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自杀受害者死后大脑中的神经营养因子水平以及生前诊断和精神药物的影响。

Neurotrophin levels in postmortem brains of suicide victims and the effects of antemortem diagnosis and psychotropic drugs.

作者信息

Karege Félicien, Vaudan Geneviève, Schwald Michèle, Perroud Nader, La Harpe Romano

机构信息

Geneva University Hospitals, Department of Psychiatry, 2 ch Petit Bel-Air, CH-1225 Chêne-Bourg, Switzerland.

出版信息

Brain Res Mol Brain Res. 2005 May 20;136(1-2):29-37. doi: 10.1016/j.molbrainres.2004.12.020. Epub 2005 Mar 5.

Abstract

Suicide is a major public health problem but the neurobiological factors of risk are poorly understood. Recent studies have mentioned changes in the serotoninergic system and in neuronal plasticity, as well. The present investigation was undertaken to examine whether there is an abnormality in brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) proteins in suicide victims. The effect of diagnosis and drug treatments on the neurotrophins was also assessed. Thirty suicide victims (11 F/19 M) and twenty-four (10 F/14 M) drug-free non-suicide subjects, devoid of psychiatric or neurological disease, were examined. Antemortem diagnoses and toxicological analyses had been performed. The ventral prefrontal cortex (PFC), the hippocampus, and the entorhinal cortex were selected. BDNF and NT-3 levels were assayed either with the Western blot or with the ELISA method. Results indicated a significant decrease in BDNF and NT-3 levels in the hippocampus and PFC (only BDNF) but not in the entorhinal cortex, of suicide victims who were drug-free compared with non-suicide controls. The decrease was observed in all suicide victims, regardless of diagnosis. In drug-treated suicide victims, neurotrophin levels were not significantly different from non-suicide controls. This study supports a role of BDNF and NT-3 neurotrophin, in the pathophysiology of suicidal behavior. Anatomically, this role may implicate the hippocampus and the PFC but not the entorhinal cortex. The absence of change in BDNF and NT-3 levels of drug-treated suicide victims suggests that both neurotrophins are mediators of psychotropic drugs. A better understanding of the neurobiology of suicide could help detect populations at risk.

摘要

自杀是一个重大的公共卫生问题,但人们对其风险的神经生物学因素知之甚少。最近的研究也提到了血清素能系统和神经元可塑性的变化。本研究旨在检查自杀受害者的脑源性神经营养因子(BDNF)和神经营养因子-3(NT-3)蛋白是否存在异常。还评估了诊断和药物治疗对神经营养因子的影响。对30名自杀受害者(11名女性/19名男性)和24名无药物使用史的非自杀受试者(10名女性/14名男性)进行了检查,这些受试者无精神或神经疾病。生前已进行诊断和毒理学分析。选取了腹侧前额叶皮质(PFC)、海马体和内嗅皮质。采用蛋白质印迹法或酶联免疫吸附测定(ELISA)法检测BDNF和NT-3水平。结果表明,与非自杀对照组相比,无药物使用史的自杀受害者海马体和PFC(仅BDNF)中的BDNF和NT-3水平显著降低,但内嗅皮质中未降低。在所有自杀受害者中均观察到这种降低,与诊断无关。在接受药物治疗的自杀受害者中,神经营养因子水平与非自杀对照组无显著差异。本研究支持BDNF和NT-3神经营养因子在自杀行为病理生理学中的作用。从解剖学角度来看,这一作用可能涉及海马体和PFC,但不涉及内嗅皮质。接受药物治疗的自杀受害者BDNF和NT-3水平没有变化,这表明这两种神经营养因子都是精神药物的介质。更好地理解自杀的神经生物学机制有助于发现高危人群。

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