We here propose a longitudinal, epidemiologic study of the genetic and environmental risk factors for major mood disorders, anxiety disorders, and alcohol dependence in male-male and male-female twin pairs from the population based Virginia Twin Registry. This study, which integrates two previously divergent traditions within psychiatric research, represents an extension of a highly successful study of female-female twin pairs from the same registry. Specifically, we propose to conduct two waves of assessment, at one year intervals, on both members of 2,800 twin pairs, of whom 1,500 will be male- male (around 55% monozygotic and 45% dizygotic) and 1,300 opposite-sex dizygotic twins. The first wave will be by phone and concentrate on major risk factors and symptom levels. The second wave will be in person and will assess risk factors, symptom levels and detailed one-year and lifetime prevalences for major depression, mania, generalized anxiety disorder, panic disorder, phobias, alcohol dependence and drug and alcohol abuse. Assessed environmental risk factors will include history of parental loss, parental rearing style, social class, personality, coping style, lifetime traumas, social support and stressful life events and difficulties. State-of-the-art sociometric and genetic analyses will produce advances in our understanding of the etiology of these conditions that have previously been beyond our grasp. We will be able to understand the etiologic role of genes and key environmental factors in these disorders in men, understand how genes and environment interact to produce illness, and clarify how these risk factors differentially impact on men and women. Insight will be gained into the role of genetic and environmental factors in the etiology of comorbidity. We will develop multivariate genetic models including specified environmental risk factors that will provide realistic etiologic models for these disorders that incorporate all major risk factor domains.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
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Epidemiologic and Services Research Review Committee (EPS)
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Virginia Commonwealth University
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Kendler, K S; Gardner, C O (2016) Depressive vulnerability, stressful life events and episode onset of major depression: a longitudinal model. Psychol Med 46:1865-74
van Loo, Hanna M; Aggen, Steven H; Gardner, Charles O et al. (2015) Multiple risk factors predict recurrence of major depressive disorder in women. J Affect Disord 180:52-61
Kendler, Kenneth S; Edwards, Alexis C; Gardner, Charles O (2015) Sex differences in the pathways to symptoms of alcohol use disorder: a study of opposite-sex twin pairs. Alcohol Clin Exp Res 39:998-1007
Otowa, Takeshi; York, Timothy P; Gardner, Charles O et al. (2014) The impact of childhood parental loss on risk for mood, anxiety and substance use disorders in a population-based sample of male twins. Psychiatry Res 220:404-9
Loken, E K; Hettema, J M; Aggen, S H et al. (2014) The structure of genetic and environmental risk factors for fears and phobias. Psychol Med 44:2375-84
Kendler, Kenneth S; Gardner, Charles O (2014) Sex differences in the pathways to major depression: a study of opposite-sex twin pairs. Am J Psychiatry 171:426-35
Kendler, K S; Aggen, S H (2014) Clarifying the causal relationship in women between childhood sexual abuse and lifetime major depression. Psychol Med 44:1213-21
Hsu, Kean J; Young-Wolff, Kelly C; Kendler, Kenneth S et al. (2014) Neuropsychological deficits in major depression reflect genetic/familial risk more than clinical history: a monozygotic discordant twin-pair study. Psychiatry Res 215:87-94
Kendler, K S; Halberstadt, L J (2013) The road not taken: life experiences in monozygotic twin pairs discordant for major depression. Mol Psychiatry 18:975-84
Kiecolt, K Jill; Aggen, Steven H; Kendler, Kenneth S (2013) Genetic and environmental influences on the relationship between mastery and alcohol dependence. Alcohol Clin Exp Res 37:905-13

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