Claire V Day1, Justine M Gatt2, Amit Etkin3, Charles DeBattista4, Alan F Schatzberg4, Leanne M Williams5. 1. The Brain Dynamics Centre, Discipline of Psychiatry, Sydney Medical School, University of Sydney, Sydney 2006, NSW, Australia; Westmead Millennium Institute, Westmead 2145, NSW, Australia; Brain Resource Ltd., 235 Jones Street, Sydney, NSW, Australia; Brain Resource Inc., 1000 Sansome Street, San Francisco, CA 94111, USA. 2. The Brain Dynamics Centre, Discipline of Psychiatry, Sydney Medical School, University of Sydney, Sydney 2006, NSW, Australia; Westmead Millennium Institute, Westmead 2145, NSW, Australia; Neuroscience Research Australia, Randwick 2031, NSW, Australia; School of Psychology, University of New South Wales, Sydney 2052, NSW, Australia. 3. Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA 94305, USA; Sierra-Pacific Mental Illness Research, Education and Clinical Center (MIRECC) Veterans Affairs Palo Alto Health Care System, Palo Alto, CA 94304, USA. 4. Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA 94305, USA. 5. Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA 94305, USA; Sierra-Pacific Mental Illness Research, Education and Clinical Center (MIRECC) Veterans Affairs Palo Alto Health Care System, Palo Alto, CA 94304, USA. Electronic address: leawilliams@stanford.edu.
Abstract
BACKGROUND: Depressed 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. METHODS: MDD 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. RESULTS: Melancholic 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. LIMITATIONS: Assessments were taken at only one medication-free time point. Reward was investigated using an emotional faces task. CONCLUSIONS: Melancholic 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.
BACKGROUND: Depressed 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 MDDpatients and controls on a neurocognitive test battery that assesses eight general and emotional cognitive domains including the hypothesized decision-making and reward-threat perception. METHODS:MDD outpatients (n=1008) were assessed using a computerized battery of tests. MDDparticipants 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. RESULTS: Melancholic 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. LIMITATIONS: Assessments were taken at only one medication-free time point. Reward was investigated using an emotional faces task. CONCLUSIONS:Melancholic 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.
Authors: Martin P Paulus; Murray B Stein; Michelle G Craske; Susan Bookheimer; Charles T Taylor; Alan N Simmons; Natasha Sidhu; Katherine S Young; Boyang Fan Journal: J Affect Disord Date: 2017-01-11 Impact factor: 4.839
Authors: Katherine A Grisanzio; Andrea N Goldstein-Piekarski; Michelle Yuyun Wang; Abdullah P Rashed Ahmed; Zoe Samara; Leanne M Williams Journal: JAMA Psychiatry Date: 2018-02-01 Impact factor: 21.596