Serotonin markers and affective disorders

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Dysfunction of the serotoninergic system has long been suspected in major depression and related disorders. Depression can successfully be treated with selective drugs which target serotonin receptors. The serotonin transporter may also be involved in susceptibility to affective disorders and in the response to treatment with these drugs. Allelic association has been suggested between the serotonin transporter gene (located on chromosome 17q11.1-12) and unipolar affective disorder. (48) The presence of one allele of this gene was significantly associated with a risk of unipolar affective disorder. This study also included a group of bipolar affective disorder patients, although no associations were found with this marker in this patient group compared to normal controls. This preliminary finding may add to our understanding of the possibility of polygenic inheritance in affective disorders. These findings were replicated in two different samples, again showing an association between this marker and unipolar affective disorder (major depression with melancholia) (49> and no association with a group of bipolar affective disorder patients. (50) A linkage study with the functional variant of the serotonin transporter gene in families with bipolar affective disorder could not exclude linkage. (51) More interestingly, a polymorphism within the promoter region of the serotonin transporter gene has been associated to treatment response to fluvoxamine, a typical selective serotonin reuptake inhibitor in major depression with psychotic features. (52) This promising preliminary finding requires to be confirmed. The tryptophan hydroxylase gene, which codes for the rate-limiting enzyme of serotonin metabolism, is also an important candidate gene for affective disorders and suicidal behaviour. Bellivier et al.5) reported a significant association between genotypes at this marker and bipolar affective disorder; no association was found with suicidal behaviour. In a previous study in depressed patients, suicidal behaviour was associated with one variant of this gene. (5.4)

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