Department of Psychiatry, Columbia University College of Physicians and Surgeons, New York, New York.
Division of Molecular Imaging and Neuropathology, Columbia University and New York State Psychiatric Institute, New York, New York.
Int J Neuropsychopharmacol. 2019 May 1;22(5):349-357. doi: 10.1093/ijnp/pyz013.
Suicide and major depression are prevalent in individuals reporting early-life adversity. Prefrontal cortex volume is reduced by stress acutely and progressively, and changes in neuron and glia density are reported in depressed suicide decedents. We previously found reduced neurotrophic factor brain-derived neurotrophic factor in suicide decedents and with early-life adversity, and we sought to determine whether cortex thickness or neuron or glia density in the dorsolateral prefrontal and anterior cingulate cortex are associated with early-life adversity or suicide.
A total of 52 brains, constituting 13 quadruplets of nonpsychiatric controls and major depressive disorder suicide decedents with and without early-life adversity, were matched for age, sex, race, and postmortem interval. Brains were collected at autopsy and frozen, and dorsolateral prefrontal cortex and anterior cingulate cortex were later dissected, postfixed, and sectioned. Sections were immunostained for neuron-specific nuclear protein (NeuN) to label neurons and counterstained with thionin to stain glial cell nuclei. Cortex thickness, neuron and glial density, and neuron volume were measured by stereology.
Cortical thickness was 6% less with early-life adversity in dorsolateral prefrontal cortex and 12% less in anterior cingulate cortex (P < .05), but not in depressed suicide decedents in either region. Neuron density was not different in early-life adversity or with suicide, but glial density was 17% greater with early-life adversity in dorsolateral prefrontal cortex and 15% greater in anterior cingulate cortex, but not in suicides. Neuron volume was not different with early-life adversity or suicide.
Reported early-life adversity, but not the stress associated with suicide, is associated with thinner prefrontal cortex and greater glia density in adulthood. Early-life adversity may alter normal neurodevelopment and contribute to suicide risk.
有研究表明,自杀和重度抑郁症在经历早期逆境的人群中较为普遍。前额皮质的体积会因急性和渐进性的压力而减少,而在患有抑郁症和自杀的死者中,神经元和神经胶质的密度也会发生变化。我们之前发现,在患有自杀的死者中,以及在经历过早期逆境的人群中,神经营养因子脑源性神经营养因子的水平降低,因此我们试图确定外侧前额叶和前扣带回皮质的皮质厚度、神经元或神经胶质密度是否与早期逆境或自杀有关。
共采集了 52 个脑样本,其中包括 13 对非精神疾病对照者和有或无早期逆境的重度抑郁症自杀死者的大脑,这些样本在年龄、性别、种族和死后间隔方面相匹配。大脑在尸检时被采集并冷冻,然后外侧前额叶和前扣带回皮质被解剖、后固定和切片。使用神经元特异性核蛋白(NeuN)对神经元进行免疫染色,并使用硫堇对神经胶质细胞核进行复染,以标记神经元和染色神经胶质细胞。通过体视学测量皮质厚度、神经元和神经胶质密度以及神经元体积。
在外侧前额叶皮质中,经历早期逆境的个体皮质厚度减少了 6%,在前扣带回皮质中减少了 12%(P<0.05),但在这两个区域的重度抑郁症自杀死者中并未出现这种情况。早期逆境或自杀并不影响神经元密度,但在前侧前额叶皮质和前扣带回皮质中,经历早期逆境的个体神经胶质密度增加了 17%和 15%,而在自杀死者中则没有出现这种情况。神经元体积在经历早期逆境或自杀时没有差异。
报告的早期逆境,而不是与自杀相关的压力,与成年后较薄的前额皮质和较大的神经胶质密度有关。早期逆境可能会改变正常的神经发育,并增加自杀风险。