Association between urban upbringing and functional brain connectivity in schizophrenia.

Background: Environmental factors considerably influence the development of the human cortex during the perinatal period, early childhood, and adolescence. Urban upbringing in the first 15 years of life is a known risk factor for schizophrenia (SCZ). Though the risk of urban birth and upbringing is well-examined from an epidemiological perspective, the biological mechanisms underlying urban upbringing remain unknown. The effect of urban birth and upbringing on functional brain connectivity in SCZ patients is not yet examined. Methods: This is a secondary data analysis of three studies that included 87 patients with SCZ and 70 healthy volunteers (HV) aged 18 to 50 years. We calculated the developmental urbanicity index using a validated method in earlier studies. Following standard pre-processing of resting functional magnetic resonance imaging (fMRI) scans, seed-return on investment (ROI) functional connectivity analysis was performed. Results: The results showed a significant association between urban birth and upbringing on functional connectivity in SCZ patients and HV (P < 0.05). In SCZ patients, connections from the right caudate, anterior cingulate cortex, left and right intracalcarine cortices, left and right lingual gyri, left posterior parahippocampal cortex to the cerebellum, fusiform gyri, lateral occipital cortex, and amygdala were significantly associated with the urbanicity index (P < 0.05). Conclusions: These study findings suggest a significant association between urban birth and upbringing on functional brain connectivity in regions involved in reward processing and social cognition in SCZ. Assessment of social cognition could have implications in developing an in-depth understanding of this impairment in persons with SCZ.

Effect of Intranasal Oxytocin on Resting-state Effective Connectivity in Schizophrenia.

OBJECTIVES: Evidence from several lines of research suggests the critical role of neuropeptide oxytocin in social cognition and social behavior. Though a few studies have examined the effect of oxytocin on clinical symptoms of schizophrenia, the underlying neurobiological changes are underexamined. Hence, in this study, we examined the effect of oxytocin on the brain's effective connectivity in schizophrenia. METHODS: 31 male patients with schizophrenia (SCZ) and 21 healthy male volunteers (HV) underwent resting functional magnetic resonance imaging scans with intra-nasal oxytocin (24 IU) and placebo administered in counterbalanced order. We conducted a whole-brain effective connectivity analysis using a multivariate vector autoregressive granger causality model. We performed a conjunction analysis to control for spurious changes and canonical correlation analysis between changes in connectivity and clinical and demographic variables. RESULTS: Three connections, sourced from the left caudate survived the FDR correction threshold with the conjunction analysis; connections to the left supplementary motor area, left precentral gyrus, and left frontal inferior triangular gyrus. At baseline, SCZ patients had significantly weaker connectivity from caudate to these three regions. Oxytocin, but not placebo, significantly increased the strength of connectivity in these connections. Better cognitive insight and lower negative symptoms were associated with a greater increase in connectivity with oxytocin. CONCLUSIONS: These findings provide a preliminary mechanistic understanding of the effect of oxytocin on brain connectivity in schizophrenia. The study findings provide the rationale to examine the potential utility of oxytocin for social cognitive deficits in schizophrenia.

Association between retinal vascular caliber and brain structure in schizophrenia.

OBJECTIVE: Several lines of research in the last decade have indicated the potential utility of retina as a window to the brain. Emerging evidence suggests abnormalities in retinal vascular caliber in schizophrenia. However, the relationship between retinal vascular measures and brain structure has not been examined in schizophrenia to date. Hence, we examined the relationship between retinal vasculature measured using fundus photography and brain structure measured using magnetic resonance imaging. METHOD: We recruited 17 healthy volunteers and 20 patients with schizophrenia. Using a non-mydriatic camera, we captured the images for left and right eyes separately and retinal vascular calibers were calculated using a semi-automated software package. Whole-brain anatomical T1 MPRAGE images were acquired using a 3-Tesla MRI scanner. Whole-brain and regional volume and cortical thickness were calculated using the Freesurfer software package. We used FreeSurfer's QDEC interface to compute vertex-by-vertex for analysis of the volume and cortical thickness. The relation between brain volume, cortical thickness, and retinal vascular caliber was examined using partial correlation and regression analysis. RESULTS: There was a significant negative correlation between average CRVE and global cortical mean thickness in schizophrenia but not in healthy. In schizophrenia patients, there was a significant negative correlation between average CRVE and cortical thickness in frontal regions - left rostral middle frontal, left superior frontal, and right caudal middle frontal gyri and posterior brain regions - left lateral occipital gyrus and left posterior cingulate cortex. DISCUSSION: The findings of the study suggest potential utility of retinal venular diameter as a proxy marker to abnormal neurodevelopment in schizophrenia.

Add on yoga treatment for negative symptoms of schizophrenia: A multi-centric, randomized controlled trial.

The efficacy of antipsychotic medications in the treatment of negative symptoms of schizophrenia is modest at best. Preliminary studies suggest the beneficial effects of add on Yoga, a traditional Indian practice, in the treatment of schizophrenia. Hence, in this study, we examined the efficacy of yoga as an add-on treatment for negative symptoms of schizophrenia in a randomized, wait-list controlled design from two clinical institutes in south India. 89 patients (age - 34.20 ± 8.06 years; education - 14.22 ± 2.69 years; 28 females) were randomized into the add-on yoga or treatment as usual (TAU - wait-list control) group. Patients had a mean illness duration of 10.97 ± 7.24 years with an age at onset of 23.34 ± 5.81 years. Central block randomization was followed to ensure concealed allocation. Participants randomized to the yoga treatment group attended 12 supervised yoga training sessions over two weeks and practiced yoga sessions at home for the subsequent 10 weeks. 64 patients completed the trial. An intent to treat analysis was conducted with 89 participants using a linear mixed model. Improvement in negative symptoms was our primary outcome measure. The two groups were matched on demographic variables and baseline psychopathology severity. Participants in the add-on yoga group had significantly greater improvement in negative symptoms (SANS baseline: 49.13 ± 2.30; 12-weeks follow up: 31.55 ± 2.53) compared to the TAU group (SANS baseline: 51.22 ± 2.40; 12-weeks follow up: 45.30 ± 2.93; t = 3.36; p = 0.006; Cohen's d-0.65). The current study findings suggest the efficacy of yoga as an add-on treatment for negative symptoms of schizophrenia. The effectiveness of yoga practice as a regular clinical intervention for patients needs to be explored in future studies by integrating yoga services along with other clinical services.

Examination of social decision making in patients with schizophrenia using ultimatum game.

Intact decision-making skills in the social context are essential for optimal functioning in the community. Despite its significance, social decision making in schizophrenia (SCZ) has not been adequately examined. Hence, we examined social decision making in SCZ using the Ultimatum Game(UG), a neuroeconomic paradigm that involves financial transactions between a proposer and a responder to split a sum of money between them. Thirty male patients with a diagnosis of schizophrenia as per DSM-IV (age = 30 ± 7.08) and thirty age-matched healthy male volunteers (HV;age = 28.48 ± 3.74) participated in the study. All participants functioned as responders and had to either accept or reject offers made by an anonymous proposer. We also examined whether the gender or emotional expression of the proposer influenced acceptance rates. SCZ had significantly lower acceptance rates than HV for slightly unequal offers (t = 3.94, p = < 0.0001). However, there was no significant difference between SCZ and HV for other offers. Gender and emotional expression of the proposer did not significantly influence the outcome. These results suggest aberrant social decision making and increased inequity aversion in patients with SCZ. The difficulty in incorporating social components while engaging in financial interactions could have important implications for rehabilitation, functional recovery, and successful community living in SCZ.

Cultural differences and neural correlates of cognitive insight in schizophrenia.

Cognitive insight refers to a person's ability to examine their psychotic experiences and the inferences they draw from these experiences. Several studies suggest that cultural factors influence cognitive insight and the processes involved therein; a few studies have suggested differences between Western and Asian societies. However, there are no studies on cognitive insight and its neural correlates in non-Western populations. Hence, we examined factor structure of Beck's cognitive insight scale (BCIS) in a large sample of patients with schizophrenia (SCZ) and healthy volunteers (HV) from India and assessed the relationship between cortical thickness and cognitive insight. We recruited 240 participants (SCZ-140; HV-100). Of these, 58 participants (SCZ-33; HV-25) underwent magnetic resonance imaging. We found a three-factor structure for BCIS which is different from the original two factor structure; self-reflection (SR) of original two-factor structure was sub-divided into- SR1, introspection and SR2, openness to feedback. There was a significant difference between HV and SCZ in the new factors, SR1 and SR2 but not in the original SR factor. Difference was also seen on MRI analysis; while there was a significant positive correlation between original SR factor and thickness of right posterior cingulate cortex, SR2 was positively correlated with thickness of left ventrolateral prefrontal cortex. The difference in factor structure in Indian participants and their distinct neural correlates point to cultural differences in cognitive insight. While in western societies the constructs of introspection and openness to feedback might integrate, they might be separate entities in Asian population.

Facial emotion recognition, socio-occupational functioning and expressed emotions in schizophrenia versus bipolar disorder.

Facial emotion recognition deficits have been consistently demonstrated in patients with severe mental disorders. Expressed emotion is found to be an important predictor of relapse. However, the relationship between facial emotion recognition abilities and expressed emotions and its influence on socio-occupational functioning in schizophrenia versus bipolar disorder has not been studied. In this study we examined 91 patients with schizophrenia and 71 with bipolar disorder for psychopathology, socio occupational functioning and emotion recognition abilities. Primary caregivers of 62 patients with schizophrenia and 49 with bipolar disorder were assessed on Family Attitude Questionnaire to assess their expressed emotions. Patients of schizophrenia and bipolar disorder performed similarly on the emotion recognition task. Patients with schizophrenia group experienced higher critical comments and had a poorer socio-occupational functioning as compared to patients with bipolar disorder. Poorer socio-occupational functioning in patients with schizophrenia was significantly associated with greater dissatisfaction in their caregivers. In patients with bipolar disorder, poorer emotion recognition scores significantly correlated with poorer adaptive living skills and greater hostility and dissatisfaction in their caregivers. The findings of our study suggest that emotion recognition abilities in patients with bipolar disorder are associated with negative expressed emotions leading to problems in adaptive living skills.

Social cognition intervention in schizophrenia: Description of the training of affect recognition program - Indian version.

Social cognition refers to mental operations involved in processing of social cues and includes the domains of emotion processing, Theory of Mind (ToM), social perception, social knowledge and attributional bias. Significant deficits in ToM, emotion perception and social perception have been demonstrated in schizophrenia which can have an impact on socio-occupational functioning. Intervention modules for social cognition have demonstrated moderate effect sizes for improving emotion identification and discrimination. We describe the Indian version of the Training of Affect Recognition (TAR) program and a pilot study to demonstrate the feasibility of administering this intervention program in the Indian population. We also discuss the cultural sensibilities in adopting an intervention program for the Indian setting. To the best of our knowledge this is the first intervention program for social cognition for use in persons with schizophrenia in India.