Science Blog: Why antidepressants cause mania/rapid cycling

Antidepressants and MAOIs both of which increase functional monoamines (contribute to stable moods, and an excess or deficiency of monoamines seems to cause or result from several mood disorders) neurotrammiters (E.G. norepinephrine, dopamine and serotonin), are known to precipitate mania or rapid-cycling in an estimated 20-30% of patients.

There has recently reported a strong association between velo-cardio-facial syndrome (VCFS) patients diagnosed with rapid-cycling bipolar disorder, and an allele encoding the low enzyme activity catechol-O-methyl (controls the degradition of the enzymes for dopamine, endrinephrine and norepinephrine) transferase variant (COMT L).

Between 85-90% of VCFS patients are hemizygous (an individual who has only one member of a chromosome pair or chromosome segment rather than the usual two) for COMT.

Homozygosity (The state of possessing two identical forms of a particular gene) for the low activity allele (COMT LL) is associated with a 3-4 fold reduction of COMT enzyme activity compared with homozygotes for the high activity variant (COMT HH).

There is nearly an equal distribution of L and H alleles in Caucasians. Individuals with COMT LL would be expected to have higher levels of transynaptic catecholamines due to a reduced COMT degradation of norepinephrine and dopamine.

It is therefore hypothesized that the frequency of COMT L would be greater in Rapid Cycling BPD ascertained from the general population. Significantly, we found that the frequency of COMT L was higher in the ultra-ultra rapid cycling variant of BPD than among all other groups studied .

These findings indicate that COMT L could represent a modifying gene that predisposes to ultra-ultra or ultradian cycling in patients with bipolar disorder.

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