Randomized controlled trial of computerized approach/avoidance training in social anxiety disorder: Neural and symptom outcomes.

Social anxiety is associated with diminished automatic approach toward positive social cues that may limit the ability to connect with others. This diminished approach bias may be a modifiable treatment target. We evaluated the effects of an approach avoidance training procedure on positive emotions, social relationship outcomes, clinical symptoms, and neural indices of social approach and reward processing. Forty-five individuals with social anxiety disorder were randomized (parallel 1:1 randomization) to complete computerized Approach Positive training (n = 21) or Balanced training(n = 24). Sessions included a standardized social interaction task. Participants were blind to training group. Participants completed clinical outcome measures and functional magnetic resonance imaging at baseline and post intervention with an MRI-compatible AAT and the social incentive delay task (SID). Both groups displayed significant improvements of similar magnitude on the primary outcome of social connectedness (between group post-treatment d = -0.21) but not positive affect (d = -0.09), from before to after treatment, persisting through follow-up. Groups demonstrated significant improvements on additional outcomes including anxiety, depression, and anhedonia symptoms. Participants in Approach Positive AAT demonstrated increased activation in the thalamus and medial prefrontal cortex during social versus neutral- approach relative to Balanced AAT during the fMRI AAT. Participants in Balanced AAT showed increased activation in regions within an a priori-defined striatum region of interest mask during anticipation of social reward (vs. baseline) in the SID relative to Approach Positive AAT. At a neural processing level AAT may influence the valuation and motivations associated with positive social cues regulated by the mPFC and thalamus. NCT02136212, NIMH R00MH090243.

Baseline executive functioning moderates treatment-related changes in quality of life in veterans with posttraumatic stress disorder and comorbid traumatic brain injury.

Posttraumatic stress disorder (PTSD) treatment has been associated with improvement in quality of life (QOL); however, little is known about factors that moderate treatment-related changes in QOL, particularly cognitive factors. Executive functioning (EF) is important for success across all aspects of everyday life and predicts better psychological and physical health. EF is important to QOL, but more work is needed to better understand the association between EF and QOL improvements following interventions. We hypothesized that poorer baseline EF would be associated with less improvement in overall life satisfaction and satisfaction with health following PTSD treatment. U.S. veterans who served after the September 11, 2001 terrorist attacks (post 9-11; N = 80) with PTSD and a history of mild-to-moderate traumatic brain injury were randomized to standard cognitive processing therapy (CPT) or CPT combined with cognitive rehabilitation (SMART-CPT). Multilevel modeling was used to examine whether baseline EF performance was associated with changes in QOL scores from pretreatment to follow-up across both groups. Results indicated that poorer baseline performance on EF tests of working memory and inhibition were associated with less treatment-related improvements in general life satisfaction and satisfaction with health, rs = .26-.36. Treatment condition did not moderate any results. Future research should examine whether implementing EF-focused techniques before and/or concurrently with CPT for individuals with poorer baseline working memory and inhibition enhances QOL treatment gains, particularly in terms of general life and health-related satisfaction.

Subjective cognitive and psychiatric well-being in U.S. Military Veterans screened for deployment-related traumatic brain injury: A Million Veteran Program Study.

The purpose of this study was to examine subjective cognitive and psychiatric functioning in post-deployed military Veterans who underwent the Veterans Health Administration's Traumatic Brain Injury (TBI) Screening and Evaluation Program and enrolled in the VA's Million Veteran Program (MVP). Veterans (N = 7483) were classified into three groups based on outcomes from the TBI Screening and Evaluation Program: (1) negative TBI screen ('Screen-'), (2) positive TBI screen but no TBI diagnosis ('Screen+/TBI-'), or (3) positive TBI screen and TBI diagnosis ('Screen+/TBI+'). Chi-square analyses revealed significant group differences across all self-reported cognitive and psychiatric health conditions (e.g., memory loss, depression), and ANCOVAs similarly showed a significant association between group and subjective symptom reporting. Specifically, the relationship between TBI group and clinical outcome (i.e., health conditions and symptoms) was such that the Screen+/TBI+ group fared the worst, followed by the Screen+/TBI- group, and finally the Screen- group. However, evaluation of effect sizes suggested that Veterans in the two Screen+ groups (Screen+/TBI+ and Screen+/TBI-) are faring similarly to one another on subjective cognitive and psychiatric functioning, but that both Screen+ groups are faring significantly worse than the Screen- group. Our results have meaningful clinical implications and suggest that Veterans who screen positive for TBI, regardless of ultimate TBI diagnosis, be eligible for similar clinical services so that both groups can benefit from valuable treatments and therapeutics. Finally, this research sets the stage for follow-up work to be conducted within MVP that will address the neurobiological underpinnings of cognitive and psychiatric distress in this population.

Mechanisms through which executive dysfunction influences suicidal ideation in combat-exposed Iraq and Afghanistan veterans.

OBJECTIVE: Executive dysfunction has previously been associated with suicidality, but it remains unclear how deficits in executive functioning contribute to increased suicidal thoughts and behaviors. Although it has been proposed that poorer executive functioning leads to difficulty generating and implementing appropriate coping strategies to regulate distress and inhibit suicidal thoughts and behaviors, studies have not systematically examined these relationships. Therefore, the present study examined various hypotheses to elucidate the mechanisms through which executive dysfunction influences suicidal ideation (SI) in combat-exposed Iraq/Afghanistan veterans. METHOD: Veterans who endorsed SI were compared to those who denied SI on demographic and diagnostic variables and measures of neuropsychological functioning, psychological symptoms, coping styles, and combat experiences. Serial mediation models were tested to examine mechanistic relationships among executive functioning, psychological distress, coping, and SI. RESULTS: Those who endorsed SI had worse executive functioning, greater psychological distress, and greater avoidant coping relative to those who denied SI. Serial mediation model testing indicated a significant indirect path, such that executive dysfunction increased psychological distress, which in turn increased avoidant coping, leading to SI. CONCLUSIONS: Findings support and extend previous hypotheses regarding how executive functioning contributes to increased risk of suicidality via increased distress and avoidant coping. Intervention efforts focused on reducing suicidality may benefit from techniques that enhance executive functioning (e.g. computerized training, cognitive rehabilitation) and in turn reduce distress prior to targeting coping strategies.

White matter integrity, suicidal ideation, and cognitive dysfunction in combat-exposed Iraq and Afghanistan Veterans.

White matter alterations in frontolimbic circuits and poorer cognitive functioning have been observed in individuals endorsing suicidality across numerous psychiatric conditions. However, relationships between white matter integrity, cognition, and suicidality in Veterans are poorly understood, particularly for those at increased risk for suicide due to mental health conditions (e.g., posttraumatic stress disorder, depression) and traumatic brain injury history. We (1) examined white matter alterations in combat-exposed Iraq/Afghanistan Veterans with and without suicidal ideation (SI) and (2) investigated relationships between white matter integrity and neuropsychological functioning in regions that differed between SI groups. No group differences were found regarding psychiatric diagnoses. Participants with SI had lower fractional anisotropy (FA) in the posterior corona radiata, superior corona radiata, and superior longitudinal fasciculus relative to those without SI. Worse processing speed/attention performance was associated with lower FA in the superior longitudinal fasciculus, while worse executive functioning performance was associated with lower FA in the superior corona radiata and superior longitudinal fasciculus. Memory performance was not associated with FA. These findings suggest that white matter integrity may be involved in cognitive dysfunction and increased risk for SI. Interventions that target cognitive dysfunction may ameliorate SI, and in turn, reduce risk for suicide among Veterans.

Baseline sleep quality moderates symptom improvement in veterans with comorbid PTSD and TBI receiving trauma-focused treatment.

Poor sleep quality is common among Veterans with posttraumatic stress disorder (PTSD) and history of traumatic brain injury (TBI). However, the relationship between sleep quality and treatment outcomes following trauma-focused interventions is less well-understood in this population. We sought to better understand whether 1) sleep quality changed as a result of trauma-focused treatment and 2) if baseline sleep quality moderated psychological and neurobehavioral treatment outcomes. Our sample consisted of 100 Iraq/Afghanistan era Veterans with PTSD and history of mild to moderate TBI who were randomized to one of two trauma-focused treatments: 1) Cognitive Processing Therapy (CPT) or 2) combined CPT and Cognitive Symptom Management and Rehabilitation Therapy (SMART-CPT). Self-reported sleep quality, psychiatric symptoms (PTSD and depression), and neurobehavioral concerns were assessed at multiple timepoints throughout the study. Multilevel modeling showed sleep quality did not improve, regardless of treatment condition. However, worse baseline sleep quality was associated with less improvement in PTSD symptoms and cognitive complaints. There was no effect of baseline sleep quality on change in depression symptoms. These findings suggest that more targeted treatments to address sleep quality either prior to or in conjunction with trauma-focused therapy may help to improve treatment outcomes for Veterans with comorbid PTSD and TBI history.

Post-concussive symptom endorsement and symptom attribution following remote mild traumatic brain injury in combat-exposed Veterans: An exploratory study.

The purpose of this study was to examine rates of and relationships between "post-concussive" symptom endorsement and symptom attribution in Veterans with a history of mild traumatic brain injury (mTBI). This cross-sectional, exploratory study included 48 combat-exposed Iraq/Afghanistan Veterans with remote history of mTBI. All Veterans completed clinical interviews and self-report questionnaires assessing sociodemographic factors, injury and combat-related variables, psychiatric distress, self-efficacy, and coping style. To assess symptom endorsement and symptom attribution, a modified version of the Neurobehavioral Symptom Inventory was administered. Results showed that the most commonly endorsed "post-concussive" symptoms were several non-specific symptoms, while the symptoms most frequently attributed to mTBI included forgetfulness, poor concentration, and headaches. Furthermore, although there were some overlapping correlates of both symptom endorsement and symptom attribution, unique variables were associated with each domain. Specifically, symptom endorsement was uniquely associated with measures of psychiatric distress, while symptom attribution was uniquely associated with having a history of loss of consciousness and a greater degree of combat exposure. Taken together, results suggest that endorsement of symptoms may be significantly impacted by the presence of mental health comorbidities, but that perceptions or beliefs as to why symptoms are occurring are related more to mTBI and combat-related characteristics. Findings offer potential avenues for therapeutic intervention, emphasize the importance of psychoeducation, and highlight the need to consider using alternate terminology for these symptoms that promotes recovery and minimizes misattribution of symptoms.

Associations Between Multiple Remote Mild TBIs and Objective Neuropsychological Functioning and Subjective Symptoms in Combat-Exposed Veterans.

OBJECTIVE: The purpose of this study was to evaluate relationships between multiple mild traumatic brain injuries (mTBIs) and objective and subjective clinical outcomes in a sample of combat-exposed Veterans, adjusting for psychiatric distress and combat exposure. METHOD: In this cross-sectional study, 73 combat-exposed Iraq/Afghanistan Veterans were divided into three groups based on mTBI history: 0 mTBIs (n = 31), 1-2 mTBIs (n = 21), and 3+ mTBIs (n = 21). Veterans with mTBI were assessed, on average, 7.78 years following their most recent mTBI. Participants underwent neuropsychological testing and completed self-report measures assessing neurobehavioral, sleep, and pain symptoms. RESULTS: MANCOVAs adjusting for psychiatric distress and combat exposure showed no group differences on objective measures of attention/working memory, executive functioning, memory, and processing speed (all p's > .05; ηp2 = .00-.06). In contrast, there were significant group differences on neurobehavioral symptoms (p's = < .001-.036; ηp2 = .09-.43), sleep difficulties (p = .037; ηp2 = .09), and pain symptoms (p < .001; ηp2 = .21). Pairwise comparisons generally showed that the 3+ mTBI group self-reported the most severe symptoms, followed by comparable symptom reporting between the 0 and 1-2 mTBI groups. CONCLUSIONS: History of multiple, remote mTBIs is associated with elevated subjective symptoms but not objective neuropsychological functioning in combat-exposed Veterans. These results advance understanding of the long-term consequences of repetitive mTBI in this population and suggest that Veterans with 3+ mTBIs may especially benefit from tailored treatments aimed at ameliorating specific neurobehavioral, sleep, and pain symptoms.