Familiality of symptom dimensions in depression.
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.


OBJECTIVE
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.


METHODS
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.
Korszun
Ania
A
Department of Psychological Medicine, University of Wales College of Medicine, Cardiff, United Kingdom. akorszun@umich.edu
Moskvina
Valentina
V
Brewster
Shyama
S
Craddock
Nick
N
Ferrero
François
F
Gill
Michael
M
Jones
Ian Richard
IR
Jones
Lisa Anne
LA
Maier
Wolfgang
W
Mors
Ole
O
Owen
Michael J
MJ
Preisig
Martin
M
Reich
Theodore
T
Rietschel
Marcella
M
Farmer
Anne
A
McGuffin
Peter
P
D000328:Adult; D017668:Age of Onset; D016022:Case-Control Studies; D003866:Depressive Disorder / Q000175:diagnosis* / Q000453:epidemiology / Q000235:genetics*; D005163:Factor Analysis, Statistical; D005190:Family / Q000523:psychology; D005260:Female; D020022:Genetic Predisposition to Disease / Q000523:psychology; D006801:Humans; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D011569:Psychiatric Status Rating Scales / Q000706:statistics & numerical data; D012720:Severity of Illness Index; D035781:Siblings / Q000523:psychology