酒精使用障碍中大脑皮质醇调节的假定标记成像

IF 4.3 2区 医学 Q1 NEUROSCIENCES Neurobiology of Stress Pub Date : 2024-01-21 DOI:10.1016/j.ynstr.2024.100609
Terril L. Verplaetse , Ansel T. Hillmer , Shivani Bhatt , Aleksandra Rusowicz , Songye Li , Nabeel Nabulsi , David Matuskey , Yiyun Huang , Sherry A. McKee , Kelly P. Cosgrove
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引用次数: 0

摘要

背景压力是下丘脑-垂体-肾上腺(HPA)轴的强效激活剂,可启动皮质醇等糖皮质激素的释放。饮酒会导致 HPA 轴功能紊乱,包括皮质醇水平的改变。直到最近,研究才得以检测与人类酒精使用障碍(AUD)相关的外周皮质醇。我们使用放射性示踪剂 [18F]AS2471907 进行正电子发射断层扫描(PET)脑成像,测量 AUD 患者与健康对照组的皮质醇再生酶 11β- 羟类固醇脱氢酶 1 型 (11β-HSD1)。参与者接受了 93.5 ± 15.6 MBq 的 11β-HSD1 抑制剂放射性示踪剂 [18F]AS2471907 的栓剂注射,并在高分辨率研究断层成像仪上进行了 150-180 分钟的成像。11β-HSD1的可用性通过[18F]AS2471907分布容积(VT;mL/cm3)进行量化。先验相关区域包括杏仁核、前扣带回皮层(ACC)、海马、腹内侧 PFC(vmPFC)和尾状核。健康对照组每周饮酒 2.8 次,每周饮酒天数为 1.3 天。初步研究结果表明,与健康对照组相比,AUD患者杏仁核、ACC、海马、vmPFC和尾状核的[18F]AS2471907 VT更高(p <0.05)。在 AUD 患者中,vmPFC [18F]AS2471907 VT 与每周饮酒量(r = 0.81,p = 0.01)和每次饮酒量(r = 0.75,p = 0.02)相关。我们的数据表明,在 AUD 患者(与对照组相比)中,大脑中皮质醇再生酶 11β-HSD1 的可用性较高,而且大脑皮质功能区 11β-HSD1 的可用性较高与饮酒量较大有关。因此,除了有文献表明 AUD 患者的外周皮质醇升高外,我们的研究结果还表明他们的中枢 HPA 活动也可能升高。这些发现为今后假设该人群 HPA 轴功能的相关机制奠定了基础。
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Imaging a putative marker of brain cortisol regulation in alcohol use disorder

Background

Stress is a potent activator of the hypothalamic-pituitary-adrenal (HPA) axis, initiating the release of glucocorticoid hormones, such as cortisol. Alcohol consumption can lead to HPA axis dysfunction, including altered cortisol levels. Until recently, research has only been able to examine peripheral cortisol associated with alcohol use disorder (AUD) in humans. We used positron emission tomography (PET) brain imaging with the radiotracer [18F]AS2471907 to measure 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), a cortisol-regenerating enzyme, in people with AUD compared to healthy controls.

Methods

We imaged 9 individuals with moderate to severe AUD (5 men, 4 women; mean age = 38 years) and 12 healthy controls (8 men, 4 women; mean age = 29 years). Participants received 93.5 ± 15.6 MBq of the 11β-HSD1 inhibitor radiotracer [18F]AS2471907 as a bolus injection and were imaged for 150–180 min on the High-Resolution Research Tomograph. 11β-HSD1 availability was quantified by [18F]AS2471907 volume of distribution (VT; mL/cm3). A priori regions of interest included amygdala, anterior cingulate cortex (ACC), hippocampus, ventromedial PFC (vmPFC) and caudate.

Results

Individuals with AUD consumed 52.4 drinks/week with 5.8 drinking days/week. Healthy controls consumed 2.8 drinks/week with 1.3 drinking days/week. Preliminary findings suggest that [18F]AS2471907 VT was higher in amygdala, ACC, hippocampus, vmPFC, and caudate of those with AUD compared to healthy controls (p < 0.05). In AUD, vmPFC [18F]AS2471907 VT was associated with drinks per week (r = 0.81, p = 0.01) and quantity per drinking episode (r = 0.75, p = 0.02).

Conclusions

This is the first in vivo examination of 11β-HSD1 availability in individuals with AUD. Our data suggest higher brain availability of the cortisol-regenerating enzyme 11β-HSD1 in people with AUD (vs. controls), and that higher vmPFC 11β-HSD1 availability is related to greater alcohol consumption. Thus, in addition to the literature suggesting that people with AUD have elevated peripheral cortisol, our findings suggest there may also be heightened central HPA activity. These findings set the foundation for future hypotheses on mechanisms related to HPA axis function in this population.

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来源期刊
Neurobiology of Stress
Neurobiology of Stress Biochemistry, Genetics and Molecular Biology-Biochemistry
CiteScore
9.40
自引率
4.00%
发文量
74
审稿时长
48 days
期刊介绍: Neurobiology of Stress is a multidisciplinary journal for the publication of original research and review articles on basic, translational and clinical research into stress and related disorders. It will focus on the impact of stress on the brain from cellular to behavioral functions and stress-related neuropsychiatric disorders (such as depression, trauma and anxiety). The translation of basic research findings into real-world applications will be a key aim of the journal. Basic, translational and clinical research on the following topics as they relate to stress will be covered: Molecular substrates and cell signaling, Genetics and epigenetics, Stress circuitry, Structural and physiological plasticity, Developmental Aspects, Laboratory models of stress, Neuroinflammation and pathology, Memory and Cognition, Motivational Processes, Fear and Anxiety, Stress-related neuropsychiatric disorders (including depression, PTSD, substance abuse), Neuropsychopharmacology.
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