Genetic variation at the catechol-O-methyltransferase (COMT) gene has been significantly associated with risk for various neuropsychiatric conditions such as schizophrenia, panic disorder, bipolar ...disorders, anorexia nervosa and others. It has also been associated with nicotine dependence, sensitivity to pain and cognitive dysfunctions especially in schizophrenia. The non-synonymous single nucleotide polymorphism (SNP) in exon 4--Val108/158Met--is the most studied SNP at COMT and is the basis for most associations. It is not, however, the only variation in the gene; several haplotypes exist across the gene. Some studies indicate that the haplotypic combinations of alleles at the Val108/158Met SNP with those in the promoter region and in the 3'-untranslated region are responsible for the associations with disorders and not the non-synonymous SNP by itself. We have now studied DNA samples from 45 populations for 63 SNPs in a region of 172 kb across the region of 22q11.2 encompassing the COMT gene. We focused on 28 SNPs spanning the COMT-coding region and immediately flanking DNA, and found that the haplotypes are from diverse evolutionary lineages that could harbor as yet undetected variants with functional consequences. Future association studies should be based on SNPs that define the common haplotypes in the population(s) being studied.
Summary
Several lines of evidence suggest that certain subtypes of obsessive‐compulsive and tic disorders might be paediatric manifestations of post‐streptococcal autoimmunity caused by ...cross‐reactive autoantibodies. As tumor necrosis factor (TNF) is known to play a seminal role in coordinating the humoral immune response, TNF gene polymorphisms have been proposed as genetic risk factors both in obsessive‐compulsive disorder (OCD) and Tourette syndrome (TS). The aim of this study was to investigate two TNF promoter polymorphisms (‐238 A/G: rs361525 and ‐308 A/G: rs1800629) on the genetic susceptibility to OCD and TS in a child psychiatric sample (102 patients with OCD and 117 patients with TS). In the case–control set‐up, the genotype and allele frequencies were compared to a control group from the general population (n = 405). As a control child psychiatric sample, 194 children with attention‐deficit hyperactivity disorder were also genotyped. Our results revealed that the TNF ‐308 G‐allele was more frequent in children with TS compared to controls (90.2% vs 84.8%, P = 0.037). For confirmation of this genetic association, a family‐based analysis, the transmission disequilibrium test was used, which showed preferential transmission of the G‐allele to patients with TS (nominal P‐value 0.011). Moreover, this allele was also transmitted more frequently to children with tic symptoms (nominal P‐value 0.039). No association was found between OCD or obsessive‐compulsive symptoms and the studied TNF polymorphisms. Based on these findings, the TNF ‐308 G‐allele can be associated with Tourette syndrome, highlighting the potential pathophysiological role of TNF dysregulation.
Part II of the European clinical guidelines for Tourette syndrome and other tic disorders (ECAP journal, 2011) provides updated information and recommendations for psychological interventions for ...individuals with tic disorders, created by a working group of the European Society for the Study of Tourette Syndrome (ESSTS). A systematic literature search was conducted to obtain original studies of psychological interventions for tic disorders, published since the initial European clinical guidelines were issued. Relevant studies were identified using computerized searches of the MEDLINE and PsycINFO databases for the years 2011–2019 and a manual search for the years 2019–2021. Based on clinical consensus, psychoeducation is recommended as an initial intervention regardless of symptom severity. According to a systematic literature search, most evidence was found for
Habit Reversal Training
(HRT), primarily the expanded package
Comprehensive Behavioral Intervention for Tics
(CBIT). Evidence was also found for
Exposure and Response Prevention
(ERP), but to a lesser degree of certainty than HRT/CBIT due to fewer studies. Currently, cognitive interventions and third-wave interventions are not recommended as stand-alone treatments for tic disorders. Several novel treatment delivery formats are currently being evaluated, of which videoconference delivery of HRT/CBIT has the most evidence to date. To summarize, when psychoeducation alone is insufficient, both HRT/CBIT and ERP are recommended as first-line interventions for tic disorders. As part of the development of the clinical guidelines, a survey is reported from ESSTS members and other tic disorder experts on preference, use and availability of psychological interventions for tic disorders.
The etiology and pathophysiology of Tourette Syndrome (TS) remain poorly understood. Multiple lines of evidence suggest that a complex genetic background and the cortico‐striato‐thalamo‐cortical ...circuit are involved. The role of Lhx6 and Lhx8 in the development of the striatal interneurons, prompted us to investigate them as novel candidate genes for TS. We performed a comparative study of the expression of Lhx6 and Lhx8 and investigated genetic association with TS using two samples of trios (TSGeneSEE and German sample ‐ 222 families). We show that Lhx6 and Lhx8 expression in the forebrain is evolutionarily conserved, underlining their possible importance in TS‐related pathophysiological pathways. Our tagging‐single nucleotide polymorphism (tSNP)‐based association analysis was negative for association with LHX8. However, we found positive association with LHX6 in the TSGeneSEE sample (corrected P‐value = 0.006 for three‐site haplotype around SNP rs3808901) but no association in the sample of German families. Interestingly, the SNP allele that was identified to be significantly associated in the TSGeneSEE dataset, showed an opposite trend of transmission in the German dataset. Our analysis of the correlation of the LHX6 region with individual ancestry within Europe, revealed the fact that this particular SNP demonstrates a high degree of population differentiation and is correlated with the North to South axis of European genetic variation. Our results indicate that further study of the LHX6 gene in relation to the TS phenotype is warranted and suggest the intriguing hypothesis that different genetic factors may contribute to the etiology of TS in different populations, even within Europe.
The
ADH1B Arg47His polymorphism has been convincingly associated with alcoholism in numerous studies of several populations in Asia and Europe. In a review of literature from the past 30 years, we ...have identified studies that report allele frequencies of this polymorphism for 131 population samples from many different parts of the world. The derived
ADH1B*47His allele reaches high frequencies only in western and eastern Asia. To pursue this pattern, we report here new frequency data for 37 populations. Most of our data are from South and Southeast Asia and confirm that there is a low frequency of this allele in the region between eastern and western Asia. The distribution suggests that the derived allele increased in frequency independently in western and eastern Asia
after humans had spread across Eurasia.
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