References pertaining to the role of stress in depression:

Annu Rev Clin Psychol. 2005;1:293-319.

Stress and depression.

Hammen C.

Department of Psychology, University of California, Los Angeles, Los Angeles, California 90095, USA. Hammen@psych.ucla.edu

Improved methods of assessment and research design have established a robust and causal association between stressful life events and major depressive episodes. The chapter reviews these developments briefly and attempts to identify gaps in the field and new directions in recent research. There are notable shortcomings in several important topics: measurement and evaluation of chronic stress and depression; exploration of potentially different processes of stress and depression associated with first-onset versus recurrent episodes; possible gender differences in exposure and reactivity to stressors; testing kindling/sensitization processes; longitudinal tests of diathesis-stress models; and understanding biological stress processes associated with naturally occurring stress and depressive outcomes. There is growing interest in moving away from unidirectional models of the stress-depression association, toward recognition of the effects of contexts and personal characteristics on the occurrence of stressors, and on the likelihood of progressive and dynamic relationships between stress and depression over time-including effects of childhood and lifetime stress exposure on later reactivity to stress.

Publication Types:
Review

PMID: 17716090 [PubMed - indexed for MEDLINE]

J Psychopharmacol. 2007 Jul;21(5):538-44. Epub 2007 Apr 19.

Review: Serotonin by stress interaction: a susceptibility factor for the development of depression?

Firk C, Markus CR.

Department of Experimental Psychology, Maastricht University, Maastricht, The Netherlands. christine.firk@psychology.unimaas.nl

A genetic predisposition to depression may be a potential risk factor in the development of depression. Although the neurobiological equivalent of the predisposition remains unclear, it seems as though the brain serotonin (5-HT) system plays an important mediating role. Therefore, individuals with a family history of depression (FH+) may be more likely to develop depression due to an innate vulnerability related to altered serotonergic neurotransmission in the brain. A major problem, however, is that the role of brain 5-HT in depression is complex and this serotonin-related innate vulnerability, by itself, is not sufficient enough to cause a depressive episode. In the search for additional factors, stress has received particular attention. Stressful life events influence and precede the onset of depression. Furthermore, depression is associated with stress hormone dysregulation and bidirectional interactions are thought to occur between stress-related changes in the neuroendocrine stress system and the 5-HT system. In the current review, we argue that healthy individuals with a positive family history of depression are more prone to develop depression due to a genetic 5-HT susceptibility, which deteriorates stress coping mechanisms and increases stress vulnerability.

Publication Types:
Review

PMID: 17446201 [PubMed - indexed for MEDLINE]

Metabolism. 2005 May;54(5 Suppl 1):16-9.

Genes, stress, and depression.

Wurtman RJ.

Department of Brain and Cognitive Sciences, and Clinical Research Center, Massachusetts Institute of Technology, Cambridge 02139, USA. dick@mit.edu

A relationship between genetic makeup and susceptibility to major depressive disorder (MDD) has long been suspected on the basis of family and twin studies. A metaanalysis of reports on the basis of twin studies has estimated MDD's degree of heritability to be 0.33 (confidence interval, 0.26-0.39). Among families exhibiting an increased prevalence of MDD, risk of developing the illness was enhanced in members exposed to a highly stressful environment. Aberrant genes can predispose to depression in a number of ways, for example, by diminishing production of growth factors that act during brain development. An aberrant gene could also increase or decrease a neurotransmitter's release into synapses, its actions, or its duration of activity. The gene products of greatest interest at present are those involved in the synthesis and actions of serotonin; among them, the serotonin-uptake protein localized within the terminals and dendrites of serotonin-releasing neurons. It has been found that the Vmax of platelet serotonin uptake is low in some patients with MDD; also, Vmax is highly correlated in twins. Antidepressant drugs such as the selective serotonin reuptake inhibitors act on this uptake protein. The specific genetic locus causing serotonin uptake to be lower in some patients with major depression involves a polymorphic region (5-HTTLPR) in the promoter region of the gene for the uptake protein. The gene itself exists as several alleles, the short "S" allele and the long "L" allele. The S variant is associated with less, and the L variant with more, of the uptake protein. The effect of stressful life events on depressive symptoms in young adults was found to be significantly stronger among SS or SL subjects than among LL subjects. Neuroimaging studies showed that people with the SS or SL alleles exhibited a greater activation of the amygdala in response to fearful stimuli than those with LL. It has been reported recently that mutations in the gene that controls serotonin synthesis in the human brain (tryptophan hydroxylase) also predispose to mood disturbances. It may be asked whether people who lack a psychiatric history should be advised to avoid stressful environments if they are found to carry the SS or SL alleles.

Publication Types:
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.
Review

PMID: 15877307 [PubMed - indexed for MEDLINE]

Psychol Rev. 2005 Apr;112(2):417-45.

Life stress, the "kindling" hypothesis, and the recurrence of depression: considerations from a life stress perspective.

Monroe SM, Harkness KL.

Department of Psychology, University of Oregon, Eugene, OR 97403-1227, USA. smonroe@uoregon.edu

Major depression is frequently characterized by recurrent episodes over the life course. First lifetime episodes of depression, however, are typically more strongly associated with major life stress than are successive recurrences. A key theoretical issue involves how the role of major life stress changes from an initial episode over subsequent recurrences. The primary conceptual framework for research on life stress and recurrence of depression is the "kindling" hypothesis (R. M. Post, 1992). Despite the strengths of the kindling hypothesis, a review of the research literature reveals inconsistencies and confusion about life stress and its implications for the recurrence of depression. Adopting a life stress perspective, the authors introduce 3 major themes that resolve the inconsistencies in the current literature. They integrate these themes and extrapolate the ideas with available data to develop a preliminary framework for evaluating competing explanatory models and to guide research on life stress and the recurrence of depression.

Publication Types:
Research Support, U.S. Gov't, P.H.S.
Review

PMID: 15783292 [PubMed - indexed for MEDLINE]

Prog Neuropsychopharmacol Biol Psychiatry. 2004 Aug;28(5):891-907.

Comment in:
Prog Neuropsychopharmacol Biol Psychiatry. 2005 Jun;29(5):775-6.
Prog Neuropsychopharmacol Biol Psychiatry. 2006 Mar;30(2):320-1; author reply 323.

Can stress cause depression?

van Praag HM.

Department of Psychiatry and Neuropsychology, Academic Hospital Maastricht, and the Brain and Behavior Research Institute, Maastricht University, P.O. Box 616, 6200 MD Maastricht, The Netherlands. h.m.van.praag@vanpraag.com

The central issue raised in this paper is: can stress cause depression? Phrased more precisely: can stress cause brain disturbances thought to underlie (certain forms of) depression or particular components of the depressive syndrome. Focussing on 5-hydroxytryptamine (5-HT) and the stress hormones, this question was answered in the affirmative, based on the following two considerations: changes in the 5-HT and stress hormone systems produced by sustained stress mimic to a substantial extent the disturbances in these systems that may be observed in depression. Substantial evidence indicates that the 5-HT and stress hormone disturbances in depression are of pathophysiological significance and not merely a consequence of the depressed state or a product of stress generated by the depressed state. Furthermore, the question was raised whether a depression type could be identified particularly stress-inducible. This question, too, was answered in the affirmative. The depression type in question was named anxiety/aggression-driven depression and characterized on three levels: psychopathologically, biologically and psychologically. Preferential treatment of this depression type was discussed. In studying stress-inducible depression, biological depression research should shift focus from depression per se to the neurobiological sequelae of stress. Treatment of stress-inducible depressions and particularly its prevention should be geared towards reduction of stress and stress sensitiveness, utilising both biological and psychological means.

Publication Types:
Review

PMID: 15363612 [PubMed - indexed for MEDLINE]

Sci STKE. 2004 Mar 16;2004(225):re5.

Life stress, genes, and depression: multiple pathways lead to increased risk and new opportunities for intervention.

Charney DS, Manji HK.

Mood and Anxiety Disorders Research Program, National Institute of Mental Health, 15K North Drive, Room 101, MSC 2670, Bethesda, MD 20892-2670, USA. charneyd@nih.gov

Major depression is a common, severe, chronic, and often life-threatening illness. There is a growing appreciation that, far from being a disease with purely psychological manifestations, major depression is a systemic disease with deleterious effects on multiple organ systems. Stressful life events have a substantial causal association with depression, and there is now compelling evidence that even early life stress constitutes a major risk factor for the subsequent development of depression. The emerging evidence suggests that the combination of genetics, early life stress, and ongoing stress may ultimately determine individual responsiveness to stress and the vulnerability to psychiatric disorders, such as depression. It is likely that genetic factors and life stress contribute not only to neurochemical alterations, but also to the impairments of cellular plasticity and resilience observed in depression. Recent preclinical and clinical studies have shown that signaling pathways involved in regulating cell plasticity and resilience are long-term targets for the actions of antidepressant agents. Agents capable of reversing the hypothesized impairments of cellular resilience, reductions in brain volume, and cell death or atrophy in depression have the potential of becoming new therapeutic classes of antidepressant drugs. Novel cellular targets include agents targeting neurotrophic pathways, glucocorticoid signaling, phosphodiesterase activity, and glutamatergic throughput. The future development of treatments that more directly target molecules in critical CNS (central nervous system) signaling pathways that regulate cellular plasticity thus hold promise as novel, improved long-term treatments for major depression.

Publication Types:
Review

PMID: 15039492 [PubMed - indexed for MEDLINE]

Aust N Z J Psychiatry. 2002 Apr;36(2):173-82.

Life events, stress and depression: a review of recent findings.

Tennant C.

Department of Psychological Medicine, Royal North Shore Hospital, St Leonards, NSW, Australia. tennant@med.usyd.edu.au

OBJECTIVE: To review recent empirical prospective studies on the relation between life event stressors and depression. METHOD: A systematic literature search focusing on predictive studies was carried out from 1980 to early 2001 using Medline, Embase and PsychInfo. RESULTS: The empirical findings for the most part support clinical impressions of the relation of stressors to depression but at the same time provide some clearer understanding in relation to differences of stressor impact on depression type and on index episode, relapse or recurrence. Twin studies now provide the strongest evidence of the relative magnitude of effect of environmental stressors and genetic factors: the former explains at least as much of the variance in depression as our genes. CONCLUSIONS: Continuing research into life events and depression have been fruitful especially those studies assessing the effect of stressors in combination with other aetiological variables such as genetic factors.

Publication Types:
Review

PMID: 11982537 [PubMed - indexed for MEDLINE]

Epidemiol Psichiatr Soc. 2001 Jul-Sep;10(3):153-62.

How does stress affect you? An overview of stress, immunity, depression and disease.

Maddock C, Pariante CM.

Maudsley Hospital, London SE5 8AZ, UK.

OBJECTIVE: Stress is a term that has become synonymous with modern life. This review aims to appraise the evidence linking stress with disease with particular reference to the major causes of morbidity and mortality in the Western World, cardiovascular disease, cancer, and depression. Changes in immune parameters in stressful situations were reviewed as a possible pathophysiological mechanism for such effects. METHOD: A Medline search was carried out for the period 1996-2000 to identify recent findings in this field using the terms "stress", "disease", "immune system". Relevant references that were found in all identified publications were also followed up. RESULTS: There is evidence to link stress with the onset of major depression and with a poorer prognosis in cardiovascular disease and cancer. Few small studies suggest that stress management strategies may help to improve survival. Chronic stress appears to result in suppression of the immune response, whereas immune activation and suppression have been associated with acute stress. Inflammatory cytokines, soluble mediators of the immune response, can result in symptoms of depression. CONCLUSION: Further prospective epidemiologically based studies are needed to clarify the role of stress on disease onset, course, and prognosis. Stress management strategies, aimed at prolonging survival in patients with cardiovascular disease, cancer, and possibly other chronic illnesses, are an exciting area of further research. Immune system changes may account for the relationship between stress and disease. We propose the "stress, cytokine, depression" model as a biological pathway to explain the link between stressful life events and depression.

Publication Types:
Review

PMID: 11787449 [PubMed - indexed for MEDLINE]

Dev Psychopathol. 2001 Summer;13(3):451-71.

Effects of early stress on brain structure and function: implications for understanding the relationship between child maltreatment and depression.

Kaufman J, Charney D.

Department of Psychiatry, Yale University, New Haven, CT 06511, USA. joan.kaufman@yale.edu

Child abuse is associated with markedly elevated rates of major depression (MDD) in child, adolescent, and adult cohorts. This article reviews preclinical (e.g., animal) studies of the effects of early stress and studies of the neurobiological correlates of MDD in adults and children, and it highlights differences in the neurobiological correlates of MDD and stress at various developmental stages. The preclinical studies demonstrate that stress early in life can alter the development multiple neurotransmitter systems and promote structural and functional alterations in brain regions similar to those seen in adults with depression. Preclinical and clinical studies suggest, however, that long-term neurobiological changes associated with early stress can be modified by familial/genetic factors, the quality of the subsequent caregiving environment, and pharmacological interventions. Little is known about how developmental factors interact with experiences of early stress and these other modifying factors. Moreover, in cases of child maltreatment, the effects of early abuse are often exacerbated by failures in the child protection system and repeat out-of-home placements. Given the number of factors that impact on the long-term outcome of maltreated children, multidisciplinary research efforts are recommended to address this problem-with foci that span from neurobiology to social policy.

Publication Types:
Review

PMID: 11523843 [PubMed - indexed for MEDLINE]

J Human Stress. 1976 Sep;2(3):3-12.

Life stress, depression and attempted suicide.

Paykel ES.

This paper summarizes a series of controlled studies into the relationship of life events to depression and to suicide attempts. Life events, particularly exit events and events regarded as undesirable, tend to cluster prior to onset of depression. These findings are supported by comparisons with general population controls, depressives after recovery, other patient groups, and by studies of relapse. Interactions with predisposing and biological causes are probably of great importance. Suicide attempters are a rather different patient group and they experience a particularly striking accumulation of threatening events. There is a marked peaking of events in the month before the attempt, suggesting a crisis response and the potential relevance of crisis intervention techniques.

Publication Types:
Comparative Study
Review

PMID: 798014 [PubMed - indexed for MEDLINE]