RESUMO
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.
Assuntos
Cocaína , Drogas Ilícitas , Transtornos Relacionados ao Uso de Substâncias , Suicídio , Masculino , Humanos , Adulto , Adolescente , Adulto Jovem , Pessoa de Meia-Idade , Autopsia , Espanha/epidemiologia , Etanol/efeitos adversos , Estudos de Casos e Controles , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Drogas Ilícitas/efeitos adversos , Fatores de Risco , AnfetaminaRESUMO
Current pharmacological therapies for depression, including selective serotonin reuptake inhibitors (SSRI), are far from ideal. The cannabinoid system has been implicated in control of mood and neural processing of emotional information, and the modulation of serotonin (5-HT) release in the synaptic clefts. The aim of the present study was to evaluate whether the combination of a selective SSRI (citalopram) with a selective cannabinoid CB1 receptor antagonist (rimonabant) represents a more effective strategy than the antidepressant alone to enhance serotonergic transmission. For this purpose extracellular 5-HT levels were monitored with microdialysis in forebrain (prefrontal cortex, PFC) and mesencephalic (locus coeruleus, LC) serotonergic terminal areas in freely awake rats. Rimonabant at 10 mg/kg, i.p., but not at 3mg/kg i.p. increased 5-HT in both areas. Citalopram at 3, 5 and 10 mg/kg i.p. increased 5-HT both in PFC and LC in a dose-dependent manner. The effect of citalopram (5mg/kg, i.p.) on 5-HT levels was significantly enhanced by rimonabant at 10 mg/kg, i.p. but not at 3 mg/kg i.p. in both areas. The present results demonstrate that the cannabinoid CB1 receptor antagonist rimonabant is able to enhance in an additive manner the citalopram-induced increase of 5-HT concentrations in serotonergic terminal areas. The combination of a cannabinoid antagonist and a SSRI may provide a novel strategy to increase 5-HT availability, reducing the dose of SSRIs, and potentially decreasing the time lag for the clinical onset of the antidepressant effect.
Assuntos
Encéfalo/efeitos dos fármacos , Antagonistas de Receptores de Canabinoides/farmacologia , Citalopram/farmacologia , Piperidinas/farmacologia , Pirazóis/farmacologia , Inibidores Seletivos de Recaptação de Serotonina/farmacologia , Neurônios Serotoninérgicos/efeitos dos fármacos , Serotonina/metabolismo , Animais , Antidepressivos/administração & dosagem , Antidepressivos/farmacologia , Encéfalo/metabolismo , Antagonistas de Receptores de Canabinoides/administração & dosagem , Citalopram/administração & dosagem , Relação Dose-Resposta a Droga , Sinergismo Farmacológico , Líquido Extracelular/efeitos dos fármacos , Líquido Extracelular/metabolismo , Injeções Intraperitoneais , Cinética , Locus Cerúleo/efeitos dos fármacos , Locus Cerúleo/metabolismo , Masculino , Microdiálise , Piperidinas/administração & dosagem , Córtex Pré-Frontal/efeitos dos fármacos , Córtex Pré-Frontal/metabolismo , Pirazóis/administração & dosagem , Ratos , Ratos Sprague-Dawley , Receptor CB1 de Canabinoide/antagonistas & inibidores , Receptor CB1 de Canabinoide/metabolismo , Rimonabanto , Neurônios Serotoninérgicos/metabolismo , Inibidores Seletivos de Recaptação de Serotonina/administração & dosagem , Transmissão SinápticaRESUMO
We evaluated the subcellular distribution of four membrane-bound aminopeptidases in the human and rat brain cortex. The particulate enzymes under study--puromycin-sensitive aminopeptidase (PSA), aminopeptidase N (APN), pyroglutamyl-peptidase I (PG I) and aspartyl-aminopeptidase (Asp-AP)--were fluorometrically measured using beta-naphthylamide derivatives. Membrane-bound aminopeptidase activity was found in all the studied subcellular fractions (myelinic, synaptosomal, mitochondrial, microsomal and nuclear fractions), although not homogenously. Human PSA showed highest activity in the microsomal fraction. APN was significantly higher in the nuclear fraction of both species, while PG I showed highest activity in the synaptosomal and myelinic fractions of the human and rat brain. The present results suggest that in addition to inactivating neuropeptides at the synaptic cleft, these enzymes may participate in other physiological processes. Moreover, these peptidases may play specific roles depending on their activity levels at the different subcellular structures where they are localized.