Prognostic implications of social anxiety comorbidity in major depressive disorder. Evidence from three large samples with adult and older patients

Background/objectives: Social anxiety disorder (SAD) frequently co-occurs with major depressive disorder (MDD). We examined the prevalence and clinical correlates of SAD across three heterogeneous MDD cohorts. Methods: Secondary analyses were conducted in adult (CO-MED: n = 482; GSRD: n = 1398) and late-life (IRL-GREY: n = 438) patients. SAD was assessed dimensionally (PDSQ) and categorically (MINI; SCID-1). Cohort-specific instruments were used to assess depressive severity (QIDS; MADRS), suicidality (CHRT; MADRS; SIS) and hypomanic symptoms (ASRM; YMRS). In late-life depression, neurocognitive tests were administered. Multivariate models were adjusted for depression and anxiety levels. Results: SAD prevalence varied markedly by samples and diagnostic definitions (CO-MED: 46.7% with PDSQ≥6; 17.0% with PDSQ>12; GSRD: 3.0%; IRL-GREY: 8.7%). Across cohorts, SAD was associated with earlier MDD onset (CO-MED: p < 0.001 d = -0.36; GSRD: p = 0.014 d = -0.39; IRL-GREY: p = 0.002 d = -0.54) and greater anxiety comorbidity (CO-MED: GAD: p < 0.001 d = 1.24; panic: p < 0.001 d = 1.29; GSRD: GAD: p < 0.001; panic: p < 0.001; IRL-GREY: agoraphobia: p < 0.001). After controlling for depression and anxiety levels, SAD was linked to higher suicide risk in both adult cohorts (CO-MED: OR 1.04 (1.01-1.08); GSRD: OR 1.29 (1.04-1.64)) and to lower 6-week remission in CO-MED cohort (OR 0.51 (0.29-0.91)). Conclusions: In MDD, SAD has consistent associations with earlier illness onset and anxiety burden, modest associations with suicidality and antidepressant outcomes, and reduced impact in late life.