John Merranko

Dialectical behavior therapy for adolescents with bipolar disorder: results from a pilot randomized trial.

OBJECTIVE The purpose of this study was to conduct a pilot randomized trial of dialectical behavior therapy (DBT) versus psychosocial treatment as usual (TAU) for adolescents diagnosed with bipolar disorder (BP). METHODS We recruited participants 12-18 years of age with a primary BP diagnosis (I, II, or operationalized not otherwise specified [NOS] criteria) from a pediatric specialty clinic. Eligible patients were assigned using a 2:1 randomization structure to either DBT (n=14) or psychosocial TAU (n=6). All patients received medication management from a study-affiliated psychiatrist. DBT included 36 sessions (18 individual, 18 family skills training) over 1 year. TAU was an eclectic psychotherapy approach consisting of psychoeducational, supportive, and cognitive behavioral techniques. An independent evaluator, blind to treatment condition, assessed outcomes including affective symptoms, suicidal ideation and behavior, nonsuicidal self-injurious behavior, and emotional dysregulation, quarterly over 1 year. RESULTS Adolescents receiving DBT attended significantly more therapy sessions over 1 year than did adolescents receiving TAU, possibly reflecting greater engagement and retention; both treatments were rated as highly acceptable by adolescents and parents. As compared with adolescents receiving TAU, adolescents receiving DBT demonstrated significantly less severe depressive symptoms over follow-up, and were nearly three times more likely to demonstrate improvement in suicidal ideation. Models indicate a large effect size, for more weeks being euthymic, over follow-up among adolescents receiving DBT. Although there were no between-group differences in manic symptoms or emotional dysregulation with treatment, adolescents receiving DBT, but not those receiving TAU, evidenced improvement from pre- to posttreatment in both manic symptoms and emotional dysregulation. CONCLUSIONS DBT may offer promise as an adjunct to pharmacotherapy in the treatment of depressive symptoms and suicidal ideation for adolescents with BP. The DBT focus on commitment to treatment may be important for the treatment of early-onset BP. Larger controlled trials are needed to establish the efficacy of this approach, examine impact on suicidal behavior, and demonstrate cost effectiveness.

The longitudinal course of sleep timing and circadian preferences in adults with bipolar disorder.

To study the longitudinal course of sleep timing and circadian preferences in individuals with bipolar disorder (BP) compared to individuals with non‐BP psychopathology and healthy controls.

Differences in sleep disturbances among offspring of parents with and without bipolar disorder: association with conversion to bipolar disorder

Disruptions in sleep and dysregulation in circadian functioning may represent core abnormalities in the pathophysiology of bipolar disorder (BP). However, it is not clear whether these dysfunctions are state or trait markers of BP. This report compared sleep and circadian phenotypes among three groups: offspring of parents with BP diagnosed with BP at intake (BP/OB; n = 47), offspring of parents with BP without BP at intake (non‐BP/OB; n = 386), and offspring of matched control parents who did not have BP (controls; n = 301). We also examined the association of baseline sleep parameters with subsequent development of BP among the non‐BP/OB group.

Assessment of a Person-Level Risk Calculator to Predict New-Onset Bipolar Spectrum Disorder in Youth at Familial Risk

Importance Early identification of individuals at high risk for the onset of bipolar spectrum disorder (BPSD) is key from both a clinical and research perspective. While previous work has identified the presence of a bipolar prodrome, the predictive implications for the individual have not been assessed, to date. Objective To build a risk calculator to predict the 5-year onset of BPSD in youth at familial risk for BPSD. Design, Setting, and Participants The Pittsburgh Bipolar Offspring Study is an ongoing community-based longitudinal cohort investigation of offspring of parents with bipolar I or II (and community controls), recruited between November 2001 and July 2007, with a median follow-up period of more than 9 years. Recruitment has ended, but follow-up is ongoing. The present analysis included offspring of parents with bipolar I or II (aged 6-17 years) who had not yet developed BPSD at baseline. Main Outcomes and Measures This study tested the degree to which a time-to-event model, including measures of mood and anxiety, general psychosocial functioning, age at mood disorder onset in the bipolar parent, and age at each visit, predicted new-onset BPSD. To fully use longitudinal data, the study assessed each visit separately, clustering within individuals. Discrimination was measured using the time-dependent area under the curve (AUC), predicting 5-year risk; internal validation was performed using 1000 bootstrapped resamples. Calibration was assessed by comparing observed vs predicted probability of new-onset BPSD. Results There were 412 at-risk offspring (202 [49.0%] female), with a mean (SD) visit age of 12.0 (3.5) years and a mean (SD) age at new-onset BPSD of 14.2 (4.5) years. Among them, 54 (13.1%) developed BPSD during follow-up (18 with BD I or II); these participants contributed a total of 1058 visits, 67 (6.3%) of which preceded new-onset BPSD within the next 5 years. Using internal validation to account for overfitting, the model provided good discrimination between converting vs nonconverting visits (AUC, 0.76; bootstrapped 95% CI, 0.71-0.82). Important univariate predictors of outcome (AUC range, 0.66-0.70) were dimensional measures of mania, depression, anxiety, and mood lability; psychosocial functioning; and parental age at mood disorder. Conclusions and Relevance This risk calculator provides a practical tool for assessing the probability that a youth at familial risk for BPSD will develop new-onset BPSD within the next 5 years. Such a tool may be used by clinicians to inform frequency of monitoring and treatment options and for research studies to better identify potential participants at ultra high risk of conversion.

Longitudinal trajectories of ADHD symptomatology in offspring of parents with bipolar disorder and community controls.

OBJECTIVE To compare the psychopathology and longitudinal course of attention-deficit/hyperactivity disorder (ADHD) symptomatology and global functioning between the offspring with ADHD of parents with bipolar disorder and the offspring with ADHD of community control parents. METHOD One hundred twenty-two offspring with ADHD of parents with bipolar disorder and 48 offspring with ADHD of control parents from the Pittsburgh Bipolar Offspring Study (BIOS) were included. DSM-IV lifetime psychiatric disorders were ascertained through the Kiddie Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime version (K-SADS-PL). The outcome measures of ADHD symptoms were ascertained at intake and every other year for a period of 6 years using the ADHD section of the K-SADS-PL and the Disruptive Behavior Disorder rating scale (DBD). Global functioning was assessed using the Childrens Global Assessment Scale (CGAS). RESULTS The offspring with ADHD of parents with bipolar disorder showed higher lifetime prevalence of mood and anxiety disorders relative to the offspring with ADHD of control parents (P values ≤ .03). For both groups of offspring with ADHD, the hyperactivity, impulsivity, and total K-SADS-PL ADHD scores decreased over time (P values < .001) without differences between the 2 groups. There were no between- or within-group differences in the inattention scores over time. The DBD ADHD scores decreased with age in both groups (P values < .002) without differences between the 2 groups. For both groups of offspring with ADHD, the global functioning did not improve over time. CONCLUSIONS Offspring with ADHD of parents with bipolar disorder have more psychopathology relative to offspring with ADHD of control parents. However, there were no differences in the developmental courses of ADHD symptomatology between these 2 groups of ADHD youth.

Longitudinal sleep phenotypes among offspring of bipolar parents and community controls

BACKGROUND Sleep disturbances are a prominent feature of bipolar disorder (BP). However, it remains unclear how sleep phenotypes may evolve among at-risk youth, and their relevance to BP onset. METHODS Pittsburgh Bipolar Offspring Study (BIOS) offspring (ages 10-18) and their parents completed assessments approximately every two years pertaining to current psychopathology and offspring sleep habits. A latent transition analysis (LTA) identified latent sleep groups within offspring based on their ratings of six sleep domains using the School Sleep Habits Survey. Demographic and clinical characteristics were compared between sleep groups. Logistic regression tested links between sleep group and BP onset at the subsequent assessment. RESULTS The LTA model identified latent groups of good, poor, and variable sleepers. We observed an overall trend of good sleep becoming variable, and then poor, as youth age. Offspring in the poor sleep group were more likely to have psychopathology. Adjusting for age and depression, poor sleepers had nearly twice the odds of developing BP relative to good (OR=1.99, CI=0.45-8.91) or variable (OR=2.03, CI=0.72-5.72) sleepers. LIMITATIONS Limitations include the use of proximal sleep phenotypes to predict BP onset, and a self-report measure of sleep CONCLUSIONS: We found three non-overlapping sleep phenotype groups in a large sample of offspring of bipolar probands and offspring of demographically-matched community control parents. Clinicians should consider that youth will likely experience variable and/or poor sleep as they age, and that at-risk youth with poor sleep may be at increased risk of developing MDD and BP at their next assessment.

Longitudinal cognitive trajectories and associated clinical variables in youth with bipolar disorder

There is substantial interest in delineating the course of cognitive functioning in bipolar (BP) youth. However, there are no longitudinal studies aimed at defining subgroups of BP youth based on their distinctive cognitive trajectories and their associated clinical variables.

The Relationship Between Stressful Life Events and Axis I Diagnoses Among Adolescent Offspring of Probands With Bipolar and Non-Bipolar Psychiatric Disorders and Healthy Controls: The Pittsburgh Bipolar Offspring Study (BIOS)

BACKGROUND Previous studies have explored the role of stressful life events in the development of mood disorders. We examined the frequency and nature of stressful life events as measured by the Stressful Life Events Schedule (SLES) among 3 groups of adolescent offspring of probands with bipolar (BD), with non-BD psychiatric disorders, and healthy controls. Furthermore, we examined the relationship between stressful life events and the presence of DSM-IV Axis I disorders in these offspring. Stressful life events were characterized as dependent, independent, or uncertain (neither dependent nor independent) and positive, negative, or neutral (neither positive nor negative). METHODS Offspring of probands with BD aged 13-18 years (n = 269), demographically matched offspring of probands with non-BD Axis I disorders (n = 88), and offspring of healthy controls (n = 81) from the Pittsburgh Bipolar Offspring Study were assessed from 2002 to 2007 with standardized instruments at intake. Probands completed the SLES for their offspring for life events within the prior year. Life events were evaluated with regard to current Axis I diagnoses in offspring after adjusting for confounds. RESULTS After adjusting for demographic and clinical between-group differences (in probands and offspring), offspring of probands with BD had greater independent (χ² = 11.96, P < .04) and neutral (χ² = 17.99, P < .003) life events compared with offspring of healthy controls and greater number of more severe stressful life events than offspring of healthy controls, but not offspring of probands with non-BD. Offspring of BD probands with comorbid substance use disorder reported more independent stressful life events compared to those without comorbid substance use disorder (P = .024). Greater frequency and severity of stressful life events were associated with current Axis I disorder in offspring of both probands with BD and probands with other Axis I disorders regardless of dependency or valence. Greater frequency and severity of stressful life events were associated with greater current Axis I disorder in all offspring. CONCLUSIONS Offspring of probands with BD have greater exposure to independent and neutral life events than offspring of healthy controls. Greater frequency and severity of stressful life events were associated with Axis I disorder in offspring of both BD and non-BD affected probands.

Psychometrics of the screen for adult anxiety related disorders (SCAARED)- A new scale for the assessment of DSM-5 anxiety disorders

OBJECTIVE To examine the psychometrics of the Screen for Adult Anxiety Related Disorders (SCAARED). METHODS The SCAARED was adapted from the Screen for Child Anxiety Related Emotional Disorders. Participants (N=336) ages 18-27 years old were evaluated using the Structured Clinical Interview for DSM-IV Disorders (SCID). The SCAARED was completed at or within two-weeks before the SCID. The psychometrics of the SCAARED were analyzed using standard statistical analyses including principal components, and Receiver Operant Curve analyses. A replication was performed in an age/sex matched independent sample (N=158). RESULTS The SCAARED showed four factors: somatic/panic/agoraphobia, generalized anxiety, separation anxiety, and social anxiety. The total and each factor scores demonstrated good internal consistency (α=0.86-0.97) and good discriminant validity between anxiety and other disorders and within anxiety disorders for generalized and social anxiety. Area Under the Curve for the total and each of the factor scores ranged between 0.72 and 0.84 (p<0.0001). These results were replicated in the independent sample. CONCLUSIONS The SCAARED showed excellent psychometric properties supporting its use to screen adults for anxiety disorders, longitudinal studies following youth into adulthood and studies comparing child and adult populations. Further replication studies in larger community and clinical samples are indicated.

5.70 A Longitudinal Study of Family Functioning in Offspring of Bipolar Parents

Objective To compare the longitudinal course of family functioning in offspring of parents with bipolar disorder (BD), offspring of parents with non-BD psychopathology, and offspring of healthy control (HC) parents. Method Offspring of parents with BD (256 parents and 481 offspring), parents without BD (82 parents and 162 offspring), and HC parents (88 parents and 175 offspring) 7 to 18 years of age at intake, from the Bipolar Offspring Study (BIOS), were followed for an average of 4.3 years. Family functioning was evaluated using the child- and parent-reported Family Adaptability and Cohesion Scale–II and the Conflict Behavior Questionnaire. The data were analyzed using multivariate multilevel regression, generalized linear estimating equation models, and path analysis. Results Families of parents with BD and parents with non-BD psychopathology showed lower cohesion and adaptability and higher conflict compared with HC families. There were no significant differences in cohesion and adaptability between families of parents with psychopathology. The effect of parental psychopathology on family functioning was mediated by parental psychosocial functioning and, to a lesser extent, offspring disorders. In all 3 groups, parent-reported family conflict was significantly higher than child-reported conflict. Across groups, family cohesion decreased over follow-up, whereas conflict increased. Conclusion Any parental psychopathology predicted family impairment. These results were influenced by the offspring’s age and were mediated by parental psychosocial functioning and, to a lesser degree, by offspring psychopathology. These findings emphasize the need to routinely assess family functioning in addition to psychopathology and provide appropriate interventions to parents and offspring.