No full-text available
To read the full-text of this research,
you can request a copy directly from the authors.
Depression as an Evolutionary Strategy for Defense Against Infection.
Abstract
Recent discoveries relating depression to inflammation and immune function may help to solve an important evolutionary puzzle: If depression carries with it so many negative consequences, including notable costs to survival and reproduction, then why is it common and heritable? What countervailing force or compensatory advantage has allowed susceptibility genes for depression to persist in the population at such high rates? A priori, compensatory advantages in combating infection are a promising candidate, given that infection has been the major cause of mortality throughout human history. Emerging evidence on deeply rooted bidirectional pathways of communication between the nervous and immune systems further supports this notion. Here we present an updated review of the infection-defense hypothesis of depression, which proposes that moods - with their ability to orchestrate a wide array of physical and behavioral responses - have played an adaptive role throughout human history by helping individuals fight existing infections, as well as helping both individuals and their kin avoid new ones. We discuss new evidence that supports several key predictions derived from the hypothesis, and compare it with other major evolutionary theories of depression. Specifically, we discuss how the infection-defense hypothesis helps to explain emerging data on psychoimmunological features of depression, as well as depression's associations with a diverse array of conditions and illnesses - including nutritional deficiencies, seasonal changes, hormonal fluctuations, and chronic disease - that previous evolutionary theories of depression have not accounted for. Finally, we note the potential implications of the hypothesis for the treatment and prevention of depression.
... Owing to selective pressures caused by parasites and pathogens, natural selection has equipped us with an immune system and many other adaptations to combat parasites and pathogens (Schmid-Hempel, 2011), including the behavioural immune system (Schaller and Park, 2011). One of these adaptations is sickness behaviour, which includes somatic, cognitive and behavioural changes that help individuals overcome infection by conserving metabolic resources for the use of the immune system, thus avoiding further infections (Anders et al., 2013). Symptoms of sickness behaviour include anorexia, psychomotor retardation, sleep disturbances, anergia, anhedonia, weakness, malaise, listlessness, hyperalgesia and impaired concentration (Dantzer, 2001). ...
... Symptoms of sickness behaviour include anorexia, psychomotor retardation, sleep disturbances, anergia, anhedonia, weakness, malaise, listlessness, hyperalgesia and impaired concentration (Dantzer, 2001). All of these symptoms seem to be adaptations against infection, helping the immune system function more effectively (Anders et al., 2013). If the infection is contagious, the social withdrawal caused by sickness behaviour may reduce the likelihood that an individual will infect their kina behavioural feature that increases an individual's inclusive fitness (cf. ...
... Gardner and West, 2014). Social withdrawal caused by anhedonia, fatigue, hypersomnia and psychomotor retardation reduces mobility and helps to conserve energy for immune defence (Anders et al., 2013). It is important to note that, in contemporary humans, the elevated low-grade inflammation in the body that is caused by an unhealthy lifestyle can lead to similar psychopathological consequences as infections do. ...
We propose that major depressive disorder is not a unitary disease. Instead, different triggering factors causing periods of low mood can give rise to different and sometimes even opposite symptom patterns. Some of the symptoms of depression are maladaptive; others may be psychobehavioural adaptions to solve the adaptive problem that triggered the depressive episode. It is therefore logical to subtype depressive episodes according to their triggering factors. In evolutionary psychiatry, depressive episodes can be classified into discrete subtypes that are induced by infection, long-term stress, loneliness, traumatic experience, hierarchy conflict, grief, romantic relationship dissolution, post-partum events, season, chemicals, somatic diseases and starvation. In hunter-gatherers and in people who have traditional lifestyles, periods of low mood only rarely turn into episodes that fulfil the diagnostic criteria of major depressive disorder. Modern lifestyles cause low-grade inflammation and an increased susceptibility to chronic stress, which introduce symptoms of sickness behaviour into reactive short-term mood changes. Therefore, features of contemporary environments may prevent the normalisation of mood after adverse life events, resulting in major depressive disorder. An evolutionary approach to depression helps to identify the factors in our environments and lifestyles that contribute to greater susceptibility to this debilitating disorder, which can inform both prevention and treatment of depression. We further propose that the treatment of major depressive disorder should be tailored according to the patient’s depression subtype, focusing on the root causes of the disorder rather than alleviating symptoms with drugs.
... Major depressive disorder is among the leading causes of disability worldwide (Vos et al., 2015), imposing an annual economic burden of $210.5 billion in the US alone (Greenberg et al., 2015). With substantial advances made in evolutionary psychology in recent decades, multiple hypotheses have been proposed to explain the evolutionary origins of major depressive disorder and the possible adaptive functions of its symptoms (Anders et al., 2013;Andrews and Thomson, 2009;Badcock et al., 2017;Nettle, 2004). Although many evolutionary explanations may seem plausible and logical, none of them has received full acceptance in the field. ...
... Due to selective pressures caused by parasites and pathogens, natural selection has equipped humans (at the ultimate level of analysis) with an immune system and many other adaptations to combat parasites and pathogens (Schmid-Hempel, 2011). One of these adaptations is sickness behaviour, which includes somatic, cognitive and behavioural changes that help individuals overcome infection by conserving metabolic resources for the use of the immune system, thus avoiding further infections (Anders et al., 2013). The behavioural patterns of sickness behaviour include anorexia, psychomotor retardation, sleep disturbances, anergy, anhedonia, weakness, malaise, listlessness, hyperalgesia and impaired concentration (Dantzer, 2001). ...
... All symptoms in behavioural changes induced by sickness seem to be adaptations against infection, helping the immune system work more effectively (Anders et al., 2013). If the infection is contagious, the social withdrawal caused by the sickness behaviour may reduce the likelihood that an individual will infect their kin-a behavioural feature which increases an individual's inclusive fitness (cf. ...
Major depressive disorder constitutes one of the leading causes of disability worldwide. However, it is not a unitary disease — it is a heterogeneous syndrome, with patients differing remarkably in symptom profile, pathophysiology and treatment responsiveness. Previous attempts to subtype major depressive disorder have showed limited clinical applicability. We present a classification of major depressive disorder episodes based on the proximate mechanisms that led to the original mood change that caused the depressive episode. We identify discrete depression subtypes that are induced by: 1) infection, 2) long-term stress, 3) loneliness, 4) traumatic experience, 5) hierarchy conflict, 6) grief, 7) romantic rejection, 8) postpartum events, 9) the season, 10) chemicals, 11) somatic diseases and 12) starvation. We further examine the ultimate functions of these subtypes and show that not all types of mood changes that trigger depression are adaptive. Instead, some are clearly maladaptive and some are byproducts of other adaptations. In modern societies, low mood after adverse life events may turn into a pathological depressive state. Modern lifestyle increases susceptibility to inflammatory dysregulation and chronic stress, both of which increase the amount of proinflammatory cytokines in peripheral blood, leading to low mood and sickness behaviour. Proinflammatory cytokines may aggravate the previously adaptive short-term mood changes to a chronic maladaptive depressive state by preventing the normalization of mood after adverse life events. Subtyping depression enables an effective and intelligent long-term treatment of patients in each subtype by treating the underlying causes of depression.
... Studies in mice have shown a peak in sickness behaviour two to six hours after treatment with the potent immunostimulator lipopolysaccharide (LPS), while depression-like behaviour did not peak until 24 h after injection [21]. Examples in humans include chronic hyperexcitability and altered pain perception after trauma-induced cytokine elevations [29], and post-vaccination depression [2]. In mice, spatial memory was impaired seven weeks after systemic inflammation [51], whereas systemic E. coli infection early in life appears to have enduring consequences for brain development [6]. ...
... LPS refers to the corresponding treatment of an individual pig in a pen with lipopolysaccharide. 1 Each pen has three pigs. 2 Within pens with the treatment sequence given in the first column. ...
Poor health is associated with an increased risk of tail biting outbreaks in pigs. We propose that this is because illness changes social dynamics either by changing the behaviour of the sick pig towards its penmates, the behaviour of the healthy penmates towards the sick pig, or both. We tested the effect of immune stimulation (lipopolysaccharide (LPS) injection: O111:B4; 1.5 μg kg-1 IV) on social behaviour in gilts housed in triplets in a cross-over experiment. Each pen was subjected to the control treatment (all three pigs injected with saline) and then LPS treatment (one pig injected with LPS, two injected with saline), or vice versa. LPS injected pigs had a shift in social motivation and performed more tail- and ear- directed behaviour than saline pigs two days after injection. They seemed to fit the description of 'sick and grumpy'. This change was seen about 40 h after the signs of acute illness dissipated and was not accompanied by a similar increase in activity. We discuss possible mechanisms for this behavioural change in light of changes in neurotransmitter levels at three days after LPS injection described in a previous experiment.
... Therefore, it has been suggested that abnormalities in the HPA axis might play a key role in the development and recurrence of depression. Increased cytokine production may contribute to the development of depression directly via activation of the HPA axis or indirectly through cytokine-induced glucocorticoid receptor resistance (Anders et al., 2013). The release of TNF-α and IL-6 increases the production of corticotrophinreleasing hormone, adrenocorticotropic hormone and cortisol by acting directly on hypothalamic and pituitary cells (Dowlati et al., 2010). ...
... The release of TNF-α and IL-6 increases the production of corticotrophinreleasing hormone, adrenocorticotropic hormone and cortisol by acting directly on hypothalamic and pituitary cells (Dowlati et al., 2010). Cytokines might also increase glucocorticoid receptor resistance through several signaling pathways, including activation of the p38 mitogen-activated protein kinase (MAPK) and by stimulating changes in the expression of glucocorticoid receptors (Anders et al., 2013;Pace et al., 2007). The high levels of circulating stress hormones in the CNS might affect the neurotransmitter homeostasis, the neuronal growth factor synthesis and ultimately, disturb the functioning of neuronal circuits of the limbic system (Guloksuz et al., 2014). ...
Major depressive disorder (MDD) is a prevalent and disabling psychiatric disease with rates of non responsiveness to antidepressants ranging from 30–50%. Historically, the monoamine depletion hypothesis has dominated the view on the pathophysiology of depression. However, the lack of responsiveness to antidepressants and treatment resistance suggests that additional mechanisms might play a role. Evidence has shown that a subgroup of depressive patients may have an underlying immune deregulation that could explain the lack of therapeutic benefit from antidepressants.
Stimuli like inflammation and infection can trigger the activation of microglia to release pro-inflammatory cytokines, acting on two main pathways: (1) activation of the hypothalamic–pituitary adrenal axis, generating an imbalance in the serotonergic and noradrenergic circuits; (2) increased activity of the enzyme indoleamine-2,3-dioxygenase, resulting in depletion of serotonin levels and the production of quinolinic acid. If this hypothesis is proven true, the subgroup of MDD patients with increased levels of pro-inflammatory cytokines, mainly IL-6, TNF-α and IL-1β, might benefit from an anti-inflammatory intervention. Here, we discuss the pre clinical and clinical studies that have provided support for treatment with non-steroidal antiinflammatory drugs in depressed patients with inflammatory comorbidities or an elevated immune profile, as well as evidences for anti-inflammatory properties of standard antidepressants.
... Therefore, we hypothesize that the increased risk for social phobia is mediated by a relatively stronger involvement of the immune system. This is in line with models linking infectious diseases with neurodevelopmental disorders-for example, the PANDAS model (8)-or with postinfectious fatigue and depression (28)(29)(30). However, in contrast to the PANDAS model, viral-and not, or not only, bacterial-pathogens are involved in social phobia. ...
... The participants in PsyCoLaus were adults up to 66 years of age. Therefore, the analyses might be biased by telescoping effects such as those found typically regarding onset of substance use (27,28) and display an age-dependent recall-bias regarding symptoms and diseases occurring in childhood and youth. However, no evidence for this was found in the analyses adjusted for age. ...
Objective
Evidence showing that infectious diseases in childhood play an important role in the etiopathogenesis of neurodevelopmental and other mental disorders is growing. The aim of this study was to explore the timing of common childhood diseases in early-onset anxiety disorders.
Materials and methods
We analyzed data from PsyCoLaus, a large Swiss Population Cohort Study (N = 3720). In this study, we regressed overanxious disorder, separation anxiety disorder, social phobia, and specific phobias on the age of onset of several childhood diseases, always adjusting for the other anxiety disorders listed above and for sex.
Results
The timing of viral childhood diseases (chickenpox, measles, and mumps) was consistently delayed in social phobia, notably both in men and women. We found no evidence for a reversed sequence of onset of phobia symptoms before that of the infections included.
Conclusion
Social phobia was the only early anxiety disorder to show an association with a delayed onset of common viral childhood diseases.
... Severe depression and anxiety can increase the risk of bloodstream infection, but their correlation with sepsis cannot be con rmed because of various confounding factors [13]. However, some reports show that depression can serve as a defensive instinct and lead to the storage of metabolic resources and adjustment of the immune system to combat the adverse effects of diseases such as infections on the body [14]. Therefore, reasonably avoiding confounding factors during assessment can more truly re ect the correlation between NEI and sepsis. ...
Background
Negative emotions and insomnia (NEI) are associated with changes in inflammatory factors, which play a role in sepsis.
Methods
We performed Mendelian randomisation (MR) analysis of genome-wide association study (GWAS) data of NEI and sepsis to investigate the causal effect of NEI on sepsis. We employed linkage disequilibrium score regression (LDSC) to calculate the genetic correlation between NEI and sepsis. Inverse variance weighting (IVW) was primarily used for investigating causality, while the weighted median and MR-Egger methods ensured the reliability of the findings. To assess heterogeneity, we employed RadialMR and Cochran’s Q test, and we used MR-Egger regression and Mendelian randomisation pleiotropy residual sum and outlier analyses to evaluate the bias of gene polymorphism. Mendelian mediation analysis was conducted to quantify the intermediate effect of inflammatory factors in mediating the relationship between NEI and sepsis, including the percentage of this mediating effect.
Results
LDSC analysis revealed a genetic correlation between NEI and sepsis. Two-sample MR analysis revealed a causal relationship between NEI and sepsis (odds ratio = 1.21, 95% confidence interval: 1.08–1.36, p = 1.07×10− 3), with no significant heterogeneity and pleiotropy bias. Mendelian mediation analysis revealed an intermediate effect of NEI on sepsis mediated by chitinase 3-like 1 (CHI3L1) (0.12, 10.31%).
Conclusions
Our findings prove the causal relationship between NEI and sepsis. We identified CHI3L1 as a potential mediator, offering insight into the pathogenesis of sepsis.
... However, Dantzer et al. [7] and McCusker and Kelle [8] state that it is now known that the sickness behavior is part of a complex motivational mechanism by which the body reorganizes its priorities to combat the infection by making the environment inhospitable to pathogens. Anders et al. [9] further explain that this sickness behavior is believed to be an adaptive process during infections by which the increase in body temperature and the aforementioned symptoms lead to a saving energy state which slows down the infecting organisms' replicating process and enhances the response of the immune system. ...
During a bacterial infection, individuals may present with behavioral changes referred to as sickness behavior, which has been suggested is induced by the inflammatory markers that are released because of the infective immunological challenge. However, few studies have explored this multidimensional phenomenon in naturally occurring conditions. A longitudinal observational study was conducted to explore the role of inflammatory cytokines in mediating the sickness behavior during a bacterial infection. There were 13, 11 and 37 participants in the infection, hospital control and healthy groups, respectively. They were all followed up for 6 weeks and their inflammatory markers were quantified throughout those weeks. Cognitive function and depressive state were assessed by means of the Mini-Mental State Examination (MMSE) and Cornell Scale for Depression in Dementia (CSDD). Reductions in proinflammatory markers C-Reactive protein (CRP), interleukin – 6 (IL6) and tumor necrosis factor-α (TNFα) and increments in anti-inflammatory markers (interleukin – 4 (IL4)) were associated with an improvement in CSDD and MSEE in patients recovering from a bacterial infection. The correlation between inflammatory makers and CSDD was statistically significant for the CRP (r = 0.535, p = 0.001), the IL6 (r = 0.499, p < 0.001), the TNFα (r = 0.235, p = 0.007) and the IL4 (r = −0.321, p = 0.018). Inflammatory cytokines may mediate sickness behavior during acute illness. These results may enhance the understanding of the pathophysiology and potential treatment strategies to palliate this sickness behavior.
... A substantial body of research has demonstrated the complex incentives of depression from the epigenetic mechanism (Nestler, 2014;Sullivan et al., 2000) to the evolutionary conservation (Anders et al., 2013) perspective. Whereas preventing depression via exercise as a recent study has shown that a small amount of physical activity was associated with a reduced risk of depression (Meyer et al., 2022). ...
... While women living in crowded homes were more likely to be depressed, men exposed to high-density environment report higher levels of withdrawal (Regoeczi, 2008). Several social and biological explanations could explain the stronger association of household crowding with depression in women, such as greater dependence of women on social structures and resources closely related to provision of security (Randolph and Nesse, 2000) or their stronger inflammatory response to social and biological threats (Anders et al., 2013). ...
Aims:
We aimed to investigate the association of household crowding in childhood with trajectories of depressive symptoms in middle-aged and older adults.
Methods:
We studied 47,010 participants (56 % women, 63 years at baseline) from SHARE. Using multinomial logistic regression, we estimated odds ratio (OR) with 95 % confidence interval (CI) for the association of household crowding in childhood (number of household members/number of rooms at the age of 10) with trajectories of depressive symptoms (EURO-D scale), which were generated with growth mixture modeling. We adjusted for resources in childhood, sociodemographic and health-related characteristics in mid-life and older age and tested effect modification by sex.
Results:
We identified four trajectories of depressive symptoms: constantly low (n = 33,969), decreasing (n = 5595), increasing (n = 5574) and constantly high (n = 1872). When compared to the those with constantly low depressive symptoms and adjusting for all covariates, household crowding in childhood was associated with greater odds of constantly high (OR 1.12; 95 % CI 1.08-1.17), decreasing (OR 1.11; 95 % CI 1.07-1.15) and increasing (OR 1.09; 95 % CI 1.06-1.13) depressive symptoms. The associations were stronger in women than in men.
Conclusions:
Prevention of household crowding in childhood may ameliorate the development of constant as well as transient depressive symptoms during ageing. The effect can be stronger in women than in men.
... GD is a common autoimmune disease in which excessive production of stimulatory autoantibodies disrupts critical physiological processes inside and outside the thyroid gland in GD, resulting in cellular and humoral immune disorders (26). Earlier studies have demonstrated the relationship between depression and immune disorders, with a focus on the role of inflammation and proinflammatory cytokines (27). A more recent study by Fam et al. observed significantly higher TSH receptor antibodies (TRAbs) concentration in depressed patients than in healthy controls, which suggested that autoimmunity responses in GD may exert neuropsychiatric effects, which increase susceptibility to depression (28). ...
Graves’ disease (GD) is characterized by diffuse enlargement and overactivity of the thyroid gland, which may be accompanied by other physical symptoms. Among them, depression can dramatically damage patients’ quality of life, yet its prevalence in GD has not received adequate attention. Some studies have established a strong correlation between GD and increased risk of depression, though the data from current study remains limited. The summary of mechanistic insights regarding GD and depression has underpinned possible pathways by which GD contributes to depression. In this review, we first summarized the clinical evidence that supported the increased prevalence of depression by GD. We then concentrated on the mechanistic findings related to the acceleration of depression in the context of GD, as mounting evidence has indicated that GD promotes the development of depression through various mechanisms, including triggering autoimmune responses, inducing hormonal disorders, and influencing the thyroid-gut-microbiome-brain axis. Finally, we briefly presented potential therapeutic approaches to decreasing the risk of depression among patients with GD.
... Until Hart (1988) pinpointed their significance, they were seen as the somewhat debilitating outcome of the pathological process. In the presence of fever, these behavioral symptoms of sickness are now recognized as being a normal response to infection mediated by the brain, in a highly organized strategy known as the "host defense hypothesis" (Anders, Tanaka, & Kinney, 2013;Chang, Szegedi, O'Connor, Dantzer, & Kelley, 2009;Dantzer, 2006;Hart, 1988;Raison & Miller, 2011). Critically, inflammatory processes that trigger sickness behaviors occur in both cancer and depressive illness (Tobias, Rosenfeld, Pessin, & Breitbart, 2015). ...
Patients with cancer are at greater risk of developing depression in comparison to the general population and this is associated with serious adverse effects, such as poorer quality of life, worse prognosis and higher mortality. Although the relationship between depression and cancer is now well established, a common underlying patho-physiological mechanism between the two conditions is yet to be elucidated. Existing theories of depression, based on monoamine neurotransmitter system dysfunction, are insufficient as explanations of the disorder. Recent advances have implicated neuroinflammatory mechanisms in the etiology of depression and it has been demonstrated that inflammation at a peripheral level may be mirrored centrally in astrocytes and microglia serving to promote chronic levels of inflammation in the brain.
Three major routes to depression in cancer, in which proinflammatory mediators are implicated, seem likely. Activation of the kynurenine pathway, involving cytokines, increased tryptophan catabolism, resulting in diminished levels of serotonin, which is widely acknowledged as being the hallmark of depression. It also results in neurotoxic effects on brain regions thought to be involved in the evolution of major depression. Proinflammatory mediators also play a crucial role in impairing regulatory glucocorticoid mediated feedback of the hypothalamic-pituitary-adrenal axis, which is activated by stress and considered to be involved in both depression and cancer. The third route is via the glutamatergic pathway, whereby glutamate excitotoxicity may lead to depression associated with cancer. A better understanding of the mechanisms underlying these dysregulated and newly emerging pathways may provide a rationale for therapeutic targeting, serving to improve the care of cancer patients.
... Tryptophan is an important precursor of serotonin synthesis and bacterial growth. Inflammatory cytokines activate indoleamine 2,3-dioxygenase (IDO) to convert tryptophan to kynuric acid (KYN), which in turn results in a significant drop in tryptophan levels and a corresponding drop in serotonin release, contributing to depression tendencies (Anders, Tanaka, and Kinney 2013). Meanwhile, it also reduces the production of growth factors such as brain-derived neurotrophic factor, leading to disruption of neurogenesis and even disruption of synaptic plasticity (Dantzer et al. 2008). ...
Depression is a global public health issue with high morbidity and mortality, which tends to cause fatigue, inability to concentrate, insomnia, and loss of appetite, especially represented by major depressive disorder (MDD). Pathologically, depression is associated with hyperactivity of hypothalamic–pituitaryadrenal (HPA) axis, inflammation, loss of monoaminergic system, and disturbance of gut microbiota. Epidemiological studies have
shown that regular tea drinking can reduce the risk of depression. Tea bioactive compounds (L-theanine, catechin, tea pigment and GABA) can regulate depression by inhibiting hyperactive HPA axis, reducing the inflammatory response, restoring the monoaminergic system, inhibiting monoamine oxidase levels, increasing the enrichment of intestinal flora and promoting microbial-gut-brain axis activity. This review discusses the composition, structure, bioavailability and safety of bioactive components from tea, and focuses on exploring the possible pathways of tea bioactive compounds in the regulation of depression. In addition, the low bioavailability of natural bioactive compounds from tea limits the efficacy on depression. Emerging technologies (such as
metabolomics, proteomics, and genomics) and nano-encapsulation can be utilized to improve the stability and bioavailability of tea active ingredients, and reduce the potential biotoxicity. The review provides a theoretical basis of utilization of tea active compounds for formulating the prevention and treatment of depression.
... From a clinical point of view, SB resembles states of depression. This view is corroborated by immunological theories, suggesting that aberrant priming of the immune system could be part of an explanation for the "depression pandemic" (Anders et al., 2013;Raison and Miller, 2017;Rook et al., 2017). Moreover, one of the first clinical observations likening immunologically induced SB with depression was that people receiving interferon beta often developed SB or even clinical depression (Felger et al., 2016). ...
In recent decades, psychiatry and the neurosciences have made little progress in terms of preventing, diagnosing, classifying, or treating mental disorders. Here we argue that the dilemma of psychiatry and the neurosciences is, in part, based on fundamental misconceptions about the human mind, including misdirected nature-nurture debates, the lack of definitional concepts of “normalcy,” distinguishing defense from defect, disregarding life history theory, evolutionarily uninformed genetic and epigenetic research, the “disconnection” of the brain from the rest of the body, and lack of attention to actual behavior in real-world interactions. All these conceptual difficulties could potentially benefit from an approach that uses evolutionary theory to improve the understanding of causal mechanisms, gene-environment interaction, individual differences in behavioral ecology, interaction between the gut (and other organs) and the brain, as well as cross-cultural and across-species comparison. To foster this development would require reform of the curricula of medical schools.
... Though pandemic-specific tools have been developed and tested in surveys, their validity and reliability remain debatable [11]. At a higher conceptual level, it is also worth noting that negative affective states, such as depression and anxiety, can be understood as defensive responses to the threat of infection or contagion [12][13][14]. Seen in this light, simple quantitative measures of depression or anxiety may not adequately distinguish between "adaptive" and "pathological" responses. ...
Background
The uncertainty and socioeconomic disruption caused by the COVID-19 pandemic have been frequently associated with negative affective responses, particularly depression and anxiety. People from countries across the globe have frequently resorted to religious coping to deal with these emotions. However, there are conflicting results in the literature about the impact of prior patterns of religious belief and practice on emotional responses to COVID-19.
Methods
In this cross-sectional, country-level study, the association between pre-pandemic measures of religious affiliation and practice, obtained from prior survey data and self-reported symptoms of depression, anxiety, and stress across 29 countries from a recent multi-country study, were examined while correcting for potential confounders.
Results
There was a trend towards a positive association between pre-pandemic religious belief and practice and anxiety in response to the pandemic (r = .36, p = .057), but this was not significant on multivariate analysis (β = .08, p = .691). Cultural individualism and urbanization were negatively associated with anxiety during the pandemic. There was also preliminary evidence of a non-linear relationship between religiosity and pandemic-related anxiety.
Conclusions
The relationship between religiosity and mental health during the COVID-19 pandemic is unlikely to be a direct one and can be influenced by demographic and cultural factors.
... (A) Specific forms of psychological distress, particularly symptoms resembling those of depression (Anders et al., 2013) and obsessive-compulsive disorder (Rajkumar, 2020a), play a specific role in protecting individuals and communities from the threat of infectious diseases. In this model, these forms of psychological distress are part of the "behavioral immune system" that has evolved to protect the human race from the survival threat posed by pathogens (Shakhar, 2019). ...
The COVID-19 pandemic has had a widespread effect on the thoughts, emotions and behavior of millions of people all around the world. In this context, a large body of scientific literature examining the mental health impact of this global crisis has emerged. The majority of these studies have framed this impact in terms of pre-defined categories derived from psychiatric nosology, such as anxiety disorders, depression or post-traumatic stress disorder. These constructs often fail to capture the complexity of the actual experiences of the individuals being studied; more specifically, they describe these experiences exclusively in terms of disease, while neglecting their potentially adaptive or “salutogenic” aspects. Similarly, discussion of psychological assistance for these individuals has largely been confined to a reiteration of “evidence-based” psychological or pharmacological techniques which can be delivered using remote access technology. In the context of the COVID-19 pandemic, these approaches are likely to be of mixed efficacy. Conversely, “negative emotions” or distressing psychological experiences may actually be functional in the setting of a disaster or crisis, serving to minimize harm, maximize social coherence and compliance, and facilitate adherence to safety measures. The limitations of the “conventional” approach are, to a certain degree, inherent to the prevailing medical model of mental health. Beyond these considerations lies the concept of “salutogenesis,” a term which refers to the innate capacity of individuals to create and maintain health and well-being in the face of adversity. Using principles derived from the second wave of positive psychology (PP2.0), particularly its emphasis on the totality of human experience and the possibility of deriving meaning and character growth from suffering, this paper conceptually analyses the relevant aspects of salutogenesis and PP2.0, and proposes an alternate approach for addressing mental health concerns during the COVID-19 pandemic. Such an approach, while acknowledging the utility of the conventional medical-psychotherapeutic model in specific cases, reduces the risk of medicalizing human experience, and provides individuals and communities with opportunities for growth and adaptation. The benefits of this proposal could potentially extend far beyond the current crisis, offering an opportunity for the field of psychiatry and mental health research to move away from a purely “disease-centered” model.
... The human cooperative breeding hypothesis proposes that women are more dependent than men on social structures and resources closely related to providing security and protection for childrearing; and associated adversities and lack of circumstantial control are suggested as leading causes of depression [33]. In addition, the infection-defense hypothesis [34] suggests that the behavioral responses triggered by both infectious diseases and depression share similar underlying mechanisms. These include increased serum cytokine levels, which interact with sex hormones and other psycho-socio-environmental factors. ...
PurposeWe aimed to study sex differences in the association of childhood socioeconomic position (SEP) with later-life depressive symptoms, the mediating effect of education and explore regional differences across Europe.Methods
The study included 58,851 participants (55% women, mean age 65 years) from the multicentre, population-based Survey on Health, Ageing and Retirement in Europe. Interviews were conducted in six waves and included measurements of childhood SEP (household characteristics at the age of 10) and depressive symptoms (EURO-D scale). Linear regression was used to study the association of childhood SEP with depressive symptoms, adjusting for covariates, and structural equation modelling assessed the mediating effect of education.ResultsIn the fully adjusted model, higher childhood SEP was associated with lower depressive symptoms with a greater magnitude in women (B = − 0.07; 95% CI − 0.08, − 0.05) than in men (B = − 0.02; 95% CI − 0.03, − 0.00). Relative to men, childhood SEP had 3 times greater direct effect on depressive symptoms in women, and education had 3.7 times stronger mediating effect against childhood SEP. These associations and the sex differences were particularly pronounced in Southern, Central and Eastern Europe.Conclusion
Growing up in poor socioeconomic conditions is a stronger risk factor for the development of depressive symptoms for women than for men. Education may have a stronger preventive potential for women in reducing the adverse effects of childhood socioeconomic hardship. Central and Eastern European populations experience disproportionately higher risk of later-life depression due to lower SEP and greater sex differences.
... As such, it reflects an adaptive evolutionarily conserved defense reaction to conserve energy and reduce the risk of being attacked in times of enhanced vulnerability [9]. Some researchers have therefore highlighted the similarities between SB and clinical depression, including immunological theories suggesting that aberrant priming of the immune system could be part of an explanation for the 'depression pandemic', because the divergent exposure to certain pathogens in modern environments compared to ancestral ones has created an evolutionary 'mismatch' [10][11][12]. Similar to people activating their BIS, individuals displaying SB avoid contact with strangers (for different reasons, however), but seek proximity to close kin, even though this may impose costs to inclusive fitness, because it increases the risk of infection of genetically related individuals [3]. ...
The coronavirus pandemic constitutes a global challenge to society and medicine. Here, we review evolutionary insights that are relevant for the understanding of how people respond to the pandemic and what to expect in the aftermath of the crisis. Specifically, we argue that the behavioral immune system (BIS) and sickness behavior (SB) comprise two adaptive responses to impending and actual infection, respectively, and that individuals activating their BIS differ from those showing SB in important ways that may have implications for the prevention and treatment of COVID-19. Moreover, we reframe some of the behavioral health issues associated with the pandemic in a game-theoretical scenario, illustrating the difficulties that arise when public health is treated as a ‘public good’.
Lay summary: The coronavirus pandemic constitutes a global challenge to society and medicine. In this article, we employ evolutionary theory to improve our understanding of how people respond to the pandemic. Specifically, we argue that human behavior is guided by ancient mechanisms involving either the avoidance of infection or defense against attacks in times of enhanced vulnerability. Moreover, we reframe some of the behavioral health issues associated with the pandemic in a game-theoretical scenario. This helps understand why most people comply with rules of social distancing, while a minority fails to do so for very different reasons. The evolutionary perspective also allows making some predictions for the course of the pandemic.
... This thus influences various neuronal events related to emotions including glia-neuron communication, neurotransmission, and synaptic pruning (32,33). This finding leads to an interesting hypothesis that emotions can act as an "infection defense" to various environmental pathogens (34). ...
Emerging evidence demonstrates the critical role of the immune response in the mechanisms relating to mood disorders, such as major depression (MDD) and bipolar disorder (BD). This has cast a spotlight on a specialized branch committed to the research of dynamics of the fine interaction between emotion (or affection) and immune response, which has been termed as "affective immunology." Inflammatory cytokines and gut microbiota are actively involved in affective immunology. Furthermore, abnormalities of the astrocytes and microglia have been observed in mood disorders from both postmortem and molecular imaging studies; however, the underlying mechanisms remain elusive. Notably, the crosstalk between astrocyte and microglia acts as a mutual and pivotal intermediary factor modulating the immune response posed by inflammatory cytokines and gut microbiota. In this study, we propose the "altered astrocyte-microglia crosstalk (AAMC)" hypothesis which suggests that the astrocyte-microglia crosstalk regulates emotional alteration through mediating immune response, and thus, contributing to the development of mood disorders.
... This thus influences various neuronal events related to emotions including glia-neuron communication, neurotransmission, and synaptic pruning (32,33). This finding leads to an interesting hypothesis that emotions can act as an "infection defense" to various environmental pathogens (34). ...
Emerging evidence demonstrates the critical role of the immune response in the mechanisms relating to mood disorders, such as major depression (MDD) and bipolar disorder (BD). This has cast a spotlight on a specialized branch committed to the research of dynamics of the fine interaction between emotion (or affection) and immune response, which has been termed as “affective immunology.” Inflammatory cytokines and gut microbiota are actively involved in affective immunology. Furthermore, abnormalities of the astrocytes and microglia have been observed in mood disorders from both postmortem and molecular imaging studies; however, the underlying mechanisms remain elusive. Notably, the crosstalk between astrocyte and microglia acts as a mutual and pivotal intermediary factor modulating the immune response posed by inflammatory cytokines and gut microbiota. In this study, we propose the “altered astrocyte-microglia crosstalk (AAMC)” hypothesis which suggests that the astrocyte-microglia crosstalk regulates emotional alteration through mediating immune response, and thus, contributing to the development of mood disorders.
... An alternative category of explanation invokes infection. Depression has been linked to innate immunological responses to infection and therefore could be interpreted as part of a mechanism that may facilitate recovery, for example, by encouraging rest, or may prevent additional infections in the depressed individual or kin (Anders et al., 2013;Kinney and Tanaka 2009;Nesse 2019;Raison and Miller 2013b). As is the case with adaptive explanations of short-term depression that rely on goal-shifting, these hypotheses of infection-induced depression do not account well for prolonged, incapacitating depression. ...
The evolutionary basis for clinical depression is not well understood. A growing body of literature that is not based on evolutionary logic links inflammation to depression. Integration of these findings with an evolutionary framework for depression, however, needs to address the reasons why the body's inflammatory response would be regulated so poorly that it would result in incapacitating depression. Pathogen induction of inflammation offers an explanation, but the extent to which the association between inflammation and depression can be attributed to general inflammation as opposed to particular effects of pro-inflammatory pathogens remains unclear. This paper reports a study of sexually transmitted pathogens, which addresses this issue. Although several sexually transmitted pathogens were associated with depression according to bivariate tests, only Chlamydia trachomatis and Trichomonas vaginalis were significantly associated with depression by a multivariate analysis that accounted for correlations among the pathogens. This finding is consistent with the hypothesis that infection may contribute to depression through induction of tryptophan restriction, and a consequent depletion of serotonin. It reinforces the idea that some depression may be caused by specific pathogens in specific evolutionary arms races with their human host.
... Numerous, closely related evolutionary theories have attempted to explain the association of inflammation and depression. Kinney and Tanaka (2009) proposed that depressive symptoms conserve energy to combat infection, discourage activities that promote transmission of infection, signal others to avoid contact, reduce the risk of conflict and therefore injuries, and reduce appetite to avoid exposure to pathogens (see also Anders, Tanaka, & Kinney, 2013). Raison and Miller (2017) propose similar ideas, adding that, ancestrally, social conflicts were good predictors of physical injury, and therefore preemptively activated the immune system (see also Raison, Capuron, & Miller, 2006;Raison & Miller, 2013). ...
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.
... Inflammation is triggered by the release of inflammatory cytokines such as interleukin (IL)-1β IL-2, IL-6, tumor necrosis factor alpha (TNF-α), and C-reactive protein (CRP), which all have been found to be up-regulated in patients with depression [84,85]. The relationship between inflammation and depression can be traced in part back to an adaptive trait called "sickness behavior", in which humans who are attempting to fight infection reduce participation in activities such as exploration or seeking mates, which compete with an active immune system for energy stores [86]. For an acute infection during evolutionary times, behaviors of anhedonia, fatigue, and internal focus allowed one to allocate bodily resources to the immune system, which can consume 30% of basal metabolic rate during an immune response. ...
This article is a comprehensive review of the literature pertaining to the antidepressant effects and mechanisms of regular tea consumption. Meta-data supplemented with recent observational studies were first analyzed to assess the association between tea consumption and depression risk. The literature reported risk ratios (RR) were 0.69 with 95% confidence intervals of 0.62–0.77. Next, we thoroughly reviewed human trials, mouse models, and in vitro experiments to determine the predominant mechanisms underlying the observed linear relationship between tea consumption and reduced risk of depression. Current theories on the neurobiology of depression were utilized to map tea-mediated mechanisms of antidepressant activity onto an integrated framework of depression pathology. The major nodes within the network framework of depression included hypothalamic-pituitary-adrenal (HPA) axis hyperactivity, inflammation, weakened monoaminergic systems, reduced neurogenesis/neuroplasticity, and poor microbiome diversity affecting the gut–brain axis. We detailed how each node has subsystems within them, including signaling pathways, specific target proteins, or transporters that interface with compounds in tea, mediating their antidepressant effects. A major pathway was found to be the ERK/CREB/BDNF signaling pathway, up-regulated by a number of compounds in tea including teasaponin, L-theanine, EGCG and combinations of tea catechins and their metabolites. Black tea theaflavins and EGCG are potent anti-inflammatory agents via down-regulation of NF-κB signaling. Multiple compounds in tea are effective modulators of dopaminergic activity and the gut–brain axis. Taken together, our findings show that constituents found in all major tea types, predominantly L-theanine, polyphenols and polyphenol metabolites, are capable of functioning through multiple pathways simultaneously to collectively reduce the risk of depression.
... Evolutionary approaches to health and medicine (Bevolutionary^or BDarwinian^medicine) concern themselves with understanding the evolutionary forces that might explain the presence of pathologies across our species (Nesse 2006). Within this framework, several hypotheses have been proposed to explain our vulnerability to somatic and psychiatric disease, including mismatches between our current environments and the conditions in which our species evolved, imperfect adaptations, and the adaptive benefit of some Bdiseases. s an example of this latter category, depression has been theorized as: an adaptive trait that prevents or minimizes wasting energy and time on potentially risky activities or lost causes (Klinger 1975;Andrews and Thompson 2009); a signal of distress that elicits assistance and care from others (Hagen 2003;Steinkopf 2017); and part of an evolved behavioral defense against infectious disease that encourages social withdrawal thereby decreasing transmission risk (Raison and Miller 2013;Anders et al. 2013). In each case, depression is beneficial in short bouts but pathological if it persists longer than is necessary to readjust motivational priorities, gain assistance, or avoid infection. ...
Rationale
As a species, humans are vulnerable to numerous mental disorders, including depression and schizophrenia. This susceptibility may be due to the evolution of our large, complex brains, or perhaps because these illnesses counterintuitively confer some adaptive advantage. Additionally, cultural and biological factors may contribute to susceptibility and variation in mental illness experience and expression. Taking a holistic perspective could strengthen our understanding of these illnesses in diverse cultural contexts.
Objectives
This paper reviews some of these potential factors and contextualizes mental disorders within a biocultural framework.
Results
There is growing evidence that suggests cultural norms may influence inflammation, neurotransmitters, and neurobiology, as well as the illness experience. Specific examples include variation in schizophrenia delusions between countries, differences in links between inflammation and emotion between the United States and Japan, and differences in brain activity between Caucasian and Asian participants indicating that cultural values may moderate cognitive processes related to social cognition and interoception.
Conclusions
Research agendas that are grounded in an appreciation of biocultural diversity as it relates to psychiatric illness represent key areas for truly interdisciplinary research that can result in culturally sensitive treatments and highlight possible biological variation affecting medical treatment.
... 57 A different theory is that depression is a defense mechanism that the body uses to promote behavior that protects a depressed person from infectious diseases. 58 for at least two reasons. As mentioned above, one reason is that they are physiological processes that occur in animals. ...
The problem of animal suffering considers whether God would allow millions of years of animal pain, disease, and death. Philosophers who debate this issue often assume that pain and suffering are evils a loving God would not allow without good reason. Moreover, a considerable amount of the debate regarding the problem of animal suffering involves whether animals are capable of experiencing pain and suffering. But this raises the question of whether pain and suffering are intrinsically evil. In this essay I explore the nature of pain and suffering from a Thomistic perspective. First I briefly explain how the intrinsic values of pain and suffering are crucial regarding the problem of evil and the problem of animal suffering in particular. Next I explain the Thomistic concepts of pain and suffering and show that they do not contradict their contemporary philosophical and scientific counterparts. Afterward I determine whether pain and suffering are intrinsically evil experiences that an all-good God should refrain from causing. I conclude that pain and suffering are not intrinsically evil and that the problem of animal suffering is not a problem in addition to the problem of natural evil.
... Most investigators agree that a likely explanation is that some cases of depression are sickness behavior activated inappropriately, but we do not understand how or why this occurs. One theory is that gene variants supporting an immune system capable of surviving childhood infections are evolutionarily selected, and that these same alleles also increase the risk of depression later in life [33]. Another common model attributes the inappropriate activation of sickness behavior to the failure of the immune system to "learn" accurately, so that in some cases of depression, there is a false immune response, similar to autoimmunity. ...
Purpose
To update clinicians on the field of psychoneuroimmunology with respect to depression.
Recent findings
A significant subset of patients with depression may have illness to which dysfunction of the immune system, typically viewed as inflammation, makes a significant contribution. Normal sickness behavior may sometimes manifest abnormally as mood episodes. Early evidence suggests that interventions that reduce inflammation may improve symptoms in these patients and that they may also respond differently to standard pharmacotherapy.
Summary
Treatment of patients with depression should consider inflammatory status, as part of medical and psychiatric health. Recommendations for healthy diet and exercise are important for all patients but may be more important for patients who have clinical evidence of inflammation. Methods of identifying patients in the inflammatory subgroup and treating them with therapy targeted specifically at the immune system are still experimental but likely to impact care for depression in the future.
... drugs have anti-inflammatory effects (Maes et al., 2009), that depressive symptoms positively correlate with inflammatory markers and pathogen load in a high pathogen-bearing population (Stieglitz et al., 2015), and inflammation precedes rather than follows emotional distress (Das, 2016). Such findings have led to the suggestion that depressive symptoms are an evolutionary adaptation to both prevent and fight infection (Anders et al., 2013;Kinney and Tanaka, 2009;Slavich et al., 2010a;Raison and Miller, 2013;Slavich and Irwin, 2014). If inflammation is predictive of, or causal to, depression then the possibility is open to identify novel risk factors on the basis of their known role in inflammatory immune activation. ...
Rationale:
A growing body of literature links both depressive symptoms generally, and those specifically in the postnatal period, with an inflammatory immune response. Evolutionary medical approaches, such as the Pathogen Host Defence Theory of Depression (PATHOS-D), have likened depression to sickness behaviour in other mammals, and propose that the characteristics associated with depression are protective when an individual is experiencing pathogenic threat. Many known risk factors for depressive symptoms are associated with activation of inflammatory pathways, opening up the potential for identifying novel risk factors based on their inflammation causing effects.
Objective:
Both the gestation of male foetuses and the experience of birth complications have documented associations with increased inflammation, yet their relationships with postnatal depression (PND) are currently unclear.
Method:
Here we use the complete reproductive histories of 296 women from contemporary, low fertility populations gathered by retrospective survey to assess whether the odds of PND increased when mothers gave birth to male infants or experienced birth complications, using generalised estimating equation models controlling for individual effects of the mother and other known PND risk factors.
Results:
We found the odds of PND increased by 71-79% when male infants were born compared to female infants. The occurrence of birth complications increased the odds of PND by 174% compared to having no complications. Testing for interaction effects found that, while always at increased risk of PND, women with a tendency towards symptoms of depression, anxiety, and stress at other points in the life course had reduced odds of PND when experiencing birth complications, suggesting such women may elicit greater support.
Conclusions:
These results highlight two novel PND risk factors, male infants and birth complications, which can be easily assessed by health professionals.
... Similar evolutionary logic has been applied to PNI as well. Chronic inflammatory diseases have been attributed to a "mismatch" between ancestral human states and current lifestyles [9]; depression has been put forth as an evolved mechanism to limit contact with, and improve recovery from, infectious disease [10]; stress reactions, via glucocorticoids, drive leukocyte migration to peripheral tissues in anticipation of wounding and subsequent pathogen contact [11]. What is often missing from this adaptationist approach is a consideration of shortterm, variable ecological contexts. ...
There is considerable research interest overlap between biological anthropology and psychoneuroimmunology (PNI), particularly given recent anthropological interest in endocrine and immune system functioning over the life span and in different environmental contexts. In this chapter, I argue that conducting research on non-WEIRD populations and applying an anthropological, evolutionary approach to PNI can greatly strengthen our understanding of immune-endocrine-behavior connections. This chapter reviews population-level variation in the human immune and endocrine systems, as well as genetic and environmental contributions to this variation. The effects of culture on shaping health outcomes and stress responses are also considered. Finally, this chapter discusses some noninvasive sampling methodologies appropriate to field research and alternatives to laboratory-based research designs. By confronting variable social and environmental contexts, PNI can greatly expand on its existing contributions to the treatment and understanding of depression, mood disorders, stress, and other aspects of health and well-being.
... The immune developmental hypothesis for MDD has been supported by several lines of evidence including increased serum levels of inflammatory markers (Liu et al. 2012;Howren et al. 2009;Dowlati et al. 2010), emergence of depressive symptoms following inflammation-based treatments (Capuron et al. 2002;Dantzer et al. 2008;Raison et al. 2013), and the link between inflammatory activation and abnormal functions in the prefrontal cortex of MDD patients (Setiawan et al. 2015). Recently, genetic studies have further highlighted the role of the immune system by detecting the susceptible genes and chromosomal regions as the risk loci of MDD (Anders et al. 2013;Goodyer, 2015). ...
Background
The pathophysiology of cognitive impairment in patients with the major depressive disorder (MDD) may involve neuroinflammation mediated by cytokines.
Objective
The aim of this study was to examine the serum interleukin-6 (IL-6) levels, sustained attention, and their association in patients with MDD.
Methods
Thirty patients with MDD and 30 healthy controls were enrolled in this case-control study. Sustained attention was measured using the Rapid Visual Information Processing (RVP) task in the Cambridge Neuropsychological Tests Automated Battery. The serum IL-6 levels of all subjects were assessed by sandwich enzyme-linked immunosorbent assays.
Results
There were significant differences in the log 10 RVP total hits, log 10 RVP total misses, and log 10 RVP mean latency between patients with MDD and healthy controls ( F = 6.04, p = 0.017; F = 19.77, p < 0.0001; F = 14.42, p < 0.0001, respectively). The serum levels of Log 10 IL-6 were significantly higher in patients with MDD than in healthy controls ( F = 192.27, p < 0.0001). The log 10 IL-6 levels were also positively correlated with the log 10 RVP mean latency in patients with MDD ( r = 0.45, p = 0.013). A further stepwise multivariate regression analysis indicated that the log 10 IL-6 levels were significantly associated with the log 10 RVP mean latency in patients with MDD ( β = 0.31, t = 2.41, p = 0.025).
Conclusions
Our data suggested that increased IL-6 levels were associated with the psychopathology of MDD, and that abnormal IL-6 levels were implicated in the impairment of sustained attention in patients with MDD.
... Genes impacting both body adiposity and advantageous behavioural traits, however, may be subjected to more complex patterns of selection than classic directional selection. To illustrate, although some argue that depression is an adaptive trait (176,177), data show increased risk of mortality among depressive patients (178) and reduced fertility among women experiencing postnatal depression (179). The link between obesity and depression is also controversial (180)(181)(182)(183). Samaan and colleagues (180) report an inverse relationship between the obesity predisposing A variant of the FTO rs9939609 and major depression, with each additional copy of the A variant associated with an 8% reduction in risk of major depression. ...
... This rationale applies not only to major depressive disorder, but also to medicine more generally. For instance, sickness behaviors such as anorexia, psychomotor retardation, sleep disturbances, anergy, anhedonia, weakness, malaise, listlessness, hyperalgesia, and impaired concentration help individuals overcome infection by conserving metabolic resources for the use of the immune system [8,9] . Likewise, if the function of pain is to promote healing by disincentivizing the use of an injured body part [10] , pharmacological reduction of pain may be detrimental to an individual's long-term health. ...
Research in pharmacopsychology has much to benefit from an evolutionary approach to psychopathology. This is because the possible benefits of medication can be properly understood only by analyzing why the symptoms of mental disorders exist in the first place. This rationale applies not only to major depressive disorder, but also to medicine more generally. For instance, sickness behaviors such as anorexia, psychomotor retardation, sleep disturbances, anergy, anhedonia, weakness, malaise, listlessness, hyperalgesia, and impaired concentration help individuals overcome infection by conserving metabolic resources for the use of the immune system. Likewise, if the function of pain is to promote healing by disincentivizing the use of an injured body part, pharmacological reduction of pain may be detrimental to an individual’s long-term health. By conceptualizing sickness behaviors, pain mechanisms, and mental disorders in relation to the problems that they evolved to solve, medical practitioners are in a better position to provide treatment options that are both more intelligent and more effective for ensuring a patient’s long-term well-being.
... Z kolei objawy depresyjne miałyby służyć ograniczeniu wydatków energetycznych w krytycznych sytuacjach (Hagen, 2011) -m.in. w przypadku infekcji, jako element odpowiedzi immunologicznej (Anders et al., 2013;Raison i Miller, 2013); mogłyby też wynikać z teorii przywiązania (pozostawionemu przez matkę młodemu najbezpieczniej jest pozostać w ukryciu, a nie eksplorować otoczenie), utrzymywać hierarchię społeczną (Gilbert, 2006), redukując zarazem agresję międzyosobniczą, zwłaszcza w stosunku do osób o wyższej pozycji społecznej (Hagen, 2011), pomagać w rozwiązywaniu problemów społecznych poprzez ruminacje, sygnalizować potrzebę pomocy lub wręcz wymuszać pomoc (Watson i Andrews, 2002) czy w końcu chronić daną jednostkę przed podejmowaniem działań zmniejszających jej dostosowanie, podobnie jak strach przed bólem powstrzymuje przed częścią ryzykownych zachowań (Wittman, 2014). Istnieją liczne koncepcje ewolucyjne dotyczące objawów depresyjnych, lecz niewielu autorów podejmuje się wytłumaczenia w podobny sposób objawów maniakalnych. ...
Psychiatria ewolucyjna to dziedzina psychiatrii wykorzystująca pojęcia i prawa odkryte przez biologię ewolucyjną do opisu
zaburzeń psychicznych. Niektóre częste zaburzenia psychiczne (psychotyczne, nastroju i lękowe), jako zależne częściowo
od czynników genetycznych, powinny podlegać doborowi naturalnemu, usuwającemu z populacji cechy, które zmniejszają
dostosowanie. Tak się nie dzieje – być może zaburzenia pełnią więc jakąś pozytywną funkcję. Funkcja ta może być zakłócana
przez terapię, pojawia się zatem pytanie o etyczne aspekty leczenia i jego potencjalną szkodliwość. Argumentacja prowadząca do wniosku o szkodliwości leczenia zaburzeń psychicznych jest jednak nieprawidłowa, ponieważ:
1. Obejmuje nieuprawnione przejście od faktów do sądów moralnych, opisane po raz pierwszy przez filozofa Davida
Hume’a (znane jako gilotyna Hume’a lub przepaść między jest a powinien). Współczesna filozofia prezentuje zróżnicowane
poglądy odnośnie do takiego wnioskowania, ale zazwyczaj traktuje się je jako niepewne.
2. Biologia ewolucyjna nie zajmuje się dobrem chorego. Dobór naturalny dotyczy dostosowania – niekoniecznie
dostosowania pacjenta, często chodzi bowiem o dostosowanie samolubnych genów bądź dostosowanie włączne grupy
osobników. Co więcej, nawet dostosowanie dotyczące pacjenta nie musi odpowiadać jego dobru.
Podsumowując, ani biologia ewolucyjna, ani psychiatria ewolucyjna nie mogą stanowić źródła sądów moralnych. Ich rola
polega na dostarczaniu wiedzy o etiologii zaburzeń psychicznych, która to wiedza może się przyczynić do poprawy terapii.
... There are suggestions, however, that disgust processing can extend into the social domain, and that heightened disgust sensitivity might reflect an emotional processing bias that constitutes social and self-related disgust, feelings of social rejection (Rozin et al. 1994), as well as feelings of shame and guilt (Surguladze et al. 2010;Giner-Sorolla & Espinosa, 2011), all of which are highly relevant to depression. Emotional responses to inflammation are also relevant to evolutionary biological theories linking inflammation and depression in which depressive behaviours, regulated by the immune system, play a role in dealing with infection both at the individual level and that of the social group (Anders et al. 2013). ...
Background
Treatment of medical patients with the inflammatory cytokine, interferon- α (IFN- α ), is frequently associated with the development of clinical depressive symptomatology. Several important biological correlates of the effect of IFN- α on mood have been described, but the neuropsychological changes associated with IFN- α treatment are largely unexplored. The aim of the present preliminary study was to assess the effect of IFN- α on measures of emotional processing.
Method
We measured changes in emotional processing over 6–8 weeks in 17 patients receiving IFN- α as part of their treatment for hepatitis C virus infection. Emotional processing tasks included those which have previously been shown to be sensitive to the effects of depression and antidepressant treatment, namely facial expression recognition, emotional categorisation and the dot probe attentional task.
Results
Following IFN- α , patients were more accurate at detecting facial expressions of disgust; they also showed diminished attentional vigilance to happy faces. IFN- α produced the expected increases in scores on depression rating scales, but there was no correlation between these scores and the changes in emotional processing.
Conclusions
Our preliminary findings suggest that IFN- α treatment produces negative biases in emotional processing, and this effect is not simply a consequence of depression. It is possible that increased recognition of disgust may represent a neuropsychological marker of depressive disorders related to inflammation.
... The Inflammation Hypothesis as proposed by Leonard and colleagues postulates that an NTBE is caused by inflammation, whereas a sustained increase in cortisol concentration is believed to be the culprit in the Hypercortisolemia Hypothesis as proposed by Duman et al. (2016) and McEwen et al. (2015). Other biological factors such as oxidative stress, infection, trauma, and impaired angiogenesis may be additional factors contributing toward a toxic brain environment (Atkinson et al., 2008;Behr et al., 2012;Anders et al., 2013;Diniz et al., 2013;Bennett and Thomas, 2014;Canli, 2014;Chen et al., 2014;Chang et al., 2015;Jiménez-Fernández et al., 2015;Réus et al., 2016;Yamada 2016;Lindqvist et al., 2017). Given that there are multiple factors that may cause or contribute toward the development of depression in susceptible individuals, antidepressant drugs targeting only monoamine neurotransmission may not benefit all patients. ...
A significant number of patients with major depression do not respond optimally to current antidepressant drugs. As depression is likely to be a heterogeneous disorder, it is possible that existing neurotransmitter-based antidepressant drugs do not fully address other pathologies that may exist in certain cases. Biological pathologies related to depression that have been proposed and studied extensively include inflammation and immunology, hypercortisolemia, oxidative stress, and impaired angiogenesis. Such pathologies may induce neurodegeneration, which in turn causes cognitive impairment, a symptom increasingly being recognized in depression. A neurotoxic brain hypothesis unifying all these factors may explain the heterogeneity of depression as well as cognitive decline and antidepressant drug resistance in some patients. Compared with neurotransmitter-based antidepressant drugs, many botanical compounds in traditional medicine used for the treatment of depression and its related symptoms have been discovered to be anti-inflammatory, immunoregulatory, anti-infection, antioxidative, and proangiogenic. Some botanical compounds also exert actions on neurotransmission. This multitarget nature of botanical medicine may act through the amelioration of the neurotoxic brain environment in some patients resistant to neurotransmitter-based antidepressant drugs. A multitarget multidimensional approach may be a reasonable solution for patients resistant to neurotransmitter-based antidepressant drugs.
... MDD is prevalent in excess of 17% among Han Chinese 3 and also becoming a leading cause of disability and mortality in the worldwide. Thus, it is one of the most urgent challenges for current psychiatric research to understand the pathogenesis of MDD It has been confirmed that the heritability of MDD is estimated up to 70% 4 and recent studies into its genetic etiology have detected a number of susceptibility genes and chromosomal regions implicated with immune system 5,6 . Clinical studies have widely demonstrated aberrant inflammation profiles of MDD patients in either central neural system (CNS) or peripheral tissues 7,8 . ...
Our previous work implied that interleukin 6 (IL6) may be a biological marker for major depressive disorder (MDD). In this study, we performed a comprehensive genetic study to determine the association between the gene encoding IL6 (IL6) and MDD in Han Chinese. There were 50 drug-naïve MDD patients and 50 healthy controls undergoing an mRNA expression study. A sample of 772 patients with MDD and 759 healthy controls were used for genetic analysis. Next, we performed an eQTL analysis to identify whether risk SNP(s) is associated with IL6 expression in brain. Our results showed that patients with MDD have higher levels of IL6 than healthy controls (P = 0.008). The SNP rs1800797 has a significant association with MDD (P = 0.01) in a dominant model. The eQTL analysis showed a marginally significant association between the rs1800797 and IL6 expression in the frontal cortex (P = 0.087). Our preliminary findings are suggestive of an association between rs1800797 and the risk of MDD. Further investigations are required to evaluate this association in larger samples to increase statistical power, and to examine the correlation between rs1800797 and IL6 methylation patterns.
... By this view, depression is not a disorder at all, but rather an adaptation for bargaining, conflict avoidance, problem-solving, disease avoidance, or other purposes (e.g. Hagen 2003; Price et al. 1994;Andrews and Thomson 2009;Anders et al. 2013). Some of these may be reasonable hypotheses for the evolutionary role of ordinary low mood, but none seem adequate to explain the severe and prolonged symptoms associated with clinical depression (Nettle, 2004). ...
Depression and anxiety disorders inflict untold harm on an enormous number of people. In the United States in a single year, nearly 10% of the population will suffer from a mood disorder and more than 20% will suffer from an anxiety disorder. Over the course of a lifetime, these numbers increase to 20% for mood disorders and 30% for anxiety disorders (National Institute of Mental Health 2016). From an evolutionary perspective, the prevalence of depression and anxiety disorders poses a serious puzzle. The typical onset of these disorders occurs before or during an individual’s reproductive years (Kessler et al., 2005) and they can be severely detrimental to even basic daily functioning. Why has natural selection left us vulnerable in this way?
Whether depression can be adaptive has long been discussed, but systematically investigation of the adaptive evolution of its genetic basis at the genomic level is sparse. Here, we conducted genome-wide analyses on 320 depression genes at two levels, i.e., across the primate phylogeny (large timescale selection), and in modern human populations (recent selection). We identified seven genes under positive selection in the human lineage, and 46 genes under positive selection in modern human populations. Most positively selected variants in modern human populations were at UTR regions and non-coding exons, indicating the importance of gene expression regulation in the adaptive evolution of depression gene networks. Positively selected genes are not only related to immune response, but also function in reproduction and dietary adaptation, extending the pathogen‒host defense hypothesis. Notably, the proportion of positively selected depression genes was significantly larger than the proportion of positively selected genes at the genomic level in certain modern human populations. We also identified two positively selected variants that happened to be depression-associated variants. We thus propose that recent selection plays important roles on the adaptive evolution of depression genes. Depression can be adaptive, or is a by-product of evolution, which is still an open question.
Scope:
It has been reported that eicosapentaenoic acid (EPA), especially EPA-enriched phospholipids (EPA-PL), significantly ameliorated depression-like behaviour in mice, while the corresponding effect of docosahexaenoic acid (DHA) is weak. However, it was still unclear whether the limited effect of DHA on alleviating depression was remedied by dose and chemical structure adjustment to DHA-PL.
Methods and results:
A mouse model with depression was established by chronic unpredictable mild stress (CUMS) coupled with lipopolysaccharide (LPS) challenge to simulate the infection-triggered immune perturbation during chronic stress, and the effects of dietary 0.2% EPA-PL, 0.2% DHA-PL, 0.6% DHA-PL and 0.6% DHA-enriched ethyl ester (DHA-EE) were comparatively investigated. The results demonstrated that dietary 0.6% DHA-PL, instead of 0.2% DHA-PL and 0.6% DHA-EE, significantly rescued the depression-like behaviour with similar effects to 0.2% EPA-PL. Further studies revealed that dietary DHA-PL regulated immune dysregulation, inhibited neuroinflammation by NLRP3 inflammasome, and further improved monoamine systems and the hypothalamic-pituitary-adrenal (HPA) axis.
Conclusion:
The limited effect of DHA on depression was remedied by chemical structure adjustment to DHA-PL and three-fold dose. The present findings provided a potential novel candidate or targeted dietary patterns to prevent and treat depression. This article is protected by copyright. All rights reserved.
Depression is one of the most prevalent mental diseases and a primary cause of disability worldwide with high incidence and high recurrence. The current deterioration of the COVID‐19 epidemic also pushes up the incidence of depression. Nevertheless, the currently available treatments remain inadequate response and limited efficacy. Therefore, discoveries of more potent and safer antidepressant drugs are urgently needed. In this review, we systematically summarized the current potential physiological and pathological mechanisms of depression, and the clinical research progresses of candidate drugs as well as the recent advances in small‐molecule drug discovery for potential treatments of depression. More importantly, the structure‐activity relationships (SARs) of compounds from different classes, the statistical analysis of the blood‐brain barrier (BBB) permeability, the pharmacological targets, and the in vivo models were comprehensively discussed. Further insights on antidepressant drug discovery were also analyzed from multidimensional perspectives. This article is protected by copyright. All rights reserved
O transtorno bipolar (TB) é crônico e incapacitante, sendo clinicamente caracterizado por episódios recorrentes de mania (ou hipomania) e depressão, além de estados mistos. O TB está associado a um aumento do risco de suicídio e a uma elevada prevalência de co-morbidades médicas e psiquiátricas, além de morte prematura e disfunção cognitiva. Os tratamentos disponíveis para o TB são insuficientes para uma proporção significativa de pacientes. Diversos novos alvos terapêuticos vêm sendo explorados para o desenvolvimento de novos fármacos com propriedades estabilizadoras do humor, incluindo: (1) a via da glicogênio sintase quinase 3 (GSK-3); (2) o via do fosfatidil-inositol e da proteína quinase C; (3) o fator de crescimento derivado do cérebro (BDNF); (4) as histonas deacetilases; (5) o sistema melatoninérgico; (6) fármacos anti-oxidantes e moduladores da função mitocondrial, além de (7) fármacos anti-inflamatórios. O presente artigo revisa o estado atual do conhecimento, além das dificuldades para o desenvolvimento de novos fármacos para o TB dentro de uma perspectiva translacional. O desenvolvimento de estratégias integrativas que analisem dados dimensionais de alta precisão, mesclando dados “ômicos” através de técnicas de bioinformática são necessárias para uma melhor elucidação da fisiopatologia complexa do TB. Tais achados podem levar ao desenvolvimento de novos fármacos para o TB, além de um tratamento personalizado.
Objectives
Sustained stress can cause physiological disruption in crucial systems like the endocrine, autonomic, and central nervous system. In general, skin damages are physical stress present in hospitalized patients. Also, these pressure injuries lead to pathophysiological mechanisms involved in the neurobiology of mood disorders. Here, we aimed to investigate the behavioral alterations, oxidative stress, and corticosterone levels in the brain areas of mice submitted to the model of pressure injury (PI).
Methods
The male mice behaviors were assessed in the open field test (OFT), elevated plus maze test (EPM), tail suspension test (TST), and sucrose preference test (SPT). Then, we isolated the prefrontal cortex (PFC), hippocampus (HP), and striatum (ST) by brain dissection. The nonprotein sulfhydryl groups (NP-SH) and malondialdehyde (MDA) were measured in the brain, and also the plasma corticosterone levels were verified.
Results
PI model decreased the locomotor activity of animals (p<0.05). Considering the EPM test, the PI group showed a decrease in the open arm activity (p<0.01), and an increase in the closed arm activity (p<0.05). PI group showed an increment in the immobility time (p<0.001), and reduced sucrose consumption (p<0.0001) compared to the control groups. Regarding the oxidative/nitrosative profile, all brain areas from the PI group exhibited a reduction in the NP-SH levels (p<0.0001–p<0.01), and an increase in the MDA level (p<0.001–p<0.01). Moreover, the PI male mice presented increased levels of plasma corticosterone (p<0.05).
Conclusions
Our findings suggest that the PI model induces depressive and anxiety-like behaviors. Furthermore, it induces pathophysiological mechanisms like the neurobiology of depression.
Background:
A better understanding of factors underlying antidepressant non-response may improve the prediction of which patients will respond to what treatment. Major depressive disorder (MDD) is associated with alterations in fatty acid metabolism, (neuro)inflammation and amygdala-reactivity. However, their mutual relations, and the extent to which they are associated with prospective antidepressant-response, remain unknown.
Purpose:
To test (I) alterations in (neuro)inflammation and its associations with fatty acid metabolism and amygdala-reactivity in MDD-patients compared to controls, and (II) whether these alterations are associated with prospective paroxetine response.
Methods:
We compared 70 unmedicated MDD-patients with 51 matched healthy controls at baseline, regarding erythrocyte membrane omega-6 arachidonic acid (AA), inflammation [serum (high-sensitivity) C-reactive protein (CRP)], and in a subgroup amygdala-reactivity to emotional faces using functional magnetic resonance imaging (fMRI) (N=42). Subsequently, we treated patients with 12 weeks paroxetine, and repeated baseline measures after 6 and 12 weeks to compare non-responders, early-responders (response at 6 weeks), and late-responders (response at 12 weeks).
Results:
Compared to controls, MDD-patients showed higher CRP (p=0.016) and AA (p=0.019) after adjustment for confounders at baseline. AA and CRP were mutually correlated (p=0.043). In addition, patients showed a more negative relation between AA and left amygdala-reactivity (p=0.014). Moreover, AA and CRP were associated with antidepressant-response: early responders showed lower AA (p=0.018) and higher CRP-concentrations (p=0.008) than non-responders throughout the study.
Conclusion:
Higher observed CRP and AA, their mutual association, and relation with amygdala-reactivity, are corroborative with a role for (neuro)inflammation in MDD. In addition, observed associations of these factors with prospective antidepressant-response suggest a potential role as biomarkers. Future studies in independent samples are needed to replicate and test the clinical applicability of these biological predictors for treatment response to result in a precision/personalized medicine approach for treatment.
Systemic inflammation is among the most prominent and most frequently observed responses of the immune system. From everyday challenges like mild infections to severe forms such as chronic inflammatory diseases or sepsis, inflammatory states can develop in many ways over the lifespan. Over the past few decades, it has become clear that inflammatory events can have a strong impact on brain functions. Inflammatory mediators released by activated immune cells induce not only adaptive behavioral responses such as sickness behavior but also can lead to cognitive impairment and may even promote the development of mood disorders. Since most of these aspects cannot be sufficiently modeled in laboratory animals, there is a need for experimental inflammatory models in humans. Intravenous or intramuscular injection of bacterial lipopolysaccharide (LPS, endotoxin) represents a model to induce transient systemic low-grade inflammation in healthy human subjects. During the past two decades, this model has been increasingly used for psychoneuroimmunology (PNI) research. After a brief introduction into sickness behavior and the history of immune-to-brain research, we will summarize work employing this promising model beginning with the first studies on sleep alterations and ending with studies on social behavior using cutting-edge neuroimaging techniques like functional magnetic resonance imaging (fMRI) or positron emission tomography (PET). We will discuss potential difficulties and limitations of the model and provide implications for future studies. In addition we give a short exposition on the immunologic properties of LPS, information pathways from the immune system to the brain, and on the cytokine hypothesis of depression.
Understanding how and why early exposure to stress may have lasting effects on behavior and biology is fundamental to developmental study of psychopathology. Significant progress in this area has been made since the previous volume, in terms of the quality and quantity of findings and the types of research targets. This chapter reviews illustrative and intriguing findings in this large and diverse area of study. Key sections of the chapter aim to outline and differentiate leading developmental models for testing hypotheses concerning early experience and psychological development; to identify leading mechanisms that may account for a carrying forward of effects in development; to articulate methodological challenges for clinical and translational research for current and future investigation; to review select model systems and research paradigms that have risen to prominence in this area; to discuss intervention studies that have shaped the early experience debate and in clinical and public contexts; and to target future directions for clinical and translational research. Although evidence from animal studies plays a prominent role, research findings from human studies are particularly emphasized.
Significant attention has been paid to the potential adaptive value of depression as it relates to interactions with people in the social world. However, in this review, we outline the rationale of why certain features of depression including its environmental and genetic risk factors, its association with the acute phase response and its age of onset and female preponderance appear to have evolved from human interactions with pathogens in the microbial world. Approaching the relationship between inflammation and depression from this evolutionary perspective yields a number of insights that may reveal important clues regarding the origin and epidemiology of the disorder as well as the persistence of its risk alleles in the modern human genome.Neuropsychopharmacology accepted article preview online, 15 September 2016. doi:10.1038/npp.2016.194.
Desde as primeiras descrições de “neurastenia”, no século XIX, muito se aprendeu
sobre as condições funcionais que envolvem dor crônica. Infelizmente, esse
conhecimento ainda não foi traduzido em melhora da qualidade de vida para seus
portadores, uma vez que apenas uma minoria experimenta melhora significativa dos
sintomas em longo prazo. Especialistas, e as entidades que os representam, assumem
abertamente sua impotência em relação a essa questão, o que acaba por abrir espaço
para um tumulto de propostas terapêuticas, algumas cabíveis e outras mirabolantes. O
Colégio Americano de Reumatologia faz referência aos “componentes existenciais,
filosóficos e sociais” dessas doenças, eximindo-se de responsabilidades que
extrapolariam sua área de atuação. Tratar adequadamente do assunto implica,
efetivamente, transitar entre esses mundos. Como fazer isso sem violentar os princípios
que regem a ciência? Como enfrentar a terrível Babel? O presente livro utiliza a ciência
como base, segue um pouco mais adiante com a lógica e, finalmente, preenche os
espaços vazios com ideias e conceitos, sedimentados ao longo de nossa história. É um
caminho que passa pela neuroanatomia, neurofisiologia, genética, epidemiologia,
psicologia, biologia, sociologia e filosofia. Antônio Damasio, Oliver Sacks, Jaak
Panksepp, Charles Darwin, Erwin Schrödinger, Sigmund Freud, Wilhelm Reich, René
Descartes, Sócrates, Aristóteles e Platão norteiam a narrativa que pretende lançar luz
sobre essas lacunas e apresentar um novo modo de ver e tratar tais condições.
Bovine respiratory disease (BRD) is the most common disorder in North American beef cattle. This work aimed to describe the BRD sickness response, identify measures to improve detection, and assess effects of a non-steroidal anti-inflammatory drug (NSAID). We hypothesized that BRD challenge would induce a sickness response, with an NSAID and antibiotics attenuating this more than antibiotics alone. Challenged steers (BRD) were infected with a respiratory virus (d 0) and bacteria (d 5) and No-challenge steers received sterile medium. All were treated once with antibiotics, and half also received one 0.5 mg/kg NSAID dose (d 8). After applying inclusion criteria, sample size was five BRD-No NSAID, four BRD-NSAID, two No-challenge-No NSAID, and three No-challenge-NSAID. Clinical examinations were performed daily, loggers tracked fever (d 3 to 10) and lying (d 0 to 13) continuously, dry matter intake (DMI) was recorded/24 h (d 0 to 12), grooming was assessed for 20 min/d (d 4, 6 to 11, 13), and mechanical nociceptive threshold (MNT) testing evaluated hyperalgesia (d 4, 6, 7, 9, 10, 13). Average daily gain (ADG) was calculated from end-of-study and baseline BW. Clinical symptoms occurred d 2 to 11, peaking on d 5. Sickness response components peaked on different days. Compared with No-challenge, BRD had fever d 3 to 7 (up to 2.1 °C higher on d 3; P < 0.001), lower DMI d 2 to 10 (88% less at the lowest point on d 5; P < 0.001), lower ADG (88% less; P = 0.002), higher total lying time (up to 11% higher on d 3; P = 0.014), longer lying bouts d 3 to 5 and d 9 (up to 87% higher on d 4; P = 0.002) and a tendency for fewer lying bouts (22% less; P = 0.072). Compared with No-challenge, BRD groomed less (58% lower; P = 0.016) and had hyperalgesia (44% lower MNT; P = 0.002). The NSAID had no effect (P ≥ 0.108) except for an interaction involving total lying time (P = 0.050), possibly due to experimental design limitations or poor efficacy. In summary, the sickness response began within 2 d of challenge, persisting for up to 10 d. Some aspects mirrored fluctuating clinical symptoms and appeared early (DMI, fever); others reflected disease in a relatively invariable manner (lying bout number, hyperalgesia, grooming). The most persistent changes lasted for ≥ 5 d (DMI, fever, hyperalgesia, and grooming). Sickness response components that occur early, persist and mirror clinical symptom progression may be better for BRD detection; from this perspective, DMI was the most promising.
Background. The vegetative symptoms of depression resemble the symptoms of malaise associated with activation of the inflammatory response system (IRS), and can be regarded as an expression of a central motivational state that resets the organism's priorities to promote recovery from infection. Early vegetative symptoms, however, may also contribute to the high rates of depression seen later in the course of immune activation. We hypothesized that the onset of vegetative-depressive symptoms early in the treatment with the pro-inflammatory cytokine IFN-α in chronic hepatitis C patients would increase the risk for subsequent depressive cognitions.
Method. Sixteen patients eligible for IFN-α treatment and free of psychiatric disorders were recruited. The DSM-IV, the Multidimensional Fatigue Inventory, and the Montgomery–Asberg Depression Rating Scale (MADRS) were administered at baseline and 1, 2, 4, 8, 12 and 24 weeks after treatment was initiated. Cognitive-depressive and vegetative-depressive symptom clusters were constructed.
Results. Fatigue and depression scores increased significantly during IFN-α treatment. Depression scores were highest at week 8 of treatment. First week increase in vegetative-depressive symptom score predicted cognitive-depressive symptom score at week 8 and at week 24.
Conclusions. During IFN-α treatment, vegetative symptoms of depression appear earlier than, and are predictive of, their cognitive counterparts. This finding suggests that low mood state may in part be driven by the increase in early vegetative-depressive symptoms in the course of IFN-α-induced immune activation.
Alteration of monoaminergic neurotransmission has been implicated in the pathophysiology of mood disorders, and CYP2C9 enzyme activity has been shown to be modulated by serotonin in vitro. The present study was aimed at analysing the frequency of CYP2C9 alleles (*1, *2, *3) among patients suffering from major depressive disorder. In all, 70 such suffering psychiatric outpatients were studied. The CYP2C9 genotypes were determined by allele-specific PCR. The CYP2C9*3 allele frequency was higher (P<0.01) among the patients suffering from major depression than in a population of 89 schizophrenic patients (odds ratio=3.3) and 138 healthy volunteers (odds ratio=2.8). The results suggest that CYP2C9 genetic polymorphism may be related to a major depressive disorder due to an alteration in endogenous metabolism, although a linkage between CYP2C9 and some other gene related to depression cannot be ruled out.Keywords: CYP2C9 gene, depression, schizophrenia
Context:
Increased concentrations of inflammatory biomarkers predict antidepressant nonresponse, and inflammatory cytokines can sabotage and circumvent the mechanisms of action of conventional antidepressants.
Objectives:
To determine whether inhibition of the inflammatory cytokine tumor necrosis factor (TNF) reduces depressive symptoms in patients with treatment-resistant depression and whether an increase in baseline plasma inflammatory biomarkers, including high-sensitivity C-reactive protein (hs-CRP), TNF, and its soluble receptors, predicts treatment response.
Design:
Double-blind, placebo-controlled, randomized clinical trial.
Setting:
Outpatient infusion center at Emory University in Atlanta, Georgia.
Participants:
A total of 60 medically stable outpatients with major depression who were either on a consistent antidepressant regimen (n = 37) or medication-free (n = 23) for 4 weeks or more and who were moderately resistant to treatment as determined by the Massachusetts General Hospital Staging method.
Interventions:
Three infusions of the TNF antagonist infliximab (5 mg/kg) (n = 30) or placebo (n = 30) at baseline and weeks 2 and 6 of a 12-week trial.
Main outcome measures:
The 17-item Hamilton Scale for Depression (HAM-D) scores.
Results:
No overall difference in change of HAM-D scores between treatment groups across time was found. However, there was a significant interaction between treatment, time, and log baseline hs-CRP concentration (P = .01), with change in HAM-D scores (baseline to week 12) favoring infliximab-treated patients at a baseline hs-CRP concentration greater than 5 mg/L and favoring placebo-treated patients at a baseline hs-CRP concentration of 5 mg/L or less. Exploratory analyses focusing on patients with a baseline hs-CRP concentration greater than 5 mg/L revealed a treatment response (≥50% reduction in HAM-D score at any point during treatment) of 62% (8 of 13 patients) in infliximab-treated patients vs 33% (3 of 9 patients) in placebo-treated patients (P = .19). Baseline concentrations of TNF and its soluble receptors were significantly higher in infliximab-treated responders vs nonresponders (P < .05), and infliximab-treated responders exhibited significantly greater decreases in hs-CRP from baseline to week 12 compared with placebo-treated responders (P < .01). Dropouts and adverse events were limited and did not differ between groups.
Conclusions:
This proof-of-concept study suggests that TNF antagonism does not have generalized efficacy in treatment-resistant depression but may improve depressive symptoms in patients with high baseline inflammatory biomarkers.
Trial registration:
clinicaltrials.gov Identifier: NCT00463580.
This article reviews the evolutionary origins and functions of the capacity for anxiety, and relevant clinical and research issues. Normal anxiety is an emotion that helps organisms defend against a wide variety of threats. There is a general capacity for normal defensive arousal, and subtypes of normal anxiety protect against particular kinds of threats. These normal subtypes correspond somewhat to mild forms of various anxiety disorders. Anxiety disorders arise from dysregulation of normal defensive responses, raising the possibility of a hypophobic disorder (too little anxiety). If a drug were discovered that abolished all defensive anxiety, it could do harm as well as good. Factors that have shaped anxiety-regulation mechanisms can explain prepotent and prepared tendencies to associate anxiety more quickly with certain cues than with others. These tendencies lead to excess fear of largely archaic dangers, like snakes, and too little fear of new threats, like cars. An understanding of the evolutionary origins, functions, and mechanisms of anxiety suggests new questions about anxiety disorders.
The aim of this study was to determine the effects of whole body heat in combination with exercise on the oxidative stress and acute phase immune response. Nine male endurance-trained athletes voluntarily performed two running bouts of 45 minutes at 75-80% of VO(2max) in a climatic chamber in two conditions: cold and hot humid environment. Leukocyte, neutrophil and basophil counts significantly rose after exercise in both environments; it was significantly greater in the hot environment. Lymphocyte and neutrophil antioxidant enzyme activities and carbonyl index significantly increased or decreased after exercise only in the hot environment, respectively. The lymphocytes expression of catalase, Hsp72 and CuZn-superoxide dismutase was increased in the hot environment and Sirt3 in the cold environment, mainly during recovery. In conclusion, the increased core body temperature results in the acute phase immune response associated to intense exercise and in the immune cell adaptations to counteract the oxidative stress situation.
Given the manifold ways that depression impairs Darwinian fitness, the persistence in the human genome of risk alleles for the disorder remains a much debated mystery. Evolutionary theories that view depressive symptoms as adaptive fail to provide parsimonious explanations for why even mild depressive symptoms impair fitness-relevant social functioning, whereas theories that suggest that depression is maladaptive fail to account for the high prevalence of depression risk alleles in human populations. These limitations warrant novel explanations for the origin and persistence of depression risk alleles. Accordingly, studies on risk alleles for depression were identified using PubMed and Ovid MEDLINE to examine data supporting the hypothesis that risk alleles for depression originated and have been retained in the human genome because these alleles promote pathogen host defense, which includes an integrated suite of immunological and behavioral responses to infection. Depression risk alleles identified by both candidate gene and genome-wide association study (GWAS) methodologies were found to be regularly associated with immune responses to infection that were likely to enhance survival in the ancestral environment. Moreover, data support the role of specific depressive symptoms in pathogen host defense including hyperthermia, reduced bodily iron stores, conservation/withdrawal behavior, hypervigilance and anorexia. By shifting the adaptive context of depression risk alleles from relations with conspecifics to relations with the microbial world, the Pathogen Host Defense (PATHOS-D) hypothesis provides a novel explanation for how depression can be nonadaptive in the social realm, whereas its risk alleles are nonetheless represented at prevalence rates that bespeak an adaptive function.Molecular Psychiatry advance online publication, 31 January 2012; doi:10.1038/mp.2012.2.
Studies consistently report that groups of individuals with major depressive disorder (MDD) demonstrate increased levels of a variety of peripheral inflammatory biomarkers when compared with groups of nondepressed individuals. These findings are often interpreted as meaning that MDD, even in medically healthy individuals, may be an inflammatory condition. In this article, we examine evidence for and against this idea by looking more closely into what the actual patterns of inflammatory findings indicate in terms of the relationship between MDD and the immune system. Data are presented in support of the idea that inflammation only contributes to depression in a subset of patients versus the possibility that the depressogenic effect of inflammatory activation is more widespread and varies depending on the degree of vulnerability any given individual evinces in interconnected physiologic systems known to be implicated in the etiology of MDD. Finally, the treatment implications of these various possibilities are discussed.
There has been an explosion in our knowledge of the pathways and mechanisms by which the immune system can influence the brain and behavior. In the context of inflammation, pro-inflammatory cytokines can access the central nervous system and interact with a cytokine network in the brain to influence virtually every aspect of brain function relevant to behavior including neurotransmitter metabolism, neuroendocrine function, synaptic plasticity, and neurocircuits that regulate mood, motor activity, motivation, anxiety and alarm. Behavioral consequences of these effects of the immune system on the brain include depression, anxiety, fatigue, psychomotor slowing, anorexia, cognitive dysfunction and sleep impairment; symptoms that overlap with those which characterize neuropsychiatric disorders, especially depression. Pathways that appear to be especially important in immune system effects on the brain include the cytokine signaling molecules, p38 mitogen-activated protein kinase and nuclear factor kappa B; indoleamine 2,3 dioxygenase and its downstream metabolites, kynurenine, quinolinic acid and kynurenic acid; the neurotransmitters, serotonin, dopamine and glutamate; and neurocircuits involving the basal ganglia and anterior cingulate cortex. A series of vulnerability factors including aging and obesity as well as chronic stress also appears to interact with immune to brain signaling to exacerbate immunologic contributions to neuropsychiatric disease. The elucidation of the mechanisms by which the immune system influences behavior yields a host of targets for potential therapeutic development as well as informing strategies for the prevention of neuropsychiatric disease in at risk populations.
Vitamin D receptors have been mapped throughout the brain suggesting a role for vitamin D in psychosomatic disorders. Results from previous epidemiological studies on relation between vitamin D status and depression are equivocal. Also, limited information is available relating vitamin D status with depression in young adult US population.
Data from the third National Health and Nutrition Examination Survey were used to assess association between serum vitamin D and depression in 7970 non-institutionalized US residents, aged 15-39 y. Assessment of depression was done using the Diagnostic Interview Schedule developed by the National Institute of Mental Health. After accounting for several confounding variables in multivariate logistic regression analysis, we estimated odds ratios (OR) for having depression in vitamin D deficient persons in comparison to vitamin D sufficient persons.
Women, non-Hispanic blacks, persons living below poverty, persons who did not consume supplements, persons living in South and West regions and in urban areas, persons with higher BMI, and persons with current depression had higher prevalence of vitamin D deficiency compared to their counterparts. OR for having current depressive episodes in persons with serum vitamin D ≤ 50 nmol/L is significantly higher relative to those with serum vitamin D ≥ 75 nmol/L (OR = 1.85; P = 0.021).
In this large population based study, likelihood of having depression in persons with vitamin D deficiency is significantly higher compared to those with vitamin D sufficiency. Early diagnosis and intervention are paramount because coexistence of vitamin D deficiency and depression has serious negative consequences on health.
Most clinical isolates that exhibit a multi-drug resistant phenotype owe that resistance to over-expressed efflux pumps. Compounds that are efflux pump inhibitors (EPIs) reduce or reverse resistance to antibiotics to which the bacterial strain is initially resistant. We have evaluated non-antibiotics to reduce resistance of commonly encountered bacterial pathogens to antibiotics.
The effect of non-antibiotics on the susceptibility of bacteria to antibiotics was conducted by minimum inhibition concentration determinations of the antibiotic in the absence and presence of the non-antibiotic.
Non-antibiotics such as chlorpromazine, amitryptiline and trans-chlorprothixene are shown to reduce or reverse resistance of a variety of bacteria to antibiotics.
The results suggest that non-antibiotics may serve as adjuncts to conventional antibiotics for the therapy of problematic antibiotic infections caused by bacteria that owe their resistance to over-expressed efflux pumps.
Increased production of peripheral cytokines and other pro-inflammatory markers has been linked to psychiatric disorders such as major depressive disorder and post-traumatic stress disorder. Recent research has pointed to early-life stress, particularly childhood maltreatment, as an independent and preventable risk factor for systemic inflammation in adulthood. Some data suggest that adults with a history of childhood maltreatment exhibit a heightened inflammatory response to acute stress challenge. To further elucidate the relationship between childhood maltreatment and pro-inflammatory cytokine production, we examined plasma IL-6 response to the Trier Social Stress Test (TSST) in 69 healthy adult subjects without depression or post-traumatic stress disorder. Serial plasma IL-6 concentrations were measured during a standardized psychosocial stressor in n=19 subjects with moderate-severe childhood maltreatment (MAL), and n=50 controls without maltreatment (CTL), as indicated by self-ratings on the childhood trauma questionnaire (CTQ). CTQ total scores were positively correlated with overall change in IL-6 response, as well as the maximum IL-6 concentration during the TSST. Greater acute IL-6 release and higher IL-6 concentrations over time were observed for the MAL group relative to the CTL group. Inflammation may be an important developmental mediator linking adverse experiences in early life to poor adult physical and mental health. The results of this preliminary study warrant further investigation in a larger sample.
Mindfulness-based stress reduction (MBSR) programs have consistently been shown to enhance the psychosocial well-being of participants. Given the well-established association between psychosocial factors and immunologic functioning, it has been hypothesized that enhanced psychosocial well-being among MBSR participants would be associated with corresponding changes in markers of immune activity.
The objectives of this study were to examine changes in psychosocial and immunologic measures in a heterogeneous patient sample following participation in a MBSR program.
A single-group, pretest/post-test design was utilized.
The intervention was conducted at an academic health center.
This pilot study involved 24 participants (aged 28-72 years). Inclusion criteria were as follows: > or =18 years of age, English-speaking, and no known autoimmune disorder.
The intervention was an 8-week MBSR program.
Distress and quality of life (QOL) measures included the Brief Symptom Inventory-18 and the Medical Outcomes Survey Short-Form Health Survey, respectively. Immunologic measures included natural killer (NK) cell cytolytic activity and C-reactive protein (CRP).
Patients completed psychosocial assessments and provided a blood sample at baseline (pre-MBSR) and within 2 weeks post-MBSR. Significant improvements in anxiety and overall distress as well as across multiple domains of QOL were observed from baseline to post-MBSR. Reductions in anxiety and overall distress were associated with reductions in CRP. Patients who reported improvement in overall mental well-being also showed increased NK cytolytic activity from pre- to post-MBSR, whereas patients who reported no improvement in mental well-being showed no change in NK cytolytic activity.
Positive improvement in psychologic well-being following MBSR was associated with increased NK cytolytic activity and decreased levels of CRP.
Objective: This article is an overview of epidemiological and treatment studies suggesting that deficits in dietary-based omega-3 polyunsaturated fatty acids may make an etiological contribution to mood disorders and that supplementation with omega-3 fatty acids may provide a therapeutic strategy. Method: Relevant published studies are detailed and considered. Results: Several epidemiological studies suggest covariation between seafood consumption and rates of mood disorders. Biological marker studies indicate deficits in omega-3 fatty acids in people with depressive disorders, while several treatment studies indicate therapeutic benefits from omega-3 supplementation. A similar contribution of omega-3 fatty acids to coronary artery disease may explain the well-described links between coronary artery disease and depression. Conclusions: Deficits in omega-3 fatty acids have been identified as a contributing factor to mood disorders and offer a potential rational treatment approach. This review identifies a number of hypotheses and studies for consideration. In particular, the authors argue for studies clarifying the efficacy of omega-3 supplementation for unipolar and bipolar depressive disorders, both as individual and augmentation treatment strategies, and for studies pursuing which omega-3 fatty acid, eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA), is likely to provide the greatest benefit.
Background:
Natural history can be characterized by incidence, recurrence, and duration of episodes. Research on the incidence of major depression is rare; studies of recurrence and duration are limited to clinical samples.Methods:
The Baltimore, Md, site of the Epidemiologic Catchment Area Program followed up its 1981 baseline cohort of 3481 respondents with an additional assessment in 1993 to 1996. Interviews were obtained from 1920 respondents (73% of the survivors). The Diagnostic Interview Schedule and the same survey procedures as in 1981 were used, augmented with a Life Chart Interview for dating the onset and duration of syndromes.Results:
There were 71 new cases of Diagnostic Interview Schedule/DSM-IVmajor depression and 23 698 person-years of exposure, generating an estimated incidence of 3.0 per 1000 per year. Incidence peaked while subjects were in their 30s, with a smaller peak when they were in their 50s. Prodromal symptoms often occurred many years before the full criteria for diagnosis were met. Women were at higher risk for becoming new cases but had neither higher risk for recurrence nor longer episodes than men. Episodes of depression lasted for 12 weeks. The duration of an episode, and time to an episodefree year, was longer in the first episode than in recurrent episodes.Conclusions:
The incidence estimated in this study is consistent with that found in the few other similar studies performed. The bimodality of onset suggests the value of further exploring the heterogeneity of depression via its natural history. Reported differences in prevalence between men and women seem to be due to differences in incidence, not chronicity.
• To investigate the contribution of genetic and environmental factors in the etiology of mood disorders, a study was initiated to examine the frequency of psychiatric disorders in the biological and adoptive relatives of adult adoptees with mood disorders and in matched normal adoptees. Psychiatric evaluations of the relatives were made on the basis of independent blind diagnoses based on mental hospital and other official records. Analysis of the data showed an eightfold increase in unipolar depression among the biological relatives of the index cases and a 15-fold increase in suicide among the biological relatives of the index cases. These data demonstrate a significant genetic contribution to unipolar depression and suicide. They fail to disclose a significant contribution of family-associated transmission in the genesis of the mood disorders.
Objectives:
To estimate the contribution of genes and shared family environment to the liability to DSM-IV major depression and to examine the influence of certain proband characteristics on twin concordance.Methods:
We studied 177 probands with major depressive disorder ascertained via the Maudsley Hospital Twin Register (London, England) and their same-sex cotwins. Diagnostic assessments were carried out blind to zygosity and information on the other member of the twin pair. Probandwise concordances were used to compute correlations in liability, and model fitting was performed using maximum likelihood procedures.Results:
The probandwise concordance was 46% in monozygotic (n=68) and 20% in dizygotic (n=109) twins, a statistically highly significant difference. There was no evidence of a sex difference in heritability or of shared environmental effects. Depending on the assumed population risks for DSM-IV, major depression estimates of heritability were between 48% and 75%. A duration of longest episode of less than 13 months, multiple episodes, and an endogenous rather than neurotic pattern of symptoms, as established by the International Classification of Diseases, Ninth Revision, in the proband were associated with a trend toward a higher monozygoticdizygotic concordance ratio. Using log-linear analysis, only the association between duration of episodes and monozygotic-dizygotic concordance ratio was significant.Conclusions:
Liability to DSM-IV major depression has a substantial heritable component, and there is no evidence of an effect of shared family environment. Some proband characteristics, especially shorter duration of episodes, may be associated with a larger degree of genetic determination.
Major depressive disorder (MDD) is one of medicine’s most prevalent and costly disorders, and it has high rates of comorbidity with a wide range of infectious diseases and serious medical disorders. MDD has been linked to immunologic alterations that include suppressed cellular immune function, excessive inflammatory response, and greater susceptibility to infection. In this chapter, we review research on environmental factors and immune factors associated with depression including: a clinical overview of MDD, current evidence on environmental risk factors and alterations in immune function, and the role of immune factors in the etiology of depression. In a concluding section, we discuss an integrative hypothesis—The Infection-Defense Hypothesis—that may help to resolve an important psychiatric puzzle, offering an explanation for why immune function is related to depression, and why depression remains common, despite its high evolutionary costs and evidence for its significant heritability.
Humans have evolved much longer lifespans than the great apes, which rarely exceed 50 years. Since 1800, lifespans have doubled again, largely due to improvements in environment, food, and medicine that minimized mortality at earlier ages. Infections cause most mortality in wild chimpanzees and in traditional forager-farmers with limited access to modern medicine. Although we know little of the diseases of aging under premodern conditions, in captivity, chimpanzees present a lower incidence of cancer, ischémie heart disease, and neurodegeneration than current human populations. These major differences in pathology of aging are discussed in terms of genes that mediate infection, inflammation, and nutrition. Apolipoprotein E alleles are proposed as a prototype of pleiotropic genes, which influence immune responses, arterial and Alzheimer's disease, and brain development.
Recombinant interleukin-lα and-β (Il-1α and - β) have been evaluated for their abilities to stimulate ACTH and catecholamine secretion in the intact adult male rat. Additionally, the role of adrenergic-dependent pathways in mediating Il-1-induced ACTH release has been assessed. The iv or intracerebroventricular injection of either II-lα or 11–1β caused doserelated increases in plasma ACTH, epinephrine, and norepinephrine levels. While at low iv doses (≤10 ng), 11–1β was more effective than Il-lα at releasing ACTH, no measurable differences were noted at higher doses. In contrast, 11–1β was significantly more active at all doses in elevating plasma ACTH levels after intracerebroventricular injection. Similarly, Il-lα was more effective than 11–1β at stimulating epinephrine, but not norepinephrine, secretion after icv injection. Because of the ability of catecholamines to alter ACTH secretion, we then examined the role of adrenergic-dependent pathways as possible mediators of Il-1-induced ACTH secretion. Blockade of adrenergic receptors by the concomitant administration of prazosin and propanolol prevented the simultaneous actions of phenylephrine and isoproterenol on the corticotrophs, but did not significantly alter the effect of peripherally administered Il-lα on ACTH release.
These results suggest that both Il-lα and 11–1β stimulate ACTH and catecholamine secretion in the rat. Despite the ability of the lymphokine to elevate plasma epinephrine and norepinephrine values, circulating catecholamines do not appear to represent essential modulators of ACTH release induced by acutely injected 11–1.
Psychotropic drugs have been shown to have antimicrobial activity against several groups of microorganisms. Some of these drugs, such as the new antidepressant agents sertraline, fluoxetine and paroxetine are known to act as efflux pump inhibitors in human cells. Their activity has been studied, alone and combined with antibiotics, against bacterial species, mainly in multiply resistant strains. These agents have surprising activity, mainly against Gram positive microorganisms. They also show synergistic activity when combined with some antibiotics against several bacteria, shown by a decrease in MICs, that converts strains previously resistant to the category of sensitive, and modify physiological aspects related with pathogenicity.
Background
Tryptophan (TRP) degradation into kynurenine (KYN) by the enzyme, indoleamine-2,3-dioxygenase, during immune activation may contribute to development of depressive symptoms during interferon (IFN)-α therapy.
This chapter presents a review of mate choice and genetic quality, defines mate choice, and discusses some of the key issues about how individuals can benefit from being choosy, including the distinction between two main types of genetic benefits. It also focuses on heterozygosity and fitness and presents an overview of the methods that have been used to estimate individual heterozygosity or relatedness among individuals. It also presents a review of the studies that have found correlations between individual heterozygosity and a variety of fitness‐related traits. The chapter consists of two parts—mate choice based on relatedness with the partner, which is choice to optimize offspring heterozygosity and the link between the evolution of promiscuity and inbreeding avoidance.
From an evolutionary perspective, psychiatric depression presents a paradox: despite disadvantages for survival and reproduction, depression has significant heritability and is remarkably prevalent. A potential explanation for this paradox is provided by the hypothesis that the immune system helps regulate mood to aid defense against infection. This “infection-defense” hypothesis proposes that immune vulnerability to infection elicits depressed mood, which in turn stimulates behaviors that help protect vulnerable individuals and their kin against infectious diseases. This paper examines evidence on predictions of the hypothesis that concern depression's relation to immune function and vulnerability to infection. A review finds support for several predictions: 1) depressed patients show elevated levels of key types of immune vulnerability; 2) in animal experiments, chronic conditions that increase vulnerability to infection also cause depressionlike behaviors; 3) there are adaptive mechanisms to fight infection that involve interactions of immune and neuroendocrine factors; 4) conditions associated with depression in humans are also associated with immune vulnerability and infection; and 5) somatic antidepressant treatments often enhance immune function and resistance to infection, with time courses of immune responses to different treatments often paralleling those for mood. 6) Finally, positive mood tends to be associated with enhanced resistance to infection. This review focuses on immune factors that are crucial for defense against infectious diseases and have been widely studied in relation to depressive symptoms and antidepressant therapies. The hypothesis has potential clinical implications for prevention and treatment of depression.
hypothesize that human mental pain is an adaptation that functions to force assessment of the circumstances surrounding social problems in the lives of individual humans
from the hypothesis of psychological pain, we derive two general and several specific predictions / (1) the proximate ecological causes of mental pain will be circumstances that affected future reproductive options of our ancestors, especially those pertaining to the inclusive fitness of individuals under social competition / (2) the more an event potentially or actually negatively affects the evolved social desires and aspirations of humans, the more psychological pain will occur surrounding the event
evolutionary psychology / adaptationist approach / rape victims in evolutionary context / hypothesis applied to rape victims' mental pain / mental pain of rape victims: predictions / mental pain: contexts other than post-rape / animal welfare (PsycINFO Database Record (c) 2012 APA, all rights reserved)
Inflammation plays an important role in cardiovascular disease. The aim of this study is to investigate the predictive value of several inflammatory markers on the incidence of cardiovascular events in well-functioning older persons.
The subjects were 2225 participants 70 to 79 years old, without baseline cardiovascular disease, who were enrolled in the Health, Aging, and Body Composition study. Incident coronary heart disease (CHD), stroke, and congestive heart failure (CHF) events were detected during an average follow-up of 3.6 years. Blood levels of interleukin-6 (IL-6), C-reactive protein (CRP), and tumor necrosis factor-alpha (TNF-alpha) were assessed. After adjustment for potential confounders, IL-6 was significantly associated with all outcomes (CHD events, per IL-6 SD increase: RR, 1.27; 95% CI, 1.10 to 1.48; stroke events, per IL-6 SD increase: RR, 1.45; 95% CI, 1.12 to 1.86; CHF events, per IL-6 SD increase: RR, 1.72; 95% CI, 1.40 to 2.12). TNF-alpha showed significant associations with CHD (per TNF-alpha SD increase: RR, 1.22; 95% CI, 1.04 to 1.43) and CHF (per TNF-alpha SD increase: RR, 1.59; 95% CI, 1.30 to 1.95) events. CRP was significantly associated with CHF events (per CRP SD increase: RR, 1.48; 95% CI, 1.23 to 1.78). A composite summary indicator of inflammation showed a strong association with incident cardiovascular events, with an especially high risk if all 3 inflammatory markers were in the highest tertile.
Findings suggest that inflammatory markers are independent predictors of cardiovascular events in older persons.
Although the incidence of hepatitis C virus (HCV) is declining, a large reservoir of patients with chronic hepatitis C exists. Unless effective HCV antiviral regimens are developed, many patients with asymptomatic HCV will develop clinical symptoms in the next 15 to 20 years. Mood disorders are common in patients with HCV referred for psychiatric consultation. Interferon is the primary treatment for chronic hepatitis C but can induce depression and other mental and neuropsychiatric syndromes. Mood disorders associated with hepatitis C may respond to psychiatric intervention. Psychiatrists need to be aware of the clinical issues in the diagnosis and treatment of depression complicating chronic hepatitis C. Depression and Anxiety 7:188–193, 1998. © 1998 Wiley-Liss, Inc.
Background: The pathophysiology of depression is associated with the hyperactivity of immune inflammatory responses. Cyclooxygenase-2 inhibitors such as celecoxib reduce the production of pro-inflammatory cytokines. The purpose of the present investigation was to assess the efficacy of celecoxib as an adjuvant agent in the treatment of major depression in a six-week double blind and placebo controlled trial. Methods: Forty adult outpatients who met the DSM-IV-TR criteria for major depression participated in the trial. Patients have a baseline Hamilton Rating Scale for Depression score of at least 18. Patients were allocated in a random fashion: 20 to fluoxetine 40 mg/day plus celecoxib 400 mg/day (200 mg bid) (morning and evening) and 20 to fluoxetine 40 mg/day plus placebo. Patients were assessed by a psychiatrist at baseline and after 1, 2, 4, and 6 weeks after the medication started. Results: Although both protocols significantly decreased the score of Hamilton Rating Scale for Depression over the trial period, the combination of fluoxetine and celecoxib showed a significant superiority over fluoxetine alone in the treatment of symptoms of major depression. There were no significant differences in the two groups in terms of observed side effects. Conclusion: The results of this study suggest that celecoxib may be an effective adjuvant agent in the management of patients with major depression and anti-inflammatory therapies should be further investigated. Depression and Anxiety, 2009. © 2009 Wiley-Liss, Inc.
Previous studies have found that although psychiatric patients tend to have more physical illness than the rest of the population,
it frequently goes unrecognized and untreated in psychiatric settings. This study investigated rates of reported physical
illness among hospitalized psychiatric patients in preparation for national reform in mental health services. Data from the
Israeli National Psychiatric Case Registry were analyzed on reported physical illness among all 38,714 psychiatric discharges
during 1989–1991. Physical illness was reported for 10.62% of patients under age 25, 14.4% of patients 25 to 44, 34.27%
of patients 45 to 65, and 61.26% of patients 65 and older. Rates differed among hospitals. Reported physical illness was considerably
lower than expected as compared with other studies. Underdiagnosis is suggested as a possible explanation. Study results were
used to add differential payment for physical comorbidity under the new National Health Insurance Law. Other corrective measures
are discussed.
A combination of elevated temperatures (within the human febrile range) and trace metal chelation were investigated for their effects on the inhibition of growth and phenotypic development of the dimorphic yeast Candida albicans (strain 3153A). The ability of specific cations to relieve the phenotypic inhibition that occurred also was tested.Elevated temperatures alone (to 41 C) only delayed the timing of the phenotypic development. When compared to the results obtained at 37 C, the recombination of elevated temperature and addition of the trace metal chelator, 1,10-phenanthroline, did not further suppress phenotypic development, but the combination did decrease the viability of C. albicans. When 24 to 48 h stationary phase singlet cells were released into a medium containing 100 M 1,10-phenanthroline (pH 6.5), supplemental iron (200 M) alleviated the suppression of mycelium formation at 41 C, whereas under conditions favoring bud formation (pH 4.5), both iron and zinc circumvented suppression and promoted budding. Through studies on the interaction of temperature stress and trace metal availability our data revealed the requirement for iron mycelium formation whereas both iron and zinc may be needed for bud formation.
Previously, it was demonstrated that antibody production against hepatitis B virus (HBV) surface antigen (anti-HBs) achieved in hemodialysis patients is suboptimal. Decreased health-related quality of life (HRQOL) and depression is common among hemodialysis patients. This study evaluated whether HRQOL and depressive behavior are associated with antibody response against HBV surface antigen in hemodialysis patients. Depressive symptoms and HRQOL were assessed by Beck Depression Inventory (BDI) and Medical Outcomes Study Short Form (SF-36), respectively. Patients were separated into non-seroconversion (anti-HBs antibody titers <10 IU/L) and seroconversion (anti-HBs antibody titers ≥10 IU/L) groups. Among 188 patients, 37 (19.7%) were diagnosed as nonresponsive to vaccination (anti-HBs antibody titers <10 1U/L). Anti-HBs response is positively associated with Physical Component Summary Score of SF-36 (odds ratio: 1.44; P: 0.009) and albumin (odds ratio: 10.615, P: 0.007), and negatively with BDI score (odds ratio: 0.903, P: 0.007). We concluded that HRQOL and depression is closely related with antibody response following HBV vaccine in hemodialysis patients.