Associations between oxytocin receptor genotypes and social cognitive performance in individuals with schizophrenia.
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ABSTRACT:
SUBMITTER: Davis MC
PROVIDER: S-EPMC4254299 | biostudies-literature | 2014 Nov
REPOSITORIES: biostudies-literature
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Associations between oxytocin receptor genotypes and social cognitive performance in individuals with schizophrenia.
Davis Michael C MC Horan William P WP Nurmi Erika L EL Rizzo Shemra S Li Wendy W Sugar Catherine A CA Green Michael F MF
Schizophrenia research 20140920 2-3
Individuals with schizophrenia often show substantial deficits in social cognitive abilities, which are strongly associated with social functioning. To advance our understanding of the genetic variation that is associated with social cognitive deficits in schizophrenia, we genotyped 74 schizophrenia outpatients who completed social cognitive performance measures assessing mentalizing, social perception, and emotional intelligence, as well as clinical symptoms. We assessed seven single nucleotide ...[more]
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Project description:Impairments in social cognition are common in schizophrenia and predict poor functional outcome. The purpose of this proof-of-concept randomized, parallel group clinical trial was to assess whether intranasal oxytocin (OT), given before social cognitive training, enhances learning of social cognitive skills. Twenty seven male outpatients with schizophrenia participated in a 6-week (12 session) training on social cognitive skills. Training focused on three domains: facial affect recognition, social perception, and empathy. Subjects were randomly assigned (double blind) to receive either intranasal OTor placebo 30 min before each session. Participants did not receive OT between sessions or on the day of assessments. We evaluated scores on social-cognition measures, as well as clinical symptoms and neurocognition, at baseline, 1 week following the final training session, and 1 month later. Our prespecified primary outcome measure was a social-cognition composite score comprised of five individual measures. There were main effects of time (indicating improvement across the combined-treatment groups) on the social-cognition composite score at both 1 week and 1 month following completion of training. Subjects receiving OT demonstrated significantly greater improvements in empathic accuracy than those receiving placebo at both posttreatment and 1 month follow up. There were no OT-related effects for the other social cognitive tests, clinical symptoms, or neurocognition. This study provides initial support for the idea that OT enhances the effectiveness of training when administered shortly before social cognitive training sessions. The effects were most pronounced on empathic accuracy, a high-level social cognitive process that is not easily improved in current social cognitive remediation programs.
| S-EPMC4104336 | biostudies-other
Project description:BackgroundA significant proportion of people with schizophrenia are characterized by impaired ability to socially engage with others. The development of effective interventions for social functioning remains a central therapeutic challenge. Cognitive-behavioral social skills training (CBSST) has been found to improve social functioning in schizophrenia, but with only medium effect sizes. Intranasal oxytocin also has prosocial effects, but also only with modest effect sizes. This study assessed whether the addition of intranasal oxytocin to CBSST can strengthen their impact on social function.MethodsParticipants (N = 62) with schizophrenia or schizoaffective disorder entered a 24-week, double-blind, placebo-controlled, randomized clinical trial with a 3-month follow-up evaluation at 2 sites: Maryland and San Diego. Participants were randomized to either intranasal oxytocin 36 IU (3 sprays) twice a day (n = 31) or intranasal placebo-oxytocin (3 sprays) twice a day (n = 31). All participants received CBSST plus a social cognition skills training module (48 total sessions).ResultsThere were no significant treatment group differences in social functioning, positive symptoms, negative symptoms, defeatist beliefs, or asocial beliefs. The interpretation of treatment effects was complicated by site effects, whereby participants in San Diego began the trial with greater severity of impairments and subsequently showed greater improvements compared with participants in Maryland.ConclusionsThe results did not support the utility of add-on intranasal oxytocin to psychosocial rehabilitation interventions like CBSST for improvement in social function (ClinicalTrials.gov trial number: NCT01752712).
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Project description:Schizophrenia (SCZ), a highly heritable mental disorder, is characterized by cognitive impairment, yet the extent of the shared genetic basis between schizophrenia and cognitive performance (CP) remains poorly understood. Therefore, we aimed to explore the polygenic overlap between SCZ and CP. Specifically, the bivariate causal mixture model (MiXeR) was employed to estimate the extent of genetic overlap between SCZ (n = 130,644) and CP (n = 257,841), and conjunctional false discovery rate (conjFDR) approach was used to identify shared genetic loci. Subsequently, functional annotation and enrichment analysis were carried out on the identified genomic loci. The MiXeR analyses revealed that 9.6 K genetic variants are associated with SCZ and 10.9 K genetic variants for CP, of which 9.5 K variants are shared between these two traits (Dice coefficient = 92.8%). By employing conjFDR, 236 loci were identified jointly associated with SCZ and CP, of which 139 were novel for the two traits. Within these shared loci, 60 exhibited consistent effect directions, while 176 had opposite effect directions. Functional annotation analysis indicated that the shared genetic loci were mainly located in intronic and intergenic regions, and were found to be involved in relevant biological processes such as nervous system development, multicellular organism development, and generation of neurons. Together, our findings provide insights into the shared genetic architecture between SCZ and CP, suggesting common pathways and mechanisms contributing to both traits.
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Project description:ImportanceCognitive impairment is a debilitating symptom of multiple sclerosis (MS) that affects up to 70% of patients. An improved understanding of the underlying pathology of MS-related cognitive impairment would provide considerable benefit to patients and clinicians.ObjectiveTo determine whether there is an association between myelin damage in tissue that appears completely normal on standard clinical imaging, but can be detected by myelin water imaging (MWI), with cognitive performance in MS.Design, setting, and participantsIn this cross-sectional study, participants with MS and controls underwent cognitive testing and magnetic resonance imaging (MRI) from August 23, 2017, to February 20, 2019. Participants were recruited through the University of British Columbia Hospital MS clinic and via online recruitment advertisements on local health authority websites. Cognitive testing was performed in the MS clinic, and MRI was performed at the adjacent academic research neuroimaging center. Seventy-three participants with clinically definite MS fulfilling the 2017 revised McDonald criteria for diagnosis and 22 age-, sex-, and education-matched healthy volunteers without neurological disease were included in the study. Data analysis was performed from March to November 2019.ExposuresMWI was performed at 3 T with a 48-echo, 3-dimensional, gradient and spin-echo (GRASE) sequence. Cognitive testing was performed with assessments drawn from cognitive batteries validated for use in MS.Main outcomes and measuresThe association between myelin water measures, a measurement of the T2 relaxation signal from water in the myelin bilayers providing a specific marker for myelin, and cognitive test scores was assessed using Pearson correlation. Three white matter regions of interest-the cingulum, superior longitudinal fasciculus (SLF), and corpus callosum-were selected a priori according to their known involvement in MS-related cognitive impairment.ResultsFor the 95 total participants, the mean (SD) age was 49.33 (11.44) years. The mean (SD) age was 50.2 (10.7) years for the 73 participants with MS and 46.4 (13.5) for the 22 controls. Forty-eight participants with MS (66%) and 14 controls (64%) were women. The mean (SD) years of education were 14.7 (2.2) for patients and 15.8 (2.5) years for controls. In MS, significant associations were observed between myelin water measures and scores on the Symbol Digit Modalities Test (SLF, r = -0.490; 95% CI, -0.697 to -0.284; P < .001; corpus callosum, r = -0.471; 95% CI, -0.680 to -0.262; P < .001; and cingulum, r = -0.419; 95% CI, -0.634 to -0.205; P < .001), Selective Reminding Test (SLF, r = -0.444; 95% CI, -0.660 to -0.217; P < .001; corpus callosum, r = -0.411; 95% CI, -0.630 to -0.181; P = .001; and cingulum, r = -0.361; 95% CI, -0.602 to -0.130; P = .003), and Controlled Oral Word Association Test (SLF, r = -0.317; 95% CI, -0.549 to -0.078; P = .01; and cingulum, r = -0.335; 95% CI, -0.658 to -0.113; P = .006). No significant associations were found in controls.Conclusions and relevanceThis study used MWI to demonstrate that otherwise normal-appearing brain tissue is diffusely damaged in MS, and the findings suggest that myelin water measures are associated with cognitive performance. MWI offers an in vivo biomarker feasible for use in clinical trials investigating cognition, providing a means for monitoring changes in myelination and its association with symptom worsening or improvement.
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Project description:ImportanceSchizophrenia is a clinically heterogeneous disorder. It is currently unclear how variability in symptom dimensions and cognitive ability is associated with genetic liability for schizophrenia.ObjectiveTo determine whether phenotypic dimensions within schizophrenia are associated with genetic liability to schizophrenia, other neuropsychiatric disorders, and intelligence.Design, setting, and participantsIn a genetic association study, 3 cross-sectional samples of 1220 individuals with a diagnosis of schizophrenia were recruited from community, inpatient, and voluntary sector mental health services across the UK. Confirmatory factor analysis was used to create phenotypic dimensions from lifetime ratings of the Scale for the Assessment of Positive Symptoms, Scale for the Assessment of Negative Symptoms, and the MATRICS Consensus Cognitive Battery. Analyses of polygenic risk scores (PRSs) were used to assess whether genetic liability to schizophrenia, other neuropsychiatric disorders, and intelligence were associated with these phenotypic dimensions. Data collection for the cross-sectional studies occurred between 1993 and 2016. Data analysis for this study occurred between January 2019 and March 2021.Main outcomes and measuresOutcome measures included phenotypic dimensions defined from confirmatory factor analysis relating to positive symptoms, negative symptoms of diminished expressivity, negative symptoms of motivation and pleasure, disorganized symptoms, and current cognitive ability. Exposure measures included PRSs for schizophrenia, bipolar disorder, major depression, attention-deficit/hyperactivity disorder, autism spectrum disorder, and intelligence.ResultsOf the 1220 study participants, 817 were men (67.0%). Participants' mean (SD) age at interview was 43.10 (12.74) years. Schizophrenia PRS was associated with increased disorganized symptom dimension scores in both a 5-factor model (β = 0.14; 95% CI, 0.07-0.22; P = 2.80 × 10-4) and a 3-factor model across all samples (β = 0.10; 95% CI, 0.05-0.15; P = 2.80 × 10-4). Current cognitive ability was associated with genetic liability to schizophrenia (β = -0.11; 95% CI, -0.19 to -0.04; P = 1.63 × 10-3) and intelligence (β = 0.23; 95% CI, 0.16-0.30; P = 1.52 × 10-10). After controlling for estimated premorbid IQ, current cognitive performance was associated with schizophrenia PRS (β = -0.08; 95% CI, -0.14 to -0.02; P = 8.50 × 10-3) but not intelligence PRS.Conclusions and relevanceThe findings of this study suggest that genetic liability for schizophrenia is associated with higher disorganized dimension scores but not other symptom dimensions. Cognitive performance in schizophrenia appears to reflect distinct contributions from genetic liabilities to both intelligence and schizophrenia.
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Project description:BACKGROUND:Deficits in neurocognition and social cognition are drivers of reduced functioning in schizophrenia spectrum disorders, with potentially shared neurobiological underpinnings. Many studies have sought to identify brain-based biomarkers of these clinical variables using a priori dichotomies (e.g., good vs. poor cognition, deficit vs. nondeficit syndrome). METHODS:We evaluated a fully data-driven approach to do the same by building and validating a brain connectivity-based biomarker of social cognitive and neurocognitive performance in a sample using resting-state and task-based functional magnetic resonance imaging (n = 74 healthy control participants, n = 114 persons with schizophrenia spectrum disorder, 188 total). We used canonical correlation analysis followed by clustering to identify a functional connectivity signature of normal and poor social cognitive and neurocognitive performance. RESULTS:Persons with poor social cognitive and neurocognitive performance were differentiated from those with normal performance by greater resting-state connectivity in the mirror neuron and mentalizing systems. We validated our findings by showing that poor performers also scored lower on functional outcome measures not included in the original analysis and by demonstrating neuroanatomical differences between the normal and poorly performing groups. We used a support vector machine classifier to demonstrate that functional connectivity alone is enough to distinguish normal and poorly performing participants, and we replicated our findings in an independent sample (n = 75). CONCLUSIONS:A brief functional magnetic resonance imaging scan may ultimately be useful in future studies aimed at characterizing long-term illness trajectories and treatments that target specific brain circuitry in those with impaired cognition and function.
| S-EPMC6177285 | biostudies-literature
Project description:Oxytocin has been well researched in association with psychological variables and is widely accepted as a key modulator of human social behaviour. Previous work indicates involvement of oxytocin receptor gene (OXTR) single nucleotide polymorphisms (SNPs) in human-human empathy, however little is known about associations of OXTR SNPs with empathy and affective reactions of humans towards animals. Five OXTR SNPs previously found to associate with human social behaviour were genotyped in 161 students. Empathy towards animals and implicit associations were evaluated. A General Linear Model was used to investigate the OXTR alleles and allelic combinations along with socio-demographic variables and their influence on empathy towards animals. Empathy towards animals showed a significant association with OXTR SNP rs2254298; homozygous G individuals reported higher levels of empathy towards animals than heterozygous (GA). Our preliminary findings show, for the first time, that between allelic variation in OXTR and animal directed empathy in humans maybe associated, suggesting that OXTRs social behaviour role crosses species boundaries, warranting independent replication.
| S-EPMC6116162 | biostudies-literature
Project description:BACKGROUND:Impairments in self-assessment are common in people with schizophrenia and impairments in self-assessment of cognitive ability have been found to predict impaired functional outcome. In this study, we examined self-assessment of social cognitive ability and related them to assessments of social cognition provided by informants, to performance on tests of social cognition, and to everyday outcomes. The difference between self-reported social cognition and informant ratings was used to predict everyday functioning. METHODS:People with schizophrenia (n=135) performed 8 different tests of social cognition. They were asked to rate their social cognitive abilities on the Observable Social Cognition Rating Scale (OSCARs). High contact informants also rated social cognitive ability and everyday outcomes, while unaware of the patients' social cognitive performance and self-assessments. Social competence was measured with a performance-based assessment and clinical ratings of negative symptoms were also performed. RESULTS:Patient reports of their social cognitive abilities were uncorrelated with performance on social cognitive tests and with three of the four domains of functional outcomes. Differences between self-reported and informant rated social cognitive ability predicted impaired everyday functioning across all four functional domains. This difference score predicted disability even when the influences of social cognitive performance, social competence, and negative symptoms were considered. IMPLICATIONS:Mis-estimation of social cognitive ability was an important predictor of social and nonsocial outcomes in schizophrenia compared to performance on social cognitive tests. These results suggest that consideration of self-assessment is critical when attempting to evaluate the causes of disability and when trying to implement interventions targeting disability reduction.
| S-EPMC6151277 | biostudies-literature
Project description:ObjectsTo explore the specific features of cognitive function in patients with schizophrenia at different stages and its influencing factors.MethodsThe MATRICS Consensus Cognitive Battery (MCCB) and the Brief Psychiatric Rating Scale (BPRS) were administered to 208 patients with schizophrenia, including 158 clinically stable schizophrenia (CSS) and 50 first-episode patients with schizophrenia (FES), and 40 healthy controls (HC). Propensity score matching (PSM) was used to match the CSS and FES.Results(1) The MCCB and it,s sub-scale scores in patients with schizophrenia were lower than HC, but the score of emotion intelligence showed no significant difference between CSS and HC. (2) Before PSM, the cognitive scores of FES were significantly lower than CSS (except trail making A test, Hopkins verbal learning, category fluency). After PSM, patients with CSS still do better in performing trail making A test, emotional intelligence, continuous performances and MCCB total score. (3) BPRS total score, gender, group (FES vs CSS) and age were independent contributors to emotion intelligence, and BPRS total score had the biggest effect. (4) The effect of group (FES vs CSS) on MCCB total score and emotional intelligence was statistically significant.ConclusionsThere are significant cognitive deficits in patients with FES and CSS compared with HC. FES have greater cognitive impairments compared with CSS. Emotion intelligence of CSS may be even close to the level of HC. BPRS total score, gender, group (FES vs CSS) and age may be the independent contributors to social cognition. Group (FES vs CSS) may play an important effect on general cognition and social cognition.
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