Modulation of anterior cingulate cortex reward and penalty signalling in medication-naive young-adult subjects with depressive symptoms following acute dose lurasidone

• Published in: Psychological medicine Vol. 49; no. 8; pp. 1365 - 1377
• Main Authors: Wolke, Selina A., Mehta, Mitul A., O'Daly, Owen, Zelaya, Fernando, Zahreddine, Nada, Keren, Hanna, O'Callaghan, Georgia, Young, Allan H., Leibenluft, Ellen, Pine, Daniel S., Stringaris, Argyris
• Format: Journal Article
• Language: English
• Published: Cambridge, UK Cambridge University Press 01.06.2019
• Subjects: Adolescent; Adult; Antidepressants; Biomedical research; Blood flow; Brain; Brain mapping; Brain research; Cerebral blood flow; Child & adolescent psychiatry; Cortex; Cortex (cingulate); Cross-Over Studies; Cues; Depressive Disorder, Major - drug therapy; Depressive Disorder, Major - physiopathology; Depressive personality disorders; Design; Dopamine; Dopamine D2 Receptor Antagonists - therapeutic use; Dopamine D2 receptors; Dopaminergic Neurons - drug effects; Dopaminergic Neurons - physiology; Double-Blind Method; Drug dosages; Expectations; Female; Fines & penalties; Functional magnetic resonance imaging; Funding; Gyrus Cinguli - drug effects; Gyrus Cinguli - physiopathology; Hostility; Humans; Information processing; Labelling; Lurasidone Hydrochloride - therapeutic use; Magnetic Resonance Imaging; Male; Medical research; Mental depression; Neostriatum; Neuroimaging; Neurosciences; Original; Original Articles; Pharmaceutical industry; Psychotropic drugs; Reinforcement; Research centers; Resting; Reward; Severity; Spin labeling; Volunteers; Young Adult; Young adults; United Kingdom > UK; United States > US; reward; lurasidone; fMRI; depression; Anterior cingulate cortex; penalty
• ISSN: 0033-2917; 1469-8978; 1469-8978
• DOI: 10.1017/S0033291718003306

Aberrations in reward and penalty processing are implicated in depression and putatively reflect altered dopamine signalling. This study exploits the advantages of a placebo-controlled design to examine how a novel D2 antagonist with adjunctive antidepressant properties modifies activity in the brain's reward network in depression. We recruited 43 medication-naïve subjects across the range of depression severity (Beck's Depression Inventory-II score range: 0-43), including healthy volunteers, as well as people meeting full-criteria for major depressive disorder. In a double-blind placebo-controlled cross-over design, all subjects received either placebo or lurasidone (20 mg) across two visits separated by 1 week. Functional magnetic resonance imaging with the Monetary Incentive Delay (MID) task assessed reward functions via neural responses during anticipation and receipt of gains and losses. Arterial spin labelling measured cerebral blood flow (CBF) at rest. Lurasidone altered fronto-striatal activity during anticipation and outcome phases of the MID task. A significant three-way Medication-by-Depression severity-by-Outcome interaction emerged in the anterior cingulate cortex (ACC) after correction for multiple comparisons. Follow-up analyses revealed significantly higher ACC activation to losses in high- v. low depression participants in the placebo condition, with a normalisation by lurasidone. This effect could not be accounted for by shifts in resting CBF. Lurasidone acutely normalises reward processing signals in individuals with depressive symptoms. Lurasidone's antidepressant effects may arise from reducing responses to penalty outcomes in individuals with depressive symptoms.