Associations of alcohol and cannabis use with change in posttraumatic stress disorder and depression symptoms over time in recently trauma-exposed individuals.

BACKGROUND: Several hypotheses may explain the association between substance use, posttraumatic stress disorder (PTSD), and depression. However, few studies have utilized a large multisite dataset to understand this complex relationship. Our study assessed the relationship between alcohol and cannabis use trajectories and PTSD and depression symptoms across 3 months in recently trauma-exposed civilians. METHODS: In total, 1618 (1037 female) participants provided self-report data on past 30-day alcohol and cannabis use and PTSD and depression symptoms during their emergency department (baseline) visit. We reassessed participant's substance use and clinical symptoms 2, 8, and 12 weeks posttrauma. Latent class mixture modeling determined alcohol and cannabis use trajectories in the sample. Changes in PTSD and depression symptoms were assessed across alcohol and cannabis use trajectories via a mixed-model repeated-measures analysis of variance. RESULTS: Three trajectory classes (low, high, increasing use) provided the best model fit for alcohol and cannabis use. The low alcohol use class exhibited lower PTSD symptoms at baseline than the high use class; the low cannabis use class exhibited lower PTSD and depression symptoms at baseline than the high and increasing use classes; these symptoms greatly increased at week 8 and declined at week 12. Participants who already use alcohol and cannabis exhibited greater PTSD and depression symptoms at baseline that increased at week 8 with a decrease in symptoms at week 12. CONCLUSIONS: Our findings suggest that alcohol and cannabis use trajectories are associated with the intensity of posttrauma psychopathology. These findings could potentially inform the timing of therapeutic strategies.

Sex-dependent differences in vulnerability to early risk factors for posttraumatic stress disorder: results from the AURORA study.

BACKGROUND: Knowledge of sex differences in risk factors for posttraumatic stress disorder (PTSD) can contribute to the development of refined preventive interventions. Therefore, the aim of this study was to examine if women and men differ in their vulnerability to risk factors for PTSD. METHODS: As part of the longitudinal AURORA study, 2924 patients seeking emergency department (ED) treatment in the acute aftermath of trauma provided self-report assessments of pre- peri- and post-traumatic risk factors, as well as 3-month PTSD severity. We systematically examined sex-dependent effects of 16 risk factors that have previously been hypothesized to show different associations with PTSD severity in women and men. RESULTS: Women reported higher PTSD severity at 3-months post-trauma. Z-score comparisons indicated that for five of the 16 examined risk factors the association with 3-month PTSD severity was stronger in men than in women. In multivariable models, interaction effects with sex were observed for pre-traumatic anxiety symptoms, and acute dissociative symptoms; both showed stronger associations with PTSD in men than in women. Subgroup analyses suggested trauma type-conditional effects. CONCLUSIONS: Our findings indicate mechanisms to which men might be particularly vulnerable, demonstrating that known PTSD risk factors might behave differently in women and men. Analyses did not identify any risk factors to which women were more vulnerable than men, pointing toward further mechanisms to explain women's higher PTSD risk. Our study illustrates the need for a more systematic examination of sex differences in contributors to PTSD severity after trauma, which may inform refined preventive interventions.

Structural inequities contribute to racial/ethnic differences in neurophysiological tone, but not threat reactivity, after trauma exposure.

Considerable racial/ethnic disparities persist in exposure to life stressors and socioeconomic resources that can directly affect threat neurocircuitry, particularly the amygdala, that partially mediates susceptibility to adverse posttraumatic outcomes. Limited work to date, however, has investigated potential racial/ethnic variability in amygdala reactivity or connectivity that may in turn be related to outcomes such as post-traumatic stress disorder (PTSD). Participants from the AURORA study (n = 283), a multisite longitudinal study of trauma outcomes, completed functional magnetic resonance imaging and psychophysiology within approximately two-weeks of trauma exposure. Seed-based amygdala connectivity and amygdala reactivity during passive viewing of fearful and neutral faces were assessed during fMRI. Physiological activity was assessed during Pavlovian threat conditioning. Participants also reported the severity of posttraumatic symptoms 3 and 6 months after trauma. Black individuals showed lower baseline skin conductance levels and startle compared to White individuals, but no differences were observed in physiological reactions to threat. Further, Hispanic and Black participants showed greater amygdala connectivity to regions including the dorsolateral prefrontal cortex (PFC), dorsal anterior cingulate cortex, insula, and cerebellum compared to White participants. No differences were observed in amygdala reactivity to threat. Amygdala connectivity was associated with 3-month PTSD symptoms, but the associations differed by racial/ethnic group and were partly driven by group differences in structural inequities. The present findings suggest variability in tonic neurophysiological arousal in the early aftermath of trauma between racial/ethnic groups, driven by structural inequality, impacts neural processes that mediate susceptibility to later PTSD symptoms.

Internal capsule microstructure mediates the relationship between childhood maltreatment and PTSD following adulthood trauma exposure.

Childhood trauma is a known risk factor for trauma and stress-related disorders in adulthood. However, limited research has investigated the impact of childhood trauma on brain structure linked to later posttraumatic dysfunction. We investigated the effect of childhood trauma on white matter microstructure after recent trauma and its relationship with future posttraumatic dysfunction among trauma-exposed adult participants (n = 202) recruited from emergency departments as part of the AURORA Study. Participants completed self-report scales assessing prior childhood maltreatment within 2-weeks in addition to assessments of PTSD, depression, anxiety, and dissociation symptoms within 6-months of their traumatic event. Fractional anisotropy (FA) obtained from diffusion tensor imaging (DTI) collected at 2-weeks and 6-months was used to index white matter microstructure. Childhood maltreatment load predicted 6-month PTSD symptoms (b = 1.75, SE = 0.78, 95% CI = [0.20, 3.29]) and inversely varied with FA in the bilateral internal capsule (IC) at 2-weeks (p = 0.0294, FDR corrected) and 6-months (p = 0.0238, FDR corrected). We observed a significant indirect effect of childhood maltreatment load on 6-month PTSD symptoms through 2-week IC microstructure (b = 0.37, Boot SE = 0.18, 95% CI = [0.05, 0.76]) that fully mediated the effect of childhood maltreatment load on PCL-5 scores (b = 1.37, SE = 0.79, 95% CI = [-0.18, 2.93]). IC microstructure did not mediate relationships between childhood maltreatment and depressive, anxiety, or dissociative symptomatology. Our findings suggest a unique role for IC microstructure as a stable neural pathway between childhood trauma and future PTSD symptoms following recent trauma. Notably, our work did not support roles of white matter tracts previously found to vary with PTSD symptoms and childhood trauma exposure, including the cingulum bundle, uncinate fasciculus, and corpus callosum. Given the IC contains sensory fibers linked to perception and motor control, childhood maltreatment might impact the neural circuits that relay and process threat-related inputs and responses to trauma.

Hippocampal Threat Reactivity Interacts with Physiological Arousal to Predict PTSD Symptoms.

Hippocampal impairments are reliably associated with post-traumatic stress disorder (PTSD); however, little research has characterized how increased threat-sensitivity may interact with arousal responses to alter hippocampal reactivity, and further how these interactions relate to the sequelae of trauma-related symptoms. In a sample of individuals recently exposed to trauma (N=116, 76 Female), we found that PTSD symptoms at 2-weeks were associated with decreased hippocampal responses to threat as assessed with functional magnetic resonance imaging (fMRI). Further, the relationship between hippocampal threat sensitivity and PTSD symptomology only emerged in individuals who showed transient, high threat-related arousal, as assayed by an independently collected measure of Fear Potentiated Startle. Collectively, our finding suggests that development of PTSD is associated with threat-related decreases in hippocampal function, due to increases in fear-potentiated arousal.Significance StatementAlterations in hippocampal function linked to threat-related arousal are reliably associated with post-traumatic stress disorder (PTSD); however, how these alterations relate to the sequelae of trauma-related symptoms is unknown. Prior models based on non-trauma samples suggest that arousal may impact hippocampal neurophysiology leading to maladaptive behavior. Here we show that decreased hippocampal threat sensitivity interacts with fear-potentiated startle to predict PTSD symptoms. Specifically, individuals with high fear-potentiated startle and low, transient hippocampal threat sensitivity showed the greatest PTSD symptomology. These findings bridge literatures of threat-related arousal and hippocampal function to better understand PTSD risk.

Neuroimaging-based classification of PTSD using data-driven computational approaches: A multisite big data study from the ENIGMA-PGC PTSD consortium.

BACKGROUND: Recent advances in data-driven computational approaches have been helpful in devising tools to objectively diagnose psychiatric disorders. However, current machine learning studies limited to small homogeneous samples, different methodologies, and different imaging collection protocols, limit the ability to directly compare and generalize their results. Here we aimed to classify individuals with PTSD versus controls and assess the generalizability using a large heterogeneous brain datasets from the ENIGMA-PGC PTSD Working group. METHODS: We analyzed brain MRI data from 3,477 structural-MRI; 2,495 resting state-fMRI; and 1,952 diffusion-MRI. First, we identified the brain features that best distinguish individuals with PTSD from controls using traditional machine learning methods. Second, we assessed the utility of the denoising variational autoencoder (DVAE) and evaluated its classification performance. Third, we assessed the generalizability and reproducibility of both models using leave-one-site-out cross-validation procedure for each modality. RESULTS: We found lower performance in classifying PTSD vs. controls with data from over 20 sites (60 % test AUC for s-MRI, 59 % for rs-fMRI and 56 % for d-MRI), as compared to other studies run on single-site data. The performance increased when classifying PTSD from HC without trauma history in each modality (75 % AUC). The classification performance remained intact when applying the DVAE framework, which reduced the number of features. Finally, we found that the DVAE framework achieved better generalization to unseen datasets compared with the traditional machine learning frameworks, albeit performance was slightly above chance. CONCLUSION: These results have the potential to provide a baseline classification performance for PTSD when using large scale neuroimaging datasets. Our findings show that the control group used can heavily affect classification performance. The DVAE framework provided better generalizability for the multi-site data. This may be more significant in clinical practice since the neuroimaging-based diagnostic DVAE classification models are much less site-specific, rendering them more generalizable.

Derivation and Validation of a Brief Emergency Department-Based Prediction Tool for Posttraumatic Stress After Motor Vehicle Collision.

STUDY OBJECTIVE: To derive and initially validate a brief bedside clinical decision support tool that identifies emergency department (ED) patients at high risk of substantial, persistent posttraumatic stress symptoms after a motor vehicle collision. METHODS: Derivation (n=1,282, 19 ED sites) and validation (n=282, 11 separate ED sites) data were obtained from adults prospectively enrolled in the Advancing Understanding of RecOvery afteR traumA study who were discharged from the ED after motor vehicle collision-related trauma. The primary outcome was substantial posttraumatic stress symptoms at 3 months (Posttraumatic Stress Disorder Checklist for Diagnostic and Statistical Manual of Mental Disorders-5 ≥38). Logistic regression derivation models were evaluated for discriminative ability using the area under the curve and the accuracy of predicted risk probabilities (Brier score). Candidate posttraumatic stress predictors assessed in these models (n=265) spanned a range of sociodemographic, baseline health, peritraumatic, and mechanistic domains. The final model selection was based on performance and ease of administration. RESULTS: Significant 3-month posttraumatic stress symptoms were common in the derivation (27%) and validation (26%) cohort. The area under the curve and Brier score of the final 8-question tool were 0.82 and 0.14 in the derivation cohort and 0.76 and 0.17 in the validation cohort. CONCLUSION: This simple 8-question tool demonstrates promise to risk-stratify individuals with substantial posttraumatic stress symptoms who are discharged to home after a motor vehicle collision. Both external validation of this instrument, and work to further develop more accurate tools, are needed. Such tools might benefit public health by enabling the conduct of preventive intervention trials and assisting the growing number of EDs that provide services to trauma survivors aimed at promoting psychological recovery.

Socio-demographic and trauma-related predictors of depression within eight weeks of motor vehicle collision in the AURORA study.

BACKGROUND: This is the first report on the association between trauma exposure and depression from the Advancing Understanding of RecOvery afteR traumA(AURORA) multisite longitudinal study of adverse post-traumatic neuropsychiatric sequelae (APNS) among participants seeking emergency department (ED) treatment in the aftermath of a traumatic life experience. METHODS: We focus on participants presenting at EDs after a motor vehicle collision (MVC), which characterizes most AURORA participants, and examine associations of participant socio-demographics and MVC characteristics with 8-week depression as mediated through peritraumatic symptoms and 2-week depression. RESULTS: Eight-week depression prevalence was relatively high (27.8%) and associated with several MVC characteristics (being passenger v. driver; injuries to other people). Peritraumatic distress was associated with 2-week but not 8-week depression. Most of these associations held when controlling for peritraumatic symptoms and, to a lesser degree, depressive symptoms at 2-weeks post-trauma. CONCLUSIONS: These observations, coupled with substantial variation in the relative strength of the mediating pathways across predictors, raises the possibility of diverse and potentially complex underlying biological and psychological processes that remain to be elucidated in more in-depth analyses of the rich and evolving AURORA database to find new targets for intervention and new tools for risk-based stratification following trauma exposure.

Altered white matter microstructural organization in posttraumatic stress disorder across 3047 adults: results from the PGC-ENIGMA PTSD consortium.

A growing number of studies have examined alterations in white matter organization in people with posttraumatic stress disorder (PTSD) using diffusion MRI (dMRI), but the results have been mixed which may be partially due to relatively small sample sizes among studies. Altered structural connectivity may be both a neurobiological vulnerability for, and a result of, PTSD. In an effort to find reliable effects, we present a multi-cohort analysis of dMRI metrics across 3047 individuals from 28 cohorts currently participating in the PGC-ENIGMA PTSD working group (a joint partnership between the Psychiatric Genomics Consortium and the Enhancing NeuroImaging Genetics through Meta-Analysis consortium). Comparing regional white matter metrics across the full brain in 1426 individuals with PTSD and 1621 controls (2174 males/873 females) between ages 18-83, 92% of whom were trauma-exposed, we report associations between PTSD and disrupted white matter organization measured by lower fractional anisotropy (FA) in the tapetum region of the corpus callosum (Cohen's d = -0.11, p = 0.0055). The tapetum connects the left and right hippocampus, for which structure and function have been consistently implicated in PTSD. Results were consistent even after accounting for the effects of multiple potentially confounding variables: childhood trauma exposure, comorbid depression, history of traumatic brain injury, current alcohol abuse or dependence, and current use of psychotropic medications. Our results show that PTSD may be associated with alterations in the broader hippocampal network.

Socio-demographic and trauma-related predictors of PTSD within 8 weeks of a motor vehicle collision in the AURORA study.

This is the initial report of results from the AURORA multisite longitudinal study of adverse post-traumatic neuropsychiatric sequelae (APNS) among participants seeking emergency department (ED) treatment in the aftermath of a traumatic life experience. We focus on n = 666 participants presenting to EDs following a motor vehicle collision (MVC) and examine associations of participant socio-demographic and participant-reported MVC characteristics with 8-week posttraumatic stress disorder (PTSD) adjusting for pre-MVC PTSD and mediated by peritraumatic symptoms and 2-week acute stress disorder (ASD). Peritraumatic Symptoms, ASD, and PTSD were assessed with self-report scales. Eight-week PTSD prevalence was relatively high (42.0%) and positively associated with participant sex (female), low socioeconomic status (education and income), and several self-report indicators of MVC severity. Most of these associations were entirely mediated by peritraumatic symptoms and, to a lesser degree, ASD, suggesting that the first 2 weeks after trauma may be a uniquely important time period for intervening to prevent and reduce risk of PTSD. This observation, coupled with substantial variation in the relative strength of mediating pathways across predictors, raises the possibility of diverse and potentially complex underlying biological and psychological processes that remain to be elucidated with more in-depth analyses of the rich and evolving AURORA data.

Cortical volume abnormalities in posttraumatic stress disorder: an ENIGMA-psychiatric genomics consortium PTSD workgroup mega-analysis.

Studies of posttraumatic stress disorder (PTSD) report volume abnormalities in multiple regions of the cerebral cortex. However, findings for many regions, particularly regions outside commonly studied emotion-related prefrontal, insular, and limbic regions, are inconsistent and tentative. Also, few studies address the possibility that PTSD abnormalities may be confounded by comorbid depression. A mega-analysis investigating all cortical regions in a large sample of PTSD and control subjects can potentially provide new insight into these issues. Given this perspective, our group aggregated regional volumes data of 68 cortical regions across both hemispheres from 1379 PTSD patients to 2192 controls without PTSD after data were processed by 32 international laboratories using ENIGMA standardized procedures. We examined whether regional cortical volumes were different in PTSD vs. controls, were associated with posttraumatic stress symptom (PTSS) severity, or were affected by comorbid depression. Volumes of left and right lateral orbitofrontal gyri (LOFG), left superior temporal gyrus, and right insular, lingual and superior parietal gyri were significantly smaller, on average, in PTSD patients than controls (standardized coefficients = -0.111 to -0.068, FDR corrected P values < 0.039) and were significantly negatively correlated with PTSS severity. After adjusting for depression symptoms, the PTSD findings in left and right LOFG remained significant. These findings indicate that cortical volumes in PTSD patients are smaller in prefrontal regulatory regions, as well as in broader emotion and sensory processing cortical regions.

Prior histories of posttraumatic stress disorder and major depression and their onset and course in the three months after a motor vehicle collision in the AURORA study.

BACKGROUND: A better understanding of the extent to which prior occurrences of posttraumatic stress disorder (PTSD) and major depressive episode (MDE) predict psychopathological reactions to subsequent traumas might be useful in targeting posttraumatic preventive interventions. METHODS: Data come from 1306 patients presenting to 29 U.S. emergency departments (EDs) after a motor vehicle collision (MVC) in the advancing understanding of recovery after trauma study. Patients completed self-reports in the ED and 2-weeks, 8-weeks, and 3-months post-MVC. Associations of pre-MVC probable PTSD and probable MDE histories with subsequent 3-months post-MVC probable PTSD and probable MDE were examined along with mediation through intervening peritraumatic, 2-, and 8-week disorders. RESULTS: 27.6% of patients had 3-month post-MVC probable PTSD and/or MDE. Pre-MVC lifetime histories of these disorders were not only significant (relative risk = 2.6-7.4) but were dominant (63.1% population attributable risk proportion [PARP]) predictors of this 3-month outcome, with 46.6% prevalence of the outcome among patients with pre-MVC disorder histories versus 9.9% among those without such histories. The associations of pre-MVC lifetime disorders with the 3-month outcome were mediated largely by 2- and 8-week probable PTSD and MDE (PARP decreasing to 22.8% with controls for these intervening disorders). Decomposition showed that pre-MVC lifetime histories predicted both onset and persistence of these intervening disorders as well as the higher conditional prevalence of the 3-month outcome in the presence of these intervening disorders. CONCLUSIONS: Assessments of pre-MVC PTSD and MDE histories and follow-ups at 2 and 8 weeks could help target early interventions for psychopathological reactions to MVCs.

The AURORA Study: a longitudinal, multimodal library of brain biology and function after traumatic stress exposure.

Adverse posttraumatic neuropsychiatric sequelae (APNS) are common among civilian trauma survivors and military veterans. These APNS, as traditionally classified, include posttraumatic stress, postconcussion syndrome, depression, and regional or widespread pain. Traditional classifications have come to hamper scientific progress because they artificially fragment APNS into siloed, syndromic diagnoses unmoored to discrete components of brain functioning and studied in isolation. These limitations in classification and ontology slow the discovery of pathophysiologic mechanisms, biobehavioral markers, risk prediction tools, and preventive/treatment interventions. Progress in overcoming these limitations has been challenging because such progress would require studies that both evaluate a broad spectrum of posttraumatic sequelae (to overcome fragmentation) and also perform in-depth biobehavioral evaluation (to index sequelae to domains of brain function). This article summarizes the methods of the Advancing Understanding of RecOvery afteR traumA (AURORA) Study. AURORA conducts a large-scale (n = 5000 target sample) in-depth assessment of APNS development using a state-of-the-art battery of self-report, neurocognitive, physiologic, digital phenotyping, psychophysical, neuroimaging, and genomic assessments, beginning in the early aftermath of trauma and continuing for 1 year. The goals of AURORA are to achieve improved phenotypes, prediction tools, and understanding of molecular mechanisms to inform the future development and testing of preventive and treatment interventions.

Impact Statement Coding of Self-Related Thought in Women With Posttraumatic Stress Disorder.

Clinical and empirical studies have documented significant alterations in self-related thought in posttraumatic stress disorder (PTSD). To our knowledge, however, few studies have examined self-referential cognition by analyzing survivors' written impact statements in individuals whose PTSD is due to interpersonal trauma. In the current study, we performed a linguistic analysis of impact statements (i.e., descriptions of how the trauma has affected the survivors' views of themselves, others, and the world) collected at the start of therapy from women with PTSD that was due to interpersonal trauma, with the goal of determining whether PTSD symptom clusters were associated with altered self-referential thought. We found that higher levels of PTSD-related hyperarousal symptoms were significantly associated with diminished self-related word use, after controlling for depression severity, f2 = .31. Similarly, diminished negative self-related word use was associated with higher levels of hyperarousal symptoms, f2 = .47. Our findings align with previous research that has provided evidence for a diminished sense of self in PTSD. These results may help inform targeted interventions aimed at improving social-affective functions in PTSD and other psychiatric conditions.

Spanish Abstracts by Asociación Chilena de Estrés Traumático (ACET) Codificación de la declaración de impacto del pensamiento auto relacionado en mujeres con trastorno de estrés postraumático. PENSAMIENTO AUTORELACIONADO EN TEPT Los estudios clínicos y empíricos han documentado alteraciones significativas en el pensamiento relacionado con el sí-mismo en el trastorno por estrés postraumático (TEPT). Sin embargo, según nuestro conocimiento, pocos estudios han examinado la cognición autorreferencial mediante el análisis de las declaraciones de impacto escritas de los sobrevivientes en individuos cuyo trastorno de estrés postraumático se debe a un trauma interpersonal. En el estudio actual, realizamos un análisis lingüístico de las declaraciones de impacto (es decir, descripciones de cómo el trauma ha afectado las opiniones de los sobrevivientes sobre ellos mismos, otros y el mundo) recopiladas antes del inicio de la terapia en mujeres con TEPT causado por un trauma interpersonal, con el objetivo de determinar si los grupos de síntomas de TEPT estaban asociados con un pensamiento auto-referencial alterado. Encontramos que un nivel más alto de síntomas de hiperactivación relacionados con el TEPT se asoció significativamente con una disminución del uso de palabras autorreferentes después de controlar la gravedad de la depresión, f2 = .31. De manera similar, la disminución del uso de palabras autorreferentes negativas también se asoció con un mayor nivel de síntomas de hiperactivación, f2 = .47. Nuestros hallazgos se alinean con investigaciones anteriores que han proporcionado evidencia de un sentido de sí mismo disminuido en el TEPT. Estos resultados pueden ayudar a informar las intervenciones dirigidas a mejorar las funciones socio-afectivas en el TEPT y otras afecciones psiquiátricas. Palabras clave: fenomenología del trastorno de estrés postraumático, emoción, cognición, culpa / culpa propia.

Neural Correlates of Trait Rumination During an Emotion Interference Task in Women With PTSD.

Rumination, defined as repetitive, negative, self-focused thinking, is hypothesized to be a transdiagnostic factor that is associated with depression, anxiety, and posttraumatic stress disorder (PTSD). Theory has suggested that in individuals with PTSD, rumination serves as a cognitive avoidance factor that contributes to the maintenance of symptoms by inhibiting the cognitive and emotional processing of the traumatic event, subsequently interfering with treatment engagement and outcome. Little is known about the neural correlates of rumination in women with PTSD. The current study utilized functional magnetic resonance imaging (fMRI) to examine neural correlates during an emotion interference task of self-reported rumination in women with PTSD. Women with PTSD (39 participants) were recruited at a university-based trauma clinic and completed a clinical evaluation that included measures of PTSD symptoms, rumination, and depressive symptoms, as well as a neuroimaging session in which the participants were administered an emotion interference task. There was a significant relationship between self-reported rumination and activity in the right orbital frontal cortex, BA 11; t(37) = 5.62, p = .004, k = 46 during the task. This finding suggested that women with PTSD, who had higher levels of rumination, may experience greater difficulty inhibiting negative emotional stimuli compared to women with lower levels of rumination.

Improvements in concentration, working memory and sustained attention following consumption of a natural citicoline-caffeine beverage.

This study examined the neurocognitive and electrophysiological effects of a citicoline-caffeine-based beverage in 60 healthy adult participants enrolled in a randomized, double-blind, placebo-controlled trial. Measures of electrical brain activity using electroencephalogram (EEG) and neuropsychological measures examining attention, concentration and reaction time were administered. Compared to placebo, participants receiving the citicoline-caffeine beverage exhibited significantly faster maze learning times and reaction times on a continuous performance test, fewer errors in a go/no-go task and better accuracy on a measure of information processing speed. EEG results examining P450 event-related potentials revealed that participants receiving the citicoline-caffeine beverage exhibited higher P450 amplitudes than controls, suggesting an increase in sustained attention. Overall, these findings suggest that the beverage significantly improved sustained attention, cognitive effort and reaction times in healthy adults. Evidence of improved P450 amplitude indicates a general improvement in the ability to accommodate new and relevant information within working memory and overall enhanced brain activation.

Pro-inflammatory markers are related to cortical network connectivity in women exposed to interpersonal trauma with PTSD.

Exposure to interpersonal violence affects a significant number of individuals each year and further increases the risk for developing Posttraumatic Stress Disorder (PTSD). A growing body of research suggests that immune system dysfunction, in particular elevated inflammation, may contribute to the pathophysiology of PTSD. However, few studies have examined the neurobiological correlates of inflammation in women with PTSD using resting-state fMRI. The present study explored the relationship between pro-inflammatory cytokine levels, C-reactive protein (CRP), tumor necrosis factor alpha TNF-alpha), and interleukin-6 (IL-6), and resting-state functional connectivity patterns in three major cortical networks (default mode network (DMN), central executive network (CEN), and salience network (SN)) in a sample of women (N=18) exposed to interpersonal violence with PTSD. Results indicated that higher CRP levels were associated with stronger functional connectivity between the SN and visual areas, but weaker functional connectivity between the CEN and visual areas. These findings suggest that pro-inflammatory markers are related to connectivity of task-positive networks in women with PTSD. Further, our results provide evidence for potential neurobiological markers of inflammation in PTSD.

Intensive longitudinal assessment following index trauma to predict development of PTSD using machine learning.

There are significant challenges to identifying which individuals require intervention following exposure to trauma, and a need for strategies to identify and provide individuals at risk for developing PTSD with timely interventions. The present study seeks to identify a minimal set of trauma-related symptoms, assessed during the weeks following traumatic exposure, that can accurately predict PTSD. Participants were 2185 adults (Mean age=36.4 years; 64% women; 50% Black) presenting for emergency care following traumatic exposure. Participants received a 'flash survey' with 6-8 varying symptoms (from a pool of 26 trauma symptoms) several times per week for eight weeks following the trauma exposure (each symptom assessed ∼6 times). Features (mean, sd, last, worst, peak-end scores) from the repeatedly assessed symptoms were included as candidate variables in a CART machine learning analysis to develop a pragmatic predictive algorithm. PTSD (PCL-5 ≥38) was present for 669 (31%) participants at the 8-week follow-up. A classification tree with three splits, based on mean scores of nervousness, rehashing, and fatigue, predicted PTSD with an Area Under the Curve of 0.836. Findings suggest feasibility for a 3-item assessment protocol, delivered once per week, following traumatic exposure to assess and potentially facilitate follow-up care for those at risk.

Post-traumatic stress and future substance use outcomes: leveraging antecedent factors to stratify risk.

Background: Post-traumatic stress disorder (PTSD) and substance use (tobacco, alcohol, and cannabis) are highly comorbid. Many factors affect this relationship, including sociodemographic and psychosocial characteristics, other prior traumas, and physical health. However, few prior studies have investigated this prospectively, examining new substance use and the extent to which a wide range of factors may modify the relationship to PTSD. Methods: The Advancing Understanding of RecOvery afteR traumA (AURORA) study is a prospective cohort of adults presenting at emergency departments (N = 2,943). Participants self-reported PTSD symptoms and the frequency and quantity of tobacco, alcohol, and cannabis use at six total timepoints. We assessed the associations of PTSD and future substance use, lagged by one timepoint, using the Poisson generalized estimating equations. We also stratified by incident and prevalent substance use and generated causal forests to identify the most important effect modifiers of this relationship out of 128 potential variables. Results: At baseline, 37.3% (N = 1,099) of participants reported likely PTSD. PTSD was associated with tobacco frequency (incidence rate ratio (IRR): 1.003, 95% CI: 1.00, 1.01, p = 0.02) and quantity (IRR: 1.01, 95% CI: 1.001, 1.01, p = 0.01), and alcohol frequency (IRR: 1.002, 95% CI: 1.00, 1.004, p = 0.03) and quantity (IRR: 1.003, 95% CI: 1.001, 1.01, p = 0.001), but not with cannabis use. There were slight differences in incident compared to prevalent tobacco frequency and quantity of use; prevalent tobacco frequency and quantity were associated with PTSD symptoms, while incident tobacco frequency and quantity were not. Using causal forests, lifetime worst use of cigarettes, overall self-rated physical health, and prior childhood trauma were major moderators of the relationship between PTSD symptoms and the three substances investigated. Conclusion: PTSD symptoms were highly associated with tobacco and alcohol use, while the association with prospective cannabis use is not clear. Findings suggest that understanding the different risk stratification that occurs can aid in tailoring interventions to populations at greatest risk to best mitigate the comorbidity between PTSD symptoms and future substance use outcomes. We demonstrate that this is particularly salient for tobacco use and, to some extent, alcohol use, while cannabis is less likely to be impacted by PTSD symptoms across the strata.