BIPOLAR DISORDER

Amygdala

Bilateral amygdala hyperactivation during both manic and depressive phases. Volume enlargement in some studies, reduction in others — likely state-dependent.

Prefrontal Cortex (PFC)

Hypofrontality — reduced gray matter volume and metabolic activity in ventrolateral and orbitofrontal PFC. More pronounced in Bipolar I than II.

Hippocampus

Volume reduction proportional to illness duration and number of depressive episodes. Manic episodes show less hippocampal impact than depressive ones.

White Matter / Corpus Callosum

Diffusion Tensor Imaging (DTI) consistently shows white matter microstructural abnormalities — reduced fractional anisotropy — in frontolimbic tracts.

Default Mode Network (DMN)

Hyperconnectivity of the DMN during rest, especially in depression. Failure to deactivate DMN during cognitive tasks contributes to rumination.