Post-traumatic stress disorder and childhood emotional abuse are markers of subthreshold bipolarity and worse treatment outcome in major depressive disorder

Post-traumatic stress disorder (PTSD) and childhood maltreatment (CMT: parental neglect; emotional, physical and sexual abuse) have been linked to bipolar disorder but they are also common in major depressive disorder (MDD). Our objective was to investigate their association with the bipolar spectrum and antidepressant treatment outcome in 482 outpatients with DSM-IV MDD treated in the Combining Medications to Enhance Depression Outcomes trial for 28 weeks Bipolar spectrum score included age of onset <21 years, subthreshold hypomania (a period of elated or irritable mood with at least two concurrent hypomanic symptoms, which did not fulfill DSM criteria for hypomanic/manic episode) and depressive mixed state (DMX). PTSD subjects (n = 107; 22%) had more severe depression (P < 0.0001), work and social impairment (P = 0.0031), comorbid anxiety disorders (P < 0.0001) and increased suicidality (P = 0.0003). Bipolar spectrum score was higher with PTSD comorbidity (P = 0.0063) and childhood emotional abuse (P = 0.0001). PTSD comorbidity was associated with residual suicidality (P = 0.0218) after 6 weeks of antidepressant use whereas childhood emotional abuse [odds ratio (OR), 1.01-2.22], subthreshold hypomania (OR, 1.04-4.09) and DMX (OR, 1.00-4.19) were predictors of mood switch. These results corroborate the role of PTSD and childhood emotional abuse as markers of bipolar spectrum and prognostic factors during antidepressant treatment.