Psychiatry & Clinical Psychobiology Unit, Division of Neuroscience, Scientific Institute Ospedale San Raffaele, Milano, Italy; University Vita-Salute San Raffaele, Milano, Italy.
Psychiatry & Clinical Psychobiology Unit, Division of Neuroscience, Scientific Institute Ospedale San Raffaele, Milano, Italy; University Vita-Salute San Raffaele, Milano, Italy.
Prog Neuropsychopharmacol Biol Psychiatry. 2022 Dec 20;119:110606. doi: 10.1016/j.pnpbp.2022.110606. Epub 2022 Jul 16.
Dysfunctional glutamatergic neurotransmission has been proposed both, as a biological underpinning of mood disorder and as a target for rapid-acting antidepressant treatments. Total sleep deprivation and light therapy (TSD + LT) can prompt antidepressant response in drug-resistant bipolar depression. Here we explored the effects of TSD + LT on dorsolateral prefrontal cortex (DLPFC) glutamate and/or glutamine+glutamate (Glx) levels.
We studied single voxel H-MRS measures of DLPFC Glu and Glx levels of 48 healthy participants and 55 inpatients with a major depressive episode in course of Bipolar Disorder, a subset of which (N = 23) underwent three cycles of repeated TSD + LT and were evaluated before and after treatment. Treatment effects of mood and on Glu and Glx concentrations were analyzed in the context of the Generalized Linear Model (GLM), correcting for age, sex and ongoing lithium treatment.
Higher concentration of Glu (adjusted Z = -2189, p = 0,0285) and Glx (adjusted Z = -3,13, p = 0,0017) were observed in BD patients compared to HC. Treatment caused a significant rapid reduction of depressive symptom severity over time (F = 63.98, p < 0.01). Change in depression levels after TSD + LT treatment was significantly influenced by delta change in Glu levels (LR χ = 4.619, p = 0.0316) and in Glx levels (LR χ = 4.486, p = 0.0341).
A reduction in Glu and Glx levels associated with depression could contribute to the mechanism of action of TSD + LT, directly acting on glutamatergic neurons, or to the interaction between the glutamatergic system and dopamine (DA) and serotonin (5-HT) levels, known to be targeted by TSD. This is in line with several studies showing a glutamatergic modulation effects of antidepressants and mood stabilizing agents. This finding deepens our understanding of antidepressant effect of chronoterapeutics.
功能失调的谷氨酸能神经传递被认为既是心境障碍的生物学基础，也是快速作用抗抑郁治疗的靶点。全睡眠剥夺和光照疗法（TSD+LT）可以促使抗药性双相抑郁症患者产生抗抑郁反应。在这里，我们探讨了 TSD+LT 对背外侧前额叶皮层（DLPFC）谷氨酸和/或谷氨酸+谷氨酰胺（Glx）水平的影响。
我们研究了 48 名健康参与者和 55 名患有双相情感障碍发作的住院患者的 DLPFC Glu 和 Glx 水平的单体素 H-MRS 测量值，其中一部分（N=23）接受了三次重复的 TSD+LT 治疗，并在治疗前后进行了评估。在广义线性模型（GLM）的背景下分析了情绪和 Glu 和 Glx 浓度的治疗效果，校正了年龄、性别和正在进行的锂治疗。
与 HC 相比，BD 患者的 Glu（调整后的 Z=-2189，p=0.0285）和 Glx（调整后的 Z=-3.13，p=0.0017）浓度更高。治疗导致抑郁症状严重程度随时间的快速降低（F=63.98，p<0.01）。TSD+LT 治疗后抑郁水平的变化与 Glu 水平的变化（LR χ=4.619，p=0.0316）和 Glx 水平的变化（LR χ=4.486，p=0.0341）显著相关。
与抑郁相关的 Glu 和 Glx 水平的降低可能有助于 TSD+LT 的作用机制，直接作用于谷氨酸能神经元，或者与谷氨酸系统与多巴胺（DA）和血清素（5-HT）水平的相互作用有关，已知 TSD 靶向这些水平。这与几项表明抗抑郁药和心境稳定剂具有谷氨酸调制作用的研究一致。这一发现加深了我们对 chronoterapeutics 抗抑郁作用的理解。
