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The options for drug-controlled anticoagulation are becoming noticeably more manifold. In the area of anaesthesiology and intensive care, there are furthermore special disease patterns, such as heparin-induced thrombocytopenia (HIT) to be known, diagnosed and treated. This article gives a review of the substance groups of the direct thrombin inhibitors (DTI) as alternative anticoagulants for HIT in combination with cardiovascular diseases. For the administration of DTIs, experience and the correct dose are the keys to success and are the deciding factors for the two sides of haemostasis: thrombosis and haemorrhage. [ABSTRACT FROM AUTHOR]

Suicidal ideation (SI), a risk factor for suicide, is prevalent in internalizing psychopathologies, including depression and anxiety. Rumination and worry are well-studied repetitive negative thinking (RNT) constructs implicated in internalizing psychopathologies. These constructs have shared and distinct characteristics. However, the relationship between rumination and worry and their associations with SI are not fully understood in clinical samples. The present study used correlational and regression analysis to evaluate these relationships as a secondary data analysis in treatment-seeking participants with internalizing psychopathologies in two independent samples (Study 1:n = 143; Study 2:n = 133). Results showed about half of the participants endorsed SI (Study 1:n = 79; Study 2:n = 71). Correlations revealed a significant, positive relationship between rumination and worry. Regression results with SI as the dependent variable showed rumination significantly positively corresponded with SI in both studies. Post-hoc partial correlations controlling for symptom severity (depression, anxiety), worry, and age showed the rumination-SI relationship was maintained in both studies. Findings for worry and SI were inconsistent between studies. Findings indicate rumination, but not worry, could be a stable, unique contributor to SI in internalizing psychopathologies. It may be useful to incorporate RNT into suicide risk assessment for individuals with internalizing conditions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Background: Passive sensing through smartphone keyboard data can be used to identify and monitor symptoms of mood disorders with low participant burden. Behavioral phenotyping based on mobile keystroke data can aid in clinical decision-making and provide insights into the individual symptoms of mood disorders., Objective: This study aims to derive digital phenotypes based on smartphone keyboard backspace use among 128 community adults across 2948 observations using a Bayesian mixture model., Methods: Eligible study participants completed a virtual screening visit where all eligible participants were instructed to download the custom-built BiAffect smartphone keyboard (University of Illinois). The BiAffect keyboard unobtrusively captures keystroke dynamics. All eligible and consenting participants were instructed to use this keyboard exclusively for up to 4 weeks of the study in real life, and participants' compliance was checked at the 2 follow-up visits at week 2 and week 4. As part of the research protocol, every study participant underwent evaluations by a study psychiatrist during each visit., Results: We found that derived phenotypes were associated with not only the diagnoses and severity of depression and mania but also specific individual symptoms. Using a linear mixed-effects model with random intercepts accounting for the nested data structure from daily data, the backspace rates on the continuous scale did not differ between participants in the healthy control and in the mood disorders groups (P=.11). The 3-class model had mean backspace rates of 0.112, 0.180, and 0.268, respectively, with a SD of 0.048. In total, 3 classes, respectively, were estimated to comprise 37.5% (n=47), 54.4% (n=72), and 8.1% (n=9) of the sample. We grouped individuals into Low, Medium, and High backspace rate groups. Individuals with unipolar mood disorder were predominantly in the Medium group (n=54), with some in the Low group (n=27) and a few in the High group (n=6). The Medium group, compared with the Low group, had significantly higher ratings of depression (b=2.32, P=.008). The High group was not associated with ratings of depression with (P=.88) or without (P=.27) adjustment for medication and diagnoses. The High group, compared with the Low group, was associated with both nonzero ratings (b=1.91, P=.02) and higher ratings of mania (b=1.46, P<.001). The High group, compared with the Low group, showed significantly higher odds of elevated mood (P=.03), motor activity (P=.04), and irritability (P<.05)., Conclusions: This study demonstrates the promise of mobile typing kinematics in mood disorder research and practice. Monitoring a single mobile typing kinematic feature, that is, backspace rates, through passive sensing imposes a low burden on the participants. Based on real-life keystroke data, our derived digital phenotypes from this single feature can be useful for researchers and practitioners to distinguish between individuals with and those without mood disorder symptoms., (©Qimin Liu, Emma Ning, Mindy K Ross, Andrea Cladek, Sarah Kabir, Amruta Barve, Ellyn Kennelly, Faraz Hussain, Jennifer Duffecy, Scott A Langenecker, Theresa M Nguyen, Theja Tulabandhula, John Zulueta, Alexander P Demos, Alex Leow, Olusola Ajilore. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 29.10.2024.)

Rumination is a vulnerability for depression and potentially linked to inhibitory control weaknesses. We aimed to replicate the association observed in adults between inhibitory control and rumination in adolescents, and to examine putative moderating roles of childhood maltreatment and perceived family cohesion in an adolescent sample at risk for depression due to familial/personal history. Ninety adolescents aged 11-17 (M = 14.6, SD = 1.8) completed self-report scales of rumination, maltreatment, and family cohesion, and performed a task assessing inhibitory control. Hierarchical regression models showed no significant relation between inhibitory control and moderator variables on rumination. However, adolescents who reported higher levels of maltreatment and who perceived lower family cohesion tended to indicate higher levels of rumination (B Chilhood Maltreatment = 27.52, 95% CIs [5.63, 49.41], B Family Cohesion = -0.40, 95% CIs [-0.65, -0.15]). These findings demonstrate an alternative understanding of factors that increase depression onset risk and recurrence in adolescents., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Clinician collaboration can help high-risk individuals to manage their suicidal crises. However, limited research has directly examined how higher patient-clinician collaboration during assessment and intervention can effectively reduce suicidal ideation. This novel randomized clinical trial compared a high vs. low level of patient-clinician collaboration by pairing commonly used assessment (Structured Interview vs. Narrative Assessment) and intervention approaches (Safety Planning Intervention vs. Crisis Response Planning). We hypothesized that the interventions involving higher (than lower) patient-clinician collaboration during assessment (Narrative Assessment) or intervention (Crisis Response Planning) would lead to larger reductions in suicidal ideation., Methods: Eighty-two participants with a history of suicide ideation and/or attempts were randomly assigned to one of the four interventions varying in patient-clinician collaboration. After attrition, sixty-six participants completed the study. Suicidal ideation via ecological momentary assessment was measured 14 days before and 14 days after treatment., Results: Although the severity of suicidal ideation decreased in all groups, the two groups that included highly collaborative assessment had larger pre-post reductions in suicidal ideation (Narrative Assessment+Safety Plan; d within  = 0.26, and Narrative Assessment+Crisis Response Plan; d within  = 0.19) than the groups that included a checklist-based assessment (Structured Interview)., Limitations: Longer follow-up periods with a larger sample would have provided an understanding of the durability of intervention effects., Conclusion: Results suggest that the inclusion of higher patient-clinician collaboration techniques during suicide risk assessment can effectively reduce suicidal thoughts. Thus, clinician-led collaborative risk assessment approaches can enhance the effects of safety planning-type interventions among patients with elevated risk for suicide versus checklist-based assessment approaches., Competing Interests: Declaration of competing interest Scott Langenecker has an interest in Secondary Triad, Inc. All other authors declare that they have no conflicts of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Cognitive behavioral therapy (CBT) is an effective treatment for patients with social anxiety disorder (SAD) or major depressive disorder (MDD), yet there is variability in clinical improvement. Though prior research suggests pre-treatment engagement of brain regions supporting cognitive reappraisal (e.g. dorsolateral prefrontal cortex [dlPFC]) foretells CBT response in SAD, it remains unknown if this extends to MDD or is specific to CBT. The current study examined associations between pre-treatment neural activity during reappraisal and clinical improvement in patients with SAD or MDD following a trial of CBT or supportive therapy (ST), a common-factors comparator arm., Methods: Participants were 75 treatment-seeking patients with SAD ( n = 34) or MDD ( n = 41) randomized to CBT ( n = 40) or ST ( n = 35). Before randomization, patients completed a cognitive reappraisal task during functional magnetic resonance imaging. Additionally, patients completed clinician-administered symptom measures and a self-report cognitive reappraisal measure before treatment and every 2 weeks throughout treatment., Results: Results indicated that pre-treatment neural activity during reappraisal differentially predicted CBT and ST response. Specifically, greater trajectories of symptom improvement throughout treatment were associated with less ventrolateral prefrontal cortex (vlPFC) activity for CBT patients, but more vlPFC activity for ST patients. Also, less baseline dlPFC activity corresponded with greater trajectories of self-reported reappraisal improvement, regardless of treatment arm., Conclusions: If replicated, findings suggest individual differences in brain response during reappraisal may be transdiagnostically associated with treatment-dependent improvement in symptom severity, but improvement in subjective reappraisal following psychotherapy, more broadly.

Objective: We examined the impact of health care workers' (HCWs) adjustment to the COVID-19 pandemic on their work-related attitudes and behaviors., Methods: HCWs ( n = 1468) participated in an observational longitudinal study in which they completed surveys of anxiety and occupational health between 2020 and 2021., Results: Most HCWs reported anxiety that was consistently below the diagnostic threshold (68%) or fell below the threshold within a year (16%). Others reported consistently high (14%) or increasing (2%) anxiety, especially women, younger HCWs, those with a weakened immune system, and allied health professionals. Consistently high or increasing anxiety was associated with poorer job satisfaction, work engagement, perceived supervisor support, burnout, and turnover intentions., Conclusions: Resources to support HCWs may be focused on those who report consistently high or increasing anxiety to minimize the effects of crises and disasters on the workforce., Competing Interests: Conflicts of interest: None declared., (Copyright © 2024 American College of Occupational and Environmental Medicine.)

Background: Trait rumination is a habitual response to negative experiences that can emerge during adolescence, increasing risk of depression. Trait rumination is correlated with poor inhibitory control (IC) and altered default mode network (DMN) and cognitive control network (CCN) engagement. Provoking state rumination in high ruminating youth permits investigation of rumination and IC at the neural level, highlighting potential treatment targets., Methods: Fifty-three high-ruminating youth were cued with an unresolved goal that provoked state rumination, then completed a modified Sustained Attention to Response Task (SART) that measures IC (commissions on no-go trials) in a functional MRI study. Thought probes measured state rumination about that unresolved goal and task-focused thoughts during the SART., Results: Greater state rumination during the SART was correlated with more IC failures. CCN engagement increased during rumination (relative to task-focus), including left dorsolateral prefrontal cortex and dorsalmedial prefrontal cortex. Relative to successful response suppression, DMN engagement increased during IC failures amongst individuals with higher state and trait rumination. Exploratory analyzes suggested more bothersome unresolved goals predicted higher left DLPFC activation during rumination., Limitations: The correlational research design did not permit a direct contrast of causal accounts of the relationship between rumination and IC., Conclusions: State rumination was associated with impaired IC and disrupted modulation of DMN and CCN. Increased CCN engagement during rumination suggested effortful suppression of negative thoughts, and this was greater for more bothersome unresolved goals. Relative task disengagement was observed during rumination-related errors. DMN-CCN dysregulation in high-ruminating youth may be an important treatment target., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: ERW receives royalties from the treatment manual for rumination-focused cognitive-behavioral therapy published by Guilford Press and licensing of rumination-focused cognitive-behavioral therapy for internet treatment packages. SEC is a co-owner of the Utah Center for Evidence Based Treatment, an outpatient psychotherapy practice, unrelated to this work. SAL receives consultant payments from Stony Brook University, Johns Hopkins University (unrelated to this work), payments from the Center for Scientific Review (unrelated to this work), and reports part ownership of Secondary Triad Inc. (unrelated to this work).

Background: Rumination-focused cognitive behavioral therapy (RF-CBT) is designed to reduce depressive rumination or the habitual tendency to dwell on experiences in a repetitive, negative, passive, and global manner. RF-CBT uses functional analysis, experiential exercises, and repeated practice to identify and change the ruminative habit. This preregistered randomized clinical trial (NCT03859297, R61) is a preregistered replication of initial work. We hypothesized a concurrent reduction of both self-reported rumination and cross-network connectivity between the left posterior cingulate cortex and right inferior frontal and inferior temporal gyri., Methods: Seventy-six youths with a history of depression and elevated rumination were randomized to 10 to 14 sessions of RF-CBT ( n  = 39; 34 completers) or treatment as usual ( n  = 37; 28 completers). Intent-to-treat analyses assessed pre-post change in rumination response scale and in functional connectivity assessed using two 5 minute, 12 second runs of resting-state functional magnetic resonance imaging., Results: We replicated previous findings: a significant reduction in rumination response scale and a reduction in left posterior cingulate cortex to right inferior frontal gyrus/inferior temporal gyrus connectivity in participants who received RF-CBT compared with those who received treatment as usual. Reductions were large ( z change = 0.84; 0.73, respectively [ p s < .05])., Conclusions: This adolescent clinical trial further demonstrates that depressive rumination is a brain-based mechanism that is modifiable via RF-CBT. Here, we replicated that RF-CBT reduces cross-network connectivity, a possible mechanism by which rumination becomes less frequent, intense, and automatic. This National Institute of Mental Health-funded fast-fail study continues to the R33 phase during which treatment-specific effects of RF-CBT will be compared with relaxation therapy., (© 2023 Published by Elsevier Inc on behalf of Society of Biological Psychiatry.)

Introduction: Emerging literature suggests that childhood trauma may influence facial emotion perception (FEP), with the potential to negatively bias both emotion perception and reactions to emotion-related inputs. Negative emotion perception biases are associated with a range of psychiatric and behavioral problems, potentially due or as a result of difficult social interactions. Unfortunately, there is a poor understanding of whether observed negative biases are related to childhood trauma history, depression history, or processes common to (and potentially causative of) both experiences., Methods: The present cross-sectional study examines the relation between FEP and neural activation during FEP with retrospectively reported childhood trauma in young adult participants with remitted major depressive disorder (rMDD, n  = 41) and without psychiatric histories (healthy controls [HC], n  = 34). Accuracy of emotion categorization and negative bias errors during FEP and brain activation were each measured during exposure to fearful, angry, happy, sad, and neutral faces. We examined participant behavioral and neural responses in relation to total reported severity of childhood abuse and neglect (assessed with the Childhood Trauma Questionnaire, CTQ)., Results: Results corrected for multiple comparisons indicate that higher trauma scores were associated with greater likelihood of miscategorizing happy faces as angry. Activation in the right middle frontal gyrus (MFG) positively correlated with trauma scores when participants viewed faces that they correctly categorized as angry, fearful, sad, and happy., Discussion: Identifying the neural mechanisms by which childhood trauma and MDD may change facial emotion perception could inform targeted prevention efforts for MDD or related interpersonal difficulties., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Reisch, Bessette, Jenkins, Skerrett, Gabriel, Kling, Stange, Ryan, Schreiner, Crowell, Kaufman and Langenecker.)

Affect regulation often is disrupted in depression. Understanding biomarkers of affect regulation in ecologically valid contexts is critical for identifying moments when interventions can be delivered to improve regulation and may have utility for identifying which individuals are vulnerable to psychopathology. Autonomic complexity, which includes linear and nonlinear indices of heart rate variability, has been proposed as a novel marker of neurovisceral integration. However, it is not clear how autonomic complexity tracks with regulation in everyday life, and whether low complexity serves as a marker of related psychopathology. To measure regulation phenotypes with diminished influence of current symptoms, 37 young adults with remitted major depressive disorder (rMDD) and 28 healthy comparisons (HCs) completed ambulatory assessments of autonomic complexity and affect regulation across one week in everyday life. Multilevel models indicated that in HCs, but not rMDD, autonomic complexity fluctuated in response to regulation cues, increasing in response to reappraisal and distraction and decreasing in response to negative affect. Higher complexity across the week predicted greater everyday regulation success, whereas greater variability of complexity predicted lower (and less variable) negative affect, rumination, and mind-wandering. Results suggest that ambulatory assessment of autonomic complexity can passively index dynamic aspects of real-world affect and regulation, and that dynamic physiological reactivity to regulation is restricted in rMDD. These results demonstrate how intensive sampling of dynamic, nonlinear regulatory processes can advance our understanding of potential mechanisms underlying psychopathology. Such measurements might inform how to test interventions to enhance neurovisceral complexity and affect regulation success in real time. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Background: Childhood trauma is commonly experienced by individuals diagnosed with bipolar disorder (BP). In BP, childhood trauma is related to a more severe clinical course, but its association with cognition remains unclear., Methods: This study evaluated 405 adult participants diagnosed with BP and 136 controls. Participants completed the Childhood Trauma Questionnaire and a comprehensive neuropsychological battery. High versus low childhood trauma was defined with one standard deviation above the control participant's mean Childhood Trauma Questionnaire score. Neuropsychological data was transformed into eight cognitive factors, including four executive functioning, auditory and visual memory, fine motor, and emotion processing. Multivariate analysis of covariance evaluated group differences in cognition, while adjusting for covariates., Results: There were significant differences among the three groups, F(16, 968) = 4.05, p < .001, Wilks' Λ = 0.88, partial η 2  = 0.06. Comparing the high and low trauma BP groups, high trauma was related to lower auditory and visual memory factor scores (p < .05). As compared to controls, the BP high trauma group had lower scores on six of eight factors (all p < .01), while the BP low trauma group had lower scores on four of eight factors (all p < .01)., Limitations: Analyses of factor score do not address which aspect of the memory process is affected and biomarkers may help guide interventions addressing underlying biological process., Conclusions: Adults diagnosed with BP with higher childhood trauma have worse memory functioning, beyond the lower childhood trauma BP group, highlighting the importance of understanding the long-term cognitive outcomes of childhood trauma., Competing Interests: Conflict of interest MM has consulted for Janssen and Otsuka Pharmaceuticals in the past 3 years. OMD has received grant/research support from the Brain and Behavior Foundation, Simons Autism Foundation, Stanley Medical Research Institute, Deakin University, Lilly, NHMRC, and Australasian Society for Bipolar and Depressive Disorders (ASBDD)/Servier. OMD has also received in kind support from BioMedica Nutracuticals, NutritionCare and Bioceuticals. SL reports part ownership of Secondary Triad, LLC, unrelated to this work., (Copyright © 2023. Published by Elsevier B.V.)

The cognitive control network (CCN) is an important network responsible for performing and modulating executive functions. In adolescents, alcohol use has been associated with weaker cognitive control, higher reward sensitivity, and later-in-life alcohol problems. Given that the CCN continues to develop into young adulthood, it is important to understand relations between early alcohol use, the CCN, and reward networks. Participants included individuals 18-23 years without alcohol use disorder. Based upon self-reported age of first alcoholic drink, participants were split into two groups: Early (onset) Drinkers (first drink < age 18, N = 52) and Late (onset) Drinkers (first drink > age 18, N = 44). All participants underwent an 8-minute resting-state fMRI scan. Seed regions of interest included the anterior dorsolateral prefrontal cortex (DLPFC), amygdala, and ventral striatum. Early Drinkers demonstrated significant reduced connectivity of CCN regions, including bilateral anterior DLPFC, compared to Late Drinkers. There were no significant differences between Early and Late Drinkers in connectivity between reward and CCN regions. These results suggest that individuals who begin drinking alcohol earlier in life may have alterations in the development of the CCN; however, longitudinal research is necessary to determine whether lower connectivity precedes or follows early alcohol use, and any other relevant factors., Competing Interests: Declaration of Competing Interest The authors declare that they have no known financial or personal interests to disclose., (Copyright © 2023. Published by Elsevier B.V.)

Introduction: Rumination, or repetitive and habitual negative thinking, is associated with psychopathology and related behaviors in adolescents, including non-suicidal self-injury (NSSI). Despite the link between self-reported rumination and NSSI, there is limited understanding of how rumination is represented at the neurobiological level among youth with NSSI., Method: We collected neuroimaging and rumination data from 39 adolescents with current or past NSSI and remitted major depression. Participants completed a rumination induction fMRI task, consisting of both rumination and distraction blocks. We examined brain activation associated with total lifetime NSSI in the context of the rumination versus distraction contrast., Results: Lifetime NSSI was associated with a greater discrepancy in activation during rumination relative to distraction conditions in clusters including the precuneus, posterior cingulate, superior, and middle frontal gyrus, and cerebellum., Conclusion: Difficulties associated with rumination in adolescents with NSSI may be related to requiring greater cognitive effort to distract from ruminative content in addition to increased attention in the context of ruminative content. Increasing knowledge of neurobiological circuits and nodes associated with rumination and their relationship with NSSI may enable us to better tailor interventions that can facilitate lasting well-being and neurobiological change., (© 2023 American Association of Suicidology.)

Objective: The current studies explored associations between exposure to potentially morally injurious events (PMIEs) and mental health outcomes among frontline workers affected by the coronavirus pandemic., Method: We administered online self-report surveys to emergency responders ( N = 473) and hospital personnel ( N = 854) in the Rocky Mountain region of the United States between April and June of 2020. Surveys assessed frequency and intensity of exposure to PMIEs alongside psychological and functional outcomes., Results: Between 20% and 30% of frontline workers reported exposure to PMIEs of at least moderate frequency and intensity. Exposure to more intense PMIEs was associated with greater psychological symptoms (i.e., stress, depression, and anxiety) and functional impairment (i.e., professional burnout), especially among emergency responders who reported frequent exposure but also hospital workers who reported few exposures., Conclusion: Efforts to facilitate and maintain the well-being of the public health workforce should specifically address critical incidents encountered by frontline workers that have embedded moral and ethical challenges. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Objective: Assessing performance validity is imperative in both clinical and research contexts as data interpretation presupposes adequate participation from examinees. Performance validity tests (PVTs) are utilized to identify instances in which results cannot be interpreted at face value. This study explored the hit rates for two frequently used PVTs in a research sample of individuals with and without histories of bipolar disorder (BD)., Method: As part of an ongoing longitudinal study of individuals with BD, we examined the performance of 736 individuals with BD and 255 individuals with no history of mental health disorder on the Test of Memory Malingering (TOMM) and the California Verbal Learning Test forced choice trial (CVLT-FC) at three time points., Results: Undiagnosed individuals demonstrated 100% pass rate on PVTs and individuals with BD passed over 98% of the time. A mixed effects model adjusting for relevant demographic variables revealed no significant difference in TOMM scores between the groups, a = .07, SE = .07, p = .31. On the CVLT-FC, no clinically significant differences were observed ( ps < .001)., Conclusions: Perfect PVT scores were obtained by the majority of individuals, with no differences in failure rates between groups. The tests have approximately >98% specificity in BD and 100% specificity among non-diagnosed individuals. Further, nearly 90% of individuals with BD obtained perfect scores on both measures, a trend observed at each time point.

Studies of moral injury among nonmilitary samples are scarce despite repeated calls to examine the prevalence and outcomes of moral injury among civilian frontline workers. The purpose of this study was to describe the prevalence of moral injury and to examine its association with psychosocial functioning among health care workers during the COVID-19 pandemic. We surveyed health care workers (N = 480), assessing exposure to potentially morally injurious events (PMIEs) and psychosocial functioning. Data were analyzed using latent class analysis (LCA) to explore patterns of PMIE exposure (i.e., classes) and corresponding psychosocial functioning. The minimal exposure class, who denied PMIE exposure, accounted for 22% of health care workers. The moral injury-other class included those who had witnessed PMIEs for which others were responsible and felt betrayed (26%). The moral injury-self class comprised those who felt they transgressed their own values in addition to witnessing others' transgressions and feeling betrayed (11%). The betrayal-only class included those who felt betrayed by government and community members but otherwise denied PMIE exposure (41%). Those assigned to the moral injury-self class were the most impaired on a psychosocial functioning composite, followed by those assigned to the moral injury-other and betrayal-only classes, and finally the minimal exposure class. Moral injury is prevalent and impairing for health care workers, which establishes a need for interventions with health care workers in organized care settings. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

The treatment of mood disorders, which can become a lifelong process, varies widely in efficacy between individuals. Most options to monitor mood rely on subjective self-reports and clinical visits, which can be burdensome and may not portray an accurate representation of what the individual is experiencing. A passive method to monitor mood could be a useful tool for those with these disorders. Some previously proposed models utilized sensors from smartphones and wearables, such as the accelerometer. This study examined a novel approach of processing accelerometer data collected from smartphones only while participants of the open-science branch of the BiAffect study were typing. The data were modeled by von Mises-Fisher distributions and weighted networks to identify clusters relating to different typing positions unique for each participant. Longitudinal features were derived from the clustered data and used in machine learning models to predict clinically relevant changes in depression from clinical and typing measures. Model accuracy was approximately 95%, with 97% area under the ROC curve (AUC). The accelerometer features outperformed the vast majority of clinical and typing features, which suggested that this new approach to analyzing accelerometer data could contribute towards unobtrusive detection of changes in depression severity without the need for clinical input.

Rumination and worry are forms of repetitive negative thinking (RNT) commonly associated with internalizing psychopathologies, although less is known about RNT in trauma-exposed individuals with internalizing psychopathologies. Separate lines of research show RNT also plays a role in problematic sleep, which is frequently experienced after trauma exposure. To address gaps in the literature, the current study examines the impact of sleep and symptoms on RNT in trauma-exposed participants. A transdiagnostic sample of 46 unmedicated treatment-seeking trauma-exposed participants completed standard measures of rumination and worry, as well as clinical measures that assessed posttraumatic stress, depression, and anxiety severity. Actigraphic sleep variables were sleep duration, wake after sleep onset (WASO), and sleep efficiency. Sleep and clinical measures were submitted to multiple regression analyses with rumination and worry as dependent variables. The regression results showed that rumination was significantly explained by WASO and posttraumatic stress symptom (PTSS) severity, and the omnibus test was significant. Depression, anxiety, and other estimates of sleep were not significant. No significant results emerged for worry. Preliminary findings suggest that PTSS and WASO, an index of fragmented sleep, may contribute to rumination, but not worry, in trauma-exposed individuals. Longitudinal studies are needed to determine potential causal relationships.

Objectives: Previous research suggests that cognitive performance worsens during manic and depressed states in bipolar disorder (BD). However, studies have often relied upon between-subject, cross-sectional analyses and smaller sample sizes. The current study examined the relationship between mood symptoms and cognition in a within-subject, longitudinal study with a large sample., Methods: Seven hundred and seventy-three individuals with BD completed a neuropsychological battery and mood assessments at baseline and 1-year follow-up. The battery captured eight domains of cognition: fine motor dexterity, visual memory, auditory memory, emotion processing, and four aspects of executive functioning: verbal fluency and processing speed; conceptual reasoning and set shifting; processing speed with influence resolution; and inhibitory control. Structural equation modeling was conducted to examine the cross-sectional and longitudinal relationships between depressive symptoms, manic symptoms, and cognitive performance. Age and education were included as covariates. Eight models were run with the respective cognitive domains., Results: Baseline mood positively predicted 1-year mood, and baseline cognition positively predicted 1-year cognition. Mood and cognition were generally not related for the eight cognitive domains. Baseline mania was predictive in one of eight baseline domains (conceptual reasoning and set shifting); baseline cognition predicted 1-year symptoms (inhibitory control-depression symptoms, visual memory-manic symptoms)., Conclusions: In a large community sample of patients with bipolar spectrum disorder, cognitive performance appears to be largely unrelated to depressive and manic symptoms, suggesting that cognitive dysfunction is stable in BD and is not dependent on mood state in BD. Future work could examine how treatment affects relationship between cognition and mood., Significant Outcomes: Cognitive dysfunction appears to be largely independent of mood symptoms in bipolar disorder., Limitations: The sample was generally highly educated (M = 15.22), the majority of the subsample with elevated manic symptoms generally presented with concurrent depressive elevated symptoms, and the study did not stratify recruitment based on mood state., (© 2022 The Authors. Acta Psychiatrica Scandinavica published by John Wiley & Sons Ltd.)

Understanding the relationship between brain measurements and behavioral performance is an important step in developing approaches for early identification of any psychiatric difficulties and interventions to modify these challenges. Conventional methods to identify associations between regional brain volume and behavioral measures are not optimized, either in scale, scope, or specificity. To find meaningful associations between brain and behavior with greater sensitivity and precision, we applied data-driven factor analytic models to identify and extract individual differences in latent cognitive functions embedded across several computerized cognitive tasks. Furthermore, we simultaneously utilized a keyword-based neuroimaging meta-analytic tool (i.e., NeuroSynth), restricted atlas-parcel matching, and factor-analytic models to narrow down the scope of search and to further aggregate gray matter volume (GMV) data into empirical clusters. We recruited an early adult community cross-sectional sample (Total n = 177, age 18-30) that consisted of individuals with no history of any mood disorder (healthy controls, n = 44), those with remitted major depressive disorder (rMDD, n = 104), and those with a diagnosis of bipolar disorder currently in euthymic state (eBP, n = 29). Study participants underwent structural magnetic resonance imaging (MRI) scans and separately completed behavioral testing using computerized measures. Factor-analyzing five computerized tasks used to assess aspects of cognitive and affective processing resulted in seven latent dimensions: (a) Emotional Memory, (b) Interference Resolution, (c) Reward Sensitivity, (d) Complex Inhibitory Control, (e) Facial Emotion Sensitivity, (f) Sustained attention, and (g)Simple Impulsivity/Response Style. These seven dimensions were then labeled with specific keywords which were used to create neuroanatomical maps using NeuroSynth. These masks were further subdivided into GMV clusters. Using regression, we identified GMV clusters that were predictive of individual differences across each of the aforementioned seven cognitive dimensions. We demonstrate that a dimensional approach consistent with core principles of RDoC can be utilized to identify structural variability predictive of critical dimensions of human behavior., Competing Interests: Declaration of competing interest PGNGS modified and developed by Langenecker, FEPT modified and developed by Langenecker, titrated MID modified and develop by Langenecker; all are free for use., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Objective: Early life trauma (ELT) and HIV are associated with social processing deficits. In people with HIV (PWH), we examined whether facial emotion identification accuracy differs by ELT and whether neuroendocrine factors including cortisol, oxytocin (OT), and arginine vasopressin, and/or immune system measures play a role in the ELT-performance association., Methods: We used secondary data from the placebo condition of a pharmacologic challenge study in PWH. Presence of ELT was measured with the Childhood Trauma Questionnaire (at least moderate experiences of sexual, physical, and/or emotional abuse). Social processing was measured with the Facial Emotion Perception Test (FEPT). Salivary immune system measures and cortisol were sampled across a 5-hour study session. Blood was collected at study session start (12 pm ) to measure OT and arginine vasopressin. We examined the association of ELT with FEPT and five biological moderators (from principal components analysis of 12 biomarkers) of ELT-FEPT associations., Results: Of 58 PWH (42 men; mean [standard deviation] age = 33.7 [8.9] years), 50% endorsed ELT. ELT-exposed PWH demonstrated lower identification accuracy across all emotional expressions (unstandardized β [ B ] = 0.13; standard error [SE] = 0.05; p = .021, d = 0.63) and had higher OT levels compared with ELT-unexposed PWH ( t(1,56) = 2.12, p = .039; d = 0.57). For total accuracy, an OT/C-reactive protein factor moderated the ELT-FEPT association ( B = 0.14; SE = 0.05; p = .014); accuracy was lower in ELT-exposed PWH versus ELT-unexposed PWH when the factor was low but not when high. Similar results were obtained for fearful, neutral, and happy faces ( p values < .05). Regardless of ELT, a myeloid migration (MCP-1/MMP-9) factor was associated with reduced accuracy ( p values < .05)., Conclusions: Our pilot findings suggest that ELT may alter social processing in PWH, and OT and C-reactive protein may be a target for improving social processing in ELT-exposed PWH, and myeloid migration markers may be a target in PWH more generally., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Psychosomatic Society.)

Introduction: Cognitive functioning in bipolar disorder is heterogeneous with evidence for multiple subgroups. However, cognitive subgroup change patterns over time remains unknown. While prior work suggests minimal differences in cognitive functioning patterns over time between those with bipolar disorder and controls, group-based analyses may obscure unique subgroup-based changes., Material and Methods: Participants diagnosed with bipolar disorder (I, II, NOS; n = 568) and unaffected controls (n = 234) completed baseline, one- and five-year neuropsychological assessments. Data reduction techniques were used to limit the number of neuropsychological variables. Bipolar disorder participant baseline neuropsychological data were entered into hierarchical cluster analyses and resultant clusters were entered in multilevel models, which tested for differences in baseline and longitudinal cognitive changes in cognition among the cluster groups and with controls., Results: Results were consistent with bipolar disorder participants forming three subgroups with high (n = 209), mid (n = 259), and low (n = 100) cognition. These groups were associated with unique clinical characteristics. Multilevel models demonstrated that over a five-year period, the low group improved, relative to the high and mid groups, and with controls, in auditory memory. Over the five-year period, the mid group, in comparison with the high group, improved in visual memory; additionally, the high group remained stable, in comparison with a slight decline in the control group, in inhibitory control., Conclusion: These results demonstrate that cognition-based subgroups of bipolar disorder participants have minimal differences in their longitudinal course in relation to each other and with unaffected controls., (© 2022 The Authors. Acta Psychiatrica Scandinavica published by John Wiley & Sons Ltd.)

Background: Mood disorders are associated with neurobiological disruptions in subliminal and supraliminal emotion processing. There may be additional variation based on sex and the presence of self-injurious thoughts and behaviors (SITBs). Examining individuals in remission allows us to understand trait-like emotion processing characteristics that persist in the absence of symptoms. This study investigates neural processing in response to supraliminal and subliminal emotional stimuli based upon mood disorder diagnosis, sex, and SITBs., Methods: Seventy-five participants with a history of any mood disorder (AMD; 52 female) and 27 healthy controls (HC; 14 female) completed a fMRI task presenting subliminal and supraliminal facial stimuli. Within the AMD group, 20 had no history of SITBs, 26 had histories of suicidal ideation only, and 27 had histories of both SI and self-injurious behavior. We examined activation of salience network regions of interest including the amygdala, insula, and subgenual anterior cingulate cortex (sgACC) during the task., Results: AMD showed greater insula activation in response to happy faces relative to sad faces, which was not seen in the HC group. Males exhibited lower insula activation in response to sad faces relative happy faces, a pattern not seen in females. Individuals with SITBs demonstrated a lack of sgACC blunting during supraliminal versus subliminal trials., Conclusions: We found different patterns of neural responses related to mood disorder status, sex, and SITBs. Findings highlight the importance of considering heterogeneity within diagnoses and examining neurobiological features in the context of remission., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Purpose: Healthcare workers are at increased risk for mental health problems during disasters such as the COVID-19 pandemic. Identifying resilience mechanisms can inform development of interventions for this population. The current study examined pathways that may support healthcare worker resilience, specifically testing enabling (social support enabled self-efficacy) and cultivation (self-efficacy cultivating support) models., Methods: Healthcare workers (N = 828) in the Rocky Mountain West completed self-report measures at four time points (once per month from April to July of 2020). We estimated structural equation models to explore the potential mediating effects that received social support and coping self-efficacy had (at time 2 and time 3) between traumatic stress symptom severity (at time 1 and time 4). Models included covariates gender, age, minority status, and time lagged co-variations between the proposed mediators (social support and coping self-efficacy)., Results: The full model fit the data well, CFI = .993, SRMR = .027, RMSEA = .036 [90% CIs (0.013, 0.057)]. Tests of sequential mediation supported enabling model dynamics. Specifically, the effects of time 1 traumatic stress severity were mediated through received social support at time 2 and time 3 coping self-efficacy, in sequential order to reduce time 4 traumatic stress severity., Conclusions: Findings show the importance of received social support and coping self-efficacy in mitigating psychopathology risk. Interventions can support mental health by focusing on social resource engagement that facilitates coping empowerment, which may decrease risk for mental health job-related problems among frontline healthcare workers exposed to highly stressful events., (© 2022. The Author(s).)

Our country is facing a resurgence of behavioral health crises from over the past 30 years, further illuminated and exacerbated by the global COVID-19 pandemic. Increasing suicide crises among youths over recent decades, untreated anxiety and depression, and serious mental illness are signs of the need for improvements in accessible, affordable, timely, and comprehensive behavioral health services. Against the backdrop of high suicide rates and low behavioral health services in Utah, statewide collaborators aligned with a common goal: deliver crisis services to anyone, anytime, and anywhere. After its initiation in 2011, the integrated behavioral health crisis response system continued to expand and excel, ultimately improving access and referral to services, flattening suicide rates, and reducing stigma. The global pandemic further motivated the expansion of Utah's crisis response system. This review focuses on the unique experiences of the Huntsman Mental Health Institute as a catalyst and partner in these changes. Our goals are to: inform about unique Utah partnerships and actions in the crisis mental health space, describe initial steps and outcomes, highlight continuing challenges, discuss pandemic-specific barriers and opportunities, and explore the long-term vision to improve quality and access to mental health resources., (Copyright © 2022 by the American Psychiatric Association.)

First responders are at high risk for disorders that arise from repeat exposure to stress and trauma (Post Traumatic Stress Disorder, depression, and problematic alcohol use). Although mental health treatments are available, first responders often do not access them, anchored by barriers that include: lack of knowledge, stigma, negative experience with mental health providers, and time-based burdens. In this study, we designed an intervention to address these barriers, extending a Planned-Action framework. Step 1 involved self-report screening for four mental health risks (PTSD, depression, anxiety, and alcohol use risk), delivered to all personnel electronically, who were free to either consent and participate or opt-out. The detection of risk(s) in Step 1 led to scheduling a Step 2 telehealth appointment with a trained clinician. We report descriptive statistics for participation/attrition/utilization in Steps 1 and 2, rates of risk on four mental health variables, and rate of adherence to follow-up treatment recommendations. Step 1: In total, 53.3% of personnel [229 of 429 full-time employees (221 males; eight females; 95% White; 48% paramedic or Emergency Medical Technician; 25% captain; 19% engineer; 7% other)] initially opted-in by consenting and completing the brief remote screening survey. Among those who opted-in and completed ( n = 229), 43% screened positive for one or more of the following mental health risks: PTSD (7.9%); depression (9.6%); anxiety (13.5%); alcohol use (36.7%). Step 2: A maximum of three attempts were made to schedule "at risk" individuals into Step 2 ( n = 99). Among the 99 who demonstrated a need for mental health treatment (by screening positive for one or more risk), 56 (56.6%) engaged in the telehealth appointment. Of the 56 who participated in Step 2 clinical appointments, 38 were recommended for further intervention (16.6% of full-time personnel who participated). Among the 38 firefighters who were recommended to seek further mental health services, 29 were adherent/followed through (76.3% of those who received recommendations for further services). Taken together, evidence-based, culturally conscious, stepped care models delivered via the virtual/telehealth medium can promote access, utilization, and cost-effective mental health services for first responders. Implications are for informing larger, more rigorous dissemination and implementation efforts., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Wright, Fuessel-Hermann, Pazdera, Lee, Ridge, Kim, Konopacki, Hilton, Greensides, Langenecker and Smith.)

Anterior cingulate cortex (ACC) response during attentional control in the context of task-irrelevant emotional faces is a promising biomarker of cognitive behavioral therapy (CBT) outcome in patients with social anxiety disorder (SAD). However, it is unclear whether this biomarker extends to major depressive disorder (MDD) and is specific to CBT outcome. In the current study, 72 unmedicated patients with SAD (n = 39) or MDD (n = 33) completed a validated emotional interference paradigm during functional magnetic resonance imaging before treatment. Participants viewed letter strings superimposed on task-irrelevant threat and neutral faces under low perceptual load (high interference) and high perceptual load (low interference). Biomarkers comprised anatomy-based rostral ACC (rACC) and dorsal ACC (dACC) response to task-irrelevant threat (>neutral) faces under low and high perceptual load. Patients were randomly assigned to 12 weeks of CBT or supportive therapy (ST) (ClinicalTrials.gov identifier: NCT03175068). Clinician-administered measures of social anxiety and depression severity were obtained at baseline and every 2 weeks throughout treatment (7 assessments total) by an assessor blinded to the treatment arm. A composite symptom severity score was submitted to latent growth curve models. Results showed more baseline rACC activity to task-irrelevant threat>neutral faces under low, but not high, perceptual load predicted steeper trajectories of symptom improvement throughout CBT or ST. Post-hoc analyses indicated this effect was driven by subgenual ACC (sgACC) activation. Findings indicate ACC activity during attentional control may be a transdiagnostic neural predictor of general psychotherapy outcome., (© 2021. The Author(s), under exclusive licence to American College of Neuropsychopharmacology.)

Strategies to link impulsivity and self-injurious behaviors (SIBs) show highly variable results, and may differ depending on the impulsivity measure used. To better understand this lack of consistency, we investigated correlations between self-report and behavioral impulsivity, inhibitory control, SIBs, and rumination. We included participants aged 13-17 years with either current or remitted psychopathology who have ( n = 31) and who do not have ( n = 14) a history of SIBs. Participants completed self-report measures of impulsivity, the Rumination Responsiveness Scale (RRS), and two behavioral measures of impulsivity: the Balloon Analogue Risk Task (BART) and Parametric Go/No-Go (PGNG). Lifetime SIBs were positively associated with self-reported impulsivity, specifically positive and negative urgency. However, individuals with greater lifetime SIBs demonstrated greater risk aversion (lower impulsivity) as measured by the BART, whereas there was no relation between lifetime SIBs and PGNG performance. There was no relation between rumination and behavioral impulsivity, although greater rumination was associated with higher negative urgency. Future research examining the role of SIBs in the context of active versus remitted psychopathology is warranted. Because most adolescents were remitted from major depressive disorder at the time of study, follow-up studies can determine if lower risk-taking may aid individuals with more prior SIBs to achieve and maintain a remitted state.

Background: Resting-state graph-based network edges can be powerful tools for identification of mood disorders. We address whether these edges can be integrated with Research Domain Criteria (RDoC) constructs for accurate identification of mood disorder-related markers, while minimizing active symptoms of disease., Methods: We compared 132 individuals with currently remitted or euthymic mood disorder with 65 healthy comparison participants, ages 18-30 years. Subsets of smaller brain parcels, combined into three prominent networks and one network of parcels overlapping across these networks, were used to compare edge differences between groups. Consistent with the RDoC framework, we evaluated individual differences with performance measure regressors of inhibitory control and reward responsivity. Within an omnibus regression model, we predicted edges related to diagnostic group membership, performance within both RDoC domains, and relevant interactions., Results: There were several edges of mood disorder group, predominantly of greater connectivity across networks, different than those related to individual differences in inhibitory control and reward responsivity. Edges related to diagnosis and inhibitory control did not align well with prior literature, whereas edges in relation to reward responsivity constructs showed greater alignment with prior literature. Those edges in interaction between RDoC constructs and diagnosis showed a divergence for inhibitory control (negative interactions in default mode) relative to reward (positive interactions with salience and emotion network)., Conclusions: In conclusion, there is evidence that prior simple network models of mood disorders are currently of insufficient biological or diagnostic clarity or that parcel-based edges may be insufficiently sensitive for these purposes., (Copyright © 2021 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Background: Research by our group and others have demonstrated the feasibility of using mobile phone derived metadata to model mood and cognition. Given the effects of age and mood on cognitive performance, it was hypothesized that using such data a model could be built to predict chronological age and that differences between predicted age and actual age could be a marker of pathology. Methods: These data were collected via the ongoing BiAffect study. Participants complete the Mood Disorders Questionnaire (MDQ), a screening questionnaire for bipolar disorder, and self-reported their birth year. Data were split into training and validation sets. Features derived from the smartphone kinematics were used to train random forest regression models to predict age. Prediction errors were compared between participants screening positive and negative on the MDQ. Results: Three hundred forty-four participants had analyzable data of which 227 had positive screens for bipolar disorder and 117 had negative screens. The absolute prediction error tended to be lower for participants with positive screens (median 4.50 years) than those with negative screens (median 7.92 years) ( W = 508, p = 0.0049). The raw prediction error tended to be lower for participants with negative screens (median = -5.95 years) than those with positive screens (median = 0.55 years) ( W = 1,037, p = 0.037). Conclusions: The tendency to underestimate the chronological age of participants screening negative for bipolar disorder compared to those screening positive is consistent with the finding that bipolar disorder may be associated with brain changes that could reflect pathological aging. This interesting result could also reflect that those who screen negative for bipolar disorder and who engaged in the study were more likely to have higher premorbid functioning. This work demonstrates that age-related changes may be detected via a passive smartphone kinematics based digital biomarker., Competing Interests: OA is a co-founder of KeyWIse AI. He also serves on the advisory boards of Embodied Labs and Blueprint Health. AL is an advisor for Buoy health and a consultant for Otsuka USA and ATAI Life Sciences, in addition to being a Co-founder of KeyWise AI. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Zulueta, Demos, Vesel, Ross, Piscitello, Hussain, Langenecker, McInnis, Nelson, Ryan, Leow and Ajilore.)

Background: Individuals with depression often demonstrate an altered peripheral inflammatory profile, as well as emotion perception difficulties. However, correlations of inflammation with overall depression severity are inconsistent and inflammation may only contribute to specific symptoms. Moreover, measurement of the association between inflammation and emotion perception is sparse in adolescence, despite representing a formative window of emotional development and high-risk period for depression onset., Methods: Serum interleukin (IL)-6, tumor necrosis factor (TNF)-α, and IL-1β were measured in 34 adolescents aged 12-17 with DSM-IV depressive disorders (DEP) and 29 healthy controls (HC). Participants were evaluated using the Children's Depression Rating Scale-Revised (CDRS-R) and symptom subscales were extracted based on factor analysis. Participants also completed a performance-based measure of emotion perception, the Facial Emotion Perception Test (FEPT), which assesses the accuracy of categorizing angry, fearful, sad, happy, and neutral facial emotions., Results: IL-6 and TNF-α correlated with reported depressed mood and somatic symptoms, respectively, but not total CDRS-R score, anhedonia or observed mood, across both DEP and HC. DEP demonstrated lower accuracy for identifying angry facial expressions. Higher IL-6 was inversely related to accuracy and discrimination of angry and neutral faces across all participants. IL-1β was associated with reduced discrimination of fearful faces., Conclusions: Inflammatory markers were sensitive to affective and somatic symptoms of depression and processing of emotional threat in adolescents. In particular, IL-6 was elevated in depressed adolescents and therefore may represent a specific target for modulating depressive symptoms and emotion processing., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Objective: The increase in smartphone usage has enabled the possibility of more accessible ways to conduct neuropsychological evaluations. The objective of this study was to determine the feasibility of using smartphone typing dynamics with mood scores to supplement cognitive assessment through trail making tests., Methods: Using a custom-built keyboard, naturalistic keypress dynamics were unobtrusively recorded in individuals with bipolar disorder (n = 11) and nonbipolar controls (n = 8) on an Android smartphone. Keypresses were matched to digital trail making tests part B (dTMT-B) administered daily in two periods and weekly mood assessments. Following comparison of dTMT-Bs to the pencil-and-paper equivalent, longitudinal mixed-effects models were used to analyze daily dTMT-B performance as a function of typing and mood., Results: Comparison of the first dTMT-B to paper TMT-B showed adequate reliability (intraclass correlations = 0.74). In our model, we observed that participants who typed slower took longer to complete dTMT-B (b = 0.189, p < .001). This trend was also seen in individual fluctuations in typing speed and dTMT-B performance (b = 0.032, p = .004). Moreover, participants who were more depressed completed the dTMT-B slower than less depressed participants (b = 0.189, p < .001). A practice effect was observed for the dTMT-Bs., Conclusion: Typing speed in combination with depression scores has the potential to infer aspects of cognition (visual attention, processing speed, and task switching) in people's natural environment to complement formal in-person neuropsychological assessments that commonly include the trail making test., (© 2021 The Authors. Brain and Behavior published by Wiley Periodicals LLC.)

Background: Individuals with bipolar I disorder (BD-I) experience both poor sleep and neuropsychological dysfunction relative to non-psychiatric populations, which limits functional recovery. Poor sleep adversely affects learning, memory, and executive functioning in healthy individuals; however, little is known about the role of poor sleep in neuropsychological functioning in BD-I. We tested whether sleep disturbance was greater in BD-I than healthy control participants (HC), and compared the effect of sleep quality on learning, memory, and executive functioning between BD-I and HC., Methods: Participants with BD-I (N=250) and HC (N=206) completed the Pittsburgh Sleep Quality Index, neuropsychological testing, and clinician-administered mood measures as part of a naturalistic study of bipolar disorder. We examined effects of both diagnosis and sleep quality on neuropsychological functioning., Results: Relative to HC, BD-I showed poorer sleep quality and neuropsychological functioning in verbal learning, verbal and visual memory, processing speed, psychomotor speed, inhibitory control, and selective attention (7/9 domains). Poor sleep quality was associated with poorer verbal learning, verbal fluency, processing speed, and interference control (4/9). Effects of poor sleep on neuropsychological functioning did not differ between BD-I and HC., Limitations: The assessment of sleep quality using a self-report measure and the effects of medications/sleeping aids (given the naturalistic study design) should be considered when interpreting results., Conclusions: Those with BD-I experiencing poor sleep may also be more vulnerable to verbal learning and executive functioning impairments. The findings of poor sleep in relation to poorer neuropsychological functioning have implications for assessment and treatment of sleep disturbance in BD-I., (Copyright © 2021 Elsevier B.V. All rights reserved.)

One sex differences in the perception of emotion is that females, particularly those with high anxiety, often show heightened identification of fearful faces. To better understand the causal role of glucocorticoids in this sex difference, we examine these associations in people with HIV(PWH) where emotion perception is impaired and mental health disorders are frequent. In a double-blind, placebo-controlled, cross-over study, we used a single low-dose of hydrocortisone (10 mg; LDH) as a mechanistic probe of the effects of elevated glucocorticoids on negative emotion perception in 65 PWH (31 women). The primary outcome was accuracy in identifying emotional expressions on the Facial Emotion Perception Test (FEPT). Salivary cortisol, self-reported stress/anxiety, and childhood trauma were also assessed. LDH increased salivary cortisol levels versus placebo. The effect of LDH versus placebo on FEPT accuracy depended on the combined influence of facial expression and sex (P = 0.03). LDH influenced accuracy only for women (P = 0.03), specifically for fearful faces (Cohen's d = 0.44, P = 0.04). Women's enhanced threat detection varied with psychological burden (mood, anxiety, and post-traumatic stress symptoms), more pronounced among those with lower burden and trauma (P < 0.05). This result suggests a role of the HPA axis in sex differences for perception of fearful faces in women with HIV, potentially due to changes in glucocorticoid receptor availability/activity, or improved integration of signals from facial recognition and emotion processing regions. The blunting of this effect in men and in individuals with more severe trauma suggests that the mechanisms underlying threat detection differ by sex and trauma history and warrant further investigation., (© 2021. Journal of NeuroVirology, Inc.)

Introduction: Alcohol, nicotine, and marijuana are the three most widely used substances among adolescents and young adults, with co-use of multiple substances being common. Few longitudinal studies have examined risk factors of alcohol, marijuana, and nicotine poly-substance use. We examined frequency of alcohol, marijuana, and cigarette poly-substance use over time and how key risk factors contribute to this substance use during adolescence and young adulthood., Methods: Participants (N = 1263 9th and 10th graders) were oversampled for ever-smoking a cigarette at baseline from 16 Chicago-area high schools between 2004 and 2006. Many participants progressed to heavier cigarette use, as well as alcohol and marijuana use over time. Participants completed questionnaires assessing substance use and psychosocial factors at baseline, 6-, 15-, 24-, 33-months, and 5-, 6-, and 7-years., Results: Longitudinal multi-level models demonstrated that at baseline and over time, more depression symptoms, more anxiety symptoms, negative mood regulation expectancies, and lower grade point average (GPA) were each associated with more poly-substance use over time. In addition, there were a number of interaction effects of gender (e.g., depression was related to substance use in males) and developmental stage moderated these relationships., Conclusions: Depression, anxiety, negative mood regulation expectancies, and GPA all significantly influence both initial and longitudinal levels of substance use across adolescence and young adulthood. Our findings underscore the importance of identifying and treating youth with depression and anxiety symptoms, as well as providing resources early for those struggling in school in order to help with substance use prevention and intervention efforts., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

The mental health of healthcare workers (HCWs) is critical to their long-term well-being and future disaster preparedness. Goal 1 of this study was to identify rates of mental health problems experienced by HCWs. Goal 2 was to test a model of risk stemming from pandemic-related stressors and vulnerability factors. This cross-sectional study included HCWs (N ​= ​2,246 [1,573 clinical providers; 673 non-clinical staff]) in the Rocky Mountain West who voluntarily completed an online survey in April/May 2020. Respondents completed measures for traumatic stress symptoms, depression, anxiety, alcohol use, and sleep. Logistic regressions stratified by professional role (clinical versus non-clinical) were specified to predict clinical screening cutoff (positive/negative) as a function of five pandemic-related stressors (immunocompromised self; immunocompromised household member; care provision to infected patients; clinical management role; positive cases). Results showed that more than half of HCWs surveyed (52.5%) screened positive (above cutoff) for traumatic stress, depression, or anxiety, with ~20% reporting problematic alcohol use, and variable insufficient sleep from ~10% off shift to ~50% on shift. Clinical employees with an immunocompromised household member had increased odds of screening positive for a mental health problem. Non-clinical HCWs who were immunocompromised were at elevated risk for screening positive a mental health problem. Being female, minority status, and younger increased odds for mental health problems. Implications include alleviating a portion of the mental health burden of HCWs involved in response to the SARS-CoV-2 pandemic by considering policies to protect immunocompromised HCWs and their families (e.g., vaccine priorities, telework options)., Competing Interests: The authors whose names are listed immediately below certify that they have NO affiliations with or involvement in any organization or entity with any financial interest or non-financial interest in the subject matter or materials discussed in this manuscript., (© 2021 Published by Elsevier Inc.)

The etiology of Major Depressive Disorder (MDD) is poorly understood, and identifying endophenotypes, or intermediate processes implicated in pathophysiology, for MDD may inform treatment and identification/prevention efforts. Impaired set-shifting and inhibition are commonly observed in MDD; however, few studies have examined they are endophenotypes for MDD. Thus, the present study tested whether set-shifting and/or inhibition satisfy several endophenotype criteria: specifically, whether they were (1) impaired in current MDD, (2) impaired in remitted MDD, and (3) familial (i.e., correlated within sibling pairs). Set-shifting and inhibition were assessed using subtests from the Delis-Kaplan Executive Function System. Psychopathology was assessed using the Structured Clinical Interview for DSM-5. Results indicated set-shifting deficits were familial and present in both current MDD and in remitted MDD individuals who had no current disorders, suggesting they may be state-independent. Inhibition was familial, but was generally not impaired in current nor remitted MDD (although the remitted MDD group with no current disorders exhibited impairments on one of the two inhibition tasks). These findings indicate that impaired set-shifting is a promising endophenotype candidate for MDD. Findings are limited to young adults, and further research is needed to test generalizability to other populations, evaluate longitudinal relationships, and examine other endophenotype criteria., (Copyright © 2021. Published by Elsevier B.V.)

Background: Rumination and worry are repetitive negative thinking (RNT) tendencies that contribute to the development and maintenance of internalizing psychopathologies. Accruing data suggest rumination and worry represent overlapping and unique transdiagnostic cognitive processes. Yet, prior neuroimaging research has mostly focused on rumination in depression, which points to involvement of resting-state brain activity in default mode, executive, salience, and/or affective networks., Methods: The current study examined relations between brain activity during rest and RNT in a transdiagnostic sample. Resting-state fMRI data was analyzed in 80 unmedicated patients with internalizing conditions. Regression analysis, controlling for anxiety and depression symptoms, was performed with seed regions implicated in default mode, executive, salience, and affective networks. Rumination and worry were assessed with standard self-report measures., Results: Whole-brain regression results showed more rumination and worry jointly corresponded with greater positive resting-state functional connectivity (rsFC) between the amygdala and prefrontal regions (i.e., middle frontal gyrus, inferior frontal gyrus). Conversely, more worry (controlling for rumination) corresponded with greater negative rsFC between amygdala and precuneus. No significant results were observed for rumination alone (controlling for worry)., Conclusions: Findings indicate the affective network plays a role in RNT, and distinct patterns of connectivity between amygdala and regions implicated in the executive and default mode networks were observed across patients with internalizing conditions. Results suggest different mechanisms contribute to RNT as a unitary construct and worry as a unique construct., (© 2021 Wiley Periodicals LLC.)

The mental health of frontline workers is critical to a community's ability to manage crises and disasters. This study assessed risks for mental health problems (traumatic stress, depression, anxiety, alcohol use, insomnia) in association with pandemic-related stressors in a sample of emergency and hospital personnel (N = 571). Respondents completed self-report surveys online from April 1st to May 7th, 2020 in the Rocky Mountain region of the United States. Results showed that roughly fifteen to thirty percent of respondents screened positive for each disorder. Odds of screening positive were similar between groups for probable acute traumatic stress, depressive disorder, anxiety disorder, and alcohol use disorder; emergency personnel reported significantly higher rates of insufficient sleep than healthcare workers. Logistic regressions showed that respondents who reported having an immunocompromised condition had higher odds of acute traumatic stress, anxiety, and depression. Having an immunocompromised household member was associated with higher odds of insufficient sleep and anxiety. Being in a direct care provision role was associated with higher odds of screening positive for risky alcohol use. Being in a management role over direct care providers was associated with higher odds of screening positive for anxiety, risky alcohol use, and insufficient sleep. There was an inverse relationship between number of positive COVID-19 cases and anxiety, such that as positive cases went up, anxiety decreased. Overall, the mental health risks that we observed early in the COVID-19 pandemic are elevated above previous viral outbreaks (SARS) and comparable to rates shown in disasters (9/11 attacks; Hurricane Katrina)., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Adolescent-onset depression often results in a chronic and recurrent course, and is associated with worse outcomes relative to adult-onset depression. Targeting habitual depressive rumination, a specific known risk factor for relapse, may improve clinical outcomes for adolescents who have experienced a depressive episode. Randomized controlled trials (RCTs) thus far have demonstrated that rumination-focused cognitive behavioral therapy (RFCBT) reduces depressive symptoms and relapse rates in patients with residual depression and adolescents and young adults with elevated rumination. This was also observed in a pilot RCT of adolescents at risk for depressive relapse. Rumination can be measured at the self-report, behavioral, and neural levels- using patterns of connectivity between the Default Mode Network (DMN) and Cognitive Control Network (CCN). Disrupted connectivity is a putative important mechanism for understanding reduced rumination via RFCBT. A feasibility trial in adolescents found that reductions in connectivity between DMN and CCN regions following RFCBT were correlated with change in rumination and depressive symptoms., Method: This is a phase III two-arm, two-stage, RCT of depression prevention. The trial tests whether RFCBT reduces identified risk factors for depressive relapse (rumination, patterns of neural connectivity, and depressive symptoms) in adolescents with partially or fully remitted depression and elevated rumination. In the first stage, RFCBT is compared to treatment as usual within the community. In the second stage, the comparator condition is relaxation therapy. Primary outcomes will be (a) reductions in depressive rumination, assessed using the Rumination Response Scale, and (b) reductions in resting state functional magnetic resonance imaging connectivity of DMN (posterior cingulate cortex) to CCN (inferior frontal gyrus), at 16 weeks post-randomization. Secondary outcomes include change in symptoms of depression following treatment, recurrence of depression over 12 months post-intervention period, and whether engagement with therapy homework (as a dose measure) is related to changes in the primary outcomes., Discussion: RFCBT will be evaluated as a putative preventive therapy to reduce the risk of depressive relapse in adolescents, and influence the identified self-report, behavioral, and neural mechanisms of change. Understanding mechanisms that underlie change in rumination is necessary to improve and further disseminate preventive interventions., Trial Registration: ClinicalTrials.gov Identifier: NCT03859297 , registered 01 March 2019.

One well-known phenotypic risk factor for the development of alcohol use disorder is sensitivity to the rewarding effects of alcohol. In the present study, we examined whether individuals who are sensitive to alcohol reward are also sensitive to nondrug rewards, thereby reflecting a broader individual difference risk factor. Specifically, we tested the hypothesis that subjective response to acute rewarding effects of alcohol would be related to neural activation during monetary reward receipt relative to loss (in the absence of alcohol). Community-recruited healthy young social drinkers (N = 58) completed four laboratory sessions in which they received alcohol (0.8 g/kg) and placebo in alternating order under double-blind conditions, providing self-report measures of subjective response to alcohol at regular intervals. At a separate visit 1-3 weeks later, they completed a reward-guessing game, the 'Doors' task, during fMRI in a drug-free state. Participants who reported greater motivation (i.e., wanting) to consume more alcohol after a single moderate dose of alcohol also exhibited greater neural activation in the bilateral ventral caudate and the nucleus accumbens during reward receipt relative to loss. Striatal activation was not related to other subjective ratings including alcohol-induced sedation, stimulation, or pleasure (i.e., feeling, liking). Our study is the first to show that measures of alcohol reward are related to neural indices of monetary reward in humans. These results support growing evidence that individual differences in responses to drug and nondrug reward are linked and together form a risk profile for drug use or abuse, particularly in young adults.

Background: Alcohol use disorder (AUD) remains an unresolved source of morbidity and mortality. Psychopharmacological challenge studies and neuroimaging experiments are two methods used to identify risk of problematic substance use. The present study combined these two approaches by examining associations between self-reported stimulation, sedation, liking or wanting more after a dose of alcohol and neural-based responses to anticipation of monetary gain and loss., Methods: Young adult binge drinkers (N = 56) aged 21-29, with no history of Substance Use Disorder completed five experimental sessions. These included four laboratory sessions in which they rated their subjective responses to alcohol (0.8 g/kg for men, 0.68 g/kg for women) or placebo, and a single functional magnetic resonance imaging session in which they completed a monetary incentive delay task. During the scan, we recorded neural signal related to anticipation of winning $5 or $1.50 compared to winning no money (WinMoney-WinZero), losing $5 or $1.50 compared to losing no money (LoseMoney-LoseZero), and winning $5 or $1.50 compared to losing $5 or $1.50 (WinMoney-LoseMoney), in reward related regions., Results: There were no significant associations between subjective ratings of "Feel Drug Effect", "Like Drug Effect", "Want More", stimulation or sedation following the acute alcohol challenge and neural activation in reward related regions during anticipation of monetary gain or loss., Conclusions: These results suggest that sensitivity of neural reward circuits is not directly related to rewarding subjective experiences from alcohol. Taken together with previous studies, the present findings indicate that the association between the subjective effects of drugs and reward-related brain activity depends on the drugs, tasks or subject samples under study., (Published by Elsevier B.V.)