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Objectives. Psychotic symptoms frequently occur in veterans with combat-related posttraumatic stress disorder (PTSD). Brain-derived neurotrophic factor (BDNF) plays a major role in neurodevelopment, neuro-regeneration, neurotransmission, learning, regulation of mood and stress responses. The Met allele of the functional polymorphism, BDNF Val66Met, is associated with psychotic disorders. This study intended to assess whether the Met allele is overrepresented in unrelated Caucasian male veterans with psychotic PTSD compared to veteran controls. Methods. The BDNF Val66Met variants were genotyped in 576 veterans: 206 veterans without PTSD and 370 veterans with PTSD subdivided into groups with or without psychotic features. Results. Veterans with psychotic PTSD were more frequently carriers of one or two Met alleles of the BDNF Val66Met polymorphism than veterans with PTSD without psychotic features and veterans without PTSD. Conclusions. The study shows that veterans with psychotic PTSD carried more Met alleles of the BDNF Val66Met than non-psychotic veterans with PTSD or veterans without PTSD. The results might add further support to the hypothesis that psychotic PTSD is a more severe subtype of PTSD.

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Alcohol dependence is frequently associated with aggressive and suicidal behaviour. Genetic factors contribute to both behaviours. Candidate genes, related to suicide and aggression, include genes involved in serotonin, norepinephrine and dopamine pathways. The enzyme catechol-O-methyl transferase (COMT) degrades dopamine, epinephrine and norepinephrine. The functional polymorphism (COMT Val108/158Met) affects COMT activity, with the valine (Val) variant associated with higher and the methionine (Met) variant with lower COMT activity. This polymorphism is associated with aggressive and suicidal behaviour, but the literature data on this relationship is contradictory and inconsistent. The hypothesis of this study was that Met allele carriers with alcohol dependence will have a higher frequency of suicide attempts compared to other genotypes. Participants were 312 male and 81 female medication-free patients with alcohol dependence and 487 male and 122 female unrelated, non-suicidal medication-free Caucasian healthy subjects. Our results showed significant (χ2 test with standardized residuals) differences in the frequencies of COMT variants in all alcoholics, alcoholics with different comorbid diagnoses, and in male but not in female alcoholics, with or without suicide attempts. Male alcoholic suicide attempters, compared to male non-attempters, had the higher frequency of Met/Met genotype or Met allele, and significantly (Kruskal-Wallis ANOVA on ranks and Mann-Whitney test) higher aggression and depression scores. These results confirmed the associations between Met allele and aggressive behaviour or violent suicide attempts in various psychiatric diagnoses, and suggested that Met allele of the COMT Val108/158 Met might be used as an independent biomarker of suicidal behaviour across different psychopathologies.

Over a half of all proteins are glycosylated, and their proper glycosylation is essential for normal function. Unfortunately, because of structural complexity of nonlinear branched glycans and the absence of genetic template for their synthesis, the knowledge about glycans is lagging significantly behind the knowledge about proteins or DNA. Using a recently developed quantitative high throughput glycan analysis method we quantified components of the plasma N-glycome in 99 children with attention-deficit hyperactivity disorder (ADHD), 81 child and 5 adults with autism spectrum disorder, and a total of 340 matching healthy controls. No changes in plasma glycome were found to associate with autism spectrum disorder, but several highly significant associations were observed with ADHD. Further structural analysis of plasma glycans revealed that ADHD is associated with increased antennary fucosylation of biantennary glycans and decreased levels of some complex glycans with three or four antennas. The design of this study prevented any functional conclusions about the observed associations, but specific differences in glycosylation appears to be strongly associated with ADHD and warrants further studies in this direction. Molecular & Cellular Proteomics 10: 10.1074/mcp.M110.004200, 1-7, 2011. Attention-deficit hyperactivity disorder (ADHD)1 and autism spectrum disorders (ASDs) are both highly heritable multifactorial and clinically heterogeneous childhood-onset neurodevelopmental disorders (1, 2). The hallmarks of ADHD are severe inattention, hyperactivity, and impulsivity whereas the characteristic symptoms of ASD include impaired communication and social interaction skills as well as repetitive and restricted behavior and interests (3). Several pieces of evidence point toward some shared heritability and thus genetic factors contributing to the occurrence of both ADHD an ASD (4). Children with ADHD and ASD frequently share symptoms of impaired communication skills, impaired social interactions (4), and develop difficulties in familial, educational, and academic functioning (5, 6). The abnormal functioning of the dopaminergic and serotonergic systems (5, 7-9), among other neurotransmitters, were repeatedly found in ADHD and ASD, and therefore the candidate genes common for both disorders are the dopaminergic transporter gene, dopaminergic receptor type 3 and type 4 genes, serotonin transporter gene, and genes for catechol-o-methyl-transferase and monoamine oxidase type A (4), although genome-wide association studies did not confirm with certainty all these candidates (10). A shared genetic basis is further suggested by the higher frequency of ADHD and ASD traits in children with a defined genetic diagnosis such as 22q11 deletion syndrome, XXYY syndrome, and microdeletions or duplications in the chromosome 15q13.2-q13.3 region (11,12). However, the molecular agents related to various biological processes and interactions between different risk factors responsible for development of ADHD and ASD remain elusive (6).Prote...

The lack of association between catechol-O-methyl-transferase Val108/158Met polymorphism and smoking in schizophrenia and alcohol dependence To the Editors Patients with schizophrenia and alcohol dependence are often smokers. There are inconsistencies across the literature on the relationship between the functional catechol-O-methyl-transferase (COMT) Val108/158Met polymorphism and smoking and/or nicotine dependence (Redden et al., 2005; Tammimaki and Mannisto, 2010). The study elucidated the association between the COMT Val108/158Met polymorphism and smoking in 828 ethnically homogeneous non-related Caucasian patients with schizophrenia (40.3 712.6 years old), 616 patients with alcohol dependence (49.7710.2 years old), diagnosed with the Structured Clinical Interview for DSM-IV, and in 1058 healthy control subjects (40.5 715.3 years old). The COMT Val108/158Met polymorphism was genotyped using a Taqman-based allele-specific polymerase chain reaction assay (Applied Biosystems, Foster City, CA, USA). COMT genotypes in the studied groups were in Hardy-Weinberg equilibrium. The present smoking status differed significantly (w 2 ¼327.71; Po0.001) between the studied groups, since male patients with schizophrenia smoked more frequently, while healthy control women smoked less frequently than other subjects. The stepwise logistic regression (odds ratio (OR)¼1.56,