Endophenotypes For Schizophrenia On Cognition,Brain Gray Matter And White Matter

ObjectiveTo examine difference of cognitive function, brain gray matter volume and white matter integrity among drug-naive, first-episode schizophrenia (FES) patients, schizophrenic healthy siblings and healthy controls, and to explore endophenotypes for schizophrenia on cognition, brain gray and white matter matter.Methods1. A battery of cognitive assessment tools was used to measure seven cognitive domains in matched groups consisting of56subjects each. Cognitive tests included the grooved pegboard test (GPT), the category fluency test (CFT), the trail making test A (TMT-A), the Wechsler memory scale-â…¢ spatial span test (WMS-â…¢ SST), the Hopkins verbal learning test-revised (HVLT-R), the brief visuospatial memory test-revised (BVMT-R), the paced auditory serial addition test (PASAT), and the Wisconsin card sorting test-64cards version (WCST-64).2. We studied51antipsychotic drug-naive, first-episode schizophrenia (FES) patients,45schizophrenic unaffected siblings (25with relation to enrolled patients) and59healthy controls with three-dimensional structural magnetic resonance imaging (3D-MRI). These data were used voxel-based morphometry (VBM) to investigate differences in gray matter volumes.3. We studied51antipsychotic drug-naive, first-episode schizophr-enia (FES) patients,45schizophrenic unaffected siblings (25with relation to enrolled patients) and59healthy controls with diffusion tensor imaging (DTI). These data were used voxel-based analysis (VBA) to investigate differences in fractional anisotropy (FA) values of white matter.Results1. Comparison of cognitive performancesThe performances of FES patients were inferior to normal controls on all neuropsychological tests, while siblings were lower than healthy controls in many of the same tasks. Patients'performances were lower than siblings' on all tests except for the CFT, the WMS-III SST backward test, and four subtsets of the WCST-64. FES patients and their siblings had significantly poorer performances than controls in the CFT and four subtsets of the WCST-64,and these tests'magnitude of ES ranged from moderate to large, and the95%CIs of these tests did not include zero.2. Comparison of gray matter volumesCompared with the normal controls, brain gray matter volume of the patients with FES was significantly reduced brain regions in the bilateral hippocampus and parahippocampal, the bilateral superior and middle temporal gyri, the left prefrontal cortex (PFC), insula and fusiform gyrus,the right amygdala (P<0.05, FEW correction); siblings with relation to enrolled patients had gray matter volume reduction in the left superior temporal gyrus(P<0.001, uncorrectoin). Patients had gray matter volume reduction in the right hippocampus and parahippocampal gyri, amygdala, the left middle temporal gyrus and middle occipital gyrus compared with siblings relation to enrolled patients (P<0.05, FEW correction).3. Comparison of white matter integrityCompared with the normal controls, White matter FA values of patients was significantly reduced brain regions of the right anterior cingulate gyrus, thalamus, hypothalamus,lentiform nucleus and caudate nucleus (P<0.05, FEW correction), the left PFC, parahippocampal gyrus, superior temporal gyrus, amygdala, olfactory tract, the posterior cingulate region and the corpus callosum(P<0.05, FDRcorrection), siblings with relation to enrolled patients had white matter FA values reduction in the posterior cingulate region and the corpus callosum (P<0.001, uncorrectoin). Patients had white matter FA values reduction in the bilateral temporal on the back area, occipital lobe, the left prefrontal lobe, parietal lobe and corpus callosum compared with siblings relation to enrolled patients (P<0.001, uncorrectoin). Conclusions1. FEP patients in drug-naive exhibited pronounced impairment of fine motor skills, speed of processing, attention,working memory, verbal memory, visual memory and executive function, while siblings exhibited deficits intermediate between those of schizophrenic patients and the control group. Semantic fluency function and executive function may be potential endophenotypes for schizophrenia.2. FEP patients in drug-naive mainly showed brain gray matter volume reduction in PFC, lateral temporal lobe, limbic lobe, and reduction of gray matter volume of Schizophrenic uneffected siblings were intermediate between those of schizophrenic patients and the controls. Schizophrenia might be a frontotemporal limbic circuit disorder, gray matter of the lateral temporal lobe may be a key point in this circuit, whose structural abnormality may be a potential endophenotype for schizophrenia:3. FEP patients in drug-naive mainly showed reduced white matter integrity in PFC, lateral temporal lobe, limbic lobe, and thalamus,and reduction of white matter integrity of Schizophrenic uneffected siblings were intermediate between those of schizophrenic patients and the controls. Schizophrenia might be a progressive cortico-striato-thalamic loop disorder, white matter of the posterior cingulum area may be a key point in this loop, whose structural abnormality may be a potential endophenotype for schizophrenia.