2 Neuroscience2.11 Integrated neurobiology of syndromes and states
2.11.8 Bipolar affective disorders
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Written by Resident Doctor Committee · Published
Genetics
Heritability is about 60 to 80%, with many common variants of small effect and some rare variants.
CACNA1C, which encodes the alpha 1C subunit of the Cav1.2 calcium channel, is a replicated risk locus.
Genetic liability overlaps substantially with schizophrenia and depression.
Structural imaging
Finding | Detail |
|---|---|
Lateral ventricles | Enlarged: the most replicated structural finding |
Amygdala, hippocampus, thalamus | Reduced or unchanged |
Cortical thickness | Reduced, most consistently in the ventrolateral prefrontal cortex (inferior frontal gyrus) |
White matter hyperintensities | Rise with vascular risk factors, hypertension foremost |
The ventrolateral prefrontal cortex exerts top-down control over emotion and impulses.
Diffusion tensor imaging shows reduced fractional anisotropy in prefrontal-limbic white matter tracts, chiefly the corpus callosum and cingulum.
Lithium and other confounds
Lithium is linked to preserved or increased grey matter, such as a larger hippocampus. This neuroprotective effect is separate from the structural markers of the illness.
Substance use, obesity and vascular illness also confound imaging findings.
No imaging finding establishes bipolar disorder in an individual.
Functional imaging
The impulsivity of mania maps to reduced orbitofrontal cortex activity, the region that codes the value of expected outcomes.
Functional results depend on the person's current mood state.
Kindling and course
Post's kindling model proposes that each episode lowers the threshold for the next, so episodes depend less on external triggers.
Episodes recur more often as the illness progresses, so cycle length shortens rather than lengthens.
Early episodes more often follow life events.
Poor recall, poor adherence, substance use and continuing adversity can also explain apparent acceleration.