Reduced GABAergic cortical inhibition in aging and depression
Reduced GABAergic cortical inhibition in aging and depression
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DOI：
10.1038/s41386-018-0093-x
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发表时间：
2018-10-01
影响因子：
7.6
通讯作者：
Blumberger, Daniel M.
中科院分区：
文献类型：
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作者：
Lissemore, Jennifer I.;Bhandari, Apoorva;Blumberger, Daniel M.
尽管假定衰老对抑郁症神经病理学有影响，但与年轻人相比，老年人抑郁症的神经生物学研究较少。使用经颅磁刺激 (TMS)（一种能够探测抑制性和兴奋性皮质神经传递的神经生理学工具）的研究已经确定了年轻抑郁症患者的 GABA 抑制活性功能失调。然而，GABA 能和谷氨酸能皮质神经传递尚未在晚年抑郁症 (LLD) 中进行研究。在这里，我们使用单脉冲和成对脉冲 TMS 来测量 92 名 LLD 患者和 41 名年龄匹配的健康对照者的皮质抑制和兴奋。为了区分年龄和抑郁的影响，我们还将这些 TMS 指数与 30 名年轻抑郁成年人和 30 名年龄和性别匹配的年轻健康成年人的指数进行了比较。 LLD 患者、老年健康成年人和年轻抑郁成年人的 GABAA 受体介导的皮质抑制显着低于年轻健康对照。相比之下，患有抑郁症和不患有抑郁症的老年人之间的皮质抑制没有显着差异。各组之间未发现 GABAB 受体介导的抑制或皮质兴奋存在显着差异。总而言之，这些发现表明，皮质抑制的减少可能与年龄增长和抑郁症有关，这（i）支持抑郁症作为一种加速衰老疾病的模型，（ii）提示未来对晚年 GABA 能神经传递减少作为抑郁症发展的生物诱发因素的研究。鉴于抑郁症和健康老年人的皮质神经生理学相似，未来的前瞻性研究需要确定年龄和抑郁症对皮质抑制缺陷的相对影响。
The neurobiology underlying depression in older adults is less extensively evaluated than in younger adults, despite the putative influence of aging on depression neuropathology. Studies using transcranial magnetic stimulation (TMS), a neurophysiological tool capable of probing inhibitory and excitatory cortical neurotransmission, have identified dysfunctional GABAergic inhibitory activity in younger adults with depression. However, GABAergic and glutamatergic cortical neurotransmission have not yet been studied in late-life depression (LLD). Here, we used single-and paired-pulse TMS to measure cortical inhibition and excitation in 92 LLD patients and 41 age-matched healthy controls. To differentiate the influence of age and depression, we also compared these TMS indices to those of 30 younger depressed adults and 30 age-and sex-matched younger healthy adults. LLD patients, older healthy adults, and younger depressed adults demonstrated significantly lower GABAA receptor-mediated cortical inhibition than younger healthy controls. By contrast, no significant differences in cortical inhibition were observed between older adults with and without depression. No significant differences in GABAB receptor-mediated inhibition or cortical excitation were found between the groups. Altogether, these findings suggest that reduced cortical inhibition may be associated with both advancing age and depression, which (i) supports the model of depression as a disease of accelerated aging, and (ii) prompts future investigation into diminished GABAergic neurotransmission in late-life as a biological predisposing factor to the development of depression. Given that cortical neurophysiology was similar in depressed and healthy older adults, future prospective studies need to establish the relative influence of age and depression on cortical inhibition deficits.