Differential Role of mGluR5 in Cognitive Processes in Posttraumatic Stress Disorder and Major Depression.
Differential Role of mGluR5 in Cognitive Processes in Posttraumatic Stress Disorder and Major Depression.
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DOI：
10.1177/24705470221105804
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发表时间：
2022-01
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影响因子：
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通讯作者：
Davis, Margaret T
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文献类型：
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作者：
Esterlis, Irina;DeBonee, Sarah;Cool, Ryan;Holmes, Sophie;Baldassari, Stephen R;Maruff, Paul;Pietrzak, Robert H;Davis, Margaret T
一篇强有力的文献支持代谢型谷氨酸受体5(MGluR5)在认知功能中的作用。MGluR5还与创伤后应激障碍(PTSD)和严重抑郁障碍(MDD)的病理生理学有关，这两种疾病的特点是认知改变。然而，mGluR5与MDD和PTSD患者认知功能的关系尚未得到直接研究。为了解决这一差距，我们研究了创伤后应激障碍、MDD和匹配的健康成年人(HA)体内mGluR5的可用性和认知之间的关系。患有创伤后应激障碍(N = 28)、精神发育迟缓(N = 21)和HA(N = 28)的患者在年龄、性别和吸烟状况方面是匹配的。参与者完成了18F-FPEB正电子发射断层扫描(PET)、精神和认知评估。在检验mGluR5可用性和不同诊断组认知领域之间关系的模型中，只有诊断*注意的交互作用显著(F4，64 = 3.011，P = .024)。在4个感兴趣的额叶边缘区域(ROI：OFC(r = −.441，P = .016)，vmPFC(r = −.408，P = .028)，dlPFC(r = −.421，P = .023)，海马区(r = −.422，P = .025)，mGluR5的可用性与创伤后应激障碍的注意力较差相关。相比之下，mGluR5在MDD组的可用性与OFC(r = .590，P = .006)、vmPFC(r = .653，P = .002)和dlPFC(r = .620，P = .004)中的注意力(ATTN)呈正相关。MDD患者海马区的发现遵循相同的模式，但在多次比较中未能幸存(r = .480，P = .036)。在HA组中，ATTN和mGluR5的可用性没有显著相关性。值得注意的是，在MANOVA分析组中，OFC中的ATTN交互作用结果没有通过多次比较(P = .046)。所有其他发现在多次比较的校正中存活下来，并且在潜在混淆(例如，抑郁情绪)的协变时仍然具有显著意义。我们观察到在患有MDD和PTSD的个体中，额叶边缘mGluR5的可用性和注意力测试中的表现之间存在显著的关系。这一发现与动物研究表明mGluR5在认知功能中的失调是一致的，并且作为诊断的功能是不同的。结果表明，针对mGluR5的干预可能有助于增强认知障碍，强调了在MDD和PTSD中采用不同的mGluR5指导治疗策略的重要性。
A robust literature supports the role of the metabotropic glutamate receptor type 5 (mGluR5) in cognitive functioning. mGluR5 is also implicated in the pathophysiology of posttraumatic stress disorder (PTSD) and major depressive disorder (MDD), which are characterized by cognitive alterations. However, the relationship between mGluR5 and cognition in MDD and PTSD has not yet been directly investigated. To address this gap, we examined the relationship between in vivo mGluR5 availability and cognition in PTSD, MDD, and matched healthy adults (HA). Individuals with PTSD (N = 28) and MDD (N = 21), and HA (N = 28) were matched for age, gender, and smoking status. Participants completed 18F-FPEB positron emission tomography (PET) scan, psychiatric and cognitive assessments. Across models examining the relationship between mGluR5 availability and different domains of cognition across diagnostic groups, only the interaction of diagnosis*attention was significant (F4,64 = 3.011, P = .024). Higher mGluR5 availability was associated with poorer attention in PTSD in 4 frontolimbic regions of interests (ROI's: OFC (r = −.441, P = .016), vmPFC (r = −.408, P = .028), dlPFC (r = −.421, P = .023), hippocampus (r = −.422, P = .025). By contrast, mGluR5 availability in the MDD group was positively related to Attention (ATTN) in the OFC (r = .590, P = .006), vmPFC (r = .653, P = .002), and dlPFC (r = .620, P = .004). Findings in the hippocampus for MDD followed the same pattern but did not survive correction for multiple comparisons (r = .480, P = .036). ATTN and mGluR5 availability were not significantly related in the HA group. Of note, in MANOVA analyses group*ATTN interaction results in the OFC did not survive multiple comparisons (P = .046). All other findings survived correction for multiple comparisons and remained significant when covarying for potential confounds (eg, depressed mood). We observed a significant relationship between frontolimbic mGluR5 availability and performance on tests of attention in individuals with MDD and PTSD. This finding aligns with animal work showing dysregulation in mGluR5 in cognitive functioning, and differed as a function of diagnosis. Results suggest interventions targeting mGluR5 may help bolster cognitive difficulties, highlighting the importance of employing different mGluR5 directed treatment strategies in MDD and PTSD.