背景:阐明导致双相情感障碍(BD)的生物学机制是改善诊断和治疗发展的关键。随着越来越多的证据表明代谢型谷氨酸受体5(mGlu5)与BD的病理有关,在这里,因此,我们检验了以下假设:最近发现的mGlu5缺陷与BD情绪处理过程中的大脑功能差异有关。
方法:使用带有[18F]FPEB的正电子发射断层扫描(PET)来测量mGlu5受体的可用性,并在参与者完成情绪处理任务时进行功能成像(fMRI)。对62名个体(33±12岁,45%女性)完成PET和fMRI,包括BD患者(n=18),重度抑郁症(MDD:n=20),和精神病学健康比较(HC:n=25)。
结果:与以前的一些报告一致,相对于MDD和HC,BD组在恐惧处理过程中显示出更大的激活,特别是在右侧额叶和顶叶脑区。在BD,(而不是MDD或HC)较低的前额叶mGlu5可用性与恐惧过程中双侧前/后中央回回和cuneus的更大激活有关。此外,BD中与mGlu5相关的前额叶大脑活动增加与精神运动功能困难(r≥0.904,p≤0.005)和注意力困难(r≥0.809,p≤0.028)相关.
结论:适度的样本量是主要的限制。
结论:BD的前额叶mGlu5缺陷与恐惧过程中皮质激活增加有关,这反过来又与冲动和注意力困难有关。这些数据进一步暗示了BD特有的mGlu5相关机制。更一般地,这些数据表明,整合PET和fMRI可以提供新的机械见解。
BACKGROUND: Elucidating biological mechanisms contributing to bipolar disorder (BD) is key to improved diagnosis and treatment development. With converging evidence implicating the metabotropic glutamate receptor 5 (mGlu5) in the pathology of BD, here, we therefore test the hypothesis that recently identified deficits in mGlu5 are associated with functional brain differences during emotion processing in BD.
METHODS: Positron emission tomography (PET) with [18F]FPEB was used to measure mGlu5 receptor availability and functional imaging (fMRI) was performed while participants completed an emotion processing task. Data were analyzed from 62 individuals (33 ± 12 years, 45 % female) who completed both PET and fMRI, including individuals with BD (n = 18), major depressive disorder (MDD: n = 20), and psychiatrically healthy comparisons (HC: n = 25).
RESULTS: Consistent with some prior reports, the BD group displayed greater activation during fear processing relative to MDD and HC, notably in right lateralized frontal and parietal brain regions. In BD, (but not MDD or HC) lower prefrontal mGlu5 availability was associated with greater activation in bilateral pre/postcentral gyri and cuneus during fear processing. Furthermore, greater prefrontal mGlu5-related brain activity in BD was associated with difficulties in psychomotor function (r≥0.904, p≤0.005) and attention (r≥0.809, p≤0.028).
CONCLUSIONS: The modest sample size is the primary limitation.
CONCLUSIONS: Deficits in prefrontal mGlu5 in BD were linked to increased cortical activation during fear processing, which in turn was associated with impulsivity and attentional difficulties. These data further implicate an mGlu5-related mechanism unique to BD. More generally these data suggest integrating PET and fMRI can provide novel mechanistic insights.