Cerebral blood flow in bipolar disorder: A systematic review

Background: Neuroimaging of cerebral blood flow (CBF) can inform our understanding of the pathophysiology of bipolar disorder (BD) as there is increasing support for the concept that BD is in part a vascular disease. Despite numerous studies examining CBF in BD, there has not yet been a review of the literature on the topic of CBF in BD.

Methods: A systematic review of the literature on CBF in BD was performed using the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA). Studies included measured CBF by single-photon emission computerized tomography (SPECT), positron emission tomography (PET), arterial spin labelling (ASL) or perfusion weighted imaging (PWI) in a group of BD patients.

Results: Thirty-three studies with a total of 508 subjects with BD and 538 controls were included (n = 15 SPECT; n = 8 PET; n = 7 ASL; n = 1 PWI; n = 2 other). The majority of studies in BD depression and mania reported widespread resting hypoperfusion in cingulate gyrus, frontal, and anterior temporal regions in comparison to healthy controls (HC). Findings in euthymic BD subjects and in symptomatically heterogeneous groups were less consistent. Studies that examined CBF responses to cognitive or emotional stimuli in BD subjects have reported hypoperfusion or different regions involved in comparison to HC.

Limitations: Important methodological heterogeneity between studies, and small number of subjects per study.

Conclusions: The most consistent findings to date are hypoperfusion in BD mood episodes, and hypoactive CBF responses to emotional or cognitive challenges. Future studies examining CBF are warranted, including prospective studies, studies examining CBF as a treatment target, and multimodal imaging studies.