Less is more: Smaller hippocampal subfield volumes predict greater improvements in posttraumatic stress disorder symptoms over 2 years.

Posttraumatic stress disorder (PTSD) is a heterogeneous disorder, and symptom severity varies over time. Neurobiological factors that predict PTSD symptoms and their chronicity remain unclear. This study investigated whether the volume of the hippocampus and its subfields, particularly cornu ammonis (CA) 1, CA3, and dentate gyrus, are associated with current PTSD symptoms and whether they predict PTSD symptom changes over 2 years. We examined clinical and structural magnetic resonance imaging measures from 252 trauma-exposed post-9/11 veterans (159 with Time 1 PTSD diagnosis) during assessments approximately 2 years apart. Automated hippocampal subfield segmentation was performed with FreeSurfer Version 7.1, producing 19 bilateral subfields. PTSD symptoms were measured at each assessment using the Clinician-Administered PTSD Scale-IV (CAPS). All models included total intracranial volume as a covariate. First, similar to previous reports, we showed that smaller overall hippocampal volume was associated with greater PTSD symptom severity at Time 1. Notably, when examining regions of interest (CA1, CA3, dentate gyrus), we found that smaller Time 1 hippocampal volumes in the bilateral CA1-body and CA2/3-body predicted decreased PTSD symptom severity at Time 2. These findings were not accounted for by combat exposure or treatment history. Additionally, both Time 1 CA1-body and CA2/3-body volume showed unique associations with changes in avoidance/numbing, but not with changes in reexperiencing or hyperarousal symptoms. This supports a more complex and nuanced relationship between hippocampal structure and PTSD symptoms, where during the posttrauma years bigger may not always mean better, and suggests that the CA1-body and CA2/3-body are important factors in the maintenance of PTSD symptoms. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Emotional reactivity linking assaultive trauma and risky behavior: Evidence of differences between cisgender women and men.

Accumulating evidence suggests that trauma exposure is positively associated with future engagement in risky behavior, such as substance misuse, aggression, risky sex, and self-harm. However, the psychological factors driving this association and their relevance across gender groups require further clarification. In a community sample of 375 adults with a high rate of trauma exposure (age range: 18-55 years, M = 32.98 years, SD = 10.64; 76.3% assaultive trauma exposure), we examined whether emotional reactivity linked lifetime assaultive trauma exposure with past-month risky behavior. We also explored whether this model differed for cisgender women (n = 178, 47.6%) and men (n = 197, 52.5%). As hypothesized, assaultive trauma was positively related to emotional reactivity, ß = .20, SE = 0.03, t(369) = 3.65, p < .001, which, in turn, partially accounted for the association between assaultive trauma and past-month risky behavior, indirect effect: ß = .03, SE = 0.01, 95% bootstrapped CI [0.01, 0.06]. Gender moderated this association such that assaultive trauma was indirectly associated with risky behavior via emotional reactivity for women but not for men, index moderation: B = -0.03, SE = 0.02, 95% bootstrapped CI [-0.07, -0.01]. Cross-sectional results suggest that emotional reactivity may be a proximal target for clinical intervention to aid in the reduction of risky behavior among women.

Neurobiological metric of cortical delay discounting differentiates risk for self- and other-directed violence among trauma-exposed individuals.

Self- and other-directed violence (SDV/ODV) contribute to elevated rates of mortality. Early trauma exposure shows robust positive associations with these forms of violence but alone does not distinguish those at heightened risk for later engagement in SDV/ODV. Novel assessment metrics could aid early identification efforts for individuals with vulnerabilities to violence perpetration. This study examined a novel neurobiological measure of impulsive choice for reward as a potential moderator of associations between childhood trauma exposure and lifetime SDV/ODV. A high-risk community sample of 177 adults (89 men; 50.3%) were assessed for childhood trauma exposure, engagement in SDV (e.g., suicide attempts), and ODV (e.g., assault). A cortical delay discounting (C-DD) measure was created using a multivariate additive model of gray matter thickness across both hemispheres, previously found to be positively associated with susceptibility to impulsivity and externalizing disorders. Childhood trauma exposure was positively associated with ODV and SDV; however, these relationships differed as a function of C-DD. Engagement in ODV increased as scores on C-DD increased, and SDV increased as scores on C-DD decreased. Furthermore, moderation revealed biological sex differences, as the association between childhood trauma and SDV depended on C-DD for women but not for men. Findings from the present work demonstrate that risk conferred by childhood trauma exposure to violence varied as a function of a C-DD. Together, these findings point to the utility of neurobiological markers of impulsive decision-making for differentiating risk for violence among individuals with a history of trauma exposure. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Inhibitory control and alcohol use history predict changes in posttraumatic stress disorder symptoms.

OBJECTIVE: Posttraumatic stress disorder (PTSD) is associated with significant disability and can become chronic. Predictors of PTSD symptom changes over time, especially in those with a PTSD diagnosis, remain incompletely characterized. METHOD: In the present study, we examined 187 post-9/11 veterans (Mage = 32.8 years, 87% male) diagnosed with PTSD who performed two extensive clinical and cognitive evaluations approximately 2 years apart. RESULTS: We found that greater PTSD symptom reductions over time were related to lower lifetime drinking history and better baseline inhibitory control ability (Color-Word Inhibition and Inhibition/Switching), though not performance on other executive function tasks. Further, groups with reliably Improved, Worsened, or Chronic PTSD symptoms demonstrated significant differences in baseline inhibitory control and lifetime drinking history, with marked drinking differences starting in the early-to-mid 20s. We also found that PTSD symptom changes showed little-to-no associations with changes in inhibitory control or alcohol consumption. CONCLUSIONS: Together, these findings suggest that, in those diagnosed with PTSD, inhibitory control and alcohol use history reflect relatively stable risk/resiliency factors predictive of PTSD chronicity. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Aberrant connectivity in the right amygdala and right middle temporal gyrus before and after a suicide attempt: Examining markers of suicide risk.

Functional neuroimaging has the potential to help identify those at risk for self-injurious thoughts and behaviors, as well as inform neurobiological mechanisms that contribute to suicide. Based on whole-brain patterns of functional connectivity, our previous work identified right amygdala and right middle temporal gyrus (MTG) connectivity patterns that differentiated Veterans with a history of a suicide attempt (SA) from a Veteran control group. In this study, we aimed to replicate and extend our previous findings by examining whether this aberrant connectivity was present prior to and after a SA. In a trauma-exposed Veteran sample (92 % male, mean age = 34), we characterized if the right amygdala and right MTG connectivity differed between a psychiatric control sample (n = 56) and an independent sample of Veterans with a history of SA (n = 17), using fMRI data before and after the SA. Right MTG and amygdala connectivity differed between Veterans with and without a history of SA (replication), while MTG connectivity also distinguished Veterans prior to engaging in a SA (extension). In a second study, neither MTG or amygdala connectivity differed between those with current suicidal ideation (n = 27) relative to matched psychiatric controls (n = 27). These results indicate a potential stable marker of suicide risk (right MTG connectivity) as well as a potential marker of acute risk of or recent SA (right amygdala connectivity) that are independent of current ideation.

An executive function subtype of PTSD with unique neural markers and clinical trajectories.

Previous work identified a cognitive subtype of PTSD with impaired executive function (i.e., impaired EF-PTSD subtype) and aberrant resting-state functional connectivity between frontal parietal control (FPCN) and limbic (LN) networks. To better characterize this cognitive subtype of PTSD, this study investigated (1) alterations in specific FPCN and LN subnetworks and (2) chronicity of PTSD symptoms. In a post-9/11 veteran sample (N = 368, 89% male), we identified EF subgroups using a standardized neuropsychological battery and a priori cutoffs for impaired, average, and above-average EF performance. Functional connectivity between two subnetworks of the FPCN and three subnetworks of the LN was assessed using resting-state fMRI (n = 314). PTSD chronicity over a 1-2-year period was assessed using a reliable change index (n = 175). The impaired EF-PTSD subtype had significantly reduced negative functional connectivity between the FPCN subnetwork involved in top-down control of emotion and two LN subnetworks involved in learning/memory and social/emotional processing. This impaired EF-PTSD subtype had relatively chronic PTSD, while those with above-average EF and PTSD displayed greater symptom reduction. Lastly, FPCN-LN subnetworks partially mediated the relationship between EF and PTSD chronicity (n = 121). This study reveals (1) that an impaired EF-PTSD subtype has a specific pattern of FPCN-LN subnetwork connectivity, (2) a novel above-average EF-PTSD subtype displays reduced PTSD chronicity, and (3) both cognitive and neural functioning predict PTSD chronicity. The results indicate a need to investigate how individuals with this impaired EF-PTSD subtype respond to treatment, and how they might benefit from personalized and novel approaches that target these neurocognitive systems.

Associations between changes in somatic and psychiatric symptoms and disability alterations in recent-era U.S. veterans.

Cross-sectional work suggests that deployment-related posttraumatic sequelae are associated with increased disability in U.S. veterans deployed following the September 11, 2001 (9/11), terrorist attacks. However, few studies have examined the psychiatric and somatic variables associated with changes in functional disability over time. A total of 237 post-9/11 veterans completed comprehensive assessments of psychiatric and cognitive functioning, as well as a disability questionnaire, at baseline and 2-year follow-up. At baseline, higher levels of PTSD, depressive, and pain-related symptoms were associated with baseline global functional disability, semipartial r2 = .036-.044. Changes in symptoms of PTSD, depression, pain, and sleep, but not anxiety or alcohol use, were independently associated with changes in functional disability, semipartial r2 = .017-.068. Baseline symptoms of these conditions were unrelated to changes in disability, and cognitive performance was unrelated to disability at any assessment point. Together, this suggests that changes in psychiatric and somatic symptoms are tightly linked with changes in functional disability and should be frequently monitored, and even subclinical symptoms may be a target of intervention.

Impaired executive function exacerbates neural markers of posttraumatic stress disorder.

BACKGROUND: A major obstacle in understanding and treating posttraumatic stress disorder (PTSD) is its clinical and neurobiological heterogeneity. To address this barrier, the field has become increasingly interested in identifying subtypes of PTSD based on dysfunction in neural networks alongside cognitive impairments that may underlie the development and maintenance of symptoms. The current study aimed to determine if subtypes of PTSD, based on normative-based cognitive dysfunction across multiple domains, have unique neural network signatures. METHODS: In a sample of 271 veterans (90% male) that completed both neuropsychological testing and resting-state fMRI, two complementary, whole-brain functional connectivity analyses explored the link between brain functioning, PTSD symptoms, and cognition. RESULTS: At the network level, PTSD symptom severity was associated with reduced negative coupling between the limbic network (LN) and frontal-parietal control network (FPCN), driven specifically by the dorsolateral prefrontal cortex and amygdala Hubs of Dysfunction. Further, this relationship was uniquely moderated by executive function (EF). Specifically, those with PTSD and impaired EF had the strongest marker of LN-FPCN dysregulation, while those with above-average EF did not exhibit PTSD-related dysregulation of these networks. CONCLUSION: These results suggest that poor executive functioning, alongside LN-FPCN dysregulation, may represent a neurocognitive subtype of PTSD.

Connectome-based functional connectivity markers of suicide attempt.

BACKGROUND: Functional brain markers of suicidality can help identify at-risk individuals and uncover underlying neurocognitive mechanism(s). Although some converging evidence has implicated dysfunction in several brain networks, suicide-related neuroimaging markers are inconsistent across studies, due to heterogeneity of neuroimaging approaches, clinical populations, and experimental methods. METHODS: The current study aimed to address these limitations by examining resting-fMRI connectivity in a sample of post-9/11 veterans with a past suicide attempt (SA; n = 16) compared to a psychiatric control group (PC; n = 124) with no SA history but comparable past and present symptomatology, as well as a trauma control group (TC; n = 66) of trauma-exposed healthy controls. We used both a novel graph-analytic and seed-based approach to characterize SA-related connectivity differences across brain networks. RESULTS: First, the graph-analytic approach identified the right amygdala and a region in the cognitive control network (right middle temporal gyrus; MTG) as regional SA-related hubs of dysfunction (HoD), or regions that exhibited a high number of SA-related connections. Aberrant SA-related connectivity between these hubs spanned multiple networks, including the cognitive control, default mode and visual networks. Second, the seed-based connectivity analysis that identifies SA-related differences in the strength of neural connections across the whole brain further implicated the right amygdala. LIMITATIONS: Small sample size and potential underreporting of SA. CONCLUSIONS: These two analytic approaches preliminarily suggest that the right amygdala and right MTG may be specific neural markers of SA that can be differentiated from neural markers of psychopathology more broadly.

Adverse Childhood Experiences in Trainees and Physicians With Professionalism Lapses: Implications for Medical Education and Remediation.

PURPOSE: Unprofessional behavior, which can include failure to engage, dishonest and/or disrespectful behavior, and poor self-awareness, can be demonstrated by medical trainees and practicing physicians. In the authors' experience, these types of behaviors are associated with exposure to adverse childhood experiences (ACEs). Given this overlap, the authors studied the percentage of ACEs among trainees and physicians referred for fitness-for-duty evaluations and patterns between the types of ACEs experienced and the reason for referral. METHOD: A final sample of 123 cases of U.S. trainees and physicians who had been referred to a Midwestern center for assessment and/or remediation of professionalism issues from 2013 to 2018 was created. Included professionalism lapses fell within 3 categories: boundary violation, disruptive behavior, or potential substance use disorder concerns. All participants completed a psychosocial developmental interview, which includes questions about ACE exposure. Overall rate of reported ACEs and types of ACEs reported were explored. RESULTS: Eighty-six (70%) participants reported at least 1 ACE, while 27 (22%) reported 4 or more. Compared with national data, these results show significantly higher occurrence rates of 1 or more ACEs and a lower occurrence rate of 0 ACEs. ACEs that predicted reasons for referral were physical or sexual abuse, feeling unwanted or unloved, witnessing abuse of their mother or stepmother, or caretaker substance use. CONCLUSIONS: In this sample, ACE exposure was associated with professionalism issues. Remediating individuals with professionalism issues and exposure to ACEs can be complicated by heightened responses to stressful stimuli, difficulties with collaboration and trust, and decreased self-efficacy. Adoption of a trauma-informed medical education approach may help those that have been impacted by trauma rebuild a sense of control and empowerment. The findings of this study may be useful predictors in identifying those at risk of problematic behavior and recidivism before a sentinel event.

Evaluating the evidence for a neuroimaging subtype of posttraumatic stress disorder.

A recent study used functional neuroimaging and cognitive tasks to identify posttraumatic stress disorder (PTSD) subtypes. Specifically, this study found that a subgroup of patients with verbal memory impairment had a unique neural signature, namely, decreased ventral attention network (VAN) resting-state functional connectivity, and these same individuals responded poorly to psychotherapy. Although this represents one of the first studies to propose a neurocognitive subtype of PTSD and has far-reaching translational potential, the generalizability and specificity of the observed neural network and cognitive domain remain unclear. We attempted to conceptually replicate and extend these findings in a similar cohort of combat-exposed veterans (n = 229) tested using a standardized battery of neuropsychological tests and a priori criteria for cognitive impairments. First, we conducted identical and complementary analyses to determine whether subjects with PTSD and neuropsychologically defined verbal memory deficits exhibited the VAN connectivity biomarker. Second, we examined whether cognitive deficits in other domains implicated in PTSD (executive functioning and attention) exhibited the VAN signature. Across multiple measures of verbal memory, we did not find that the subgroup of individuals with PTSD and memory impairments had lower VAN connectivity. However, a subgroup of individuals with PTSD and attentional impairments did have lower VAN connectivity, suggesting that the original subtype could have been related to attention and not memory impairments. Overall, our findings suggest that the previously identified memory-impaired PTSD subtype may not generalize. Further consideration of neuropsychological methods will be important for neurocognitive markers to be implemented clinically.

Characterizing developmental prosopagnosia beyond face perception: Impaired recollection but intact familiarity recognition.

Converging lines of research suggests that many developmental prosopagnosics (DPs) have impairments beyond face perception, but currently no framework exists to characterize these impaired mechanisms. One potential extra-perceptual deficit is that DPs encode/retrieve faces in a distinct manner from controls that does not sufficiently support individuation. To test this possibility, 30 DPs and 30 matched controls performed an old/new face recognition task while providing confidence ratings, to which a model-based ROC analysis was applied. DPs had significantly reduced recollection compared to controls, driven by fewer 'high-confidence target' responses, but intact familiarity. Recollection and face perception ability uniquely predicted objective and subjective prosopagnosia symptoms, together explaining 51% and 56% of the variance, respectively. These results suggest that a specific deficit in face recollection in DP may represent a core aspect of the difficulty in confidently identifying an individual by their face.

Clinically significant cognitive dysfunction in OEF/OIF/OND veterans: Prevalence and clinical associations.

OBJECTIVE: Cognitive performance in trauma-exposed populations, such as combat Veterans, has been shown to be worse than in nonexposed peers. However, cognitive performance has typically been within the normal range (within 1 SD of normative mean), and the prevalence of clinically significant cognitive dysfunction (i.e., performance more than 1 SD below the mean on multiple measures in a domain) in younger adults with trauma exposure remains unknown. The objective of our study was to measure this. METHOD: We applied Diagnostic and Statistical Manual of Mental Disorders (5th ed.; DSM-5) cutoffs for clinically significant cognitive dysfunction (>1 SD below the mean in multiple measures within a domain) in the domains of memory, executive function, and attention to a sample of combat-exposed Operation Enduring Freedom/Operation Iraqi Freedom/Operation New Dawn (OEF/OIF/OND; N = 368, mean age = 31.7 years, 90% men) Veterans. We then compared psychiatric, physiological, and neural measures, as well as functional outcomes, between those with and without cognitive dysfunction. RESULTS: Veterans with cognitive dysfunction (n = 129, 35.1%) had lower premorbid reading ability and more severe psychological distress, including increased anxiety, depression, posttraumatic stress disorder (PTSD), sleep difficulties, pain, and alcohol consumption. Those with cognitive dysfunction also had worse functional outcomes, with mild but significant disability. In contrast, we found associations between outcome and age, traumatic brain injury, physiological and neural measures to be weak or not significant. CONCLUSIONS: Together, this suggests that premorbid abilities and trauma-related psychological symptoms contribute significantly to cognitive dysfunction in OEF/OIF/OND Veterans, and that neurological insult and aging may play less of a role. Cognitive dysfunction may be at least partially ameliorated by treating trauma-related symptoms. (PsycINFO Database Record (c) 2019 APA, all rights reserved).