From the Research
Bipolar affective disorder is believed to arise from multiple biological mechanisms, including genetic factors, neurotransmitter dysregulation, structural and functional brain abnormalities, neuroendocrine dysfunction, circadian rhythm disruptions, neuroinflammation, oxidative stress, and mitochondrial dysfunction, as supported by recent studies 1, 2, 3. The primary theories include genetic factors, with heritability estimated at 60-85% and associations with genes like CACNA1C, ANK3, and BDNF 4. Some key points to consider are:
- Neurotransmitter dysregulation plays a crucial role, particularly involving serotonin, dopamine, norepinephrine, glutamate, and GABA imbalances.
- Structural and functional brain abnormalities are evident, especially in the prefrontal cortex, amygdala, hippocampus, and anterior cingulate cortex, with altered connectivity between these regions.
- Neuroendocrine dysfunction, particularly involving the hypothalamic-pituitary-adrenal (HPA) axis, leads to cortisol dysregulation and stress response abnormalities.
- Circadian rhythm disruptions affect sleep-wake cycles and mood regulation through altered melatonin and clock gene expression.
- Neuroinflammation and oxidative stress contribute through increased inflammatory markers and free radical damage.
- Mitochondrial dysfunction impairs energy production in neurons, while intracellular signaling pathway abnormalities, especially in the phosphoinositide and protein kinase C systems, affect neuronal communication. The most recent and highest quality study 3 suggests that lithium and valproate remain the pharmacological cornerstone to treat bipolar disorder, with different response patterns occurring according to the phases of illness and individual pretreatment variables. Treatment often requires combinations of mood stabilizers (lithium, valproate, carbamazepine), antipsychotics, antidepressants, and therapies targeting specific biological systems 5, 3. It is essential to consider clinical and preclinical factors to select the best treatment strategy, as lithium may be effective in treating acute mania and preventing both manic and depressive episodes, while valproate may be more effective as an antimanic rather than prophylactic agent 3.