¹Peking University Sixth Hospital, Department of Clinical Psychopharmacology, Beijing, China, ²Peking University Institute of Mental Health, Department of Clinical Psychopharmacology, Beijing, China

Background: Bipolar disorder (BD) is uniquely characterized by fluctuations of opposing moods (mania/ hypomania and depression) as well as shifts between pathologic and euthymic states. Advances in functional MRI methodologies have helped delineate the functional neuroanatomy associated with BD. Nevertheless, the pathophysiological mechanisms responsible for mood instability, transitions between mood states, and the emergence of extreme mood episodes remain inadequately elucidated.

Aims & Objectives: To offer a thorough synthesis of evidence derived from functional MRI investigations, analyzed through the lens of mood states. Specifically, the focus will be both on studies conducted in patients with specific mood states and on studies comparing patients between mood states.

Method: This narrative review synthesizes current evidence on trait and state-related functional neuroimaging measures in bipolar disorder.

Results: It begins by outlining patterns of abnormal brain activation and functional connectivity observed in bipolar disorder across varying mood states. Subsequent sections concentrate on studies involving patients in a single mood episode to clarify core pathophysiology, as well as comparative analyses across different mood states to isolate mood-specific neural correlates. The presentation also provides a concise summary of prevailing theoretical frameworks and suggests promising directions for further investigation.

Discussion & Conclusions: A nuanced comprehension of pathophysiology that incorporates mood state considerations may not only advance neurophysiological insights into acute mood episode formation but also promote the discovery of biologically grounded targets for tailored therapies and novel treatment approaches for bipolar disorder.