Psychiatry Neuroimaging Laboratory, Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States.
Psychiatry Neuroimaging Laboratory, Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States; Department of Neurology, University Hospital, LMU Munich, Munich, Germany.
Neuroimage Clin. 2020;26:102190. doi: 10.1016/j.nicl.2020.102190. Epub 2020 Jan 22.
Post-traumatic stress disorder (PTSD) is a psychiatric disorder that afflicts many individuals, yet the neuropathological mechanisms that contribute to this disorder remain to be fully determined. Moreover, it is unclear how exposure to mild traumatic brain injury (mTBI), a condition that is often comorbid with PTSD, particularly among military personnel, affects the clinical and neurological presentation of PTSD. To address these issues, the present study explores relationships between PTSD symptom severity and the microstructure of limbic and paralimbic gray matter brain regions, as well as the impact of mTBI comorbidity on these relationships.
Structural and diffusion MRI data were acquired from 102 male veterans who were diagnosed with current PTSD. Diffusion data were analyzed with free-water imaging to quantify average CSF-corrected fractional anisotropy (FA) and mean diffusivity (MD) in 18 limbic and paralimbic gray matter regions. Associations between PTSD symptom severity and regional average dMRI measures were examined with repeated measures linear mixed models. Associations were studied separately in veterans with PTSD only, and in veterans with PTSD and a history of military mTBI.
Analyses revealed that in the PTSD only cohort, more severe symptoms were associated with higher FA in the right amygdala-hippocampus complex, lower FA in the right cingulate cortex, and lower MD in the left medial orbitofrontal cortex. In the PTSD and mTBI cohort, more severe PTSD symptoms were associated with higher FA bilaterally in the amygdala-hippocampus complex, with higher FA bilaterally in the nucleus accumbens, with lower FA bilaterally in the cingulate cortex, and with higher MD in the right amygdala-hippocampus complex.
These findings suggest that the microstructure of limbic and paralimbic brain regions may influence PTSD symptomatology. Further, given the additional associations observed between microstructure and symptom severity in veterans with head trauma, we speculate that mTBI may exacerbate the impact of brain microstructure on PTSD symptoms, especially within regions of the brain known to be vulnerable to chronic stress. A heightened sensitivity to the microstructural environment of the brain could partially explain why individuals with PTSD and mTBI comorbidity experience more severe symptoms and poorer illness prognoses than those without a history of brain injury. The relevance of these microstructural findings to the conceptualization of PTSD as being a disorder of stress-induced neuronal connectivity loss is discussed.
创伤后应激障碍（PTSD）是一种影响许多人的精神疾病，但导致这种疾病的神经病理学机制仍有待充分确定。此外，目前尚不清楚轻度创伤性脑损伤（mTBI）的暴露，这种情况通常与 PTSD 共病，尤其是在军事人员中，如何影响 PTSD 的临床和神经表现。为了解决这些问题，本研究探讨了 PTSD 症状严重程度与边缘和边缘下灰质脑区微观结构之间的关系，以及 mTBI 共病对这些关系的影响。
从 102 名被诊断为当前 PTSD 的男性退伍军人中获取结构和扩散 MRI 数据。使用自由水成像分析扩散数据，以量化 18 个边缘和边缘下灰质区域的平均 CSF 校正分数各向异性（FA）和平均弥散度（MD）。使用重复测量线性混合模型检查 PTSD 症状严重程度与区域平均 dMRI 测量值之间的关联。分别在仅患有 PTSD 的退伍军人和患有 PTSD 和军事 mTBI 病史的退伍军人中进行了关联研究。
分析表明，在仅患有 PTSD 的队列中，更严重的症状与右侧杏仁核-海马复合体的 FA 升高、右侧扣带回的 FA 降低以及左侧内侧眶额皮质的 MD 降低有关。在 PTSD 和 mTBI 队列中，更严重的 PTSD 症状与双侧杏仁核-海马复合体的 FA 升高、双侧伏隔核的 FA 升高、双侧扣带回的 FA 降低以及右侧杏仁核-海马复合体的 MD 升高有关。
这些发现表明，边缘和边缘下脑区的微观结构可能会影响 PTSD 的症状表现。此外，鉴于在头部创伤的退伍军人中观察到的微观结构与症状严重程度之间的额外关联，我们推测 mTBI 可能会加剧大脑微观结构对 PTSD 症状的影响，尤其是在已知易受慢性应激影响的大脑区域。对大脑微观环境的敏感性增加可能部分解释了为什么 PTSD 和 mTBI 共病的个体比没有脑损伤病史的个体经历更严重的症状和更差的疾病预后。讨论了这些微观结构发现与 PTSD 作为一种应激诱导神经元连接丧失障碍的概念化之间的相关性。
