ArticleLiterature Review

Etiology of Depression: Genetic and Environmental Factors

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Abstract

In summary, depressed patients with a history of childhood trauma may have a distinct depression endophenotype characterized by a specific neurobiology and risk genotype that may be responsive to different treatment strategies than depressed patients without childhood adversity. Based on current findings, treatment strategies should be multimodal and include the following: 1. Psychotherapy that addresses a number of domains, such as emotional regulation, cognitive reframing, careful exploration of past traumatic events, attachment, and interpersonal relationships in a safe and trusting therapeutic environment. 2. The therapy should likely be longer term in order to effectively impact those domains. 3. Pharmacotherapy that will be effective in quieting the body’s hyperresponsiveness to stress and reverse epigenetic modifications induced by trauma and stress. 4. Environmental interventions that provide a support network (maternal care, a positive family environment, the support of a close friend) have all been shown to attenuate the impact of childhood abuse. In addition, there is great potential in the identification of genomic biomarkers to help guide us in the identification of traumatized individuals who are susceptible to depression. These indices may also help identify those for whom the immediate provision of treatment may have a preventive effect and may someday guide us in the development of novel pharmacologic approaches.

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... Depression is an increasingly diagnosed disease worldwide [171]. According to the World Health Organization (WHO), depression is the fourth most serious disease in the world and is predicted to become the most common CNS disease by 2030 [172]. ...
... The current increase of the incidence of depression results in serious consequences, since this disease not only is the main cause of suicide (the fourth leading cause of death in 15-29-year-olds), but also increases predisposition to other diseases [173]. It affects people of all ages, especially adolescents, young adults and the elderly [171]. Disorders of the functions of neurotransmitter systems (serotonin, norepinephrine, dopamine) are the pathophysiological basis of depression. ...
... Some evidence supports the involvement of other neurotransmitter systems in the aetiology of depression, such as glutamate, GABA, substance P and BDNF [171]. ...
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The ketogenic diet (KD) is a high-fat, low-carbohydrate and adequate-protein diet that has gained popularity in recent years in the context of neurological diseases (NDs). The complexity of the pathogenesis of these diseases means that effective forms of treatment are still lacking. Conventional therapy is often associated with increasing tolerance and/or drug resistance. Consequently, more effective therapeutic strategies are being sought to increase the effectiveness of available forms of therapy and improve the quality of life of patients. For the moment, it seems that KD can provide therapeutic benefits in patients with neurological problems by effectively controlling the balance between pro- and antioxidant processes and pro-excitatory and inhibitory neurotransmitters, and modulating inflammation or changing the composition of the gut microbiome. In this review we evaluated the potential therapeutic efficacy of KD in epilepsy, depression, migraine, Alzheimer’s disease and Parkinson’s disease. In our opinion, KD should be considered as an adjuvant therapeutic option for some neurological diseases.
... Research is therefore trying to find markers that may help to classify and specify symptoms to adapt to individual therapy. The extent to which treatment can become more effective for MDD arguably depends on a deeper understanding of its etiology and pathophysiology (Saveanu & Nemeroff, 2012). ...
... Some studies report that MDD patients have typical alterations in the hypothalamicpituitary-adrenal (HPA) axis (Ehlert et al., 2001;Varghese & Brown, 2001). Most MDD patients demonstrate hypersecretion of cortisol partly due to an impaired endogenous glucocorticoid feedback regulation of HPA axis activity (Saveanu & Nemeroff, 2012;Stetler & Miller, 2011). Cortisol secretion in the after awakening is considered to be one of the most relevant measures to classify the function of the HPA axis (Stalder et al., 2016). ...
Article
The cortisol awakening response is a non-invasive biomarker for hypothalamic-pituitary-adrenal axis (HPA) dysregulation, reflecting accumulated stress over time. In a previous study we reported that a blunted CAR before an inpatient treatment predicted self-reported depressive symptoms six weeks and six months after discharge (XXXXXXXXX et al., 2019). This replication study adopted an improved overall methodology with more stringent assessment protocols and monitoring. The longitudinal design included 122 inpatients from a psychosomatic hospital with a diagnosis of Major Depression Disorder displaying symptoms of moderate to severe major depression (n=80 females). The Cortisol awakening response (CAR) was measured at intake. Depression severity was assessed as Beck Depression Inventory II scores at intake, discharge, six weeks and six months following discharge. Results from the original study were replicated in terms of effect size but did not reach statistical significance (correlation between BDI-II 6 months after discharge and AUCg: r=-.213; p=.054). The replication study yielded nearly identical correlation coefficients as in the original study (BDI-II 6 months and CAR, r=-.223, p<.05). The replication of previously reported effect sizes with a concurrent lack of statistical significance in the more restrictive, larger and better controlled replication study may well inform research on psycho-endocrinological predictors for treatment success, but suggests a rather limited practical relevance for cortisol awakening response measures in this clinical context.
... Moreover, depression has severe impacts on a person's physical and mental health and social economy, accounting for 10.3% of the total disease burden [4,5]. Depression is a multifactorial disease attributed to heredity, environment, epigenetics, and others, whose underlying mechanism is complex and has not yet been elucidated [6], thereby making its clinical diagnosis and treatment difficult. Meanwhile, most antidepressant drugs are associated with severe adverse events and unsatisfactory responses. ...
... Globally, the CUMS model is one of the classic depression models widely recognized by researchers [27] for searching for depression, a psychiatric disorder with high prevalence [6]. According to our experiments, a decline was identified in CUMS rats in body weight, preference for sucrose, time BioMed Research International preference, free movement ability, memory, and pathological damage of rats to varying degrees. ...
Article
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Objective: Red raspberry serves as a proven natural product to produce anti-inflammatory, antioxidant, and anticancer functions, but limited findings are available on its effects on depression. This study, by using a chronic unpredictable mild stress- (CUMS-) induced depression model, thus investigated the effects and underlying mechanism of red raspberry extract (RRE) on depressive behavior, inflammation, and oxidative stress. Methods: Different treatments were given after random grouping of Sprague-Dawley rats, including no intervention (control), CUMS induction, and CUMS+different concentrations of RRE, and subsequently, depression-like behavior tests were performed. HE staining was designed to observe the pathological damage of the hippocampal tissue in rats. The levels of oxidative stress, endocrine hormones, and inflammatory factors were determined by biochemical assay and ELISA, and gene expression (mRNA and protein) in the hippocampal tissue by qRT-PCR and Western blot. Results: On completion of CUMS treatment, the rats showed severe depression-like behavior, with obvious hippocampal tissue damage, oxidative inflammatory response, and endocrine imbalance. Importantly, RRE treatment significantly improved such depression-like behavior and attenuated histopathological damage in CUMS rats when reducing inflammation and oxidative stress and endocrine imbalance with upregulation of glutathione (GSH), superoxide dismutase (SOD), and interleukin- (IL-) 10 and downregulation of adrenocorticotropic hormone (ACTH), corticosterone (CORT), malondialdehyde (MDA), IL-1β, cyclooxygenase- (COX-) 2, and human macrophage chemoattractant protein- (MCP-) 1. In addition, for CUMS rats, RRE was a contributor to increasingly expressed brain-derived neurotrophic factor (BDNF), neurotrophic tyrosine receptor kinase 2 (TrkB), and p-mTOR but inhibited p-GSK-3β expression in the hippocampal tissue. All the above antidepressant effects of RRE were concentration-dependent. Conclusion: By regulating neuroinflammation, oxidative stress response, endocrine level, and BDNF/TrkB level, RRE showed potential efficacy in alleviating depression-like behavior and histopathological damage of hippocampal tissue in CUMS rats by regulating the GSK3β and mTOR signaling pathways.
... It has long been known that family history is one of the most important predictive tools for the diagnosis of depression, as twin studies suggest between 33% and 46% of the vari-ance is due to inherited genetic factors [30]. An array of studies suggests a preeminent role of genetic alterations of the three major monoamine systems (serotonin, norepinephrine, and dopamine circuits), with more recent conceptual approach involving several critical brain regions and associated pathways, as well as other structural, neuroendocrine, and immunologic changes in the body, influenced by epigenetic mechanisms and the environment [51]. Early studies used a number of approaches and faced many difficulties identifying any specific inherited factors, most likely due to depression being complex and vastly heterogeneous, with a great number of genetic loci, each contributing only a small effect [52]. ...
... As the genetic associations for major depression tend to occur in genomic regions conserved in many placental mammals, it seems that these genes have important functional roles, which might also contribute to the possibility of the genes being related to a number of conditions [52]. We further theorize that highly symptomatic disease, such as cancer, experienced by a child's primary caregiver, contribute to the parent not being able to provide continuous care, and could be considered as a stressful or traumatic childhood event, also predisposing an individual to develop depression later in life [51]. Indeed, cancer was shown as a particularly significant disease group in the bivariate analysis (p = 0.011; table not shown). ...
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Despite depression being a major driver of morbidity and mortality, the majority of primary care patients remain undiagnosed, so this study aimed to assess the prevalence of depression and the association with demographic and clinical variables, genetic risk, and quality of life. The participants were presumably healthy model family medicine practice (MFMP) attendees between 30 and 65 years of age and recruited during a preventive check-up in 2019. Each of the 40 pre-selected MFMP pragmatically invited 30 attendees to voluntarily participate. They completed a questionnaire of demographic, clinical, and social determinants, as well as a three-generational family history. The results were analyzed using multivariable modelling to calculate the associations with signs of depression. A modified Scheuner method was used to calculate the level genetic risk level using family history. Of 968 participants, aged 42.8 ± 8.6 years, 627 (64.8%) were women. The prevalence of depression was 4.1%. Signs of depression were negatively associated with health-related quality of life score, in particular in the domains of self-care (p = 0.001) and anxiety/depression (p < 0.001). Depression was also associated with predicted high risk for comorbidities given the family history (p = 0.030). Primary care directed at improving patients' quality of life should implement more widespread screening for mental health disorders. Family history for disease even beyond depression can be used by physicians as an important primary prevention tool.
... En lo relativo a los factores estructurales, donde la neuroanatomía del cerebro es alterada, se encuentra la reducción del hipocampo (entre otras áreas del sistema límbico) y núcleo caudado y el aumento de la glándula pituitaria, además de una disfunción en la corteza prefrontal (CPF) que afecta las funciones ejecutivas y el componente afectivo (Cruzblanca, Lupercio, Collas & Castro, 2016;Nedic Erjavec et al., 2021;Saveanu & Nemeroff, 2012). Se ha identificado una fuerte asociación entre factores biológicos (genética/estructuras) y el efecto de eventos traumáticos tempranos, como, por ejemplo, el abuso sexual, emocional y físico, la negligencia y perdida de figuras paternas, estas se constituyen como factores ambientales para el desarrollo de la depresión (Li et al., 2021;Saveanu & Nemeroff, 2012 Recientemente se ha formulado la hipótesis de que el TDM representa alteraciones en la estructura y función del sistema nervioso central (SNC), con la capacidad de perdurar en el tiempo, en reacción a niveles permanentes y excesivos de estrés (Lam, 2012;Pérez-Padilla, Cervantes-Ramírez, Hijuelos-García, Pineda-Cortés, & Salgado-Burgos, 2016). ...
... En lo relativo a los factores estructurales, donde la neuroanatomía del cerebro es alterada, se encuentra la reducción del hipocampo (entre otras áreas del sistema límbico) y núcleo caudado y el aumento de la glándula pituitaria, además de una disfunción en la corteza prefrontal (CPF) que afecta las funciones ejecutivas y el componente afectivo (Cruzblanca, Lupercio, Collas & Castro, 2016;Nedic Erjavec et al., 2021;Saveanu & Nemeroff, 2012). Se ha identificado una fuerte asociación entre factores biológicos (genética/estructuras) y el efecto de eventos traumáticos tempranos, como, por ejemplo, el abuso sexual, emocional y físico, la negligencia y perdida de figuras paternas, estas se constituyen como factores ambientales para el desarrollo de la depresión (Li et al., 2021;Saveanu & Nemeroff, 2012 Recientemente se ha formulado la hipótesis de que el TDM representa alteraciones en la estructura y función del sistema nervioso central (SNC), con la capacidad de perdurar en el tiempo, en reacción a niveles permanentes y excesivos de estrés (Lam, 2012;Pérez-Padilla, Cervantes-Ramírez, Hijuelos-García, Pineda-Cortés, & Salgado-Burgos, 2016). ...
Article
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El objetivo de esta investigación fue establecer el diseño y la validez de contenido de una Guía de Práctica Clínica (GPC) de análisis funcional (AF) para población con trastorno depresivo mayor (TDM). Se realizó por medio de una metodología cuantitativa de tipo instrumental, implementando la técnica de validación por jueces expertos, con la participación de seis jueces con experiencia en psicología clínica y cuatro en análisis del comporta- miento. Resultado de la evaluación de los jueces, se obtuvo un índice de validez de contenido de 0.85, permitiendo establecer la validez de la GPC de análisis funcional para evaluar el TDM. Se concluye que los procedimientos para realizar AF en TDM corresponden con los referentes teórico-prácticos disponibles y con la tradición del enfoque conductual en psicología.Palabras clave: Guía de Práctica Clínica, análisis funcional, depresión, diseño de contenido, validación de contenido.
... Its prevalence among the general population varies from less than 10% and up to 25%, is higher in women than men (Bromet et al., 2011), and, by 2030, is estimated to top the ranking of burden of disease, as measured in disability-adjusted life years (W.H.O, 2008). Both genetic and environmental factors have been implicated in developmental pathways to depression (Saveanu & Nemeroff, 2012;Sullivan, Neale, & Kendler, 2000). In relation to diagnosis, it has been seen that depression is not only misdiagnosed but also frequently overdiagnosed and also underdiagnosed, depending on the population studied and the professionals in charge of diagnosis (Cepoiu et al., 2008). ...
Chapter
This chapter introduces the study of the etiopathogenic field of depression, i.e., the study of causes and pathways through which subjects become depressed. Our goal is not without difficulties. First of all, we encounter a theoretical problem: we still do not know well what mental illness consist of, and we don’t have a precise definition of what depression is; within psychiatric conditions, depression is particularly pleomorphic. On the other hand, empirical research has described a wide range of risk factors for psychiatric illness that led to a variety of etiopathogenic models (from genetics to sociocultural models) that have tended to develop more in isolation than in an integrated manner, which has diminished their heuristic capacity. Depression is better understood as a complex behavior of a complex system that depends on multiple causes and multiple levels of organization. Nevertheless, what remains to be known are the relationships between the properties and behaviors at the different levels. The aim of this introductory chapter is to review the clinical phenomenon we call depression by critically considering the main aspects of its psychopathological diagnosis and its conceptual history as well as to understand the epistemological relationship between the clinical picture and the various causal fields in psychiatry, proposing ways, and explaining difficulties for the integration of theories and models in depression, taking into account the most relevant findings of research. Finally, we conclude that it is necessary to develop empirical studies that include integrative models that account for the dynamic interaction between the different levels of causality.
... At present, the pathogenesis of depression has not been clearly identified, with genetic, socioeconomic, environmental, and behavioral factors potentially acting jointly (6)(7)(8). Among these factors, stress is acknowledged as an important risk factor for depression (9,10). ...
Article
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Although it is widely acknowledged that older adults who have gone through negative life events are more likely to develop depression, there is limited evidence on whether and which type of social ties moderate this perceived relationship. Based on 2016 and 2018 waves of Chinese Longitudinal Aging Social Survey (4,466 individuals, 8,932 observations), we apply linear fixed effects models and confirm that negative life events are associated with depressive symptoms for older adults (Coef. = 0.35; 95% CIs 0.11–0.61), and social ties are negatively associated with depression (Coef. = −0.08; 95% CIs −0.10 to −0.07). Our study further suggests that the association between negative life events and depressive symptoms is significantly moderated by friendship ties (Coef. = −0.18, 95% CIs −0.30 to −0.07), rather than family ties (Coef. = −0.03, 95% CIs −0.09 to 0.15). Moreover, the buffering effects of friendship ties are more prominent for the less resilient and less privileged groups, namely male, rural, and less educated older adults. Our findings point to the importance of expanding and strengthening social networks for Chinese older adults in promoting their psychological health.
... Personality -an individual's patterns of thoughts, feelings and behaviours -has typically been studied by personality psychologists who apply quantitative methods such as factor analysis to examine how people differ from one another 1,2 , how these differences develop over time 3 and how personality differences are related to important life outcomes, such as income, health and relationship satisfaction 4,5 . Psychiatric disorders have typically been studied by psychiatrists and clinical psychologists who use diagnostic models generated by committee consensus 6 to determine the prevalence 7 , course 8,9 , aetiology 10,11 and effective treatments 12,13 of different disorder categories, such as depression, anxiety and substance use disorders. With some noteworthy exceptions [14][15][16][17][18][19] , these traditions have proceeded relatively separately. ...
Article
Personality and psychopathology have generally been regarded as distinct aspects of human behaviour, largely studied by researchers from different disciplines. However, an established body of research shows a common structure for personality and psychopathology phenotypes. This evidence has led to significant changes in how psychiatric problems are conceptualized and studied, as well as new questions about the differences between personality traits and mental disorders. In this Perspective, we suggest that models that differentiate personality and psychopathology based on the structure or stability of individual differences depict models of risk for psychopathology at the population level, rather than frameworks for psychiatric diagnosis at the individual level. We propose that person–environment transactions, across different timescales, hold the key for differentiating personality and psychopathology, and thus for psychiatric diagnosis. This proposal points to the need for new approaches to studying personality, psychopathology and the differences between the two.
... It is a feeling of sadness, emptiness, pessimitic thoughts, suicidal thoughts and insomnia. [40][41] The etiology in development of depression involved both genetic and environmental factors [42] Generally it is believed that stress is the primary environmental factor that lead to depression but only half of the population experience such events in life. The genetic factors have a vital role to decide the individual sensitivity to stress. ...
Article
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5-HT3 receptor antagonist have major role play in the management of neuro psychiatric and GIT disorders. Palonosetron is a newly generated 2nd generation of 5HT3 receptor antagonist. FDA first approved Palonosetron in 2003 for prevention of acute nausea and vomiting associated with chemotherapy and used as antiemetic agent. It also used in pediatric patients to control sickness. The first generation of 5-HT3 receptor antagonist such as ondansetron, granisetron, dolasetron and tropisetron are found to have similar efficacies in preventing acute cancer induced nausea and vomiting. Palonosetron hydrochloride is white to grayish, non-hygroscopic, glasslike powder, uninhibitedly dissolvable in water and dissolvable in methanol. It has two chiral focuses while the dynamic substance in the item comprises of a solitary stereoisomer. Palonosetron hydrochloride is known to show polymorphism. Its chemical name is (3aS)- 2-[(3S)- 1-azabicyclo[2.2.2]oct-3-l]- 2,3,3a,4,5,6-hexahydro-1H-benz[de]-isoquinolin-1-one hydrochloride relating to the atomic equation C19H24N2O·HCl and has an overall sub-atomic mass of 332.87g/mol. The pharmacokinetics of Palonosetron have half-life around 40 hours and shows to be broadly appropriated in the body, bound to plasma proteins at an extent of 62%, processed by cytochrome P450 compounds, basically CYP2D6, with minor commitments from CYP1A2 and CYP3A4 and eliminates through urine. This review highlights the therapeutic, pharma kinetic and pharmacological properties of palonosetron that have been reported since 2003 and also displays the gaps in our knowledge about both the compounds and its characteristic limitations which deserves more exploration.
... A range of factors are involved in the pathogenesis of depression including biological, hormonal, environmental, socio-economical, socio-cultural, and genetic factors (Nagy et al., 2018;Schaakxs et al., 2017). From all the depressive cases, approximately one-third involve inheritance while the remaining two-third occur in response to above mentioned causative factors other than genetics (Saveanu & Nemeroff, 2012). The biological factors and mechanisms possibly involved in pathophysiology of depression may include neural plasticity, endogenous toxicant attacks leading to altered brain activities and decreased volume of frontal cortex & hippocampus. ...
Article
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Neurological disorders are increasing at a faster pace due to oxidative stress, protein aggregation, excitotoxicity, and neuroinflammation. It is reported that the Mediterranean diet including olives as a major dietary component prevents and ameliorates neurological anomalies. Oleuropein is the major bioactive component in different parts of the Olive (Olea europaea L.) tree. Several mechanisms have been reported for the neuroprotective role of oleuropein including induction of apoptosis and autophagy, enhancing the antioxidant pool of the cerebral region, decreasing the unnecessary release of proinflammatory cytokines and chemokines by deactivating the microglia cells and astrocytes thus preventing the occurrence of neuroinflammation. Regular intake of oleuropein seems to be correlated with decreased risks of neural disorders including Alzheimer's, Parkinson's, strokes, depression, anxiety, epilepsy, and others. This review majorly discusses the chemistry, biosynthesis, and metabolism of oleuropein along with an updated vision of its neuroprotective role in counteracting the acute and chronic neurodegenerative and neuropsychiatric disorders. Moreover, mechanisms by which oleuropein may prevent neurodegeneration are reviewed. Practical application Neurological disorders are negatively affecting the health and life quality of individuals around the globe. Although various medicinal solutions are available to tackle such ailments, none has proven to fully cure and being deprived of side effects. In this respect, the prevention of such disorders using natural remedies may be an effective strategy to overcome the incidence of the increasing cases. Furthermore, the natural compounds provide a safer alternative to pharmaceutical drugs. Hence, oleuropein from olive tree products is found to be efficacious against neurological disorders. This review provides an updated insight on the positive effects of oleuropein against neurodegenerative and neuropsychiatric disorders. The diet practitioners and nutraceutical companies may benefit from the provided information to design and develop strategies to improve the mental health of suffering individuals.
... A la fecha se han identificado diversos factores asociados a la etiología de la depresión, que incluyen tanto antecedentes genéticos y alteraciones fisiopatológicas, como factores ambientales y psicosociales, y sus interacciones 5,6 . Entre los con mayor evidencia apuntan al riesgo aumentado en mujeres 1,7,8 , en personas en situación de vulnerabilidad, como pobreza 9 , frente a estrés financiero 10 , presencia de dolor 11 , morbilidad 12 y experiencias traumáticas, particularmente en etapas tempranas del desarrollo 13,14 . ...
Article
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Background: Depression is a highly prevalent disease in Chilean adults. Aim: To identify sociodemographic, biomedical, and psychosocial factors related with depression in a representative sample of the Chilean adult population. Material and methods: Analysis of data from the National Health Survey 2016-2017 which included 5,291 participants aged > 15 years. Depression was assessed using the Composite International Diagnostic Interview (CIDI-SF). Association between sociodemographic data, health and psychosocial variables and depression was analyzed using Poisson regression with robust error. Results: The probability of depression was higher in women than in men (prevalence ratio (PR) = 2.13 [95% confidence intervals (CI): 1.65, 2.75]). In both genders, the probability was higher in people with frailty (women: PR = 10.0 [95% CI: 1.86, 18.1] and men: PR = 3.38 [95% CI: 2.72; 4.20]), severe chronic pain (women: PR = 2.84 [95% CI: 1.93, 4.18 and men: PR = 6.41 [95% CI: 3.59, 9.40]), presence of two or more diseases (women: PR = 4.15 [95% CI: 2.78, 6.20 and men: PR = 2.60 [95% CI: 1.39, 3.81]), perception of permanent stress (women: PR = 11.0 [95% CI: 6.13, 16.0], men: PR = 21.0 [95% CI: 10.2, 31.7]), financial stress (women: PR = 2.57 [95% CI: 1.87, 3.27] men: PR = 4.27 [95% CI: 2.48, 6.06] and poor or very poor perception of health (women: PR = 5.02 [95% CI: 1.92, 8.12], men: 2.09 [95% CI: 0.49, 3.69]). In men, the probability of depression was higher for widowers than married man (PR = 5.58 [95% CI: 2.5, 8.25]), presence of goiter (PR = 4.03 [95% CI: 1.99, 6.07]) and low social support (PR = 1.95 [95% CI: 1.18; 2.72]). Conclusions: The factors associated with a higher probability of depression are diverse in nature. Among these being women, frailty, chronic pain, multimorbidity and high perception of stress are important factors.
... [17] Neuroplasticity, which involves structural and functional brain adaptations in response to changes in environmental life-event, is abnormal in individuals with depression. [18] ...
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Depression is a psychiatric disorder that is widespread around the world and affects more than 300 million individuals. Treatment of depression divides into psychological counseling and antidepressant medication. Although antidepressants are an effective method of treating depression, alternative treatments are necessary due to their strong adverse effects. As an alternative treatment of depression, commonly used psychedelics are classic serotonergic psychedelics, entactogens, the atypical psychedelic ibogaine, and dissociative anesthetics. Psilocybin in particular, as well as LSD (lysergic acid diethylamide) and ayahuasca containing DMT (N, N-dimethyltryptamine), are seen as promising novel treatments for depression. In this review, the effect of psychedelic drugs, in particular LSD, psilocybin, and DMT on the treatment of depression will be discussed.
... In pharmacotherapy, with the use of antidepressant group drugs, it is possible to cope with depression by affecting the amygdala region of the brain, increasing the production of positive emotions and reducing the production of negative emotions. [27] ...
Article
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Major depressive disorder (MDD) is a long-term mood disorder that occurs in an individual's mood. It is a disease that is mostly encountered in the adolescence period of living things, but it can also occur in other life stages. Social environment or genetic factors can be effective in the emergence of depression. The person constantly feels sad and tired, changes in eating habits, not being able to enjoy the work done, loss of concentration, and this process may result in suicide. MDD is medically treatable, but relapses occur in most individuals. Copper mineral, which plays a role in the strengthening of the skeletal-muscular system and the regeneration of tissues, is the most abundant mineral in the tissues after zinc and iron and is taken into the body through diet. It is known that in cases where copper homeostasis is not provided, it causes the development of diseases by affecting many cellular processes. In this article, the link between depression and high copper concentration in the organism will be discussed.
... Specifically among older adults, depression is a serious health issue, as late-life depression is strongly associated with all-cause and cardiovascular mortality [5]. The etiology of depression is multifactorial different genetic, environmental and behavioral factors can contribute to its onset and development [4,6,7]. ...
Article
Objectives : To investigate the cross-sectional and prospective associations of lifestyle risk behaviors clustering with elevated depressive symptoms and to explore synergic prospective associations of different combinations of lifestyle risk behaviors with subsequent depressive symptoms. Study design : Prospective cohort study. Data on 31,190 middle-aged and older adults from waves 4 (2011) and 6 (2015) of the Survey of Health, Ageing and Retirement in Europe (SHARE) were used. Main outcome measures : Elevated depressive symptoms were estimated using the EURO-D 12-item scale. Lifestyle risk behaviors composing the cluster included physical inactivity, inadequate consumption of fruit and/or vegetables, binge drinking, and tobacco smoking. Gender, age group, education, place of residence, country, number of chronic diseases and body mass index were considered as confounders. Results : With the exception of binge drinking, all lifestyle risk behaviors were associated with higher odds of elevated depressive symptoms in cross-sectional and prospective analyses. The clustering of unhealthy lifestyle behaviors was cross-sectionally associated with elevated depressive symptoms and the clustering of two [odds ratio [OR]: 1.39; 95%CI: 1.28-1.51) and three or four (OR: 1.60; 95%CI: 1.38-1.85) was prospectively associated with elevated depressive symptoms. Conclusions : Our findings support the need for interventions integrating multiple health behaviors to prevent elevated depressive symptoms among middle-aged and older adults.
... Along with genetic, lifestyle behaviors, including diet, might have roles in the incidence of anxiety and depression (8) . Earlier studies demonstrated the association between consumption of dairy products, vegetables, fruits, olive oil and phytochemicals and lower risk of depression (9; 10; 11; 12) . ...
Article
Previous investigations have mostly studied an individual methyl donor nutrient in relation to psychological disorders and the findings were inconsistent. We investigated the association of methyl donor micronutrients (folate, B 6 , B 12 , choline, betaine, and methionine) with psychological disorders (depression, anxiety, psychological distress) in Iranian adults. In this cross-sectional study, dietary intakes of 3299 adults were collected using a validated food frequency questionnaire. Methyl donor micronutrient score (MDMS) was calculated based on energy-adjusted deciles of each nutrient. Hospital Anxiety and Depression Scale (HADS) and General Health Questionnaire (GHQ), validated for Iranians, have been applied to assess depression, anxiety, and psychological distress. Participants had a mean age of 36.3±7.9 years, of whom 58.5% were women. After considering potential confounders, adults in the top quartile of MDMS, compared to the bottom one, had decreased odds of anxiety (OR: 0.53, 95%CI: 0.37–0.75), depression (OR: 0.75, 95%CI: 0.58–0.97) and psychological distress (OR: 0.61, 95%CI: 0.46–0.80). Stratified analysis revealed that the highest category of MDMS among men was related to a 68% lower odds of anxiety (95%CI: 0.15–0.68). Among women, the top quartile of MDMS was protectively associated with anxiety (OR: 0.60, 95%CI: 0.40–0.90), depression (OR: 0.68, 95%CI: 0.50–0.93) and psychological distress (OR: 0.53, 95%CI: 0.38–0.74). Overweight and obese subjects in the highest quartile of MDMS had a 67%, 35%, and 53% lower odds of anxiety (95%CI: 0.20–0.56), depression (95%CI: 0.44–0.94), and psychological distress (95%CI: 0.31–0.70), respectively. We found that high consumption of methyl donor micronutrients was related to a reduced odds of psychological disorders, especially in women and overweight or obese individuals. Further prospective studies are needed to affirm these findings.
... Findings from GWAS analysis may help to fill in gaps in our knowledge about the pathogenesis of MDD. Currently, the major hypothesized mechanisms focus on altered activity of neurotransmitters (e.g., monoamines and acetylcholine), growth factor signaling (especially brain-derived neurotrophic factor, BDNF), immune system components (cytokines), defective regulation of the hypothalamus-pituitary-adrenal (HPA) axis and environmental factors including childhood trauma and stress (1,(27)(28)(29). Presumably, the genetic risk variants affect the function of these pathways directly and/or else the resiliency phenotype needed to cope with adverse psychosocial impacts. ...
Article
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Major depressive disorder (MDD) affects around 15% of the population at some stage in their lifetime. It can be gravely disabling and it is associated with increased risk of suicide. Genetics play an important role; however, there are additional environmental contributions to the pathogenesis. A number of possible risk genes that increase liability for developing symptoms of MDD have been identified in genome-wide association studies (GWAS). The goal of this study was to characterize the MDD risk genes with respect to the degree of evolutionary conservation in simpler model organisms such as Caenorhabditis elegans and zebrafish, the phenotypes associated with variation in these genes and the extent of network connectivity. The MDD risk genes showed higher conservation in C. elegans and zebrafish than genome-to-genome comparisons. In addition, there were recurring themes among the phenotypes associated with variation of these risk genes in C. elegans . The phenotype analysis revealed enrichment for essential genes with pleiotropic effects. Moreover, the MDD risk genes participated in more interactions with each other than did randomly-selected genes from similar-sized gene sets. Syntenic blocks of risk genes with common functional activities were also identified. By characterizing evolutionarily-conserved counterparts to the MDD risk genes, we have gained new insights into pathogenetic processes relevant to the emergence of depressive symptoms in man.
... According to the biopsychosocial model, MDD is caused by a combination of biological, psychological, and social variables [2]. According to the diathesis-stress concept, depression occurs when stressful life events trigger an underlying susceptibility. ...
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Background Disturbances in structural and synaptic plasticity have been linked to depression and suicidal ideation. One of the major neurotrophic factors, the brain-derived neurotrophic factor (BDNF), is involved in the maintenance and survival of neurons and synaptic plasticity. This case–control study assesses the serum BDNF and suicidal ideation among drug-naïve and drug-treated MDD patients attending university hospitals and comparing them to healthy control. A simple random sample of 57 MDD patients and 57 age- and sex-comparable controls were enrolled. The researchers conducted a semi-structured interview to collect the demographic characteristics and disease history. Structured Clinical Interview for DSM-5 (SCID-5), Hamilton Depression Rating Scale (HDRS), and Beck Scale for Suicidal Ideation (BSS) were applied to the participants. Blood samples were collected to measure plasma BDNF level. Results The MDD group had lower BDNF than the control group. Within the MDD group, drug-naïve patients had significantly lower BDNF than drug-treated patients. Female patients had lower BDNF than male patients. Positive family history of MDD was associated with low BDNF. Severe and moderate cases had lower BDNF than mild cases. High BSS (≥24) was associated with low BDNF. A statistically significant positive correlation was found between BDNF and age, disease duration, duration of the current episode, and the number of previous episodes. On the other hand, a statistically significant negative correlation was found between BDNF and age of MDD onset, HDRS, and BSS. A regression model was highly statistically significant in the prediction of HDRS. BDNF and disease duration were negatively correlated with HDRS. On the other hand, depression treatment status was not significantly associated with the HDRS prediction model. Conclusion Our findings extend the neurotrophic concept of depression by identifying the decreased BDNF levels as a peripheral biomarker of MDD. Our assessment of depression and suicidal ideation (SI) and their relationship to decreased BDNF levels shed light on the etiopathology of MDD and its related suicidality. They should be more studied to understand better the mechanisms by which they develop. To further explore the effect of BDNF in suicide, larger study sizes and a range of psychiatric diagnoses associated with suicide attempts are required.
... INTRODUCTION -Behavioral adaptation to stressful environment 2 | P a g e review). Thus, if stress is essential for survival, it can also precipitate psychiatric disorders such as anxiety-related disorders, depression, and post-traumatic stress disorder (see reviews : Heim et al., 2008;Martin et al., 2009;Walsh, 2011;Saveanu and Nemeroff, 2012;Nemeroff, 2016;Godoy et al., 2018). ...
Thesis
Adapting our behavioral response when facing a threating environment is essential to survival. This ability is supported by a wide brain network. The lateral habenula (LHb) seems to be an important structure of the stress response as it shows important activation in the presence of various stressors; it is postulated to interact with limbic structures such as the medial prefrontal cortex, the extended amygdala, and the hippocampus in order to participate to stress coping. However, these interactions remain poorly explored. The goal of my PhD project was to study in rats the role of the LHb in the stress response and how it is integrated into the wide network supporting such response, at the emotional, cognitive, and behavioral levels. In a first study, we demonstrated the implication of the LHb in fear memory, as well as its interaction with the key limbic structures engaged in this process. In our second study, we explored the functional network engaged during restraint stress and found the close interaction between the LHb and the whole stress response network, also including monoaminergic systems, suggesting the LHb contributes to the balance of the monoaminergic control over key limbic structures involved in the stress response. In our last study, using local field potential recordings, we discovered that the LHb was differentially engaged during the different steps of the response to immobilization stress, whether they take place during periods of active waking, or during sleep. Altogether, these results increase our knowledge of the engagement of the LHb in stress coping, in coordination with the key limbic regions involved in emotional processes; they further support the idea that this structure is a crucial hub of information integration, updating the network supporting the stress response.
... A la fecha se han identificado diversos factores asociados a la etiología de la depresión, que incluyen tanto antecedentes genéticos y alteraciones fisiopatológicas, como factores ambientales y psicosociales, y sus interacciones 5,6 . Entre los con mayor evidencia apuntan al riesgo aumentado en mujeres 1,7,8 , en personas en situación de vulnerabilidad, como pobreza 9 , frente a estrés financiero 10 , presencia de dolor 11 , morbilidad 12 y experiencias traumáticas, particularmente en etapas tempranas del desarrollo 13,14 . ...
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Background: Depression is a highly prevalent disease in Chilean adults. Aim: To identify sociodemographic, biomedical, and psychosocial factors related with depression in a representative sample of the Chilean adult population. Material and Methods: Analysis of data from the National Health Survey 2016-2017 which included 5,291 participants aged > 15 years. Depression was assessed using the Composite International Diagnostic Interview (CIDI-SF). Association between sociodemographic data, health and psychosocial variables and depression was analyzed using Poisson regression with robust error. Results: The probability of depression was higher in women than in men (prevalence ratio (PR) = 2.13 [95% confidence intervals (CI): 1.65, 2.75]). In both genders, the probability was higher in people with frailty (women: PR = 10.0 [95% CI: 1.86, 18.1] and men: PR = 3.38 [95% CI: 2.72; 4.20]), severe chronic pain (women: PR = 2.84 [95% CI: 1.93, 4.18 and men: PR = 6.41 [95% CI: 3.59, 9.40] ), presence of two or more diseases (women: PR = 4.15 [95% CI: 2.78, 6.20 and men: PR = 2.60 [95% CI: 1.39, 3.81]) , perception of permanent stress (women: PR = 11.0 [95% CI: 6.13, 16.0], men: PR = 21.0 [95% CI: 10.2, 31.7]), financial stress (women: PR = 2.57 [95% CI: 1.87, 3.27] men: PR = 4.27 [95% CI: 2.48, 6.06] and poor or very poor perception of health (women: PR = 5.02 [95% CI: 1.92, 8.12], men: 2.09 [95% CI: 0.49, 3.69]). In men, the probability of depression was higher for widowers than married man (PR = 5.58 [95% CI: 2.5, 8.25]), presence of goiter (PR = 4.03 [95% CI: 1.99, 6.07]) and low social support (PR = 1.95 [95% CI: 1.18; 2.72]). Conclusions: The factors associated with a higher probability of depression are diverse in nature. Among these being women, frailty, chronic pain, multimorbidity and high perception of stress are important factors. (Rev Med Chile 2021; 149: 1430-1439) Key words: Depression; Risk;Risk Factors.
... Depression is one of the most prevalent psychiatric disorders worldwide (Institute of Health Metrics and Evaluation, 2019). The etiology of depression is complex and multifactorial, being the cumulative contribution of many genetic and environmental risk factors (Sullivan et al., 2000;Saveanu and Nemeroff, 2012;McIntosh et al., 2019). Recently, exposures to environmental factors such as air pollution, noise, trace pharmaceuticals, and others have received considerable recognition as risk factors for adverse health outcomes (reviewed in: (van den Bosch and Meyer-Lindenberg, 2019; Costa and Steffen, 2019)). ...
Article
Organophosphate (OP) chemicals include commonly used pesticides and chemical warfare agents, and mechanistically they are potent inhibitors of the cholinesterase (ChE) enzyme. Epidemiological studies report long-term neuropsychiatric issues, including depression and cognitive impairments in OP-exposed individuals. Chlorpyrifos (CPF) is one of the most widely used pesticides worldwide. Multiple laboratory studies have reported on either the long-term behavioral effect of an acute high-dose CPF (30-250 mg/kg) or studied sub-chronic behavioral effects, particularly the motor and cognitive effects of repeated low-dose CPF. However, studies are lacking on chronic mood and depression-related morbidities following repeated CPF doses that would mimic occupationally relevant OP exposures. In this study, adult male rats were injected with CPF (1, 3, 5, or 10 mg/kg/d, s.c.) for 21 consecutive days. Dependent on the CPF dose, ChE activity was inhibited approximately 60-80% in the blood and about 20-50% in the hippocampus at 2-days after the end of CPF exposures. Following a 12-week washout period, a complete recovery of ChE activity was noted. However, CPF-treated rats exhibited a dose-dependent increase in signs related to anhedonia (sucrose preference test), anxiety (open-field and elevated plus-maze), and despair (forced swim test) at this stage. To the best of our knowledge, this could be the first laboratory study that demonstrates a cause-effect relationship between occupational-like CPF exposures in adult rats and the development of long-term depression-related outcomes and could provide an experimental system to study molecular mechanisms underlying environmental OP exposures and the elevated risk for chronic behavioral deficits.
... The World Health Organization's (2021) Fact Sheet highlights that depression is "a major contributor to the overall global burden of disease" and that it contributes to over 700,000 deaths annually, mainly due to suicide. The development of depression may involve a combination of both biological and psychosocial factors, including gene-environment interactions (Saveanu & Nemeroff, 2012). Among different etiological risk factors for mental health problems in general and depression specifically, the experiences of childhood adversities such as childhood abuse and family conflicts have been proposed to be the most preventable risk factor for severe mental health problems, particularly depression (The Childhood Adversity Narratives, 2015). ...
Article
Background: Childhood adversities have been increasingly recognized as a significant risk factor for depression. However, the underlying mediating mechanism between childhood adversities and depression requires further investigation. The literature shows that childhood adversities are also closely associated with post-traumatic stress disorder (PTSD) symptoms and that PTSD symptoms can predict depressive symptoms. It remains unexplored whether PTSD symptoms can act as a mediator between childhood adversities and depression. Objectives: The primary goal of this study was to examine whether PTSD symptoms would mediate the relationship between childhood adversities and depressive symptoms. Participants and setting: We examined in a convenience sample of Hong Kong adults aged 18 or above (N = 418) whether PTSD symptoms would mediate the relationship between childhood adversities and depressive symptoms. We then examined and compared the results with those in another convenience sample of Chinese-speaking young adults (mainly from Taiwan and Hong Kong) aged between 18 to 24 (N = 205). Participants in both samples completed online surveys that included measures of childhood adversities, PTSD symptoms and depressive symptoms. Results: Childhood adversities were significantly associated with depressive symptoms; and this relationship was mediated by PTSD symptoms in both samples. Conclusion: This study is one of very few studies demonstrating that PTSD symptoms mediate the relationship between childhood adversities and depressive symptoms. Our findings suggest that addressing unresolved PTSD symptoms for adults with childhood adversities may help in preventing or treating depressive symptoms. Therefore, PTSD symptoms should be taken into account in the prevention and management of depression. Keywords: Childhood adversities, Depression, Post-traumatic stress disorder (PTSD), Trauma-informed perspective, Child protection
... The causes of depression are complex. They include interactions between social, psychological, and biological factors, such as changes in neurotransmitter systems, dysregulation of the hypothalamicpituitary-adrenal axis, inflammations, and epigenetics [2][3][4][5][6]. Research shows a strong link between depression and physical health. ...
Article
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Depression is a common mental disorder that occurs all over the world with treatment resistance commonly seen in clinical practice. Ketamine exhibits an antidepressant that is more often used in the case of treatment-resistant depression (TRD) in MDD and BP. Research emphasizes that a healthy diet and the nutrients it contains can lower the risk of developing depression and form a strategy that supports conventional treatment. The aim of the study was to evaluate the patients’ diet and to analyze the effect of ketamine on food intake among patients with TRD. The study involved 15 patients suffering from treatment-resistant depression and 15 healthy volunteers. The data required for the analysis were collected using the food frequency questionnaire (FFQ) and 4-day food diaries. The study group was statistically significantly less likely to consume milk and plain milk beverages, plain white cheese, wholemeal bread, various vegetables, wine, and drinks. Our results show several disorders in the eating habits of patients with treatment–resistant depression. After the administration of ketamine, the patients consumed significantly less protein, fats, monounsaturated fatty acids (MUFA) and polyunsaturated fatty acids (PUFA), fiber, tryptophan, vitamins, and minerals compared to the control group. There is a lack of research describing the effects of ketamine on nutrition. In order to confirm the results of the study, more participants are required, and the assessment of food diaries filled in at the patient’s home with a longer interval after the last dose of ketamine as well.
... The causes of depression are complex but still not fully understood. It is suggested that the appearance of this disease is primarily affected by genetic factors, psychological factors, and atypical brain structure and function [1]. Recently, an increasingly important role is attributed to nutritional and inflammatory factors [2,3]. ...
Article
The causes of depression are diverse and are still not fully understood. Recently, an increasing role is attributed to nutritional and inflammatory factors. The aim of this study was to evaluate selected metabolites of the tryptophan kynurenine pathway in depressive patients with small intestinal bacterial overgrowth (SIBO). The study involved 40 healthy people (controls) and 40 patients with predominant small intestinal bacterial overgrowth (SIBO-D). The lactulose hydrogen breath test (LHBT) was performed to diagnose SIBO. The severity of symptoms was assessed using the Gastrointestinal Symptom Rating Scale (GSRS-IBS) and the Hamilton Depression Rating Scale (HAM-D). The concentration of tryptophan (TRP), kynurenine (KYN), kynurenic acid (KYNA), and quinolinic acid (QA) in urine was determined using an LC-MS/MS method, before and after cyclic treatment with an antibiotic drug, rifaximin, for three months. The number of intraepithelial lymphocytes (IELs) in the duodenum and small intestinal mucosa, fecal calprotectin (FC) and serum level of C-reactive protein (CRP) were also determined. In patients with SIBO, a higher level of KYN and QA were found as compared to the control group. These two groups also differed in KYN/TRP (higher in SIBO) and KYNA/KYN ratios (lower in SIBO). A positive correlation was found between HAM-D and the number of IELs and the level of FC. Treatment with rifaximin improves the kynurenic pathway, as well as abdominal and mental complaints. Therefore, small intestinal bacterial overgrowth can be a cause of abdominal symptoms, but also mental disorders.
... This pilot study is the first to explore the feasibility and effectiveness of CBASP adapted for children and adolescents suffering from depression. Considering the current low treatment outcomes [15] as well as the high proportion of interactional problems in the context of depressive disorders [77,78], this treatment program is highly relevant. It will provide important knowledge on the feasibility and effectiveness of this program, and reveal the potential of including caregivers in psychotherapy. ...
Article
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Background Depression is a serious disorder in childhood and adolescence. Affected children and adolescents show significant impairments in various aspects of life. Studies on the effectiveness or efficacy of psychotherapy in depressed children and adolescents are qualitatively very heterogeneous and reveal small effect sizes. There is thus a need to better tailor psychotherapy approaches to these age groups to improve outcomes like parent-child relationship, symptomatology, or quality of life. To address this gap, we designed a modular, individualized treatment program for children and adolescents based on the Cognitive Behavioral Analysis System of Psychotherapy (CBASP) including caregiver involvement. Method This quasi-experimental pilot feasibility trial is a phase 1 to phase 2 study investigating the feasibility and effectiveness of CBASP@YoungAge by including an intervention group (CBASP@YoungAge) and a treatment-as-usual control group. The treatment of depressive symptoms as well as interpersonal problems with primary caregivers are the main targets of CBASP@YoungAge. Personalization is ensured concerning the treatment course, caregivers’ involvement, and the patient’s age. The primary outcome relates to two areas: the feasibility of the CBASP@YoungAge treatment program in an outpatient context and a change in patients' depressive symptomatology from before to after treatment. We conduct a brief process evaluation after each session in the intervention group to closely monitor the treatment process and examine feasibility from the therapists' and patients' perspectives and mechanisms of symptom change. In addition, we consider interpersonal behavior between children and caregivers, parenting behavior, and monitor the global-health-index in children and parents as secondary outcomes. Pre-, post-, and follow-up data are evaluated. Discussion This is the first study of a modular-based intervention program for children and adolescents with depression and a clear focus on the interpersonal problems between the depressed young patient and her/his caregiver. It will provide important knowledge on the feasibility and effectiveness of the program and potential benefits of including caregivers in psychotherapy. Based on this study’s results, we plan a multicenter, randomized, controlled trial whose long-term aim is to improve the psychotherapeutic care of young patients with depression while preventing persistent courses of depressive disorders. Trial registration German Clinical Trials Register, DRKS (identifier DRKS00023281 ). Registered 17 November 2020–Retrospectively registered
... But in major depression, CRH receptors are reduced along with disruption of feedback inhibition of CRH release leading to elevated levels of CRH in cerebrospinal fluid (CSF) [30]. Stress-induced hypersecretion of cortisol as well as alterations in serotonergic, noradrenergic and dopaminergic play significant role in the pathogenesis of major depression [31]. ...
... According to an estimate recently presented by World Health Organization (WHO), depression stands at the 4th place among the main causes of disability in the world, women being two times more susceptible to depression during their lifetime as compared to men. The developed countries harbor higher number of depressed people than the underdeveloped world [22]. ...
Article
Depression is a psychosomatic disorder. The pharmacological treatment of depression has been based on the pathophysiology of deficiency in monoamines, mainly serotonin and noradrenaline. All approved antidepressants designed to enhance central monoaminergic tone possess many limitations such as 2 to 5 weeks delay in response, a limited clinical efficacy, and severe side effects. Since the pathophysiological aberrations associated to depression go beyond monoamines, the development of better antidepressants would depend on the identification and understanding of new cellular targets. The pharmacological studies of antidepressants, however, indicate the involvement of the blockade of neuronal uptake systems for norepinephrine and serotonin (5-hydroxytryptamine) including receptors for neurotransmitters. Many preclinical studies have suggested that hippocampus containing abundant agonists such as5-HT1A and 5-HT4 receptor subtypes in the dentate gyrus (DG) is critically involved in the mechanism of action of antidepressants. DG being a part of hippocampus possibly contributes to the brain functions such as formation of new sporadic memories. It is reported that antidepressants cause significant alterations in the structure and function of different brain regions in order to finally lead to their therapeutic effects. This review presents an overview of structural changes in the brain during depression; different neurobiological theories and novel drug development; strategy of augmentation with combinatorial therapy; receptors and targets of actions of antidepressants; and involvement of key signaling factors in the regulation of depression, pharmacology, metabolism, and the underlying principles involved in displaying how the application of antidepressants modulates the structure and function of the brain.
... There have been studies on the aetiology of depression Durisko et al., 2015;Saveanu & Nemeroff, 2012), which is the most common mental health disorder in the general population (Lim et al., 2018). Efforts have been made in line with this during the pandemic (Hajek et al., 2022;Liu et al., 2022). ...
Article
Objectives: The COVID-19 pandemic has negatively affected the lives of millions of individuals physiologically, behaviorally, socially, and/or psychologically. Moreover, there is now much empirical evidence that mental health problems have increased during the pandemic period and these problems have various consequences. The changes in the mood states of individuals due to the pandemic underpins the rationale of the present study. The aim of the study was to identify the cross-sectional associations between fear of COVID-19, stress, anxiety, and depression by using two stage-meta-analytic structural equation modeling (TS-MASEM). Design: This is a meta-analytic structural equation modelling study. Method: A systematic literature review initially identified 4840 studies. As a result of applying inclusion and exclusion criteria, 25 studies comprising 28 samples (reporting 120 effect sizes) were eligible for inclusion in the current TS-MASEM (N = 16,452). Results: The results showed significant associations between fear of COVID-19, stress, anxiety, and depression. Additionally, the mediation role of anxiety in the association between depression and fear of COVID-19 and stress was explored. Conclusions: Although the results did not allow for causal inferences regarding depression, they provide insight into the possible consequences of fear of COVID-19 and comorbid problems for clinicians and researchers.
... For example, some depressed patients have been shown to suffer a decrease in monoamines and their metabolites, as well as the corresponding transporters and precursors. These findings led to the formulation of the monoaminergic hypothesis of depression, which is the basis for the standard pharmacological treatment of the disease [5]. To date, however, it has not been possible to demonstrate this hypothesis conclusively; although treated patients generally regain their normal mood and behavior, it cannot be said that antidepressants "normalize" brain activity because the brains of patients treated with antidepressants are in a different state than those of people who are not depressed [6]. ...
Article
Depression is a syndrome characterized by deep sadness and the inhibition of psychic functions, sometimes accompanied by neurovegetative disorders, with symptoms of anxiety almost always present. The disease produces alterations in a variety of neural networks and neurotransmission systems, along with a dysfunction of the hypothalamic-pituitary-adrenal axis, which leads to concomitant alterations in the immunological response. Generally, there is a parallel increase in proinflammatory mediators as well as oxidative and nitrosative damage caused by a reduction of antioxidant defenses. In a previous review, we compiled and examined studies of medicinal plants that had been evaluated in preclinical assays, including existing data on 155 species studied and reported as antidepressants or as sources of active principles for treating this condition. This review will thus limit its focus to the 95 clinical trials found in PubMed among the 670 articles on antidepressant-like medicinal plants. To this end, we have reviewed the publications cited in the Cochrane Database of Systematic Reviews, PubMed, and the Science Citation Index from 2000 to 2020. Our review emphasizes those species that have demonstrated the greatest pharmacological potential when studied for their antidepressant properties in humans through clinical trials. Saffron, turmeric, St. Johnʼs wort, ginkgo, kava, and golden root are the most relevant plants that have provided important evidence for the treatment of depression in clinical trials.
... Moreover, the hippocampus is a key component linked to the HPA axis (Jacobson and Sapolsky, 1991). Corticosterone, the final product of the HPA axis, has a major target in the hippocampus, and the action of this hormone on the hippocampus is correlated with the pathogenesis and progression of depression (Saveanu and Nemeroff, 2012). According to the experiment of Zhang et al., we hypothesized that drugs used for inhibition of corticosterone-induced neurotoxicity in the hippocampus can be applied for clinical treatment of PSD (Zhang et al., 2021b). ...
Article
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Post-stroke depression (PSD) is the most frequent and important neuropsychiatric consequence of stroke. It is strongly associated with exacerbated deterioration of functional recovery, physical and cognitive recoveries, and quality of life. However, its mechanism is remarkably complicated, including the neurotransmitters hypothesis (which consists of a monoaminergic hypothesis and glutamate-mediated excitotoxicity hypothesis), inflammation hypothesis, dysfunction of the hypothalamic-pituitary-adrenal (HPA) axis, and neurotrophic hypothesis and neuroplasticity. So far, the underlying pathogenesis of PSD has not been clearly defined yet. At present, selective serotonin reuptake inhibitors (SSRIs) have been used as the first-line drugs to treat patients with PSD. Additionally, more than SSRIs, a majority of the current antidepressants complied with multiple side effects, which limits their clinical application. Currently, a wide variety of studies revealed the therapeutic potential of natural products in the management of several diseases, especially PSD, with minor side effects. Accordingly, in our present review, we aim to summarize the therapeutic targets of these compounds and their potential role in-clinic therapy for patients with PSD.
... Several factors have been associated with risk of depression and anxiety, but the underlying causes are still unknown. Diverse hereditary and environmental factors, such as coding for serotonergic pathway and dietary intakes, were indicated to be correlated with risk of both depression and anxiety (7). Previous investigations have also shown that body fat distribution is a strong risk factor for anxiety and depression (8,9). ...
Article
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Background The association between linoleic acid (LA) intake and mental disorders has not been extensively studied in Middle-Eastern populations. We investigated the association between LA intake and the prevalence of depression, anxiety, and psychological distress in a large group of Iranian adults. Methods This cross-sectional study was conducted on 3,362 middle-aged adults. LA intake was determined through a validated dish-based 106-item semiquantitative food frequency questionnaire (FFQ). The validated Hospital Anxiety and Depression Scale (HADS) and General Health Questionnaire (GHQ) were used to define psychological disorders. Results The prevalence of depression, anxiety, and psychological distress among the study population was 28.6, 13.6, and 22.6%, respectively. After adjustment for potential confounders, individuals in the top quartile of LA intake had 41% more likely to be depressed compared to those in the bottom quartile (OR = 1.41, 95% CI: 1.02–1.95). Stratified analysis by sex revealed that men in the fourth quartile of LA intake, compared to the first quartile, had 80% higher odds of depression, after considering all potential confounders (OR = 1.80, 95% CI: 1.01–3.19). More consumption of LA was also associated with higher odds of depression in older adults (OR = 2.45, 95% CI: 1.46–4.10) and normal-weight individuals (OR = 1.75, 95% CI: 1.13–2.72). Additionally, higher intake of LA was related to 90% higher odds of psychological distress in older participants (OR = 1.90, 95% CI: 1.08–3.36). No significant relation was found between LA intake and anxiety. Conclusion We found that higher intake of LA, as percentage of energy, was positively associated with depression, especially in men, older adults, and normal-weight subjects. Higher intake of LA was also related to higher odds of psychological distress in older individuals. More studies, particularly prospective cohorts, are needed to confirm these findings.
... According to an estimate recently presented by World Health Organization (WHO), depression stands at the 4th place among the main causes of disability in the world, women being two times more susceptible to depression during their lifetime as compared to men. The developed countries harbor higher number of depressed people than the underdeveloped world [22]. ...
Article
Full-text available
Depression is a psychosomatic disorder. The pharmacological treatment of depression has been based on the pathophysiology of deficiency in monoamines, mainly serotonin and noradrenaline. All approved antidepressants designed to enhance central monoaminergic tone possess many limitations such as 2 to 5 weeks delay in response, a limited clinical efficacy, and severe side effects. Since the pathophysiological aberrations associated to depression go beyond monoamines, the development of better antidepressants would depend on the identification and understanding of new cellular targets. The pharmacological studies of antidepressants, however, indicate the involvement of the blockade of neuronal uptake systems for norepinephrine and serotonin (5-hydroxytryptamine) including receptors for neurotransmitters. Many preclinical studies have suggested that hippocampus containing abundant agonists such as5-HT1A and 5-HT4 receptor subtypes in the dentate gyrus (DG) is critically involved in the mechanism of action of antidepressants. DG being a part of hippocampus possibly contributes to the brain functions such as formation of new sporadic memories. It is reported that antidepressants cause significant alterations in the structure and function of different brain regions in order to finally lead to their therapeutic effects. This review presents an overview of structural changes in the brain during depression; different neurobiological theories and novel drug development; strategy of augmentation with combinatorial therapy; receptors and targets of actions of antidepressants; and involvement of key signaling factors in the regulation of depression, pharmacology, metabolism, and the underlying principles involved in displaying how the application of antidepressants modulates the structure and function of the brain.
Article
In this volume, Dialogical Self Theory is innovatively presented as a guide to help elucidate some of the most pressing problems of our time as they emerge at the interface of self and society. As a bridging framework at the interface of the social sciences and philosophy, Dialogical Self Theory provides a broad view of problem areas that place us in a field of tension between liberation and social imprisonment. With climate change and the coronavirus pandemic serving as wake-up calls, the book focuses on the experience of uncertainty, the disenchantment of the world, the pursuit of happiness, and the cultural limitations of the Western self-ideal. Now more than ever we need to rethink the relationship between self, other, and the natural environment, and this book uses Dialogical Self Theory to explore actual and potential responses of the self to these urgent challenges.
Article
Objective: The immediate impact of child maltreatment on health and developmental trajectories over time is unknown. Longitudinal studies starting in the direct aftermath of exposure with repeated follow-up are needed. Method: We assessed health and developmental outcomes in 6-month intervals over 2 years in 173 children, aged 3-5 years at study entry, including 86 children with exposure to emotional and physical abuse or neglect within 6 months and 87 nonmaltreated children. Assessments included clinician-administered, self- and parent-report measures of psychiatric and behavioral symptoms, development, and physical health. Linear mixed models and latent growth curve analyses were used to contrast trajectories between groups and to investigate the impact of maltreatment features on trajectories. Results: Maltreated children exhibited greater numbers of psychiatric diagnoses (b = 1.998, p < .001), externalizing (b = 13.29, p < .001) and internalizing (b = 11.70, p < .001) symptoms, impairments in cognitive (b = -11.586, p < .001), verbal (b = -10.687, p < .001), and motor development (b = -7.904, p = .006), and greater numbers of medical symptoms (b = 1.021, p < .001) compared to nonmaltreated children across all time-points. Lifetime maltreatment severity and/or age at earliest maltreatment exposure predicted adverse outcomes over time. Conclusion: The profound, immediate, and stable impact of maltreatment on health and developmental trajectories supports a biological embedding model and provides foundation to scrutinize the precise underlying mechanisms. Such knowledge will enable the development of early risk markers and mechanism-driven interventions that mitigate adverse trajectories in maltreated children.
Article
Chronic social stress is closed related to major depressive disorder, torturing millions of people and may destroy their lives. The prefrontal cortex is one of the core brain areas involved in pathological development and behavior changes in depression. CELF4 is a neuronal RNA-binding protein and plays an essential role in RNA processing. It is closely related to some neurological disorders, including seizures and neuroticism. Most recently, GWAS analysis indicates it is one of the significant genes associated with depression. Nonetheless, we are still unknown whether and how CELF4 gets involved in depression. Here, we reported that the protein and mRNA expression levels of CELF4 in the PFC were decreased in the CSDS depression model, as well as the spine number. Furthermore, we disturbed CELF4 expression in the PFC by using the AAV-shCELF4 virus. Unexpectedly, the spine number showed a decrease in PFC because of the impaired CELF4 expression, and the AAV-shCELF4 mice displayed depression-like behaviors. Our results suggest that CELF4 is critical for spine number and acts a critical role in depression-like behaviors of mice.
Article
Objective: Fibromyalgia (FM) is characterized by chronic widespread pain and both physical and emotional alterations, which in turn may affect the individual's quality of life. Thus, interventions aimed at treating such symptoms, without increasing fatigue, are needed. The aim of this study was to explore the effect of high-frequency transcranial magnetic stimulation (HF-TMS) and physical exercise (PE) on pain, impact of FM, physical conditioning, and emotional status in people with FM. Methods: Forty-nine women with FM were randomly allocated to a PE group (PEG, n = 16), who underwent an 8-week (two 60-minute sessions/week) low intensity PE program; TMS group (TMSG, n = 17), receiving a 2-week (five 20-minute sessions/week) HF-TMS intervention and a control group (CG, n = 16). Pain (ie, perceived pain and average pressure pain threshold (PPT), perceived impact of FM (ie, overall impact, symptoms, and perceived physical function), physical conditioning (ie, endurance and functional capacity, fatigue, gait velocity, and power) and emotional status (ie, anxiety, depression, stress, and satisfaction) were assessed at baseline (T1) and after the intervention (T1, at 2 weeks for TMSG and at 8 weeks for PEG and CG). Results: TMSG showed to significantly improve all studied variables after the intervention except for satisfaction, whereas PEG improved average PPT, perceived overall impact of FM and total score, endurance and functional capacity, velocity and power, anxiety, depression, and stress. In contrast, the CG showed no improvements in any variable. Conclusions: Both PE and HF-TMS are effective in improving pain, impact of FM, physical conditioning, and emotional status in people with FM, while HF-TMS achieved larger improvements in emotional status than PE.
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In this volume, Dialogical Self Theory is innovatively presented as a guide to help elucidate some of the most pressing problems of our time as they emerge at the interface of self and society. As a bridging framework at the interface of the social sciences and philosophy, Dialogical Self Theory provides a broad view of problem areas that place us in a field of tension between liberation and social imprisonment. With climate change and the coronavirus pandemic serving as wake-up calls, the book focuses on the experience of uncertainty, the disenchantment of the world, the pursuit of happiness, and the cultural limitations of the Western self-ideal. Now more than ever we need to rethink the relationship between self, other, and the natural environment, and this book uses Dialogical Self Theory to explore actual and potential responses of the self to these urgent challenges.
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Based upon epidemiological surveys, adverse childhood events are proposed to be risk factors for adult depressive and anxiety disorders. However, the extent to which these events are seen in clinical patient populations is less clear. We examined the prevalence of a number of proposed risk factors for depression in 650 patients with mood and anxiety disorders at the time of presentation for treatment in an outpatient subspecialty clinic. Emotional abuse, physical abuse, or sexual abuse (childhood adversity) was found in approximately 35% of patients with major depression and panic disorder, was more common in women than men, and was associated with an earlier onset of symptoms. Childhood adversity was also strongly associated with marital discord/divorce, and psychopathology in a parent, suggesting family discord predisposes to childhood abuse. Furthermore, the association of childhood abuse with parental mental illness suggests that genetic and environmental factors are difficult to separate as etiological factors in vulnerability. Depression and Anxiety 5:66–72, 1997. © 1997 Wiley-Liss, Inc
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Childhood maltreatment and depressive disorders have both been associated with a dysregulation of the hypothalamic–pituitary–adrenal axis. The FKBP5 gene codes for a co-chaperone regulating the glucocorticoid-receptor sensitivity. Previous evidence suggests that subjects carrying the TT genotype of the FKBP5 gene single-nucleotide polymorphism (SNP) rs1360780 have an increased susceptibility to adverse effects of experimental stress. We therefore tested the hypothesis of an interaction of childhood abuse with rs1360780 in predicting adult depression. In all, 2157 Caucasian subjects from the Study of Health in Pomerania (German general population) completed the Beck Depression Inventory (BDI-II) and Childhood Trauma Questionnaire. The DSM-IV diagnosis of major depressive disorder (MDD) was assessed by interview. Genotypes of rs1360780 were taken from the Affymetrix Human SNP Array 6.0. Significant interaction (p=0.006) of physical abuse with the TT genotype of rs1360780 was found increasing the BDI-II score to 17.4 (95% confidence interval (CI)=12.0–22.9) compared with 10.0 (8.2–11.7) in exposed CC/CT carriers. Likewise, the adjusted odds ratio for MDD in exposed TT carriers was 8.2 (95% CI=1.9–35.0) compared with 1.3 (0.8–2.3) in exposed subjects with CC/CT genotypes. Relative excess risk due to interaction (RERI) analyses confirmed a significant additive interaction effect (RERI=6.8; 95% CI=0.64–33.7; p<0.05). In explorative analyses, the most severe degree of sexual and emotional abuse also yielded significant interaction effects (p<0.05). This study revealed interactions between physical abuse and rs1360780 of the FKBP5 gene, confirming its role in the individual susceptibility to depression. Given the large effect sizes, rs1360780 could be included into prediction models for depression in individuals exposed to childhood abuse.Keywords: major depression; childhood abuse; general population; FKBP5 gene; gene–environment interaction; CTQ
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Mentalization has been proposed as a key concept in understanding therapeutic change in patients with Borderline Personality Disorder (BPD). However, little is known about mentalization in chronic depression. This study investigated the role of mentalization in the long-term psychoanalytic treatment of chronic depression. Mentalization measured with the Reflective Functioning Scale (RFS) was examined in patients with chronic depression (n = 20) in long-term psychoanalytic treatment and compared to healthy controls (n = 20). Results show that global RF scores did not differ significantly between patients and controls. However, depressed patients tended to have lower RF scores concerning issues of loss. Furthermore, RF was unrelated to symptoms and distress as assessed by the Beck Depression Inventory (BDI) and the SCL-90. RF did not predict therapeutic outcome as measured with the BDI but predicted changes in general distress after 8 months of psychoanalytic treatment as measured by the SCL-90. Moreover, correlations between RF and the Helping Alliance Questionnaire indicated that patients with higher RF were able to establish a therapeutic alliance more easily compared to patients with low RF.
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Maternal care influences hypothalamic-pituitary-adrenal (HPA) function in the rat through epigenetic programming of glucocorticoid receptor expression. In humans, childhood abuse alters HPA stress responses and increases the risk of suicide. We examined epigenetic differences in a neuron-specific glucocorticoid receptor (NR3C1) promoter between postmortem hippocampus obtained from suicide victims with a history of childhood abuse and those from either suicide victims with no childhood abuse or controls. We found decreased levels of glucocorticoid receptor mRNA, as well as mRNA transcripts bearing the glucocorticoid receptor 1F splice variant and increased cytosine methylation of an NR3C1 promoter. Patch-methylated NR3C1 promoter constructs that mimicked the methylation state in samples from abused suicide victims showed decreased NGFI-A transcription factor binding and NGFI-A-inducible gene transcription. These findings translate previous results from rat to humans and suggest a common effect of parental care on the epigenetic regulation of hippocampal glucocorticoid receptor expression.
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Depression is one of the most prevalent and debilitating of the psychiatric disorders. Studies have shown that cognitive therapy is as efficacious as antidepressant medication at treating depression, and it seems to reduce the risk of relapse even after its discontinuation. Cognitive therapy and antidepressant medication probably engage some similar neural mechanisms, as well as mechanisms that are distinctive to each. A precise specification of these mechanisms might one day be used to guide treatment selection and improve outcomes.
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The possibility that hypersecretion of corticotropin-releasing factor (CRF) contributes to the hyperactivity of the hypothalamo-pituitary-adrenal axis observed in patients with major depression was investigated by measuring the concentration of this peptide in cerebrospinal fluid of normal healthy volunteers and in drug-free patients with DSM-III diagnoses of major depression, schizophrenia, or dementia. When compared to the controls and the other diagnostic groups, the patients with major depression showed significantly increased cerebrospinal fluid concentrations of CRF-like immunoreactivity; in 11 of the 23 depressed patients this immunoreactivity was greater than the highest value in the normal controls. These findings are concordant with the hypothesis that CRF hypersecretion is, at least in part, responsible for the hyperactivity of the hypothalamo-pituitary-adrenal axis characteristic of major depression.
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Context: Aprevious study reported a gene X environment interaction in which a haplotype in the corticotropin-releasing hormone receptor 1 gene (CRHR1) was associated with protection against adult depressive symptoms in individuals who were maltreated as children (as assessed by the Childhood Trauma Questionnaire [CTQ]). Objective: To replicate the interaction between childhood maltreatment and a TAT haplotype formed by rs7209436, rs110402, and rs242924 in CRHR1, predicting adult depression. Design: Two prospective longitudinal cohort studies. Setting: England and New Zealand. Participants: Participants in the first sample were women in the E-Risk Study (N=1116), followed up to age 40 years with 96% retention. Participants in the second sample were men and women in the Dunedin Study (N=1037), followed up to age 32 years with 96% retention. Main Outcome Measure: Research diagnoses of past-year and recurrent major depressive disorder. Results: In the E-Risk Study, the TAT haplotype was associated with a significant protective effect. In this effect, women who reported childhood maltreatment on the CTQ were protected against depression. In the Dunedin Study, which used a different type of measure of maltreatment, this finding was not replicated. Conclusions: A haplotype in CRHR1 has been suggested to exert a protective effect against adult depression among research participants who reported maltreatment on the CTQ, a measure that elicits emotional memories. This suggests the hypothesis that CRHR1's protective effect may relate to its function in the consolidation of memories of emotionally arousing experiences.
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Three variables have been hypothesized to play important roles in prolonging the course of depressive episodes: a ruminative response style, significant interpersonal relationships, and childhood adversity. The authors examined whether these variables predicted the short-term course of major depressive disorder (MDD). Participants (n = 84) were college students with a recent-onset major depressive episode. Assessments included several interview and self-report measures, and data on interpersonal relationships were obtained from close confidants. Follow-up interviews were conducted 6 months later. After controlling for baseline severity, harsh discipline in childhood significantly predicted mean level of depression across the follow-up and level of depression at follow-up. Harsh discipline was also significantly associated with relapse but not with recovery. After controlling for baseline severity, rumination and the interpersonal variables did not predict the outcome of MDD.
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THIS paper will attempt to clarify the relation of clinical features of depressive illness to the secretory activity of the adrenal cortex. The discovery that psychological stress stimulates the anterior pituitary-adrenocortical system1 has led to considerable interest in studying the function of the adrenal cortex in patients with mental illnesses, including depressions. In a recent review paper,2 Sachar pointed out that the extensive literature describing levels of adrenocortical hormones in depressed patients was quite inconsistent, with many reports suggesting elevated corticosteroid levels and other reports suggesting normal corticosteroid levels, some suggesting good correlation of severity of illness with adrenocortical indices, and others reporting poor correlations. It appeared that neglect of several significant control issues had contributed to the apparent diversity in findings. These necessary controls include eliminating all drugs which may interfere with the release of adrenocorticotropic hormone (ACTH), giving the patient enough time to get over
Article
Context Evidence suggests that early adverse experiences play a preeminent role in development of mood and anxiety disorders and that corticotropin-releasing factor (CRF) systems may mediate this association.Objective To determine whether early-life stress results in a persistent sensitization of the hypothalamic-pituitary-adrenal axis to mild stress in adulthood, thereby contributing to vulnerability to psychopathological conditions.Design and Setting Prospective controlled study conducted from May 1997 to July 1999 at the General Clinical Research Center of Emory University Hospital, Atlanta, Ga.Participants Forty-nine healthy women aged 18 to 45 years with regular menses, with no history of mania or psychosis, with no active substance abuse or eating disorder within 6 months, and who were free of hormonal and psychotropic medications were recruited into 4 study groups (n = 12 with no history of childhood abuse or psychiatric disorder [controls]; n = 13 with diagnosis of current major depression who were sexually or physically abused as children; n = 14 without current major depression who were sexually or physically abused as children; and n = 10 with diagnosis of current major depression and no history of childhood abuse).Main Outcome Measures Adrenocorticotropic hormone (ACTH) and cortisol levels and heart rate responses to a standardized psychosocial laboratory stressor compared among the 4 study groups.Results Women with a history of childhood abuse exhibited increased pituitary-adrenal and autonomic responses to stress compared with controls. This effect was particularly robust in women with current symptoms of depression and anxiety. Women with a history of childhood abuse and a current major depression diagnosis exhibited a more than 6-fold greater ACTH response to stress than age-matched controls (net peak of 9.0 pmol/L [41.0 pg/mL]; 95% confidence interval [CI], 4.7-13.3 pmol/L [21.6-60.4 pg/mL]; vs net peak of 1.4 pmol/L [6.19 pg/mL]; 95% CI, 0.2-2.5 pmol/L [1.0-11.4 pg/mL]; difference, 8.6 pmol/L [38.9 pg/mL]; 95% CI, 4.6-12.6 pmol/L [20.8-57.1 pg/mL]; P<.001).Conclusions Our findings suggest that hypothalamic-pituitary-adrenal axis and autonomic nervous system hyperreactivity, presumably due to CRF hypersecretion, is a persistent consequence of childhood abuse that may contribute to the diathesis for adulthood psychopathological conditions. Furthermore, these results imply a role for CRF receptor antagonists in the prevention and treatment of psychopathological conditions related to early-life stress. Figures in this Article The relative contribution of genetic and environmental factors in the etiology of psychiatric disorders has long been a hotly debated area of investigation. Considerable evidence from a variety of studies suggests a preeminent role of early adverse experiences in the development of mood and anxiety disorders. One study1 composed of almost 2000 women revealed that those with a history of childhood sexual or physical abuse exhibited more symptoms of depression and anxiety and had more frequently attempted suicide than women without a history of childhood abuse. Women who have been abused in childhood are 4 times more likely to develop syndromal major depression in adulthood than women who have not been abused, and the magnitude of the abuse is correlated with the severity of depression.2 Early parental loss predominantly due to parental separation has also been found to increase the risk for major depression in case-control and epidemiological studies.3- 8 Twin studies9- 10 have provided concordant findings. Childhood abuse also predisposes to the development of anxiety disorders in adulthood, including panic disorder and generalized anxiety disorder.11- 12 In addition, posttraumatic stress disorder (PTSD) may be a direct consequence of childhood abuse, and, moreover, such trauma early in life also appears to increase an individual's risk of developing PTSD in response to other traumas in adulthood.13 Depression and anxiety disorders, including PTSD, are often comorbid in individuals with a history of diverse early adversities.14 There is evidence that central nervous system (CNS) corticotropin-releasing factor (CRF) systems are likely to mediate the association between early-life stress and the development of mood and anxiety disorders in adulthood. Corticotropin-releasing factor neurons are found not only in the hypothalamus, but also in the neocortex and the central nucleus of the amygdala, which are believed to be involved in cognitive and emotional processing and in brainstem nuclei that contain the bulk of the noradrenergic and serotonergic perikarya that project to the forebrain. These CNS CRF systems have also been strongly implicated in the pathophysiology of both depression and anxiety disorders.15 Thus, when administered directly into the CNS of laboratory animals, CRF produces many physiological and behavioral changes that closely parallel symptoms of depression and anxiety, such as elevations of peripheral adrenocorticotropic hormone (ACTH), corticosterone, and catecholamine concentrations, increases in heart rate and mean arterial pressure, changes in gastrointestinal activity, decreased reproductive behavior, decreased appetite, disruption of sleep, increased grooming behavior, increased locomotor activity in a familiar environment, suppression of exploratory behavior in a novel environment, potentiation of acoustic startle responses, facilitation of fear conditioning, and enhancement of shock-induced freezing and fighting behavior.16- 20 Enhanced release of CRF from 1 or more CNS circuits may, thus, account for many of the symptoms of depression and anxiety and for the frequent comorbidity between these disorders.21- 22 Indeed, our group and others have repeatedly measured increased CRF-like immunoreactivity in cerebrospinal fluid (CSF) of untreated depressed patients compared with healthy controls and patients with other psychiatric disorders.23- 26 Moreover, increased numbers of CRF-positive neurons and increased CRF messenger RNA (mRNA) expression have recently been measured in the paraventricular nucleus (PVN) in postmortem hypothalamic tissue of untreated depressed patients.27- 28 Similar to findings in depression, increased CSF CRF concentrations have been reported in patients with PTSD and obsessive-compulsive disorder.29- 31 Of particular relevance to the current study is evidence from preclinical studies that suggests that increased activity of CRF circuits may be the persisting neurobiological consequence of stress early in development. Adult rats repeatedly separated from their dams for 180 min/d on postnatal days 2 to 14 demonstrate increased CRF concentrations in the median eminence, hypothalamohypophysial portal blood, and CSF and increased CRF mRNA expression in the hypothalamic PVN under resting conditions. In response to a variety of stressors, these maternally separated rats exhibit increased CRF mRNA expression in the hypothalamic PVN and increased ACTH and corticosterone responses.32- 33 Similarly, nonhuman primates reared as neonates with their mothers in a variable foraging demand condition for 12 weeks demonstrate significantly elevated CSF CRF concentrations along with stable traits of anxiety as adults.34- 35 We hypothesize that stress early in life results in a persistent sensitization or hyperactivity of CNS CRF systems to even mild stress in adulthood, contributing to the development of mood and anxiety disorders. This study sought to test this hypothesis in human subjects.
Article
Objectives. —To determine the prevalence of childhood physical or sexual abuse in women seen in primary care practices; to identify physical and psychologic problems associated with that abuse; and to compare the effects of childhood physical vs sexual abuse and childhood vs adult abuse.
Article
Reigning measures of psychological well-being have little theoretical grounding, despite an extensive literature on the contours of positive functioning. Aspects of well-being derived from this literature (i.e., self-acceptance, positive relations with others, autonomy, environmental mastery, purpose in life, and personal growth) were operationalized. Three hundred and twenty-one men and women, divided among young, middle-aged, and older adults, rated themselves on these measures along with six instruments prominent in earlier studies (i.e., affect balance, life satisfaction, self-esteem, morale, locus of control, depression). Results revealed that positive relations with others, autonomy, purpose in life, and personal growth were not strongly tied to prior assessment indexes, thereby supporting the claim that key aspects of positive functioning have not been represented in the empirical arena. Furthermore, age profiles revealed a more differentiated pattern of well-being than is evident in prior research. (PsycINFO Database Record (c) 2012 APA, all rights reserved)
Article
Human responses to stress and trauma vary widely. Some people develop trauma-related psychological disorders, such as posttraumatic stress disorder (PTSD) and depression; others develop mild to moderate psychological symptoms that resolve rapidly; still others report no new psychological symptoms in response to traumatic stress. Individual variability in how animals and humans respond to stress and trauma depends on numerous genetic, developmental, cognitive, psychological, and neurobiological risk and protective factors.
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Increasing evidence suggests that activation of the innate immune system may play a seminal role in the patho-physiology of depression. Several lines of evidence support the association of inflammation and depression. Peripheral administration of cytokines, such as interferon-alpha, can induce many of the symptoms of the depressive syndrome. In addition, medically healthy patients with major depression exhibit elevated plasma levels of proinflammatory cytokines. Moreover, cytokines produce effects on a variety of neurobiological substrates previously implicated in the pathogenesis of depression. Thus, proinflammatory cytokines alter neuroendocrine function, several neurotransmitter systems including dopamine and glutamate, neural plasticity, and neuronal activity in limbic regions. The burgeoning evidence that depres-sion is an inflammatory disease is reviewed.
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This study examined the effectiveness of Emotion Focused Therapy with 32 adult survivors (EFT-AS) of childhood abuse (emotional, physical, and sexual). EFT-AS is a 20-week individual psychotherapy based on current emotion theory and experiential therapy theory and research. The study employed a quasi-experimental design in which participants, who met screening criteria, were assigned to therapy or a variably delayed therapy condition. Clients receiving EFT-AS achieved significant improvements in multiple domains of disturbance. Clients in the delayed treatment condition showed minimal improvements over the wait interval but after EFT-AS showed significant improvements comparable to the immediate therapy group. These effects were maintained at 9 months (on average) follow-up.
Article
Background: Serotonin abnormalities have been reported in the brain of suicide victims. Evidence of a serotonin deficiency in suicide attempters is less consistent. We hypothesized that a serotonin deficiency may be present in suicide attempters whose attempt behavior more closely approximates completed suicide. Method: Sixty-seven (67) drug-free depressed inpatients (46 suicide attempters, 21 nonattempters) underwent research clinical assessments and a lumbar puncture. Cerebrospinal fluid (CSF) monoamine metabolites were assayed. Degree of medical damage and intent of the most recent suicide attempt were rated. Results: CSF amine metabolites did not differentiate suicide attempters as a group from nonattempters. However, reduced serotonergic activity, as indicated by lower levels of CSF-5-hydroxyindoleacetic acid (5-HIAA) was associated with a history of planned suicide attempts and with suicide attempts that resulted in greater medical damage. Other monoamine metabolites did not correlate with seriousness of suicidal behavior, except for low CSF homovanillic acid and higher medical damage. No correlation was found with violent method. Conclusions: Planned and more medically damaging suicide attempts appear to be associated specifically with low serotonergic activity and, therefore, resemble completed suicide both behaviorally and biochemically. It remains to be determined whether low levels of CSF 5-HIAA can predict greater medical damage in future suicide attempts.
Article
Background: Like major depression, dysthymia has been associated with elevated production of interleukin-1 (IL-1 beta) in mitogen-stimulated lymphocytes. In the present investigation, we assessed whether the elevated IL-1 beta production in dysthymic patients would normalize following treatment with sertraline. Methods: The production of IL-1 beta was determined in dysthymic patients and in nondepressed control subjects. Patients then received 12 weeks of doses of either sertraline or placebo in a double-blind trial, after which cytokine production was again determined. Results: Basal IL-1 beta was elevated in dysthymic patients relative to control subjects. Cytokine production was modestly correlated with the severity of symptoms and with the age of illness onset. Relative to placebo treatment, sertraline attenuated the symptoms of depression; however, this was not accompanied by normalization of IL-1 beta production. Conclusions: While dysthymia is associated with elevated IL-1 beta production, the failure for the cytokine to normalize following symptom alleviation suggests that either the IL-1 beta may be a trait marker of the illness, or that more sustained treatment is necessary to reduce cytokine production. Given the neuroendocrine and central neurochemical consequences of exogenously administered IL-1 beta, the possibility ought to be explored that increased IL-1 beta production may play a role in the pathophysiology of dysthymia.
Article
The primary thesis of this paper is that most patients who have experienced sexual abuse or early loss of a parent are optimally treated with psychotherapy as a core component of their treatment, though pharmacotherapy is often also required. We briefly review the prevalence and clinical sequelae of early sexual abuse and parental loss. Then, we present an overview of a biopsychosocial model that can inform and guide clinical practice and serve as a heuristic framework for clinical research. We review the extant outcome studies with a focus on controlled clinical trials. We conclude with some practical clinical suggestions based on our experiences with treatment that combines psychotherapy and pharmacotherapy for patients who have suffered from complex clinical syndromes secondary to abuse and parental loss during critical developmental periods of their lives.
Article
Child abuse is an important risk for adult psychiatric morbidity. However, not all maltreated children experience mental health problems as adults. The aims of the present study were to address the extent of resilience to adult psychopathology in a representative community sample, and to explore predictors of a good prognosis. Data are drawn from a follow-up of the Isle of Wight study, an epidemiological sample assessed in adolescence and at midlife. Ratings of psychiatric disorder, peer relationships and family functioning were made in adolescence; adult assessments included a lifetime psychiatric history, personality and social functioning assessments, and retrospective reports of childhood sexual and physical abuse. Ten percent of individuals reported repeated or severe physical or sexual abuse in childhood. Prospective measures revealed increased rates of adolescent psychiatric disorders in this group. Rates of adult psychopathology were also high. A substantial minority of abused individuals reported no mental health problems in adult life. Resilience of this kind was related to perceived parental care, adolescent peer relationships, the quality of adult love relationships, and personality style. Good quality relationships across childhood, adolescence and adulthood appear especially important for adult psychological well being in the context of childhood abuse.