Neuroscience in pictures: Bipolar disorder

Bipolar disorder is a chronic, episodic mood illness characterized by recurrent oscillations between mania, depression, and euthymia, affecting an estimated 2.4% of the global population. This pictorial review explores its pathophysiology through the case of a young individual presenting with a first manic episode with psychotic features. We examine the convergence of genetic loading (∼70-90% heritability), neurodevelopmental vulnerability, and environmental precipitants-including sleep restriction and antidepressant exposure-in unmasking this individual's illness. We review interconnected pathophysiological mechanisms underlying bipolar disorder, including fronto-limbic, reward, and cognitive control circuit dysfunction; opposing catecholaminergic-cholinergic imbalances driving mania vs depression; peripheral and central neuroinflammation; BDNF-mediated synaptic plasticity disruption; hypothalamic-pituitary-adrenal, thyroid, and gonadal axis dysregulation; and circadian rhythm disturbance. Recurrent episodes may drive progressive, heterogeneous brain changes that are potentially modifiable, reinforcing early intervention and adherence. Emerging biomarkers and phase-specific pharmacotherapy reflect progress toward personalized, multimodal treatment integrating mood stabilization with chronobiological and psychosocial optimization.