Differential Role of mGluR5 in Cognitive Processes in Posttraumatic Stress Disorder and Major Depression.

Q1 Psychology Chronic Stress Pub Date : 2022-08-04 eCollection Date: 2022-01-01 DOI:10.1177/24705470221105804

Irina Esterlis, Sarah DeBonee, Ryan Cool, Sophie Holmes, Stephen R Baldassari, Paul Maruff, Robert H Pietrzak, Margaret T Davis

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引用次数: 2

Abstract

Background: 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).

Methods: 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.

Results: Across models examining the relationship between mGluR5 availability and different domains of cognition across diagnostic groups, only the interaction of diagnosis*attention was significant (F _4,64 = 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).

Conclusions: 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.

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mGluR5在创伤后应激障碍和重度抑郁症认知过程中的差异作用。

背景:大量文献支持代谢性谷氨酸受体5型(mGluR5)在认知功能中的作用。mGluR5也与创伤后应激障碍(PTSD)和重度抑郁症(MDD)的病理生理有关，这两种疾病的特征是认知改变。然而，mGluR5与认知在MDD和PTSD中的关系尚未被直接研究。为了解决这一差距，我们研究了体内mGluR5可用性与PTSD、MDD和匹配健康成人(HA)认知之间的关系。方法:将PTSD (N = 28)、MDD (N = 21)、HA (N = 28)患者按年龄、性别、吸烟状况进行匹配。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。结果:在检查mGluR5可用性与诊断组不同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 = 0.024)。较高的mGluR5可用性与PTSD患者4个感兴趣的额叶边缘区域(ROI’s: OFC)的注意力较差相关(r = -)。441, P = 0.016)， vmPFC (r = -。408, P = 0.028)， dlPFC (r = -。421, P = 0.023)，海马(r = -。422, p = 0.025)。相比之下，MDD组的mGluR5可用性与OFC的注意力(ATTN)呈正相关(r =。(P = .006)， vmPFC (r =。653, P = .002)， dlPFC (r =。620, p = .004)。在海马体中，重度抑郁症的发现遵循相同的模式，但在多次比较中没有幸存下来(r =)。480, p = 0.036)。在HA组中，ATTN和mGluR5可用性无显著相关。值得注意的是，在方差分析中，组*ATTN相互作用的结果在OFC中没有存活多次比较(P = 0.046)。所有其他发现在多重比较校正后仍然有效，并且在协变潜在混杂因素(如抑郁情绪)时仍然显著。结论:我们观察到前额叶mGluR5的可用性与MDD和PTSD患者在注意力测试中的表现之间存在显著关系。这一发现与动物实验一致，表明mGluR5在认知功能中失调，但在诊断功能上有所不同。结果表明，针对mGluR5的干预措施可能有助于改善认知困难，强调了在MDD和PTSD中采用不同的mGluR5指导治疗策略的重要性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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