Clinical guidelines on long-term pharmacotherapy for bipolar disorder in children and adolescents

Bipolar disorder is a severe affective disorder which can present in adolescence, or sometimes earlier, and often requires a pharmacotherapeutic approach. The phenomenology of bipolar disorder in children and adolescents appears to differ from that of adult patients, prompting the need for specific pharmacotherapy guidelines for long-term management in this patient population. Current treatment guidelines were mainly developed based on evidence from studies in adult patients, highlighting the requirement for further research into the pharmacotherapy of children and adolescents with bipolar disorder. This review compares and critically analyzes the available guidelines, discussing the recommended medication classes, their mechanisms of action, side effect profiles and evidence bas

Analysis of the child and adolescent needs and strengths assessment in a First Nation population

First Nations youth are one of the fastest growing demographics in Canada, yet they are more likely to experience adverse health and life circumstances than non-Indigenous Canadians. Developing and implementing appropriate interventions for mental health is a priority area in decreasing this health gap, and requires the incorporation of First Nation models of mental wellness. Mental Wellness for First Nations’ youth is tied to interpersonal and cultural factors such as relationships with caregivers and the greater community, caregiver and/or community access to necessary resources, and cultural identities. Examining these wider sociocultural factors, in combination with youth characteristics and strengths, provides a more comprehensive understanding of how to address mental health needs in First Nation communities. Working in collaboration with a First Nation based community health provider, the Child and Adolescents Needs and Strengths (CANS) assessment was analyzed for 178 First Nation children to identify specific mental health intervention needs and explore predictors of mental health needs. The CANS is a reliable measure that assesses youth mental health needs, caregiver needs, individual strengths, environmental strengths, as well as many other factors. The most commonly reported mental health intervention needs were seen for Anxiety, Mood, Emotional Control, and Adjustment to Trauma. Hierarchical regression identified referents’ age, sex, Functioning, Individual Strengths, and Family/Caregiver Needs and Strengths domain scores as predictive of mental health intervention needs. Age and Functioning domain scores were robust individual predictors of mental health needs across most models, yet sex was not individually predictive in any model

Early-Onset Bipolar Spectrum Disorders: Diagnostic Issues

Since the mid 1990s, early-onset bipolar spectrum disorders (BPSDs) have received increased attention in both the popular press and scholarly press. Rates of diagnosis of BPSD in children and adolescents have increased in inpatient, outpatient, and primary care settings. BPSDs remain difficult to diagnose, particularly in youth. The current diagnostic system makes few modifications to accommodate children and adolescents. Researchers in this area have developed specific BPSD definitions that affect the generalizability of their findings to all youth with BPSD. Despite knowledge gains from the research, BPSDs are still difficult to diagnose because clinicians must: (1) consider the impact of the child’s developmental level on symptom presentation (e.g., normative behavior prevalence, environmental limitations on youth behavior, pubertal status, irritability, symptom duration); (2) weigh associated impairment and course of illness (e.g., neurocognitive functioning, failing to meet full DSM criteria, future impairment); and (3) make decisions about appropriate assessment (differentiating BPSD from medical illnesses, medications, drug use, or other psychiatric diagnoses that might better account for symptoms; comorbid disorders; informant characteristics and assessment measures to use). Research findings concerning these challenges and relevant recommendations are offered. Areas for further research to guide clinicians’ assessment of children with early-onset BPSD are highlighted

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

Background 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. Method 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. Results 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%. Conclusions 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

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

Improving Clinical Prediction of Bipolar Spectrum Disorders in Youth.

This report evaluates whether classification tree algorithms (CTA) may improve the identification of individuals at risk for bipolar spectrum disorders (BPSD). Analyses used the Longitudinal Assessment of Manic Symptoms (LAMS) cohort (629 youth, 148 with BPSD and 481 without BPSD). Parent ratings of mania symptoms, stressful life events, parenting stress, and parental history of mania were included as risk factors. Comparable overall accuracy was observed for CTA (75.4%) relative to logistic regression (77.6%). However, CTA showed increased sensitivity (0.28 vs. 0.18) at the expense of slightly decreased specificity and positive predictive power. The advantage of CTA algorithms for clinical decision making is demonstrated by the combinations of predictors most useful for altering the probability of BPSD. The 24% sample probability of BPSD was substantially decreased in youth with low screening and baseline parent ratings of mania, negative parental history of mania, and low levels of stressful life events (2%). High screening plus high baseline parent-rated mania nearly doubled the BPSD probability (46%). Future work will benefit from examining additional, powerful predictors, such as alternative data sources (e.g., clinician ratings, neurocognitive test data); these may increase the clinical utility of CTA models further

Stability of Satellite Planes in M31 II: Effects of the Dark Subhalo Population

The planar arrangement of nearly half the satellite galaxies of M31 has been a source of mystery and speculation since it was discovered. With a growing number of other host galaxies showing these satellite galaxy planes, their stability and longevity have become central to the debate on whether the presence of satellite planes are a natural consequence of prevailing cosmological models, or represent a challenge. Given the dependence of their stability on host halo shape, we look into how a galaxy plane's dark matter environment influences its longevity. An increased number of dark matter subhalos results in increased interactions that hasten the deterioration of an already-formed plane of satellite galaxies in spherical dark halos. The role of total dark matter mass fraction held in subhalos in dispersing a plane of galaxies present non trivial effects on plane longevity as well. But any misalignments of plane inclines to major axes of flattened dark matter halos lead to their lifetimes being reduced to < 3 Gyrs. Distributing > 40% of total dark mass in subhalos in the overall dark matter distribution results in a plane of satellite galaxies that is prone to change through the 5 Gyr integration time period.Comment: 11 pages, 9 figures, accepted to MNRAS September 22 201

Factors Influencing Mental Health Service Utilization by Children with Serious Emotional and Behavioral Disturbance: Results from the LAMS Study

The official published article is available online at http://doi.org/10.1176/appi.ps.62.6.650.OBJECTIVE: To describe service utilization of a cohort of children with emotional and behavioral disorders who visited outpatient mental health clinics in four Midwest cities. METHOD: Data come from the Longitudinal Assessment of Manic Symptoms (LAMS) Study. 707 youth (ages 6–12 years) and their parents completed diagnostic assessments, demographic information and an assessment of mental health service utilization. Analyses examined the relationship of demographics, diagnoses, impairment, and comorbidity to the type and level of services utilized. RESULTS: Service utilization is multimodal with half of the youth receiving both outpatient and school services during their lifetime. Non-need factors including age, sex, race, and insurance, were related to types of services used. Youth diagnosed with a bipolar spectrum disorder had higher utilization of inpatient services and two or more services at one time compared to youth diagnosed with depressive or disruptive disorders. More than half of youth diagnosed with bipolar or depressive disorders had received both medication and therapy during their lifetime whereas for youth diagnosed with a disruptive disorder therapy only was more common. Impairment and comorbidity were not related to service utilization. CONCLUSIONS: Use of mental health services for children begins at a very young age and occurs in multiple service sectors. Type of service use is related to insurance and race/ethnicity, underscoring the need for research on treatment disparities. Contrary to findings from results based on administrative data, medication alone was infrequent. However, the reasonably low use of combination therapy suggests that clinicians and families need to be educated on the effectiveness of multimodal treatment

Maintenance treatment of adolescent bipolar disorder: open study of the effectiveness and tolerability of quetiapine

<p>Abstract</p> <p>Background</p> <p>The purpose of the study was to determine the effectiveness and tolerability of quetiapine as a maintenance treatment preventing against relapse or recurrence of acute mood episodes in adolescent patients diagnosed with bipolar disorder.</p> <p>Methods</p> <p>Consenting patients meeting DSM-IV lifetime criteria for a bipolar disorder and clinically appropriate for maintenance treatment were enrolled in a 48-week open prospective study. After being acutely stabilized (CGI-S ≤ 3 for 4 consecutive weeks), patients were started or continued on quetiapine and other medications were weaned off over an 8-week period. Quetiapine monotherapy was continued for 40-weeks and other mood stabilizers or antidepressants were added if clinically indicated. A neurocognitive test battery assessing the most reliable findings in adult patients was administered at fixed time points throughout the study to patients and matched controls.</p> <p>Results</p> <p>Of the 21 enrolled patients, 18 completed the 48-week study. Thirteen patients were able to be maintained without relapse or recurrence in good quality remission on quetiapine monotherapy, while 5 patients required additional medication to treat impairing residual depressive and/or anxiety symptoms. According to symptom ratings and global functioning scores, the quality of remission for all patients was very good.</p> <p>Neurocognitive test performance over treatment was equivalent to that of a matched control group of never ill adolescents. Quetiapine was generally well tolerated with no serious adverse effects.</p> <p>Conclusion</p> <p>This study suggests that a proportion of adolescent patients diagnosed with bipolar disorder can be successfully maintained on quetiapine monotherapy. The good quality of clinical remission and preserved neurocognitive functioning underscores the importance of early diagnosis and effective stabilization.</p> <p>Clinical Trials Registry</p> <p>D1441L00024</p