Schizophrenia is widely acknowledged as being a syndrome, consisting of an undefined number of di... more Schizophrenia is widely acknowledged as being a syndrome, consisting of an undefined number of diseases probably with differing pathologies. Although studying a syndrome makes the identification of an underlying pathology more difficult; neuroimaging, neuropsychopharmacological and post-mortem brain studies all implicate muscarinic acetylcholine receptors (CHRM) in the pathology of the disorder. We have established that the CHRM1 is selectively decreased in the dorsolateral prefrontal cortex of subjects with schizophrenia. To expand this finding, we wanted to ascertain whether decreased cortical CHRMs might (1) define a subgroup of schizophrenia and/or (2) be related to CHRM1 genotype. We assessed cortical [ 3 H]pirenzepine binding and sequenced the CHRM1 in 80 subjects with schizophrenia and 74 age sex-matched control subjects. Kernel density estimation showed that [ 3 H]pirenzepine binding in BA9 divided the schizophrenia, but not control, cohort into two distinct populations. One of the schizophrenia cohorts, comprising 26% of all subjects with the disorder, had a 74% reduction in mean cortical [ 3 H]pirenzepine binding compared to controls. We suggest that these individuals make up 'muscarinic receptor-deficit schizophrenia' (MRDS). The MRDS could not be separated from other subjects with schizophrenia by CHRM1 sequence, gender, age, suicide, duration of illness or any particular drug treatment. Being able to define a subgroup within schizophrenia using a central biological parameter is a pivotal step towards understanding the biochemistry underlying at least one form of the disorder and may represent a biomarker that can be used in neuroimaging.
It is known that individuals with schizophrenia exhibit signs of impaired face processing, howeve... more It is known that individuals with schizophrenia exhibit signs of impaired face processing, however, the exact perceptual and cognitive mechanisms underlying these deficits are yet to be elucidated. One possible source of confusion in the current literature is the methodological and conceptual inconsistencies that can arise from the varied treatment of different aspects of face processing relating to emotional and non-emotional aspects of face perception. This review aims to disentangle the literature by focusing on the performance of patients with schizophrenia in a range of tasks that required processing of non-emotional features of face stimuli (e.g., identity or gender). We also consider the performance of patients on non-face stimuli that share common elements such as familiarity (e.g., cars) and social relevance (e.g., gait). We conclude by exploring whether observed deficits are best considered as "face-specific" and note that further investigation is required to properly assess the potential contribution of more generalized attentional or perceptual impairments.
AbstractÐA number of studies suggested that cannabis use can cause or exacerbate psychoses and ma... more AbstractÐA number of studies suggested that cannabis use can cause or exacerbate psychoses and may increase the risk of developing schizophrenia. These ®ndings suggest that changes in the cannabinoid system of the brain may be involved in the pathology of schizophrenia. To determine whether changes in the cannabinoid system were present in the brains of subjects with schizophrenia, we used in situ radioligand binding and autoradiography to measure the binding of [ 3 H]CP-55940 to the cannabinoid-1 receptor in the dorsolateral prefrontal cortex (Brodmann's area 9), caudate±putamen and areas of the temporal lobe from schizophrenic and control subjects, some of whom had ingested cannabis close to death. There was an increase in the density of [ 3 H]CP-55940 binding to cannabinoid-1 receptors in the dorsolateral prefrontal cortex from subjects with schizophrenia (mean^S.E.M.: 142^9.9 vs 119^6.6 fmol/mg estimated tissue equivalents; P , 0.05) that was independent of recent cannabis ingestion. There was an increase in the density of cannabinoid-1 receptors in the caudate±putamen from subjects who had recently ingested cannabis (151^9.0 vs 123^7.2 fmol/mg estimated tissue equivalents; P , 0.05) that was independent of diagnoses.
Naunyn-Schmiedeberg's Archives of Pharmacology, 2005
Antipsychotic drugs are effective in the treatment of cannabis-induced psychosis, but only clozap... more Antipsychotic drugs are effective in the treatment of cannabis-induced psychosis, but only clozapine appears effective in the treatment of comorbid schizophrenia and cannabis use. The unique effects of clozapine on cannabis use could, therefore, be due to an as yet unidentified interaction between clozapine and the endogenous cannabinoid system. To address this hypothesis, we used in situ radioligand binding and quantitative autoradiography with the selective cannabinoid CB 1 receptor agonist,
... nursing. Type, book chapter. Language, en-aus. Relation, Mental health in Australia : collabo... more ... nursing. Type, book chapter. Language, en-aus. Relation, Mental health in Australia : collaborative community practice / edited by Graham Meadows, Bruce Singh, and Margaret Grigg. Melbourne, Vic. : Oxford University Press, 2007. ...
Schizophrenia is widely acknowledged as being a syndrome, consisting of an undefined number of di... more Schizophrenia is widely acknowledged as being a syndrome, consisting of an undefined number of diseases probably with differing pathologies. Although studying a syndrome makes the identification of an underlying pathology more difficult; neuroimaging, neuropsychopharmacological and post-mortem brain studies all implicate muscarinic acetylcholine receptors (CHRM) in the pathology of the disorder. We have established that the CHRM1 is selectively decreased in the dorsolateral prefrontal cortex of subjects with schizophrenia. To expand this finding, we wanted to ascertain whether decreased cortical CHRMs might (1) define a subgroup of schizophrenia and/or (2) be related to CHRM1 genotype. We assessed cortical [ 3 H]pirenzepine binding and sequenced the CHRM1 in 80 subjects with schizophrenia and 74 age sex-matched control subjects. Kernel density estimation showed that [ 3 H]pirenzepine binding in BA9 divided the schizophrenia, but not control, cohort into two distinct populations. One of the schizophrenia cohorts, comprising 26% of all subjects with the disorder, had a 74% reduction in mean cortical [ 3 H]pirenzepine binding compared to controls. We suggest that these individuals make up 'muscarinic receptor-deficit schizophrenia' (MRDS). The MRDS could not be separated from other subjects with schizophrenia by CHRM1 sequence, gender, age, suicide, duration of illness or any particular drug treatment. Being able to define a subgroup within schizophrenia using a central biological parameter is a pivotal step towards understanding the biochemistry underlying at least one form of the disorder and may represent a biomarker that can be used in neuroimaging.
It is known that individuals with schizophrenia exhibit signs of impaired face processing, howeve... more It is known that individuals with schizophrenia exhibit signs of impaired face processing, however, the exact perceptual and cognitive mechanisms underlying these deficits are yet to be elucidated. One possible source of confusion in the current literature is the methodological and conceptual inconsistencies that can arise from the varied treatment of different aspects of face processing relating to emotional and non-emotional aspects of face perception. This review aims to disentangle the literature by focusing on the performance of patients with schizophrenia in a range of tasks that required processing of non-emotional features of face stimuli (e.g., identity or gender). We also consider the performance of patients on non-face stimuli that share common elements such as familiarity (e.g., cars) and social relevance (e.g., gait). We conclude by exploring whether observed deficits are best considered as "face-specific" and note that further investigation is required to properly assess the potential contribution of more generalized attentional or perceptual impairments.
AbstractÐA number of studies suggested that cannabis use can cause or exacerbate psychoses and ma... more AbstractÐA number of studies suggested that cannabis use can cause or exacerbate psychoses and may increase the risk of developing schizophrenia. These ®ndings suggest that changes in the cannabinoid system of the brain may be involved in the pathology of schizophrenia. To determine whether changes in the cannabinoid system were present in the brains of subjects with schizophrenia, we used in situ radioligand binding and autoradiography to measure the binding of [ 3 H]CP-55940 to the cannabinoid-1 receptor in the dorsolateral prefrontal cortex (Brodmann's area 9), caudate±putamen and areas of the temporal lobe from schizophrenic and control subjects, some of whom had ingested cannabis close to death. There was an increase in the density of [ 3 H]CP-55940 binding to cannabinoid-1 receptors in the dorsolateral prefrontal cortex from subjects with schizophrenia (mean^S.E.M.: 142^9.9 vs 119^6.6 fmol/mg estimated tissue equivalents; P , 0.05) that was independent of recent cannabis ingestion. There was an increase in the density of cannabinoid-1 receptors in the caudate±putamen from subjects who had recently ingested cannabis (151^9.0 vs 123^7.2 fmol/mg estimated tissue equivalents; P , 0.05) that was independent of diagnoses.
Naunyn-Schmiedeberg's Archives of Pharmacology, 2005
Antipsychotic drugs are effective in the treatment of cannabis-induced psychosis, but only clozap... more Antipsychotic drugs are effective in the treatment of cannabis-induced psychosis, but only clozapine appears effective in the treatment of comorbid schizophrenia and cannabis use. The unique effects of clozapine on cannabis use could, therefore, be due to an as yet unidentified interaction between clozapine and the endogenous cannabinoid system. To address this hypothesis, we used in situ radioligand binding and quantitative autoradiography with the selective cannabinoid CB 1 receptor agonist,
... nursing. Type, book chapter. Language, en-aus. Relation, Mental health in Australia : collabo... more ... nursing. Type, book chapter. Language, en-aus. Relation, Mental health in Australia : collaborative community practice / edited by Graham Meadows, Bruce Singh, and Margaret Grigg. Melbourne, Vic. : Oxford University Press, 2007. ...
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