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Official websites use. Share sensitive information only on official, secure websites. Inhibition of serotonergic raphe neurons is mediated by somatodendritic 5-HT1A autoreceptors, which may be increased in depressed patients. We report an association of the C G 5-HT1A promoter polymorphism with major depression and suicide in separate cohorts.

NUDR protein was colocalized with 5-HT1A receptors in serotonergic raphe cells, hippocampal and cortical neurons, and adult brain regions including raphe nuclei, indicating a role in regulating 5-HT1A autoreceptor expression.

Our data indicate that NUDR is a repressor of the 5-HT1A receptor in raphe cells the function of which is abrogated by a promoter polymorphism. We suggest a novel transcriptional model in which the G allele derepresses 5-HT1A autoreceptor expression to reduce serotonergic neurotransmission, predisposing to depression and suicide. Keywords: promoter, polymorphism, major depression, suicide, serotonin, transcription.

The serotonin system of the brain originates from neurons of the raphe nuclei that project widely throughout the brain to innervate various cortical, limbic, and hypothalamic areas that are involved in regulation of mood, emotion, stress, etc.