scholarly journals Dysbindin (DTNBP1) variants are associated with hallucinations in schizophrenia

2015 ◽  
Vol 30 (4) ◽  
pp. 486-491 ◽  
Author(s):  
S.-Y. Cheah ◽  
B.R. Lawford ◽  
R.M. Young ◽  
C.P. Morris ◽  
J. Voisey
Keyword(s):  
Visual Processing ◽  
Auditory Processing ◽  
Multiple Testing ◽  
Auditory Hallucination ◽  
Susceptibility Gene ◽  
Auditory Hallucinations ◽  
Opiate Dependence ◽  
Nucleotide Polymorphisms ◽  
Post Traumatic Stress ◽  
Third Person

AbstractBackground:Dystrobrevin binding protein 1 (DTNBP1) is a schizophrenia susceptibility gene involved with neurotransmission regulation (especially dopamine and glutamate) and neurodevelopment. The gene is known to be associated with cognitive deficit phenotypes within schizophrenia. In our previous studies, DTNBP1 was found associated not only with schizophrenia but with other psychiatric disorders including psychotic depression, post-traumatic stress disorder, nicotine dependence and opiate dependence. These findings suggest that DNTBP1 may be involved in pathways that lead to multiple psychiatric phenotypes. In this study, we explored the association between DTNBP1 SNPs (single nucleotide polymorphisms) and multiple psychiatric phenotypes included in the Diagnostic Interview of Psychosis (DIP).Methods:Five DTNBP1 SNPs, rs17470454, rs1997679, rs4236167, rs9370822 and rs9370823, were genotyped in 235 schizophrenia subjects screened for various phenotypes in the domains of depression, mania, hallucinations, delusions, subjective thought disorder, behaviour and affect, and speech disorder. SNP-phenotype association was determined with ANOVA under general, dominant/recessive and over-dominance models.Results:Post hoc tests determined that SNP rs1997679 was associated with visual hallucination; SNP rs4236167 was associated with general auditory hallucination as well as specific features including non-verbal, abusive and third-person form auditory hallucinations; and SNP rs9370822 was associated with visual and olfactory hallucinations. SNPs that survived correction for multiple testing were rs4236167 for third-person and abusive form auditory hallucinations; and rs9370822 for olfactory hallucinations.Conclusion:These data suggest that DTNBP1 is likely to play a role in development of auditory related, visual and olfactory hallucinations which is consistent with evidence of DTNBP1 activity in the auditory processing regions, in visual processing and in the regulation of glutamate and dopamine activity.

Psychedelic drugs and perception: a narrative review of the first era of research

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Jacob S. Aday ◽  
Julia R. Wood ◽  
Emily K. Bloesch ◽  
Christopher C. Davoli
Keyword(s):  
Visual Processing ◽  
Auditory Processing ◽  
Body Schema ◽  
Neural Correlates ◽  
Narrative Review ◽  
Auditory Hallucinations ◽  
Visual Effects ◽  
Future Studies ◽  
Psychedelic Drugs ◽  
Work Done

Abstract Psychedelic drugs are well-known for transiently altering perception, and in particular, for their visual effects. Although scientific interest into the substances’ effects on perception increased during the first era of psychedelic research during the early to mid-20th century, there is currently no source where these findings have been synthesized. In addressing this gap, the current narrative review found that psychedelics were examined for their influences across all levels of the visual system (e.g., retinal, cortical, subcortical, simple visual processing, complex imagery, hallucinations). Psychedelics were also shown to affect auditory discrimination/generalization, neural correlates of auditory processing, and led to auditory hallucinations in subsets of participants. Several studies demonstrated that psychedelics can distort representations of body schema and time perception. Concerns regarding methodological standards of this era are a limitation to the findings and are discussed. Collectively, this review preserves and increases the accessibility of the work done by pioneering psychedelic/perception researchers, synthesizes findings, and critically analyzes areas of discrepancy to inform future studies.

Transcription Factor Enrichment Analysis in Enhancers Identifies EZH2 as a Susceptibility Gene for Osteoporosis

2019 ◽  
Vol 105 (4) ◽  
pp. e1152-e1161
Author(s):  
Meng Li ◽  
Shi Yao ◽  
Yuan-Yuan Duan ◽  
Yu-Jie Zhang ◽  
Yan Guo ◽  
...  
Keyword(s):  
Chinese Population ◽  
Multiple Testing ◽  
Association Studies ◽  
Susceptibility Gene ◽  
Enrichment Analysis ◽  
Genome Wide Association Studies ◽  
Nucleotide Polymorphisms ◽  
Mineral Density ◽  
Association Analyses ◽  
Hip Bmd

Abstract Purpose Genome-wide association studies (GWASs) have identified hundreds of single nucleotide polymorphisms (SNPs) associated with osteoporosis. Most of these SNPs are noncoding variants and could be mapped to enhancers. Transcription factors (TFs) play important roles in gene regulation via enhancers harboring these SNPs; thus, we aimed to identify common regulatory TFs binding to enhancers associated with osteoporosis. Methods We first annotated all the osteoporosis-related SNPs identified by GWASs to enhancers and conducted TF enrichment analyses to identify common TFs binding to osteoporosis-associated enhancers. We further conducted genetic association analyses between the identified TFs and bone mineral density (BMD) in a Han Chinese population. Results After functional annotation, a total of 5081 osteoporosis-related SNPs were mapped to enhancers. TF enrichment analyses identified 2 significant TFs after multiple testing adjustments, which are EZH2 (Padj = .028) and NRSF (Padj = .038). We also found 1 SNP, rs111851041, in EZH2 was significantly associated with BMD both at the hip and spine after multiple testing adjustments (hip BMD: P = 4.32 × 10–4; spine BMD: P = 2.72 × 10–3). The expression of EZH2 decreased significantly from 12 to 48 hours of osteogenic differentiation. And functional validation showed that EZH2 was associated with osteoporosis-related phenotypes in knockout mice. Conclusions By conducting TF enrichment analyses, we identified EZH2 as a common TF binding to osteoporosis-associated enhancers, and EZH2 was also associated with BMD in a Chinese population. EZH2 is functionally related to bone phenotypes. The identified gene could provide new insight into osteoporosis pathophysiology and highlight opportunities for future clinical and pharmacological research on osteoporosis.

scholarly journals Relating C-reactive Protein to Psychopathology after Cardiac Surgery and Intensive Care Unit Admission: A Mendelian Randomization Study

2017 ◽  
Author(s):  
Lotte Kok ◽  
Bochao Danae Lin ◽  
Juliette Broersen ◽  
Erwin Bekema ◽  
Jelena Medic ◽  
...  
Keyword(s):  
Intensive Care Unit ◽  
Intensive Care ◽  
Multiple Testing ◽  
Mendelian Randomization ◽  
Genetic Risk Score ◽  
Nucleotide Polymorphisms ◽  
Post Traumatic Stress ◽  
C Reactive Protein ◽  
Reactive Protein ◽  
Individual Snps

AbstractPatients admitted to an intensive care unit (ICU) are subjected to a high burden of stress, rendering them prone to develop stress-related psychopathology. Dysregulation of inflammation and, more specifically, upregulation of inflammatory markers such as C-reactive protein (CRP) is potentially key in development of post-ICU psychopathology.To investigate the effects of state-independent CRP on symptoms of post-traumatic stress disorder (PTSD) and depression after ICU admission, we analysed the three leading single nucleotide polymorphisms (SNPs) of loci most strongly associated with blood CRP levels (i.e. rs2794520, rs4420638, and rs1183910) in an ICU survivor cohort. Genetic association was estimated by linear and logistical regression models of individual SNPs and genetic risk score (GRS) profiling. Mendelian Randomization (MR) was used to investigate potential causal relationships.Single-SNP analyses were non-significant for both quantitative and binary trait analyses after correction for multiple testing. In addition, GRS results were non-significant and explained little variance in psychopathology. Moreover, MR analysis did not reveal any causality and MR-Egger regression showed no evidence of pleiotropic effects (p-pleiotropy >0.05). Furthermore, estimation of causality between these loci and other psychiatric disorders was similarly non-significant.In conclusion, by applying a range of statistical models we demonstrate that the strongest plasma CRP-influencing genetic loci are not associated with post-ICU PTSD and depressive symptoms. Our findings add to an expanding body of literature on the absence of associations between trait CRP and neuropsychiatric phenotypes.

scholarly journals KPNA3Variation Is Associated with Schizophrenia, Major Depression, Opiate Dependence and Alcohol Dependence

2012 ◽  
Vol 33 (4) ◽  
pp. 163-170 ◽  
Author(s):  
Charles P. Morris ◽  
Bernhard T. Baune ◽  
Katharina Domschke ◽  
Volker Arolt ◽  
Christopher D. Swagell ◽  
...  
Keyword(s):  
Major Depression ◽  
Alcohol Dependence ◽  
Psychiatric Disorders ◽  
Opiate Dependence ◽  
Nucleotide Polymorphisms ◽  
Post Traumatic Stress ◽  
Post Traumatic ◽  
Block Based ◽  
Alcohol Dependent

KPNA3is a gene that has been linked to schizophrenia susceptibility. In this study we investigated the possible association betweenKPNA3variation and schizophrenia. To investigate a wider role ofKPNA3across psychiatric disorders we also analysed major depression, PTSD, nicotine dependent, alcohol dependent and opiate dependent cohorts. Using a haplotype block-based gene-tagging approach we genotyped sixKPNA3single nucleotide polymorphisms (SNPs) in 157 schizophrenia patients, 121 post-traumatic stress disorder patients, 120 opiate dependent patients, 231 alcohol dependent patients, 147 nicotine dependent patients and 266 major depression patients. One SNP rs2273816 was found to be significantly associated with schizophrenia, opiate dependence and alcohol dependence at the genotype and allele level. Major depression was also associated with rs2273816 but only at the allele level. Our study suggests that KPNA3 may contribute to the genetic susceptibility to schizophrenia as well as other psychiatric disorders.

scholarly journals An artificial neural network approach integrating plasma proteomics and genetic data identifies PLXNA4 as a new susceptibility locus for pulmonary embolism

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Misbah Razzaq ◽  
Maria Jesus Iglesias ◽  
Manal Ibrahim-Kosta ◽  
Louisa Goumidi ◽  
Omar Soukarieh ◽  
...  
Keyword(s):  
Pulmonary Embolism ◽  
Genome Wide Association Study ◽  
Susceptibility Gene ◽  
Biological Traits ◽  
Nucleotide Polymorphisms ◽  
Ann Model ◽  
Neural Network Approach ◽  
A Genome ◽  
Increased Risk ◽  
Artificial Neural

AbstractVenous thromboembolism is the third common cardiovascular disease and is composed of two entities, deep vein thrombosis (DVT) and its potential fatal form, pulmonary embolism (PE). While PE is observed in ~ 40% of patients with documented DVT, there is limited biomarkers that can help identifying patients at high PE risk. To fill this need, we implemented a two hidden-layers artificial neural networks (ANN) on 376 antibodies and 19 biological traits measured in the plasma of 1388 DVT patients, with or without PE, of the MARTHA study. We used the LIME algorithm to obtain a linear approximate of the resulting ANN prediction model. As MARTHA patients were typed for genotyping DNA arrays, a genome wide association study (GWAS) was conducted on the LIME estimate. Detected single nucleotide polymorphisms (SNPs) were tested for association with PE risk in MARTHA. Main findings were replicated in the EOVT study composed of 143 PE patients and 196 DVT only patients. The derived ANN model for PE achieved an accuracy of 0.89 and 0.79 in our training and testing sets, respectively. A GWAS on the LIME approximate identified a strong statistical association peak (rs1424597: p = 5.3 × 10–7) at the PLXNA4 locus. Homozygote carriers for the rs1424597-A allele were then more frequently observed in PE than in DVT patients from the MARTHA (2% vs. 0.4%, p = 0.005) and the EOVT (3% vs. 0%, p = 0.013) studies. In a sample of 112 COVID-19 patients known to have endotheliopathy leading to acute lung injury and an increased risk of PE, decreased PLXNA4 levels were associated (p = 0.025) with worsened respiratory function. Using an original integrated proteomics and genetics strategy, we identified PLXNA4 as a new susceptibility gene for PE whose exact role now needs to be further elucidated.

Previously reward-associated sounds interfere with goal-directed auditory processing

2021 ◽  
pp. 174702182199003
Author(s):  
Andy J Kim ◽  
David S Lee ◽  
Brian A Anderson
Keyword(s):  
Visual Processing ◽  
Auditory Processing ◽  
Dichotic Listening ◽  
Auditory Information ◽  
Correct Identification ◽  
Subsequent Test ◽  
Dichotic Listening Task ◽  
Listening Task ◽  
Task Irrelevant ◽  
Visual Domain

Previously reward-associated stimuli have consistently been shown to involuntarily capture attention in the visual domain. Although previously reward-associated but currently task-irrelevant sounds have also been shown to interfere with visual processing, it remains unclear whether such stimuli can interfere with the processing of task-relevant auditory information. To address this question, we modified a dichotic listening task to measure interference from task-irrelevant but previously reward-associated sounds. In a training phase, participants were simultaneously presented with a spoken letter and number in different auditory streams and learned to associate the correct identification of each of three letters with high, low, and no monetary reward, respectively. In a subsequent test phase, participants were again presented with the same auditory stimuli but were instead instructed to report the number while ignoring spoken letters. In both the training and test phases, response time measures demonstrated that attention was biased in favour of the auditory stimulus associated with high value. Our findings demonstrate that attention can be biased towards learned reward cues in the auditory domain, interfering with goal-directed auditory processing.

Comparing Primary Voice-Hearers with and without Hallucinations in Other Sensory Modalities

2021 ◽  
pp. 214-220
Author(s):  
Wei Lin Toh ◽  
Neil Thomas ◽  
Susan L. Rossell
Keyword(s):  
Functional Impairment ◽  
Auditory Hallucination ◽  
Sensory Modality ◽  
Clinical Information ◽  
Auditory Hallucinations ◽  
Auditory Modality ◽  
Positive Symptoms ◽  
Psychotic Experiences ◽  
Sensory Modalities ◽  
Preliminary Study

There has been burgeoning interest in studying hallucinations in psychosis occurring across multiple sensory modalities. The current study aimed to characterize the auditory hallucination and delusion profiles in patients with auditory hallucinations only versus those with multisensory hallucinations. Participants with psychosis were partitioned into groups with voices only (AVH; <i>n</i> = 50) versus voices plus hallucinations in at least one other sensory modality (AVH+; <i>n</i> = 50), based on their responses on the Scale for the Assessment of Positive Symptoms (SAPS). Basic demographic and clinical information was collected, and the Questionnaire for Psychotic Experiences (QPE) was used to assess psychosis phenomenology. Relative to the AVH group, greater compliance to perceived commands, auditory illusions, and sensed presences was significantly elevated in the AVH+ group. The latter group also had greater levels of delusion-related distress and functional impairment and was more likely to endorse delusions of reference and misidentification. This preliminary study uncovered important phenomenological differences in those with multisensory hallucinations. Future hallucination research extending beyond the auditory modality is needed.

scholarly journals TERT rs2736100 and TERC rs16847897 genotypes moderate the association between internalizing mental disorders and accelerated telomere length attrition among HIV+ children and adolescents in Uganda

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Allan Kalungi ◽  
Eugene Kinyanda ◽  
Jacqueline S. Womersley ◽  
Moses L. Joloba ◽  
Wilber Ssembajjwe ◽  
...  
Keyword(s):  
Mental Disorders ◽  
Children And Adolescents ◽  
Telomere Length ◽  
Cellular Aging ◽  
Nucleotide Polymorphisms ◽  
Moderating Effects ◽  
Post Traumatic Stress ◽  
Single Nucleotide ◽  
Post Traumatic ◽  
Component Gene

Abstract Background Internalizing mental disorders (IMDs) (depression, anxiety and post-traumatic stress disorder) have been associated with accelerated telomere length (TL) attrition; however, this association has not been investigated in the context of genetic variation that has been found to influence TL. We have previously reported an association between IMDs and accelerated TL attrition among Ugandan HIV+ children and adolescents. This study investigated the moderating effects of selected single nucleotide polymorphisms in the telomerase reverse transcriptase gene (TERT) (rs2736100, rs7726159, rs10069690 and rs2853669) and the telomerase RNA component gene (TERC) (rs12696304, rs16847897 and rs10936599) on the association between IMDs and TL, among Ugandan HIV+ children (aged 5–11 years) and adolescents (aged 12–17 years). Results We found no significant interaction between IMDs as a group and any of the selected SNPs on TL at baseline. We observed significant interactions of IMDs with TERT rs2736100 (p = 0.007) and TERC rs16847897 (p = 0.012), respectively, on TL at 12 months. Conclusions TERT rs2736100 and TERC rs16847897 moderate the association between IMDs and TL among Ugandan HIV+ children and adolescents at 12 months. Understanding the nature of this association may shed light on the pathophysiological mechanisms underlying advanced cellular aging in IMDs.

scholarly journals NRG1 Genetic Variant Influences the Efficacy of Androgen-Deprivation Therapy in Men with Prostate Cancer

Biomedicines ◽  
2021 ◽  
Vol 9 (5) ◽  
pp. 528
Author(s):  
Shu-Pin Huang ◽  
Yei-Tsung Chen ◽  
Lih-Chyang Chen ◽  
Cheng-Hsueh Lee ◽  
Chao-Yuan Huang ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Androgen Deprivation Therapy ◽  
Tyrosine Kinases ◽  
Multiple Testing ◽  
Cox Regression ◽  
Progression Free Survival ◽  
Androgen Deprivation ◽  
Nucleotide Polymorphisms ◽  
Multiple Testing Correction ◽  
Cancer Specific Survival

Neuregulins (NRGs) activate receptor tyrosine kinases of the ErbB family, and play essential roles in the proliferation, survival, and differentiation of normal and malignant tissue cells. We hypothesized that genetic variants of NRG signalling pathway genes may influence treatment outcomes in prostate cancer. To test this hypothesis, we performed a comprehensive analysis to evaluate the associations of 459 single-nucleotide polymorphisms in 19 NRG pathway genes with cancer-specific survival (CSS), overall survival (OS), and progression-free survival (PFS) in 630 patients with prostate cancer receiving androgen-deprivation therapy (ADT). After multivariate Cox regression and multiple testing correction, we found that NRG1 rs144160282 C > T is significantly associated with worsening CSS, OS, and PFS during ADT. Further analysis showed that low expression of NRG1 is closely related to prostate cancer, as indicated by a high Gleason score, an advanced stage, and a shorter PFS rate. Meta-analysis of 16 gene expression datasets of 1,081 prostate cancer samples and 294 adjacent normal samples indicate lower NRG1 expression in the former compared with the latter (p < 0.001). These results suggest that NRG1 rs144160282 might be a prognostic predictor of the efficacy of ADT. Further studies are required to confirm the significance of NRG1 as a biomarker and therapeutic target for prostate cancer.

scholarly journals Associations between neurochemical receptor genes, 2D:4D, impulsivity and relationship quality

2018 ◽  
Vol 14 (12) ◽  
pp. 20180642 ◽  
Author(s):  
Eiluned Pearce ◽  
Rafael Wlodarski ◽  
Anna Machin ◽  
Robin I. M. Dunbar
Keyword(s):  
Relationship Quality ◽  
Multiple Testing ◽  
Romantic Relationship ◽  
Preliminary Evidence ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Digit Ratios ◽  
The Relationship ◽  
Romantic Relationship Quality

The ratio between the second and fourth digits (2D:4D) has been widely used as a proxy for fetal exposure to androgens and has been linked to a number of sociosexual traits in humans. However, the role of genes in this equation remains unknown. Here ( N = 474), we test, firstly, for associations between 2D:4D and single-nucleotide polymorphisms (SNPs) in nine neurochemical receptor genes ( AR, OXTR, AVPR1A, OPRM1, DRD1/2, ANKK1, 5HTR1A/2A ), and secondly, whether digit ratios mediate the relationship between genetic variation and sociosexuality. We demonstrate significant associations between AR , OPRM1 and AVPR1A and 2D:4D. Moreover, mediation analysis indicates that, in women, AR and OPRM1 variation drives digit ratios, which are related positively to impulsivity and, for OPRM1 , negatively to romantic relationship quality. Although these findings are subject to multiple testing issues, this study provides preliminary evidence that in women genetic factors may affect both impulsivity and perceived relationship quality through influencing factors indexed by digit ratios.

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