Sleep patterns among preschool offspring of parents with and without psychopathology: Association with the development of psychopathology in childhood.

BACKGROUND: Disturbed sleep during early childhood predicts social-emotional problems. However, it is not known how various early childhood sleep phenotypes are associated with the development of childhood psychopathology, nor whether these relationships vary as a function of parental psychopathology. We identified sleep phenotypes among preschool youth; examined whether these phenotypes were associated with child and parent factors; and determined if early sleep phenotypes predicted later childhood psychopathology. METHODS: Using data from the Pittsburgh Bipolar Offspring study, parents with bipolar disorder (BD), non-BD psychopathology, and healthy controls reported about themselves and their offspring (n = 218) when their children were ages 2-5. Offspring and parents were interviewed directly approximately every 2 years from ages 6-18. Latent class analysis (LCA) identified latent sleep classes; we compared these classes on offspring demographics, parental sleep variables, and parental diagnoses. Kaplan-Meier survival models estimated hazard of developing any new-onset Axis-I disorders, as well as BD specifically, for each class. RESULTS: The optimal LCA solution featured four sleep classes, which we characterized as (1) good sleep, (2) wake after sleep onset problems, (3) bedtime problems (e.g., trouble falling asleep, resists going to bed), and (4) poor sleep generally. Good sleepers tended to have significantly less parental psychopathology than the other three classes. Risk of developing new-onset Axis-I disorders was highest among the poor sleep class and lowest among the good sleep class. CONCLUSIONS: Preschool sleep phenotypes are an important predictor of the development of psychopathology. Future work is needed to understand the biopsychosocial processes underlying these trajectories.

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.

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 having ADHD. 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.

Early indicators of bipolar risk in preschool offspring of parents with bipolar disorder.

BACKGROUND: Offspring of parents with bipolar disorder (BD-I/II) are at increased risk to develop the disorder. Previous work indicates that bipolar spectrum disorder (BPSD) is often preceded by mood/anxiety symptoms. In school-age offspring of parents with BD, we previously built a risk calculator to predict BPSD onset, which generates person-level risk scores. Here, we test whether preschool symptoms predict school-age BPSD risk. METHODS: We assessed 113 offspring of parents with BD 1-3 times during preschool years (2-5 years old) and then approximately every 2 years for a mean of 10.6 years. We used penalized (lasso) regression with linear mixed models to assess relationships between preschool mood, anxiety, and behavioral symptoms (parent-reported) and school-age predictors of BPSD onset (i.e., risk score, subthreshold manic symptoms, and mood lability), adjusting for demographics and parental symptomatology. Finally, we conducted survival analyses to assess associations between preschool symptoms and school-age onset of BPSD and mood disorder. RESULTS: Of 113 preschool offspring, 33 developed new-onset mood disorder, including 19 with new-onset BPSD. Preschool irritability, sleep problems, and parental factors were lasso-selected predictors of school-age risk scores. After accounting for demographic and parental factors, preschool symptoms were no longer significant. Lasso regressions to predict mood lability and subthreshold manic symptoms yielded similar predictors (irritability, sleep problems, and parental affective lability), but preschool symptoms remained predictive even after adjusting for parental factors (ps < .005). Exploratory analyses indicated that preschool irritability univariately predicted new-onset BPSD (p = .02) and mood disorder (p = .02). CONCLUSIONS: These results provide initial prospective evidence that, as early as preschool, youth who will develop elevated risk scores, mood lability, and subthreshold manic symptoms are already showing symptomatology; these preschool symptoms also predict new-onset BPSD. While replication of findings in larger samples is warranted, results point to the need for earlier assessment of risk and development of early interventions.

Asthma and anxiety in children and adolescents: characteristics and treatment outcomes.

OBJECTIVE: This study (a) examined anxious youth with and without asthma on measures of negative self-talk, parental psychopathology, worry content, physical symptoms, panic symptoms, generalized symptoms, and separation anxiety symptoms, and (b) tested if outpatient CBT or medication were differentially effective in reducing anxiety for youth with asthma and anxiety. METHODS: This secondary analysis separated youth with an anxiety disorder into asthma and non-asthma groups. Youth were also compared on response to treatments (i.e. CBT, sertraline, combined, and placebo). RESULTS: A total of 488 participants participated in the original study, with an average age of 10 years (SD 2.87). Youth with comorbid asthma and anxiety demonstrated higher rates of negative self-talk. Youth with comorbid asthma and anxiety did not differ from the non-asthma group on measures of physical symptoms, anxiety disorder specific symptoms, parental psychopathology, or worry content. Youth with asthma and anxiety responded similarly to the non-asthma group to treatment across treatment conditions. CONCLUSIONS: Treatment was comparably effective for youth with comorbid asthma and anxiety and youth with anxiety. Future research could examine the effects of psychopharmaceuticals on asthma and anxiety comorbidity.

Do youth anxiety measures assess the same construct consistently throughout treatment? Results are...complicated.

Interventionists interpret changes in symptoms as reflecting response to treatment. However, changes in symptom functioning and the measurement of the underlying constructs may be reflected in reported change. Longitudinal measurement invariance (LMI) is a statistical approach that assesses the degree to which measures consistently capture the same construct over time. We examined LMI in measures of anxiety severity/symptoms [i.e., Pediatric Anxiety Rating Scale (PARS), Multidimensional Anxiety Scale for Children (MASC), Screen for Child Anxiety and Related Disorders (SCARED)] in anxious youth at baseline and posttreatment. Initial fit was inadequate for 27 of 38 baseline and posttreatment models, but model modifications resulted in acceptable fit. Tests of LMI supported scalar invariance for the PARS and many, but not all, MASC and SCARED subscales. Findings suggest that the PARS, and many MASC and SCARED subscales can accurately be used to measure change over time, however, others may reflect changes in measurement properties.

Inflammatory markers, brain-derived neurotrophic factor, and the symptomatic course of adolescent bipolar disorder: A prospective repeated-measures study.

BACKGROUND: Numerous studies have found elevated pro-inflammatory markers and reduced brain-derived neurotrophic factor (BDNF) during symptomatic episodes of bipolar disorder (BD) in adults. There is a paucity of research examining these markers in youth with BD, or longitudinally in any BD age group. METHODS: 79 adolescents, ages 13-19 years, were enrolled, including 43 symptomatic adolescents with BD and 36 age-matched healthy controls (HC). Blood samples were collected from all participants at intake, and repeatedly from BD participants at pre-specified intervals over the course of two years. Serum was assayed for levels of pro-inflammatory markers (c-reactive protein [CRP], interleukin [IL]-6, tumor necrosis factor alpha [TNF-α]), BDNF and the anti-inflammatory marker, IL-10. Week-by-week severity of mood symptoms was assessed using semi-structured interviews. RESULTS: Adolescents with BD provided an average of 4.6 blood samples, on average every 5.0 months. During the most severe symptomatic interval (i.e., highest sum of mood symptom scores) among BD adolescents, levels of CRP (p = 0.01) and pro- to anti-inflammatory ratios (CRP/IL-10; p < 0.001 and IL-6/IL-10; p = 0.046) were significantly greater, and IL-10 levels (p = 0.004) were significantly lower, vs. HC. There were no differences between BD and HC in IL-6, TNF-α or BDNF. Within BD participants, higher BDNF (p = 0.01) and IL-10 levels (p = 0.001) significantly predicted greater burden of mood symptoms over the subsequent epoch. Moreover, higher CRP levels (p = 0.009) at intake predicted greater time to recovery from the index symptomatic episode. CONCLUSIONS: In the first repeated-measures study on this topic in adolescents with BD, we found evidence that CRP, an inexpensive and ubiquitous blood test, may be useful in predicting the prospective course of BD symptoms. Future larger studies are warranted.

A risk calculator to predict suicide attempts among individuals with early-onset bipolar disorder.

OBJECTIVES: To build a one-year risk calculator (RC) to predict individualized risk for suicide attempt in early-onset bipolar disorder. METHODS: Youth numbering 394 with bipolar disorder who completed ≥2 follow-up assessments (median follow-up length = 13.1 years) in the longitudinal Course and Outcome of Bipolar Youth (COBY) study were included. Suicide attempt over follow-up was assessed via the A-LIFE Self-Injurious/Suicidal Behavior scale. Predictors from the literature on suicidal behavior in bipolar disorder that are readily assessed in clinical practice were selected and trichotomized as appropriate (presence past 6 months/lifetime history only/no lifetime history). The RC was trained via boosted multinomial classification trees; predictions were calibrated via Platt scaling. Half of the sample was used to train, and the other half to independently test the RC. RESULTS: There were 249 suicide attempts among 106 individuals. Ten predictors accounted for >90% of the cross-validated relative influence in the model (AUC = 0.82; in order of relative influence): (1) age of mood disorder onset; (2) non-suicidal self-injurious behavior (trichotomized); (3) current age; (4) psychosis (trichotomized); (5) socioeconomic status; (6) most severe depressive symptoms in past 6 months (trichotomized none/subthreshold/threshold); (7) history of suicide attempt (trichotomized); (8) family history of suicidal behavior; (9) substance use disorder (trichotomized); (10) lifetime history of physical/sexual abuse. For all trichotomized variables, presence in the past 6 months reliably predicted higher risk than lifetime history. CONCLUSIONS: This RC holds promise as a clinical and research tool for prospective identification of individualized high-risk periods for suicide attempt in early-onset bipolar disorder.

Smartphone-based interventions in bipolar disorder: Systematic review and meta-analyses of efficacy. A position paper from the International Society for Bipolar Disorders (ISBD) Big Data Task Force.

BACKGROUND: The clinical effects of smartphone-based interventions for bipolar disorder (BD) have yet to be established. OBJECTIVES: To examine the efficacy of smartphone-based interventions in BD and how the included studies reported user-engagement indicators. METHODS: We conducted a systematic search on January 24, 2022, in PubMed, Scopus, Embase, APA PsycINFO, and Web of Science. We used random-effects meta-analysis to calculate the standardized difference (Hedges' g) in pre-post change scores between smartphone intervention and control conditions. The study was pre-registered with PROSPERO (CRD42021226668). RESULTS: The literature search identified 6034 studies. Thirteen articles fulfilled the selection criteria. We included seven RCTs and performed meta-analyses comparing the pre-post change in depressive and (hypo)manic symptom severity, functioning, quality of life, and perceived stress between smartphone interventions and control conditions. There was significant heterogeneity among studies and no meta-analysis reached statistical significance. Results were also inconclusive regarding affective relapses and psychiatric readmissions. All studies reported positive user-engagement indicators. CONCLUSION: We did not find evidence to support that smartphone interventions may reduce the severity of depressive or manic symptoms in BD. The high heterogeneity of studies supports the need for expert consensus to establish ideally how studies should be designed and the use of more sensitive outcomes, such as affective relapses and psychiatric hospitalizations, as well as the quantification of mood instability. The ISBD Big Data Task Force provides preliminary recommendations to reduce the heterogeneity and achieve more valid evidence in the field.

Prospectively ascertained mania and hypomania among young adults with child- and adolescent-onset bipolar disorder.

OBJECTIVES: While adults with bipolar disorder (BD) often report symptoms starting in childhood, continuity of mania and/or hypomania (mania/hypomania) from childhood to adulthood has been questioned. Using longitudinal data from the Course and Outcome of Bipolar Youth (COBY) study, we assessed threshold mania/hypomania in young adults who manifested BD as youth. METHODS: COBY is a naturalistic, longitudinal study of 446 youth with BD (84% recruited from outpatient clinics), 7-17 years old at intake, and over 11 years of follow-up. Focusing on youth with BD-I/II (n = 297), we examined adult mania/hypomania risk (>18 years old; mean 7.9 years of follow-up) according to child (<13 years old) versus adolescent (13-17 years old) onset. We next used penalized regression to test demographic and clinical predictors of young adult mania/hypomania. RESULTS: Most participants (64%) had child-onset mania/hypomania, 57% of whom also experienced mania/hypomania in adolescence. Among those who experienced an episode in adolescence, over 40% also had mania/hypomania during adulthood; the risk did not differ according to child versus adolescent onset. In contrast, 7% with mania/hypomania in childhood, but not adolescence, experienced mania/hypomania in adulthood. Family history (of mania and suicide attempts) predicted mania/hypomania in young adulthood (p-values <0.05); age of onset was not a significant predictor. Among participants with no mania/hypomania during adulthood, 53% (105/198) still experienced subthreshold manic episodes. DISCUSSION: We find substantial continuity across developmental stage indicating that, in this carefully characterized sample, children who experience mania/hypomania-particularly those who also experience mania/hypomania in adolescence-are likely to experience mania/hypomania in young adulthood.

Consensus on nomenclature for clinical staging models in bipolar disorder: A narrative review from the International Society for Bipolar Disorders (ISBD) Staging Task Force.

OBJECTIVES: Clinical staging is widely used in medicine to map disease progression, inform prognosis, and guide treatment decisions; in psychiatry, however, staging remains a hypothetical construct. To facilitate future research in bipolar disorders (BD), a well-defined nomenclature is needed, especially since diagnosis is often imprecise with blurred boundaries, and a full understanding of pathophysiology is lacking. METHODS: Under the auspices of the International Society of Bipolar Disorders, a Task Force of international experts was convened to review, discuss, and integrate findings from the scientific literature relevant to the development of a consensus staging model and standardize a terminology that could be used to advance future research including staging of BD and related disorders. RESULTS: Consensus opinion and areas of uncertainty or difference were identified in regard to terms referring to staging as it may apply to BD, to at-risk status and subthreshold stages, and to various clinical stages of BD as it is currently diagnosed. CONCLUSION: The use of a standardized nomenclature about the clinical stages of BD will facilitate communication about research on clinical and pathological components of this heterogeneous group of disorders. The concepts presented are based on current evidence, but the template provided allows for further refinements as etiological advances come to light.

A Bayesian multilevel analysis of the longitudinal associations between relationship quality and suicidal ideation and attempts among youth with bipolar disorder.

BACKGROUND: Youth with bipolar disorder (BD) are at high risk for suicidal thoughts and behaviors and frequently experience interpersonal impairment, which is a risk factor for suicide. Yet, no study to date has examined the longitudinal associations between relationship quality in family/peer domains and suicidal thoughts and behaviors among youth with BD. Thus, we investigated how between-person differences - reflecting the average relationship quality across time - and within-person changes, reflecting recent fluctuations in relationship quality, act as distal and/or proximal risk factors for suicidal ideation (SI) and suicide attempts. METHODS: We used longitudinal data from the Course and Outcome of Bipolar Youth Study (N = 413). Relationship quality variables were decomposed into stable (i.e., average) and varying (i.e., recent) components and entered, along with major clinical covariates, into separate Bayesian multilevel models predicting SI and suicide attempt. We also examined how the relationship quality effects interacted with age and sex. RESULTS: Poorer average relationship quality with parents (ß = -.33, 95% Bayesian highest density interval (HDI) [-0.54, -0.11]) or friends (ß = -.33, 95% HDI [-0.55, -0.11]) was longitudinally associated with increased risk of SI but not suicide attempt. Worsening recent relationship quality with parents (ß = -.10, 95% HDI [-0.19, -0.03]) and, to a lesser extent, friends (ß = -.06, 95% HDI [-0.15, 0.03]) was longitudinally associated with increased risk of SI, but only worsening recent relationship quality with parents was also associated with increased risk of suicide attempt (ß = -.15, 95% HDI [-0.31, 0.01]). The effects of certain relationship quality variables were moderated by gender but not age. CONCLUSIONS: Among youth with BD, having poorer average relationship quality with peers and/or parents represents a distal risk factor for SI but not suicide attempts. Additionally, worsening recent relationship quality with parents may be a time-sensitive indicator of increased risk for SI or suicide attempt.

Antidepressant Use in a 3- to 12-Year Follow-up of Anxious Youth: Results from the CAMELS Trial.

The current study explored whether patient characteristics predicted patterns of antidepressant use (i.e., never used, single episode of use, or two or more episodes) in a naturalistic follow-up. Participants in the child/adolescent multimodal (CAMS) extended long-term study. (n = 318) indicated medication use over the course of eight follow-up visits, 3-12 years after receiving treatment in CAMS. 40.6% of participants reported never using an antidepressant during follow-up, 41.4% reported a single episode of antidepressant use, and 18.0% reported multiple episodes of antidepressant use. Greater baseline anxiety severity marginally predicted a single episode of antidepressant use; baseline depression severity predicted multiple episodes of use. Reasons for discontinuing antidepressants included perceived ineffectiveness (31.8%), side effects (25.5%), and improvement in symptoms (18.5%). Exploratory analyses examined predictors of medication use. Findings suggest that antidepressant use is common among anxious youth, as is discontinuation of antidepressant use. Clinical implications and future directions are discussed.

Predictors of Hospitalization in a Cohort of Children with Elevated Symptoms of Mania.

Describe hospitalization rates in children with elevated symptoms of mania and determine predictors of psychiatric hospitalizations during the 96 month follow-up. Eligible 6-12.9 year olds and their parents visiting 9 outpatient mental health clinics were invited to be screened with the Parent General Behavior Inventory 10-item Mania Scale. Of 605 children with elevated symptoms of mania eligible for follow-up, 538 (88.9%) had ≥ 1 of 16 possible follow-up interviews and are examined herein. Multivariate Cox regression indicated only four factors predicted hospitalizations: parental mental health problems (HR 1.80; 95% CI 1.21, 2.69); hospitalization prior to study entry (HR 3.03; 95% CI 1.80, 4.43); continuous outpatient mental health service use (HR 3.73; 95% CI 2.40, 5.50); and low parental assessment of how well treatment matched child's needs (HR 3.97; 95% CI 2.50, 6.31). Parental perspectives on mental health services should be gathered routinely, as they can signal treatment failures.

Clinical, cortical thickness and neural activity predictors of future affective lability in youth at risk for bipolar disorder: initial discovery and independent sample replication.

We aimed to identify markers of future affective lability in youth at bipolar disorder risk from the Pittsburgh Bipolar Offspring Study (BIOS) (n = 41, age = 14, SD = 2.30), and validate these predictors in an independent sample from the Longitudinal Assessment of Manic Symptoms study (LAMS) (n = 55, age = 13.7, SD = 1.9). We included factors of mixed/mania, irritability, and anxiety/depression (29 months post MRI scan) in regularized regression models. Clinical and demographic variables, along with neural activity during reward and emotion processing and gray matter structure in all cortical regions at baseline, were used to predict future affective lability factor scores, using regularized regression. Future affective lability factor scores were predicted in both samples by unique combinations of baseline neural structure, function, and clinical characteristics. Lower bilateral parietal cortical thickness, greater left ventrolateral prefrontal cortex thickness, lower right transverse temporal cortex thickness, greater self-reported depression, mania severity, and age at scan predicted greater future mixed/mania factor score. Lower bilateral parietal cortical thickness, greater right entorhinal cortical thickness, greater right fusiform gyral activity during emotional face processing, diagnosis of major depressive disorder, and greater self-reported depression severity predicted greater irritability factor score. Greater self-reported depression severity predicted greater anxiety/depression factor score. Elucidating unique clinical and neural predictors of future-specific affective lability factors is a step toward identifying objective markers of bipolar disorder risk, to provide neural targets to better guide and monitor early interventions in bipolar disorder at-risk youth.

Longitudinal course and risk factors associated with psychosis in bipolar youths.

OBJECTIVES: To compare the longitudinal clinical course of youths with bipolar disorder (BD) spectrum with lifetime (past, intake, and/or follow-up) psychosis (BDP+) to youths with BD without lifetime psychosis (BDP-). Also, to identify risk factors associated with increased risk of first onset of psychosis during prospective follow-up. METHOD: Bipolar disorder youths (BDP+ = 137, BDP- = 233), aged 7-17 years old, were followed on average every 7 months for 11.7 years and were evaluated using standardized instruments. Data were analyzed using linear and generalized linear models for the full sample, as well as for youths who developed first period of psychosis (n = 55). RESULTS: After adjusting for confounders, BDP+ youths with one, and in particular ≥2 lifetime psychotic episodes, had higher rates and more severe mood and anxiety symptoms, higher rates of suicidality, psychiatric hospitalizations, and sexual/physical abuse, and poorer psychosocial functioning than BDP- youths. Even before the first onset of psychosis during follow-up, BDP+ youths showed more psychopathology and had more family history of psychiatric illness than those who never developed psychosis. First-onset psychosis was associated with low socioeconomic status (SES), living with one parent, bipolar disorder type one and type two, comorbid anxiety, history of hospitalizations, and family history of mania and suicidality. CONCLUSION: BDP+ is associated with poor prognosis and worse clinical picture, even before the onset of psychosis, indicating the need for prompt identification and treatment of these youths. Studies aimed to treat acute symptoms of psychosis, as well as prevent the onset of psychosis, including risk factors amenable to change, are warranted.

Symptom-specific effects of cognitive-behavioral therapy, sertraline, and their combination in a large randomized controlled trial of pediatric anxiety disorders.

BACKGROUND: Pediatric anxiety disorders are highly prevalent and associated with significant functional disabilities and lifelong morbidity. Cognitive-behavioral therapy (CBT), sertraline, and their combination are effective treatments, but little is known about how these treatments exert their effects. METHODS: Using network intervention analysis (NIA), we analyzed data from the largest randomized controlled treatment trial of pediatric anxiety disorders (Child/Adolescent Anxiety Multimodal Study, NCT00052078, clinicaltrials.gov/ct2/show/NCT00052078) and outlined the causal symptom domain-specific effects of CBT, sertraline, and their combination over the course of the 12-week treatment while taking into account both specificity and overlap between symptom domains. RESULTS: All active treatments produced positive effects with the most pronounced and consistent effects emerging in relation to psychological distress, family interference, and avoidance. Psychological distress was consistently the most and physical symptoms the least central symptom domain in the disorder network. CONCLUSIONS: All active treatments showed beneficial effects when compared to placebo, and NIA identified that these effects were exerted similarly across treatments and primarily through a reduction of psychological distress, family interference, and avoidance. CBT and sertraline may have differential mechanisms of action in relation to psychological distress. Given the lack of causal effects on interference outside family and physical symptoms, interventions tailored to target these domains may aid in the building of more effective treatments. Psychological distress and avoidance should remain key treatment focuses because of their central roles in the disorder network. The findings inform and promote developing more effective interventions.

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

OBJECTIVE: To examine development of bipolar spectrum disorders (BPSD) and other disorders in prospectively followed children with attention-deficit/hyperactivity disorder (ADHD). METHOD: 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 8 years, retention averaged 6.2 years. 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. RESULTS: 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 across new 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. CONCLUSIONS: 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.

Associations between Parental Psychopathology and Sexual Behavior in an Outpatient Psychiatric Sample.

Early age of sexual debut is associated with an increase in negative outcomes, including higher incidence of nonconsensual sexual experiences, higher rates of sexually transmitted infections, and risky sexual practices. Little research has examined the role of parental psychopathology as a predictor of adolescent sexual activity, however. The current study aims to close this gap by examining the relationship between parental psychopathology and sexual activity in a longitudinal sample of youth. Participants were 685 adolescents from the Longitudinal Assessment of Manic Symptoms study, the majority of whom were male (67%) and White (65%). Analyses considering likelihood of sexual initiation included the full sample, whereas analyses considering predictors of the age of sexual debut included the 162 participants who reported ever having sexual intercourse (62% male, 51% White) via the Youth Risk Behavior Surveillance-High School version. Cox regression analyses suggested that maternal generalized anxiety disorder predicted decreased likelihood of initiating sex during the 8-year follow-up period, whereas paternal conduct disorder predicted increased likelihood of initiating sex. Multivariate linear regressions also showed that maternal conduct disorder predicted earlier age of sexual debut among those who had initiated, whereas paternal antisocial personality disorder predicted later age of sexual debut. These associations were observed in both male and female adolescents. Furthermore, these effects were largely not explained by the established relationship between youth psychopathology and sexual behavior. Results have implications for interventions aimed at decreasing sexual risk taking in vulnerable youth.

Person-Centered Profiles Among Treatment-Seeking Children and Adolescents with Anxiety Disorders.

Latent profile analysis (LPA) was used to derive homogeneous subgroups within the Child/Adolescent Anxiety Multimodal Study sample (N = 488; 7-17 years, M = 10.69, SD = 2.80) and examine whether class membership predicted or moderated treatment response. Subgroups were identified on baseline multi-informant measures of variables most consistently associated with outcome (youth anxiety/diagnosis, impairment, family psychopathology/functioning). Subgroup membership was examined as a predictor/moderator of outcome across the four treatment conditions (CBT, Sertraline, CBT+Sertraline, pill placebo) at posttreatment (12 weeks) and open-extension follow-up (24 weeks). Four subgroups emerged: mild symptoms/impairment, moderate symptoms/impairment, moderate symptoms/impairment with family dysfunction/parental psychopathology, and severe symptoms/impairment. There were significant between-class differences on socioeconomic status (SES; lower reported SES in the moderate with family dysfunction/parental psychopathology class compared to the mild and moderate class) and age (older age in the severe symptoms class compared to the other three classes). Youth in the mild symptoms/impairment class showed lower posttreatment anxiety across conditions but reported significantly lower symptom severity at baseline. Controlling for demographic differences, response to treatment type did not differ across classes. Analyses indicate that elevated family dysfunction/parental psychopathology clusters primarily within one subgroup of anxious youth rather than mapping onto symptom severity, highlighting the utility of LPA for clarifying within-person combinations of predictor/moderator variables. Implications for development of interventions targeting class-relevant variables are discussed.