Childhood adversity, accelerated GrimAge, and associated health consequences.

Childhood adversity is linked to psychological, behavioral, and physical health problems, including obesity and cardiometabolic disease. Epigenetic alterations are one pathway through which the effects of early life stress and adversity might persist into adulthood. Epigenetic mechanisms have also been proposed to explain why cardiometabolic health can vary greatly between individuals with similar Body Mass Index (BMIs). We evaluated two independent cross-sectional cohorts of adults without known medical illness, one of which explicitly recruited individuals with early life stress (ELS) and control participants (n = 195), and the other a general community sample (n = 477). In these cohorts, we examine associations between childhood adversity, epigenetic aging, and metabolic health. Childhood adversity was associated with increased GrimAge Acceleration (GAA) in both cohorts, both utilizing a dichotomous yes/no classification (both p < 0.01) as well as a continuous measure using the Childhood Trauma Questionnaire (CTQ) (both p < 0.05). Further investigation demonstrated that CTQ subscales for physical and sexual abuse (both p < 0.05) were associated with increased GAA in both cohorts, whereas physical and emotional neglect were not. In both cohorts, higher CTQ was also associated with higher BMI and increased insulin resistance (both p < 0.05). Finally, we demonstrate a moderating effect of BMI on the relationship between GAA and insulin resistance where GAA correlated with insulin resistance specifically at higher BMIs. These results, which were largely replicated between two independent cohorts, suggest that interactions between epigenetics, obesity, and metabolic health may be important mechanisms through which childhood adversity contributes to long-term physical and metabolic health effects.

Increased plasminogen activator inhibitor-1 (PAI-1) and its associations with metabolic risk in healthy young adults with early life stress.

OBJECTIVES: We aimed to characterize the interplay between early life stress (ELS), metabolic syndrome (MetS), and plasminogen activator inhibitor-1 (PAI-1), a major inhibitor of the fibrinolytic system implicated in cardiometabolic diseases. We also examined the understudied intersection of ELS, physical activity and PAI-1. METHODS: Healthy young adults ages 18-40 (N=200; 68% female) were recruited from the community. Participants with ELS (N=118) experienced childhood maltreatment, and the majority (n=92) also experienced childhood parental loss. Control participants (N=82) had no history of childhood maltreatment or parental loss. Participants had no current cardiometabolic or thrombotic conditions. Fasting plasma samples were assessed for markers of metabolic risk and total PAI-1 using the Bio-Plex Pro Human Diabetes Panel (Bio-Rad Laboratories). A composite metabolic risk z-score (MetS risk) was computed from the mean standardized z-scores of waist-to-height ratio, systolic and diastolic blood pressure, triglycerides, total cholesterol, LDL and HLD cholesterol, fasting plasma glucose, and hemoglobin A1c. RESULTS: We found that a history of ELS was linked to both higher PAI-1 levels and a higher MetS risk score. ELS was associated with a higher MetS Z-score in adulthood via increased circulating PAI-1 levels (Average Causal Mediation Effect [ACME]= 0.07, p = 0.036). ELS was also linked to increased PAI-1 levels via greater MetS z-scores (ACME = 0.02, p < 0.001). There was a significant interaction effect of ELS and exercise on PAI-1 levels (p = 0.03), such that engaging in higher levels of daily exercise was linked to lower PAI-1 levels in individuals with ELS. CONCLUSION: Healthy young adults with ELS have elevated PAI-1 levels and metabolic risk scores. Among individuals with ELS, exercise is linked to lower PAI-1 levels, suggesting a potential direction for early intervention.

Micro-sequences of anger and shame and non-suicidal self-injury in youth: an ecological momentary assessment study.

OBJECTIVE: Non-suicidal self-injury (NSSI) is a significant mental health concern with the highest prevalence among adolescents. NSSI has been conceptualized as one of the maladaptive strategies to cope with challenging affect or a form of self-punishment. Although characterizing moment-to-moment associations between shame and NSSI in individuals' real-world environment and partitioning between- and within-person effects is critical for mobile and timely interventions, most studies examined habitual experiences of negative affective states and focused on adults. METHOD: In this study, we focused on in vivo anger at self and others and shame and NSSI among 158 adolescents 3 weeks following their psychiatric hospitalizations using ecological momentary assessment (EMA) technology. RESULTS: We found that greater between-person levels of anger at self and others were linked to a higher number of subsequent NSSI occurrences within a day. These findings remained primarily unchanged when we statistically adjusted for participants' age, sex assigned at birth, the number of current psychiatric diagnoses, EMA response rates, and youth lifetime history of SI. Within-person increases in NSSI were linked to increased anger at self over and beyond between-person average levels of NSSI. CONCLUSIONS: These findings highlight the potential regulatory role of NSSI to decrease negative affective states and point to the clinical utility of assessing and early mobile interventions targeting challenging affect in youth.

Cognitive inflexibility and suicidal ideation among adolescents following hospitalization: The moderating role of life stress.

BACKGROUND: Cognitive inflexibility has recently been investigated as potential vulnerability factor for suicidal ideation (SI), but the context in which it may convey risk is unclear. Life stress has also been reliably associated with SI among adolescents, and following a stress-diathesis model, may be a factor that moderates the relationship between cognitive inflexibility and SI. METHODS: Psychiatrically hospitalized adolescents (N = 259) at high risk for future SI were followed for 18 months after discharge. Interviews assessing life stress and SI and a neurocognitive task assessing cognitive inflexibility were conducted at six- and 12-months. SI was also assessed at 18-month post-discharge. Linear mixed models were used to determine the moderating effect of stress on the relationship between cognitive inflexibility and SI, accounting for relevant clinical and demographic covariates. RESULTS: Chronic stress moderated the association between cognitive inflexibility and SI, with a stronger association found among youth with greater levels compared to lower levels of chronic stress. This finding was maintained after statistically adjusting for depressive symptoms and relevant demographic covariates. No prospective associations between cognitive inflexibility, life stress, and SI were found. LIMITATIONS: SI was measured at 6-month intervals, precluding evaluation of the relationship on a more proximal timescale. CONCLUSIONS: Cognitively inflexible adolescents under conditions of high chronic stress are more likely to experience increased SI severity, supporting a cognitive inflexibility stress-diathesis model of SI in adolescents. The findings highlight the importance of assessing these modifiable factors among adolescents at a high risk for SI.

Sleep disturbance and suicidality in psychiatrically hospitalized adolescents: The role of specific emotion regulation domains.

BACKGROUND: Sleep disturbance is associated with broadband measurements of emotion regulation (ER). The linkage between ER, a multidimensional process, and suicidal ideation and suicide attempt is also documented in theoretical and empirical work. Recent research indicates that distinct profiles of ER are associated with psychiatric outcomes, including adolescent suicidal ideation and attempt. The present study examined whether specific domains of ER would explain the association between sleep disturbance, and ideation and attempt among psychiatrically hospitalized adolescents. METHOD: The sample included 284 adolescents who completed self-report measures on sleep disturbance, ER, suicidal ideation, suicide attempt, and psychiatric symptoms upon inpatient hospitalization. RESULTS: Findings indicated that sleep disturbance was associated with suicidal ideation. Further, a single ER domain (perceived limited access to ER strategies) fully accounted for the significant association between sleep disturbance and suicidal ideation. A reported suicide attempt in the past week was correlated with the nonacceptance of emotional responses, perceived limited access to ER strategies, and emotional clarity, but was not associated with sleep disturbance. DISCUSSION: The current findings highlight the importance of examining narrowband ER and indicate the presence of differential associations between sleep disturbance, ER, and suicide-related outcomes. Findings further elucidate the possible role of impaired cognitive responses to emotional experiences in the co-occurrence of sleep disturbance and youth psychiatric outcomes.

Maltreatment history and reasons for self-injurious behavior among adolescents engaged in non-suicidal self-injury versus adolescents who attempted suicide.

OBJECTIVE: Self-injurious behavior (SIB) is a significant public health concern in the United States, especially among adolescents with histories of maltreatment. This study compared maltreatment characteristics and reasons for SIB between three homogenous samples of adolescents with either: (1) non-suicidal self-injury (NSSI); (2) suicide attempt/s (SA), and (3) typically developing controls (TDC). METHOD: Participants (N = 124) aged 13-17 years completed questionnaires about their maltreatment and SIB histories. RESULTS: Maltreatment rates were as follows: 90% NSSI group, 76% SA group, and 40% TDC group. Adolescents in the NSSI group reported significantly higher rates of emotional neglect compared to the SA group. Maltreated adolescents in the NSSI and SA groups reported the same top three SIB reasons: (1) get rid of bad feelings, (2) mental state at the time, and (3) problems with family. However, maltreated NSSI participants were significantly more likely to engage in SIB for emotion regulation reasons than maltreated SA participants, who were more likely to engage in SIB for interpersonal reasons. Physical neglect and physical abuse also arose as significant predictors of specific SIB reasons. CONCLUSIONS: Our findings help elucidate the maltreatment profiles and reasons for SIB among adolescents engaged in NSSI or SA. Specific maltreatment experiences may also influence the reasons why adolescents engaged in SIB.

Dialectical behavior therapy for adolescents (DBT-A): Outcomes among sexual minorities at high risk for suicide.

The alarming rates and pervasiveness of suicidal and self-destructive behaviors (e.g., non-suicidal self-injury) among young sexual minorities represent a major public health concern. We set out to examine whether an empirically driven treatment for suicide and self-harm, dialectical behavior therapy for adolescents (DBT-A), provides benefits for adolescents who identify as gay, lesbian, bisexual, or questioning (LGBQ). LGBQ adolescents (n = 16) were compared with non-LGBQ peers (n = 23). Psychological measures were collected before and after participation in a comprehensive DBT-A program. LGBQ participants demonstrated significant improvements in emotion regulation, depression, borderline symptoms, and coping strategies; changes were comparable to their heterosexual peers.

Sex and age moderate the trajectory of guilt among children and adolescents with and without recent suicidal ideation.

We aimed to examine whether the trajectories of ecologically derived guilt differ among a transdiagnostic sample of youth with and without recent suicidal ideation and whether sex and age moderated this association. We assessed guilt 3 times a day over a 2-week period via ecological momentary assessment (EMA) technology in 102 children recruited from the community, outpatient, and inpatient settings. The average age of children was 10.95 y.o. (SD = 2.26, range 8-16) and the majority were male (54.9%) and White (76.5%). We found that the real-world guilt during a two-week EMA period was higher among youth with greater suicidal ideation severity in the past six months. Moreover, there was a significant moderating effect of sex and age on this association, such that the association between suicidal ideation severity and guilt was particularly strong among females compared to males and youth who were 10 years old or older. The findings were maintained when we adjusted for the relevant demographic and clinical characteristics, including age, minority status, parental income, EMA response rate, and current internalising symptoms. These preliminary findings highlight the clinical relevance of assessing and targeting feelings of guilt in the day-to-day lives of youth, particularly for females and older youth.

COVID-19-Specific Suicidal Thoughts and Behaviors in Psychiatrically Hospitalized Adolescents.

This study examined the presence and correlates of COVID-specific suicidal thoughts and behaviors (i.e., thoughts of or engaging in intentional COVID-19 exposure with associated suicidal intent) among psychiatrically hospitalized adolescents. Adolescents (N = 143) completed study measures as part of the standard intake process between March 13th and August 14th, 2020. Participants answered questionnaires assessing COVID-specific passive and active suicidal ideation (SI) and suicidal behavior, as well as COVID-related stressors and emotions, and public health guidance compliance. Findings highlights that COVID-specific SI is common in high-risk youth. COVID-specific SI was associated with COVID-19-related negative emotions, elevated stress, and decreased public health guidance compliance. Results suggest that COVID-specific suicidal thoughts and behaviors, and risk correlates, should be assessed within high-risk populations to facilitate prevention of risky behavior associated with intentional COVID-19 exposure.

COVID-19 Related Daily Stressors, Coping, and Suicidal Ideation in Psychiatrically Hospitalized Youth.

Background: Given reports of the adverse effects of COVID-19 on adolescent mental health, it is critical to understand how it impacts psychiatrically hospitalized youth who may be particularly vulnerable to its effects. Objective: This study aimed to advance our understanding of high-risk adolescents' experiences of COVID-19, including COVID-19-related stress, changes in daily functioning, and coping as they relate to suicidal ideation (SI). Method: Participants were 107 youth (ages 11-18; M = 15.06, SD = 1.79) admitted to an adolescent psychiatric inpatient unit during the time when the initial COVID-19 safety measures (i.e., school closure, stay-at-home- order) and reopening initiatives (Phase I, II, and III) were implemented in Rhode Island between March 13th and July 19th 2020. Adolescents completed measures of COVID-19-related stress, coping, functioning, and SI at the time of admission. Results: Nearly half of the sample (43%) reported a negative impact of COVID-19 on daily functioning. Youth who endorsed COVID-19-related decline in functioning evidenced higher levels of SI compared to youth with no change or improvement in functioning due to COVID-19. Overall levels of stress were not associated with SI. Greater coping repertoire, but not the use of specific coping strategies was associated with higher levels of SI. Conclusions: Findings demonstrate the importance of examining COVID-19-related changes in functioning and broadening repertoire of coping strategies among adolescents at high risk for SI. Supplementary Information: The online version contains supplementary material available at 10.1007/s10566-021-09641-1.

Relationship between cognitive flexibility and subsequent course of mood symptoms and suicidal ideation in young adults with childhood-onset bipolar disorder.

Neurocognitive deficits, such as cognitive flexibility impairments, are common in bipolar disorder (BD) and predict poor academic, occupational, and functional outcomes. However, the association between neurocognition and illness trajectory is not well understood, especially across developmental transitions. This study examined cognitive flexibility and subsequent mood symptom and suicidal ideation (SI) course in young adults with childhood-onset BD-I (with distinct mood episodes) vs. BD-not otherwise specified (BD-NOS) vs. typically-developing controls (TDCs). Sample included 93 young adults (ages 18-30) with prospectively verified childhood-onset DSM-IV BD-I (n = 34) or BD-NOS (n = 15) and TDCs (n = 44). Participants completed cross-sectional neuropsychological tasks and clinical measures. Then participants with BD completed longitudinal assessments of mood symptoms and SI at 6-month intervals (M = 39.18 ± 16.57 months of follow-up data). Analyses included ANOVAs, independent-samples t tests, chi-square analyses, and multiple linear regressions. Participants with BD-I had significant deficits in cognitive flexibility and executive functioning vs. BD-NOS and TDCs, and impaired spatial working memory vs. TDCs only. Two significant BD subtype-by-cognitive flexibility interactions revealed that cognitive flexibility deficits were associated with subsequent percentage of time depressed and with SI in BD-I but not BD-NOS, regardless of other neurocognitive factors (full-scale IQ, executive functioning, spatial working memory) and clinical factors (current and prior mood and SI symptoms, age of BD onset, global functioning, psychiatric medications, comorbidity). Thus, cognitive flexibility may be an important etiological brain/behavior mechanism, prognostic indicator, and intervention target for childhood-onset BD-I, as this deficit appears to endure into young adulthood and is associated with worse prognosis for subsequent depression and SI.

Social media use, sleep, and psychopathology in psychiatrically hospitalized adolescents.

Sleep disruption among adolescents represents a major public health concern, and social media use may play an important role in affecting sleep and subsequent mental health. While prior studies of youth sleep and mental health have often focused on social media use frequency and duration, adolescents' emotional experiences related to social media have been underexplored, particularly among clinically acute populations. This study offers a preliminary investigation of associations among negative emotional experiences using social media, sleep disturbance, and clinical symptom severity in a sample of psychiatrically hospitalized youth. A sample of 243 adolescents (Mage = 15.34) completed self-report measures at a single time point. Measures assessed social media use, including frequency and duration, subjective experiences of use, and emotional responses to use, as well as sleep disturbance and clinical symptom severity, including suicidal ideation, internalizing symptoms, and attention problems. Results revealed that more frequent negative emotional responses to social media use were linked to greater sleep disturbance and higher clinical symptom severity. Furthermore, sleep disturbance mediated the relation between negative emotional responses to social media and clinical symptom severity. While gender differences were revealed in characteristics of social media use, sleep disturbance, and clinical outcomes, the associations among these constructs did not vary across gender groups. Overall, these findings highlight sleep disturbance as a potential mechanism through which negative emotional experiences on social media may impact clinical symptoms in psychiatrically vulnerable youth.

Social media use and self-injurious thoughts and behaviors: A systematic review and meta-analysis.

Despite considerable public and scholarly debate about the role of social media in self-injurious thoughts and behaviors (SITBs), no comprehensive, quantitative synthesis of this literature has previously been undertaken. The current systematic review and meta-analysis examines associations between social media use and SITBs, including suicidal ideation, suicide plans, suicide attempts, and nonsuicidal self-injury (NSSI). A range of social media behaviors and experiences were identified, including cybervictimization and perpetration, exposure to and generation of SITB-related content, problematic use, sexting, social media importance, and frequency of use. A systematic search of PsycINFO, Medline, CINAHL, and the references of prior reviews yielded 61 eligible studies. Results largely suggested medium effect sizes for associations between specific social media constructs (cybervictimization, SITB-related social media use, problematic social media use) and SITBs. There was no association between frequency of social media use and SITBs; however, studies on this topic were limited. The majority of studies identified focused on cybervictimization, and results suggested positive associations with all SITBs, with the association between cybervictimization and suicidal ideation stronger for adolescents than adults. Overall, findings highlight the utility of examining specific social media behaviors and experiences, and point to the need for more research in this area.

Facial emotion recognition and mood symptom course in young adults with childhood-onset bipolar disorder.

Facial emotion recognition deficits are common in bipolar disorder (BD) and associated with impairment. However, the relationship between facial emotion recognition and mood course is not well understood. This study examined facial emotion recognition and subsequent mood symptoms in young adults with childhood-onset BD versus typically developing controls (TDCs). The sample included 116 young adults (ages 18-30, 58% male, 78% White) with prospectively verified childhood-onset BD (n = 52) and TDCs (n = 64). At baseline, participants completed a facial emotion recognition task (Diagnostic Analysis of Non-Verbal Accuracy-2) and clinical measures. Then, participants with BD completed mood symptom assessments every 6 months (M = 8.7 ± 5.2 months) over two years. Analyses included independent-samples t tests and mixed-effects regression models. Participants with BD made significantly more recognition errors for child expressions than TDCs. There were no significant between-group differences for recognition errors for adult expressions, or errors for specific child or adult emotional expressions. Participants had moderate baseline mood symptoms. Significant time-by-facial emotion recognition interactions revealed more recognition errors for child emotional expressions predicted lower baseline mania and stable/consistent trajectory; fewer recognition errors for child expressions predicted higher baseline mania and decreasing trajectory. In addition, more recognition errors for adult sad expressions predicted stable/consistent depression trajectory and decreasing mania; fewer recognition errors for adult sad expressions predicted decreasing depression trajectory and stable/consistent mania. Effects remained when controlling for baseline demographics and clinical variables. Facial emotion recognition may be an important brain/behavior mechanism, prognostic indicator, and intervention target for childhood-onset BD, which endures into young adulthood and is associated with mood trajectory.

Suicidal thoughts and behaviors in psychiatrically hospitalized adolescents pre- and post- COVID-19: A historical chart review and examination of contextual correlates.

BACKGROUND: Psychiatrically vulnerable adolescents may be at heightened risk for suicide during the COVID-19 pandemic. This study characterizes suicidal ideation (SI) and suicide attempts (SA) in a sample of adolescents psychiatrically hospitalized during COVID-19. Rates of SI and SA are compared to a historical hospital sample from a matched period in the year prior. Associations between specific stressors and COVID-related SI are also explored. METHODS: This cross-sectional chart review utilizes hospital intake data, including self-reports of SA, SI (general and COVID-related), and COVID-specific stressors. RESULTS: SA and SI ratings were higher in the COVID-19 sample compared to the historical sample. Stressors related to missing special events, financial problems, in-home conflict, and changes in living circumstances were associated with COVID-related SI. Among first-time admissions, several interpersonal stressors were linked to COVID-related SI. LIMITATIONS: Analyses were cross-sectional, limiting our ability to draw conclusions about causality. CONCLUSIONS: This study offers preliminary evidence that COVID-19 may be contributing to suicidal thoughts and behaviors in high-risk adolescents.

Children's history of suicidal ideation and synchrony of facial displays of affect during mother-child interactions.

BACKGROUND: Suicidal thoughts and behavior can begin early in childhood and are a leading cause of death in youth. Although specific mechanisms of risk remain largely unknown, theorists and researchers highlight the importance of the parent-child relationship. The current study focused on one aspect of this relationship: the dynamic exchange of facial affect during interactions. Specifically, we examined the relation between children's history of suicidal ideation (SI) and synchrony of facial expressions during positive and negative mother-child interactions. METHODS: Participants were 353 mother-child dyads. Of these, 44 dyads included a child with an SI history. Dyads engaged in positive and negative discussions during which their facial electromyography was recorded from mothers and children to index second-to-second changes in positive (zygomaticus) and negative (corrugator) facial affect. RESULTS: Child SI dyads were characterized specifically by reduced synchrony of positive facial affect during the positive discussion compared to dyads without child SI. CONCLUSIONS: These findings suggest child SI dyads exhibit reduced synchrony of normative positive expressions during mother-child interactions. If replicated and extended in longitudinal research, these results may help to explain one mechanism of risk among children with SI.

Attentional biases to emotional faces among women with a history of single episode versus recurrent major depression.

Major depressive disorder (MDD) is a highly prevalent psychiatric disorder, and recurrent depression is associated with severe and chronic impairment. Identifying markers of risk is imperative to improve our ability to predict which individuals are likely to experience a recurrence. According to cognitive theories, biases in attention for affectively-salient information may serve as one mechanism of risk. Existing research has combined participants with a single episode (sMDD) and those with recurrent MDD (rMDD); therefore, little is known about whether these biases track the severity of disease course. The current study examined attentional biases to facial displays of emotion among 115 women with a history of rMDD, sMDD, or no history of psychopathology using a passive viewing eye-tracking task. Women with rMDD exhibited significantly lower sustained attention to happy faces compared to both healthy controls and sMDD women. These results extend previous research on the presence of attentional avoidance of positive stimuli in individuals with a history of MDD and provide preliminary evidence that this bias is strongest among individuals with a history of rMDD.

Maladaptive personality traits and the course of suicidal ideation in young adults with bipolar disorder: Cross-sectional and prospective approaches.

BACKGROUND: Childhood-onset bipolar disorder (BD) has considerable morbidity and mortality, including suicide. Many risk factors have been identified for suicidality, but the potential role of personality traits as assessed by a computer-assisted self-report measure remains unclear. AIMS: To address this gap in knowledge, we tested relations between pathological-range personality traits and suicidal ideation among young adults whose childhood-onset BD was prospectively confirmed by enrollment in the Course and Outcome of Bipolar Youth study (COBY) as children (n = 45) and a newly enrolled group of typically developing controls (TDCs; n = 52) both cross-sectionally and longitudinally after 1.5 years of follow up. MATERIALS & METHODS: Personality traits were assessed with the computerized Schedule for Nonadaptive and Adaptive Personality-2 (SNAP-2). RESULTS: Cross-sectionally, we found that participants with BD had elevated Suicide Proneness and Low Self-esteem versus TDCs at baseline. Furthermore, longitudinal analyses in the BD participants for whom we had 1.5 years of prospectively collected illness-course data showed that greater Suicide Proneness and Low Self-esteem prospectively predicted greater levels, shorter time until occurrence, and greater frequency of suicidal ideation during the follow-up. CONCLUSION: Our findings suggest the role of specific personality-related vulnerabilities in the course of BD that, pending replication, could contribute to development of interventions focused on personality traits among individuals with BD.

White matter correlates of cognitive flexibility in youth with bipolar disorder and typically developing children and adolescents.

Prior studies using behavioral tasks and neuroimaging have shown that children and adolescents with bipolar disorder (BD) have deficits in cognitive flexibility (CF)-defined as adaptation to changing rewards and punishments. However, no study, to our knowledge, has examined the white matter microstructural correlates of CF in youth with BD. To address this gap, we examined the relationship between CF assessed with the Cambridge Neuropsychological Testing Automated Battery (CANTAB)'s Intra-Extra Dimensional Set Shift task (ID/ED) and diffusion tensor imaging analyzed with FSL's preprocessing tools and Tract-Based Spatial Statistics (TBSS). We found a significantly different relationship between microstructural integrity of multiple white matter regions and CF performance in BD (n=28) and age-matched typically developing control (TDC) youths (n=26). Evaluation of the slopes of linear regressions in BD vs. TDC (ID/ED Simple Reversal error rate vs. fractional anisotropy) revealed significantly different slopes across the groups, indicating an aberrant relationship between CF and underlying white matter microstructure in youth with BD. These results underscore the importance of examining specific CF-neuroimaging relationships in BD youth. Future longitudinal studies could seek to define the white matter microstructural trajectories in BD vs. TDC, and relative to CF deficits and BD illness course.