Serotonergic Neurotransmission in Limbic Regions May Reflect Therapeutic Response of Depressive Patients: A PET Study With 11C-WAY-100635 and 18F-MPPF.

IF 4.5 2区 医学 Q1 CLINICAL NEUROLOGY International Journal of Neuropsychopharmacology Pub Date : 2023-07-31 DOI:10.1093/ijnp/pyad026
Soichiro Kitamura, Yasuyuki Kimura, Keisuke Takahata, Sho Moriguchi, Manabu Kubota, Hitoshi Shimada, Hironobu Endo, Yuhei Takado, Kazunori Kawamura, Ming-Rong Zhang, Tetsuya Suhara, Makoto Higuchi
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Abstract

Background: Central serotonin (5-hydroxytryptamine [5-HT]) neurotransmission has been implicated in the etiology of depression. Most antidepressants ameliorate depressive symptoms by increasing 5-HT at synaptic clefts, but their effect on 5-HT receptors has yet to be clarified. 11C-WAY-100635 and 18F-MPPF are positron emission tomography (PET) radioligands for 5-HT1A receptors. While binding of both ligands reflects 5-HT1A receptor density, 18F-MPPF biding may also be affected by extracellular 5-HT concentrations. This dual-tracer PET study explored the neurochemical substrates underlying antidepressant effects in patients with depression.

Methods: Eleven patients with depression, including 9 treated with antidepressants, and 16 age- and sex-matched healthy individuals underwent PET scans with 11C-WAY-100635 and 18F-MPPF. Radioligand binding was determined by calculating the nondisplaceable binding potential (BPND).

Results: Patients treated with antidepressants showed significantly lower 18F-MPPF BPND in neocortical regions and raphe nuclei, but not in limbic regions, than controls. No significant group differences in 11C-WAY-100635 BPND were found in any of the regions. Significant correlations of BPND between 11C-WAY-100635 and 18F-MPPF were observed in limbic regions and raphe nuclei of healthy controls, but no such associations were found in antidepressant-treated patients. Moreover, 18F-MPPF BPND in limbic regions was significantly correlated with the severity of depressive symptoms.

Conclusions: These results suggest a diversity of antidepressant-induced extracellular 5-HT elevations in the limbic system among depressive patients, which is associated with the individual variability of clinical symptoms following the treatment.

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边缘区5 -羟色胺能神经传递可能反映抑郁症患者的治疗反应:11C-WAY-100635和18F-MPPF的PET研究
背景:中枢5-羟色胺(5-羟色胺[5-HT])神经传递与抑郁症的病因有关。大多数抗抑郁药通过增加突触间隙的5-羟色胺来改善抑郁症状,但它们对5-羟色胺受体的作用尚未明确。11C-WAY-100635和18F-MPPF是5-HT1A受体的正电子发射断层扫描(PET)放射配体。虽然这两种配体的结合反映了5-HT1A受体的密度,但18F-MPPF的结合也可能受到细胞外5-HT浓度的影响。这项双示踪PET研究探讨了抑郁症患者抗抑郁作用的神经化学基础。方法:11名抑郁症患者,包括9名接受抗抑郁药物治疗的患者,以及16名年龄和性别匹配的健康个体,使用11C-WAY-100635和18F-MPPF进行PET扫描。通过计算不可置换结合势(BPND)来确定放射性配体的结合。结果:与对照组相比,接受抗抑郁药物治疗的患者新皮质区和中缝核的18F-MPPF BPND显著降低,但边缘区无显著降低。11C-WAY-100635 BPND在所有地区均无显著组间差异。11C-WAY-100635与18F-MPPF在健康对照的边缘区和中缝核中存在显著相关性,但在抗抑郁治疗的患者中未发现这种相关性。此外,边缘区18F-MPPF BPND与抑郁症状的严重程度显著相关。结论:这些结果表明,抑郁患者边缘系统中抗抑郁药诱导的细胞外5-HT升高存在多样性,这与治疗后临床症状的个体差异有关。
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来源期刊
CiteScore
8.40
自引率
2.10%
发文量
230
审稿时长
4-8 weeks
期刊介绍: The central focus of the journal is on research that advances understanding of existing and new neuropsychopharmacological agents including their mode of action and clinical application or provides insights into the biological basis of psychiatric disorders and thereby advances their pharmacological treatment. Such research may derive from the full spectrum of biological and psychological fields of inquiry encompassing classical and novel techniques in neuropsychopharmacology as well as strategies such as neuroimaging, genetics, psychoneuroendocrinology and neuropsychology.
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