], 15.1-17.3) (32.6-35.1 million US adults) and for 12-month was 6.6% (95% CI, 5.9-7.3) (13.1-14.2 million US adults). Virtually all CIDI 12-month cases were independently classified as clinically significant using the QIDS-SR, with 10.4% mild, 38.6% moderate, 38.0% severe, and 12.9% very severe. Mean episode duration was 16 weeks (95% CI, 15.1-17.3). Role impairment as measured by SDS was substantial as indicated by 59.3% of 12-month cases with severe or very severe role impairment. Most lifetime (72.1%) and 12-month (78.5%) cases had comorbid CIDI/DSM-IV disorders, with MDD only rarely primary. Although 51.6% (95% CI, 46.1-57.2) of 12-month cases received health care treatment for MDD, treatment was adequate in only 41.9% (95% CI, 35.9-47.9) of these cases, resulting in 21.7% (95% CI, 18.1-25.2) of 12-month MDD being adequately treated. Sociodemographic correlates of treatment were far less numerous than those of prevalence. Major depressive disorder is a common disorder, widely distributed in the population, and usually associated with substantial symptom severity and role impairment. While the recent increase in treatment is encouraging, inadequate treatment is a serious concern. Emphasis on screening and expansion of treatment needs to be accompanied by a parallel emphasis on treatment quality improvement.
Article
In a national representative survey, 1,403 people were interviewed on their attitudes to depression and its sufferers and their understanding of the causes, treatability and treatment of depression. Some two-thirds of the interviewees regarded depressives as being neither mentally ill, weak willed, nor as feeling sorry for themselves. Stress, bereavement and hereditary were considered to be the most frequent causes of depression. Seventy-three per cent said that depression could be successfully treated. While 81 per cent recommended getting professional help, only 17 per cent mentioned their GP as a source of treatment for depression. People who had depression, or who had a friend or relative who had depression and those who had visited a patient in a psychiatric hospital expressed more positive attitudes to depression and its management.
Article
This semiotic analysis demonstrates how pharmaceutical companies strategically frame depression within the hotly contested terrain of direct-to-consumer (DTC) advertising. The study tracks regulation of the pharmaceutical industry, relative to DTC advertising, including recent industry codes of conduct. Focusing on the antidepressant category, and its three major brands—Paxil (GlaxoSmithKline), Prozac (Eli Lilly), and Zoloft (Pfizer)—this comparative study analyzes 7 years of print advertising following deregulation in 1997. The authors glean themes from within the advertising texts, across the drug category and within individual-brand campaigns. The findings indicate that DTC advertising of antidepressants frames depression within the biochemical model of causation, privileges benefits over risks, fails to adequately educate consumers, and frames depression as a female condition. The authors close with commentary on the potential implications, with particular focus on the new codes of conduct, and offer suggestions for future research.
Article
Tianeptine is an antidepressant agent with a novel neurochemical profile. It increases serotonin (5-hydroxytryptamine; 5-HT) uptake in the brain (in contrast with most antidepressant agents) and reduces stress-induced atrophy of neuronal dendrites. Like the selective serotonin reuptake inhibitors (SSRIs) and in contrast with most tricyclic antidepressant agents, tianeptine does not appear to be associated with adverse cognitive, psychomotor, sleep, cardiovascular or bodyweight effects and has a low propensity for abuse. Tianeptine has a comparatively favourable pharmacokinetic profile. It is not subject to first-pass hepatic metabolism, has high bioavailability and limited distribution, and is rapidly eliminated. While this offers advantages for tianeptine over the tricyclic antidepressant agents in terms of dose titration, treatment changes and potential drug interactions, its rapid elimination makes adherence to dosage schedules more important. Tianeptine differs from most antidepressants in that it is not primarily metabolised by the hepatic cytochrome P450 system, indicating less likelihood of drug-drug interactions; this is of particular interest for elderly patients. Tianeptine, in dosages of 25 to 50 mg/day, has been investigated in patients with major depression, depressed bipolar disorder, dysthymia or adjustment disorder. It has equivalent antidepressant efficacy to several classical antidepressant agents (amitriptyline, clomipramine, imipramine, mianserin) and the SSRIs fluoxetine (in most patients), paroxetine and sertraline. Comparison with maprotiline indicated superior efficacy for tianeptine but dothiepin appeared superior in another study. Extended treatment with tianeptine decreases the incidence of relapse/ recurrence of depression. Tianeptine appears to be as effective as fluoxetine, sertraline, amitriptyline, clomipramine and mianserin and more effective than maprotiline in improving associated anxiety in patients with depressive disorders. Depression and anxiety symptoms in alcohol dependant patients also respond well to tianeptine. The adverse effects associated with tianeptine are similar in many respects to those of the SSRIs and minimal in comparison with the tricyclic antidepressants. The most common adverse effects are nausea, constipation, abdominal pain, headache, dizziness and changes in dreaming. Anticholinergic effects occur less often with tianeptine than with tricyclic agents. Hepatoxicity is rare. The dosage should be decreased in elderly patients and those with severe renal failure, but adjustment is not necessary in patients with alcoholism or hepatic impairment, or those undergoing haemodialysis. Conclusions: The antidepressant efficacy and favourable tolerability and pharmacokinetic profiles of tianeptine in patients with depression, including those with associated anxiety, have been proven; the data indicate that it may have additional potential in specific subgroups of depressed patients such as the elderly and those with chronic alcoholism. Pharmacodynamic Profile Tianeptine is an antidepressant drug with structural similarities to the tricyclic antidepressant agents but a novel neurochemical profile. The main difference between this and other antidepressant agents is its action on serotonin (5-hydroxytryptamine; 5-HT): tianeptine increases serotonin uptake in the brain and platelets. The behavioural (in animal models) and physical (atrophy of neuronal dendrites) effects of stress on the hypothalamic-pituitary-adrenal axis are reduced by tianeptine, and levels of noradrenaline (norepinephrine) and dopamine are indirectly increased in several regions of the brain. The main metabolite (MC5; pentanoic acid) has some minor antidepressant activity. Clinical studies indicate that, unlike tricyclic antidepressant agents, tianeptine is not associated with adverse effects on driving skills or cognitive function (such as sedation or impaired memory) and may have slight activating properties, particularly in aspects of attention. Similarly, there appear to be few effects on sleep in healthy volunteers or patients with concurrent depression and alcoholism after withdrawal of alcohol. Like the selective serotonin reuptake inhibitors (SSRIs) and in contrast with the tricyclic antidepressants, tianeptine has a favourable cardiovascular profile in healthy volunteers and patients with depression, with and without concurrent alcoholism. Pharmacokinetic Profile The maximum plasma concentration (Cmax) of tianeptine was 0.3 mg/L, time to Cmax (tmax) was 0.94 hours and bioavailability was 99% after a single oral dose of tianeptine 12.5mg in healthy volunteers. The drug is not subject to first-pass hepatic metabolism. Food decreases Cmax and prolongs tmax but does not affect the extent of absorption. Although the distribution of tianeptine is rapid (distribution half-life 0.7 hours) protein binding is high (95%), resulting in alow volume of distribution (0.5 to 0.8 L/kg) in healthy volunteers. Tianeptine undergoes extensive extrarenal metabolism and has a short elimination half-life (t1/2β; 2.5 hours in healthy volunteers). The major metabolic pathway of tianeptine is a 2-step β-oxidation process of the aliphatic chain, leading to the formation of 2 main metabolites MC5 and MC3 (propionic acid). MC3 is the main metabolite of tianeptine in urine and MC5 is the main metabolite in plasma. Tianeptine does not undergo cytochrome P450—dependent biotransformation to any significant extent, thus reducing the risk of drug interactions. The pharmacokinetic profile of a single dose of tianeptine in adults with depression appears similar to that in healthy adult volunteers, although the tmax and t12β were prolonged. Steady-state pharmacokinetics were achieved after 1 month of treatment with tianeptine 37.5 mg/day and were maintained over 3 months. Most values were similar to those seen in depressed patients after a single dose, but the area under the concentration-time curve (AUC) was significantly greater after extended treatment (1.3 vs 1 mg/L · h; p < 0.03). The pharmacokinetic profile of oral tianeptine was not significantly altered in patients with compromised renal function. However, the t1/2β and AUC of the MC5 metabolite were increased compared with controls, suggesting a decreased clearance of this metabolite in patients with renal failure. Although bioavailability of tianeptine remained high (85%) in elderly individuals, clearance was lower than that reported in younger individuals. The pharmacokinetic profile of tianeptine is not altered in patients with alcoholic cirrhosis and depression. Therapeutic Efficacy The clinical antidepressant efficacy of tianeptine 25 to 50 mg/day has been proven against placebo in patients aged 18 to 60 years with major depression (single episode or recurrent) or bipolar disorder (depressed) in 2 double-blind trials. Initial improvements were seen after 7 days, and improvement continued throughout the 6 weeks of study. Improvements from baseline on the Montgomery-Åsberg Depression Rating Scale (MÅDRS) were 44 and 54% with tianeptine and 28 and 38% in placebo recipients (p < 0.05 and p < 0.01, respectively). Tianeptine 25 to 37.5 mg/day for 1.5 to 3 months had equivalent antidepressant efficacy to fluoxetine 20 mg/day in patients with major depression (single episode or recurrent), bipolar disorder (depressed) or dysthymic disorder in several studies. However, although equivalence was noted in several parameters in elderly patients receiving tianeptine or fluoxetine in one study, reductions from baseline in the MÅDRS scores were statistically significantly greater in those receiving fluoxetine (62 vs 51% in fluoxetine and tianeptine recipients, respectively, compared with 50 vs 51%, respectively, in a study in patients aged 18 to 65 years which used this assessment tool). The antidepressant efficacy of tianeptine 37.5 mg/day (reduction in MÅDRS score of 56%) was equivalent to that of sertraline 50 mg/day (reduction of 54%) after 1.5 months in patients with major depression or bipolar disorder. A study published only in abstract form indicates that tianeptine 37.5 mg/day has similar efficacy to paroxetine 20 mg/day for 3 months (reductions in MÅDRS scores of 62 and 61%, respectively). In comparative studies with tricyclic or tetracyclic antidepressant agents, the antidepressant efficacy of tianeptine 25 to 50 mg/day (44 to 64% reduction in MÅDRS scores) was equivalent to that of amitriptyline 50 to 100 mg/day for 1 or 1.5 months (53 and 69%), clomipramine 100 to 200 mg/day for 6 months (55%), imipramine 100 to 200 mg/day for 1.5 months (41%) and mianserin 30 to 80 mg/day for 1.5 or 6 months (48 and 50%) in patients with major depression (single episode or recurrent), bipolar disorder (depressed), dysthymic disorder or adjustment disorder. Tianeptine 37.5 mg/day (56% reduction in MÅDRS score) was more effective than maprotiline 75 mg/day for 2 months (47%) in a study of perimenopausal women with anxio-depressive symptoms and less effective than dothiepin 150 to 225 mg/day for 1 month in a small study of patients with depressive disorders. The anxiolytic efficacy of tianeptine was assessed in several comparative trials of patients with concurrent depression and anxiety. Tianeptine 25 to 50 mg/day appears to have equivalent anxiolytic efficacy to fluoxetine 20 mg/day for 1.5 to 3 months, sertraline 50 mg/day for 1.5 months, amitriptyline 50 to 100 mg/day for 1 to 1.5 months, clomipramine 100 to 200 mg/day for 6 months and mianserin 30 to 80 mg/day for 1.5 or 6 months. Superior anxiolytic efficacy was attributed to tianeptine over maprotiline 75 mg/day for 2 months in a study of perimenopausal women with anxio-depressive symptoms. Tianeptine 25 to 50 mg/day is effective as long term treatment to prevent relapse or recurrence in patients with depression. It also appears to have potential for use in specific subgroups. The efficacy of tianeptine 25 or 37.5 mg/day was equivalent to that of mianserin 30 mg/day and similar in some but not all parameters to that of fluoxetine 20 mg/day in elderly patients. Patients with chronic alcoholism often develop depression, especially on withdrawal of alcohol. Assessments of antidepressant and anxiolytic efficacy for tianeptine 37.5 mg/day were equivalent to those for amitriptyline 75 mg/day over 1 to 2 months in this patient population. Improvements in quality-of-life scales with depressed tianeptine recipients were similar to those in patients receiving mianserin or fluoxetine. Tolerability The adverse effect profile of tianeptine appears to be similar in many respects to that of the SSRIs, in that cognitive, cardiovascular and bodyweight effects are minimal in comparison with the classical tricyclic antidepressant agents. In fact, in comparisons with placebo, the only symptom appearing significantly more often with tianeptine was headache. In clinical trials, the most common adverse effects seen in patients with depressive disorders receiving tianeptine were gastrointestinal (nausea, constipation, abdominal pain) or CNS (headache, dizziness, change in dreaming) disturbances, which decreased in frequency with continued treatment. Effects such as dry mouth, hot flushes, somnolence, vertigo, gastrointestinal disturbances, increased bodyweight, increased heart rate and tremor occurred significantly more often in patients receiving tri- or tetracyclic antidepressant agents than in those receiving tianeptine. In studies comparing tianeptine with fluoxetine, paroxetine or sertraline, in contrast, the incidence of most adverse effects was similar; nausea, tremor and palpitations tended to occur more often in fluoxetine recipients, and the incidence of dry mouth tended to be higher in tianeptine recipients. Tianeptine has only rarely been associated with hepatoxicity. The favourable tolerability profile of tianeptine has been confirmed in long term trials, and in elderly patients (including those with cardiovascular pathology before treatment initiation) and patients with alcoholism. The low incidence of anticholinergic and neurological effects associated with tianeptine is of particular importance in these subgroups, who have increased sensitivity to the adverse effects of psychotropic drugs. Tianeptine has a wide therapeutic margin; overdosage has been associated with only minor transient adverse effects. Dosage and Administration The recommended dosage of tianeptine in patients with depression is 37.5 mg/day orally in 3 divided doses, with meals. The dosage should be reduced in elderly patients and patients with severe renal failure, but dosage reduction is not required in patients with chronic alcoholism or hepatic impairment or those undergoing haemodialysis. The dosage of tianeptine should be reduced over 1 to 2 weeks when discontinuing treatment, although there is little evidence of psychological or physical dependence on the drug. As with other antidepressants, tianeptine is contraindicated in patients taking monoamine oxidase inhibitors.
Article
explanatory style is a cognitive personality variable that reflects how people habitually explain the causes of events / explanatory style is part of a tradition within psychology that focuses on individual differences in people's thoughts and beliefs and how these influence motivation, emotion, and behavior / [explanatory style involves 3 dimensions: internal vs external, stable vs unstable, and global vs specific] psychologists have become interested in the possibility that certain individuals habitually favor certain sorts of explanations over others / start . . . by locating explanatory style in its historical context / explanatory style tradition is both theoretical and empirical / [the authors] suspect that a large part of the popularity of explanatory style is due to this grounding in well-defined theory, on the one hand, and straightforward measures, on the other / [the authors] discuss the [critical] shortcomings [of explanatory style] (PsycINFO Database Record (c) 2012 APA, all rights reserved)
Article
The distribution of 5-hydroxyindoleacetic acid (5-HIAA) concentrations in the cerebrospinal fluid of 68 depressed patients was bimodal. Twenty-nine percent of the patients were in the lower mode, with a concentration of 5-HIAA below 15 nanograms per milliliter. Although there were no differences in overall severity of depression between the two modes, there was a significant correlation between the concnetration of 5-HIAA and severity of depression in the lower, but not in the upper, mode. The finding suggests the existence of a biochemical subgroup of depressive disorder, characterized by a disturbance of serotonin turnover.
Article
Modern treatment of mental depression started with the availability of monoamine oxidase (MAO) inhibitors and tricyclic antidepressants. These drugs also contributed to the early development of psychopharmacology. Attempts to improve the anti-tuberculous action of the hydrazine derivative isoniazid by developing derivatives thereof led to the synthesis of iproniazid. Its introduction as the first modern antidepressant was based on three unexpected actions of the drug: MAO-inhibition, 'reversal' of reserpine-induced sedation, and the presence of psychostimulation as a clinical side effect in man. However, the initial success of iproniazid and other MAO inhibitors, hydrazides and non-hydrazides, was curtailed by the occurrence of undesirable side effects such as potentiation of the blood-pressure elevating action of food amines. The tricyclic antidepressants were a development of the class of antihistamines, one of which, chlorpromazine, showed neuroleptic activity. A congener of this compound, imipramine, was discovered by clinical observation to have unexpected antidepressant effects. The clinical success of this drug (which is still in use) led to the development of a successful series of other tricyclic and non-tricyclic antidepressants. Progress in the elucidation of possible mechanisms of the action of the tricyclic compounds has helped this development. Recent advances in basic research have also induced a revival of MAO-inhibitors since, due to the discovery of MAO-subtypes, inhibitors with higher specificity and fewer undesirable side effects are now available.
Article
Brain serotonin content is dependent on plasma levels of the essential amino acid tryptophan. We investigated the behavioral effects of rapid tryptophan depletion in patients in antidepressant-induced remission. Twenty-one patients who were depressed by DSM-III-R criteria received a 24-hour, 160-mg/d, low-tryptophan diet followed the next morning by a 16-amino acid drink, in a double-blind, placebo-controlled (acute tryptophan depletion and control testing), crossover fashion. Total and free tryptophan levels decreased 87% and 91%, respectively, during acute tryptophan depletion. Fourteen of the 21 remitted depressed patients receiving antidepressants experienced a depressive relapse after the tryptophan-free amino acid drink, with gradual (24 to 48 hours) return to the remitted state on return to regular food intake. Control testing produced no significant behavioral effects. Free plasma tryptophan level was negatively correlated with depression score during acute tryptophan depletion. The therapeutic effects of some antidepressant drugs may be dependent on serotonin availability.
The three main purposes of the present study are: 1) to review the studies on CSF amines in patients with depression, with specific attention to diagnostic classification and to variables - unspecific to depression - which might partly explain the poor agreement obtained in CSF studies especially on amine metabolites, 2) to give a status on relevance and results obtained in CSF peptide studies in depression, and 3) finally to discuss the relevance of CSF research as such in depression.
Article
The "catecholamine hypothesis of affective disorders" proposes that some, if not all, depressions are associated with an absolute or relative decrease in catecholamines, particularly norepinephrine, available at central adrenergic receptor sites. Elation, conversely, may be associated with an excess of such amines. Evidence supporting this hypothesis was reviewed. Data from pharmacological studies, mainly in animals, suggest that the actions of both major classes of antidepressant drugs are mediated through the catecholamines. The monoamine oxidase inhibitors increase brain concentrations of norepinephrine while imipramine-like agents potentiate the physiological effects of norepinephrine. Reserpine, a drug which can cause clinical depression, depletes catecholamines, but other amines may also be involved in its mechanism of action. A rigorous extrapolation from pharmacological studies to pathophysiology clearly cannot be made. Clinical studies relevant to the catecholamime hypothesis are limited and the findings are inconclusive. It is not possible, therefore, to confirm definitively or to reject the catecholamine hypothesis on the basis of data currently available. In our present state of knowledge, however, the catecholamine hypothesis is of considerable heuristic value, providing the investigator and the clinician with a frame of reference integrating much of our experience with those pharmacological agents which produce alterations in human affective states.
Article
In 60 physically and mentally healthy human subjects, lumbar cerebrospinal fluid was analysed by mass fragmentography for 5-HIAA, HVA and MOPEG. Individuals with a family history of psychiatric morbidity had significantly greater variation in monoamine metabolite concentrations than subjects without such a family history. In subjects with a family history of schizophrenic psychosis 5-HIAA and HVA concentrations were significantly higher than in subjects with depressive disorders within the family. For subjects with deviant 5-HIAA levels the probability of having a psychiatric family history was 2.7 times higher than in subjects with normal values. For HVA and MOPEG similar relationships, but of a lower significance level, were found. The results suggest that the cerebral monoaminergic transmitter amines play critical roles in the pathophysiology of psychotic and depressive disorders with a family disposition. They also indicate a value of monoamine metabolite determination in CSF for the prediction of family vulnerability for psychiatric morbidity in healthy subjects.
Article
The neurotransmitter metabolites 5-hydroxyindoleacetic acid (5-HIAA), homovanillic acid (HVA) and 4-hydroxy-3-methoxyphenyl glycol (HMPG) in cerebrospinal fluid (CSF) were measured by mass fragmentography in 83 patients with melancholia (diagnosed by the Newcastle Inventory and the Research Diagnostic Criteria), and 66 healthy volunteer controls. After adjustment by analysis of covariance for differences between the subject groups in body height, age and sex distribution, significantly (P less than 0.001) lower concentrations of 5-HIAA and HVA were found in the melancholia patients than in the controls. HMPG did not differ between the groups. The differences could not be accounted for by differences in timing or examination techniques, and not by previously administered drugs (all patients were drug-free at the examination, but a minority had taken small amounts of psychotropic drugs prior to the wash-out period). The differences persisted after excluding the suicidal patients. There were no clear-cut differences between unipolar and bipolar patients. It is suggested that the reduced concentrations of 5-HIAA and HVA in the melancholic patients may be due to altered serotonin and/or dopamine functions in the central nervous system, which may be connected with an increased vulnerability to certain types of affective illness.
Article
Brain catecholamines can be rapidly reduced by inhibiting their synthesis with alpha-methyl-para-tyrosine (AMPT). In order to assess the role of catecholamines in antidepressant action AMPT challenges were administered in a double-blind, placebo-controlled, crossover fashion to 14 depressed patients having maintained a therapeutic antidepressant response for > or = 2 weeks (3 desipramine, 2 mazindol, 5 fluoxetine, 4 sertraline). Each patient participated in two challenges one week apart. Each challenge included a baseline, two days of either AMPT or diphenhydramine (active placebo), and a followup. Antidepressant drugs were continued throughout testing. The 3 desipramine- and 2 mazindol-responders had a rapid increase in depression score during AMPT but not placebo (diphenhydramine) challenge whereas only 1 of 9 selective serotonin reuptake inhibitor (SSRI)-treated patients did. The implication of this is that the antidepressant response to desipramine may be more acutely dependent on brain catecholamine content than the response to SSRIs. In the context of our previous work with tryptophan depletion, these results suggest that the neurobiological mechanisms underlying the antidepressant responses to different drugs involve alterations in the functioning of different neurotransmitter systems and reinforce the importance of changes in both the serotonin and catecholamine systems for successful antidepressant responses.
Article
The results from these and other studies provide an opportunity to critically re-examine the role of brain monoamine function in the pathophysiology of depression and the mechanism of action of antidepressant drugs. The following observations are most salient: 1. Tryptophan depletion, which reduces brain serotonin function, reverses the therapeutic effects of specific serotonin reuptake inhibitors (SSRIs) but not drugs which potently inhibit noradrenaline reuptake. In contrast, depletion of noradrenaline and dopamine, as a consequence of AMPT administration, reverses the remission induced by noradrenaline (desipramine) and dopamine (mazindol) reuptake inhibitors, but not SSRIs. These data suggest that the efficacy of antidepressant drugs may not be due to a common mechanism involving a single monoamine system. SSRIs and noradrenaline reuptake inhibitors may work via primary actions on serotonin and noradrenaline function, respectively. Alternatively, these two classes of antidepressant drugs may exert their therapeutic properties by affecting the function of an, as yet, unknown neuronal system that is regulated by these monoamine systems; 2. In both drug-free depressed patients and healthy subjects, tryptophan depletion and AMPT do not produce marked alterations in depressed mood. These results suggest that alterations in serotonin, dopamine, and noradrenaline systems may not reflect the primary pathology causing depressive illness. An alternative explanation is that in depressed patients these systems are maximally dysfunctional such that further manipulations do not worsen depressive systems. 3. Clinical experience and the results from several controlled studies indicate that the efficacy of SSRIs and noradrenaline inhibiting drugs are approximately equal.(ABSTRACT TRUNCATED AT 250 WORDS)
Article
Most hypotheses of the therapeutic mechanism of action of antidepressant drugs have focused on the role of the monoamines. We examined the effect of catecholamine depletion on antidepressant-induced remission. The tyrosine hydroxylase inhibitor alpha-methylparatyrosine and the antihistamine diphenhydramine hydrochloride were administered, during separate test sessions, to depressed patients in remission maintained with either norepinephrine reuptake inhibitors (desipramine [n = 7] or mazindol [n = 2]) or serotonin reuptake inhibitors (fluoxetine hydrochloride [n = 9] or sertraline hydrochloride [n = 1]). Because of considerable sedation associated with alpha-methylparatyrosine testing, diphenhydramine was used as an active control rather than an inactive placebo. The effects of alpha-methylparatyrosine and diphenhydramine on depression, anxiety, and plasma catecholamine metabolites were assessed. alpha-Methylparatyrosine produced similar significant decreases in plasma 3-methoxy-4-hydroxyphenylethyleneglycol and homovanillic acid levels in the treatment groups. alpha-Methylparatyrosine produced a robust increase in depressive symptoms on the Hamilton Depression Rating Scale, including depressed mood, decreased concentration, anhedonia, loss of interest, and feelings of worthlessness, helplessness, and hopelessness, in the desipramine-mazindol but not in the fluoxetine-sertraline group. Diphenhydramine had no effects on mood in either treatment group. The therapeutic effects of norepinephrine reuptake inhibitors, but not serotonin reuptake inhibitors, are reversed by catecholamine depletion. Considered with previous reports that serotonin depletion produces depressive relapses in patients in remission maintained with serotonin reuptake inhibitors, but not norepinephrine reuptake inhibitors, these findings suggest that antidepressants may not work via a single monoamine-related mechanism.
Article
A variety of biologic studies have demonstrated abnormal regulation of the norepinephrine (NE) system in patients with major depression, suggesting a role for NE in the etiology of depression. Brain NE and dopamine levels can be rapidly reduced by blocking synthesis with the tyrosine hydroxylase inhibitor alpha-methyl-para-tyrosine (AMPT). In the current investigation, AMPT was administered to drug-free depressed patients to evaluate the effect on mood of diminished catecholamine levels. Seventeen drug-free patients meeting DSM-III-R criteria for major depressive episode were tested with AMPT and an active placebo control, diphenhydramine. Testing was accomplished in a double-blind, crossover fashion, with random assignment to test conditions. Each test included baseline evaluation, 2 days with administration of either AMPT or diphenhydramine, and a follow-up day. Diphenhydramine was used as an active control because of the significant sedation associated with AMPT. Behavioral ratings, including visual analogue scales for a variety of feeling states, the Hamilton Depression Rating Scale (HDRS), and plasma for 3-methoxy-4-hydroxyphenelethyleneglycol (MPHG) and homovanillic acid (HVA) levels, were obtained. AMPT significantly reduced plasma HVA by 70% and MHPG by 50%, but it had no significant effects on the HDRS. AMPT also significantly increased visual analogue ratings of "tired" and decreased ratings of "energetic." Diphenhydramine significantly decreased HDRS scores, but the change was small and was not clinically apparent. The lack of AMPT effects on depressed mood, in conjunction with a prior report that large reductions in plasma tryptophan do not systematically alter depressed mood, indicate that monoamine deficiency by itself is insufficient explanation of the cause of depression. The role of the noradrenergic system needs to be considered in relationship to the many other neurobiologic factors that could be involved in the pathophysiology of depression.
Article
So far, researchers have, for the most part, used lists of Likert-scaled items in their quantitative analysis of lay beliefs about the causes of mental disorders. With the help of factor analyses they have then sought to identify the independent dimensions of the attitudinal space. In contrast, it is the aim of multiple unidimensional unfolding, which shall be presented in this paper, to establish a latent dimension of the order of preference regarding the causes offered as an explanation for the development of mental disorders. Using data from a representative survey examining the attitude of the general public of the new "Länder" of the Federal Republic of Germany towards mental disorders, which was conducted during 1993, it can be shown that 11 of the 15 causal factors offered may be arranged along an unfolding scale. The centre of the scale was characterized by the item "God's will or fate". Psychosocial stress factors constituted one pole of the scale, personality disorders, the other. In between we found both external and biological influences over which the afflicted individuals had no control. Analogies to the concept of locus of control are discussed.
Article
This study was designed to determine the behavioral effects of a reduction in catecholamine and indoleamine function in healthy subjects. Eight healthy subjects received the tyrosine hydroxylase inhibitor, alpha-methyl-para-tyrosine (AMPT) in combination with a full-strength tryptophan-depleting amino acid drink during one 4-day test session, and AMPT and tryptophan-supplemented amino acid drink (n = 2), or a 25% strength tryptophan-depleting amino acid drink (n = 6) during a second 4-day test session. The combined administration of AMPT and the tryptophan-free amino acid drink did not produce statistically significant or even clinically noticeable changes in mood among the healthy subjects. The implications of these observations for the monoamine hypotheses of depression are discussed.
Article
The objective of this study was to carry out a national survey to assess the Australian public's beliefs about causes and risk factors for mental disorders. A national household survey of 2,031 Australian adults was carried out. Half the respondents were presented with a vignette describing a person with major depression and the other half with a vignette describing schizophrenia. Respondents were asked to rate whether various factors are likely causes of problems such as that described in the vignette and to rate whether various groups are at higher or lower risk. For depression, social environmental factors were often seen as likely causes, which is consistent with the epidemiological evidence. However, genetic factors were considered as a likely cause by only half the population. For schizophrenia, social environmental factors were also often seen as causes, which is in contrast to the weak epidemiological evidence for such a role. Genetic factors attracted more support as a cause of schizophrenia than of depression. These findings point to areas where the mental health literacy of the population could be improved, particularly the over-emphasis on social environmental factors in schizophrenia. Of some concern was the belief of half the population that weakness of character is a likely cause of both depression and schizophrenia. This belief implies a negative evaluation of the sufferer as a person.
Article
Although state-related alterations in catecholamine function have been well-described in depressed subjects, enduring abnormalities have been less reliably identified. In our study, medication-free subjects with fully remitted major depression underwent a paradigm of catecholamine depletion, via use of the tyrosine hydroxylase inhibitor alpha-methylparatyrosine. Subjects underwent 2 sets of testing conditions in a double-blind, random-ordered, crossover design, approximately 1 week apart. They underwent active catecholamine depletion (via oral administration of 5 g alpha-methylparatyrosine) or sedation-controlled, sham catecholamine depletion (via oral administration of 250 mg diphenhydramine hydrochloride), during a 2-day observation. Serial mood ratings and blood samples were obtained. Fourteen subjects completed the active testing condition; 13 completed sham testing. Subjects experienced marked, transient increases in core depressive and anxiety symptoms, as demonstrated by a mean 21-point increase on Hamilton Depression Rating Scale scores. Furthermore, 10 (71%) of 14 subjects fulfilled relapse criteria during active testing, whereas 1 (8%) of 13 subjects did so during sham testing. The severity of the depressive reaction correlated with baseline plasma cortisol levels (r = 0.59; P =.04). Euthymic, medication-free subjects with a history of major depression demonstrate significant depressive symptoms when undergoing testing with alpha-methylparatyrosine. This depressive reaction may represent a reliable marker for a history of depression. Further work is needed to clarify the significance of this finding.
Article
Background: Brain serotonin (5-HT) content is dependent on plasma levels of the essential amino acid, tryptophan (TRP). We have previously reported that rapid TRP depletion more frequently reversed the antidepressant response to monoamine oxidase inhibitors and 5-HT reuptake inhibitors than to desipramine (DMI). This study further investigates the relationship of relapse during TRP depletion to antidepressant type in nonrefractory, depressed patients randomly assigned to treatment with either DMI or fluoxetine (FLU). Methods: Fifty-five drug-free depressed (DSM-III-R) patients were randomly assigned to antidepressant treatment with either DMI or FLU. All patients were either treatment naive (n = 34) or had previously received successful antidepressant treatment (n = 21). During the treatment phase, 35 patients had therapeutic responses by predetermined criteria (DMI 18/25; FLU 17/23) and 30 of these (15 DMI responders and 15 FLU responders) went on to TRP depletion testing. Patients received two 2-day test sessions involving administration of similar amino acid drinks. One session led to rapid TRP depletion and the other did not. Behavioral ratings [Hamilton Depression Scale (HDRS)] and plasma for TRP levels were obtained prior to, during, and after testing. Relapse was defined as a 50% increase in HDRS with total < or = 17. Results: Total and free TRP decreased 70% to 80% 5 hours after the TRP-free drink. While 8/15 FLU responders relapsed, only 1/15 of the DMI responders relapsed. No patient experienced significant depressive symptoms during control testing. Conclusions: Rapid depletion of plasma TRP transiently reverses the antidepressant response in many patients on FLU but not DMI. Depressive relapse during TRP depletion appears to be more related to antidepressant type than to patient variables since patients were randomly assigned to the two treatments. Antidepressant response to FLU appears to be more dependent on 5-HT availability than that of DMI, suggesting that antidepressants mediate their therapeutic effects through different mechanisms.
Article
Acute tryptophan (TRP) depletion was evaluated in healthy volunteers with or without a family history of major affective disorder (FH+ versus FH-). Twenty-seven subjects (16 FH+, 11 FH-) received 100 g of an amino acid mixture with and without TRP according to a placebo-controlled, double-blind cross-over design and a diet devoid of TRP for the next 24 hours. The ratio TRP/large neutral amino acids declined to 22% of baseline values after 6 hours, and increased during the night reaching 85% of baseline after 24 hours. Overall, after 6 hours, TRP depletion lead to a lowering of mood, but after 24 hours, these changes were no longer detected. Mood changes and gastrointestinal side effects were significantly more evident in FH+ subjects than in FH- subjects. Our data support the hypothesis that subjects with a positive family history for depression are predisposed to increased vulnerability to the adverse consequences of serotonergic imbalance.
Article
The pathophysiology and effects of antidepressants in the brain are still poorly understood. While it is generally accepted that increasing the levels of monoamine in the brain is an effective way to alleviate depression, the precise neurobiological mechanisms are unclear. The evidence that monoamine function is impaired in individuals with depression is largely indirect. However, the neurotransmitter depletion model allows a more direct investigation of the role of the monoamines. In this model, tryptophan depletion is used to lower levels of serotonin and alpha-methylparatyrosine is used to induce catecholamine depletion in the brain. Studies have shown that such depletion transiently reverses antidepressant responses in the majority of patients, the response being dependent on the type of antidepressant used. However, depletion in unmedicated patients with depression did not worsen the depressive symptoms, neither did it cause depression in healthy subjects with no history of mental illness. The cause(s) of depression therefore appears to be more complex than simply a reduction in levels of monoamine or diminished function in these systems. The pathophysiology of depression may relate to dysfunction in brain areas modulated by monoamine systems. Antidepressant drugs may mediate their effects by causing adaptive changes in neurones localised in these brain areas.
Article
Selective serotonin-reuptake inhibitors (SSRIs), including fluoxetine, sertraline, paroxetine, fluvoxamine, and citalopram, represent an important advance in the pharmacotherapy of mood and other disorders. They are chemically unrelated to tricyclic, heterocyclic, and other first-generation antidepressants. SSRIs are the treatment of choice for many indications, including major depression, dysthymia, panic disorder, obsessive-compulsive disorder, eating disorders, and premenstrual dysphoric disorder, because of their efficacy, good side-effect profile, tolerability, and safety in overdose, as well as patient compliance. A review of the literature was conducted using Medline and the terms "SSRIs," "fluoxetine," "sertraline," "paroxetine," "fluvoxamine," and "citalopram." Articles were limited to those published in English within the last 15 years. The search revealed that indications for antidepressants include unipolar depression, dysthymia, bipolar depression, treatment-resistant depression, depression in the medically ill, panic disorder, obsessive-compulsive disorder, eating disorders, social phobia, and premenstrual dysphoric disorder. One SSRI, fluoxetine, has demonstrated safety in pregnancy. Side effects of SSRIs include gastrointestinal disturbances, headache, sedation, insomnia, activation, weight gain, impaired memory, excessive perspiration, paresthesia, and sexual dysfunction.