Psychotic features in bipolar and unipolar depression

Background: While some prior studies have found higher rates of psychotic depression in those with bipolar disorder or a bipolar relative, others have failed to confirm these observations. We examined the relationship of psychotic depression to polarity in several large familial samples of mood disorder. Methods: A total of 4,724 subjects with major mood disorder in three family studies on the genetics of bipolar I disorder (BPI) or recurrent major depressive disorder (MDDR) were administered semi‐structured interviews by clinicians. Determination of psychotic features was based on a report of hallucinations and/or delusions during the most severe depressive episode in the Schedule for Affective Disorders and Schizophrenia‐Lifetime Version or the Diagnostic Interview for Genetic Studies interview. Rates of psychotic depression were calculated by diagnostic category and comparisons were made between diagnoses within and across studies using the generalized estimating equation. Results: A diagnosis of BPI disorder was strongly predictive of psychotic features during depression compared to MDDR [odds ratio (OR) = 4.61, p < 0.0005]. Having bipolar II compared to MDDR was not predictive of psychosis (OR = 1.05, p = 0.260), nor was having a family history of BPI in MDDR subjects (OR = 1.20, p = 0.840). Conclusions: Psychotic features during a depressive episode increased the likelihood of a BPI diagnosis. Prospective studies are needed to confirm these findings. The potential genetic underpinnings of psychotic depression warrant further study.