A Comparison of Telehealth and In-Person Therapy for Youth Anxiety Disorders.

OBJECTIVE: At the onset of the COVID-19 pandemic, telehealth service use increased. However, little research has compared the efficacy of individual cognitive behavioral therapy (CBT) for youth with anxiety administered via (a) telehealth and (b) in-person. The present study used non-inferiority analyses to examine outcomes for youth with anxiety disorders (diagnosed by an Independent Evaluator; IE) treated via telehealth during the COVID-19 pandemic and youth treated via in-person therapy prior to the COVID-19 pandemic. METHOD: Participants (n = 92; Mage = 11.5 years; 60.1% female; 75.0% White) were 46 youth who completed telehealth treatment and 46 youth who completed services in-person, matched on age and principal anxiety diagnosis. One-sided t-tests for non-inferiority were first estimated. Next, ANOVAs and regression models were performed, examining treatment differences and candidate moderators (e.g. social anxiety disorder, comorbid attention problems). RESULTS: Results support non-inferiority across multiple indices of outcomes (i.e. self- and caregiver-reported anxiety symptoms, IE-rated functional impairment, and IE-rated treatment response). Analyses indicate that both treatments were effective in reducing anxiety symptoms and functional impairment. Caregivers reported higher post-treatment levels of anxiety for youth treated via telehealth than youth treated in person. No variables moderated the differences in outcomes between treatment modalities. CONCLUSIONS: Findings support that CBT administered via telehealth is similarly efficacious as CBT administered in-person for youth with anxiety. Implications regarding the availability and accessibility of evidence-based treatment for youth with anxiety are discussed.

Measurement invariance of the Suicide Cognitions Scale-Revised (SCS-R).

The Suicide Cognitions Scale-Revised (SCS-R) is a unidimensional measure of suicidal cognitions theorized to assess the suicide belief system. Several solutions have been proposed for the Suicide Cognitions Scale and SCS-R (e.g., bifactor model with two specific factors, bifactor model with two specific factors, three correlated factors model). Research indicates the endorsement of thoughts of suicide and suicide-related cognitions varies across demographics. Thus, the current investigation tested the measurement invariance (MI) of the SCS-R across gender, race, and sexual orientation within these proposed solutions and a unidimensional model. A national sample of N = 10,625 adults completed an online survey that included the SCS-R and self-report measures of demographics. Results indicated that the bifactor model with three specific factors, the bifactor model with two specific factors, and the three correlated factors models achieved scalar invariance across gender, race, and sexual orientation; a unidimensional model was not scalar invariant by gender. Tests of latent mean differences revealed significant differences in the general factor (i.e., suicidal belief system) and the specific unlovability, unbearability, and unsolvability factors between a few demographic groups. Implications for theory, measurement, and modeling are discussed. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Mechanisms mediating ethnoracial discrimination and suspiciousness in Asian, Black, and Hispanic United States college students.

BACKGROUND: Despite the robust relationship between ethnoracial discrimination and positive psychotic-like experiences (PLEs) like subclinical suspiciousness in adulthood, the underlying mechanisms remain underexamined. Investigating the mechanisms previously implicated in trauma and positive PLEs - including negative-self schemas, negative-other schemas, perceived stress, dissociative experiences, and external locus of control - may inform whether ethnoracial discrimination has similar or distinct effects from other social stressors. METHOD: We examined the indirect effects of experiences of discrimination (EOD) to suspicious PLEs and total positive PLEs through negative-self schemas, negative-other schemas, perceived stress, dissociative experiences, and external locus of control in Asian (nAsian = 268), Black (nBlack = 301), and Hispanic (nHispanic = 129) United States college students. RESULTS: Among Asian participants, results indicated a significant indirect effect of EOD to suspicious PLEs and EOD to positive PLEs via perceived stress, and EOD to positive PLEs via negative-self schemas. Among Hispanic participants, results indicated a significant indirect effect of EOD to suspicious PLEs and EOD to positive PLEs via dissociative experiences. No mechanisms appeared significant in Black participants nor were any significant direct effects observed across models, despite them reporting significantly greater experiences of ethnoracial discrimination. CONCLUSIONS: Our findings suggest some shared but potentially distinct mechanisms contribute to increased suspicious PLEs and positive PLEs in Asian, Black, and Hispanic college students, with results differing by group, compared to the mechanisms underlying trauma and positive PLEs, with implications for the treatment of PLEs in college students exposed to ethnoracial discrimination.

Re-assessing the assessment of fears of positive and negative evaluation: Scale development and psychometric evaluation of the Bivalent Fear of Evaluation Scale (BFOES).

The bivalent fear of evaluation (BFOE) model of social anxiety divides fear of evaluation into two distinct valences: fear of positive evaluation (FPE) and fear of negative evaluation (FNE). However, there is evidence that the two most widely utilized and psychometrically supported measures of FNE and FPE contain items which are ambiguous with regard to valence of evaluative fear. To formally address this, the BFOE Scale (BFOES) was developed, by merging items from measures of FNE and FPE into a single scale with an integrated response format. The present studies examined the psychometric profile of the BFOES across a large pooled archival dataset (N = 2216), which included approximately 10 % (n = 224) patients with social anxiety disorder (SAD). The factorial validity, internal consistency, and construct validity of the BFOES were examined. Additionally, item response theory analyses were employed for the purpose of merging items from self-report scales which utilized different Likert-type response formats. Results from both studies provided support for the psychometric profile of the BFOES. The implications of the BFOES for the assessment of social anxiety, and theoretical models of fear of evaluation and SAD, are discussed.

Test-retest reliability of the play-or-pass version of the Iowa Gambling Task.

The Iowa Gambling Task (IGT) is used to assess decision-making in clinical populations. The original IGT does not disambiguate reward and punishment learning; however, an adaptation of the task, the "play-or-pass" IGT, was developed to better distinguish between reward and punishment learning. We evaluated the test-retest reliability of measures of reward and punishment learning from the play-or-pass IGT and examined associations with self-reported measures of reward/punishment sensitivity and internalizing symptoms. Participants completed the task across two sessions, and we calculated mean-level differences and rank-order stability of behavioral measures across the two sessions using traditional scoring, involving session-wide choice proportions, and computational modeling, involving estimates of different aspects of trial-level learning. Measures using both approaches were reliable; however, computational modeling provided more insights regarding between-session changes in performance, and how performance related to self-reported measures of reward/punishment sensitivity and internalizing symptoms. Our results show promise in using the play-or-pass IGT to assess decision-making; however, further work is still necessary to validate the play-or-pass IGT.

Prenatal maternal Inflammation, childhood cognition and adolescent depressive symptoms.

BACKGROUND: Accumulating evidence indicates that higher prenatal maternal inflammation is associated with increased depression risk in adolescent and adult-aged offspring. Prenatal maternal inflammation (PNMI) may increase the likelihood for offspring to have lower cognitive performance, which, in turn, may heighten risk for depression onset. Therefore, this study explored the potential mediating role of childhood cognitive performance in the relationship between PNMI and adolescent depressive symptoms in offspring. METHODS: Participants included 696 mother-offspring dyads from the Child Health and Development Studies (CHDS) cohort. Biomarkers of maternal inflammation [interleukin (IL)-6, IL-8, IL-1 receptor antagonist (IL-1RA) and soluble TNF receptor-II (sTNF-RII)] were assayed from first (T1) and second trimester (T2) sera. Childhood (ages 9-11) cognitive performance was assessed via standardized Peabody Picture Vocabulary Test (PPVT), a measure of receptive vocabulary correlated with general intelligence. Adolescent (ages 15-17) depressive symptoms were assessed via self-report. RESULTS: There were no significant associations between T1 biomarkers and childhood PPVT or adolescent depressive symptoms. Higher T2 IL1-RA was directly associated with lower childhood PPVT (b = -0.21, SE = 0.08, t = -2.55, p = 0.01), but not with adolescent depressive symptoms. T2 IL-6 was not directly associated with childhood PPVT, but higher T2 IL-6 was directly associated at borderline significance with greater depressive symptoms in adolescence (b = 0.05, SE = 0.03, t = 1.96, p = 0.05). Lower childhood PPVT predicted significantly higher adolescent depressive symptoms (b = -0.07, SE = 0.02, t = -2.99, p < 0.01). There was a significant indirect effect of T2 IL-1RA on adolescent depressive symptoms via childhood PPVT (b = 0.03, 95 % CI = 0.002-0.03) indicating a partially mediated effect. No significant associations were found with T2 sTNF-RII nor IL-8. CONCLUSIONS: Lower childhood cognitive performance, such as that indicated by a lower PPVT score, represents a potential mechanism through which prenatal maternal inflammation contributes to adolescent depression risk in offspring.

Examining the influence of episode number and age of onset on individual depressive symptoms across episodes of major depression.

Major depression is characterized by an episodic course with symptom manifestations differing across episodes. Previous work has found that symptom presentation differs across age. However, studies of symptom presentation have largely focused on symptoms in individual episodes, requiring further investigation of longitudinal symptom change. This study explored the impact of the initial age of onset, the number of episodes, and age of onset of each episode on individual depressive symptoms, while accounting for episode severity. We used data from the Oregon Adolescent Depression Project (N = 629) examining participants with at least one major depressive episode, assessed by diagnostic interview, across a 15-year follow-up. Multilevel logistic regression models revealed that approximately 20-25% of the main effects were significant and some were qualified by cross-level interactions. However, only a few associations remained robust after correcting for multiple comparisons. Specifically, older initial age of onset was associated with fatigue, younger initial age of onset for the first episode was associated with suicidal ideation, and a lower episode number was associated with weight loss. These findings highlight potential initial age of onset and scar effects influencing symptom manifestation, but require replication.

Measurement invariance of the Child Behavior Checklist (CBCL) across race/ethnicity and sex in the Adolescent Brain and Cognitive Development (ABCD) study.

There are numerous studies examining differences in the experience of disorders and symptoms of psychopathology in adolescents across racial or ethnic groups and sex. Though there is substantial research exploring potential factors that may influence these differences, few studies have considered the potential contribution of measurement properties to these differences. Therefore, this study examined whether there are differences across racial or ethnic groups and sex in the measurement of psychopathology, assessed in mother-reported behavior of 9-11 year old youth from the Adolescent Brain Cognitive Development study sample using updated Child Behavior Checklist scales (CBCL; Achenbach & Rescorla, 2001). Tests of measurement invariance of the CBCL utilized the higher order factor structure identified by Michelini et al. (2019) using this same Adolescent Brain Cognitive Development cohort. The dimensions include internalizing, somatoform, detachment, externalizing, and neurodevelopmental problems. The configural model had a good-to-excellent fit on all subscales of the CBCL across racial or ethnic groups and sex. The metric and scalar models fit just as well as the configural models, indicating that the scales are measuring the same constructs across racial or ethnic groups and sex and are not influenced by measurement properties of items on the CBCL, although some high-severity response options were not endorsed for youth in all racial or ethnic groups. These findings support the use of the CBCL in research examining psychopathology in racially or ethnically diverse samples of youth. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Comparison of Global and Daily Ratings of Associations between Anxiety and Depressive Behaviors and Impairment in Preschool-Aged Children.

Anxiety and depressive difficulties can emerge during early childhood and cause impairment in functioning. Anxiety and depressive behaviors and impairment are typically assessed with global questionnaires that require recall of children's behavior over an extended period which could reduce the accuracy of parent report of children's behavior and functioning. The current study compared parents' report of children's anxiety and depressive behaviors and impairment when evaluated with global measures versus a daily diary measure. Participants (N = 901 parents of 3-5-year-old children) completed global and daily measures of children's behavior and impairment during enrollment to the study. Global measures were completed at baseline and the 14 daily diary measures were completed consecutively for two weeks. Across most measures, daily associations between parent-reported anxiety and depressive behaviors and impairment were stronger compared to associations with global measures. These results suggest that daily measures may better capture links between young children's typical behavior and functioning compared to global measures. In addition, daily assessment might be more effective for measuring mild to moderate yet still impairing behaviors that may be missed on global reports that require longer periods of recall.

Ethnoracial Risk Variation Across the Psychosis Continuum in the US: A Systematic Review and Meta-Analysis.

Importance: Studies suggest a higher risk of schizophrenia diagnoses in Black vs White Americans, yet a systematic investigation of disparities that include other ethnoracial groups and multiple outcomes on the psychosis continuum is lacking. Objective: To identify ethnoracial risk variation in the US across 3 psychosis continuum outcomes (ie, schizophrenia and other psychotic disorders, clinical high risk for psychosis [CHR-P], and psychotic symptoms [PSs] and psychotic experiences [PEs]). Data Sources: PubMed, PsycINFO and Embase were searched up to December 2022. Study Selection: Observational studies on ethnoracial differences in risk of 3 psychosis outcomes. Data Extraction and Synthesis: Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines were followed. Using a random-effects model, estimates for ethnoracial differences in schizophrenia and PSs/PEs were pooled and moderation by sampling and setting was determined, along with the assessment of heterogeneity and risk of bias. Main Outcomes and Measures: Risk of schizophrenia and other psychotic disorder, CHR-P, and conversion to psychosis among CHR-P and PSs/PEs. Results: Of 64 studies in the systematic review, 47 were included in the meta-analysis comprising 54 929 people with schizophrenia and 223 097 with data on PSs/PEs. Compared with White individuals, Black individuals had increased risk of schizophrenia (pooled odds ratio [OR], 2.07; 95% CI, 1.64-2.61) and PSs/PEs (pooled standardized mean difference [SMD], 0.10; 95% CI, 0.03-0.16), Latinx individuals had higher risk of PSs/PEs (pooled SMD, 0.15; 95% CI, 0.08-0.22), and individuals classified as other ethnoracial group were at significantly higher risk of schizophrenia than White individuals (pooled OR, 1.81; 95% CI, 1.31-2.50). The results regarding CHR-P studies were mixed and inconsistent. Sensitivity analyses showed elevated odds of schizophrenia in Asian individuals in inpatient settings (pooled OR, 1.84; 95% CI, 1.19-2.84) and increased risk of PEs among Asian compared with White individuals, specifically in college samples (pooled SMD, 0.16; 95% CI, 0.02-0.29). Heterogeneity across studies was high, and there was substantial risk of bias in most studies. Conclusions and Relevance: Findings of this systematic review and meta-analysis revealed widespread ethnoracial risk variation across multiple psychosis outcomes. In addition to diagnostic, measurement, and hospital bias, systemic influences such as structural racism should be considered as drivers of ethnoracial disparities in outcomes across the psychosis continuum in the US.

Mapping the duration and severity of preschool-aged children's depressive moods and behaviors.

BACKGROUND: Depressive moods and behaviors are developmentally normative, yet potentially impairing, in preschool-aged children. In addition to frequency, duration of behavior is an important parameter to consider when characterizing risk for worsening mood dysregulation. The goal of this study was to identify the duration and severity of depressive moods and behaviors and associations with impairment in a large community sample of preschool-aged children using an online parent-report daily diary. METHODS: Primary caregivers (N = 900) of 3-5-year-old children reported the daily duration of each instance of seven depressive moods and behaviors for 14 days. We used item response theory analyses to examine duration item characteristics. RESULTS: Moods and behaviors occurred at specific durations to be considered psychometrically severe/rare; for example, instances of sadness had to last an average total of 32 min per day or more, irritability at least 38 min, tantrums at least 30 min, and tearfulness/sensitivity at least 35 min. Longer durations of mood and behavior were associated with daily impairment, as well as older child age and less parental education. CONCLUSIONS: To our knowledge, this is the first study to delineate specific duration ranges for depressive moods and behaviors in preschool-aged children. These data, coupled with information about the frequency of mood-related behaviors, can assist child practitioners in differentiating normative patterns from less normative mood problems to evaluate which children may be at risk. Future work should identify the duration of depressive moods and behaviors in early childhood that predict clinically significant psychopathology over time.

Sex-Specific Pathways From Prenatal Maternal Inflammation to Adolescent Depressive Symptoms.

Importance: Prenatal maternal inflammation has been associated with major depressive disorder in offspring in adulthood as well as with internalizing and externalizing symptoms in childhood; however, the association between prenatal inflammation and offspring depression in adolescence has yet to be examined. Objective: To determine whether maternal levels of inflammatory biomarkers during pregnancy are associated with depressive symptomatology in adolescent-aged offspring and to examine how gestational timing, offspring sex, and childhood psychiatric symptoms impact these associations. Design, Setting, and Participants: This was an observational study of a population-based birth cohort from the Child Health and Development Studies (CHDS), which recruited almost all mothers receiving obstetric care from the Kaiser Foundation Health Plan (KFHP) in Alameda County, California, between June 1959 and September 1966. Pregnancy data and blood sera were collected from mothers, and offspring psychiatric symptom data were collected in childhood (ages 9-11 years) and adolescence (ages 15-17 years). Mother-offspring dyads with available maternal prenatal inflammatory biomarkers during first and/or second trimesters and offspring depressive symptom data at adolescent follow-up were included. Data analyses took place between March 2020 and June 2023. Exposures: Levels of inflammatory biomarkers (interleukin 6 [IL-6], IL-8, IL-1 receptor antagonist [IL-1RA], and soluble tumor necrosis factor receptor-II) assayed from maternal sera in the first and second trimesters of pregnancy. Main Outcomes and Measures: Self-reported depressive symptoms at adolescent follow-up. Results: A total of 674 mothers (mean [SD] age, 28.1 [5.9] years) and their offspring (350 male and 325 female) were included in this study. Higher second trimester IL-6 was significantly associated with greater depressive symptoms in offspring during adolescence (b, 0.57; SE, 0.26); P = .03). Moderated mediation analyses showed that childhood externalizing symptoms significantly mediated the association between first trimester IL-6 and adolescent depressive symptoms in male offspring (b, 0.18; 95% CI, 0.02-0.47), while childhood internalizing symptoms mediated the association between second trimester IL-1RA and adolescent depressive symptoms in female offspring (b, 0.80; 95% CI, 0.19-1.75). Conclusions and Relevance: In this study, prenatal maternal inflammation was associated with depressive symptoms in adolescent-aged offspring. The findings of the study suggest that pathways to adolescent depressive symptomatology from prenatal risk factors may differ based on both the timing of exposure to prenatal inflammation and offspring sex.

Substance use outcomes from the Child/Adolescent Anxiety Multimodal Extended Long-term Study (CAMELS).

BACKGROUND: Substance use problems and anxiety disorders are both highly prevalent and frequently cooccur in youth. The present study examined the benefits of successful anxiety treatment at 3-12 years after treatment completion on substance use outcomes (i.e. diagnoses and lifetime expected use). METHODS: The sample was from the Child/Adolescent Anxiety Multimodal Extended Long-term Study (CAMELS), a naturalistic follow-up study to the Child/Adolescent Anxiety Multimodal Study (CAMS) which randomized youth to cognitive behavioral therapy (CBT; Coping cat), medication (sertraline), their combination, or pill placebo. The first CAMELS visit occurred an average of 6.5 years following CAMS randomization. Participants were 319 youth (65.4% of the CAMS sample), aged 7-17 years at CAMS baseline assessment with a mean age of 17.6 years (range: 11-26 years) at the time of the first CAMELS follow-up. Substance use outcomes included diagnoses as well as lifetime substance use (i.e. alcohol and tobacco use). RESULTS: Eleven of 319 (3.4%) CAMELS participants were diagnosed with a substance use disorder at the initial follow-up visit. When compared to the population lifetime rate of 11.4%, the rate of diagnoses in the posttreated sample was significantly lower. Additionally, rates of lifetime alcohol use were lower than population rates at the initial and final follow-up visits. Rates of lifetime tobacco use were similarly lower than lifetime population rates at the initial visit (driven by significantly lower rates in the CBT treatment condition), but higher by the final visit. Furthermore, treatment remission (but not treatment response) was associated with a lower rate of substance use diagnoses at the initial follow-up visit, although rates of lifetime alcohol and tobacco use did not differ by treatment outcome. CONCLUSIONS: Anxiety treatments confer a beneficial impact on problematic substance use (i.e. diagnoses) as well as on expected substance use (i.e. alcohol and tobacco use) for on average, a period of 6.5 years.

Neural activation and connectivity in offspring of depressed mothers during monetary and social reward tasks.

Multiple previous studies show associations between history of and familial risk for depression and reward function. These previous studies have predominantly focused on neural activation during monetary tasks. Fewer studies of have examined functional connectivity and social reward tasks, particularly in offspring of mothers with depression. This study examined brain function in older children (aged 9-14 years) through both regional activation and functional connectivity during monetary (n = 103) and social reward (n = 115) tasks. Overall, our study failed to find significant differences between offspring of mothers with and without depression on monetary (65 offspring of mothers without and 38 offspring of mother with depression) and social reward (73 offspring of mothers without and 42 offspring of mother with depression) tasks on task activation and functional connectivity. We discuss possibilities for developmental timing of finding differences between offspring of mothers with and without depression on monetary and social reward tasks.

Therapeutic Alliance, Attendance, and Outcomes in Youths Receiving CBT or Client-Centered Therapy for Anxiety.

OBJECTIVE: Positive associations between therapeutic alliance and outcome (e.g. youth symptom severity) have been documented in the youth anxiety literature; however, little is known about the conditions under which early alliance contributes to positive outcomes in youth. The present study examined the relations between therapeutic alliance, session attendance, and outcomes in youths (N = 135; 55.6% female) who participated in a randomized clinical trial testing the efficacy of cognitive-behavioral therapy or client-centered therapy for anxiety. METHOD: We evaluated a conceptual model wherein: (1) early alliance indirectly contributes to positive outcomes by improving session attendance; (2) alliance-outcome associations differ by intervention type, with stronger associations in cognitive-behavioral therapy compared to client-centered therapy; and (3) alliance-outcome associations vary across outcome measurement timepoints, with the effect of early alliance on outcomes decaying over time. RESULTS: Contrary to hypotheses, provider ratings of early alliance predicted greater youth-rated anxiety symptom severity post-treatment (i.e. worse treatment outcomes). Session attendance predicted positive youth-rated outcomes, though there was no indirect effect of early alliance on outcomes through session attendance. CONCLUSIONS: Results show that increasing session attendance is important for enhancing outcomes and do not support early alliance as a predictor of outcomes.

Adolescents at risk for depression show increased white matter microstructure with age across diffuse areas of the brain.

Maternal history of depression is a strong predictor of depression in offspring and linked to structural and functional alterations in the developing brain. However, very little work has examined differences in white matter in adolescents at familial risk for depression. In a sample aged 9-14 (n = 117), we used tract-based spatial statistics (TBSS) to examine differences in white matter microstructure between adolescents with (n = 42) and without (n = 75) maternal history of depression. Microstructure was indexed using fractional anisotropy (FA). Threshold-free cluster enhancement was applied and cluster maps were thresholded at whole-brain family-wise error < .05. There was no significant main effect of risk status on FA. However, there was a significant interaction between risk status and age, such that large and diffuse portions of the white matter skeleton showed relatively increased FA with age for youth with a maternal history of depression compared to those without. Most tracts identified by the interaction were robust to controlling for sex, youth internalizing, in-scanner motion, neighborhood SES, and intra-cranial volume, evidence that maternal depression is a unique predictor of white matter alterations in youth. Widespread increases in FA with age may correspond to a global pattern of accelerated brain maturation in youth at risk for depression.

An Initial examination of fear of negative and positive evaluation in youth.

Fear of negative evaluation (FNE) and fear of positive evaluation (FPE) are both core features of social anxiety. The majority of research with these constructs has been done with older adolescents and adults, with only one previous study examining FNE and FPE in childhood. However, this previous work relied exclusively on parent-report of youth FNE and FPE. Here, we examined the factor structure of FNE and FPE using youth self-reports. Moreover, we examined the associations with dimensions of internalizing and externalizing problems. We found that two-factor structure of FNE and FPE was a marginal fit to the data. Exploratory models identified three items that showed significant cross-loadings on non-target factors. Overall, we found that FNE was associated with dimensions of internalizing problems reported by youth and their mothers. FPE was associated with internalizing problems reported by youth, but not parents. Associations between FNE and clinical outcomes were stronger than those for FPE. This study demonstrates promise of FNE and FPE in youth and highlights important directions for future research.

Circadian, Reward, and Emotion Systems in Teens prospective longitudinal study: protocol overview of an integrative reward-circadian rhythm model of first onset of bipolar spectrum disorder in adolescence.

BACKGROUND: Bipolar spectrum disorders (BSDs) are associated with a heightened sensitivity to rewards and elevated reward-related brain function in cortico-striatal circuitry. A separate literature documents social and circadian rhythm disruption in BSDs. Recently, integrated reward-circadian models of BSDs have been proposed. These models draw on work indicating that the two systems influence each other and interact to affect mood functioning. When dysregulated, reward and circadian system signaling may combine to form a positive feedback loop, whereby dysregulation in one system exacerbates dysregulation in the other. Project CREST (Circadian, Reward, and Emotion Systems in Teens) provides a first systematic test of reward-circadian dysregulation as a synergistic and dynamic vulnerability for first onset of BSD and increases in bipolar symptoms during adolescence. METHODS: This NIMH-funded R01 study is a 3-year prospective, longitudinal investigation of approximately 320 community adolescents from the broader Philadelphia area, United States of America. Eligible participants must be 13-16 years old, fluent in English, and without a prior BSD or hypomanic episode. They are being selected along the entire dimension of self-reported reward responsiveness, with oversampling at the high tail of the dimension in order to increase the likelihood of BSD onsets. At Times 1-6, every 6 months, participants will complete assessments of reward-relevant and social rhythm disruption life events and self-report and diagnostic assessments of bipolar symptoms and episodes. Yearly, at Times 1, 3, and 5, participants also will complete self-report measures of circadian chronotype (morningness-eveningness) and social rhythm regularity, a salivary dim light melatonin onset (DLMO) procedure to assess circadian phase, self-report, behavioral, and neural (fMRI) assessments of monetary and social reward responsiveness, and a 7-day ecological momentary assessment (EMA) period. During each EMA period, participants will complete continuous measures of sleep/wake and activity (actigraphy), a daily sleep diary, and three within-day (morning, afternoon, evening) measures of life events coded for reward-relevance and social rhythm disruption, monetary and social reward responsiveness, positive and negative affect, and hypo/manic and depressive symptoms. The fMRI scan will occur on the day before and the DLMO procedure will occur on the first evening of the 7-day EMA period. DISCUSSION: This study is an innovative integration of research on multi-organ systems involved in reward and circadian signaling in understanding first onset of BSD in adolescence. It has the potential to facilitate novel pharmacological, neural, and behavioral interventions to treat, and ideally prevent, bipolar conditions.

Characterizing heterogeneity in early adolescent reward networks and individualized associations with behavioral and clinical outcomes.

Associations between connectivity networks and behavioral outcomes such as depression are typically examined by comparing average networks between known groups. However, neural heterogeneity within groups may limit the ability to make inferences at the individual level as qualitatively distinct processes across individuals may be obscured in group averages. This study characterizes the heterogeneity of effective connectivity reward networks among 103 early adolescents and examines associations between individualized features and multiple behavioral and clinical outcomes. To characterize network heterogeneity, we used extended unified structural equation modeling to identify effective connectivity networks for each individual and an aggregate network. We found that an aggregate reward network was a poor representation of individuals, with most individual-level networks sharing less than 50% of the group-level network paths. We then used Group Iterative Multiple Model Estimation to identify a group-level network, subgroups of individuals with similar networks, and individual-level networks. We identified three subgroups that appear to reflect differences in network maturity, but this solution had modest validity. Finally, we found numerous associations between individual-specific connectivity features and behavioral reward functioning and risk for substance use disorders. We suggest that accounting for heterogeneity is necessary to use connectivity networks for inferences precise to the individual.

Specificity of associations between parental psychopathology and offspring brain structure.

Multiple forms of parental psychopathology have been associated with differences in subcortical brain volume. However, few studies have considered the role of comorbidity. Here, we examine if alterations in child subcortical brain structure are specific to parental depression, anxiety, mania, or alcohol/substance use parental psychopathology, common across these disorders, or altered by a history of multiple disorders. We examined 6581 children aged 9 to 10 years old from the ABCD study with no history of mental disorders. We found several significant interactions such that the effects of a parental history of depression, anxiety, and substance use problems on amygdala and striatal volumes were moderated by comorbid parental history of another disorder. Interactions tended to suggest smaller volumes in the presence of a comorbid disorder. However, effect sizes were small, and no associations remained significant after correcting for multiple comparisons. Results suggest that associations between familial risk for psychopathology and offspring brain structure in 9-10-year-olds are modest, and relationships that do exist tend to implicate the amygdala and striatal regions and are moderated by a comorbid parental psychopathology history. Several methodological factors, including controlling for intracranial volume and other forms of parental psychopathology and excluding child psychopathology, likely contribute to inconsistencies in the literature.