LAUSR

Abstract Background Urban 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. Methods We 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. Results In 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. Discussion The 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.