Serotonin transporter and seasonal variation in blood serotonin in families with obsessive-compulsive disorder

Department of Pediatrics, University of Chicago, Chicago, Illinois, United States
Neuropsychopharmacology (Impact Factor: 7.05). 03/1998; 18(2):102-11. DOI: 10.1016/S0893-133X(97)00097-3
Source: PubMed


The serotonin transporter (HTT) is a candidate gene for obsessive-compulsive disorder (OCD) that has been associated with anxiety-related traits. The long (l) and short (s) variants of the HTT promoter have different transcriptional efficiencies. HTT promoter genotype and blood 5-HT concentration were examined in 70 subjects from 20 families ascertained through children and adolescents with a DSM-III-R diagnosis of OCD. The HTT promoter variant had a significant effect on blood 5-HT content. Subjects with the l/l and l/s genotypes had significantly higher blood 5-HT levels than did those with the s/s genotype. There was a significant interaction between HTT promoter genotype and seasonal variation in blood 5-HT content, with significant seasonal differences in 5-HT occurring only in the subjects with the l/l genotype. Further studies of the regulation of HTT gene expression are indicated.

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Available from: Gregory L Hanna, May 14, 2014
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    • "Heils et al. (1995, 1996) first reported the 5-HTT promoter region polymorphism identified at the promoter site of approximately 1 kb and demonstrated that the polymorphism could alter transcriptional levels of 5-HTT whilst, Collier et al. (1996) reported that the polymorphism (44 bp insertion and deletion) affected the expression efficiency of 5-HT, and proposed that it was linked to various mental disorders. The short (s) and long (l) allele variants of 5-HTT functional length promoter polymorphic region are called 5-HTTLPR and it has been shown that subjects with s allele (s/s or s/l) have lower 5-HT levels in blood platelets, lymphoblast cell and brain (Hanna et al., 1998; Lesch et al., 1996; Little et al., 1998). These studies prompted several research groups to investigate the role of 5-HTTLPR in depression and other neuroticism, of which some of the studies showed 5-HTTLPR association with anxiety, agreeableness, other neuroticism (Lesch et al., 1996, Greenberg et al., 2000, Melke et al., 2001), anticipatory worry and fear of uncertainity (Mazzanti et al., 1998) while others did not (Gustavsson et al., 1999; Jorm et al., 1998). "
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    ABSTRACT: Stress is clearly associated with the quality of life and many diseases, including mental disorders, with cortisol being a recognized biomarker for stress. Polymorphisms of the serotonin transporter gene (5-HTT), which results in long and short forms, have been reported to be associated with depression among major depressive disorder (MDD) patients. We have previously shown that 5-HTTLPR and waking cortisol do not predict depression in a general population sample, however, psychological resilience is a defence against depression. Reelin is an emerging biomarker for psychological resilience that plays an active role in neuronal migration. It is responsible for cytoarchitechtonic pattern formation in brain and modulates the migration of newly generated postmitotic neurons from the ventricular zone. In mice, overexpression of reelin in the hippocampus has anti-depressant activity by increasing neurogenesis and improving learning. A number of single nucleotide polymorphisms (SNPs), methylation of the promoter and coding region of the reelin (RELN) gene have been identified which affect the level of RELN mRNA and protein expression. Thus RELN is a potential candidate as a biomarker of psychological resilience and we have developed a rapid high-resolution melting (HRM) PCR analysis technique for the RELN SNPs and loci using gDNA isolated from buccal cells to test this hypothesis.
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    • "Subjects with the l/l and l/s genotypes had significantly higher blood 5-hydroxytryptamine (5-HT) levels than those with the s/s genotype. There was a significant interaction between HTT promoter genotype and seasonal variation in blood 5-HT content, with significant seasonal differences in 5-HT occurring only in the subjects with the l/l genotype[21]. Yoney et al.[22]found that the patients with OCD did not report a greater degree of seasonal variations than normal and no response was seen to bright light therapy in the small number of patients treated. On the other hand, Höflich et al.[23]reported the case of a 40-year-old woman with a seasonal form of OCD which was usually accompanied by obsessions and occurred only in autumn or winter. "
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    • "Two polymorphisms of the serotonin transporter gene have usually been examined with respect to their relation with behavioral variation. The first polymorphism, the 'linked polymorphic region' (LPR; or 5HTTLPR), has two common repeat alleles—short (S; 14 repeat) or long (L; 16 repeat)—that differentially modulate the transcription of SLC6A4, with the S allele demonstrated to have less transcriptional efficiency (Greenberg et al., 1999; Hanna et al., 1998; Heinz et al., 2000). Because the S allele is believed to be functionally dominant, SS and SL genotypes are often grouped together and compared with the LL genotype in analyses. "
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