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Repetitive negative thinking (RNT) is a transdiagnostic symptom observed across mood and anxiety disorders and is characterized by frequent, distressing thoughts that are perceived as uncontrollable. Specific forms of RNT have been linked to increased suicide risk. However, most work examining links between RNT and suicide has been conducted within specific disorders and subtypes of RNT (e.g., rumination in individuals with depression). The present study aimed to investigate associations between transdiagnostic RNT and suicidal ideation. We hypothesized RNT would be associated with suicide risk beyond disorder-specific clinical symptoms. Fifty-four participants with mood, anxiety, and/or traumatic stress disorders completed an interview assessing suicidal risk (Columbia-Suicide Severity Rating Scale (C-SSRS)) and self-report questionnaires assessing transdiagnostic RNT, depression, and anxiety. Based on C-SSRS, we divided participants into high or low suicide risk groups. We analyzed the relationship between suicidal risk group and RNT and found that RNT was uniquely associated with suicidal risk group, controlling for depression and anxiety severity. Our results suggest including assessments of RNT may have clinical utility for understanding the degree of suicide risk in individuals and point to the potential utility of including clinical interventions to target this symptom for those at high risk of suicide.

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Reasoning requires the ability to manipulate mental representations and understand relationships between objects. There is a paucity of research regarding the functional connections between multiple brain areas that may interact during commonly used reasoning tasks. The present study aimed to examine functional activation and connectivity of frontoparietal regions during a Matrix Decision Making Task, completed by twenty-one right-handed healthy participants while undergoing fMRI. Voxel-wise whole brain analysis of neural response to the task revealed activation spanning dorsal and lateral prefrontal, occipital, and parietal regions. Utilizing Group Iterative Multiple Model Estimation, a data-driven approach that estimates the presence and direction of connectivity between specific ROIs, connectivity between prefrontal and sensory processing regions were revealed. Moreover, the magnitude of connectivity strength between the left precentral gyrus and left dorsal cingulate (dACC) was positively correlated with MR behavioral performance. Taken together, results are consistent with earlier work demonstrating involvement of regions comprising the central executive network in relational reasoning. These data expand existing knowledge regarding communication of key brain regions during the task and demonstrate that understanding how key brain regions are interconnected can effectively predict the quality of behavioral output.

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Exposure-based cognitive behavioral therapy (CBT) is the gold standard for treating social anxiety disorder (SAD), yet response is not universal. CBT is thought to operate via extinction-related learning during exposure, which in turn relies on cognitive processes such as working memory. The present proof-of-concept study investigates the potential for training working memory to improve anxiety related outcomes following exposure. Thirty-three adults with elevated social anxiety were randomized to complete a working memory training or sham training condition. Post-training, participants completed a working memory assessment, speech exposure session, and two fMRI tasks. Participants who received working memory training demonstrated lower distress ratings by the end of the speech exposures and better performance on the fMRI working memory task than those in sham. Working memory training completers had greater neural activation in frontoparietal regions during an in-scanner working memory task and exhibited less neural activation in the fusiform gyrus in response to an emotional face processing task than those in sham. Adding working memory training to exposure procedures could strengthen functioning of frontoparietal regions and alter emotional processing - key mechanisms implicated in extinction learning. Findings provide preliminary evidence that training working memory in conjunction with exposure may enhance exposure success.

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BACKGROUND: Alcohol use disorder (AUD) is highly prevalent and commonly co-occurs with other psychiatric disorders among Veterans. Provisional evidence supports the use of Approach Avoidance Training (AAT) - a form of computer-delivered cognitive bias modification designed to target implicit approach bias for alcohol-related cues - as an adjunctive program to treat AUD. However, the extent to which AAT is effective for improving AUD recovery outcomes in outpatient Veteran samples and those with psychiatric comorbidities has been understudied to date. Here we describe a double-blind randomized controlled trial of AAT versus a comparison condition (Sham) being conducted in Veterans with comorbid psychiatric conditions completing outpatient standard care. METHODS: One hundred thirty-six Veterans currently receiving outpatient treatment for AUD will be recruited for this randomized controlled trial with parallel group assignment. Participants will be randomized to either 6 weeks of AAT (n = 68) or Sham (n = 68) training in conjunction with usual care. Assessments will occur at baseline and 6 weeks, 3 months, and 6 months post-baseline. Primary outcome variables will include functional consequences of drinking. Secondary outcome variables will include alcohol consumption, and behavioral indicators of alcohol approach bias. A subset of participants (n = 51) will also complete functional magnetic resonance imaging (fMRI) to assess neural response during an alcohol approach bias assessment. DISCUSSION: This study is the first randomized controlled trial of AAT administered as an adjunctive treatment to standard care in Veterans with AUD and comorbid psychiatric disorders. Additionally, behavioral and neuroimaging data will be used to determine the extent to which AAT targets approach bias for alcohol cues. If effective, AAT may be a promising low-cost adjunctive treatment option for individuals with AUD. REGISTRY NAME: AAT for Alcohol Use Disorder in Veterans. TRIAL REGISTRATION: ClinicalTrials.gov: NCT05372029; Date of Registration: 5/9/2022.

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BACKGROUND: Anxiety disorders are debilitating conditions that can be treated with cognitive behavioral therapy (CBT). Increased understanding of the neurobiological correlates of CBT may inform treatment improvements and personalization. Prior neuroimaging studies point to treatment-related changes in anterior cingulate, insula, and other prefrontal regions during emotional processing, yet to date the impact of CBT on neural substrates of "top down" emotion regulation remains understudied. We examined the relationship between symptom changes assessed over the course of CBT treatment sessions and pre- to post-treatment neural change during an emotion regulation task. METHOD: In the current study, a sample of 30 participants with panic disorder or generalized anxiety disorder completed a reappraisal-based emotion regulation task while undergoing fMRI before and after completing CBT. RESULTS: Reduced activation in the parahippocampal gyrus was observed from pre- to post-treatment during periods of reducing versus maintaining emotion. Parahippocampal activation was associated with change in symptoms over the course of treatment and post-treatment responder status. Results suggest that, from pre- to post-CBT, participants demonstrated downregulation of neural responses during effortful cognitive emotion regulation. LIMITATIONS: Effects were not observed in frontoparietal systems as would be hypothesized based on prior literature, suggesting that treatment-related change could occur outside of fronto-parietal and limbic regions that are central to most models of neural functioning in anxiety disorders. CONCLUSIONS: Continued work is needed to better understand how CBT affects cognitive control and memory processes that are hypothesized to support reappraisal as a strategy for emotion regulation.

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BACKGROUND: Suicide is a significant health concern among veterans, and suicidal ideation is a common and functionally debilitating condition that frequently precedes suicidal behavior. Characterizing neurobiological substrates associated with suicidal ideation in veterans may inform evaluation of risk for this population. Associations between suicidal ideation and functional abnormalities in prefrontal, temporal, and striatal regions supporting cognitive task performance have been documented in individuals with mood and psychotic disorders, suggesting a potential role for neurocognitive vulnerabilities in this condition. To date, however, relatively little research has explored neural correlates of suicidal ideation, particularly among individuals with posttraumatic stress disorder (PTSD). METHODS: Twenty three combat veterans diagnosed with PTSD completed an adapted Reading Span (Rspan) working memory task during functional magnetic resonance imaging (fMRI). Participants were classified based on presence of current SI. We evaluated differences between these groups on neural activation in response to interference-based working memory demands within the task. Primary analyses were conducted using a voxel-wise between-group t-test. RESULTS: Task-based activations were observed in regions including the cingulate, middle frontal, parietal, and occipital cortex, striatum, and cerebellum. Relative to individuals without SI, individuals with SI demonstrated less activation in a large region spanning the lateral prefrontal cortex and cingulate cortex, as well as the inferior temporal cortex, in response to interference demands. CONCLUSIONS: Results are consistent with models proposing that prefrontal neural substrates involved in cognitive regulation are implicated in suicidal ideation. Involvement of temporal functioning may also exist based on current findings. Future research is needed to understand whether disturbances in prefrontal regulatory control reflect a specific profile subtype with distinct neural correlates, and how such neural patterns may be used to improve detection and treatment personalization.

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OBJECTIVE: This study examined the Minnesota Multiphasic Personality Inventory-Second Edition-Restructured Form (MMPI-2-RF) to better understand symptom presentation in a sample of treatment-seeking Operation Enduring Freedom/Operation Iraqi Freedom (OEF/OIF) Veterans with self-reported history of mild traumatic brain injury (mTBI). METHOD: Participants underwent a comprehensive clinical neuropsychological battery including performance and symptom validity measures and self-report measures of depressive, posttraumatic, and post-concussive symptomatology. Those with possible symptom exaggeration (SE+) on the MMPI-2-RF were compared with those without (SE-) with regard to injury, psychiatric, validity, and cognitive variables. RESULTS: Between 50% and 87% of participants demonstrated possible symptom exaggeration on one or more MMPI-2-RF validity scales, and a large majority were elevated on content scales related to cognitive, somatic, and emotional complaints. The SE+ group reported higher depressive, posttraumatic, and post-concussive symptomatology, had higher scores on symptom validity measures, and performed more poorly on neuropsychological measures compared with the SE- group. There were no group differences with regard to injury variables or performance validity measures. Participants were more likely to exhibit possible symptom exaggeration on cognitive/somatic compared with traditional psychopathological validity scales. CONCLUSIONS: A sizable portion of treatment-seeking OEF/OIF Veterans demonstrated possible symptom exaggeration on MMPI-2-RF validity scales, which was associated with elevated scores on self-report measures and poorer cognitive performance, but not higher rates of performance validity failure, suggesting symptom and performance validity are distinct concepts. These findings have implications for the interpretation of clinical data in the context of possible symptom exaggeration and treatment in Veterans with persistent post-concussive symptoms.

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BACKGROUND: Traumatic brain injury (TBI) is common in military personnel and associated with high rates of posttraumatic stress disorder (PTSD). TBI impacts widely-distributed neural patterns, some of which influence affective processing. Better understanding how TBI and PTSD/TBI alters affective neural activity may improve our understanding of comorbidity mechanisms, but to date the neural correlates of emotional processing in these groups has been relatively understudied. METHODS: Military controls, military personnel with a history of TBI, and military personnel with both TBI and PTSD (N = 53) completed an emotional face processing task during fMRI. Whole-brain activation and functional connectivity during task conditions were compared between groups. RESULTS: Few whole-brain group differences emerged in planned pairwise contrasts, though the TBI group showed some areas of hypoactivation relative to other groups during processing of faces versus shapes. The PTSD/TBI group compared to the control and TBI groups demonstrated greater connectivity between the amygdala and insula seed regions and a number of prefrontal and posterior cingulate regions. LIMITATIONS: Generalizability to other patient groups, including those with only PTSD, has not yet been established. CONCLUSION: TBI alone was associated with hypoactivation during a condition processing faces versus shapes, but PTSD with TBI was associated altered functional connectivity between amygdala and insula regions and cingulate and prefrontal areas. Altered connectivity patterns across groups suggests that individuals with PTSD/TBI may need to increase frontal connectivity with the insulae in order to achieve similar task-based activity.

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Growing evidence suggests that intolerance of uncertainty (IU) is a cognitive vulnerability that is a central feature across diverse anxiety disorders, including generalized anxiety disorder (GAD). Although cognitive behavioral therapy (CBT) has been shown to reduce IU, it remains to be established whether or not reductions in IU mediate reductions in worry. This study examined the process of change in IU and worry in a sample of 28 individuals with GAD who completed CBT. Changes in IU and worry, assessed bi-weekly during treatment, were analyzed using multilevel mediation models. Results revealed that change in IU mediated change in worry (ab = -0.20; 95% CI [-.35, -.09]), but change in worry did not mediate change in IU (ab = -0.16; 95% CI [-.06, .12]). Findings indicated that reductions in IU accounted for 59% of the reductions in worry observed over the course of treatment, suggesting that changes in IU are not simply concomitants of changes in worry. Findings support the idea that IU is a critical construct underlying GAD.

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The purpose of this review was to compare and contrast Prolonged Exposure (PE) and Narrative Exposure Therapy (NET). We examined the treatment manuals to describe the theoretical foundation, treatment components, and procedures, including the type, manner, and focus of exposure techniques and recording methods used. We examined extant clinical trials to investigate the range of treatment formats reported, populations studied, and clinical outcome data. Our search resulted in 32 studies on PE and 15 studies on NET. Consistent with prior reviews of PTSD treatment, it is evident that PE has a solid evidence base and its current status as a first line treatment for the populations studied to this date is warranted. We argue that NET may have advantages in treating complex traumatization seen in asylum seekers and refugees, and for this population NET should be considered a recommended treatment. NET and PE have several commonalities, and it is recommended that studies of these treatments include a broader range of populations and trauma types to expand the current knowledge on the treatment of PTSD.

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The present study examined rates of trauma exposure, clinical characteristics associated with trauma exposure, and the effect of trauma exposure on treatment outcome in a large sample of primary care patients without posttraumatic stress disorder (PTSD). Individuals without PTSD (N = 1263) treated as part of the CALM program (Roy-Byrne et al., 2010) were assessed for presence of trauma exposure. Those with and without trauma exposure were compared on baseline demographic and diagnostic information, symptom severity, and responder status six months after beginning treatment. Trauma-exposed individuals (N = 662, 53%) were more likely to meet diagnostic criteria for Obsessive Compulsive Disorder and had higher levels of somatic symptoms at baseline. Individuals with and without trauma exposure did not differ significantly on severity of anxiety, depression, or mental health functioning at baseline. Trauma exposure did not significantly impact treatment response. Findings suggest that adverse effects of trauma exposure in those without PTSD may include OCD and somatic anxiety symptoms. Treatment did not appear to be adversely impacted by trauma exposure. Thus, although trauma exposure is prevalent in primary care samples, results suggest that treatment of the presenting anxiety disorder is effective irrespective of trauma history.