Longitudinal Assessment Of Manic Symptoms Research Articles

The stability and persistence of symptoms in childhood-onset ADHD.

The course of childhood-onset attention deficit hyperactivity disorder (ADHD) varies across individuals; some will experience persistent symptoms while others' symptoms fluctuate or remit. We describe the longitudinal course of ADHD symptoms and associated clinical characteristics in adolescents with childhood-onset ADHD. Participants (aged 6-12 at baseline) from the Longitudinal Assessment of Manic Symptoms (LAMS) study who met DSM criteria for ADHD prior to age 12 were evaluated annually with the Kiddie Schedule for Affective Disorders and Schizophrenia for eight years. At each timepoint, participants were categorized as meeting ADHD criteria, subthreshold criteria, or not havingADHD. Stability of course was defined by whether participants experienced consistent ADHD symptoms, fluctuating symptoms, or remission. The persistence of the symptoms was defined by symptom status at the final two follow-ups (stable ADHD, stable remission, stable partial remission, unstable). Of 685 baseline participants, 431 had childhood-onset ADHD and at least two follow-ups. Half had a consistent course of ADHD, nearly 40% had a remitting course, and the remaining participants had a fluctuating course. More than half of participants met criteria for ADHD at the end of their participation; about 30% demonstrated stable full remission, 15% had unstable symptoms, and one had stable partial remission. Participants with a persistent course and stable ADHD outcome reported the highest number of symptoms and were most impaired. This work builds on earlier studies that describe fluctuating symptoms in young people with childhood-onset ADHD. Results emphasize the importance of ongoing monitoring and detailed assessment of factors likely to influence course and outcome to help young people with childhood-onset ADHD.

Reorienting Latent Variable Modeling for Supervised Learning

Despite its potentials benefits, using prediction targets generated based on latent variable (LV) modeling is not a common practice in supervised learning, a dominating framework for developing prediction models. In supervised learning, it is typically assumed that the outcome to be predicted is clear and readily available, and therefore validating outcomes before predicting them is a foreign concept and an unnecessary step. The usual goal of LV modeling is inference, and therefore using it in supervised learning and in the prediction context requires a major conceptual shift. This study lays out methodological adjustments and conceptual shifts necessary for integrating LV modeling into supervised learning. It is shown that such integration is possible by combining the traditions of LV modeling, psychometrics, and supervised learning. In this interdisciplinary learning framework, generating practical outcomes using LV modeling and systematically validating them based on clinical validators are the two main strategies. In the example using the data from the Longitudinal Assessment of Manic Symptoms (LAMS) Study, a large pool of candidate outcomes is generated by flexible LV modeling. It is demonstrated that this exploratory situation can be used as an opportunity to tailor desirable prediction targets taking advantage of contemporary science and clinical insights.

35.1 Adequacy of Children’s Mental Health Services: Variations by Race and Clinical Characteristics

ObjectivesThis study utilized an expert consensus approach to determine adequacy of children’s mental health services and examined whether adequacy varied by demographic and/or clinical characteristics.MethodsData were obtained from 687 children aged 6 to 12 years old who had visited 1 of 9 outpatient mental health clinics and participated in the Longitudinal Assessment of Manic Symptoms (LAMS) study. Children and their parents were interviewed using the K-SADS and the Service Assessment for Children and Adolescents (SACA) to assess youths’ psychiatric symptoms and lifetime mental health services use, respectively. Analyses employed an expert consensus approach (informed by published treatment guidelines) to determine children’s psychotropic treatment adequacy.ResultsBlack youth (compared to White youth; OR = 2.03; 95% CI, 1.53-2.70), and those with anxiety disorders (vs no anxiety disorder; OR = 1.57; 95% CI, 1.10-2.24) were more likely to receive inadequate care. Youth whose caregivers had a bachelor’s or more advanced degree (vs GED, high school, or less education; OR = 0.71; 95% CI, 0.60-0.83) were less likely to receive inadequate care.ConclusionsUsing the consensus rater approach permitted the use of published treatment efficacy data and patient characteristics (eg, age, diagnoses, history of recent hospitalization, psychotherapy). These results replicate racial disparities found in previous research using traditional methods to determine treatment adequacy (eg, with a minimum number of treatment sessions) and highlight the continued need for research on racial disparities and strategies to improve access to high-quality care.EBP, BRD, DEI ObjectivesThis study utilized an expert consensus approach to determine adequacy of children’s mental health services and examined whether adequacy varied by demographic and/or clinical characteristics. This study utilized an expert consensus approach to determine adequacy of children’s mental health services and examined whether adequacy varied by demographic and/or clinical characteristics. MethodsData were obtained from 687 children aged 6 to 12 years old who had visited 1 of 9 outpatient mental health clinics and participated in the Longitudinal Assessment of Manic Symptoms (LAMS) study. Children and their parents were interviewed using the K-SADS and the Service Assessment for Children and Adolescents (SACA) to assess youths’ psychiatric symptoms and lifetime mental health services use, respectively. Analyses employed an expert consensus approach (informed by published treatment guidelines) to determine children’s psychotropic treatment adequacy. Data were obtained from 687 children aged 6 to 12 years old who had visited 1 of 9 outpatient mental health clinics and participated in the Longitudinal Assessment of Manic Symptoms (LAMS) study. Children and their parents were interviewed using the K-SADS and the Service Assessment for Children and Adolescents (SACA) to assess youths’ psychiatric symptoms and lifetime mental health services use, respectively. Analyses employed an expert consensus approach (informed by published treatment guidelines) to determine children’s psychotropic treatment adequacy. ResultsBlack youth (compared to White youth; OR = 2.03; 95% CI, 1.53-2.70), and those with anxiety disorders (vs no anxiety disorder; OR = 1.57; 95% CI, 1.10-2.24) were more likely to receive inadequate care. Youth whose caregivers had a bachelor’s or more advanced degree (vs GED, high school, or less education; OR = 0.71; 95% CI, 0.60-0.83) were less likely to receive inadequate care. Black youth (compared to White youth; OR = 2.03; 95% CI, 1.53-2.70), and those with anxiety disorders (vs no anxiety disorder; OR = 1.57; 95% CI, 1.10-2.24) were more likely to receive inadequate care. Youth whose caregivers had a bachelor’s or more advanced degree (vs GED, high school, or less education; OR = 0.71; 95% CI, 0.60-0.83) were less likely to receive inadequate care. ConclusionsUsing the consensus rater approach permitted the use of published treatment efficacy data and patient characteristics (eg, age, diagnoses, history of recent hospitalization, psychotherapy). These results replicate racial disparities found in previous research using traditional methods to determine treatment adequacy (eg, with a minimum number of treatment sessions) and highlight the continued need for research on racial disparities and strategies to improve access to high-quality care.EBP, BRD, DEI Using the consensus rater approach permitted the use of published treatment efficacy data and patient characteristics (eg, age, diagnoses, history of recent hospitalization, psychotherapy). These results replicate racial disparities found in previous research using traditional methods to determine treatment adequacy (eg, with a minimum number of treatment sessions) and highlight the continued need for research on racial disparities and strategies to improve access to high-quality care.

25.4 41032: Neural Predictors of Mood Dysregulation in Youth at Familial and Symptomatic Risk of Bipolar Disorder

Biomarkers of bipolar disorder are needed to aid in early diagnosis, and identifying neural markers of known prodromal behaviors is a step toward that goal. Mood dysregulation factors within affective lability scales are recognized as prodromal to the development of bipolar disorder. We identified neural and behavioral markers of future affective lability in at-risk youth from the Pittsburgh Bipolar Offspring Study (BIOS) and validated these in an independent sample of youth from the Longitudinal Assessment of Manic Symptoms (LAMS) study.

30.3 Adolescent Borderline Personality Symptoms and Interactions With Co-Occurring Psychopathology Predict Functional Outcomes

Borderline personality disorder (BLP) symptoms emerge in youth and are associated with poor outcomes. However, since BLP symptoms often co-occur with other mental health problems, it is unclear to what extent BLP symptoms uniquely influence functional outcomes or how BLP symptoms interact with these more commonly identified problems to influence functioning. This study examines the unique effect of adolescent BLP symptoms in predicting functional outcomes 2 years later. Data from the Longitudinal Assessment of Manic Symptoms (LAMS) Study, a prospective study of 621 clinical youth with elevated mania and 86 clinical youth without elevated mania symptoms (Mage = 9.4 years; SD = 2.0), were examined. For this study, 152 youth with available data at the 48- and 72-month follow-up waves were identified. Dimensional ratings of BLP, inattention and hyperactive/impulsive symptoms of ADHD, depression, and mania were collected at the 48-month follow-up wave. Functional outcomes, including emotional and physical well-being, self-esteem, family, friend, and school functioning, as well as overall functioning were collected at the 72-month follow-up wave. Regression analyses were conducted with BLP, inattention, hyperactivity/impulsivity, depression, mania, age, and sex as independent variables. Interactions between BLP and inattention, hyperactivity/impulsivity, depression, mania, age, and sex were tested. Due to the number of tests, p < 0.01 identified significance. Interactions between BLP and inattention emerged. At higher levels of inattention, BLP was associated with poorer physical (partial r = –0.21), emotional (partial r = –0.37), and overall functioning (partial r = –0.32), whereas at lower levels of inattention, BLP was associated with better functioning. Significant interactions at the p < 0.01 level did not emerge between BLP and inattention in predicting self-esteem, school, or friend functioning, or between BLP and other measures of psychopathology. Main effects of psychopathology on functional outcomes did not emerge. Inattentive symptoms of ADHD moderated the prospective association between BLP symptoms and functional outcomes. Future research that attends to the complex and heterogeneous presentations of youth with BLP symptoms is needed to develop targeted interventions to improve clinical outcomes.

Attention-Deficit/Hyperactivity Disorder Symptoms and Externalizing Progression in the LAMS Study: A Test of Trait Impulsivity Theory

To test differential prospective prediction of growth in externalizing behavior, including oppositional defiant disorder, conduct disorder, and substance use disorders, by earlier hyperactive-impulsive (HI) vs inattentive (IN) symptoms of attention-deficit/hyperactivity disorder (ADHD). Participants in the Longitudinal Assessment of Manic Symptoms (LAMS) Study (N= 685 at study entry), including 458 boys and 227 girls ages 6-12, completed full parent report and self-report assessments every year for 8 years on the Schedule for Affective Disorders and Schizophrenia for School-Age Children. Three sets of analyses were conducted. First, hierarchal regression (block entry) was used to test independent associations between HI symptoms and later externalizing outcomes, controlling for IN symptoms, and IN symptoms and later externalizing outcomes, controlling for HI symptoms. Second, logistic regression was used to test progression of DSM externalizing disorders. Third, tests of mediation were used to assess potentiation of externalizing progression through environmental risk mediators (eg, family environment, neighborhood violence). Consistent with hypotheses derived from trait impulsivity theories of externalizing behavior, HI symptoms of ADHD were associated independently with long-term externalizing outcomes, whereas IN symptoms were not. Between months 48 and 96, ADHD-HI/combined symptom subtype diagnoses predicted later oppositional defiant disorder diagnoses, oppositional defiant disorder diagnoses predicted later conduct disorder diagnoses, and conduct disorder diagnoses predicted later substance use disorder diagnoses. Evidence for environmental risk mediation (eg, parental monitoring, neighborhood violence) was also found. Findings support trait impulsivity models of externalizing progression, whereby ADHD-HI/combined symptoms subtypes predispose to increasingly severe externalizing behaviors, which are magnified in contexts of environmental risk.

Generalizing the Prediction of Bipolar Disorder Onset Across High-Risk Populations

Risk calculators (RC) to predict clinical outcomes are gaining interest. An RC to estimate risk of bipolar spectrum disorders (BPSD) could help reduce the duration of undiagnosed BPSD and improve outcomes. Our objective was to adapt an RC previously validated in the Pittsburgh Bipolar Offspring Study (BIOS) sample to achieve adequate predictive ability in both familial high-risk and clinical high-risk youths. Participants (aged 6-12 years at baseline) from the Longitudinal Assessment of Manic Symptoms (LAMS) study (N= 473) were evaluated semi-annually. Evaluations included a Kiddie Schedule for Affective Disorders (K-SADS) interview. After testing an RC that closely approximated the original, we made modifications to improve model prediction. Models were trained in the BIOS data, which included biennial K-SADS assessments, and tested in LAMS. The final model was then trained in LAMS participants, including family history of BPSD as a predictor, and tested in the familial high-risk sample. Over follow-up, 65 youths newly met criteria for BPSD. The original RC identified youths who developed BPSD only moderately well (area under the curve [AUC]= 0.67). Eliminating predictors other than the K-SADS screening items for mania and depression improved accuracy (AUC= 0.73) and generalizability. The model trained in LAMS, including family history as a predictor, performed well in the BIOS sample (AUC= 0.74). The clinical circumstances under which the assessment of symptoms occurs affects RC accuracy; focusing on symptoms related to the onset of BPSD improved generalizability. Validation of the RC under clinically realistic circumstances will be an important next step.

Affective Processing Biases in Relation to Past, Current, and Future Depression in Children and Adolescents

BackgroundThe affective go/no-go (AGN) task has been used to assess affective biases in attention set-shifting and deficits in inhibitory control of emotional information among depressed youth, but results have been inconsistent. We aimed to test AGN robustness and clarify temporal relationships between depressive symptoms and affective processing in youth. MethodsWe evaluated AGN performance twice (Time 1 N = 306; Time 2 N = 238) in relation to current, previous, and future depression in the same children/adolescents with depression and those without diagnoses who participated in the Longitudinal Assessment of Manic Symptoms (LAMS) study. Mixed repeated ANCOVAs were powered to detect small-medium group by valence interactions in response latency and errors. Supplemental regression analyses examined depressive symptoms as a continuous variable in relation to AGN performance. ResultsNo clear pattern emerged, mirroring the broader AGN literature. In primary analyses, group by valence interactions were only observed at one AGN administration; none replicated across administrations. Similarly, in regression analyses depressive symptoms had no relation to affective processing biases/deficits at AGN Time 1, though some relationships were detected between symptoms and AGN Time 2. LimitationsRelatively few youth met criteria for a depressive disorder, though analyses were appropriately powered and supplemental analyses examined depressive symptoms continuously. Comparison groups were not healthy controls at recruitment but were free from any Axis I disorder at AGN administration. ConclusionsGiven the inconsistency of AGN findings, attention should be focused on tasks that provide more sensitive, robust measures of emotional information processing in depressed youth.

Development of bipolar disorder and other comorbidity among youth with attention-deficit/hyperactivity disorder.

To examine development of bipolar spectrum disorders (BPSD) and other disorders in prospectively followed children with attention-deficit/hyperactivity disorder (ADHD). In the Longitudinal Assessment of Manic Symptoms (LAMS) study, 531 of 685 children age 6-12 (most selected for scores>12 on General Behavior Inventory 10-item Mania scale) had ADHD, 112 with BPSD, and 419 without. With annual assessments for 8years, retention averaged 6.2years. Chi-square analyses compared rate of new BPSD and other comorbidity between those with versus without baseline ADHD and between retained versus resolved ADHD diagnosis. Cox regression tested factors influencing speed of BPSD onset. Of 419 with baseline ADHD but not BPSD, 52 (12.4%) developed BPSD, compared with 16 of 110 (14.5%) without either baseline diagnosis. Those who developed BPSD had more nonmood comorbidity over the follow-up than those who did not develop BPSD (p=.0001). Of 170 who still had ADHD at eight-year follow-up (and not baseline BPSD), 26 (15.3%) had developed BPSD, compared with 16 of 186 (8.6%) who had ADHD without BPSD at baseline but lost the ADHD diagnosis (χ2 =3.82, p=.051). There was no statistical difference in whether ADHD persisted or not acrossnew BPSD subtypes (χ2 =1.62, p=.446). Of those who developed BPSD, speed of onset was not significantly related to baseline ADHD (p=.566), baseline anxiety (p=.121), baseline depression (p=.185), baseline disruptive behavior disorder (p=.184), age (B=-.11 p=.092), maternal mania (p=.389), or paternal mania (B=.73, p=.056). Those who started with both diagnoses had more severe symptoms/impairment than those with later developed BPSD and reported having ADHD first. In a cohort selected for symptoms of mania at age 6-12, baseline ADHD was not a significant prospective risk factor for developing BPSD. However, persistence of ADHD may marginally mediate risk of BPSD, and early comorbidity of both diagnoses increases severity/impairment.

Developing and Validating a Definition of Impulsive/Reactive Aggression in Youth

The goal of this study is to develop a rational data-driven definition of impulsive/reactive aggression and establish distinctions between impulsive/reactive aggression and other common childhood problems. This is a secondary analysis of data from Assessing Bipolar: A Community Academic Blend (ABACAB; N = 636, ages 5–18), Stanley Medical Research Institute N = 392, ages 5–17), and the Longitudinal Assessment of Manic Symptoms (LAMS; N = 679, ages 6–12) studies, which recruited youths seeking outpatient mental health services in academic medical centers and community clinics. Following Jensen et al.’s (2007) procedure, 3 judges independently rated items from several widely used scales in terms of assessing impulsive/reactive aggression. Principal components analyses (PCA) modeled structure of the selected items supplemented by items related to mood symptoms, rule-breaking behavior, and hyperactivity/impulsivity to better define the boundaries between impulsive/reactive aggression and other common childhood symptoms. In the rational item selection process, there was good agreement among the 3 experts who rated items as characterizing impulsive/reactive aggression or not. PCA favored 5 dimension solutions in all 3 samples. Across all samples, PCA resulted in rule-breaking behavior, aggression-impulsive/reactive (AIR), mania, and depression dimensions; there was an additional hyperactive/impulsive dimension in the LAMS sample and a self-harm dimension in ABACAB and Stanley samples. The dimensions demonstrated good internal consistency; criterion validity coefficients also showed consistency across samples. This study is a step toward developing an empirically derived nosology of impulsive aggression/AIR. Findings support the validity of the AIR construct, which can be distinguished from manic and depressive symptoms as well as rule-breaking behavior.

Comparing the DSM-5 construct of Disruptive Mood Dysregulation Disorder and ICD-10 Mixed Disorder of Emotion and Conduct in the UK Longitudinal Assessment of Manic Symptoms (UK-LAMS) Study

It is important to understand new diagnostic entities in classifications of psychopathology such as the Diagnostic and Statistical Manual of Mental Disorders-5 (DSM-5) (code F34.8) construct of Disruptive Mood Dysregulation Disorder (DMDD) and to compare it with possible equivalent disorders in other classificatory systems such as the International Classification of Diseases-10 (ICD-10), which has a category that superficially appears similar, that is, Mixed Disorder of Emotion and Conduct (MDEC) (code F92). In this study, the United Kingdom (UK) arm (UK-LAMS) of the US National Institute of Mental Health (NIMH) supported Longitudinal Assessment of Manic Symptoms (LAMS) multi-site study was used to evaluate and retrospectively construct DMDD and MDEC diagnoses in order to compare them and understand the conditions they co-occur with, in order to improve the clinical understanding. In particular, the phenomenology of UK-LAMS participants (n = 117) was used to determine whether DMDD is a unique entity within the DSM-5. The findings showed that 24 of 68 participants with either DMDD or MDEC (35.3%) fulfilled both diagnostic criteria for DMDD and MDEC, suggesting that these entities do contain overlapping features, particularly symptoms relating to Oppositional Defiant Disorder (ODD)/Conduct Disorder (CD), Attention Deficit Hyperactivity Disorder (ADHD)/Hyperkinetic Disorder (HKD) and/or an anxiety disorder. The data also showed that most of the participants who met DMDD criteria also fulfilled the diagnostic criteria for ODD/CD, ADHD, followed by an anxiety disorder. In this context, this raises the issue whether DMDD is a unique construct or whether the symptomology for DMDD can be better explained as a specifier for ODD/CD and ADHD. Unlike DMDD, MDEC clearly specifies that the label should only be used if emotional and conduct disorders co-exist.

Diagnostic Accuracy of the CASI-4R Psychosis Subscale for Children Evaluated in Pediatric Outpatient Clinics

Diagnostic accuracy of the Diagnostic and Statistical Manual of Mental Disorders–oriented Child and Adolescent Symptom Inventory (CASI-4R) Psychotic Symptoms scale was tested using receiver operating characteristic analyses to identify clinically significant psychotic symptoms. Participants were new outpatients (N = 700), ages 6.0 to 12.9 years (M = 9.7, SD = 1.8) at 9 child outpatient mental health clinics, who participated in the Longitudinal Assessment of Manic Symptoms (LAMS) Study baseline assessment. Because LAMS undersampled participants with low mania scores by design, present analyses weighted low scorers to produce unbiased estimates. Psychotic symptoms, operationally defined as a score of 3 or more for hallucinations or 4 or more for delusions based on the Schedule for Affective Disorders and Schizophrenia (K-SADS) psychosis items, occurred in 7% of youth. K-SADS diagnoses for those identified with psychotic symptoms above threshold included major depressive disorder, bipolar spectrum disorder, attention deficit/hyperactivity disorder, posttraumatic stress disorder, psychotic disorders, and autism spectrum disorder. The optimal psychosis screening cut score (maximizing sensitivity and specificity) was 2.75+ (corresponding diagnostic likelihood ratio [DiLR] = 4.29) for the parent version and 3.50+ (DiLR = 5.67) for the teacher version. The Area under the Curve for parent and teacher report was .83 and .74 (both p < .001). Parent report performed significantly better than teacher report for identifying psychotic symptoms above threshold (p = .03). The CASI-4R Psychosis subscale (J) appears clinically useful for identifying psychotic symptoms in children because of its brevity and accuracy.

Using machine learning and surface reconstruction to accurately differentiate different trajectories of mood and energy dysregulation in youth.

Difficulty regulating positive mood and energy is a feature that cuts across different pediatric psychiatric disorders. Yet, little is known regarding the neural mechanisms underlying different developmental trajectories of positive mood and energy regulation in youth. Recent studies indicate that machine learning techniques can help elucidate the role of neuroimaging measures in classifying individual subjects by specific symptom trajectory. Cortical thickness measures were extracted in sixty-eight anatomical regions covering the entire brain in 115 participants from the Longitudinal Assessment of Manic Symptoms (LAMS) study and 31 healthy comparison youth (12.5 y/o;-Male/Female = 15/16;-IQ = 104;-Right/Left handedness = 24/5). Using a combination of trajectories analyses, surface reconstruction, and machine learning techniques, the present study aims to identify the extent to which measures of cortical thickness can accurately distinguish youth with higher (n = 18) from those with lower (n = 34) trajectories of manic-like behaviors in a large sample of LAMS youth (n = 115; 13.6 y/o; M/F = 68/47, IQ = 100.1, R/L = 108/7). Machine learning analyses revealed that widespread cortical thickening in portions of the left dorsolateral prefrontal cortex, right inferior and middle temporal gyrus, bilateral precuneus, and bilateral paracentral gyri and cortical thinning in portions of the right dorsolateral prefrontal cortex, left ventrolateral prefrontal cortex, and right parahippocampal gyrus accurately differentiate (Area Under Curve = 0.89;p = 0.03) youth with different (higher vs lower) trajectories of positive mood and energy dysregulation over a period up to 5years, as measured by the Parent General Behavior Inventory-10 Item Mania Scale. Our findings suggest that specific patterns of cortical thickness may reflect transdiagnostic neural mechanisms associated with different temporal trajectories of positive mood and energy dysregulation in youth. This approach has potential to identify patterns of neural markers of future clinical course.

Longitudinal course and characteristics of cyclothymic disorder in youth

ObjectivesEpidemiological studies suggest that cyclothymic disorder is the most prevalent subtype of bipolar disorder (BD). However, it is rarely diagnosed, especially in youth. This may be because it can be difficult to ascertain whether a youth meets diagnostic criteria. Clearer, easy-to-apply criteria could reduce misdiagnosis. The objective oftable this study was to determine whether proposed research diagnostic criteria for cyclothymic disorder (RDCyc), based on DSM-5 criteria, could be quantified and validated in youth. MethodsParticipants from the Longitudinal Assessment of Manic Symptoms (LAMS) study were recruited based on symptoms of mania and followed prospectively. RDCyc criteria were: 1) At least one core symptom each of mania and depression; 2) one additional symptom of mania and of depression; 3) persistence over two consecutive six-month periods, and 4) impairment. Exclusionary criteria were having a [hypo]manic or depressive episode. Outcomes at the two-year follow-up were compared between RDCyc youth and other diagnostic groups (BD I/II, BD NOS/non-RDCyc cyclothymic disorder, disruptive behavior disorders [DBD], depression). ResultsThirty-seven youth met RDCyc criteria. There were no consistent differences between the RDCyc youth and youth with other BD subtypes (ps=0.001–0.960, with all-but-one p value >0.02). RDCyc youth had higher depression (p<0.0005) and mania scores (p=0.001), lower functioning (p=0.012), and higher suicide risk than DBD youth (p=0.001). They had higher mania scores than depressed youth (p.018). LimitationsThe majority of youth in the sample were recruited due to elevated symptoms of mania, which may limit the generalizability of the results. Youth were followed for two years, which may not be long enough to determine whether or not they will eventually develop a manic or depressive episode. ConclusionsApplying RDCyc criteria identified youth who were similar to others with BD and were more impaired than those with DBD. Using these criteria could reduce misdiagnosis and increase our understanding of this prevalent, but largely ignored, diagnosis.

Reward-related neural activity and structure predict future substance use in dysregulated youth.

Identifying youth who may engage in future substance use could facilitate early identification of substance use disorder vulnerability. We aimed to identify biomarkers that predicted future substance use in psychiatrically un-well youth. LASSO regression for variable selection was used to predict substance use 24.3 months after neuroimaging assessment in 73 behaviorally and emotionally dysregulated youth aged 13.9 (s.d. = 2.0) years, 30 female, from three clinical sites in the Longitudinal Assessment of Manic Symptoms (LAMS) study. Predictor variables included neural activity during a reward task, cortical thickness, and clinical and demographic variables. Future substance use was associated with higher left middle prefrontal cortex activity, lower left ventral anterior insula activity, thicker caudal anterior cingulate cortex, higher depression and lower mania scores, not using antipsychotic medication, more parental stress, older age. This combination of variables explained 60.4% of the variance in future substance use, and accurately classified 83.6%. These variables explained a large proportion of the variance, were useful classifiers of future substance use, and showed the value of combining multiple domains to provide a comprehensive understanding of substance use development. This may be a step toward identifying neural measures that can identify future substance use disorder risk, and act as targets for therapeutic interventions.

Development of Alcohol and Drug Use in Youth With Manic Symptoms

This analysis examined alcohol and drug use over a 6-year follow-up of children in the Longitudinal Assessment of Manic Symptoms (LAMS) study. LAMS screened 6- to 12.9-year-old children visiting 9 child outpatient mental health (MH) clinics, using the Parent General Behavior Inventory 10-item mania scale. All children with scores≥12 and a matched group with scores≤12 were invited to enroll. Children were assessed every 6 months. Assessments included demographics, family, MH history, child diagnoses, child stress, and alcohol and drug use. Univariate, bivariate, and interval censored survival analyses were conducted. Of those >9 years at baseline, 34.9% used alcohol at least once, with 11.9% regular users; 30.1% used drugs at least once, with 16.2% regular users. Predictors of any alcohol use were parental marital status, older age at study entry, a primary diagnosis of disruptive behavior disorders at baseline, and number of impactful child life events. Predictors of regular alcohol use included parental marital status, age, and sustained high mania symptoms over the first 24 months of follow-up. Predictors of any drug use were single parent, parental substance use, and stressful child life events. Predictors of regular drug use were parental marital status, stressful child life events, and a baseline disruptive behavior disorder diagnosis. Baseline medications decreased the risk of regular drug use. Longitudinal data on youth with elevated manic symptoms suggest that comorbid disruptive behavior disorder, manic symptom burden, family environment, and stress are predictors of initiation and regular use of substances.

Amygdala-prefrontal cortical functional connectivity during implicit emotion processing differentiates youth with bipolar spectrum from youth with externalizing disorders

ObjectiveBoth bipolar spectrum disorders (BPSD) and attention deficit hyperactivity disorder (ADHD) present with emotion-regulation deficits, but require different clinical management. We examined how the neurobiological underpinnings of emotion regulation might differentiate youth with BPSD versus ADHD (and healthy controls, HCs), specifically assessing functional connectivity (FxC) of amygdala-prefrontal circuitry during an implicit emotion processing task. MethodsWe scanned a subset of the Longitudinal Assessment of Manic Symptoms (LAMS) sample, a clinically recruited cohort with elevated behavioral and emotional dysregulation, and age/sex-ratio matched HCs. Our sample consisted of 22 youth with BPSD, 30 youth with ADHD/no BPSD, and 26 HCs. We used generalized psychophysiological interaction (gPPI) to calculate group differences to emerging emotional faces vs. morphing shapes in FxC between bilateral amygdala and ventral prefrontal cortex/anterior cingulate cortex. ResultsFxC between amygdala and left ventrolateral prefrontal cortex (VLPFC) in response to emotions vs. shapes differed by group (p=.05): while BPSD showed positive FxC (emotions>shapes), HC and ADHD showed inverse FxC (emotions<shapes). A group x emotion interaction was found in amygdala-subgenual cingulate FxC (p=.025), explained by differences in FxC in response to negative emotions. While BPSD showed positive FxC, HC showed inverse FxC; ADHD were intermediate. Amygdala-subgenual FxC was also positively associated with depressive symptoms and stimulant medication. LimitationsCo-morbidity and relatively small sample size. ConclusionsYouth with BPSD showed abnormally positive FxC between amygdala and regions in the ventral prefrontal cortex during emotion processing. In particular, the amygdala-VLPFC finding was specific to BPSD, and not influenced by other diagnoses or medications.

26.3 LONGITUDINAL RELATIONSHIPS AMONG EMOTIONAL REGULATION NEURAL CIRCUITRY FUNCTION AND SYMPTOM SEVERITY IN AT-RISK YOUTH WITH BIPOLAR DISORDER

Identifying relationships among longitudinal changes in neural circuitry function and psychiatric symptom severity can aid in the understanding of the neural basis of psychiatric symptom evolution over time. In a longitudinal neuroimaging study of youth at risk for bipolar spectrum disorders from the Longitudinal Assessment of Manic Symptoms (LAMS) cohort of emotionally dysregulated youth, we aimed to identify relationships among activity changes in emotional regulation neural circuitry and changes in affective and anxiety symptom severity over time.

Predicting clinical outcome from reward circuitry function and white matter structure in behaviorally and emotionally dysregulated youth

Behavioral and emotional dysregulation in childhood may be understood as prodromal to adult psychopathology. Additionally, there is a critical need to identify biomarkers reflecting underlying neuropathological processes that predict clinical/behavioral outcomes in youth. We aimed to identify such biomarkers in youth with behavioral and emotional dysregulation in the Longitudinal Assessment of Manic Symptoms (LAMS) study. We examined neuroimaging measures of function and white matter in the whole brain using 80 youth aged 14.0(sd=2.0) from 3 clinical sites. Linear regression using the LASSO method for variable selection was used to predict severity of future behavioral and emotional dysregulation [measured by the Parent General Behavior Inventory-10 Item Mania Scale (PGBI-10M)] at a mean of 14.2 months follow-up after neuroimaging assessment. Neuroimaging measures, together with near-scan PGBI-10M, a score of manic behaviors, depressive behaviors, and sex, explained 28% of the variance in follow-up PGBI-10M. Neuroimaging measures alone, after accounting for other identified predictors, explained approximately one-third of the explained variance, in follow-up PGBI-10M. Specifically, greater bilateral cingulum length predicted lower PGBI-10M at follow-up. Greater functional connectivity in parietal-subcortical reward circuitry predicted greater PGBI-10M at follow-up. For the first time, data suggest that multimodal neuroimaging measures of underlying neuropathologic processes account for over a third of the explained variance in clinical outcome in a large sample of behaviorally and emotionally dysregulated youth. This may be an important first step toward identifying neurobiological measures with the potential to act as novel targets for early detection and future therapeutic interventions.

Parents' Perceived Treatment Match and Treatment Retention Over 12 Months Among Youths in the LAMS Study.

The goal of these analyses was to describe the 12-month prevalence of mental health services retention for youths ages six to 12 years and identify predictors of treatment retention. Data were from the Longitudinal Assessment of Manic Symptoms study. In a longitudinal cohort study, 416 children and their parents completed measures of mental health services use and parents' perception of the services and participated in semistructured psychodiagnostic interviews during a baseline and 12-month assessment. Logistic regression analyses examined the effects on 12-month treatment retention of demographic and clinical variables and parents' perception of how well their children's treatment matched their needs. Sixty-nine percent of youths (N=289) continued to use services at 12 months. After the analyses controlled for other demographic and clinical factors, white race (p<.001) and greater functional impairment (p=.024) were associated with treatment retention; greater perceived treatment match at baseline significantly predicted retention above and beyond the effects of sociodemographic and clinical variables (p=.001). Parents' perceptions about appropriateness of treatment, white race, and functional impairment predicted 12-month treatment retention.