Department of Medical Sciences, Psychiatry, Uppsala University, Uppsala, Sweden.
PET-Centre, Uppsala University Hospital, Uppsala, Sweden.
Neuropsychobiology. 2024;83(1):17-27. doi: 10.1159/000535512. Epub 2023 Dec 27.
Gamma-aminobutyric acid (GABA) deficiency is suggested in depressive disorders, along with alterations in cortical excitability. However, whether these excitability changes are related to GABAA receptor availability is largely unknown. Our aim was to assess the correlation between these measures in depressed patients and healthy controls.
Twenty-eight patients with a major depressive episode, measured before and after participating in a clinical trial with repetitive transcranial magnetic stimulation (TMS), and 15 controls underwent [11C]flumazenil positron emission tomography to assess GABAA receptor availability and paired pulse TMS (ppTMS) to evaluate cortical excitability. Both whole-brain voxel-wise GABAA receptor availability and mean values from left hand motor cortex and left paracentral lobule were correlated to the ppTMS outcomes: short-interval intracortical inhibition reflecting GABAA receptor activity, long-interval intracortical inhibition representing GABAB receptor activity, intracortical facilitation reflecting glutamate N-methyl-D-aspartate-receptor activity, as well as the resting motor threshold (rMT), considered a global measure of corticospinal excitability.
No significant differences in baseline GABAA receptor availability or cortical excitability were found between patients and controls. Additionally, no correlations were observed between baseline measurements of GABAA receptor availability and TMS outcomes. Changes in GABAA receptor availability in the hand motor cortex, between pre- and post-assessments, were inversely related to pre-post changes in hand rMT.
We found that a change in GABAA receptor availability was inversely related to a change in rMT, suggesting a link between GABA deficiency and increased rMT previously observed in depressive episodes. The results highlight the complex mechanisms governing cortical excitability measures and offer new insight into their properties during the depressive state.
在抑郁障碍中，γ-氨基丁酸（GABA）缺乏以及皮质兴奋性改变被认为与之相关。然而，这些兴奋性变化是否与 GABAA 受体的可用性有关尚不清楚。我们的目的是评估抑郁患者和健康对照组之间这些测量值之间的相关性。
28 名患有重度抑郁发作的患者，在参加重复经颅磁刺激（rTMS）临床试验前后进行了测量，15 名对照者接受了[11C]氟马西尼正电子发射断层扫描以评估 GABAA 受体的可用性，以及配对脉冲 TMS（ppTMS）以评估皮质兴奋性。从全脑体素水平到左手运动皮层和左侧旁中央小叶的 GABAA 受体可用性平均值均与 ppTMS 结果相关：短间隔皮质内抑制反映 GABAA 受体活性，长间隔皮质内抑制代表 GABAB 受体活性，皮质内易化反映谷氨酸 N-甲基-D-天冬氨酸受体活性，以及静息运动阈值（rMT），被认为是皮质脊髓兴奋性的整体测量指标。
患者和对照组之间在基线 GABAA 受体可用性或皮质兴奋性方面没有显著差异。此外，在基线 GABAA 受体可用性和 TMS 结果之间未观察到相关性。在手部运动皮层中，评估前后 GABAA 受体可用性的变化与手部 rMT 的前后变化呈负相关。
我们发现 GABAA 受体可用性的变化与 rMT 的变化呈负相关，这表明在抑郁发作中观察到的 GABA 缺乏与 rMT 增加之间存在联系。这些结果突出了调节皮质兴奋性测量的复杂机制，并为其在抑郁状态下的特性提供了新的见解。
