Serum Neurosteroid Levels Are Associated With Cortical Thickness in Individuals Diagnosed With Posttraumatic Stress Disorder and History of Mild Traumatic Brain Injury

Abstract

<jats:p> Posttraumatic stress disorder (PTSD) co-occurring with mild traumatic brain injury (mTBI) is common in veterans. Worse clinical outcome in those with PTSD has been associated with decreased serum neurosteroid levels. Furthermore, decreased cortical thickness has been associated with both PTSD and mTBI. However, it is not known whether decreased neurosteroids are associated with decreased cortical thickness in PTSD co-occurring with mTBI. This study included 141 individuals divided into the following groups: ( a) mTBI group (n = 32 [10 female, 22 male] veterans with a history of mTBI); ( b) PTSD + mTBI group (n = 41 [6 female, 35 male] veterans with current PTSD with a history of mTBI); and ( c) control group (n = 68 [35 female, 33 male] control participants), which were acquired through the Injury and Traumatic Stress (INTRuST) Clinical Consortium. Subjects underwent clinical assessment, magnetic resonance imaging at 3 T, and serum neurosteroid quantifications of allopregnanolone (ALLO) and pregnenolone (PREGN). Group differences in cortical thickness and associations between serum neurosteroid levels and cortical thickness were investigated. Cortical thickness was decreased in the PTSD + mTBI group compared with the other groups. In the PTSD + mTBI group, decreased cortical thickness was also associated with lower serum ALLO (right superior frontal cortex) and lower serum PREGN (left middle temporal and right orbitofrontal cortex). Cortical thickness in the middle temporal and orbitofrontal cortex was associated with PTSD symptom severity. There were no significant associations between neurosteroids and cortical thickness in the mTBI or control groups. Decreased cortical thickness in individuals with PTSD + mTBI is associated with decreased serum neurosteroid levels and greater PTSD symptom severity. Causality is unclear. However, future studies might investigate whether treatment with neurosteroids could counteract stress-induced neural atrophy in PTSD + mTBI by potentially preserving cortical thickness. </jats:p>

A mega-analysis of vertex and gyral cortical thickness differences in adults with and without PTSD

“…The ndings of present mega-analysis across entire hemispheres are consistent with PTSD-related cortical thinning in individual studies 17,19,24,25,27,28,30,31,33,34,53 , with thinner cortex in right LING and left SMG that has not been reported previously. The present parallel mega-analyses of vertex and gyral cortical thicknesses in the same subjects identi ed substantial overlap between the two measurements, suggesting that the thinner vertex clusters do not stem from confounds of spatial transformations during vertex-based analysis.…”

“…Single-cohort studies with small sample sizes have reported lower gyral mean thickness [24][25][26][27] and thinner focal vertex clusters within a gyrus 19,[28][29][30] . Affected regions in adult PTSD patients include the prefrontal 17,[24][25][26][28][29][30][31] , cingulate 17,25,27,29,32 , parietal 26,28,29,31 , temporal 24,27,28,30,31,33,34 , occipital 17,29,30 , parahippocampal 26 and fusiform gyri 19,31 . Cortical thickness measures in PTSD patients have been reported to be negatively associated with PTSD symptom severity 20,33,35 .…”

“…Cortical thickness measures have been analyzed in animal 16 and human cortical thickness studies have investigated the effects of childhood trauma 17 , combat exposure [18][19][20] , and genetic factors [21][22][23] on cortical structure. Single-cohort studies with small sample sizes have reported lower gyral mean thickness [24][25][26][27] and thinner focal vertex clusters within a gyrus 19,[28][29][30] . Affected regions in adult PTSD patients include the prefrontal 17,[24][25][26][28][29][30][31] , cingulate 17,25,27,29,32 , parietal 26,28,29,31 , temporal 24,27,28,30,31,33,34 , occipital 17,29,30 , parahippocampal 26 and fusiform gyri 19,31 .…”

Improving Cognitive Function Through High-Intensity Interval Training in Breast Cancer Patients Undergoing Chemotherapy: Protocol for a Randomized Controlled Trial

“…Automated brain region segmentation is performed using the open-source FreeSurfer program (Martinos Center for Biomedical Imaging) [ 19 ] with manual correction [ 20 ]. Segmentation is used for primary volumetric analyses [ 21 , 22 ]. We examine the amygdala-hippocampus complex and thalamic and ventricular volumes and perform an exploratory comprehensive volumetric analysis.…”

Sleep Quality Disturbances Are Associated with White Matter Alterations in Veterans with Post-Traumatic Stress Disorder and Mild Traumatic Brain Injury

“…The final sample for the current project consisted of 180 participants, which were classified into four groups based on lifetime diagnoses of PTSD and mTBI: PTSD only (n = 38), mTBI only (n = 25), comorbid PTSD+mTBI (n = 94), and no history of PTSD or mTBI (n = 23). We opted for this grouping approach based on previous studies in veteran populations [52,71]. We used cumulative lifetime diagnoses, as previous studies demonstrate a stronger influence on GM and WM structure when considering lifetime diagnoses [51,72], suggesting that disorder-related neurobiological effects persist or even increase over time.…”