Brain activity during reappraisal and associations with psychotherapy response in social anxiety and major depression: a randomized trial.

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.

State rumination predicts inhibitory control failures and dysregulation of default, salience, and cognitive control networks in youth at risk of depressive relapse: Findings from the RuMeChange trial.

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.

The Impact of Adjustment on Workplace Attitudes and Behaviors Among Health Care Workers During the COVID-19 Pandemic.

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.

Rumination-Focused Cognitive Behavioral Therapy Reduces Rumination and Targeted Cross-network Connectivity in Youth With a History of Depression: Replication in a Preregistered Randomized Clinical Trial.

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 [ps < .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.

Human emotion processing accuracy, negative biases, and fMRI activation are associated with childhood trauma.

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.

Rumination Induction Task in fMRI: Test-Retest Reliability in Youth and Potential Mechanisms of Change with Intervention.

Background: Rumination is a transdiagnostic problem that is common in major depressive disorder (MDD). Rumination Focused Cognitive Behavioral Therapy (RF-CBT) explicitly targets the ruminative habit. This study examined changes in brain activation during a rumination induction task in adolescents with remitted MDD following RF-CBT. We also evaluated the reliability of the rumination task among adolescents who received treatment as usual (TAU). Method: Fifty-five adolescents ages 14-17 completed a self-relevant rumination induction fMRI task and were then randomized to either RF-CBT (n = 30) or TAU (n = 25). Participants completed the task a second time either following 10-14 sessions of RF-CBT or the equivalent time delay for the TAU group. We assessed activation change in the RF-CBT group using paired-samples t-tests and reliability by calculating intraclass correlation coefficients (ICCs) of five rumination-related ROIs during each of three blocks for the TAU and RF-CBT groups separately (Rumination Instruction, Rumination Prompt, and Distraction). Results: Following treatment, participants in the RF-CBT group demonstrated an increase in activation of the left precuneus during Rumination Instruction and the left angular and superior temporal gyri during Rumination Prompt ( p < .01). The TAU group demonstrated fair to excellent reliability ( M = .52, range = .27-.86) across most ROIs and task blocks. In contrast, the RF-CBT group demonstrated poor reliability across most ROIs and task blocks ( M = .21, range = -.19-.69). Conclusion: RF-CBT appears to lead to rumination-related brain change. We demonstrated that the rumination induction task has fair to excellent reliability among individuals who do not receive an intervention that explicitly targets the ruminative habit, whereas reliability of this task is largely poor in the context of RF-CBT. This has meaningful implications in longitudinal and intervention studies, particularly when conceptualizing it as an important target for intervention. It also suggests one of many possible mechanisms for why fMRI test-retest reliability can be low that appears unrelated to the methodology itself.

Autonomic complexity dynamically indexes affect regulation in everyday life.

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).

Childhood trauma relates to worse memory functioning in bipolar disorder.

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 η2 = 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.

Reduced connectivity of the cognitive control neural network at rest in young adults who had their first drink of alcohol prior to age 18.

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.

Negative association between non-suicidal self-injury in adolescents and default mode network activation during the distraction blocks of a rumination task.

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.

A Novel Approach to Clustering Accelerometer Data for Application in Passive Predictions of Changes in Depression Severity.

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.

Actigraphic Wake after Sleep Onset and Symptom Severity Correspond with Rumination in Trauma-Exposed Individuals.

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.

Early Emergence of Rumination has no Association with Performance on a Non-affective Inhibitory Control Task.

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 (BChilhood Maltreatment = 27.52, 95% CIs [5.63, 49.41], BFamily 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.

Moral injury and psychosocial functioning in health care workers during the COVID-19 pandemic.

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).

Low rate of performance validity failures among individuals with bipolar disorder.

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.

Exposure to potentially morally injurious events and mental health outcomes among frontline workers affected by the coronavirus pandemic.

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).

Relations of gray matter volume to dimensional measures of cognition and affect in mood disorders.

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.

Early Life Trauma and Social Processing in HIV: The Role of Neuroendocrine Factors and Inflammation.

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 ß [ 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.

Cognitive subgroups and their longitudinal trajectories in bipolar disorder.

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.