Esterlis Irina, DeBonee Sarah, Cool Ryan, Holmes Sophie, Baldassari Stephen R, Maruff Paul, Pietrzak Robert H, Davis Margaret T
Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA.
Department of Psychology, Yale University, New Haven, CT, USA.
Chronic Stress (Thousand Oaks). 2022 Aug 4;6:24705470221105804. doi: 10.1177/24705470221105804. eCollection 2022 Jan-Dec.
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 mGluR5 availability and cognition in PTSD, MDD, and matched healthy adults (HA).
Individuals with PTSD ( = 28) and MDD ( = 21), and HA ( = 28) were matched for age, gender, and smoking status. Participants completed F-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 diagnosisattention was significant ( = 3.011, = .024). Higher mGluR5 availability was associated with poorer attention in PTSD in 4 frontolimbic regions of interests (ROI's: OFC ( = -.441, = .016), vmPFC ( = -.408, = .028), dlPFC ( = -.421, = .023), hippocampus ( = -.422, = .025). By contrast, mGluR5 availability in the MDD group was positively related to Attention (ATTN) in the OFC ( = .590, = .006), vmPFC ( = .653, = .002), and dlPFC ( = .620, = .004). Findings in the hippocampus for MDD followed the same pattern but did not survive correction for multiple comparisons ( = .480, = .036). ATTN and mGluR5 availability were not significantly related in the HA group. Of note, in MANOVA analyses groupATTN interaction results in the OFC did not survive multiple comparisons ( = .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.
大量文献支持代谢型谷氨酸受体5（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）的病理生理学有关，这两种疾病都以认知改变为特征。然而，mGluR5与MDD和PTSD认知之间的关系尚未得到直接研究。为了填补这一空白，我们研究了PTSD、MDD患者以及匹配的健康成年人（HA）中mGluR5可用性与认知之间的关系。
PTSD患者（n = 28）、MDD患者（n = 21）和HA（n = 28）在年龄、性别和吸烟状况方面进行了匹配。参与者完成了F-FPEB正电子发射断层扫描（PET）、精神科和认知评估。
在检查mGluR5可用性与不同诊断组认知不同领域之间关系的模型中，只有诊断注意力的交互作用显著（F = 3.011，p = 0.024）。在4个前额叶边缘感兴趣区域（ROI：眶额皮质（OFC）（r = -0.441，p = 0.016）、腹内侧前额叶皮质（vmPFC）（r = -0.408，p = 0.028）、背外侧前额叶皮质（dlPFC）（r = -0.421，p = 0.023）、海马体（r = -0.422，p = 0.025））中，PTSD患者中较高的mGluR5可用性与较差的注意力相关。相比之下，MDD组中mGluR5可用性与OFC（r = 0.590，p = 0.006）、vmPFC（r = 0.653，p = 0.002）和dlPFC（r = 0.620，p = 0.004）的注意力（ATTN）呈正相关。MDD患者海马体中的结果遵循相同模式，但在多重比较校正后不显著（r = 0.480，p = 0.036）。HA组中ATTN与mGluR5可用性无显著相关性。值得注意的是，在多变量方差分析（MANOVA）中，OFC中组ATTN交互作用结果在多重比较后不显著（p = 0.046）。所有其他结果在多重比较校正后仍然显著，并且在对潜在混杂因素（如抑郁情绪）进行协变量调整时仍然显著。
我们观察到MDD和PTSD患者前额叶边缘mGluR5可用性与注意力测试表现之间存在显著关系。这一发现与动物研究结果一致，表明mGluR5在认知功能中存在失调，并且因诊断而异。结果表明，针对mGluR5的干预可能有助于改善认知困难，突出了在MDD和PTSD中采用不同的mGluR5导向治疗策略的重要性。
