Differentiating bipolar disorder from unipolar depression in youth: A systematic literature review of neuroimaging research studies

Differentiating bipolar disorder from unipolar depression is one of the most difficult clinical questions posed in pediatric psychiatric practices, as misdiagnosis can lead to severe repercussions for the affected child. This study aimed to examine the existing literature that investigates brain differences between bipolar and unipolar mood disorders in children directly, across all neuroimaging modalities. We performed a systematic literature search through PubMed, PsycINFO, Embase, and Medline databases with defined inclusion and exclusion criteria. Nine research studies were included in the systematic qualitative review, including three structural MRI studies, five functional MRI studies, and one MR spectroscopy study. Relevant variables were extracted and brain differences between bipolar and unipolar mood disorders in children as well as healthy controls were qualitatively analyzed. Across the nine studies, our review included 228 subjects diagnosed with bipolar disorder, 268 diagnosed with major depressive disorder, and 299 healthy controls. Six of the reviewed studies differentiated between bipolar and unipolar mood disorders. Differentiation was most commonly found in the anterior cingulate cortex (ACC), insula, and dorsal striatum (putamen and caudate) brain areas. Despite its importance, the current neuroimaging literature on this topic is scarce and presents minimal generalizability.