Neuroanatomical Risk Factors for Post Traumatic Stress Disorder (PTSD) in Recent Trauma Survivors

Abstract

Background: Low hippocampal volume could serve as an early risk factor for Post-traumatic Stress Disorder (PTSD) in interaction with other brain anomalies of developmental origin. One such anomaly may well be a presence of large Cavum Septum Pellucidum (CSP), which has been loosely associated with PTSD. Here, we performed a longitudinal prospective study of recent trauma survivors. We hypothesized that at one-month after trauma exposure, the relation between hippocampal volume and PTSD symptom severity will be moderated by CSP volume, and that this early interaction will account for persistent PTSD symptoms at subsequent time-points. Methods: 171 adults (87 females, average age=34.22, range=18-65) admitted to a general hospital's emergency department following a traumatic event, underwent clinical assessment and structural MRI within one-month after trauma. Follow-up clinical evaluations were conducted at six (n=97) and fourteen (n=78) months after trauma. Hippocampus and CSP volumes were measured automatically by FreeSurfer software and verified manually by a neuroradiologist.Results: At one-month following trauma, CSP volume significantly moderated the relation between hippocampal volume and PTSD severity (p=0.026), and this interaction further predicted symptom severity at fourteen months post-trauma (p=0.018). Specifically, individuals with smaller hippocampus and larger CSP at one-month post-trauma, showed more severe symptoms at one-and fourteen months following trauma exposure. Conclusions:Our study provides evidence for an early neuroanatomical risk factors for PTSD, which could also predict the progression of the disorder in the year following trauma exposure.Such a simple-to-acquire neuroanatomical signature for PTSD could guide early management, as well as long-term monitoring. Trial Registration: Neurobehavioral Moderators of Post-traumatic Disease Trajectories. ClinicalTrials.gov registration: NCT03756545. https://clinicaltrials.gov/ct2/show/NCT03756545 National Institute of Mental Health (NIMH) given to AS (PI), IL and TH (co-Investigators, subcontractors), and had undergone critical review by the NIMH Adult Psychopathology and Disorders of Aging study section. Nevertheless, the NIMH had no role in the design, execution, data management and data analysis of the current study. Sagol School of Neuroscience at Tel-Aviv University supported ZB fellowships, and Sagol Brain Institute at Tel-Aviv Sourasky Medical Center supported NK and HS fellowships. A preliminary version of this work was previously published in Biorxiv (https://www.biorxiv.org/content/10.1101/721068v1). Disclosures:The authors declare that they have no financial disclosures and no conflict of interests.As mentioned in the participants section, the present study is part of a larger on-going project that examines PTSD development in trauma survivors. The authors declare that they report all measures, conditions and data exclusions, as pertain to outlined hypotheses, obtained from all the participants who completed assessments within one-m...

Neural Responsivity to Reward Versus Punishment Shortly After Trauma Predicts Long-Term Development of Posttraumatic Stress Symptoms

“…An intermediary point of 6-months post-trauma might be too early to capture the tangible chronic PTSD subtype, whereas 14-months may portray a more stable representation of the chronic disorder, as it was shown to predict over 90% of the expected recovery from PTSD 113,114 . A similar trend of null-results at TP2 was observed in a previous analysis of this data set examining neuroanatomical risk factors for PTSD 115 .…”

Deep learning model of fMRI connectivity predicts PTSD symptom trajectories in recent trauma survivors

“…It is worth noting that our resting state connectivity patterns were less significant at T2. Nevertheless, as was shown in previous work ( Ben-Zion, Artzi, Niry, Keynan, Zeevi, et al., 2019 , Ben-Zion, Shany, Admon, Keynan, Avisdris, Balter, Shalev, Liberzon, Hendler ), it might be explained by the dynamic clinical manifestations during the first critical year after trauma ( Hepp et al., 2008 ), in which an intermediary point of six-months might be too ”noisy” to isolate chronic PTSD symptom cluster. This is also supported by similar results in previous work examining structural abnormalities in this cohort ( Ben-Zion et al., 2019a ), as well as the lowered prediction results at Table 2 , Table 3 , Table 4 for T2.…”

“…The development of PTSD in a subgroup of survivors, and the tenacity of the protracted disorder, suggest a long-lasting trauma induced neuro-behavioral alteration ( Pitman et al., 2012 ). Longitudinal studies examining multi-modal dimensions of the response to trauma (e.g., symptoms, cognitive functions, brain structure and functioning) are optimally suited to detect the underlying neuro-behavioral moderators of non remitting PTSD ( Ben-Zion, Artzi, Niry, Keynan, Zeevi, et al., 2019 , Ben-Zion, Fine, Keynan, Admon, Green, Halevi, Fonzo, Achituv, et al., 2018 , Pitman, Rasmusson, Koenen, Shin, Orr, Gilbertson, Milad, Liberzon, 2012 , Shalev, Liberzon, Marmar, 2017 ).…”

Altered brain activity and functional connectivity after MDMA-assisted therapy for post-traumatic stress disorder

“…We found a trend suggesting that RSFC between the amygdala and hippocampus was strengthened post-therapy, particularly in the left hemisphere (Figure 3). Prior work suggests that modulation of amygdalae-hippocampal RSFC may be an important component of MDMA-AT for PTSD (43,(51)(52)(53)(54)(55), thus investigating this connection in future studies is warranted. We also found participants had increased activation in areas involved with self-referential processing and autobiographical memory while listening to traumatic versus neutral memory narrations pre-therapy (Figures 4A-D), and that no significant contrast existed after MDMA-AT (Figure 4E).…”

“…Sripada et al (43) found combat veterans with PTSD have decreased amygdala-hippocampal resting-state functional connectivity (RSFC) compared to combat veterans without PTSD, which the authors speculate may represent an inability to contextualize affective information in PTSD. Increased amygdala-hippocampal RSFC following stress/trauma exposure has been shown to correlate with recovery from stress or trauma symptoms (51)(52)(53), suggesting a possible adaptive mechanism to threat exposure. In healthy volunteers, the acute administration of MDMA increases amygdala-hippocampal RSFC (54).…”