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

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. 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. 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)). 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. • Social anxiety disorder (SAD) is common in major depressive disorder, with prevalence strongly influenced by diagnostic approach and sample characteristics. • Across adult and late-life cohorts, SAD is consistently associated with earlier onset of major depressive disorder and greater anxiety burden. • After adjustment for depression and anxiety severity, SAD shows a modest but significant association with suicide risk in adult patients with MDD. • SAD is linked to reduced short-term antidepressant remission in one adult cohort, but not consistently across samples. • The prognostic relevance of SAD appears attenuated in late-life depression, suggesting age-related differences in its clinical impact.