Abstract

Background: Diagnostic criteria for a major depressive episode capture heterogeneous presentations across unipolar (UD) and bipolar (BD) and first-onset (FDE) depression. We evaluated the contribution of each depressive and (hypo)manic symptom to worse functioning in UD/BD/FDE subgroups. Methods: A post-hoc analysis of the BRIDGE-II-Mix study. Acutely depressed patients were stratified into UD, BD and FDE. Each (hypo)manic or depressive symptom was included in a diagnosis-specific logistic regression model with functioning as dependent variable. Better/worse functioning was set with median diagnosis-specific GAF scores cutoffs. All p values were two-tailed. Statistical significance was set at p < 0.05. Results: A total of 2768/2811 depressed individuals were enrolled. In BD (N= 716), "recurrent thoughts of death" (OR 2.48, p < 0.0001) and "feelings of worthlessness" (OR 2.28, p < 0.0001) among depressive symptoms, "aggressiveness" (OR 1.67, p= 0.022) as the unique (hypo)manic symptom, significantly contributed to worse functioning. In UD (N= 1357), "depressed mood" (OR 5.6, p= 0.031) and "diminished interest or pleasure" (OR 4.77, p < 0.0001) among depressive, "grandiosity" (OR 3.5, p= 0.014) among (hypo)manic symptoms, most significantly contributed to worse functioning. In FDE (N= 677) "recurrent thoughts of death" (OR 1.99, p < 0.0001) and "insomnia/hypersomnia" (OR 1.88, p= 0.039) among depressive, "grandiosity" (OR 5.98, p= 0.038) as (hypo)manic symptoms significantly contributed to worse functioning. Limitations: The post-hoc and cross-sectional design do not allow for prognostic or causal inferences. Conclusions: Key depressive and (hypo)manic symptoms distinctively associate with worse functional outcome in acute depression, with differential diagnostic-specific magnitude of effect. Core depressive symptoms are associated with worse functioning in unipolar depression, but not in bipolar or first-episode depression.