人类抑郁有着复杂的遗传基础并存在性别差异.抑郁遗传基础的性别 差异主要表现在遗传的直接效应及遗传与环境的交互效应两个方面.本文在回顾、梳理既有抑郁遗传基础性别差异相关研究的基础上,进一步探讨了性激素、个体环 境敏感性和中间表型在性别差异形成中的作用.未来该领域应关注遗传对抑郁的动态影响,进一步探讨多基因交互作用、不同类型与性质的环境指标与抑郁遗传基础 性别差异的关联.

抑郁具有复杂的、非孟德尔式的多基因遗传模式,但是目前多数抑郁的遗传研究集中于考察单个候选基因,不能全面揭示遗传因素的作用机制。近年来,多基因遗传得分研究和基因-基因交互研究分别为抑郁的多基因累加效应和交互效应提供了新的证据。多基因不仅直接影响抑郁,还通过与环境因素的交互作用影响抑郁的发生发展,并且这一复杂交互作用存在性别差异。抑郁的内表型研究发现多基因可能通过认知因素、人格、压力荷尔蒙等间接影响个体的抑郁水平。未来研究应更加关注多基因与多种环境因素如何相互作用影响抑郁,探索多基因遗传机制的性别差异,考察多基因对抑郁影响随年龄的发展动态变化。

DSM-Ⅳ是使用最广泛的精神障碍诊断标准之一,但其中的躯体形式障碍诊断标准在临床实践中存在应用性低,标准模糊,分类重叠等问题。因此DSM-5针对这些问题将其修改为躯体症状障碍,删去医学无法解释症状的要求,增加心理标准,合并和简化亚型,以改善该诊断标准的临床应用。本文分析了DSM-5躯体症状障碍修订的主要内容和原因,并讨论了新标准在未来面临的问题和可能的进展。

基于神经生物学的心身交互作用是当前躯体化病理机制的一个研究重 点。在生理-心理的功能连续体中，认知学习、感觉监控、注意、记忆过程等都会影响躯体症状的呈现。文化则会通过这些过程塑造个体对症状的归因和解释，引发 躯体症状的呈现和扩大，最终通过不同文化特有的民族生理学模式形成具有文化特异性的疑病焦虑和医学无法解释症状。

产后抑郁是产后时期出现的抑郁症状,对女性及其后代甚至家人都会造成严重的负面影响。产后抑郁稳定的预测因素是遗传基因、依恋风格、童年负性生活经历和激素水平的变化;涉及的脑区和神经网络集中在前额叶皮层、扣带回、杏仁核和海马等脑区及相应神经网络。未来应在探索综合的预测模型、男性伴侣的对照试验和基于大脑可塑性特征的干预模式等方面展开深入研究。

意象思维是中国人的传统思维模 式,它通过观物取象和取象比类的方式认知世界、推演联系。这种思维模式塑造了中国人特有的身心不分而非两分的身体观、疾病观和治疗观。在中国人的观念中, 身体不仅仅是一具生理躯体,还具有气、阴阳、五行等本土概念所体现的弥合物质与精神、联结生理与心理的模糊性与开放性。人们在表达疾病感觉时通常不分生理 与心理,任何一方面出现不适感觉即可认为自己生病,在面对心理医生时也倾向于同时报告躯体状况与心理感觉,从而使得临床报告出现较高的躯体化报告率。这正 是文化心理影响疾病表达的体现。这也使得疾病不仅是一种医学现象,也是一种文化现象;医学不仅需要生理知识,也需要人文知识。

抑郁症具有中等的遗传度。通过影像遗传学方法探讨抑郁相关基因的多态性对神经活动的影响,发现编码五羟色胺、促肾上腺素释放激素受体、多巴胺等神经递质或受体的基因多态性会影响杏仁核、前扣带等情绪加工脑区的功能或结构,且多数基因与压力生活经历发生交互作用。表明基因与环境的交互作用在抑郁症发病机理中扮演重要角色。未来的研究应拓展遗传和神经影像分析方法,重视环境因素的测量,通过整合遗传、神经影像及环境变量构建抑郁病理模型。

缰核是哺乳动物神经系统中连接前脑和中脑的重要节点,这一古老的核团因其与抑郁症的密切联系,近来获得国内外研究者的关注.缰核接受来自边缘系统、基底神经节等的传入信号,向下投射到中脑5-羟色胺系统和多巴胺系统.在应激条件下缰核免疫活动增强,向下游的投射信号增强,以此调节单胺类递质释放,参与抑郁症的发病机制,并且参与抗抑郁治疗的起效途径.这些证据提示缰核在抑郁症中具有重要作用,将成为研究和治疗的新途径.未来研究应从缰核与上下游核团的神经联系、与丘脑-垂体-肾上腺轴的相互影响、以及与免疫激活的交互作用等方面进一步探索,为研究抑郁症病理机制和治疗方法提供线索.

医学无法解释症状是指无法通过实验医学的生理性病因进行合理解释的功能性躯体症状,也是躯体化等躯体性心理障碍诊断标准的核心条件之一。医学无法解释症状的界定及其历史变迁反映了西方医学体系中普通医学和精神病学的二元分裂。而从本土身心合一和整体医学观的视角看,医学专科的二元分裂并不是天然存在的。这种差异也成为躯体化诊断在中国产生不适应性的原因之一。

Cultural competence training is mandatory in the United States of America to alleviate minority health disparities though few studies have examined perceptions across stakeholders. We conducted separate focus groups with patients, clinicians, and administrators from the psychiatry department at one community hospital and compared responses to hospital policies. Stakeholders defined cultural competence through group-based or person-centered traits despite policies recommended person-centered approaches. Administrators and clinicians named clinician techniques for psycho-education whereas patients named these techniques for enlistment in treatment planning as equals. All groups named patient cultural views and institutional challenges as barriers to care, but only patients and administrators additionally named clinician biases as possible barriers. We discuss these discrepant perceptions and possible solutions to improve research, practice, and policy on cultural competence in mental health.

Abstract The authors hypothesize that depressed states evolved to minimize risk in social interactions in which individuals perceive that the ratio of their social value to others, and their social burden on others, is at a critically low level. When this ratio reaches a point where social value and social burden are approaching equivalence, the individual is in danger of exclusion from social contexts that, over the course of evolution, have been critical to fitness. Many features of depressed states can be understood in relation to mechanisms that reduce social risk in such circumstances, including (a) hyper-sensitivity to signals of social threat from others, (b) sending signals to others that reduce social risks, and (c) inhibiting risk-seeking (e.g., confident, acquisitive) behaviors. These features are discussed in terms of psychosocial and neurobiological research on depressive phenomena.

Over the last ten years, there has been increased interest in the evolutionary origins of depressive phenomena. The current article provides a review of the major schools of thought that have emerged in this area. First, we consider important Darwinian explanations of depressed mood, including an integrative social risk hypothesis recently proposed by the authors. According to the social risk hypothesis, depression represents an adaptive response to the perceived threat of exclusion from important social relationships that, over the course of evolution, have been critical to maintaining an individual's fitness prospects. We argue, moreover, that in the ancestral environment, depression minimized the likelihood of exclusion by inducing: (i) cognitive hypersensitivity to indicators of social risk/threat; (ii) signaling behaviours that reduce social threat and elicit social support; and (iii) a generalized reduction in an individual's propensity to engage in risky, appetitive behaviours. Neurobiological support for this argument is also provided. Finally, we review three models that endeavour to explain the relationship between the adaptations that underlie depressed mood and clinically significant, depressed states, followed by a consideration of the merits of each.

Data on birth order and parent-offspring relations for 1,601 adolescents participating in the National Longitudinal Study of Adolescent Health were used to test hypotheses about the role of adolescent suicidal behavior in parent-offspring conflict. Among adolescents highly dissatisfied with their mothers, the odds that middleborns would make at least one suicide attempt was 23% that of first- and lastborns (p<.001), but their odds of receiving medical treatment for their attempts was 8.5 times greater than the odds for first- and lastborns (p=.032). The results are tentatively interpreted as supporting the hypothesis that adolescents use suicide attempts to leverage investment from their parents.

Abstract Depression is the primary emotional condition for which help is sought. Depressed people often report persistent rumination, which involves analysis, and complex social problems in their lives. Analysis is often a useful approach for solving complex problems, but it requires slow, sustained processing, so disruption would interfere with problem solving. The analytical rumination hypothesis proposes that depression is an evolved response to complex problems, whose function is to minimize disruption and sustain analysis of those problems by (a) giving the triggering problem prioritized access to processing resources, (b) reducing the desire to engage in distracting activities (anhedonia), and (c) producing psychomotor changes that reduce exposure to distracting stimuli. As processing resources are limited, sustained analysis of the triggering problem reduces the ability to concentrate on other things. The hypothesis is supported by evidence from many levels-genes, neurotransmitters and their receptors, neurophysiology, neuroanatomy, neuroenergetics, pharmacology, cognition, behavior, and efficacy of treatments. In addition, the hypothesis provides explanations for puzzling findings in the depression literature, challenges the belief that serotonin transmission is low in depression, and has implications for treatment. Copyright (c) 2009 APA, all rights reserved.

Abstract Mechanisms of self-destruction are difficult to reconcile with evolution's first rule of thumb: survive and reproduce. However, evolutionary success ultimately depends on inclusive fitness. The altruistic suicide hypothesis posits that the presence of low reproductive potential and burdensomeness toward kin can increase the inclusive fitness payoff of self-removal. The bargaining hypothesis assumes that suicide attempts could function as an honest signal of need. The payoff may be positive if the suicidal person has a low reproductive potential. The parasite manipulation hypothesis is founded on the rodent-Toxoplasma gondii host-parasite model, in which the parasite induces a "suicidal" feline attraction that allows the parasite to complete its life cycle. Interestingly, latent infection by T. gondii has been shown to cause behavioral alterations in humans, including increased suicide attempts. Finally, we discuss how suicide risk factors can be understood as nonadaptive byproducts of evolved mechanisms that malfunction. Although most of the mechanisms proposed in this article are largely speculative, the hypotheses that we raise accept self-destructive behavior within the framework of evolutionary theory.

Objectives: (1) Describe the concept, mechanisms and outcome of evolution; (2) review the current topics in research and clinical psychiatry where evolutionary concepts are explicitly applied. Methods: The authors reviewed relevant textbooks of evolution, evolutionary psychiatry/psychology and articles in scientific journals, and discussed these topics in a college course at McGill University School of Medicine, Montreal, Canada. Results: (1) Most natural scientists agree that evolution has occurred in all living beings. However, the mechanisms and outcomes of evolution are controversial. (2) In the first three quarters of the 20th century, several authors provided theories about human psychology based on ethological concepts. The so-called evolutionary psychology/psychiatry developed more recently, and it explores the adaptive/nonadaptive features of psychopathology and mental disorders. In the 1990s a concept of mental disorder (as a harmful dysfunction) based on evolutionary theory has been developed. Conclusions: Evolution is a pivotal concept in biology with relevant applications in psychiatry. We suggest encouraging the interaction between psychiatric educators and researchers in evolutionary psychiatry and biology in order to improve the education of psychiatric residents in this subject.

Background Diagnosis and management of depression occurs frequently in the primary care setting. Current diagnostic and management of treatment practices across clinical populations focus on eliminating signs and symptoms of depression. However, there is debate that some interventions may pathologize normal, adaptive responses to stressors. Analytical rumination (AR) is an example of an adaptive response of depression that is characterized by enhanced cognitive function to help an individual focus on, analyze, and solve problems. To date, research on AR has been hampered by the lack of theoretically-derived and psychometrically sound instruments. This study developed and tested a clinically meaningful measure of AR. Methods Using expert panels and an extensive literature review, we developed a conceptual framework for AR and 22 candidate items. Items were field tested to 579 young adults; 140 of whom completed the items at a second time point. We used Rasch measurement methods to construct and test the item set; and traditional psychometric analyses to compare items to existing rating scales. Results Data were high quality (<1% missing; high reliability: Cronbach's alpha = 0.92, test-retest intraclass correlations >0.81; evidence for divergent validity). Evidence of misfit for 2 items suggested that a 20-item scale with 4-point response categories best captured the concept of AR, fitting the Rasch model (2 = 95.26; df = 76, p = 0.07), with high reliability (rp = 0.86), ordered response scale structure, and no item bias (gender, age, time). Conclusion Our study provides evidence for a 20-item Analytical Rumination Questionnaire (ARQ) that can be used to quantify AR in adults who experience symptoms of depression. The ARQ is psychometrically robust and a clinically useful tool for the assessment and improvement of depression in the primary care setting. Future work is needed to establish the validity of this measure in people with major depression.

OBJECTIVE: The present research addressed the following important question in pediatric medicine: can participation in an efficacious preventive intervention ameliorate the risk that a genetic vulnerability factor is hypothesized to confer on increases in risk behaviors across preadolescence? METHODS: As part of the Strong African American Families preventive intervention study, data were collected from 641 black families in rural Georgia, assigned randomly to the prevention or control condition. The prevention condition consisted of 7 consecutive meetings at community facilities, with separate parent and youth skill-building curricula and a family curriculum. Each meeting included separate, concurrent sessions for parents and youths, followed by a joint parent-youth session in which families practiced skills they learned in the separate sessions. Involvement in risk behaviors was assessed when the youths were 11 (pretest), 12 (posttest), and 14 (long-term follow-up) years of age. A genetic vulnerability factor, that is, a variable-nucleotide repeat polymorphism in the promoter region of the SLC6A4 gene (5HTT), was assessed 2 years after the long-term follow-up assessment. RESULTS: Youths at genetic risk who were assigned to the control condition displayed greater increases in risk behaviors across the 29 months that separated the pretest and long-term follow-up assessments, compared with youths at genetic risk who were assigned to the Strong African American Families condition and youths without genetic risk who were assigned to either condition. CONCLUSION: This is the first study to demonstrate that participation in an efficacious preventive intervention can ameliorate a genetic risk for increasing involvement in health-compromising risk behaviors across preadolescence.

Purpose of review;It has been hypothesized that increased cleanliness, reduced family size, and subsequent decreased microbial exposure could explain the increases in global asthma prevalence. This review considers the recent evidence for and against the 'hygiene hypothesis'.Recent findings;Recent evidence does not provide unequivocal support for the hygiene hypothesis: the hygiene hypothesis specifically relates to atopic asthma, but some of the protective effects (e. g. farm exposures) appear to apply to both atopic and nonatopic asthma; asthma prevalence has begun to decline in some western countries, but there is little evidence that they have become less clean; Latin American countries with high infection rates have high asthma prevalence and the hygiene hypothesis relates to early-life exposures, but exposures throughout life may be important.Summary;There is a considerable body of evidence which warrants scepticism about the hygiene hypothesis. However, these anomalies contradict the 'narrow' version of it in which microbial pressure early in life protects against atopic asthma by suppressing T-helper 2 immune responses. It is possible that a more general version of the hygiene hypothesis is still valid, but the aetiologic mechanisms involved are currently unclear.

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Unlike rare mendelian diseases, which are due to new mutations (i.e. derived alleles), several alleles that increase the risk to common diseases are ancestral. Moreover, population genetics studies suggest that some derived alleles that protect against common diseases became advantageous recently. These observations can be explained within an evolutionary framework in which ancestral alleles reflect ancient adaptations to the lifestyle of ancient human populations, whereas the derived alleles were deleterious. However, with the shift in environment and lifestyle, the ancestral alleles now increase the risk of common diseases in modern populations. In this article, we develop an explicit evolutionary model and use population genetics simulations to investigate the expected haplotype structure and type of disease-association signals of ancestral risk alleles.

Ruminating when depressed is thought to lower mood and impair problem-solving, while distraction is thought to alleviate mood and assist problem-solving. The present study investigates each of these proposals using both naturally occurring and experimentally induced rumination and distraction in a sample of patients with major depression.Thirty-six patients with major depression and 36 control participants were randomly allocated to either a rumination or distraction induction condition. Levels of trait rumination and distraction were measured at baseline, mood and problem-solving were measured before and after the inductions.In terms of trait measures, depressed patients with higher levels of trait rumination reported poorer mood and gave less effective problem solutions than those who were less ruminative. Trait distraction was not associated with mood or problem-solving. In terms of induced responses, depressed patients who were made to ruminate experienced a deterioration in their mood and gave poorer problem solutions. For those receiving the distraction induction, mood improved in all patients and problem-solving improved in patients who were not naturally ruminating at a high level. Neither induction had an impact on mood or problem-solving in control participants.Treatment for depression associated with adverse life events may need to target rumination as well as problem-solving deficits if interventions are to be effective. The differential effects of self-applied versus experimentally induced distraction require further investigation. Future research will need to consider that high levels of trait rumination may interfere with the impact of experimental inductions.

Using functional MRI in a large multisite sample of more that 1,000 patients, four distinct neurophysiological biotypes of depression are defined. These biotypes are used to develop diagnostic classifiers that distinguish patients with depression from controls in separate multisite validation and replication cohorts, and can predict patient responsiveness to therapy.

Major depressive disorder (MDD) presents with a variety of symptoms and responds to a wide range of treatment interventions. Diagnostic criteria collapse multiple syndromes with distinct etiologies into the same disorder. MDD is typically understood as a malfunction of neurotransmission or brain circuitry regulating mood, pleasure and reward, or executive function. However, research from an evolutionary perspective suggests that the - ormal functioning of adaptations may also generate symptoms meeting diagnostic criteria. Functioning adaptations may be an underappreciated etiological pathway to MDD. Many adaptive functions for depressive symptoms have been suggested: biasing cognition to avoid losses, conserving energy, disengaging from unobtainable goals, signaling submission, soliciting resources, and promoting analytical thinking. We review the potential role of these adaptive functions and how they can lead to specific clusters of depressive symptoms. Understanding MDD from such a perspective reduces the heterogeneity of cases and may help to select the best intervention for each patient. We discuss the implications of different adaptive and maladaptive etiological pathways for the use of antidepressants and various modes of psychotherapy. In particular, instances of MDD caused by functioning adaptations may benefit most from treatments that support the adaptive function, or that target the precipitating causal stressor. We conclude that an evolutionary approach to the study of MDD may be one of the more promising approaches to reduce its heterogeneity and to better match patients and treatment.

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Abstract Mounting evidence indicates that inflammatory cytokines contribute to the development of depression in both medically ill and medically healthy individuals. Cytokines are important for development and normal brain function, and have the ability to influence neurocircuitry and neurotransmitter systems to produce behavioral alterations. Acutely, inflammatory cytokine administration or activation of the innate immune system produces adaptive behavioral responses that promote conservation of energy to combat infection or recovery from injury. However, chronic exposure to elevated inflammatory cytokines and persistent alterations in neurotransmitter systems can lead to neuropsychiatric disorders and depression. Mechanisms of cytokine behavioral effects involve activation of inflammatory signaling pathways in the brain that results in changes in monoamine, glutamate, and neuropeptide systems, and decreases in growth factors, such as brain-derived neurotrophic factor. Furthermore, inflammatory cytokines may serve as mediators of both environmental (e.g. childhood trauma, obesity, stress, and poor sleep) and genetic (functional gene polymorphisms) factors that contribute to depression's development. This review explores the idea that specific gene polymorphisms and neurotransmitter systems can confer protection from or vulnerability to specific symptom dimensions of cytokine-related depression. Additionally, potential therapeutic strategies that target inflammatory cytokine signaling or the consequences of cytokines on neurotransmitter systems in the brain to prevent or reverse cytokine effects on behavior are discussed. Copyright 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

Abstract Myalgic encephalopathy/chronic fatigue syndrome (ME/CFS) is a debilitating disease of unknown etiology, with hallmark symptoms including postexertional malaise and poor recovery. Metabolic dysfunction is a plausible contributing factor. We hypothesized that changes in serum amino acids may disclose specific defects in energy metabolism in ME/CFS. Analysis in 200 ME/CFS patients and 102 healthy individuals showed a specific reduction of amino acids that fuel oxidative metabolism via the TCA cycle, mainly in female ME/CFS patients. Serum 3-methylhistidine, a marker of endogenous protein catabolism, was significantly increased in male patients. The amino acid pattern suggested functional impairment of pyruvate dehydrogenase (PDH), supported by increased mRNA expression of the inhibitory PDH kinases 1, 2, and 4; sirtuin 4; and PPAR未 in peripheral blood mononuclear cells from both sexes. Myoblasts grown in presence of serum from patients with severe ME/CFS showed metabolic adaptations, including increased mitochondrial respiration and excessive lactate secretion. The amino acid changes could not be explained by symptom severity, disease duration, age, BMI, or physical activity level among patients. These findings are in agreement with the clinical disease presentation of ME/CFS, with inadequate ATP generation by oxidative phosphorylation and excessive lactate generation upon exertion.

The American Psychiatric Association has released the long-awaited fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5). This commentary notes that the DSM-5 "introduced several high-prevalence diagnoses at the fuzzy boundary with normality" and recommends that "physicians ... use the DSM-5 cautiously, if at all."

Abstract Depression is well recognized to be rooted in the down-regulation of positive affect systems. This paper reviews some of the social and non-social theories that seek to explain the potential adaptive advantages of being able to tone down positive affect, and how dysfunctions in such affect control can occur in some contexts. Common to most evolutionary theories of depression is the view that loss of control over aversive events and/or major resources/rewards exert downward pressure on positive affect. Social theories, however, suggest that it is loss of control over the social environment that is particularly depressogenic. Two evolutionary theories (the attachment-loss, and the defeat-loss theories) are briefly reviewed and their interaction considered. It is suggested that phenotypes for toning down positive affect, in the face of loss of control, may become more severe in the context of socially hostile, unsupportive and/or excessively competitive environments. The paper briefly considers how human competencies for self-evaluation in relation to others, rumination, self-criticism, and modern social contexts can accentuate dysfunctional expressions of affect regulation.

It was recently hypothesized that depression might function, in part, as a bargaining strategy when cooperation imposes a net cost, but there are social constraints on defection [Evol. Hum. Behav. 20 (1999) 325.]. If so, such social constraints should be associated with depression, and depression in one partner should be associated with increased investment by other partners. Several predictions of this hypothesis were tested using postpartum depression (PPD) as a model for depression in general. The depression levels, abortion attitudes, additional mating opportunities, and investment in childrearing of 240 mothers and fathers with a new child were measured using self-report instruments. Mothers were also asked whether the new child was planned and whether it was wanted. Perceived constraints on abortion correlated significantly with PPD levels, but, as predicted, only for mothers with an unplanned or unwanted child. Contrary to predictions, perceived constraints imposed by family and friends did not correlate with PPD levels. Sexual opportunities correlated significantly with PPD levels, but, as predicted, only for men. As predicted, PPD levels in one spouse correlated significantly with increased investment in childrearing as reported by the other spouse. PPD levels correlated positively with parity for older women with few future reproductive opportunities, as predicted.

A single nucleotide polymorphism (SNP) in the brain-derived neurotrophic factor (BDNF) gene Val66Met has been associated with depression. However, the relationship between this SNP and depression has been mixed, especially when comparing studies of child and adult depression. We examined whether Val66Met would predict depression differentially in mothers versus their daughters. We also examined whether rumination, the tendency to brood and repetitively think about negative information, might serve as a mediator in the path between genotype and depressive symptoms. Participants included 200 individuals (100 mother-aughter pairs) from a high-risk population. The BDNF Val66Met polymorphism was examined in DNA samples from the mothers and daughters, and measures of depressive symptoms and rumination were also obtained. Among the young adolescent girls (ages 10-14), the Val/Val genotype was associated with more depressive symptoms and higher rumination scores compared to the Val/Met genotype. Furthermore, rumination mediated the relationship between genotype and depressive symptoms. However, in the mothers with adult-onset depression the Val/Met genotype was associated with more depressive symptoms, and rumination again mediated the relationship between genotype and depression. Rumination may be an endophenotype in the pathway from the BDNF Val66Met polymorphism to depression. Future work should further explore this mechanism and pursue explanations for its effects at different times in development.

Recent work has called attention to large differences among traits in the amount of standardized genetic variance they possess. There are four general factors which could play a role in causing this variation: mutation, elimination of deleterious variation, selection of favorable alleles, and balancing selection. Three factors could directly influence the mutational variability of traits: canalization, the mutational target size, and the timing of trait expression. Here I carry out simple tests of the importance of some of these factors using data from Drosophila melanogaster. I compiled information from the literature on the mutational and standing genetic variances in outbred populations, inferred the relative mutational target size of each trait, its a timing of expression, and used models of life history to calculate fitness sensitivities for each trait. Mutation variation seems to play an important role, as it is highly correlated with standing variance. The target size hypothesis was supported by a significant correlation between mutational variance and inferred target size. There was also a significant relationship between the timing of trait expression and mutational variance. These hypotheses are confounded by a correlation between timing and target size. The elimination and canalization hypotheses were not supported by these data, suggesting that they play a quantitatively less important role in determining overall variances. Additional information concerning the pleiotropic consequences of mutations would help to validate the fitness sensitivities used to test the elimination and canalization hypotheses.

In the terms melancholia and depression and their cognates, we have well over two millennia of the Western world’s ways of referring to a goodly number of different dejected states. At any particular

Abstract BACKGROUND: Functional difficulties are determined as one of the reasons for the public health priority given to depression. However, previous literature shows that the evidence on treatment effectiveness in depression does not reflect all relevant functional areas affected. This paper aimed to review recent literature and identify which areas are addressed and what are the gaps in the measurement of treatment effectiveness in depression. METHODS: Electronic search was performed in PsycINFO, PubMed, Web of science, and the Cochrane Central Register of Controlled Trials. A content item analysis of outcome measures was performed. RESULTS: Two hundred and fourty-seven studies were included. The functional areas addressed in the measurement process did not vary across studies assessing psychotherapeutic, pharmacological or alternative interventions. The content analysis revealed that 80% of the areas covered by instruments represented symptomatology. Many functional areas were insufficiently covered, whereas others like handling stress, solving problems, maintaining daily routine, problems in education, or participation in community, political or religious life were not addressed at all. LIMITATIONS: Only articles in English were included and the time frame was limited. CONCLUSIONS: More than 10 years after the first global burden of disease studies have been published evidence on the treatment effectiveness in depression is still based primarily on symptoms. Many important functional areas remain unexplored. Consequently the effectiveness of well recognized interventions might be overestimated. Future steps should include use of comprehensive tools, provision of detailed information on functional areas instead of global scores of instruments, and design of functional impairment oriented therapies. Copyright 2015 Elsevier B.V. All rights reserved.

Abstract BACKGROUND: Although severe depression is dysfunctional, the capacity to experience normal low mood may be useful in certain fitness-threatening situations. Moreover, if specific kinds of situations recurred often enough in the course of evolution, natural selection may have shaped partially differentiated subtypes of low mood that are parallel to the subtypes of anxiety that protect against different kinds of danger. To test this hypothesis, we examined how symptoms of low mood differ depending upon the precipitating situation, and whether these differences match expectations of symptoms useful in each kind of situation. METHOD: 337 subjects who experienced a period of low mood within the last year wrote accounts describing perceived causes of their low mood and they filled out the CES-D depression inventory. Seven symptom scales were derived from analysis of CES-D data. Independent judges blindly coded the accounts into one of six precipitant categories. RESULTS: Different untoward situations were associated with different symptoms that were predicted to be useful in those situations. Social losses (death of a loved one, romantic breakups, and social isolation) were associated with greater crying and arousal. Failure to reach a goal, stress, and winter seasons were associated with more fatigue and pessimism. DISCUSSION: These results suggest that natural selection shaped not only a generic state of low mood but also partially differentiated subtypes shaped to cope with specific situations that were associated with fitness losses among our ancestors.

The author reviews conceptual and empirical issues regarding the interaction of neurasthenia, somatization and depression in Chinese culture and in the West. The historical background of neurasthenia and its current status are discussed, along with the epidemiology and phenomenology of somatization and depression. Findings are presented from a combined clinical and anthropological field study of 100 patients with neurasthenia in the Psychiatry Outpatient Clinic at the Hunan Medical College. Eighty-seven of these patients made the DSM-III criteria of Major Depressive Disorder; diagnoses of anxiety disorders were also frequent. Forty-four patients were suffering from chronic pain syndromes previously undiagnosed, and cases of culture-bound syndromes also were detected. For three-quarters of patients the social significances and uses of their illness behavior chiefly related to work. Although from the researchers' perspective 70% of patients with Major Depressive Disorder experienced substantial improvement and 87% some improvement in symptoms when treated with antidepressant medication, fewer experienced decreased help seeking, and a much smaller number perceived less social impairment and improvement in illnes problems (the psychosocial accompaniment of disease including maladaptive coping and work, family and school problems). These findings are drawn on to advance medical anthropology and cultural psychiatry theory and research regarding somatization in Chinese culture, the United States and cross culturally. The author concludes that though neurasthenia can be understood in several distinctive ways, it is most clinically useful to regard it as bioculturally patterned illness experience (a special form of somatization) related to either depression and other diseases or to culturally sanctioned idioms of distress and psychosocial coping.

The following article identifies new areas for engaged medical anthropological research on health insurance in low- and middle-income countries (LMICs). Based on a review of the literature and pilot research, we identify gaps in how insurance is understood, administered, used, and abused. We provide a historical overview of insurance as an emerging global health panacea and then offer brief assessments of three high-profile attempts to provide universal health coverage. Considerable research on health insurance in LMICs has been quantitative and focused on a limited set of outcomes. To advance the field, we identify eight productive areas for future ethnographic research that will add depth to our understanding of the social life and impact of health insurance in LMICs. Anthropologists can provide unique insights into shifting health and financial practices that accompany insurance coverage, while documenting insurance programs as they evolve and respond to contingencies.

Abstract This collection of essays opens a critical examination of compassionate acts responding to social suffering in the intensely complex moral context of a rapidly changing and globalizing China. Jeanne Shea describes self-compassion among older women in China as a post-revolutionary response to changing opportunities and resistance to consumerism. Khun Eng Kuah-Pearce's essay frames the Buddhist organizations as NGOs and shows compassion being mobilized and its acts being spiritual-philanthropic, not political. The next three papers illuminate the complexity of mobility in a moral sea of changing values. Even as modernity facilitates movement of people away from suffering, the grinding of entangled moral experiences within the mobile group can be the cause of suffering. Shu-Min Huang critiques 'cultural petrification' as the diasporic Yunnan Chinese community in Thailand attempt to preserve the cultural forms and procedures of the world they left behind. Likewise, Richard Madsen shows that the idea of a universalized cultural heritage fails in the face of the 'micro-ecologies'. And yet the modern impulse to universalize beyond China has important implications for transnational compassion and cooperation. The work of the humanitarian organization M decins Sans Fronti res in China, discussed by Kuah-Pearce and Guiheux, challenges the universality of global humanitarian actions. Following the series of essays threaded across intersections of compassion, suffering, and a morally-divided China, the collection closes by looking at the West. Iain Wilkinson discusses the origins of social suffering as a focus of the social sciences, as well as the difficulties of making engaged compassion its task in a morally-divided world.

Price’s social competition hypothesis interprets the depressive state as an unconscious, involuntary losing strategy, which enables individuals to yield and accept defeat in competitive situations. We investigated whether patients who suffer from major depressive disorder (MDD) would avoid competition more often than either patients suffering from borderline personality disorder (BPD) or healthy controls. In a simple paper-folding task healthy participants and patiens with MDD and BPD were matched with two opponents, one with an unknown diagnosis and one who shared their clinical diagnosis, and they had to choose either a competitive or cooperative payment scheme for task completion. When playing against an unknown opponent, but not the opponent with the same diagnosis, the patients with depression chose the competitive payment scheme statistically less often than healthy controls and patients diagnosed with BPD. The competition avoidance against the unknown opponent is consistent with Price’s social competition hypothesis. G.H. received research support, consulting fees and speaker honoraria from Lundbeck, AstraZeneca, Servier, Eli Lilly, Roche and Novartis. 08 The Royal College of Psychiatrists 2016. This is an open access article distributed under the terms of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) licence.

Abstract BACKGROUND AND OBJECTIVES: Although there is supporting evidence for the stress generation hypothesis (i.e., the tendency for depression-prone individuals to experience more negative dependent events influenced by their behaviors and characteristics), additional research is required to advance current understanding of the specific types of dependent events relevant to this effect. The present study elaborated on the stress generation hypothesis, in which the content of negative dependent events experienced by individuals is contingent upon, and matches, the nature of their particular vulnerabilities. This extension was tested within the context of Cole's competency-based model of depression. DESIGN: Participants (n=185) were assessed at two time-points separated by a four-month interval. METHODS: Self-perceived competence in academic, social, and appearance domains at the initial time-point were examined in relation to negative life events prospectively occurring over the four-month follow-up period, assessed using the "contextual threat" method. RESULTS: Partial support was obtained for vulnerability-specific stress generation. Stress-generation specificity was found for self-perceived competence in appearance and academic domains, but not for self-perceived social competence. CONCLUSIONS: The current findings are consistent with the possibility of a more complex relation between self-perceived social competence and domain-congruent stress generation. Individuals may be more likely to experience negative dependent events in domains matching their specific vulnerabilities.

Consistent evidence links major depression and its affective components to negative health outcomes. Although the pathways of these effects are likely complex and multifactorial, recent evidence suggests that innate inflammatory processes may play a role. An overview of current literature suggests that pathways between negative moods and inflammation are bi-directional. Indeed, negative moods activate peripheral physiologic mechanisms that result in an up regulation of systemic levels of inflammation. Conversely, peripheral inflammatory mediators signal the brain to affect behavioral, affective and cognitive changes that are consistent with symptoms of major depressive disorder. It is likely that these pathways are part of a complex feedback loop that involves the nervous, endocrine, and immune systems and plays a role in the modulation of peripheral inflammatory responses to central and peripheral stimuli, in central responses to peripheral immune activation and in the maintenance of homeostatic balance. Further research is warranted to fully understand the role of central processes in this feedback loop, which likely contributes to the pathophysiology of mental and physical health.

Cognitive models of depression have been well supported with adults, but the developmental origins of cognitive vulnerability are not well understood. The authors hypothesized that temperament, parenting, and negative life events in childhood would contribute to the development of cognitive style, with withdrawal negativity and negative parental feedback moderating the effects of negative life events to predict more depressogenic cognitive styles. These constructs were assessed in 289 children and their parents followed longitudinally from infancy to 5th grade; a subsample (n = 120) also participated in a behavioral task in which maternal feedback to child failure was observed. Results indicated that greater withdrawal negativity in interaction with negative life events was associated with more negative cognitive styles. Self-reported maternal anger expression and observed negative maternal feedback to child's failure significantly interacted with child's negative events to predict

Background: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is characterized by unexplained persistent fatigue, commonly accompanied by cognitive dysfunction, sleeping disturbances, orthostatic intolerance, fever, lymphadenopathy, and irritable bowel syndrome (IBS). The extent to which the gastrointestinal microbiome and peripheral inflammation are associated with ME/CFS remains unclear. We pursued rigorous clinical characterization, fecal bacterial metagenomics, and plasma immune molecule analyses in 50 ME/CFS patients and 50 healthy controls frequency-matched for age, sex, race/ethnicity, geographic site, and season of sampling. Results: Topological analysis revealed associations between IBS co-morbidity, body mass index, fecal bacterial composition, and bacterial metabolic pathways but not plasma immune molecules. IBS co-morbidity was the strongest driving factor in the separation of topological networks based on bacterial profiles and metabolic pathways. Predictive selection models based on bacterial profiles supported findings from topological analyses indicating that ME/CFS subgroups, defined by IBS status, could be distinguished from control subjects with high predictive accuracy. Bacterial taxa predictive of ME/CFS patients with IBS were distinct from taxa associated with ME/CFS patients without IBS. Increased abundance of unclassified Alistipes and decreased Faecalibacterium emerged as the top biomarkers of ME/CFS with IBS; while increased unclassified Bacteroides abundance and decreased Bacteroides vulgatus were the top biomarkers of ME/CFS without IBS. Despite findings of differences in bacterial taxa and metabolic pathways defining ME/CFS subgroups, decreased metabolic pathways associated with unsaturated fatty acid biosynthesis and increased atrazine degradation pathways were independent of IBS co-morbidity. Increased vitamin B6 biosynthesis/salvage and pyrimidine ribonucleoside degradation were the top metabolic pathways in ME/CFS without IBS as well as in the total ME/CFS cohort. In ME/CFS subgroups, symptom severity measures including pain, fatigue, and reduced motivation were correlated with the abundance of distinct bacterial taxa and metabolic pathways. Conclusions: Independent of IBS, ME/CFS is associated with dysbiosis and distinct bacterial metabolic disturbances that may influence disease severity. However, our findings indicate that dysbiotic features that are uniquely ME/CFS-associated may be masked by disturbances arising from the high prevalence of IBS co-morbidity in ME/CFS. These insights may enable more accurate diagnosis and lead to insights that inform the development of specific therapeutic strategies in ME/CFS subgroups. Electronic supplementary material The online version of this article (doi:10.1186/s40168-017-0261-y) contains supplementary material, which is available to authorized users.

Emotions research is now routinely grounded in evolution, but explicit evolutionary analyses of emotions remain rare. This article considers the implications of natural selection for several classic questions about emotions and emotional disorders. Emotions are special modes of operation shaped by natural selection. They adjust multiple response parameters in ways that have increased fitness in adaptively challenging situations that recurred over the course of evolution. They are valenced because selection shapes special processes for situations that have influenced fitness in the past. In situations that decrease fitness, negative emotions are useful and positive emotions are harmful. Selection has partially differentiated subtypes of emotions from generic precursor states to deal with specialized situations. This has resulted in untidy emotions that blur into each other on dozens of dimensions, rendering the quest for simple categorically distinct emotions futile. Selection has shaped flexible mechanisms that control the expression of emotions on the basis of an individual's appraisal of the meaning of events for his or her ability to reach personal goals. The prevalence of emotional disorders can be attributed to several evolutionary factors.

There has been a recent surge of interest in the evolutionary basis of depression. One approach argues that the affective mechanisms that are dysregulated in depression are adaptations, whilst a second approach argues that depression itself is an adaptation. The evidence relating to whether depression could itself be an adaptation is reviewed. Adaptations generally have four hallmarks; they lack heritable variation, show evidence of good design, are evoked by appropriate triggers, and fitness is reduced where they are absent. Depression shows none of these hallmarks. It is characterized by heritability, recurrence, cognitive impairment, and poor social outcome. In an alternative evolutionary formulation, I argue that evolution has produced a continuous population distribution of affective reactivity that is subject to stabilizing selection. Individuals vulnerable to depression are at the upper end of this distribution. This conceptualization, in which depression itself is not selected for, is compatible with the known clinical and epidemiological facts.

The term 'mood' in its scientific usage refers to relatively enduring affective states that arise when negative or positive experience in one context or time period alters the individual's threshold for responding to potentially negative or positive events in subsequent contexts or time periods. The capacity for mood appears to be phylogenetically widespread and the mechanisms underlying it are highly conserved in diverse animals, suggesting it has an important adaptive function. In this review, we discuss how moods can be classified across species, and what the selective advantages of the capacity for mood are. Core moods can be localised within a two-dimensional continuous space, where one axis represents sensitivity to punishment or threat, and the other, sensitivity to reward. Depressed mood and anxious mood represent two different quadrants of this space. The adaptive function of mood is to integrate information about the recent state of the environment and current physical condition of the organism to fine-tune its decisions about the allocation of behavioural effort. Many empirical observations from both humans and non-human animals are consistent with this model. We discuss the implications of this adaptive approach to mood systems for mood disorders in humans.

The aetiology of depression is not fully understood, which allows many different perspectives on aetiology to be adopted. Researchers and clinicians may be attracted to concepts of aetiology that parallel other diagnoses with which they are familiar. Such parallels may assume the role of informal models or metaphors for depressive disorders. They may even function as informal scientific theories of aetiology, energising research activities by guiding hypothesis generation and organising new knowledge. Parallels between different types of disease may ultimately prove valuable as frameworks supporting the emergence and maturation of new knowledge. However, such models may be counterproductive if their basis, which is likely to lay at least partially in analogy, is unacknowledged or overlooked. This could cause such models to appear more compelling than they really are. Listing examples of situations in which models of depression may arise from, or be strengthened by, parallels to other familiar conditions may increase the accessibility of such models either to criticism or support. However, such a list has not yet appeared in the literature. The present paper was written with the modest goal of stating several examples of models or metaphors for depression.This paper adopted narrative review methods. The intention was not to produce a comprehensive list of such ideas, but rather to identify prominent examples of ways of thinking about depression that may have been invigorated as a result parallels with other types of disease.Eight possible models are identified: depressive disorders as chemical imbalances (e.g., a presumed or theoretical imbalance of normally balanced neurotransmission in the brain), degenerative conditions (e.g., a brain disease characterised by atrophy of specified brain structures), toxicological syndromes (a result of exposure to a noxious psychological environment), injuries (e.g., externally induced brain damage related to stress), deficiency states (e.g., a serotonin deficiency), an obsolete category (e.g., similar to obsolete terms such as 'consumption' or 'dropsy'), medical mysteries (e.g., a condition poised for a paradigm-shifting breakthrough) or evolutionary vestiges (residual components of once adaptive mechanisms have become maladaptive in modern environments).Conceptualisation of depressive disorders may be partially shaped by familiar disease concepts. Analogies of this sort may ultimately be productive (e.g., through generating hypotheses by analogy) or destructive (e.g., by structuring knowledge in incorrect, but intellectually seductive, ways).

Background: No satisfactory basis in normal function characterizes major depression and its co-morbid disorders. Yet these may represent maladaptive expression of adaptive communicational states exhibited normally in many species. Methods: We examined the signal value of depressive and anxious mood states, fatigue syndrome and somatoform disorders and found them to resemble appeasement or submission to conspecifics (members of a same species) as studied in other animals. Moreover, applying game theory formulations of conflict resolution and the triune brain theory of MacLean supported the hypothesis. Limitations: Direct experimental evidence must still test hypotheses that emanate from the presented framework. Conclusions: Implications for this approach include improved understanding and treatment of depression, improved research strategies, and a potential future pathogenesis-focused nosology.

Abstract Evolved mechanisms underpinning attachment and social rank behavior may be the basis for some forms of major depression, especially those associated with chronic stress. We note the heterogeneity of depression, but suggest that some of its core symptoms, such as behavioral withdrawal, low self-esteem and anhedonia, may have evolved in order to regulate behavior and mood and convey sensitivity to threats and safety. Focusing on the evolved mental mechanisms for attachment and social rank helps to make sense of (1) depression's common early vulnerability factors (e.g., attachment disruptions, neglect and abuse), (2) the triggering events (e.g., loss of close relationships, being defeated and/or trapped in low socially rewarding or hostile environments), and (3) the psychological preoccupations of depressed people (e.g., sense of unlovableness, self as inferior and a failure). This focus offers clues as to how these two systems interact and on how to intervene.

Abstract BACKGROUND: Despite research supporting moderate heritability of depression, efforts to replicate candidate gene associations to depression have yielded inconsistent results. We tested whether Val66Met and 5-HTTLPR exhibit utility as genetic markers of depression risk, testing for replicable associations to cognitive and interpersonal endophenotypes of depression (rumination and co-rumination), and further exploring developmental and sex moderation. METHOD: In Study I, 228 youth (ages 8-14) of mothers with or without a history of MDD during the child's lifetime were recruited from the community. Replication tests were carried out in Study II, a sample of 87 youth with similar recruitment. RESULTS: In Study I, the Val66Met single-nucleotide polymorphism (SNP) was associated with rumination in adolescents, but not children, such that adolescents homozygous for the Val allele reported higher rumination levels. Further, a cumulative genetic score (CGS) (Val66Val and 5-HTTLPR) predicted higher levels of co-rumination, specifically among adolescent girls. Both genetic associations maintained significance after covarying for current depressive symptomology, and the other endophenotype. Finally, both genetic associations exhibited similar effect sizes in Study II, although results did not reach statistical significance. CONCLUSIONS: RESULTS replicate a previously reported association between the brain derived neurotrophic factor (BDNF) Val allele and rumination in adolescents, and provide preliminary support for a CGS predictive of co-rumination in adolescent girls. The current study indicates that candidate genes may demonstrate utility as consistent genetic markers of depression risk when focused on specific phenotypes, and supports the need to explore potential differential effects of developmental stage and sex. However, given the small sample sizes and possibility of chance findings, these results should be interpreted with caution pending replication.

From an evolutionary perspective, suicide is a puzzle, because it has serious adverse effects, yet is remarkably common and heritable. An hypothesis is proposed to explain this puzzle, by explaining how suicide could be adaptive through reducing risk that individuals will transmit infections to kin. Empirical evidence supports four predictions from the hypothesis. There are well-established mechanisms by which infections and immune factors increase risk for mental disorders that contribute to suicide. Suicide is more prevalent in occupations with greater exposure to infection and immune-compromising factors and at higher latitudes, where key environmental factors increase vulnerability to infection. In several other highly social species, suicide-like behaviors have evolved to reduce transmission of infections. If the hypothesis is correct, detection and treatment of underlying infections and immune dysfunction should help predict and prevent suicidal behavior, while also combating spread of infectious diseases.

Abstract Defeat and entrapment are psychological constructs that have played a central role in evolutionary accounts of depression. These concepts have since been implicated in theoretical accounts of anxiety disorders and suicidality. The current article reports on a systematic review of the existing research investigating the links among defeat, entrapment, and psychopathology in the domains of depression, suicidality, posttraumatic stress disorder (PTSD), and other anxiety syndromes. Fifty-one original research articles were identified and critically reviewed. There was strong convergent evidence for a link with depressive symptoms, across a variety of clinical and nonclinical samples. Preliminary support for an association with suicidality was also observed, with effects not readily explainable in terms of comorbid depression. There was strong evidence for an association between defeat and PTSD, although this may have been partly accounted for by comorbid depression. The findings for other anxiety disorders were less consistent. There was, however, evidence that social anxiety in individuals with psychosis may be related to perceptions of entrapment. Overall, there was evidence that perceptions of defeat and entrapment were closely associated with various forms of human psychopathology. These effects were often in the moderate to large range and superseded the impact of other environmental and psychological stressors on psychopathology. We provide a unified theoretical model of how defeat and entrapment may contribute to these different psychopathological conditions. Clinical implications and avenues for future research are discussed. 2011 American Psychological Association

In the last few decades, there has been a genuine ‘adaptive turn’ in psychiatry, resulting in evolutionary accounts for an increasing number of psychopathologies. In this paper, I explore the advantages and problems with the two main evolutionary approaches to depression, namely the mismatch and persistence accounts . I will argue that while both evolutionary theories of depression might provide some helpful perspectives, the accounts also harbor significant flaws that might question their authority and usefulness as explanations.

Valid diagnostic criteria support generalizations about treatment effectiveness, allowing progress in developing empirically supported treatments. The DSM-5 revision provides an opportunity to consider whether diagnostic changes are increasing validity. In this paper, I first offer broad suggestions for conceptually advancing diagnostic validity while awaiting greater etiological understanding. These include, for example, improving “conceptual validity” (disorder/nondisorder differentiation); extending diagnosis beyond disorders to include mismatches between normal variation and social demands (“psychological justice”); placing disorder etiology in evolutionary context as harmful failure of biologically designed functioning (“harmful dysfunction”); and taking an integrative theoretical approach to human meaning systems. The paper then examines the DSM-5's controversial decision to eliminate the major depression bereavement exclusion (BE), detailing the evidence and attendant debate. Elimination was defended by citing several hypotheses (e.g., excluded cases are similar to other MDD; exclusions risk missing suicidal cases; medication works with excluded cases), all of which were either empirically falsified or based on faulty arguments. Most dramatically, excluded cases were empirically demonstrated to have no more depression on follow-up than those who never had MDD. I conclude that BE elimination undermined rather than increased conceptual validity and usefulness for treatment research. Finally, I draw some general lessons from the DSM-5 BE debacle.

Because obesity is associated with diverse chronic diseases, little attention has been directed to the multiple beneficial functions of adipose tissue. Adipose tissue not only provides energy for growth, reproduction and immune function, but also secretes and receives diverse signaling molecules that coordinate energy allocation between these functions in response to ecological conditions. Importantly, many relevant ecological cues act on growth and physique, with adiposity responding as a counterbalancing risk management strategy. The large number of individual alleles associated with adipose tissue illustrates its integration with diverse metabolic pathways. However, phenotypic variation in age, sex, ethnicity and social status is further associated with different strategies for storing and using energy. Adiposity therefore represents a key means of phenotypic flexibility within and across generations, enabling a coherent life-history strategy in the face of ecological stochasticity. The sensitivity of numerous metabolic pathways to ecological cues makes our species vulnerable to manipulative globalized economic forces. The aim of this article is to understand how human adipose tissue biology interacts with modern environmental pressures to generate excess weight gain and obesity. The disease component of obesity might lie not in adipose tissue itself, but in its perturbation by our modern industrialized niche. Efforts to combat obesity could be more effective if they prioritized ‘external’ environmental change rather than attempting to manipulate ‘internal’ biology through pharmaceutical or behavioral means.

This introductory chapter of The Palgrave Handbook of Sociocultural Perspectives on Global Mental Health highlights how understanding about aberrant behaviours has varied across time, geography and cu

Abstract This paper is designed as an invitation to debate the value of research and writing on social suffering in relation to practices of caregiving. It offers a brief account of the origins and development of 'social suffering' as a concern for social inquiry. Henry Mayhew and Jane Addams are profiled in terms of their pioneering roles as social researchers heavily preoccupied with problems of social suffering. The contrast between Henry Mayhew's frustrated attempts at caregiving and Jane Addams' success in instituting the pedagogy of caregiving in the work of Hull House is set up for analysis. These examples are used to issue an invitation to readers to question the cultural and institutional circumstances that make possible forms of social inquiry that recognise caregiving both as a means to social understanding and as an aim for social research in practice.

Sadness and low levels of depression are adaptive since they lead the individual to try and make up a loss. By contrast, severe or clinical depression is not adaptive, but can be thought of as sadness having become malignant.