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Reduced GABAergic cortical inhibition in aging and depression.
Neuropsychopharmacology ( IF 7.6 ) Pub Date : 2018-10-01 , DOI: 10.1038/s41386-018-0093-x
Jennifer I. Lissemore , Apoorva Bhandari , Benoit H. Mulsant , Eric J. Lenze , Charles F. Reynolds , Jordan F. Karp , Tarek K. Rajji , Yoshihiro Noda , Reza Zomorrodi , Etienne Sibille , Zafiris J. Daskalakis , Daniel M. Blumberger

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.

中文翻译:

在衰老和抑郁症中降低了GABA能皮质的抑制作用。

尽管衰老对抑郁症的神经病理学有影响,但对老年人抑郁症的神经生物学的评估不如年轻人。使用经颅磁刺激(TMS)(一种能够探测抑制性和兴奋性皮层神经传递的神经生理学工具)的研究已经确定了患有抑郁症的年轻成年人中功能失调的GABA能抑制活性。然而,尚未在晚期抑郁症(LLD)中研究GABA能和谷氨酸能皮质神经传递。在这里,我们使用单脉冲和成对TMS测量92位LLD患者和41位年龄相匹配的健康对照者的皮质抑制和兴奋性。为了区分年龄和抑郁症的影响,我们还将这些TMS指标与30个年轻的抑郁症成年人以及30个年龄和性别相匹配的年轻健康成年人的TMS指数进行了比较。LLD患者,健康长者和较年轻的抑郁症成年人的GABA值明显降低受体介导的大脑皮层的抑制比年轻健康对照。相比之下,在患有抑郁症和没有抑郁症的老年人之间,没有观察到皮质抑制的显着差异。GABA B无显着差异在两组之间发现了受体介导的抑制或皮层兴奋。总而言之,这些发现表明,皮质抑制的降低可能与年龄的增长和抑郁症有关,这(i)支持抑郁症作为加速衰老的疾病,并且(ii)促进了对晚年GABA能神经传递减少的研究。是导致抑郁症发展的生物学诱因。鉴于抑郁和健康的老年人皮质神经生理学相似,因此未来的前瞻性研究需要确定年龄和抑郁对皮质抑制缺陷的相对影响。
更新日期:2018-05-17
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