Abstract: Clinical response to antidepressant compounds correlates with a selective down-regulation of presynaptic 5-HT1A receptors in serotonergic raphe neurons. Thus regulation of the 5-HT1A receptor gene could play a crucial role in the treatment or etiology of major depression. The promoter and repressor activities of the human 5-HT1A receptor gene have been examined. The analysis of the 5?-flanking regions of the 5-HT1A receptor gene has revealed a segment located between about ?3438 and about ?393 bp upstream from the initiator ATG that mediates cell-specific repression of the gene that is greater in cells that do not express the 5-HT1A receptor. The sequence of part of this region in patients with major depression were examined and a polymorphic C-G change located at ?1017 bp was identified, which is associated with major depression. Thus, this sequence can be used as a genetic marker for major depression and related mental illnesses. A protein that binds to the DNA at the ?1017 locus has been identified.

Abstract: Clinical response to antidepressant compounds correlates with a selective down-regulation of presynaptic 5-HT1A receptors in serotonergic raphe neurons. Thus regulation of the 5-HT1A receptor gene could play a crucial role in the treatment or etiology of major depression. The promoter and repressor activities of the human 5-HT1A receptor gene have been examined. The analysis of the 5?-flanking regions of the 5-HT1A receptor gene has revealed a segment located between about ?3438 and about ?393 bp upstream from the initiator ATG that mediates cell-specific repression of the gene that is greater in cells that do not express the 5-HT1A receptor. The sequence of part of this region in patients with major depression were examined and a polymorphic C-G change located at ?1017 bp was identified, which is associated with major depression. Thus, this sequence can be used as a genetic marker for major depression and related mental illnesses. A protein that binds to the DNA at the ?1017 locus has been identified.

Abstract: Clinical response to antidepressant compounds correlates with a selective down-regulation of presynaptic 5-HT1A receptors in serotonergic raphe neurons. Thus regulation of the 5-HT1A receptor gene could play a crucial role in the treatment or etiology of major depression. The promoter and repressor activities of the human 5-HT1A receptor gene have been examined. The analysis of the 5′-flanking regions of the 5-HT1A receptor gene has revealed a segment located between about −3438 and about −393 bp upstream from the initiator ATG that mediates cell-specific repression of the gene that is greater in cells that do not express the 5-HT1A receptor. The sequence of part of this region in patients with major depression was examined and a polymorphic C-G change located at −1019 bp (numbered earlier as −1017) was identified, which is associated with major depression. Thus, this sequence can be used as a genetic marker for major depression and related mental illnesses.