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Amaç: Psikotik bozukluklar ile Katekol-O-metiltransferaz (COMT) val158met (rs4680) ve beyin kökenli nörotrofik faktör (Brain-derived neurotrophic factor; BDNF) val66met (rs6265) polimorfizmleri arasında ilişki olabileceği düşünülmektedir. Bu araştırmada genel toplumdan seçilmiş bir örneklemde eşik altı psikotik yaşantılardan şizofreniye geniş psikoz fenotipi boyunca bu polimorfizmlerin dağılımının incelenmesi amaçlanmıştır. Yöntem: Örneklem, uzunlamasına bir izlem araştırması olan Psikozlarda Gen-Çevre Etkileşimi İçin İzmir Akıl Sağlığı Araştırması’na (TürkSch) dayanmaktadır ve psikotik yaşantı ve bozuklukların tarandığı bir genel toplum örneklemi içinden seçilen 437 kişiden oluşmaktadır. Geniş psikoz fenotipi, tarama ve klinik tanı görüşmelerine göre psikotik yaşantısı olmayanlar (n: 194), eşik altı psikotik yaşantısı olanlar (n: 87), psikotik yaşantısı olanlar (n: 104) ve şizofreni-benzeri bozukluk (n: 52) grupları olarak oluşturulmuştur. BDNF rs6265 genotiplendirmesi araştırmaya katılan tüm kişilerde ve COMT rs4680 genotiplendirmesi ise 366 kişide yapılmıştır. Bulgular: Geniş psikoz fenotipi grupları arasında BDNF rs6265 ve COMT rs4680 polimorfizmleri açısından anlamlı farklılık bulunmamıştır. Sadece herhangi bir psikotik yaşantı bildirmeyenlere göre eşik altı psikotik yaşantı bildirenlerde BDNF rs6265 genotipinde met taşıyanların bulunma olasılığı anlamlılığa yakın düzeyde daha düşük bulunmuştur (p=0,08). Sonuç: Geniş psikoz fenotipinin farklı basamakları ile BDNF rs6265 ve COMT rs4680 arasında bir ilişki bulunmaması altta yatan gen-gen etkileşimi, gen-çevre ve gen-gen-çevre etkileşimi gibi daha karmaşık mekanizmaların varlığıyla ilişkili olabilir., Objective: Psychotic disorders were previously associated with catechol- O-methyltransferase (COMT) val158met (rs4680) and brain-derived neurotrophic factor (BDNF) val66met (rs6265) polymorphisms. This article evaluates the association between COMT/BDNF polymorphisms and the extended psychosis phenotype which covers not only schizophrenia but also subclinical expressions of psychotic experiences. Method: The participants of this study were part of the TürkSch (Izmir Mental Health Survey for Gene-Environment Interaction in Psychoses), a longitudinal study Psychotic experiences and disorders were screened 437. The extended psychosis phenotype was grouped into four: (1) no psychotic experiences (n: 194), (2) subclinical psychotic experiences (n: 87), (3) clinically relevant psychotic experiences (n: 104), and (4) schizophrenia-like disorders (n: 52). BDNF rs6265 was genotyped occurred in every participant whereas COMT rs4680 genotyping could be done on 366 individuals. Results: There was no association between the extended psychosis phenotype and BDNF rs6265/COMT rs4680 polymorphisms. The frequency of met carriers in the BDNF rs6265genotype was slightly higher in individuals with subclinical psychotic experiences than in the group with no psychotic experiences, which was just below the significance level (p=0.08). Conclusion: The lack of an association between different expression levels of the extended psychosis phenotype and the BDNF rs6265/ COMT rs4680 polymorphism might be related to sample characteristics, underlying gene-gene, gene-environment and gene-environment-gene interactions.

The pharmacogene, CYP2D6, is commonly used to infer metabolizer phenotype of many marketed drugs and endogenous toxins in ante- and post-mortem patients but only represents the efficiency of phase 1 metabolism. Downstream metabolic enzymes encoded by UGT2B7, ABCB1, OPRM1, and COMT also have been implicated in variable individual response to drugs due to their activity at different stages of the tramadol ADME (absorption, distribution, metabolism, and excretion) process. While commonly studied as single genes using targeted genotyping approaches, a more comprehensive tramadol metabolism profile has not been evaluated. 1000 Genomes Project data for UGT2B7, ABCB1, OPRM1, and COMT were used to characterize full-gene haplotypes and their effect on protein function using in-house excel-based workbooks, PopART, and TreeView. Population genetic summary statistics and intergenic analyses associated these haplotypes with full-gene CYP2D6-inferred metabolizer phenotype. The findings suggest that UGT2B7, ABCB1, OPRM1, and COMT may contribute to predicted metabolizer phenotype as opposed to relying solely on CYP2D6.

Background22q11 deletion syndrome (22q11DS) is associated with mild or borderline intellectual disability (ID). There are hardly any reports on subjects with 22q11DS with moderate or severe ID, and therefore its behavioural and psychiatric characteristics are unknown. MethodWe describe behavioural and psychiatric characteristics of 33 adults with 22q11DS and a Full-Scale IQ (FSIQ) below 55. Participants were divided into two groups: one group having a FSIQ55 caused by intellectual decline (n=21) and one group with a FSIQ55 who had always functioned at this level (n=12). ResultsHigh scores on psychopathology sub-scales were found for both subgroups. 22q11DS patients with intellectual decline showed higher rates of co-morbid psychopathology, particularly psychosis. Furthermore, psychosis and intellectual decline were positive correlated. ConclusionThis is the first report addressing adult patients with 22q11DS and moderate to severe ID. Overall we found high levels of psychopathology with higher scores of psychopathology in the intellectual decline group. Life time psychosis seems to be related to deterioration.

Objectives Although the Val(158)Met catechol-O-methyltransferase (COMT) gene has been linked with the temperament dimension Novelty Seeking (NS), new insights in this polymorphism might point to a major role for character features as well. Given that individual life experiences may influence Val(158) and Met(158) allele carriers differently it has been suggested that the character trait cooperativeness could be implicated. Case report A homogeneous group of eighty right-handed Caucasian healthy female university students were assessed with the TCI and genotyped for the COMT Val(158)Met polymorphism (rs4680). Gene determination showed that eighteen were Val(158) homozygotes, forty-four Val/Met(158) heterozygotes, and eighteen were Met(158) homozygotes. All were within the same age range and never documented to have suffered from any neuropsychiatric illness. Bonferroni corrected non-parametric analyses showed that only for the character scale cooperativeness Val(158) homozygotes displayed significant higher scores when compared to Met(158) homozygotes. No significant differences on cooperativeness scores were found between Val(158) and Val/Met(158) carriers or between Met(158) and Val/Met(158) carriers. No differences were observed for the COMT Val(158)Met polymorphism and the other temperament and character scales. Conclusions Our findings support the assumption that the Val(158)Met single nucleotide polymorphism (SNP) influences character traits and not only temperament. Our results add to the notion that Val(158) homozygotes are considered to be helpful and empathic and it suggest that these cooperativeness character traits are related to the dopaminergic system.

This study could not confirm the association between the Catechol-O-Methyltransferase Val158Met polymorphism (COMT) and electroencephalographic (EEG) alpha peak frequency (APF) in two independent cohorts of 187 (96 depressed and 91 healthy participants) and 413 healthy participants. If COMT and APF play a role in depression or antidepressant treatment response, they do not have a shared pathway. We emphasize the importance of publishing null-findings for obtaining more accurate overall estimates of genetic effects. (C) 2014 Elsevier Ireland Ltd. All rights reserved.

The catecholamines dopamine and noradrenaline have been implicated in spontaneous low-frequency fluctuations in reaction time, which are associated with attention deficit hyperactivity disorder (ADHD) and subclinical attentional problems. The molecular genetic substrates of these behavioral phenotypes, which reflect frequency ranges of intrinsic neuronal oscillations (Slow-4: 0.027-0.073 Hz; Slow-5: 0.010-0.027 Hz), have not yet been investigated. In this study, we performed regression analyses with an additive model to examine associations between low-frequency fluctuations in reaction time during a sustained attention task and genetic markers across 23 autosomal catecholamine genes in a large young adult population cohort (n = 964), which yielded greater than 80% power to detect a small effect size (f2 = 0.02) and 100% power to detect a small/medium effect size (f2 = 0.15). At significance levels corrected for multiple comparisons, none of the gene variants were associated with the magnitude of low-frequency fluctuations. Given the study's strong statistical power and dense coverage of the catecholamine genes, this either indicates that associations between low-frequency fluctuation measures and catecholamine gene variants are absent or that they are of very small effect size. Nominally significant associations were observed between variations in the alpha-2A adrenergic receptor gene (ADRA2A) and the Slow-5 band. This is in line with previous reports of an association between ADRA2A gene variants and general reaction time variability during response selection tasks, but the specific association of these gene variants and low-frequency fluctuations requires further confirmation. Pharmacological challenge studies could in the future provide convergent evidence for the noradrenergic modulation of both general and time sensitive measures of intra-individual variability in reaction time.

Background22q11 deletion syndrome (22q11DS) is associated with mild or borderline intellectual disability (ID). There are hardly any reports on subjects with 22q11DS with moderate or severe ID, and therefore its behavioural and psychiatric characteristics are unknown. MethodWe describe behavioural and psychiatric characteristics of 33 adults with 22q11DS and a Full-Scale IQ (FSIQ) below 55. Participants were divided into two groups: one group having a FSIQ55 caused by intellectual decline (n=21) and one group with a FSIQ55 who had always functioned at this level (n=12). ResultsHigh scores on psychopathology sub-scales were found for both subgroups. 22q11DS patients with intellectual decline showed higher rates of co-morbid psychopathology, particularly psychosis. Furthermore, psychosis and intellectual decline were positive correlated. ConclusionThis is the first report addressing adult patients with 22q11DS and moderate to severe ID. Overall we found high levels of psychopathology with higher scores of psychopathology in the intellectual decline group. Life time psychosis seems to be related to deterioration.

Obsessive-Compulsive Disorder (OCD) is characterized by the presence of obsessions and compulsions, and shows considerable phenotypic variability. Family and twin studies have indicated a genetic component in the etiology of OCD, and the catechol-O-methyl transferase (COMT) gene is an important candidate gene for OCD. This study investigates the influence of the functional COMT Val158Met polymorphism on the phenotypic expression of OCD, using an item-level factor-analytic approach in a large sample. The COMT Val158Met variant was genotyped in 373 patients and 462 controls. It was tested whether there was an association between the COMT Val158Met polymorphism and OCD or dimensional phenotypes such as YBOCS severity score, age of onset of obsessive-compulsive symptoms and six symptom dimensions recently found in a large item-level factor-analytic study [Katerberg et al., submitted]. We further investigated possible sex-specific associations between the COMT Val158Met polymorphism and OCD or dimensional phenotypes. There was a trend for an association of the COMT 158Met allele with OCD in males, and an interaction between the COMT Val158Met genotype and sex on the somatic and sensory phenomena symptom dimension, with females showing lower scores. In conclusion, a dimensional approach seems fruitful in detecting genes of importance for OCD. (C) 2009 Wiley-Liss, Inc.