Ethanol and illicit drugs acute use and abuse as risk factors for suicide: A case-control study based on forensic autopsies in the Basque Country, Spain.

INTRODUCTION: Abuse/dependence and acute use of ethanol and illicit drug are considered risk factors for suicide. The risk is also influenced by demographic conditions and/or psychiatric comorbidity. The aim of the study was to test the association between presence of ethanol, illicit substances and prescribed drugs in suicide decedents and controls. MATERIALS AND METHODS: Case-control study of autopsies performed in the Biscay Forensic Pathology Service, Basque Country, Spain from 01/01/2010 to 30/06/2021 in subjects between 15 and 55 years old. Suicide deaths (n=481) with completed autopsy were evaluated. Concurrent natural deaths were chosen as controls (n=330). The risk for suicide according to demographic, toxicological and psychiatric variables was analyzed using logistic regression. RESULTS: Ethanol was present in 21% and illicit drugs, mainly cannabis, cocaine and amphetamine, in 27% of suicide deaths. Illicit drugs were more frequent among males. In 63% of suicide cases, prescribed psychotropic drugs were detected. In a multivariate analysis, the main risk factors for suicide were psychiatric diagnosis of illicit drug abuse/dependence (OR=5.56, 95% CI 2.74-11.30) or another mental disease as mood or psychotic disorders (OR=13.05, 95% CI 8.79-19.37). Acute presence of ethanol (OR=4.22, 95% CI 2.52-7.08), recent use of cocaine (OR=2.52, 95% CI 1.05-6.07) and age <35 years (OR=2.50, 95% CI 1.62-3.87) were also associated with suicide deaths. CONCLUSIONS: The presence of drugs of abuse in suicide deaths of people ≤55 years old is high. Recent use of ethanol and cocaine is significantly associated with an increased suicide risk. Specific prevention strategies against exposition to substances of abuse should be promoted, especially in psychiatric patients.

5-HT2A receptor-mediated Gαq/11 activation in psychiatric disorders: A postmortem study.

OBJECTIVES: Serotonin-2A (5-HT2A) receptors play an important role in the regulation of many brain functions that are disturbed in patients with such psychiatric diseases as mood disorders and schizophrenia. The objective of this study was to evaluate 5-HT2A receptor-mediated signalling pathway through Gαq/11 activation in psychiatric patients by using post-mortem brain samples. METHODS: Functional activation of Gαq/11 proteins coupled to 5-HT2A receptors was determined by means of [35S]GTPγS binding/immunoprecipitation assay in post-mortem prefrontal cortex of psychiatric patients diagnosed as bipolar disorder (BP), major depressive disorder (MDD), and schizophrenia, and individually matched controls. The effects of antipsychotic treatment as well as suicide were also analysed. RESULTS: There was no significant difference in maximum percent increase (%Emax) or slope factor among the four groups. The negative logarithm of concentration eliciting the half-maximal effect (pEC50) was significantly reduced in BP and schizophrenia patients as compared to controls. These alterations were attributable to antipsychotic medication. The pEC50 values in 'non-suicide' group of schizophrenia, but not in 'suicide' group, were significantly reduced as compared with controls. CONCLUSIONS: Altered 5-HT2A receptor-mediated signalling pathway through Gαq/11 proteins in prefrontal cortex might be apparently involved in pathophysiology and pharmacotherapy of BP and schizophrenia. In schizophrenic patients, these alterations as a result of successful treatment with antipsychotic agents may help in prevention of suicidal behaviour.