Depression Research Today is a free monthly online journal that collates and summarizes the latest research about Depression, including details on clinical depression, medication, symptoms, treatment, counselling, therapy.

Interaction between the serotonin transporter gene (5-HTTLPR), stressful life events, and risk of depression: a meta-analysis.

Risch N, Herrell R, Lehner T, Liang KY, Eaves L, Hoh J, Griem A, Kovacs M, Ott J, Merikangas KR

Institute for Human Genetics, University of California at San Francisco, and Kaiser Permanente Northern California Division of Research, Oakland, USA.

CONTEXT: Substantial resources are being devoted to identify candidate genes for complex mental and behavioral disorders through inclusion of environmental exposures following the report of an interaction between the serotonin transporter linked polymorphic region (5-HTTLPR) and stressful life events on an increased risk of major depression. OBJECTIVE: To conduct a meta-analysis of the interaction between the serotonin transporter gene and stressful life events on depression using both published data and individual-level original data. DATA SOURCES: Search of PubMed, EMBASE, and PsycINFO databases through March 2009 yielded 26 studies of which 14 met criteria for the meta-analysis. STUDY SELECTION: Criteria for studies for the meta-analyses included published data on the association between 5-HTTLPR genotype (SS, SL, or LL), number of stressful life events (0, 1, 2, > or = 3) or equivalent, and a categorical measure of depression defined by the Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) or the International Statistical Classification of Diseases, 10th Revision (ICD-10) or use of a cut point to define depression from standardized rating scales. To maximize our ability to use a common framework for variable definition, we also requested original data from all studies published prior to 2008 that met inclusion criteria. Of the 14 studies included in the meta-analysis, 10 were also included in a second sex-specific meta-analysis of original individual-level data. DATA EXTRACTION: Logistic regression was used to estimate the effects of the number of short alleles at 5-HTTLPR, the number of stressful life events, and their interaction on depression. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated separately for each study and then weighted averages of the individual estimates were obtained using random-effects meta-analysis. Both sex-combined and sex-specific meta-analyses were conducted. Of a total of 14,250 participants, 1769 were classified as having depression; 12,481 as not having depression. RESULTS: In the meta-analysis of published data, the number of stressful life events was significantly associated with depression (OR, 1.41; 95% CI,1.25-1.57). No association was found between 5-HTTLPR genotype and depression in any of the individual studies nor in the weighted average (OR, 1.05; 95% CI, 0.98-1.13) and no interaction effect between genotype and stressful life events on depression was observed (OR, 1.01; 95% CI, 0.94-1.10). Comparable results were found in the sex-specific meta-analysis of individual-level data. CONCLUSION: This meta-analysis yielded no evidence that the serotonin transporter genotype alone or in interaction with stressful life events is associated with an elevated risk of depression in men alone, women alone, or in both sexes combined.

Published 17 June 2009 in JAMA, 301(23): 2462-71.
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Articles on Depression published 5 June 2009:

Peripheral tumors induce depressive-like behaviors and cytokine production and alter hypothalamic-pituitary-adrenal axis regulation.   Proc Natl Acad Sci U S A, 106(22): 9069-74.

A strong and positive correlation exists between chronic disease and affective disorders, but the biological mechanisms underlying this relationship are not known. Here we show that rats with mammary cancer exhibit depression- and anxiety-like behaviors in the absence of overt sickness behaviors. The production of proinflammatory cytokines, known to induce depressive-like behaviors, was elevated in the periphery and in the hippocampus of rats with tumors compared with controls. In tumor-bearing ... [Abstract] [Full-text]

Articles on Depression published 3 June 2009:

Prevention of depression in at-risk adolescents: a randomized controlled trial.   JAMA, 301(21): 2215-24.

CONTEXT: Adolescent offspring of depressed parents are at markedly increased risk of developing depressive disorders. Although some smaller targeted prevention trials have found that depression risk can be reduced, these results have yet to be replicated and extended to large-scale, at-risk populations in different settings. OBJECTIVE: To determine the effects of a group cognitive behavioral (CB) prevention program compared with usual care in preventing the onset of depression. DESIGN, SETTING, ... [Abstract] [Full-text]

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Articles on Depression published 2 June 2009:

Persisting decline in depression treatment after FDA warnings.   Arch Gen Psychiatry, 66(6): 633-9.

CONTEXT: In October 2003 the Food and Drug Administration (FDA) issued a Public Health Advisory about the risk of suicidality for pediatric patients taking antidepressants; a boxed warning, package insert, and medication guide were implemented in February 2005. The warning was extended to young adults aged 18 to 24 years in May 2007. Immediately following the 2003 advisory, unintended declines in case finding and non-selective serotonin reuptake inhibitor substitute treatment were shown for ... [Abstract] [Full-text]

Major depressive disorder and hypothalamic-pituitary-adrenal axis activity: results from a large cohort study.   Arch Gen Psychiatry, 66(6): 617-26.

CONTEXT: There is a central belief that depression is associated with hyperactivity of the hypothalamic-pituitary-adrenal axis, resulting in higher cortisol levels. However, results are inconsistent. OBJECTIVE: To examine whether there is an association between depression and various cortisol indicators in a large cohort study. Design, Setting, and PARTICIPANTS: Data are from 1588 participants of the Netherlands Study of Depression and Anxiety who were recruited from the community, general ... [Abstract] [Full-text]

Effect of maternal psychopathology on behavioral problems in preschool children exposed to terrorism: use of generalized estimating equations to integrate multiple informant reports.   Arch Pediatr Adolesc Med, 163(6): 531-9.

OBJECTIVE: To examine whether the number of maternal psychopathologies is associated with increased clinically significant behavioral problems in preschool children exposed to disaster, using child behavior ratings from multiple informants. DESIGN: Cross-sectional study. SETTING: Lower Manhattan, New York, New York. PARTICIPANTS: One hundred two preschool child-mother dyads directly exposed to the World Trade Center attacks. EXPOSURES: Maternal disorders: 2 (posttraumatic stress disorder [PTSD] ... [Abstract] [Full-text]

Articles on Depression published 1 June 2009:

Screening for postpartum depression at well-child visits: is once enough during the first 6 months of life?   Pediatrics, 123(6): e982-8.

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