Cerebral cortex schizophrenia

Montel H, Starke K, Taube HD (1975) Morphine tolerance and dependence in noradrenaline neurons of the rat cerebral cortex. Naunyn-Schmiedeberg s Arch Pharmacol 258 415-26 Potkin SG, Saha AR, Kujawa MJ, Carson WH, Ali M, Stock E, Strinfellow J, Ingenito G, Marder SR (2003) Aripiprazole, an antipsychotic with a novel mechanism of action and risperidone vs. placebo in patients with schizophrenia and psychoaffective disorder. Arch Gen Psychiat 60 681-90... 

Eastwood SL, Cairns NJ, Harrison PJ. 2000. Synaptophysin gene expression in schizophrenia. Investigation of synaptic pathology in the cerebral cortex. Br J Psychiatry 176 236-242. 

Such imbalanced antioxidant systems in schizophrenia could lead to oxidative stress- and ROS-mediated injury as supported by increased lipid peroxidation products and reduced membrane polyunsaturated fatty acids (PUFAs). Decrease in membrane phospholipids in blood cells of psychotic patients (Keshavan et al., 1993 Reddy et al., 2004) and fibroblasts from drug-naive patients (Mahadik et al., 1994) as well as in postmortem brains (Horrobin et al., 1991) have indeed been reported. It has also been suggested that peripheral membrane anomalies correlate with abnormal central phospholipid metabolism in first-episode and chronic schizophrenia patients (Pettegrewet al., 1991 Yao et al., 2002). Recently, a microarray and proteomic study on postmortem brain showed anomalies of mitochondrial function and oxidative stress pathways in schizophrenia (Prabakaran et al., 2004). Mitochondrial dysfunction in schizophrenia has also been observed by Ben-Shachar (2002) and Altar et al. (2005). As main ROS producers, mitochondria are particularly susceptible to oxidative damage. Thus, a deficit in glutathione (GSH) or immobilization stress induce greater increase in lipid peroxidation and protein oxidation in mitochondrial rather than in cytosolic fractions of cerebral cortex (Liu et al., 1996). 

Raedler TJ, Knable MB, Weinberger DR. 2000. Schizophrenia as a developmental disorder of the cerebral cortex. Curr Opin Neurobiol 8 157-161. 

Currently, there is a commonly expressed view that decreased cortical volume in schizophrenia is the result of a reduction of cortical neuropil, presumably due to an atrophy of neural dendrites and axons (e.g., (Selemon and Goldman-Rakic, 1999)). A direct prediction of this model is that neuron density should be increased in proportion to the decrease in cortical volume. While there is some evidence for increased density in the prefrontal cortex (Selemon et al., 1995, 2003), there are also a number of negative findings (Akbarian et al., 1995 Cotter et al., 2002 Cullen et al., 2006 Thune et al., 2001). In auditory areas, the available studies have not shown an altered neuron density, even with hemispheric comparisons (Beasley et al., 2005 Cotter et al., 2004 Smiley et al., 2002). An alternative hypothesis is that reduced cortical volume is accompanied by a loss of neuron number, but this issue remains to be addressed in the auditory cortex. In other brain areas, there is some evidence for decreased neuron number, although the differences are often subtle and statistically nonsignificant (Benes et al., 1986 Dorph-Petersen et al., 2007 Stark et al., 2004 Thune et al., 2001). Changes in total cell number in the cerebral cortex have been difficult to determine, because these measurements require a clearly identified reference volume. 

Kuperberg GR, Broome MR, McGuire PK, David AS, Eddy M, et al. 2003. Regionally localized thinning of the cerebral cortex in schizophrenia. Arch Gen Psychiatry 60(9) 878-888. 

Around the central core of the brain are a number of structures that collectively make up the deep brain nuclei, which are organized into the limbic system, and the basal nuclei. These systems are closely connected to the thalamus, the hypothalamus and the sensory and motor areas of the cerebral cortex. The limbic system is concerned with emotions, behaviour and memory and the basal nuclei are concerned with control of movement, although there is overlap between the two. Malfunction of these areas is implicated in disorders such as Parkinson s disease and schizophrenia. 

In studies of 5-HT receptor density in post-mortem brain tissues from patients with schizophrenia, Bennett et al. found a decrease in [ HJlysergic acid diethylamide (LSD) binding in Brodmann areas 6,8,11,44, and 47. LSD produces hallucinations by disrupting the action of the neurotransmitter serotonin, although precisely how it does this is unclear. LSD acts on certain groups of serotonin receptors, especially in the cerebral cortex and locus ceruleus. 

One of the most prominent positive symptoms in schizophrenia is the auditory hallucinations that are perceived as distinct voices emanating from outside the individual. Regional cerebral-blood-flow studies in patients experiencing auditory hallucinations reveal activation of the associational auditory cortex during the episodes of hallucinations, but not in their absence. One theory holds that auditory hallucinations occur as a consequence of the inability of individuals with schizophrenia to monitor effectively their inner speech. fMRI studies suggest that... 

Weinberger, D. R., Berman, K. F. and Zee, R. F. Physiologic dysfunction of dorsolateral prefrontal cortex in schizophrenia. I. Regional cerebral blood flow evidence. Arch. Gen. Psychiatry 43 114-124,1986. 

Regional Cerebral Blood Flow Mapping. Such mapping techniques use radioactive probes (e.g., xenon-13) to delineate perfusion of cortical structures. For example, they have generally confirmed prefrontal cortex dysfunction in schizophrenia ( 37). 

Liddle PF, Friston KJ, Frith CD, Hirsch SR, Jones T, Frackowiak RS (1992) Patterns of cerebral blood flow in Schizophrenia. Br J Psychiatry 160 179-186 Lidow MS, Wang F, Cao Y, Goldman-Rakic PS (1998) Layer V neurons bear the majority of mRNAs encoding the five distinct dopamine receptor subtypes in the primate prefrontal cortex. Synapse 28(1) 10-20... 

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