Translational Psychiatry ( IF 6.8 ) Pub Date : 2020-06-08 , DOI: 10.1038/s41398-020-00871-w Daniel Martins 1 , Monica Leslie 2 , Sarah Rodan 1 , Fernando Zelaya 1 , Janet Treasure 2 , Yannis Paloyelis 1
Advances in the treatment of bulimia nervosa and binge-eating disorder (BN/BED) have been marred by our limited understanding of the underpinning neurobiology. Here we measured regional cerebral blood flow (rCBF) to map resting perfusion abnormalities in women with BN/BED compared with healthy controls and investigate whether intranasal oxytocin (OT), proposed as a potential treatment, can restore perfusion in disorder-related brain circuits. Twenty-four women with BN/BED and 23 healthy women participated in a randomized, double-blind, crossover, placebo-controlled study. We used arterial spin labelling MRI to measure rCBF and the effects of an acute dose of intranasal OT (40 IU) or placebo over 18–26 min post dosing, as we have previously shown robust OT-induced changes in resting rCBF in men in a similar time-window (15–36 min post dosing). We tested for effects of treatment, diagnosis and their interaction on extracted rCBF values in anatomical regions-of-interest previously implicated in BN/BED by other neuroimaging modalities, and conducted exploratory whole-brain analyses to investigate previously unidentified brain regions. We demonstrated that women with BN/BED presented increased resting rCBF in the medial prefrontal and orbitofrontal cortices, anterior cingulate gyrus, posterior insula and middle/inferior temporal gyri bilaterally. Hyperperfusion in these areas specifically correlated with eating symptoms severity in patients. Our data did not support a normalizing effect of intranasal OT on perfusion abnormalities in these patients, at least for the specific dose (40 IU) and post-dosing interval (18–26 min) examined. Our findings enhance our understanding of resting brain abnormalities in BN/BED and identify resting rCBF as a non-invasive potential biomarker for disease-related changes and treatment monitoring. They also highlight the need for a comprehensive investigation of intranasal OT pharmacodynamics in women before we can fully ascertain its therapeutic value in disorders affecting predominantly this gender, such as BN/BED.
中文翻译:
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研究患有神经性贪食症和暴食症的女性以及健康对照组的静息脑灌注异常和鼻内催产素对疾病靶点的参与。
由于我们对基础神经生物学的了解有限,神经性贪食症和暴食症 (BN/BED) 的治疗取得了进展。在这里,我们测量了局部脑血流量 (rCBF),以绘制与健康对照组相比 BN/BED 女性的静息灌注异常情况,并研究作为潜在治疗方案提出的鼻内催产素 (OT) 是否可以恢复与疾病相关的脑回路的灌注。24 名患有 BN/BED 的女性和 23 名健康女性参加了一项随机、双盲、交叉、安慰剂对照研究。我们使用动脉自旋标记 MRI 来测量 rCBF 和急性剂量的鼻内 OT(40 IU)或安慰剂在给药后 18-26 分钟内的影响,因为我们之前已经显示了 OT 诱导的男性静息 rCBF 的强烈变化。类似的时间窗口(给药后 15-36 分钟)。我们测试了治疗、诊断及其相互作用对提取的感兴趣解剖区域中的 rCBF 值的影响,这些感兴趣区域之前与其他神经影像学方式涉及 BN/BED,并进行了探索性全脑分析以调查以前未识别的大脑区域。我们证明,患有 BN/BED 的女性在内侧前额叶和眶额叶皮质、前扣带回、后岛叶和双侧颞中/下回的静息 rCBF 增加。这些区域的过度灌注与患者的进食症状严重程度特别相关。我们的数据不支持鼻内 OT 对这些患者灌注异常的正常化作用,至少对于检查的特定剂量 (40 IU) 和给药后间隔 (18-26 分钟)。我们的研究结果增强了我们对 BN/BED 中静息脑异常的理解,并将静息 rCBF 确定为疾病相关变化和治疗监测的非侵入性潜在生物标志物。他们还强调需要对女性的鼻内 OT 药效学进行全面调查,然后才能完全确定其在主要影响该性别的疾病中的治疗价值,例如 BN/BED。