In:
Psychological Medicine, Cambridge University Press (CUP), Vol. 49, No. 8 ( 2019-06), p. 1365-1377
Abstract:
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 D 2 antagonist with adjunctive antidepressant properties modifies activity in the brain's reward network in depression. Methods 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. Results 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. Conclusions 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.
Type of Medium:
Online Resource
ISSN:
0033-2917
,
1469-8978
DOI:
10.1017/S0033291718003306
Language:
English
Publisher:
Cambridge University Press (CUP)
Publication Date:
2019
detail.hit.zdb_id:
1470300-2
SSG:
5,2
