Neurosteroids are synthesized in the brain and modulate brain excitability. There is increasing evidence of their\r\nsedative, anesthetic and antiseizure properties, as well as their influence on mood. Currently neurosteroids are\r\nclassified as pregnane neurosteroids (allopregnanolone and allotetrahydrodeoxycorticosterone), androstane\r\nneurosteroids (androstanediol and etiocholanone) or sulfated neurosteroids (pregnenolone sulfate and\r\ndehydroepiandrosterone sulfate). Both preclinical and clinical findings indicate that progesterone derivative\r\nneurosteroids such as allopregnanolone and allotetrahydrodeoxycorticosterone play a role in mood disorders.\r\nClozapine and olanzapine, which were shown to be effective in stabilizing bipolar disorder, elevate pregnenolone\r\nlevels in rat hippocampus, cerebral cortex, and serum. In lithium-treated mice, the blood levels of allopregnanolone\r\nand pregnenolone were elevated compared to control levels. Women diagnosed with bipolar disorder typically\r\nshow symptomatic exacerbation in relation to the menstrual cycle, and show vulnerability to the onset or\r\nrecurrence of mood disorders immediately after giving birth, when the levels of neurosteroid derivatives of\r\nprogesterone drop. Whereas in women who had recovered from bipolar disorder, the plasma concentration of\r\nallopregnanolone was elevated compared to either healthy controls or women with major depressive disorder\r\nduring the premenstrual period. During depressive episodes, blood level of allopregnanolone is low. Treatment\r\nwith fluoxetine tends to stabilize the levels of neurosteroids in depression. These findings converge to suggest that\r\nthese steroids have significant mood-stabilizing effect. This hypothesis is consistent with the observation that a\r\nnumber of anticonvulsants are effective therapies for bipolar disorder, a finding also consistent with the antiseizure\r\nproperties of neurosteroids. Further exploration of action of neuroactive steroids is likely to open new frontiers in\r\nthe investigation of the etiology and treatment of mood disorders, particularly bipolar disorders.
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