Association of the serotonin transporter polymorphism and obsessive‐compulsive disorder: Systematic review

Abstract

We investigated the association between the long (l) and short (s) alleles of the serotonin transporter polymorphism (5-HTTLPR) in the promoter region of the SLC6A4 gene and obsessive-compulsive disorder (OCD) using meta-analysis to combine all published data from case-control and family based association studies (2,283 cases). In stratified meta-analysis we investigated whether age of sample (child and adult), ethnicity (Caucasian and Asian) and study design (case-control and family-based association studies) moderated any association. In the overall meta-analysis we found no evidence of association between genetic variation at the 5-HTTLPR locus and OCD. We did find significant heterogeneity between studies. In the stratified meta-analyses, we demonstrated a significant association between the l-allele and OCD in family-based association studies and in studies involving children and Caucasians. Our meta-analysis suggests the possibility that the l-allele may be associated with OCD in specific OCD subgroups such as childhood-onset OCD and in Caucasians. Further meta-analyses based on individual patient data would be helpful in determining whether age of OCD onset, gender and the presence of comorbid illness (e.g., tics) moderates the relationship between 5-HTTLPR and OCD.

Sex determines which section of the SLC6A4 gene is linked to obsessive–compulsive symptoms in normal Chinese college students

“…The 10R allele of STin2 has been associated with lower transcriptional activity than the 12R allele (Fiskerstrand et al, 1999). Earlier studies Hu et al, 2006;Kim et al, 2005;McDougle et al, 1998) and a recent review (Bloch et al, 2008b) reported that the l allele of 5-HTTLPR was a risk factor for OCD while some other studies reported that the s allele was a risk factor (Lin, 2007;Perez et al, 2006). As mentioned early, interactions of SLCA64 by gender on OCD (Dickel et al, 2007;Voyiaziakis et al, 2011) and OCPD (Blom et al, 2011), were also reported.…”

“…The estimated heritability for OCD ranges from 0.45 to 0.65 for children and adolescents and from 0.27 to 0.47 for adults in twin and family studies (van Grootheest et al, 2005), indicating that early-onset OCD may have a different etiology (including genetic factors) from late-onset OCD. Molecular genetic association studies have specifically provided further evidence for the genetic contributions of SLC6A4 to OCD (Bloch et al, 2008b;Hu et al, 2006;Lin, 2007;Voyiaziakis et al, 2011). SLC6A4 transports serotonin from the synaptic cleft to presynaptic neurons, thereby attenuating current serotonin neurotransmission while also maintaining the pool of available serotonin for subsequent release (Lesch and Gutknecht, 2005).…”

“…Only one recent association study examined 5-HTTLPR and obsessiveecompulsive personality disorder (OCPD) trait in a community sample of European ancestry, with the finding that the s allele was linked to lower obsessiveecompulsive personality trait scores in males and to higher obsessiveecompulsive trait scores in females (Blom et al, 2011). The second limitation of previous research is that most studies were done with European ancestry populations (Bloch et al, 2008b;Blom et al, 2011;Lin, 2007;Voyiaziakis et al, 2011). Considering that allele frequencies of SLC6A4 polymorphisms have substantial differences between Asian and European ancestry individuals (Gelernter et al, 1997;Zhong et al, 2009), these allele frequency diversities may reflect different behavioral adaptive functions in different cultures and living environments (Chiao and Blizinsky, 2010) or differential physiological functions of the SLC6A4 gene in different populations (Smits et al, 2004).…”

Psychiatric genetics in South Africa: cutting a rough diamond

“…The SLC6A4 gene is involved in serotonin reuptake at the synapses and variation of this gene has been linked to various psychiatric disorders, including OCD. 60 A functional promoter polymorphism, 5-HTTLPR, has been extensively studied. The resulting alleles differ in transcriptional activity, with the short (S-) allele linked to lower expression of the gene than the long (L-) allele.…”

“…This may explain the inconsistent results obtained from case-control association studies of this polymorphism. 60 With regards to the serotonin receptor genes: (i) the genotype distribution of the 5-HT1Db G861C polymorphism differed significantly between Afrikaner OCD patients and healthy controls, with more C-homozygotes observed in this patient subgroup 51 , and, (ii) interestingly, although variants in the 5-HT2A gene were not found to be associated with OCD in the abovementioned studies, the T-allele of the T102C variant was found to be associated with trichotillomania in South African patients. 56 Trichotillomania is a psychiatric disorder that is characterised by repetitive pulling of hair, which may have a biological overlap with OCD.…”