Postsynaptic α2A-adrenoceptor density is enhanced in the dorsolateral prefrontal cortex (DLPFC) of antipsychotic-treated schizophrenia subjects. This alteration might be due to transcriptional activation, and could be regulated by epigenetic mechanisms such as histone posttranslational modifications (PTMs). The aim of this study was to evaluate ADRA2A and ADRA2C gene expression (codifying for α2-adrenoceptor subtypes), and permissive and repressive histone PTMs at gene promoter regions in the DLPFC of subjects with schizophrenia and matched controls (n = 24 pairs). We studied the effect of antipsychotic (AP) treatment in AP-free (n = 12) and AP-treated (n = 12) subgroups of schizophrenia subjects and in rats acutely and chronically treated with typical and atypical antipsychotics. ADRA2A mRNA expression was selectively upregulated in AP-treated schizophrenia subjects (+93%) whereas ADRA2C mRNA expression was upregulated in all schizophrenia subjects (+53%) regardless of antipsychotic treatment. Acute and chronic clozapine treatment in rats did not alter brain cortex Adra2a mRNA expression but increased Adra2c mRNA expression. Both ADRA2A and ADRA2C promoter regions showed epigenetic modification by histone methylation and acetylation in human DLPFC. The upregulation of ADRA2A expression in AP-treated schizophrenia subjects might be related to observed bivalent chromatin at ADRA2A promoter region in schizophrenia (depicted by increased permissive H3K4me3 and repressive H3K27me3) and could be triggered by the enhanced H4K16ac at ADRA2A promoter. In conclusion, epigenetic predisposition differentially modulated ADRA2A and ADRA2C mRNA expression in DLPFC of schizophrenia subjects.
The association between drug abuse and criminal activity has been deeply established, but the nature of this relationship is controversial. The incidence and types of criminal activity were analyzed in 837 arrests of 578 subjects who were also interviewed for psychiatric diagnosis and evaluation of criminal responsibility. There was a significant prevalence of heroin abuse/dependence (50.5 %) in the sample. Another 124 subjects (21.5 %) in whom no psychiatric disorder could be observed were considered as the control group. Heroin abusers were younger (26 years, SD 5.9) than controls (29 years, SD 11.2) and showed some different ethnic characteristics. Heroin abuse/dependence was the most important risk factor (O.R. = 10.15) for criminal recidivism. Females were more related to nonviolent criminal activity than males. There was a higher incidence of offenses against property among heroin abusers (burglary 57.8%; robbery 19.5%) than in the control group (burglary 15.3% robbery 4.8%). In contrast, aggression or resistance to police authorities and nonfatal offenses against persons were more frequent among controls (12% and 13.7%, respectively) than among heroin abusers (3.7% and 3%, respectively). The results of this study confirm the hypothesis of a relationship between criminal activity and heroin abuse/dependence, probably based on financial needs. However, the association seems not to be a single and direct cause-effect relationship, as other factors show influence on the criminal activity.
Doctors sometimes assess allegations of ill-treatment. Reports from such examinations may be used if the practice of the police is to be appraised; they should therefore be relevant and exhaustive.
We assessed, retrospectively, the quality of 318 medical documents concerning 100 persons held in central police stations in Madrid, Spain, from 1991 to 1994. In 71 documents concerning 44 persons the doctors quoted the detainee as alleging ill-treatment. Most of the documents appeared to lack significant information on history of ill-treatment and description of the clinical examination. Of 34 conclusions, ten were unacceptable and the premises were insufficient in 16. These observations point to weaknesses and needs for improvements in the fulfillment of the role of doctors as safeguards of the rights of detainees.
Medical examinations should be conducted outside the control of police officers, by a neutral doctor using a check-list/protocol. The quality of the report should fulfill international standards.
Cannabis use disorder is frequent in schizophrenia patients, and it is associated with an earlier age of onset and poor schizophrenia prognosis. Serotonin 2A receptors (5‐HT2AR) have been involved in psychosis and, like Akt kinase, are known to be modulated by THC. Likewise, endocannabinoid system dysregulation has been suggested in schizophrenia. The presence of these molecules in blood makes them interesting targets, as they can be evaluated in patients by a minimally invasive technique. The aim of the present study was to evaluate 5‐HT2AR protein expression and the Akt functional status in platelet homogenates of subjects diagnosed with schizophrenia, cannabis use disorder, or both conditions, compared with age‐ and sex‐matched control subjects. Additionally, endocannabinoids and pro‐inflammatory interleukin‐6 (IL‐6) levels were also measured in the plasma of these subjects. Results showed that both platelet 5‐HT2AR and the active phospho (Ser473)Akt protein expression were significantly increased in schizophrenia subjects, whereas patients with a dual diagnosis of schizophrenia and cannabis use disorder did not show significant changes. Similarly, plasma concentrations of anandamide and other lipid mediators such as PEA and DEA, as well as the pro‐inflammatory IL‐6, were significantly increased in schizophrenia, but not in dual subjects. Results demonstrate that schizophrenia subjects show different circulating markers pattern depending on the associated diagnosis of cannabis use disorder, supporting the hypothesis that there could be different underlying mechanisms that may explain clinical differences among these groups. Moreover, they provide the first preliminary evidence of peripherally measurable molecules of interest for bigger prospective studies in these subpopulations.
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