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.
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.
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.
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).
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.