Cognitive and emotional biomarkers of melancholic depression: An iSPOT-D report

BackgroundDepressed patients with melancholic features have distinct impairments in cognition and anhedonia, but it remains unknown whether these impairments can be quantified on neurocognitive biomarker tests of behavioral performance. We compared melancholic major depressive disorder (MDD) patients to non-melancholic MDD patients and controls on a neurocognitive test battery that assesses eight general and emotional cognitive domains including the hypothesized decision-making and reward-threat perception.MethodsMDD outpatients (n=1008) were assessed using a computerized battery of tests. MDD participants met DSM-IV criteria for MDD and had a score ≥16 on the 17-item Hamilton Rating Scale for Depression. Melancholic MDD was defined using the Mini-International Neuropsychiatric Interview and a psychomotor disturbance observer-rated CORE measure score >7. Controls were age- and gender-matched with no previous DSM-IV or significant medical history.ResultsMelancholic participants (33.7% of the MDD sample) exhibited significantly poorer performance than controls across each domain of cognitive function and for speed of emotion identification and implicit emotion priming. Compared to the non-melancholic group, specific disturbances were seen on tests of information speed, decision speed, and reward-relevant emotional processing of happy expressions, even after co-varying for symptom severity.LimitationsAssessments were taken at only one medication-free time point. Reward was investigated using an emotional faces task.ConclusionsMelancholic MDD is distinguished by a specific neurocognitive marker profile consistent with reduced decision-making capacity under time demands and loss of reward sensitivity. This profile suggests an underlying deficit in mesolimbic-cortical circuitry for motivationally-directed behavior.