The 5-HT1A receptor gene is repressed by NUDR/DEAF-1 in raphe cells at the C-, but not at the G-allele of the C(-1019)G polymorphism that is associated with major depression and suicide.
The 5-HT1A receptor gene is repressed by NUDR/DEAF-1 in raphe cells at the C-, but not at the G-allele of the C(-1019)G polymorphism that is associated with major depression and suicide.
The association with major depression, suicide, and panic disorder of a new functional 5-HT1A polymorphism at C(-1019)G that selectively blocks repression of the 5-HT1A autoreceptor by NUDR further suggests a causative role for altered regulation of this receptor in predisposition to mental illness.
This study reveals sex-specific alterations in gene expression of the pre-synaptic 5-HT1D autoreceptors and 5-HT-related transcription factors, NUDR and REST, in DR neurons of women with MDD.
The serotonin 1A receptor (5-HT1A) and its associated transcriptional regulators, five prime repressor element under dual repression (Freud-1) and nuclear-deformed epidermal autoregulatory factor (NUDR/Deaf-1) have been previously found to be the repressors for 5-HT1A in the serotonergic raphe neurons, and are also altered in postmortem brains of individuals with major depressive disorder (MDD) and in rats exposed to chronic restraint stress.
The functional human 5-HT1A C(-1019)G promoter polymorphism (rs6295), which prevents the binding of Deaf-1/NUDR leading to dysregulation of the receptor, has been associated with major depression.