الفهرس 
Cognitive dysfunction in schizophreniaOnly 14 pages are availabe for public view
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Abstract
The last 20 years have brought about a virtual explosion of studies on brain connectivity in schizophrenia. These studies have shown that white matter organization is disrupted in schizophrenia, and that these disruptions have important implications for psychiatric symptomatology and sensory and cognitive deficits seen in the disorder. Recent studies showing that variations in white matter integrity are associated with genetic variants (e.g., in neuregulin) that have been implicated in schizophrenia offer an exciting and important avenue to better understand the mechanism of these abnormalities, as do converging neuro-pathological studies of white matter (Dwork et al., 2012).
While gray matter deficits in schizophrenia have been widely reported (Kim et al., 2003; Lui et al., 2009a,b; Whitford et al., 2005), only a few studies have focused on cerebral white matter, and they have produced inconsistent results. However, studying the white matter is crucial to understanding the neurobiological substrate of schizophrenia, because the abnormalities in white matter may play a fundamental role in the neurobehavioral manifestations of schizophrenia (Guo et al., 2012).
Furthermore, one of the debated hypotheses of the etiopathogenesis of schizophrenia is the dysfunction in the neural connectivity (misconnection) of different cerebral areas or the neural circuitry (Andreasen et al., 1999; McGuire and Frith, 1996).
In recent decades, diffusion tensor imaging (DTI), a magnetic resonance imaging technique sensitive to the orientation of water diffusion restricted within the neuron sheath and myelination, has been widely used in psychiatric research. One of the commonly used DTI measures is fractional anisotropy (FA), which is thought to reflect the anatomical features of neural fibers, such as the axon caliber, fiber density and myelination (Scholz et al., 2009).
At present there is substantial DTI data available on the early phase of schizophrenia from the current study and other research groups. Taking the current study results and the results of other studies together, DTI abnormalities in first-episode patients appear less robust than in chronic patients, suggesting that progression to more extensive abnormalities occurs after illness onset. There are also indications for accelerated aging effects in schizophrenia. These findings suggest the possibility that early intervention may help to preserve white matter integrity (Peters et al., 2010)
Patients with schizophrenia show deficits in several neurocognitive domains. However, the relationship between white matter integrity and performance in these domains is poorly understood.
Severity of symptoms and performance of cognitive functions (attention, executive function, memory) were examined and their relationships with fractional anisotropy at the regions of interest were examined by using voxelwise correlation analyses. In each case, better performance on these tasks was associated with higher levels of fractional anisotropy in task-relevant regions.
Cortical anatomical connectivity has been examined in vivo using diffusion tensor imaging, which measures the directionality and magnitude of diffusion in tissues. With barriers to diffusion, including myelin, cell membranes, or organized white matter tracts, diffusion will be greater parallel than perpendicular to the long axis of fibers (anisotropic diffusion). The degree of diffusion anisotropy can be measured with fractional anisotropy, which has been found to be reduced in white matter in most studies of schizophrenia. This reduction has been interpreted as evidence of impaired white matter integrity, which is consistent with findings of reduced expression of myelin-related genes and a reduced number of oligodendrocytes (Hof et al., 2002).
The current study aimed to:
4) To assess the deficit in the cognitive function domains in 1st episode Schizophrenic patients, (executive function, attention and verbal memory).
5) To investigate the white matter integrity in the region of interest related to such cognitive domains using the diffusion tensor imaging.
6) To investigate the white matter integrity in the region of interest related to positive and negative symptoms of Schizophrenia.
We hypothesized that there is a significant correlation between the defect in the neurocognitive tasks performance, symptoms profile and the white matter integrity, as measured by diffusion tensor image in patients with first episode schizophrenia.
The present study evaluated collectively 30 patients with first episode schizophrenia and 30 controls. The study sample was selected from patients admitted in the Institute of psychiatry, Ain-Shams University.
We obtained an informed consent and inclusion criteria were insured before the study which included age between 18-45 years of Egyptian male and female subjects, their IQ level is average or above average, diagnosed as first episode Schizophrenia and didn’t receive any psychotropic drugs before or if previously treated with a total life time exposures less than 6 weeks.
The tools were carefully selected to serve for the purpose of the study, this included Structured Clinical Interview for DSM-IV (SCIDI), positive and negative syndrome scale (PANSS), Wechsler Adult Intelligence Scale (WAIS), Wechsler Memory Scale (WMS), Wisconsin Card Sorting Test (WCST), Continuous Performance Test (CPT) and diffusion tensor image (DTI).
All data gathered were recorded, tabulated and transferred on Statistical Package for Social Sciences (SPSS) Version 16, using personal computer and the suitable statistical parameters were used. Results were displayed to answer questions raised in the hypothesis of this study.
The following results were obtained:
• Patients group have a lower IQ mean compared to healthy control.
• Patients have significant impairment in all cognitive functions (attention, executive functions, memory) compared to healthy control.
• Patients have significant dysfunction in the white matter integrity in all regions of interest (anterior cingulate cortex, uncinate fasciculus, superior longitudinal fasciculus and insula) bilaterally compared to healthy control.
• There is a significant correlation between dysfunction in the white matter integrity in right anterior cingulate cortex and sustained attention.
• There is a significant correlation between dysfunction in the white matter integrity in right anterior cingulate cortex and executive functions.
• There is a significant correlation between dysfunction in the white matter integrity in the uncinate fasciculus bilaterally and memory functions
• There is no correlation between dysfunction in the white matter integrity in the superior longitudinal fasciculus, insula bilaterally and cognitive dysfunctions
• There is no correlation between dysfunction in the white matter integrity in the anterior cingulate cortex, uncinate fasciculus and severity of symptoms.
• There is a significant negative correlation between the dysfunction in the white matter integrity in the left superior longitudinal fasciculus and positive symptoms.
• So the deterioration in symptoms associated with the dysfunction in the white matter integrity in the superior longitudinal fasciculus.
• There is a significant correlation between the dysfunction in the white matter integrity in the left insula and severity of negative symptoms and deterioration.
• There were certain areas concerned with cognitive function deterioration in schizophrenia ( anterior cingulate cortex , uncinate fasciculus) while other areas (superior longitudinal fasciculus, insula) were concerned with symptoms formation.
• So the cognitive dysfunction in schizophrenia is a separate entity and not related or secondary to other symptoms.