Distinct neural signatures of reward processing underlying bipolar disorder and major depressive disorder: a systematic review and meta-analysis

Abstract

The misdiagnosis of bipolar disorder (BD) as major depressive disorder (MDD) delays appropriate treatment. Identifying distinct biomarkers is essential for improving diagnostic accuracy. Neuroimaging studies highlight disorder-specific neural signatures of reward processing in BD and MDD, particularly during reward anticipation and consumption. This meta-analysis investigates differential neural activation patterns in BD and MDD relative to healthy controls. A systematic search of PUBMED, Web of Science, Brainmap.org, EMBASE, MEDLINE, PsycINFO, PsycARTICLES, and Scopus identified twenty-three fMRI studies including a total of 1,264 participants. During reward anticipation, BD exhibits hyperactivity in the left inferior frontal gyrus and insula, with reduced activity in the right inferior frontal gyrus and insula. No consistent amplification or attenuation was observed during reward delivery. In contrast, MDD only shows blunted responses in the bilateral caudate during reward delivery. These findings reveal distinct neural signatures of reward processing in BD and MDD, offering potential neurobiological biomarkers for differentiation. This may contribute to precision psychiatry by enhancing diagnostic accuracy and informing targeted interventions.