A Population-Based Twin Study of Major Depression in Women: The Impact of Varying Definitions of Illness

Department of Psychiatry, Medical College, Virginia Commonwealth University, Richmond 23298-0710.
Archives of General Psychiatry (Impact Factor: 14.48). 05/1992; 49(4):257-66. DOI: 10.1001/archpsyc.1992.01820040009001
Source: PubMed


Although depression aggregates in families, the degree to which this aggregation results from genetic vs environmental factors remains uncertain. We examined this question in 1033 female-female twin pairs from a population-based registry. Both members of each twin pair were "blindly" assessed by structured psychiatric interview. Nine commonly used definitions of major depression, which produced life-time prevalence rates ranging from 12% to 33%, were examined. For all definitions, the results of model fitting to twin correlations suggested that the liability to depression results from genetic factors and environmental experiences unique to the individual. For seven of the definitions, the estimated heritability of liability was similar, ranging from 33% to 45%. For the two definitions that included only primary cases of depression, the heritability was lower (21% to 24%). The results document that in women (1) genetic factors play a substantial, but not overwhelming, role in the cause of depression; (2) the tendency for depression to aggregate in families results largely from shared genetic and not from shared environmental factors; (3) except for definitions that exclude secondary cases, the magnitude of genetic influence is similar in broadly and narrowly defined forms of major depression; and (4) most environmental experiences of causative importance for depression are those not shared by members of an adult twin pair.

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    • "While the relative risk of depression changes throughout the female reproductive life cycle, the windows of increased vulnerability for depression occur during periods of significant hormonal fluctuations (Lokuge et al. 2011). One of the most vulnerable periods for a woman to become depressed is after childbirth (Kendler et al. 1992). Postpartum depression (PPD) affects approximately 13% of women and has a negative impact on the lives of the mother and infant. "
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    ABSTRACT: Postpartum depression (PPD) affects approximately 13% of women and has a negative impact on mother and infant, hence reliable biological tests for early detection of PPD are essential. We aimed to identify robust predictive biomarkers for PPD using peripheral blood gene expression profiles in a hypothesis-free genome-wide study in a high-risk, longitudinal cohort. Method We performed a genome-wide association study in a longitudinal discovery cohort comprising 62 women with psychopathology. Gene expression and hormones were measured in the first and third pregnancy trimesters and early postpartum (201 samples). The replication cohort comprised 24 women with third pregnancy trimester gene expression measures. Gene expression was measured on Illumina-Human HT12 v4 microarrays. Plasma estradiol and estriol were measured. Statistical analysis was performed in R. We identified 116 transcripts differentially expressed between the PPD and euthymic women during the third trimester that allowed prediction of PPD with an accuracy of 88% in both discovery and replication cohorts. Within these transcripts, significant enrichment of transcripts implicated that estrogen signaling was observed and such enrichment was also evident when analysing published gene expression data predicting PPD from a non-risk cohort. While plasma estrogen levels were not different across groups, women with PPD displayed an increased sensitivity to estrogen signaling, confirming the previously proposed hypothesis of increased sex-steroid sensitivity as a susceptibility factor for PPD. These results suggest that PPD can be robustly predicted in currently euthymic women as early as the third trimester and these findings have implications for predictive testing of high-risk women and prevention and treatment for PPD.
    Full-text · Article · Feb 2014 · Psychological Medicine
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    • "As noted earlier, these interviews were administered by telephone. Telephone administration is now widely accepted in clinical reappraisal studies based on evidence of comparable validity to inperson administration (Kendler et al., 1992; Rohde et al., 1997; Sobin et al., 1993). A great advantage of telephone administration is that a centralized and closely supervised clinical interview staff can carry out the interviews without the geographic restrictions required for face-to-face clinical assessment. "
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    ABSTRACT: A clinical reappraisal study was carried out in conjunction with the Army Study to Assess Risk and Resilience in Servicemembers (Army STARRS) All-Army Study (AAS) to evaluate concordance of the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) diagnoses based on the Composite International Diagnostic Interview Screening Scales (CIDI-SC) and post-traumatic stress disorder (PTSD) checklist (PCL) with diagnoses based on independent clinical reappraisal interviews (Structured Clinical Interview for DSM-IV [SCID]). Diagnoses included: lifetime mania/hypomania, panic disorder, and intermittent explosive disorder; six-month adult attention-deficit/hyperactivity disorder; and 30-day major depressive episode, generalized anxiety disorder, PTSD, and substance (alcohol or drug) use disorder (abuse or dependence). The sample (n = 460) was weighted for over-sampling CIDI-SC/PCL screened positives. Diagnostic thresholds were set to equalize false positives and false negatives. Good individual-level concordance was found between CIDI-SC/PCL and SCID diagnoses at these thresholds (area under curve [AUC] = 0.69-0.79). AUC was considerably higher for continuous than dichotomous screening scale scores (AUC = 0.80-0.90), arguing for substantive analyses using not only dichotomous case designations but also continuous measures of predicted probabilities of clinical diagnoses. Copyright © 2013 John Wiley & Sons, Ltd.
    Full-text · Article · Dec 2013 · International Journal of Methods in Psychiatric Research
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    • "We assumed a liability-threshold model. The strengths and limitations of this model have been outlined previously (Kendler et al. 1992a; Neale and Maes 2004). In factor analysis, one seeks to explain the covariation between a number of variables, e.g. "
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    ABSTRACT: The specificity of genetic and environmental risk factors for illicit substance use and substance use disorders (SUD) was investigated by utilizing self and co-twin reports in 1,791 male twins. There was a high rate of comorbidity between both use of, and SUD from, different classes of illicit substances. For substance use, the model that included one common genetic, one shared environmental, and one individual-specific (i.e., unique) environmental factor, along with substance-specific effects that were attributed entirely to genetic factors fit the data best. For illicit SUD, one common genetic and one common unique environmental risk factor, and substance specific shared environmental and unique environmental risk factors were identified. Risk factors for illicit substance use and SUD are mainly non-specific to substance class. Co-twin rating of illicit substance use and SUD was a reliable source of information, and by taking account of random and systematic measurement error, environmental exposures unique to the individual were of lesser importance than found in earlier studies.
    Full-text · Article · Nov 2013 · Behavior Genetics
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