This study identifies a significant association between the SLC1A1 glutamate transporter gene and OCD in a haplotype overlapping with that recently reported.

This study provides preliminary supportive evidence for the effectiveness of memantine as a glutamatergic augmenting agent in severe OCD. Future randomized double-blind placebo-controlled trials are warranted.

Context: Obsessive-compulsive disorder (OCD) is a debilitating familial psychiatric illness with associated brain abnormalities in the white matter. The gene for oligodendrocyte lineage transcription factor 2 (OLIG2) is an essential regulator in the development of cells that produce white matter (myelin). The OLIG2 gene is also highly expressed in brain regions implicated in OCD.Objectives: To examine OLIG2 as a candidate gene for OCD susceptibility and to explore whether comorbidity subtypes of OCD have distinct associations with OLIG2 and the functionally related OLIG1 gene. It was hypothesized a priori that OLIG2 and OLIG1 were associated with OCD regardless of the presence of comorbid Tourette disorder (TD), but not with TD alone.Design: Family-based association candidate gene study.Setting: Participants and their family members were recruited from tertiary care OCD and TD specialty clinics.Participants: Families of 66 probands with OCD with and without TD and 31 probands with TD without OCD. Main Outcome Measures:Genotypes of single nucleotide polymorphism markers and related haplotypes. Results:The following 3 single nucleotide polymorphism markers on OLIG2 were associated with the OCD without TD phenotype: rs762178 (minor allele frequency, 35%; PϽ.001), rs1059004 (minor allele frequency, 44%; P=.005), and rs9653711 (minor allele frequency, 44%; P = .004). A 5-marker haplotype (A/C/T/ T/G) constituting these single nucleotide polymorphisms and exonic single nucleotide polymorphisms rs6517137 and rs13046814 was undertransmitted (frequency, 32%; permuted P=.004), whereas the G/A/T/T/C haplotype (frequency, 22%; permuted P=.02) was overtransmitted to probands with OCD alone, with a significant global P value (permuted P=.008).Conclusions: This is the first study reporting an association between OLIG2 and OCD, specifically when TD comorbidity is absent. The findings support a role for white matter abnormalities in the etiology of the disorder.

Tourette Syndrome (TS) has a significant genetic component, yet no TS susceptibility genes have been identified definitively. Several studies have determined that first degree relatives of TS patients have at least a 5-15 fold increased risk of developing the disorder compared to the general population, an increase that represents one of the highest familial recurrence risks among neuropsychiatric diseases that are inherited in a non-Mendelian fashion 1. Recently, Slit-and Trk-like 1 (SLITRK1) was proposed as a candidate TS susceptibility gene, and a non-coding polymorphism in the 3' untranslated region of this gene (var321) was reported to be associated with TS in a case-control sample 2. Additional studies in small samples or population isolates have failed to replicate this association 3, 4. As part of a twenty year collaborative effort, the Tourette Syndrome Association International Consortium for Genetics (TSAICG) has systematically collected a clinical sample of over 1,000 TS patients and their family members 5. We chose to screen these individuals for SLITRK1 var321 in order to determine a more accurate estimate of the prevalence of this variant in the Caucasian TS clinic population and to test for any association between var321 and TS.