Polymorphism Rs4680 Research Articles

Prediction of the cognitive impairment development in patients with autoimmune thyroiditis and hypothyroidism.

Objective. The aim of the present work is to define the risk factors that can affect the presence of a cognitive impairment and analyze the associations of the brain-derived neurotrophic factor (BDNF) gene polymorphism (rs6265), vitamin D receptor (VDR) gene polymorphism (rs2228570), and N-methyl-D-aspartate (NMDA) receptor gene polymorphism (rs4880213) with the cognitive impairment in patients with autoimmune thyroiditis and hypothyroidism in the Western Ukraine population and predict the development of cognitive disorders in these patients. Methods. The study involved 153 patients with various forms of thyroid pathology (hypothyroidism, autoimmune thyroiditis, elevated serum antibodies anti-thyroglobulin and anti-thyroid peroxidase). Cognitive impairment in the examined patients was evaluated based on the results of the Mini-Mental State Examination (MMSE) test. BDNF, GRIN2B, and 25-OH Vitamin D levels in the serum of the patients and healthy individuals were quantified using highly sensitive commercial enzyme-linked immunosorbent assay kits. Genotyping of the VDR (rs2228570), BDNF (rs6265), and NMDA receptor (rs4880213) gene polymorphism was performed using TaqMan probes and Taq-Man Genotyping Master Mix (4371355) on CFX96™Real-Time PCR Detection System. Polymerase chain reaction (PCR) for TaqMan genotyping was carried out according to the kit instructions. Results. Strong direct relationship between the "Level GRIN2B" and cognitive impairments (p=0.006) was established after evaluating the complex model based on the values of the regression coefficient. An increase in the likelihood of cognitive impairment by 24.898-fold (p=0.012) was seen after assessing the effect of the CT rs6265 genotype. In addition, direct relationship between the influence of the TT rs6265 genotype and an increase in the likelihood of cognitive impairment by a factor of 21.734 (p=0.024) was also established. Conclusion. The present data indicate that the BDNF, TSH, fT4, and vitamin D levels prognostically belong to the significant indicators of the cognitive impairment development.

Ассоциация самооценок по эмпатии, помощи, агрессии и личностным установкам с пальцевым индексом и полиморфизмом rs53576 гена OXTR у школьников европеоидного происхождения

Introduction. The evolution of mutual help and cooperation in humans has been actively analyzed using the methods of ethology, psychology, anthropometry and genetics. The goal of this study was to identify associations between the finger index (2D:4D), the rs53576 polymorphism of the OXTR gene, gender and age with a willingness to help others and adherence to certain cultural standards in Russian schoolchildren of Caucasian origin. Materials and methods. The samples for this study were collected in the schools of the city Ussuriysk (Primorsky Krai) and the city Yelizovo (Kamchatka Krai) in 2015-2019. The total sample size was 853 (416 boys and 437 girls), represented exclusively by children of European origin. The average age of the participants was 14.2 ± 1.6 years (ranged from 10 to 18 years). Data collection methods included: questionnaires, anthropometric measurements, and collection of DNA samples (buccal epithelium or saliva). The data were analyzed using the SPSS-27 software package. Results. Significant differences were obtained for the finger index, 2D:4D, three scales of the Bass-Perry aggression questionnaire (anger, hostility, physical aggression), the generalized Baron-Cohen empathy coefficient and Boyko's level of empathy, dominance and social success, self-esteem, attitudes towards helping others. Readiness to help relatives was significantly associated with the GG variant of OXTR_rs53576 gene polymorphism. Adherence to moral norms (the weak need to be protected) was significantly associated with the finger index. Discussion. The results of our study indicate the significant gender differences in masculinity, including the 2D:4D ratio on the right and left hands, self-assessments of dominance and social status, one's own role in the group, attitudes towards aggression and related (group) solidarity. Boys performed more expressed self-assessments on physical aggression, and showed more parochialism, declaring a willingness to take the side of friends (relatives), regardless of who was right in the conflict and a willingness to follow cultural standards, concerning protection of the weakest. Girls outperformed boys in emotionality, and gave higher scores on anger and hostility. Our data, in combination with the findings of other authors, demonstrate the association of the homozygous variant GG OXTR_rs53576 with prosociality, altruism, and help.

The combined effect between BDNF genetic polymorphisms and exposure to metals on the risk of Chinese dyslexia

BDNF gene has been implicated in the development of cognition and language. Meanwhile, exposure to metals might interact with BDNF gene to increase the risk of neurodevelopmental disorders. The present study aimed to explore the association between BDNF genetic polymorphisms and dyslexic risk and examine whether BDNF polymorphisms would interact with metal exposures, jointly contributing to dyslexia. Among a case-control study composed of 238 children with dyslexia and 228 healthy controls, the BDNF genetic polymorphisms were genotyped by the Sequenom MassARRAY system, and the exposure to eight metals, such as lead (Pb), mercury (Hg) and copper (Cu), were measured using an inductively coupled plasma-mass spectrometer (ICP-MS). Multivariable logistic regression models were used to assess the adjusted odds ratios (ORs) and 95% confidence interval (CI) of dyslexia. After multivariate adjustment, significant associations of dyslexic risk with rs6265 polymorphisms of the BDNF gene were observed (OR = 1.99; 95% CI: 1.15–3.44). Furthermore, exposure to Cu could interact with rs6265 to increase the risk of dyslexia (P interaction = 0.045). High-Cu children with the rs6265 TT genotype were more likely to have dyslexia compared with low-Cu children carrying CC + CT genotypes (OR = 3.19; 95% CI: 1.38–7.39). The findings of this study suggested that the polymorphism of rs6265 in BDNF gene could interact with Cu exposure to increase the occurrence of dyslexia.

BDNF rs6265 Genotype Influences Outcomes of Pharmacotherapy and Subthalamic Nucleus Deep Brain Stimulation in Early-Stage Parkinson's Disease

IntroductionThe efficacy of pharmacotherapy and deep brain stimulation of the subthalamic nucleus in treating Parkinson's disease motor symptoms is highly variable and may be influenced by patient genotype. The relatively common (prevalence about one in three) and protein-altering rs6265 single nucleotide polymorphism (C > T) in the gene BDNF has been associated with different clinical outcomes with levodopa. ObjectiveWe sought to replicate this reported association in early-stage Parkinson's disease subjects and to examine whether a difference in clinical outcomes was present with subthalamic nucleus deep brain stimulation. Materials and MethodsFifteen deep brain stimulation and 13 medical therapy subjects were followed for 24 months as part of the Vanderbilt DBS in Early Stage PD clinical trial (NCT00282152, FDA IDE #G050016). Primary outcome measures were the Unified Parkinson's Disease Rating Scale (UPDRS) and Parkinson's Disease Questionnaire-39. ResultsOutcomes with drug therapy in subjects carrying the rs6265 T allele were significantly worse following 12 months of treatment compared to C/C subjects (UPDRS: +20 points, p = 0.019; PDQ-39: +16 points, p = 0.018). In contrast, rs6265 genotype had no effect on overall motor response to subthalamic nucleus deep brain stimulation at any time point; further, rs6265 C/C subjects treated with stimulation were associated with worse UPDRS part II scores at 24 months compared to medical therapy. ConclusionsGenotyping for the rs6265 polymorphism may be useful for predicting long-term response to drug therapy and counseling Parkinson's disease patients regarding whether to consider earlier subthalamic nucleus deep brain stimulation. Validation in a larger cohort of early-stage Parkinson's disease subjects is warranted.

Significant Association of the Catechol-O-Methyltransferase Gene Polymorphism (rs4680) and Opioid Use Disorder in Asian Populations, but not Caucasian Populations: A Meta-analysis.

Objective: Previous studies have reported on the association between the rs4680 polymorphism in the Catechol-O-methyltransferase (COMT) gene and opioid use disorder (OUD) with inconsistent outcomes. The goal of this study was to examine the correlation of the rs4680 polymorphism and OUD using a meta-analysis approach. Methods: Six electronic databases, including PubMed, Web of Science, Cochrane Library, EMBASE, Wanfang and CNKI, were searched thoroughly for relevant studies on the association of the rs4680 polymorphism and OUD up to September, 2021. Summary odds ratios (ORs) with 95% confidence intervals (CIs) were utilized to test the association. Statistical analyses was performed using RevMan 5.3 software. Results: Eleven studies with 13 independent cohorts encompassing 2538 cases and 2519 controls were included in this study. In the overall analysis, the rs4680 polymorphism was not associated with OUD susceptibility. Subgroup analyses suggested that rs4680 was significantly correlated with OUD in Asian populations: VV vs. MM, OR = 1.46, 95% CI 1.05-2.02, p = 0.02; VM vs. MM, OR = 1.44, 95% CI 1.04-2.00, p = 0.03; VV+VM vs. MM, OR = 1.45, 95% CI 1.07-1.99, p = 0.02. However, the pooled data did not suggest any significant association in the Caucasian population. Conclusion: This meta-analysis supports a significant association between the rs4680 polymorphism and predisposition to OUD in Asians, carriers of VV and VM genotypes appear to have an increased susceptibility to OUD. However, the association does not exist in Caucasians.

The impact of the oxytocin receptor gene (OXTR) on facial affect recognition in psychosis

IntroductionOxytocin is considered as potential treatment targeting social dysfunctions in psychoses. However, results of clinical trials are inconsistent which may be due to genetic variation in the oxytocin system involved in social information processing.ObjectivesTo examine the effect of the OXTR polymorphism and its interaction with childhood adversity (CA) on facial affect recognition (FAR) in psychotic patients.MethodsPatients with schizophrenic and affective psychotic disorders (n=934) completed a task that required labeling six basic and three social emotions. The polymorphisms rs53576 and rs7632287 within the OXTR locus were genotyped and dichotomized based on prior research. For 65% of the sample, information on CA defined as parental alcoholism or psychiatric illness was collected. The polymorphisms’ role in FAR was assessed using ANCOVAs adjusted for sex, age, and diagnosis.ResultsAfter Bonferroni correction, there was a significant effect of rs53576, mainly driven by the difference between genotypes in the affective patients. GG-homozygotes recognized emotions better than A-allele carriers. A nominally significant effect in the expected direction was also found for rs7632287. CA influenced FAR but did not interact with any genotype.ConclusionsThe results provide further evidence that OXTR impacts social cognition and behavior in diverse cohorts, including psychotic patients, with rs53576 GG-homozygotes having enhanced social competencies. However, we have failed to confirm that OXTR modulates the relations between CA and FAR in psychosis. The difference in FAR between genotypes was more pronounced in affective patients, which might be due to more severe FAR deficits in schizophrenia.DisclosureNo significant relationships.

Childhood violence experience interacts with BDNF Val158Met polymorphism and modify internet addiction risk

IntroductionInternet-addiction (IA) is one of the most common non-chemical (or behavioral) addictions with genetic impact and substantial effects of psychological and personality characteristics, taking into account the childhood traumatic experience. Gene-environment interactions (GxE) may substantially impact on the risk of Internet-addiction (IA).ObjectivesAim: to test the associations between the functional polymorphism rs6265 (Val66Met) in brain-derived neurotrophic factor (BDNF) gene, affecting BDNF function, and childhood traumatic experience and their GxE interactions with IA risk.MethodsIn total 456 participants were screened with Chinese Internet Addiction Scale (CIAS) to cut a cohort on two groups: IA (CIAS total score ≥ 65, n=100) and controls (CIAS total score less 64, n=356). The Adverse Childhood Experiences International Questionnaire (ACE-IQ) was used to assess childhood traumatic experience using its main domains: parents (P), family (F), abuse (A) and violence (V). BDNF Val158Met polymorphism was detected by RT-PCR.ResultsLogistic regression revealed associations of P scores with increased IA risk only after adjustment for sex and age (p=0.01, OR=1.166, 95%CI[1.038-1.309]) and V scores with decreased IA risk (p=0.000, OR=0.799, 95%CI [0,233;0,744] only before adjustment. No associations of F and A with IA risk were found. BDNF Val158Met per se was not associated with IA risk, but significant effect of interaction V score*BDNF rs6265 CC on IA risk in “protective” manner was revealed (р=0.039, OR=0.873, 95%CI[0.768-0.993]) in a model adjusted for sex and age.ConclusionsChildhood violence experience interacts with BDNF Val158Met polymorphism and CC (ValVal) genotype may be possibly protective factor decreasing the internet addiction riskDisclosureThis work was carried out with the financial support of the Russian Foundation for Basic Research: RFBR grant # 18-29-22079

Association of Catechol-O-Methyltransferase Gene rs4680 Polymorphism and Levodopa Induced Dyskinesia in Parkinson's Disease: A Meta-Analysis and Systematic Review.

Long-term levodopa therapy for Parkinson's disease (PD) can cause levodopa induced dyskinesia (LID). Genetic predisposition has a significant role to play in inter-individual heterogeneity in the clinical manifestation of LID. Despite accumulating evidence for the role of COMT gene polymorphism (rs4680) as a genetic basis for LID, to date results have been inconsistent. Early assessment of the Catechol-O-Methyltransferase (COMT) genotype might be helpful to stratify PD patients concerning their individual risk for LID. In this meta-analysis, we have used 9 studies, which were selected through online databases. Statistical analysis was performed using R (v-3.6) software. 5 genetic models have been used in the present study: Allele model (A vs. G), Dominant model (AA+AG vs. GG), Homozygote model (AA vs. GG), Co-dominant/heterozygote model (AG vs. GG), and Recessive model (AA vs. AG + GG). The results indicated a significant association between COMT rs4680 (Val158Met) polymorphism and LID risk. The genotype AA of COMT rs4680 is a risk factor for LID in PD patients under the recessive model (AA vs GG+AG) in the random-effect model. Analysis based on ethnicity showed that COMT rs4680 SNP allele A is a risk factor for LID development in Asian PD patients, while GG genotype is a risk factor for LID development in non-Asian PD patients using different genetic models. The results of the present meta-analysis support that the COMT Val158Met polymorphism is a risk factor for the development of LID in PD patients having ethnic variations.

Association of serum BDNF level and Val66Met polymorphism with response to treatment in patients of major depressive disease: A step towards personalized therapy

BackgroundMajor depressive disorder (MDD) is one of the most common psychiatric disorders and only less than 50% of MDD patients achieve remission after the first antidepressant trial. Hence, it is important to understand the factors associated with response to various antidepressant medications. Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophin family. BDNF and Val66Met polymorphism in the BDNF gene has a role in MDD. This study aimed to determine the association of rs6265 polymorphism and serum BDNF level with response to treatment in MDD patients. MethodsThe study included 200 subjects, consisting of 100 MDD patients treated with oral antidepressants and 50 treated with ECT, and 50 healthy controls. Serum BDNF levels were estimated using ELISA and rs6265 polymorphism was genotyped using tetra-primer ARMS PCR. ResultsVal66Met polymorphism had an association with MDD, and in MDD patients with Met allele was associated with a better response to antidepressants. Serum BDNF level was significantly higher in MDD patients compared to healthy individuals. In MDD patients, lower serum BDNF level was associated with better ECT outcomes. ConclusionsVal66Met polymorphism in BDNF gene and serum BDNF level has the potential to be used as a biomarker for the prediction of response to oral antidepressants and ECT in MDD patients. The presence of the Met allele might be used to predict the chances of occurrence of MDD in the future. The results of our study might form a basis for the development of personalized treatment for MDD in the future.

Association of Catechol-O-Methyltransferase Gene Polymorphisms and Haplotypes in the Levodopa-Induced Adverse Events in Subjects with Parkinson's Disease.

The presence of dyskinesia is the most common side effect of chronic administration of levodopa in Parkinson's disease (PD) subjects. Genetic polymorphisms in levodopa metabolizing gene, catechol-O-methyl transferase (COMT), is shown to influence the inter-individual variability in drug response and adverse events. In the present study, the association of COMT rs6269, rs4633, rs4818, and rs4680 polymorphisms and haplotypes on pharmacokinetics and adverse events with levodopa was investigated in 150 PD patients. The age of onset of PD was 58.00 ± 10 yrs. The most common side effect faced by 78% of the subjects was dyskinesia. The AUC of levodopa was found to be significantly higher in subjects with dyskinesia (1695 ± 113ng/ml/hr, p < 0.0001) than those without dyskinesia (1550 ± 122ng/ml/hr). We found that the frequency of subjects presenting dyskinesia was significantly higher in subjects carrying variant genotype of COMT rs6269, rs4633, and rs4680 than that with wild genotype and these subjects presented higher AUC of levodopa. In addition, in subjects with dyskinesia, the AUC of levodopa was found to be significantly higher with low COMT (ACCG) haplotype. The association of COMT rs6269, COMT rs4633, COMT rs4818, and COMT rs4680 variant genotypes with the risk of dyskinesia due to levodopa therapy showed an ROC AUC of 0.67 indicating the moderate prediction of dyskinesia (p = 0.0021) with these COMT variants. In conclusion, PD subjects carrying the variant genotypes of COMT strongly influence high levodopa-induced dyskinesia. Hence the genotyping of COMT before the levodopa therapy will be useful to reduce the adverse events associated with the chronic levodopa treatment.

HTR1A Gene Polymorphism in Type 2 Diabetes Mellitus Comorbid with Major Depressive Disorder in a Chinese Population.

BackgroundMajor depressive disorder is a frequent mental illness, which is common in patients with type 2 diabetes. Type 2 diabetes comorbid with depression has a worse prognosis. There are multiple risk factors for depression, and genetic studies have shown that gene polymorphism may play an important role in the pathogenesis of depression.MethodsA total of 874 patients with type 2 diabetes were recruited for this study and divided into two groups: depressive group (DDM group, n = 234) and non-depressive group (NDDM group, n = 640). HTR1A gene polymorphisms (rs6295, rs878567, rs1800044) genotyping work was performed using a custom by design 48-Plex SNPscanTM Kit.ResultsThe rs6295, rs878567, and rs1800044 SNPs were not associated with type 2 diabetes comorbid with depression. Female sex, age, and FBG level increased the risk of depression in patients with type 2 diabetes.ConclusionHTR1A rs6295, rs878567, and rs1800044 SNPs polymorphism is not associated with type 2 diabetes comorbid with depression. Rather, female sex, age, and FBG level are risk factors for depression among patients with type 2 diabetes. Larger studies are needed to further confirm our findings.

Brain‐derived Neurotrophic Factor in Duchenne Muscular Dystrophy Myopathy

Brain‐derived neurotrophic factor (BDNF) and its receptor tropomyosin receptor kinase B (TrkB) are crucial for neuronal growth and survival, and loss of this signaling nexus invariably leads to neurodegeneration. In a small cohort of Duchenne muscular dystrophy (DMD) patients we found that BDNF blood levels positively correlated with better heart function, and carriers of the common BDNF single nucleotide polymorphism rs6265 (Val66‐Met) exhibited significantly worse skeletal muscle function and earlier loss of ambulation, compared to non‐carriers. We thus hypothesized that BDNF/TrkB signaling delays progression of myopathy in DMD. To test this hypothesis, we administered the TrkB agonist 7,8‐dihydroxyflavone (DHF) to mdx mice in their drinking water for 26 weeks, beginning at 8 weeks of age. Based on functional assessment using the hang test, DHF treatment preserved skeletal muscle function compared to vehicle‐treated controls. Trichrome staining of gastrocnemius and cardiac tissues also showed reduced levels of fibrosis, which correlated with BDNF expression levels. Using humanized BDNF polymorphic mice, which have the Val66‐Met mutation, and mice with a point mutation in the equivalent position of murine BDNF (Val68‐Met), we found that skeletal muscle strength was significantly reduced in mice with the Met allele, compared to Val/Val littermate controls. Although Val/Met and Met/Met mice weighed considerably more than control mice, they exhibited significantly increased activity, as measured by voluntary wheel running. Based on transmission electron microscopy, individual gastrocnemius muscle fibers of Met/Met mice were smaller and less organized compared to those of Val/Val. Finally, we crossed Val66‐Met mice with mdx mice to assess the effects of the BDNF polymorphism on the dystrophic background. As was found for DMD patients who harbor the BDNF rs6265 polymorphism, dystrophic mice with the Met allele exhibited worse skeletal muscle function compared to noncarriers. Considered together, our results indicate that BDNF plays a protective role in dystrophic muscle and might represent a novel therapeutic candidate for DMD myopathy.

육상투척 선수군에서 ACTN3 유전자의 R577X 다형성과 COMT 유전자의 Val158Met 다형성의 분포

The aim of this study was to compare the genotype and allele distributions of the R577X(C1747T, rs1815739) polymorphism in α-actinin 3(ACTN3) gene and the Val158Met(G/A, rs4680) polymorphism in catechol-O-methyltransferase(COMT) gene between controls and athletes of throwing event in order to search for the useful genetic marker(s) influencing the athletic performance of throwing event. On the whole, seventy eight individuals were included in this study, and they grouped in controls(n=55) and throwers(n=23), respectively. Total genomic DNA was isolated from all subjects, and two genetic polymorphisms in each gene were assayed by SNaPshot method. In the case of the Val158Met polymorphism in COMT gene, there were no significant differences in genotype and allele distributions between controls and throwers, respectively. But, there were the significant differences in both genotype and allele frequencies of the R577X polymorphism in ACTN3 gene between two groups, respectively(p .05). Especially, the frequencies of RR genotype and R allele in this genetic polymorphism were overrepresented in throwers compared to controls, respectively. Thus, these results suggest that the R577X polymorphism in ACTN3 gene is likely to significantly influence the athletic performance of throwing event in at least Koreans. Because the genotype and allele frequencies of each genetic polymorphism can vary by ethnicity with different genetic bacjground, further studies by using other ethnic groups will be needed to replicate our positive association study result observed in the R577X polymorphism of ACTN3 gene.

The Interaction between Serotonin Transporter Allelic Variation and Maternal Care Modulates Instagram Sociability in a Sample of Singaporean Users.

Human social interactions ensure recognition and approval from others, both in offline and online environments. This study applies a model from behavioral genetics on Instagram sociability to explore the impact of individual development on behavior on social networks. We hypothesize that sociable attitudes on Instagram resulted from an interaction between serotonin transporter gene alleles and the individual’s social relationship with caregivers. We assess the environmental and genetic components of 57 Instagram users. The self-report questionnaire Parental Bonding Instrument is adopted to determine the quality of parental bonding. The number of posts, followed users (“followings”), and followers are collected from Instagram as measures of online social activity. Additionally, the ratio between the number of followers and followings (“Social Desirability Index”) was calculated to estimate the asymmetry of each user’s social network. Finally, buccal mucosa cell samples were acquired, and the polymorphism rs25531 (T/T homozygotes vs. C-carriers) within the serotonin transporter gene was examined. In the preliminary analysis, we identified a gender effect on the number of followings. In addition, we specifically found a gene–environment interaction on the standardized Instagram “Social Desirability Index” in line with our predictions. Users with the genotype more sensitive to environmental influences (T/T homozygotes) showed a higher Instagram “Social Desirability Index” than nonsensitive ones (C-carriers) when they experienced positive maternal care. This result may contribute to understanding online social behavior from a gene*environment perspective.

Experiences of ethnic discrimination and COMT rs4680 polymorphism are associated with depressive symptoms in Latinx adults at risk for cardiovascular disease

BackgroundEthnic discrimination is frequently experienced among U.S. Latinx communities, and is linked to CVD risk factors, such as depression. Genetic variants may influence this relationship. ObjectivesThe objectives of this study were to examine associations between experiences of discrimination, rs4680 genotype, and depressive symptoms in Latinx adults. MethodsWe analyzed data from 124 Latinx adults with two or more CVD risk factors, and conducted hierarchical linear regression, adjusting for sex, age, income, education, and acculturation. ResultsParticipants were predominately female (74.2%) and aged 40.2 ± 9.3 years. More experiences of discrimination were associated with higher depressive symptoms (p = 0.041). Those with Met-Met-and Val-Met-genotypes had increased depressive symptoms than those with Val-Val-genotype (p = 0.049). Rs4680 was not a moderator. ConclusionFindings suggest discrimination and rs4680 genotype are associated with depressive symptoms in Latinx adults, which may increase CVD risk. Further research is needed to better understand biological mechanisms of these relationships.

BDNF gene polymorphisms predicting treatment response to CBT-based rehabilitation of depression

Genetic factors were shown to play a major role in both variation of treatment response and incidence of adverse effects to medication in affective disorders. Nevertheless, there is still a lack of therapygenetic studies, investigating the prediction of psychological therapy outcomes from genetic markers. Neuroplasticity and one of its mediators, brain-derived neurotrophic factor (BDNF), are potential research targets in this field.We aimed to investigate Tag SNP polymorphisms of the BDNF gene in depressed patients treated with cognitive behavioral therapy (CBT) in the context of a standardized 6-weeks outpatient rehabilitation program. Treatment response was assessed calculating the mean differences in BDI-II (Beck Depression Inventory) scores from admission to discharge. Six BDNF SNPs, including the Val66Met polymorphism (rs6265), were genotyped. Both genotypic data and BDI-II-scores at admission and discharge were available for 277 patients. Three SNPs, rs10501087 (p = 0.005, FDRp=0.015), rs11030104 (p = 0.006, FDRp=0.012), and the Val66Met polymorphism (rs6265, p<0.001, FDRp=0.006), were significantly associated with treatment response in depressed patients, even after multiple testing correction using the false discovery rate method (FDRp).We conclude that BDNF might serve as promising genetic marker for treatment response to psychological treatment in depression. However, due to our limited sample size, further studies are needed to disentangle the role of BDNF as potential therapygenetic marker.

Catechol-O-methyltransferase (COMT) Val158Met Polymorphism and Prepulse Inhibition of the Change-related Cerebral Response

Change-related potentials elicited by an abrupt sound feature's change are attenuated by a leading weak sound (prepulse inhibition: PPI). We investigated whether the PPI index is associated with the catechol-methyltransferase (COMT) Val158Met polymorphism (rs4680), which is involved in the metabolism of dopamine in the prefrontal cortex. Healthy subjects with normal hearing were recruited (n = 70). A train of 100-Hz clicks 650 ms in duration was used. The test stimulus was an abrupt increase in sound intensity (+10 dB) from the baseline (70 dB) provided at 400 ms after the sound onset. Three consecutive clicks at 30, 40, and 50 ms before the change's onset were greater (+3 or +5 dB) from the baseline as a prepulse. The targeting auditory evoked potential component was Change-N1 peaking approx. 130 ms after the change onset. We calculated the inhibition level as the% inhibition of the Change-N1 amplitude by a prepulse. The %PPI in the Met-carriers was significantly greater than that in the Val/Val-individuals. Our results suggest that dopamine might play a role in the PPI of the change-related response. We propose that this index has the potential to identify an intermediate phenotype in psychiatric disorders such as schizophrenia.

Clustering of Parkinson subtypes reveals strong influence of DRD2 polymorphism and gender

Most classification approaches for idiopathic Parkinson’s disease subtypes primarily focus on motor and non-motor symptoms. Besides these characteristics, other features, including gender or genetic polymorphism of dopamine receptors are potential factors influencing the disease’s phenotype. By utilizing a kmeans-clustering algorithm we were able to identify three subgroups mainly characterized by gender, DRD2 Taq1A (rs1800497) polymorphism—associated with changes in dopamine signaling in the brain—and disease progression. A subsequent regression analysis of these subgroups further suggests an influence of their characteristics on the daily levodopa dosage, an indicator for medication response. These findings could promote further enhancements in individualized therapies for idiopathic Parkinson’s disease.

In vivo imaging translocator protein (TSPO) in autism spectrum disorder.

Converging evidence points to the significant involvement of the immune system in autism spectrum disorders (ASD). Positron emission tomography (PET) can quantify translocator protein 18 kDa (TSPO), a marker with increased expression mainly in microglia and, to some extent astroglia during neuropsychiatric diseases with inflammation. This preliminary analysis explored, for the first time, whether TSPO binding was altered in male and female participants with ASD in vivo using full kinetic quantification. Thirteen individuals with ASD (IQ > 70 [n = 12], IQ = 62 [n = 1]), 5 F, 25 ± 5 years) were scanned with [18F]FEPPA PET. Data from 13 typically developing control participants with matching age and TSPO rs6971 polymorphism (9 F, age 24 ± 5 years) were chosen from previous studies for comparison. The two tissue compartment model (2TCM) was used to determine the total volume of distribution ([18F]FEPPA VT) in four previously identified regions of interest (ROI): prefrontal, temporal, cerebellar, and anterior cingulate cortices. We observe no significant difference in [18F]FEPPA VT relative to controls (F(1,26)= 1.74, p = 0.20). However, 2 ASD participants with higher VT had concurrent major depressive episodes (MDE), which has been consistently reported during MDE. After excluding those 2 ASD participants, in a post-hoc analysis, our results show lower [18F]FEPPA VT in ASD participants compared to controls (F(1,24)= 6.62, p = 0.02). This preliminary analysis provides evidence suggesting an atypical neuroimmune state in ASD.

Dopamine DRD2 and DRD3 Polymorphisms Involvement in Nicotine Dependence in Patients with Treatment-Resistant Mental Disorders.

Patients affected by mental disorders smoke more than the general population. The reasons behind this habit are genetic, environmental, etc. This study aims to investigate the correlations between some polymorphisms and the smoking habits and nicotine dependence in patients with psychiatric disorders. We recruited 88 patients with treatment-resistant mental disorders, including 35 with major depressive disorder, 43 with bipolar spectrum disorder, and 10 with schizophrenia spectrum disorder. We carried out a clinical and psychometric assessment on current smoking habits, years of smoking, number of daily cigarettes, and level of nicotine addiction. The patients performed a peripheral blood sample for DNA analyses of different polymorphisms. We searched for correlations between the measures of nicotine addiction and analysed genotypes. The expression of the T allele of the DRD2 rs1800497 and DRD3 rs6280 polymorphisms significantly correlated with a lower level of nicotine dependence and lower use of cigarettes. We did not find significant correlations between nicotine dependence and OPRM1 rs1799971, COMT rs4680 and rs4633 polymorphisms, CYP2A6 rs1801272 and rs28399433, or 5-HTTLPR genotype. Concluding, DRD2 rs1800497 and DRD3 rs6280 polymorphisms are involved in nicotine dependence and cigarette smoking habits in patients with treatment-resistant mental disorders