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Familiality of Symptom Dimensions in Depression
Ania Korszun, PhD, MD, MRCPsych;
Valentina Moskvina, PhD;
Shyama Brewster, BSc Joint (Hons);
Nick Craddock, MB, PhD, MRCPsych;
François Ferrero, MD;
Michael Gill, MD, MRCPsych, FTCD;
Ian Richard Jones, MB, PhD, MRCPsych;
Lisa Anne Jones, BSc (Hons), PhD;
Wolfgang Maier, MD;
Ole Mors, MD, PhD;
Michael J. Owen, PhD, FRCPsych;
Martin Preisig, MD, MPH;
Theodore Reich, MD;
Marcella Rietschel, MD;
Anne Farmer, MD, FRCPsych;
Peter McGuffin, MB, PhD, FRCP, FRCPsych
Arch Gen Psychiatry. 2004;61:468-474.
Background Depression is a clinically heterogeneous disorder thought to result from multiple genes interacting with environmental and developmental components. A dimensional rather than a categorical approach to depressive phenotype definition may be more useful for identification of susceptibility genes.
Objectives To perform an exploratory factor analysis on a range of depressive and anxiety symptoms in a large, well-defined sample of depressed siblings, as well as a confirmatory factor analysis in a separate large group of unrelated depressed subjects, and to analyze correlations of identified symptom dimensions between depressed siblings.
Design Subjects (N = 1034), including 475 sibling pairs, with a history of at least 2 depressive episodes were recruited from the Depression Network Study, a large-scale multicenter collection of families affected by recurrent unipolar depression. Subjects were interviewed using the Schedules for Clinical Assessment in Neuropsychiatry (SCAN) and diagnosed according to the DSM-IV and the International Classification of Diseases, 10th Revision, using a computerized scoring program (CATEGO5). Factor analysis was carried out on 26 depression symptom items, including 4 anxiety screening items. Confirmatory factor analysis was performed on an independent sample of 485 depressed individuals.
Results Four interpretable factors were identified: (1) mood symptoms and psychomotor retardation; (2) anxiety; (3) psychomotor agitation, guilt, and suicidality; and (4) appetite gain and hypersomnia. For each symptom group, a quantitative scale was constructed, and correlations between siblings were calculated. There was a moderate degree of sibling homotypia for some depressive symptoms, and factors 1, 2, and 3 showed significant positive familial correlation (0.145 [P = .001], 0.335 [P<.001], and 0.362 [P<.001], respectively).
Conclusions This is the first study of large, well-defined samples of depressed subjects in whom symptom dimensions have been derived and then confirmed using independent material. The significant correlations between siblings for 3 of the dimensions suggest substantial familial, perhaps genetic, etiologies.
From the Department of Psychological Medicine, University of Wales College of Medicine, Cardiff (Dr Korszun, Moskvina, Craddock, and Owen), GlaxoSmithKline Medical Genetics, Middlesex (Ms Brewster), Department of Psychiatry, University of Birmingham, Birmingham (Drs I. R. Jones and L. A. Jones), and Medical Research Council Social Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, King's College, London (Drs Farmer and McGuffin), England; Department of Psychiatry, University of Geneva, Geneva (Dr Ferrero), and Departement Universitaire de Psychiatrie Adult, Prilly-Lausanne (Dr Preisig), Switzerland; Department of Psychiatry, Trinity Centre for Health Sciences, St James' Hospital, Dublin, Ireland (Dr Gill); Department of Psychiatry, University of Bonn, Bonn (Dr Maier), and Division of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Mannheim (Dr Rietschel), Germany; Department of Psychiatric Demography, Psychiatric Hospital in Aarhus, Aarhus, Denmark (Dr Mors); and Department of Psychiatry, Washington University School of Medicine, St Louis, Mo (Dr Reich).
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