Association between oxytocin receptor gene polymorphisms and self-rated 'empathic concern' in schizophrenia

The nonapeptide oxytocin (OXT) and its receptor (OXTR) have been implicated in social cognition, empathy, emotion and stress regulation in humans. Previous studies reported associations between OXT and OXTR genetic polymorphisms and risk for disorders characterized by impaired socio-emotional functioning, such as schizophrenia and autism. Here we investigate the influence of two single nucleotide polymorphisms (SNPs) within the OXTR gene on a measure of socio-emotional functioning in schizophrenic patients. OXTR SNPs that were previously investigated in other studies were genotyped in 145 patients diagnosed with schizophrenia according to DSM-IV and 145 healthy controls matched for age and gender. The Interpersonal Reactivity Index (IRI) was used to assess cognitive ('perspective taking'), affective ('empathic concern') and self-related ('personal distress') dimensions of empathy. No group differences in genotype frequencies were observed. MANCOVA revealed a significant main (F [1,282] = 10.464; pGG) with 'empathic concern'. Within the schizophrenia group, linear regression analysis determined OXTR rs2254298 genotype, PANSS negative and general symptom score, and age of disease onset as being significantly associated with 'empathic concern'. OXTR rs2254298 significantly impacted PANSS general psychopathology scores. No associations were found for OXTR rs53576, IRI 'perspective taking' or 'personal distress' ratings. Our preliminary findings support hypotheses about an involvement of OXTR rs2254298 in emotional empathy in schizophrenic and healthy individuals, warranting independent replication

Feasibility, Impact on Symptoms and Mentalising Capacity

This pilot study aimed to evaluate the feasibility of an assessor-blind, randomised controlled trial of psychodynamic art therapy for the treatment of patients with schizophrenia, and to generate preliminary data on the efficacy of this intervention during acute psychotic episodes. Fifty-eight inpatients with DSM-diagnoses of schizophrenia were randomised to either 12 twice-weekly sessions of psychodynamic group art therapy plus treatment as usual or to standard treatment alone. Primary outcome criteria were positive and negative psychotic and depressive symptoms as well as global assessment of functioning. Secondary outcomes were mentalising function, estimated with the Reading the mind in the eyes test and the Levels of emotional awareness scale, self- efficacy, locus of control, quality of life and satisfaction with care. Assessments were made at baseline, at post-treatment and at 12 weeks' follow- up. At 12 weeks, 55% of patients randomised to art therapy, and 66% of patients receiving treatment as usual were examined. In the per-protocol sample, art therapy was associated with a significantly greater mean reduction of positive symptoms and improved psychosocial functioning at post-treatment and follow-up, and with a greater mean reduction of negative symptoms at follow-up compared to standard treatment. The significant reduction of positive symptoms at post-treatment was maintained in an attempted intention- to-treat analysis. There were no group differences regarding depressive symptoms. Of secondary outcome parameters, patients in the art therapy group showed a significant improvement in levels of emotional awareness, and particularly in their ability to reflect about others' emotional mental states. This is one of the first randomised controlled trials on psychodynamic group art therapy for patients with acute psychotic episodes receiving hospital treatment. Results prove the feasibility of trials on art therapy during acute psychotic episodes and justify further research to substantiate preliminary positive results regarding symptom reduction and the recovery of mentalising function

Endogenous oxytocin response to film scenes of attachment and loss is pronounced in schizophrenia

Oxytocin (OXT) is critically involved in the regulation of attachment and interpersonal function. In this study, emotional childrens movies were used to stimulate OXT secretion in patients with schizophrenia and healthy controls (HCs). Furthermore, associations of OXT levels with measures of attachment style (Psychosis Attachment Measure), childhood adversity (Childhood Trauma Questionnaire) and symptom severity [Positive and Negative Syndrome Scale (PANSS)] were considered. In 35 patients with schizophrenia and 35 matched HCs, radioimmunoassay with sample extraction was used to determine OXT plasma levels before and after viewing of movie scenes portraying emotional bonding and loss and compared to a non-emotional condition. Statistical analysis indicated lower baseline OXT levels in female patients than in all other groups. OXT reactivity during emotional movies was significantly higher in patients when compared to HCs. OXT reactivity during the control movie related to PANSS `general psychopathology. No significant associations appeared between baseline or induced OXT levels and other PANSS subscales, attachment style or childhood adversity in patients. Our findings suggest differences of baseline OXT and a higher OXT reactivity toward strong emotional stimuli in patients with schizophrenia, suggesting a role of OXT as a gender- and context-dependent modulator of socio-emotional function

The Myth of Blunted Gamers: No Evidence for Desensitization in Empathy for Pain after a Violent Video Game Intervention in a Longitudinal fMRI Study on Non-Gamers

Background/Aims: It is a common concern in the research field and the community that habitual violent video gaming reduces empathy for pain in its players. However, previous fMRI studies have only compared habitual game players against control participants cross-sectionally. However the observed pattern of results may be due to a priori differences in people who become gamers and who not. In order to derive the causal conclusion that violent video game play causes desensitisation, longitudinal studies are needed. Methods: Therefore we conducted a longitudinal fMRI intervention study over 16 weeks. Participants were randomly assigned to 1) play a violent video game (Grand Theft Auto 5), 2) perform a social life simulation game (The Sims 3) 30 min/day for 8 weeks, 3) serve as passive control. To assess empathy processing, participants were exposed to painful and non-painful stimuli (e.g. someone cutting a cucumber with or without hurting herself) either as real photographs or video-game like depictions in a 3T MRI scanner before and after the training intervention as well as two months after training. Results: We did not find any evidence for desensitization in the empathy network for pain in the violent video game group at any time point. Conclusions: The present results provide strong evidence against the frequently proclaimed negative effects of playing violent video games and will therefore help to communicate a more realistic scientific perspective of the effects of violent video gaming in real life

Randomized parcellation based inference.

International audienceNeuroimaging group analyses are used to relate inter-subject signal differences observed in brain imaging with behavioral or genetic variables and to assess risks factors of brain diseases. The lack of stability and of sensitivity of current voxel-based analysis schemes may however lead to non-reproducible results. We introduce a new approach to overcome the limitations of standard methods, in which active voxels are detected according to a consensus on several random parcellations of the brain images, while a permutation test controls the false positive risk. Both on synthetic and real data, this approach shows higher sensitivity, better accuracy and higher reproducibility than state-of-the-art methods. In a neuroimaging-genetic application, we find that it succeeds in detecting a significant association between a genetic variant next to the COMT gene and the BOLD signal in the left thalamus for a functional Magnetic Resonance Imaging contrast associated with incorrect responses of the subjects from a Stop Signal Task protocol

Functional polymorphism in the neuropeptide Y gene promoter (rs16147) is associated with serum leptin levels and waist-hip ratio in women

OBJECTIVE: The neuropeptide-Y (NP-Y) gene is a strong candidate gene in the pathophysiology of obesity-linked behavior, and several single-nucleotide polymorphisms of NP-Y have already been linked to body weight and appetite. However, the results from current studies remain inconclusive. The aim of the present study was to test whether a certain functional genetic variant (SNP rs16147) in the NP-Y promoter gene is associated with serum leptin levels and body fat distribution. METHOD: We genotyped and measured the serum leptin levels of the NP-Y rs16147 polymorphism in 1,097 Caucasian subjects in the context of a population-based, case-control multicenter study. We measured weight, height and waist circumference, from which we then calculated BMI and waist-to-hip ratio (WHR). RESULTS: We found the CT-genotype of the SNP rs16147 to be significantly associated with lower WHRs and higher serum leptin levels in women, compared to homozygote gene carriers. No association between rs16147, WHR and serum leptin levels was found in men. CONCLUSION: Our results provide evidence that the functionally relevant SNP in the NP-Y promoter gene affects body fat distribution and serum leptin levels in women, pointing towards possible behavioral effects of NPY in obesity

Reduced Sensitivity to Non-Fear-Related Stimulus Changes in Panic Disorder

Panic disorder (PD) is associated with increased body vigilance and reduced cognitive resources directed at non-fear-related stimuli, particularly in the absence of stimulus-rich environments. To date, only few studies have investigated whether this deficit in PD is reflected in reduced mismatch negativity (MMN), an event-related potential indexing preattentive sensitivity to unexpected stimulus changes. We tested 35 patients affected by PD and 42 matched healthy controls in an oddball paradigm, using frequency and duration deviant stimuli to measure auditory MMN. PD patients displayed reduced duration MMN amplitudes in comparison to healthy controls. No group differences were detected for duration MMN latency, as well as frequency MMN indices. Results support the notion of reduced larly with regard to the preattentive processing of sound duration deviants. Additionally, our findings are in line with clinical studies reporting divergent deficits in preattentive processing of frequency and duration deviants

GABRB1 Single Nucleotide Polymorphism Associated with Altered Brain Responses (but not Performance) during Measures of Impulsivity and Reward Sensitivity in Human Adolescents.

Variations in genes encoding several GABAA receptors have been associated with human drug and alcohol abuse. Among these, a number of human studies have suggested an association between GABRB1, the gene encoding GABAA receptor β1 subunits, with Alcohol dependence (AD), both on its own and comorbid with other substance dependence and psychiatric illnesses. In the present study, we hypothesized that the GABRB1 genetically-associated increased risk for developing alcoholism may be associated with impaired behavioral control and altered sensitivity to reward, as a consequence of altered brain function. Exploiting the IMAGEN database (Schumann et al., 2010), we explored in a human adolescent population whether possession of the minor (T) variant of the single nucleotide polymorphism (SNP) rs2044081 is associated with performance of tasks measuring aspects of impulsivity, and reward sensitivity that are implicated in drug and alcohol abuse. Allelic variation did not associate with altered performance in either a stop-signal task (SST), measuring one aspect of impulsivity, or a monetary incentive delay (MID) task assessing reward anticipation. However, increased functional magnetic resonance imaging (fMRI) blood-oxygen-level dependent (BOLD) response in the right hemisphere inferior frontal gyrus (IFG), left hemisphere caudate/insula and left hemisphere inferior temporal gyrus (ITG) during MID performance was higher in the minor (T) allelic group. In contrast, during SST performance, the BOLD response found in the right hemisphere supramarginal gyrus, right hemisphere lingual and left hemisphere inferior parietal gyrus indicated reduced responses in the minor genotype. We suggest that β1-containing GABAA receptors may play a role in excitability of brain regions important in controlling reward-related behavior, which may contribute to susceptibility to addictive behavior