Neurotrophin levels in postmortem brains of suicide victims and the effects of antemortem diagnosis and psychotropic drugs
Neurotrophin levels in postmortem brains of suicide victims and the effects of antemortem diagnosis and psychotropic drugs
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DOI：
10.1016/j.molbrainres.2004.12.020
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发表时间：
2005-05-20
期刊：
影响因子：
--
通讯作者：
La Harpe, R
中科院分区：
文献类型：
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作者：
Karege, F;Vaudan, G;La Harpe, R
自杀是一个主要的公共卫生问题，但神经生物学因素的风险知之甚少。最近的研究也提到了胆碱能系统和神经元可塑性的变化。本研究旨在探讨自杀者脑源性神经营养因子（BDNF）和神经营养素-3（NT-3）蛋白表达是否存在异常。同时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 F/19 M）和24名（10 F/14 M）无精神或神经疾病的无药物非自杀受试者进行了检查。已进行死前诊断和毒理学分析。选择腹侧前额叶皮质（PFC）、海马和内嗅皮质。用Western blot和ELISA方法检测BDNF和NT-3的水平。结果表明，与非自杀对照组相比，无药物自杀受害者的海马和PFC（仅BDNF）中BDNF和NT-3水平显著降低，但内嗅皮层中没有。在所有自杀受害者中观察到这种下降，无论诊断如何。在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没有显著差异。这项研究支持BDNF和NT-3神经营养因子在自杀行为的病理生理学中的作用。从解剖学上讲，这种作用可能涉及海马和PFC，但不涉及内嗅皮层。药物治疗的自杀受害者的BDNF和NT-3水平没有变化，表明这两种神经营养因子是精神药物的介质。更好地了解自杀的神经生物学可以帮助发现高危人群。(c)2005 Elsevier B.V保留所有权利。
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 (I I 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. (c) 2005 Elsevier B.V All rights reserved.