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Background: Cognitive impairment is a core feature of schizophrenia and has been observed in subjects with and without a family history of schizophrenia. Nonetheless, there is a paucity of research directly contrasting cognitive profiles in schizophrenia patients and normal people where family history is present and those where the family history is absent. Aim: This stydy aimed to compare cognitive functions in patients with schizophrenia who had a family history with those that did not and healthy controls. Materials and Methods: Fifty consecutive schizophrenia patients were assessed on admission and follow-up after 6 months of treatment using a specially prepared pro forma, the Positive and Negative Syndrome Scale, and the PGI Battery of brain dysfunction is the name give to the test. An equal number of age- and sex-matched normal control subjects were also assessed. Results: Visual memory scores in this study show improvement between baseline and follow-up in schizophrenia patients with/without a family history. Both verbal learning and memory increase between baseline and follow-up but do not reach control levels. Reasoning and problem-solving deficits follow a similar pattern and are causative in the inability to adapt to a changing world. Speed of processing shows improvement with treatment. Working memory deficits in patients improve with treatment. Conclusions: In this study, all six cognitive domain scores in schizophrenia improved after 6 months of treatment but did not reach the control population level. Individuals with the highest cognitive deficits in the scales were the ones who had a family history of schizophrenia. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the executive functions in patients with sporadic schizophrenia (SS) and familial schizophrenia (FS), and the executive func- tions in their parents. Methods: The study included 30 patients with FS and their 37 parents with a positive family history of schizophrenia; 30 patients with SS and their 44 parents; 30 controls matched with the patients for gender, age and education, and 40 controls matched with the parents for gender, age and education (211 subjects in total). All the subjects were interviewed with the Structured Clinical Interview for DSM-lV-Axis I (SCID-l). The executive functions were as- sessed using the Verbal Fluency Test (VFT), the Trail Making Test (TMT), the Wisconsin Card Sorting Test (WCST) and the Stroop Test. Results: Patients with FS and their parents, and patients with SS performed significantly worse than their controls on the VFT, TMT, WCST and the Stroop test. There were no statistically significant differences between parents of patients with SS and their controls on any of the tests except for the Stroop color score. FS parents performed significaritly worse than 55 parents on all tests. FS patients performed significantly worse than 55 patients on the VFT, TMT, Stroop test. Conclusion: Previous studies that investigated the cognitive functions of relatives of patients with schizo- phrenia brought out inconsistent results. The present study investigated relatives with and without a family history of schizophrenia separately and found that executive functions were impaired only in parents with a positive family history of schizophrenia. These findings suggest that impairment in executive functions may represent a genetic endophenotype for schizophrenia. [ABSTRACT FROM AUTHOR]

Schizophrenia is a disabling neuropsychiatric disorder of adulthood onset with high heritability. Worldwide collaborations have identified an association of ~270 common loci, with small individual effects and hence weak clinical implications. The recent technological feasibility of exome sequencing enables the identification of rare variants of high penetrance that refine previous findings and improve risk assessment and prognosis. We recruited two multiplex Pakistani families, having 11 patients and 19 unaffected individuals in three generations. We performed genome-wide SNP genotyping, next-generation mate pairing and whole-exome sequencing of selected members to unveil genetic components. Candidate variants were screened in unrelated cohorts of 508 cases, 300 controls and fifteen families (with 51 affected and 47 unaffected individuals) of Pakistani origin. The structural impact of substituted residues was assessed through in silico modeling using iTASSER. In one family, we identified a rare novel microduplication (5q14.1_q14.2) encompassing critical genes involved in glutamate signaling, such as CMYA5, HOMER and RasGRF2. The second family segregates two ultra-rare, predicted pathogenic variants in the GRIN2A (NM_001134407.3: c.3505C>T, (p.R1169W) and in the NRG3 NM_001010848.4: c.1951G>A, (p.E651K). These genes encode for parts of AMPA and NMDA receptors of glutamatergic neurotransmission, respectively, and the variants are predicted to compromise protein function by destabilizing their structures. The variants were absent in the aforementioned cohorts. Our findings suggest that rare, highly penetrant variants of genes involved in glutamatergic neurotransmission are contributing to the etiology of schizophrenia in these families. It also highlights that genetic investigations of multiplex, multigenerational families could be a powerful approach to identify rare genetic variants involved in complex disorders. [ABSTRACT FROM AUTHOR]