The relationship between Hippocampal asymmetry and working memory processing in combat-related PTSD: a monozygotic twin study

BACKGROUND: PTSD is associated with reduction in hippocampal volume and abnormalities in hippocampal function. Hippocampal asymmetry has received less attention, but potentially could indicate lateralised differences in vulnerability to trauma. The P300 event-related potential component reflects the immediate processing of significant environmental stimuli and has generators in several brain regions including the hippocampus. P300 amplitude is generally reduced in people with PTSD. METHODS: Our study examined hippocampal volume asymmetry and the relationship between hippocampal asymmetry and P300 amplitude in male monozygotic twins discordant for Vietnam combat exposure. Lateralised hippocampal volume and P300 data were obtained from 70 male participants, of whom 12 had PTSD. We were able to compare (1) combat veterans with current PTSD; (2) their non-combat-exposed co-twins; (3) combat veterans without current PTSD and (4) their non-combat-exposed co-twins. RESULTS: There were no significant differences between groups in hippocampal asymmetry. There were no group differences in performance of an auditory oddball target detection task or in P300 amplitude. There was a significant positive correlation between P300 amplitude and the magnitude of hippocampal asymmetry in participants with PTSD. CONCLUSIONS: These findings suggest that greater hippocampal asymmetry in PTSD is associated with a need to allocate more attentional resources when processing significant environmental stimuli.Timothy Hall, Cherrie Galletly, C.R. Clark, Melinda Veltmeyer, Linda J. Metzger, Mark W. Gilbertson, Scott P. Orr, Roger K. Pitman and Alexander McFarlan

Biol Psychiatry Cogn Neurosci Neuroimaging

Background:Posttraumatic Stress Disorder (PTSD) is a debilitating disorder and there is no current accurate prediction of who develops it after trauma. Neurobiologically, individuals with chronic PTSD exhibit aberrant resting-state functional connectivity (rsFC) between the hippocampus and other brain regions (e.g., amygdala, prefrontal cortex, posterior cingulate), and these aberrations correlate with severity of illness. Prior small-scale research (n < 25) has also shown that hippocampal-rsFC measured acutely after trauma is predictive of future severity using an ROI-based approach. While a promising biomarker, to-date no study has employed a data-driven approach to test whole-brain hippocampal-FC patterns in forecasting the development of PTSD symptoms.Methods:Ninety-eight adults at risk of PTSD were recruited from the emergency department following traumatic injury and completed resting functional magnetic resonance imaging (rsfMRI; 8min) within 1-month; 6-months later they completed the Clinician-Administered PTSD Scale (CAPS-5) for assessment of PTSD symptom severity. Whole-brain rsFC values with bilateral hippocampi were extracted (CONN) and used in a machine learning kernel ridge regression analysis (PRoNTo); both a k-folds (k=10) and 70/30 testing vs. training split approach were used for cross-validation (1,000 iterations to bootstrap confidence intervals for significance values).Results:Acute hippocampal-rsFC significantly predicted CAPS-5 scores at 6-months (r=0.30, p=0.006; MSE=120.58, p=0.006; R2=0.09, p=0.025). In post-hoc analyses, hippocampal-rsFC remained significant after controlling for demographics, PTSD symptoms at baseline, and depression, anxiety, and stress severity at 6-months (B=0.59, SE=0.20, p=0.003).Conclusions:Findings suggest functional connectivity of the hippocampus across the brain acutely after traumatic injury is associated with prospective PTSD symptom severity.TL1 TR001437/TR/NCATS NIH HHSUnited States/R01 MH106574/MH/NIMH NIH HHSUnited States/U01 CE002944/CE/NCIPC CDC HHSUnited States/UL1 TR001436/TR/NCATS NIH HHSUnited States/U01 NS088034/NS/NINDS NIH HHSUnited States

Avoidant symptoms in PTSD predict fear circuit activation during multimodal fear extinction

Convergent evidence suggests that individuals with posttraumatic stress disorder (PTSD) exhibit exaggerated avoidance behaviors as well as abnormalities in Pavlonian fear conditioning. However, the link between the two features of this disorder is not well understood. In order to probe the brain basis of aberrant extinction learning in PTSD, we administered a multimodal classical fear conditioning/extinction paradigm that incorporated affectively relevant information from two sensory channels (visual and tactile) while participants underwent fMRI scanning. The sample consisted of fifteen OEF/OIF veterans with PTSD. In response to conditioned cues and contextual information, greater avoidance symptomatology was associated with greater activation in amygdala, hippocampus, vmPFC, dmPFC, and insula, during both fear acquisition and fear extinction. Heightened responses to previously conditioned stimuli in individuals with more severe PTSD could indicate a deficiency in safety learning, consistent with PTSD symptomatology. The close link between avoidance symptoms and fear circuit activation suggests that this symptom cluster may be a key component of fear extinction deficits in PTSD and/or may be particularly amenable to change through extinction-based therapie

The Impact of the Brain-Derived Neurotrophic Factor Gene on Trauma and Spatial Processing.

The influence of genes and the environment on the development of Post-Traumatic Stress Disorder (PTSD) continues to motivate neuropsychological research, with one consistent focus being the Brain-Derived Neurotrophic Factor (BDNF) gene, given its impact on the integrity of the hippocampal memory system. Research into human navigation also considers the BDNF gene in relation to hippocampal dependent spatial processing. This speculative paper brings together trauma and spatial processing for the first time and presents exploratory research into their interactions with BDNF. We propose that quantifying the impact of BDNF on trauma and spatial processing is critical and may well explain individual differences in clinical trauma treatment outcomes and in navigation performance. Research has already shown that the BDNF gene influences PTSD severity and prevalence as well as navigation behaviour. However, more data are required to demonstrate the precise hippocampal dependent processing mechanisms behind these influences in different populations and environmental conditions. This paper provides insight from recent studies and calls for further research into the relationship between allocentric processing, trauma processing and BDNF. We argue that research into these neural mechanisms could transform PTSD clinical practice and professional support for individuals in trauma-exposing occupations such as emergency response, law enforcement and the military

Autonomic and brain morphological predictors of stress resilience

Stressful life events are an important cause of psychopathology. Humans exposed to aversive or stressful experiences show considerable inter-individual heterogeneity in their responses. However, the majority does not develop stress-related psychiatric disorders. The dynamic processes encompassing positive and functional adaptation in the face of significant adversity have been broadly defined as resilience. Traditionally, the assessment of resilience has been confined to self-report measures, both within the general community and putative high-risk populations. Although this approach has value, it is highly susceptible to subjective bias and may not capture the dynamic nature of resilience, as underlying construct. Recognizing the obvious benefits of more objective measures of resilience, research in the field has just started investigating the predictive value of several potential biological markers. This review provides an overview of theoretical views and empirical evidence suggesting that individual differences in heart rate variability (HRV), a surrogate index of resting cardiac vagal outflow, may underlie different levels of resilience toward the development of stress-related psychiatric disorders. Following this line of thought, recent studies describing associations between regional brain morphometric characteristics and resting state vagally-mediated HRV are summarized. Existing studies suggest that the structural morphology of the anterior cingulated cortex (ACC), particularly its cortical thickness, is implicated in the expression of individual differences in HRV. These findings are discussed in light of emerging structural neuroimaging research, linking morphological characteristics of the ACC to psychological traits ascribed to a high-resilient profile and abnormal structural integrity of the ACC to the psychophysiological expression of stress-related mental health consequences. We conclude that a multidisciplinary approach integrating brain structural imaging with HRV monitoring could offer novel perspectives about brain-body pathways in resilience and adaptation to psychological stres

Neural Impact of Neighborhood Socioeconomic Disadvantage in Traumatically Injured Adults

Nearly 14 percent of Americans live in a socioeconomically disadvantaged neighborhood. Lower individual socioeconomic position (iSEP) has been linked to increased exposure to trauma and stress, as well as to alterations in brain structure and function; however, the neural effects of neighborhood SEP (nSEP) factors, such as neighborhood disadvantage, are unclear. Using a multi-modal approach with participants who recently experienced a traumatic injury (N = 185), we investigated the impact of neighborhood disadvantage, acute post-traumatic stress symptoms, and iSEP on brain structure and functional connectivity at rest. After controlling for iSEP, demographic variables, and acute PTSD symptoms, nSEP was associated with decreased volume and alterations of resting-state functional connectivity in structures implicated in affective processing, including the insula, ventromedial prefrontal cortex, amygdala, and hippocampus. Even in individuals who have recently experienced a traumatic injury, and after accounting for iSEP, the impact of living in a disadvantaged neighborhood is apparent, particularly in brain regions critical for experiencing and regulating emotion. These results should inform future research investigating how various levels of socioeconomic circumstances may impact recovery after a traumatic injury as well as policies and community-developed interventions aimed at reducing the impact of socioeconomic stressors