A number of studies have suggested that the α-7-nicotinic receptor D15S1360 polymorphism is associated with schizophrenia and a deficiency in the normal inhibition of the P50 auditory-evoked response. Schizophrenia patients and some of their unaffected relatives show a failure of inhibition in their 50-ms response to the second of a pair of tones. Biochemical studies have suggested that the α7 nicotinic acetylcholine receptor is involved in this sensory gating deficit. Furthermore, high-dose nicotine transiently normalizes the abnormality in P50 inhibition in schizophrenic patients and in their relatives. Schizophrenic patients are unusually heavy smokers, and up to 85% of hospitalized schizophrenic patients smoke. This rate is three times higher than the general population, and may represent an attempt to self-medicate through this pathophysiologic mechanism. Despite schizophrenics' extremely heavy nicotine use, nicotinic receptor genes have not been previously investigated in relation to smoking in schizophrenia. In this study, we hypothesized that the D15S1360 marker is associated with smoking in patients with schizophrenia. We found an association between the homozygous 113 bp allele and smoking risk (χ2=10.37, 3 df, p=0.015). Although this novel finding requires replication, it suggests that further study into the relationship between schizophrenia and nicotine system genes is warranted.
Objective: To develop a virtual reality platform that would serve as a functionally meaningful measure of cognition in schizophrenia that would complement standard batteries of cognitive tests during clinical trials for cognitive treatments in schizophrenia, be amenable to human neuroimaging research, yet lend itself to neurobiological comparison with rodent analogues. Method: Thirty-three patients with schizophrenia and 33 healthy controls matched for age, sex, video gaming experience and education completed eight rapid, single-trial virtual navigation tasks within a naturalistic virtual city. Four trials tested their ability to find different targets seen during the passive viewing of a closed path that led them around different city blocks. Four subsequent trials tested their ability to return to four different starting points after viewing a path that took them several blocks away from the starting position. Results: Individuals with schizophrenia had difficulties in way-finding, measured as distance travelled to find targets previously encountered within the virtual city. They were also more likely not to notice the target during passive viewing, less likely to find novel shortcuts to targets and more likely to become lost and fail completely in finding the target. Total travel distances across all eight trials strongly correlated (negatively) with neurocognitive measures and, for 49 participants who completed the Quality of Life Scale, psychosocial functioning. Conclusion: Single-trial, goal-directed navigation in a naturalistic virtual environment is a functionally meaningful measure of cognitive functioning in schizophrenia.
Abstract Background Interneuron deficits are one of the most consistent findings in post-mortem studies of schizophrenia patients and are likely important in the cognitive deficits associated with schizophrenia. Disrupted-in-Schizophrenia 1 (DISC1), a strong susceptibility gene for schizophrenia and other mental illnesses, is involved in neurodevelopment, including that of interneurons. However, the mechanism by which DISC1 regulates interneuron development remains unknown. In this study, we analyzed interneuron histology in the Disc1 -L100P single point mutation mouse, that was previously shown to have behavioral abnormalities and cortical developmental defects related to schizophrenia. Results We sought to determine whether a Disc1 -L100P point mutation in the mouse would alter interneuron density and location. First, we examined interneuron position in the developing mouse cortex during embryonic days 14–16 as an indicator of interneuron tangential migration, and found striking migration deficits in Disc1 -L100P mutants. Further analysis of adult brains revealed that the Disc1 -L100P mutants have selective alterations of calbindin- and parvalbumin-expressing interneurons in the cortex and hippocampus, decreased GAD67/PV co-localization and mis-positioned interneurons across the neocortex when compared to wild-type littermates. Conclusion Our results are consistent with the anomalies seen in post-mortem schizophrenia studies and other Disc1 mutant mouse models. Future research is required to determine the specific mechanisms underlying these cellular deficits. Overall, these findings provide further evidence that DISC1 participates in interneuron development and add to our understanding of how DISC1 variants can affect susceptibility to psychiatric illness.
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