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Abstract 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.

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.

Abstract Background Decision making in a social situation is an essential aspect for optimal societal functioning. Despite its importance, only a few studies have examined social decision making in schizophrenia (SCZ), a disorder with impairments in several sub-domains of social cognition. One important reason is the difficulty in examining social decision making in lab setting due to its interactive nature. Neuroeconomic paradigms permit simulation of social interaction in a lab setting. In this study we examined social decision making in SCZ using a valid neuroeconomic paradigm, Ultimatum Game (UG) in comparison with healthy volunteers (HV). Methods Thirty male patients with Structured Clinical Interview for DSM-IV (SCID-I) diagnosed SCZ (age=30 + 7.08 years) and thirty male HV (age=28.48 + 3.73 years) participated in the study. Clinical severity was assessed using Positive and Negative Syndrome Scale, Scale for the Assessment of Negative Symptoms, and Calgary Depression Rating Scale. Participants played a previously validated version of Ultimatum game (Güth,W. et.al. J. Econ. Behav. Organ. (1982)) Participants played the role of a responder and had to either accept or reject offers made by an anonymous proposer for sum of money Rs.10/- in each trial. In each trial, one of the six split possibilities (proposer: responder - 9:1, 8:2, 7:3, 6:4, 5:5, 4:6) were offered as split. A total of 48 trials were played with each split played 8 times. The order of splits was randomized. For analysis, the offers were grouped into fair offers (6:4, 5:5, 4:6) or unfair offers (9:1, 8:2, 7:3) as per the previous studies. Data was analyzed using SPSS v 24. Since the data was not normally distributed, Mann-Whitney test was used to examine group differences. Results The groups were matched in age (p=0.48). SCZ had significantly lower acceptance rates for fair offers (median=15.00, range = 13.75 to 16.00) compared to HV (median =16, range = 15 to 16) (U= 311.50; p=0.02). However, there was no significant difference between SCZ (median =13.50, range = 4.00 to 19.75) and HV (median = 11.50, range =6.50 to 26.25) for unfair offers (U= 431.50; p= 0.78). When individual offers were analyzed, lower acceptance rate for 6:4 split was significantly higher (U=291; p=0.01) in SCZ (median =4.00, range =3.00 to 7.00) compared to HV (median =8.00, range =4.75 to 8.00) but not for 5:5 (U=344; p=0.06) or 4:6 (U=349.50; p=0.07). There was no significant correlation between rejection rates and clinical severity scores on PANSS, SANS or CDS. Discussion The results of the study suggest significantly higher rate of lower acceptance in SCZ for slightly unequal offers. While healthy volunteers refused unfair offers but accepted slightly unequal offers as fair, SCZ refused these offers. This indicates SCZ may have a higher threshold to accept division as fair as there was no significant difference when the split was equal or favorable to respondent. Whether these deficits are primary or secondary to deficits in other domains of social cognition, like theory of mind, need to be examined in the future. Considering the importance of economic interactions and social decision making in recovery, findings of the study could have implication in rehabilitation and functional recovery.

Abstract Background Diminished cognitive insight is exhibited by substantial proportion of patients suffering from schizophrenia and is an important determinant of poor treatment adherence. While the clinical correlates of cognitive insight are well examined the neural correlates of cognitive insight is less explored. We examined relation between cortical thickness and cognitive insight in schizophrenia patients. Methods We examined 37 schizophrenia patients in comparison with 19 healthy volunteers. We measured cortical thickness using a high resolution anatomical magnetic resonance image and cognitive insight using Beck’s Cognitive Insight Scale (BCIS). We measured the difference between schizophrenia patients and healthy volunteers using Analysis of covariance and relation between cortical thickness and BCIS scores in schizophrenia patients using stepwise regression analysis. Results Patients had significantly thinner cortices than healthy volunteers in orbitofrontal cortex, superior temporal gyrus, occipital cortex, dorsomedial prefrontal cortex and posterior cingulate cortex. Significant positive correlations were found between self-reflection and cortical thickness in posterior cingulate cortex, dorso-medial frontal gyrus, occipital lobe. Significant negative correlations were observed between self-certainty scores and bilateral Posterior cingulate and orbitofrontal cortex. Discussion We found significant differences in cortical thickness between SCZ and HV in brain regions implicated in cognitive insight. Our findings also suggest higher self-certainty to be associated with thinner cortices in bilateral PCC and OFC. Significant relations between cortical thickness and cortical midline structures supports the critical role of these self-evaluative brain regions in cognitive insight in schizophrenia.

BackgroundUrban birth and upbringing are considered to be risk factors for schizophrenia, but recent studies do not support the same. While several hypotheses are suggested, the pathogenic mechanisms are not known. Notably, no study has examined brain changes, if any, associated with an urban upbringing in schizophrenia. Hence, in this study, we examined the effect of urban upbringing on the cortical gyrification in schizophrenic patients.MethodsWe recruited 108 persons with DSM-IV schizophrenia and 74 healthy volunteers. Study participants underwent clinical assessments using Positive and negative syndrome scale, Calgary depression scale to measure severity of clinical symptoms. All participants were scanned using 3T MRI scanner and a high resolution T1 structural scan was obtained. Cortical gyrification measurements were conducted on these images using Freesurfer software. Statistical maps were generated in Query, design, Estimate, Contrast (QDEC) interface. A Monte Carlo Simulation (MCS) was run for FWE correction with the threshold 1.3 (p<0.05) in QDEC. Participants upbringing place was noted with respect to the place where they lived for the first 15 years of life. Based on Census India of 2011, the places were categorized into 1) rural 2) statutory town and 3) census town. These 3 groups and assigned values 1,2 and 3, respectively, which were then rated for each year of life (1–15) and urbanicity index was calculated using a previously used method (range from 15 to 45). A regression analysis was implemented in QDEC with age, sex, education and demean ICV as covariates to examine the relation between Urban upbringing and cortical gyrification index.ResultsIn the overall population, HV had higher gyrification index in the left superior parietal cortex (p<0.008) than SCZ. There was a significant negative correlations between gyrification index and urbanicity index in left postcentral (p<0.0001), left insula (p<0.0001), left fusiform (p<0.0005), left rostral middle frontal (p<0.01), right supramarginal (p<0.0001), right fusiform (p<0.0001), and right superior temporal (p<0.005) cortices.DiscussionThe results indicate a significant effect of urbanicity on cortical gyrification in patients with SCZ as well as HV. The presence of deficits in frontal areas indicate the likely effect of urban upbringing on growth and maturation of the frontal cortex. Interestingly, the presence of difference in areas implicated in schizophrenia provides support to the possible increased risk of urban upbringing on schizophrenia. The preliminary evidence from this analysis provides the necessary rationale to further examine the impact of urban upbringing on brain structure/ function and the risk of developing schizophrenia.

Background: Despite several neuroimaging studies in the past few years, the exact pathophysiology responsible for the development of bipolar disorder (BD) is still not completely known. Importantly, to the best of our knowledge, no study from India has examined resting state (RS) connectivity abnormalities in BD using regional homogeneity (ReHo). Hence, we examined spontaneous brain activity in patients with BD using RS functional magnetic resonance imaging (RS-fMRI). Aim: The aim of the study is to examine the spontaneous brain activity in patients with BD-I using ReHo approach and RS-fMRI compared to age- and gender-matched healthy control (HC). Materials and Methods: A total of 20 patients with BD and 20 age-, gender-, and education-matched HCs participated in the study. The fMRI data were obtained using 1.5T scanner. RS-fMRI abnormalities were analyzed using ReHo method. Results: Compared to healthy adults, significantly increased ReHo in the BD group was found in the right precuneus, right insula, right supramarginal gyrus, left superior frontal gyrus, right inferior frontal gyrus, right precentral gyrus, and right paracentral lobule. No region had significantly lower ReHo values in BD patients compared to controls. Conclusion: These results suggested that abnormal local synchronization of spontaneous brain activity is present in the frontoparietoinsular region which may be related to the pathophysiology of BD.

Introduction Increasing incidence of fragility fractures has spurred development of protocols, largely focused on peri-operative care, with numerous proven benefits. The purpose of this investigation was to evaluate outcomes of our hip fracture treatment program regarding successful protocol implementation, compliance, effect on subsequent fracture rates, and mortality during the first decade of adoption. Methods A retrospective review identified patients >65 years old with fragility hip fractures between 2010 and 2022. The HiROC (+) cohort consisted of patients who received a “High-Risk Osteoporosis Clinic” (HiROC) referral for bone health evaluation and bisphosphonate initiation as indicated. Additional fracture rates and mortality at 3 years were calculated. Protocol implementation and compliance over the first 10 years was analyzed in the four identified cohorts. Results A total of 1671 fragility hip fractures were identified, with 386 excluded due to insufficient follow-up, with an average age of 81.6 years and a median follow-up of 36.4 months. Of the 1280 included cases, 56% (n = 717) had a HiROC referral placed. HiROC(+) groups had lower subsequent fracture rates at two years, compared to those without referral (28% vs 13%, P < 0.0001) and those completing more steps of the protocol had lower subsequent fracture rates (28% vs 15% vs 13% vs 5%, P < 0.0001). No statistically significant difference was observed between the cohorts for anatomic site of subsequent fractures. Discussion Greater than half of all eligible patients were successfully captured by the protocol. Patients completing more steps of the protocol had lower subsequent fracture rates. Captured patients demonstrated reduced mortality rates when compared to current literature. Conclusion Successful implementation of this geriatric hip fracture protocol was associated with reduced additional fractures and mortality rates. Identifying steps of process failures in the protocol can provide opportunities for increased compliance and reduction in future fracture occurrences.

The aim of the study was to assess the prevalence of oral mucosal lesions among fishermen population in the coastal region of Kutch, Gujarat, India. A descriptive cross-sectional survey was conducted to assess the prevalence of oral mucosal lesions among the 979 fishermen of Kutch District, Gujarat, India. The proforma included information on demographic details, habits (tobacco and alcohol), oral hygiene practices and presence and location of oral mucosal lesions according to World Health Organisation, 2013. Chi-square test was used for comparisons. Confidence level and p-value were set at 95% and 5%, respectively. The majority of study population consumed tobacco and alcohol (88.1%) in some or the other form and used chewsticks (42.9%) for cleaning their teeth. Amongst all, 30.03% of the study subjects suffered from oral mucosal lesions. Leukoplakia (13.8%) was found to be the most prevalent lesion. The most affected sites were lips and vermillion border. The prevalence of oral mucosal lesions was found to be significantly associated with age, gender, oral hygiene practices and adverse habits. Oral mucosal lesions were prevalent among 30.03% of the study population. More detailed studies probing this issue should be conducted and efforts should be directed towards primordial prevention of the conditions.