Short- and Long-Term Outcomes of Suboptimal Medication Adherence in Adolescents with Attention-Deficit/Hyperactivity Disorder: A Systematic Literature Review.

Introduction: Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental condition with severe and life-long consequences. Adolescents and young adults represent a particularly vulnerable subgroup because of the unique demands of their developmental stage. Despite the well-known efficacy of medication treatment for ADHD, there remains a notable concern regarding poor medication adherence in this population. Objectives: This systematic literature review aimed to synthesize the existing empirical evidence on the outcomes and consequences of medication nonadherence among adolescents and young adults with ADHD. Methods: An extensive database search was conducted on September 26, 2022, with no time limits applied. The databases included Scopus, PubMed, CINAHL, Cochrane, and PsycINFO. Results: Six studies met the inclusion criteria. Each study revealed that medication nonadherence was associated with a range of adverse outcomes, including decreased academic performance, heightened familial, and psychological stress, and an increased likelihood of substance use, pregnancy, obesity, and injury. Conversely, adherence led to improvements in at least one ADHD-related outcome. Conclusions: Research exploring the consequences of suboptimal medication adherence in adolescents and young adults with ADHD is currently limited, and effective strategies to address this issue remain scarce. A thorough understanding of such consequences is critical for developing interventions aimed at improving medication adherence and mitigating the risk of adverse outcomes, especially considering the susceptibility of this population.

Mind-Body Interventions for Youth with Chronic Medical Conditions: A Scoping Review of the Literature.

Background and purpose: Little is known about the applicability, utilization, and effectiveness of mind-body interventions (MBIs) for conditions that are not predominantly pain, neoplastic, or psychiatric, particularly in pediatric patients. This scoping review describes research pertaining to such interventions in youth with nonpain, noncancer, and nonpsychiatric predominant chronic medical conditions. Methods: Searches of EBSCO CINAHL, Elsevier Scopus, Ovid for MEDLINE, and Ovid PsycInfo were conducted to investigate MBIs in youth under 18 years of age with nonpain, noncancer, and nonpsychiatric predominant chronic medical conditions. Articles published between 2010 and 2020 were included. Abstracts were screened by three authors for inclusion, and disagreements were resolved by a designated author. Selected full-text articles were divided among all authors for review of study quality, intervention feasibility and acceptability, and effectiveness. Results: The search yielded 1010 titles with 15 meeting the final inclusion criteria, studying a total of 641 youth. Participants ranged in age from 6 to 19 years (included studies had data on participants <18 years reported separately); 61.5% were female (n = 394) and 38.5% were male (n = 247). The two most common conditions studied were asthma and irritable bowel syndrome, with yoga being the most popular intervention. Overall, MBIs showed promising preliminary evidence for improving symptoms and quality of life in youth with chronic medical conditions. Conclusion: MBIs have been successfully delivered and show promise in symptom palliation and quality of life improvement for youth with a variety of chronic medical conditions. More data from high-quality randomized controlled trials are needed to further characterize the effectiveness of specific modalities for specific conditions.

International Care programs for Pediatric Post-COVID Condition (Long COVID) and the way forward.

BACKGROUND: Pediatric Post-COVID-Condition (PPCC) clinics treat children despite limited scientific substantiation. By exploring real-life management of children diagnosed with PPCC, the International Post-COVID-Condition in Children Collaboration (IP4C) aimed to provide guidance for future PPCC care. METHODS: We performed a cross-sectional international, multicenter study on used PPCC definitions; the organization of PPCC care programs and patients characteristics. We compared aggregated data from PPCC cohorts and identified priorities to improve PPCC care. RESULTS: Ten PPCC care programs and six COVID-19 follow-up research cohorts participated. Aggregated data from 584 PPCC patients was analyzed. The most common symptoms included fatigue (71%), headache (55%), concentration difficulties (53%), and brain fog (48%). Severe limitations in daily life were reported in 31% of patients. Most PPCC care programs organized in-person visits with multidisciplinary teams. Diagnostic testing for respiratory and cardiac morbidity was most frequently performed and seldom abnormal. Treatment was often limited to physical therapy and psychological support. CONCLUSIONS: We found substantial heterogeneity in both the diagnostics and management of PPCC, possibly explained by scarce scientific evidence and lack of standardized care. We present a list of components which future guidelines should address, and outline priorities concerning PPCC care pathways, research and international collaboration. IMPACT: Pediatric Post-COVID Condition (PPCC) Care programs have been initiated in many countries. Children with PPCC in different countries are affected by similar symptoms, limiting many to participate in daily life. There is substantial heterogeneity in diagnostic testing. Access to specific diagnostic tests is required to identify some long-term COVID-19 sequelae. Treatments provided were limited to physical therapy and psychological support. This study emphasizes the need for evidence-based diagnostics and treatment of PPCC. The International Post-COVID Collaboration for Children (IP4C) provides guidance for guideline development and introduces a framework of priorities for PPCC care and research, to improve PPCC outcomes.

Evidence for Altered Electroencephalography Coherence in Depressed Adolescents with Suicidal Ideation and Behaviors.

Introduction: Major depressive disorder (MDD) is a primary risk factor for suicide, which is one of the leading causes of death among adolescents worldwide. Understanding the heterogeneity of suicidality in adolescents with MDD is critical for suicide prevention and intervention discovery. Quantitative electroencephalography (EEG) is a promising tool to address the knowledge gaps related to the neurophysiological characteristics of depression and suicidality. This study sought to examine resting-state EEG coherence differences in adolescents with MDD and suicidal ideation (SI)/behaviors (SB) and healthy controls (HC) to assess the utility of coherence as a biomarker of suicide. Methods: Twenty-six adolescents with MDD who were hospitalized for suicidality and 30 HC were recruited. The clinical sample was divided into SI (n = 9) and SB (n = 19) subgroups. Eyes closed resting-state EEG were recorded, and coherence was calculated. Depression severity and suicidality were assessed with the Children's Depression Rating Scale Revised and the Columbia Suicide Severity Rating Scale, respectively. Results: There were intrahemispheric differences in the right hemisphere across multiple electrode pairs. Delta, alpha, and beta coherence were higher in the SB group over the right prefrontofrontal and left parietooccipital electrode pairs, while alpha coherence was higher in the HC group over the right centroparietal electrode pair. There were no significant differences between HC and SI groups in any electrode pair. Conclusions: Patients with recent SB showed increased coherence in right frontal regions compared with patients with SI, suggesting altered cognitive states between those with SB and SI. These findings may have implications for suicide prevention in adolescents and could serve as useful biomarkers in clinical settings, but larger studies are needed to confirm the results.

Health Disparities among Rural Individuals with Mental Health Conditions: A Systematic Literature Review.

There is growing concern about the availability of healthcare services for rural patients. This systematic literature review evaluates original research on health disparities among rural and urban populations with mental health conditions in North America. Using PRISMA guidelines, we used four electronic databases (Pubmed, Cochrane, PsychInfo, Web of Science) and hand searches and included original research conducted in the United States or Canada before July 2021 that compared health outcomes of patients with any mental health disorder in rural versus non-rural areas. Both qualitative and quantitative data were extracted including demographics, mental health condition, health disparity measure, rural definition, health outcome measures/main findings, and delivery method. To evaluate study quality, the modified Newcastle Ottawa Scale was used. Our initial search returned 491 studies and 17 studies met final inclusion criteria. Mental health disorders included schizophrenia (4 studies), PTSD (10), mood disorders (9), and anxiety disorders (6). Total sample size was 5,314,818 with the majority being military veterans. Six studies (35.2%) showed no significant rural-urban disparities while eleven (64.7%) identified at least one. Of those, nine reported worse outcomes for rural patients. The most common disparities were diagnostic differences, increased suicide rates and access problems. This review found mixed results regarding outcomes in rural patients with mental health disorders. Disparities were found regarding risk of suicide and access to services. Telehealth in addition to in person outreach to these rural communities may be alternatives to impact these outcomes.

A self-management plus mind body intervention for adolescents and young adults with type 2 diabetes: Trial design and methodological report.

BACKGROUND: The onset of type 2 diabetes (T2D) is increasingly common in adolescents and young adults (AYAs). Improving self-management skills and the mental health of this population is important, but understudied. METHODS: The goal of this research was to develop a mind-body intervention which could serve as an adjunctive therapy to support AYAs with T2D (INTEND intervention). Toward that end, we used an iterative process, including use of focus groups, advisory board, and cognitive semi-structured interviews with patients, parents of patient and clinical providers, to understand the gaps in the current information provided to AYAs with T2D. Based on the data gathered from the focus groups and interviews, we enhanced an existing self-management intervention for adults with T2D to include an additional mind body intervention for AYAs with T2D. The INTEND intervention will be piloted in a group of AYAs with T2D. RESULTS: This report describes the methodology and design of the InterveNTion for Early oNset type 2 Diabetes (INTEND) study. The details of this single arm pre-post pilot feasibility trial are described. DISCUSSION: If successful, the INTEND approach has the potential to advance care for vulnerable youth with T2D.

Association Between Symptom Severity and Medication Adherence in Adolescents with Bipolar Disorder Demonstrating Suboptimal Adherence.

Objective: While medication non-adherence is common in bipolar disorder (BD), few studies have specifically assessed non-adherent BD adolescents and young adults (AYAs). This analysis, using screening and baseline data from an ongoing randomized controlled trial, examined the relationship between BD symptoms and adherence in poorly adherent AYAs. Methods: AYAs ages 13-21 had sub-optimal adherence defined as missing ⩾ 20% of prescribed BD medication. Mean sample (N = 36) age was 19.1 years (SD = 2.0), 66.7 % (N = 24) female, 25.0 % (n = 9) non-white. Adherence was measured via: 1) self-reported Tablets Routine Questionnaire (TRQ) and 2) electronic monitoring (SimpleMed pillbox). Symptoms were measured with the Hamilton Depression Rating Scale (HAM-D), the Young Mania Rating Scale (YMRS), and the Clinical Global Impression Scale (CGI). Results: Mean percentage of missed BD medications using TRQ was 34.9 (SD = 28.9) at screening and 30.6 (SD = 33.0) at baseline. Mean percentage of missed medication using SimpleMed at baseline was 42.1 (SD = 37.0). The correlation between TRQ and SimpleMed was r = 0.36 (p = 0. 13). Neither CGI nor age were correlated with adherence. Neither TRQ nor SimpleMed were significantly related to HAM-D. YMRS was positively associated with worse adherence for TRQ (r = 0.36, p = 0.03), but not significantly associated with SimpleMed. Adherence did not differ by other demographic attributes. Conclusion: Adherence levels varied widely in AYA with BD. Adherence monitoring increased adherence by approximately 4.5%, and use of electronic pill monitoring identified a greater proportion of missed medication vs. self-report. BD symptoms may not consistently identify AYA with adherence challenges.

A Multicenter Double-Blind, Placebo-Controlled Trial of Escitalopram in Children and Adolescents with Generalized Anxiety Disorder.

Objective: Generalized anxiety disorder (GAD) in children and adolescents is associated with substantial morbidity and increases the risk of future psychopathology. However, relatively few psychopharmacologic studies have examined treatments for GAD in pediatric populations, especially in prepubertal youth. Methods: Children and adolescents aged 7-17 years of age with a primary diagnosis of GAD were treated with flexibly dosed escitalopram (10-20 mg daily, n = 138) or placebo (n = 137) for 8 weeks. Efficacy measures included the Pediatric Anxiety Rating Scale (PARS) for GAD, Clinical Global Impression of Severity (CGI-S) scale, Children's Global Assessment Scale (CGAS); safety measures included the Columbia-Suicide Severity Rating Scale (C-SSRS) as well as adverse events (AEs), vital signs, and electrocardiographic and laboratory monitoring. Results: Escitalopram was superior to placebo in reducing anxiety symptoms of GAD, as seen in the difference in mean change from baseline to week 8 on the PARS severity for GAD score (least squares mean difference = -1.42; p = 0.028). Functional improvement, as reflected by CGAS score, was numerically greater in escitalopram-treated patients compared with those receiving placebo (p = 0.286), and discontinuation owing to AEs did not differ between the two groups. Vital signs, weight, laboratory, and electrocardiographic results were consistent with previous pediatric studies of escitalopram. Conclusions: Escitalopram reduced anxiety symptoms and was well tolerated in pediatric patients with GAD. These findings confirm earlier reports of escitalopram efficacy in adolescents aged 12-17 years and extend the safety and tolerability data to children with GAD aged 7-11 years. ClinicalTrials.gov Identifier: NCT03924323.

Updated strategies for the management of poor medication adherence in patients with bipolar disorder.

INTRODUCTION: Suboptimal adherence is a well-established, pervasive problem in individuals with bipolar disorder (BD) causing disability, suffering, and cost. AREAS COVERED: This review covers new research since January 2016 regarding internal (patient-centered) and external (system level) barriers and facilitators to adherence. Measures of adherence, the efficacy of psychosocial adherence enhancement interventions in individuals with BD, and, finally, novel delivery systems for BD medication are also covered. Measures of adherence continue to fall broadly into objective measures (i.e. drug levels) and more subjective, self-report measures and a combination of these likely provides the most comprehensive picture. Efficacious components of psychosocial adherence enhancement interventions include psychoeducation, motivational interviewing, and cognitive behavioral strategies, yet methods for delivery vary. Long-acting injectable (LAI) medications for BD are the drug delivery system with the most promise for BD. Combining psychosocial components with novel drug delivery systems has the potential for establishing and maintaining medication adherence. EXPERT OPINION: Psychosocial interventions improve adherence in individuals with BD. Psychoeducation is a necessary but not sufficient component in psychosocial interventions. LAIs should be considered earlier for adherence improvement than many treatment guidelines currently suggest. Comparative studies are lacking as is research into novel systems of medication delivery.

Evaluation of the Relationship of Sleep Disturbances to Severity and Common Behaviors in Autism Spectrum Disorder.

Background: Autism spectrum disorder (ASD) is one of the most puzzling disorders of childhood. Recent research of comorbidities that accompany ASD and are commonly attributed to the diagnosis, indicate that they may contribute to the severity of behavioral symptoms of the disorder.Disturbed sleep in all children can decrease cognition, decrease focus, increase performance problems, and alter mood and behavior. Children with ASD experience an increased sensitivity to disturbed sleep that may increase the severity of the disorder. Disturbed sleep patterns, such as increased sleep latency, nighttime waking and early arousal, have been identified in up to 80% of children with ASD. This study explored the relationship of disturbed sleep and the severity of the core ASD symptoms. Methods: Actigraphy and an accompanying sleep diary captured disturbed sleep patterns in 24 children, ages 6-12, with ASD. Participants wore a GT3X actigraphy monitor for 7 nights to collect data on patterns of disturbed sleep. Parents completed a sleep diary and the Autism Spectrum Rating Scale (ASRS) questionnaire.A descriptive analysis was used to report the characteristics of nighttime sleep and sleep efficiency as well as sleep disturbances. Pearson's r determined the relationships between the number of sleep disturbances and the severity of ASD behavioral scores and diagnostic severity (determined by the ASRS). Results: Of the 24 study participants, almost 92% had one or more sleep disturbances. A positive correlation was present between the number of sleep disturbances and the severity of delays in social and communication symptoms. A moderate effect size was found between the number of sleep disturbances and unusual behaviors in ASD suggests a possible, unanticipated, inverse relationship. Conclusions: Exploring the relationship of disturbed sleep to behavior and symptom severity in children with ASD can provide an understanding of how poor sleep influences ASD symptoms. This study identified distinct differences in ASD symptom severity between and within individual participants and found unique, and unexpected, symptom patterns. This finding supports the need, in research and treatment, to identify comorbidities and symptoms that contribute to individual behavioral profiles and phenotypes of the disorder.

Mental health comorbidity and youth onset type 2 diabetes: A systematic review of the literature.

BACKGROUND: Type 2 diabetes (T2D) is a burgeoning epidemic in children and adolescents. Adult T2D doubles the risk of depression and mental health comorbidity, makes it more difficult to make the lifestyle, medication adherence and health behavior changes needed to optimize outcomes. There is limited research on the impact of depression and depressive symptoms on youth T2D. METHODS: A search of the literature in the last 10 years regarding youth with depression and T2D was conducted. Abstracts were screened by 2 randomly assigned authors for inclusion, and disagreement was resolved by a third author. Selected full-text articles were divided among all authors for review. RESULTS: 13 publications from 8 studies (N=2244, age 6-17) were included. 6 of 13 publications utilized Treatment Options for Type 2 Diabetes in Youth (TODAY) study data. While studies included evaluation of depressive symptoms, most did not formally assess for major depressive disorder (MDD) and excluded participants with a previous diagnosis of MDD. Depressive symptoms were common in this population and were associated with negative T2D outcomes. CONCLUSIONS: While there is a growing body of adult literature highlighting the extensive relationship between T2D and mental health, there is a dearth of data in youth. Future studies are needed that include, 1.) youth with diagnosed MDD, 2.) treatment studies of both T2D and MDD, 3.) larger, more racially diverse samples of youth with T2D, and 4.) studies that evaluate the impact of social determinants of health, including mental health comorbidity on outcomes of T2D.

Elevation of C-reactive protein in adolescent bipolar disorder vs. anxiety disorders.

Bipolar disorder (BD) largely begins in adolescence, but diagnosis lags for years, causing significant morbidity and mortality, and demonstrating the need for better diagnostic tools. Suggesting an association between BD and immune activity, elevated levels of peripheral inflammatory markers, including C-reactive protein (CRP), have been found in adults with BD. As similar data are extremely limited in adolescents, this study examined CRP levels in adolescents with BD (n = 37) compared to those with anxiety disorders (ADs, n = 157) and healthy controls with no psychiatric diagnoses (HCs, n = 2760). CRP blood levels for patients aged 12-17 years were retrieved from a nationwide repository of deidentified clinical data. After excluding patients with inflammatory conditions, differences in CRP were examined using multivariate and weighted regressions (covariates: demographics and BMI). Mean CRP levels were significantly elevated in adolescents with BD relative to those with ADs and HCs. Mean CRP levels were lower in the ADs cohort versus HCs. Although CRP levels were significantly higher in males and younger patients, the significant between-cohort differences in CRP remained after controlling for multiple confounders. To our knowledge, our study is the first to compare CRP levels between adolescent BD, ADs, and HCs, comprising a novel and essential contribution. Our results suggest the presence of a unique immune process in adolescents with BD and indicate that CRP may represent a biomarker with a crucial role in the diagnostic assessment of adolescent BD.

A Predictive Biomarker Model Using Quantitative Electroencephalography in Adolescent Major Depressive Disorder.

Background: With evolving understanding of psychiatric diagnosis and treatment, demand for biomarkers for psychiatric disorders in children and adolescents has grown dramatically. This study utilized quantitative electroencephalography (qEEG) to develop a predictive model for adolescent major depressive disorder (MDD). We hypothesized that youth with MDD compared to healthy controls (HCs) could be differentiated using a singular logistic regression model that utilized qEEG data alone. Methods: qEEG data and psychometric measures were obtained in adolescents aged 14-17 years with MDD (n = 35) and age- and gender-matched HCs (n = 14). qEEG in four frequency bands (alpha, beta, theta, and delta) was collected and coherence, cross-correlation, and power data streams obtained. A two-stage analytical framework was then used to develop the final logistic regression model, which was then evaluated using a receiver-operating characteristic curve (ROC) analysis. Results: Within the initial analysis, six qEEG dyads (all coherence) had significant predictive values. Within the final biomarkers, just four predictors, including F3-C3 (R frontal) alpha coherence, P3-O1 (R parietal) theta coherence, CZ-PZ (central) beta coherence, and P8-O2 (L parietal occipital) theta power were used in the final model, which yielded an ROC area of 0.8226. Conclusions: We replicated our previous findings of qEEG differences between adolescents and HCs and successfully developed a single-value predictive model with a robust ROC area. Furthermore, the brain areas involved in behavioral disinhibition and resting state/default mode networks were again shown to be involved in the observed differences. Thus, qEEG appears to be a potential low-cost and effective intermediate biomarker for MDD in youth.

A customized adherence enhancement program for adolescents and young adults with suboptimal adherence and bipolar disorder: Trial design and methodological report.

BACKGROUND: The onset of bipolar disorder (BD) is common during late adolescence and young adulthood (AYA). Suboptimal medication adherence is a critical yet modifiable risk factor for negative outcomes among AYAs with BD. METHODS: This research used an iterative process (e.g., focus groups, advisory board, cognitive interviews) to modify an existing adherence intervention to address suboptimal adherence in AYAs with BD. The modified version of Customized Adherence Enhancement for Adolescents and Young Adults (CAE-AYA) will be compared to an Enhanced Treatment as Usual condition (ETAU) in 40 AYAs intervention using a 6-month prospective, randomized controlled trial (RCT) in a high-risk group of 16-21 year old AYAs with BD with demonstrated non-adherence to their prescribed BD medications. CONCLUSIONS: This report describes the methodology and design of the ImprovinG adhereNce In adolescenTs with bipolar disordEr (IGNITE) study. If successful, the CAE-AYA approach has the potential to advance care for vulnerable youth with BD.

Narrative Analyses: Cognitive Behavior Group Therapy for Women with Menopause and Bipolar or Major Depressive Disorders.

Background: Bipolar and depressive disorders (bipolar disorder [BD], major depressive disorder [MDD]), as well as menopause affect millions of women. Although there are three known cognitive behavioral group treatment (CBGT) protocols to help women with problematic menopause symptoms, they do not target women on the BD or MDD spectrum. The purpose of this qualitative study was to learn more about the treatment needs and group experiences of women with problematic menopause symptoms and diagnosed on the BD and MDD spectrum, who participated in a CBGT intervention for menopausal symptoms. Methods: Narrative data recorded by clinicians (Interventionists' notes) and participants (Evaluation of Groups Survey) were analyzed using content analyses. Results: Several themes emerged from (n = 11 BD; n = 48 MDD) what women wanted help with (specific symptoms and general aspects of menopause), what women liked about CBGT (specific and general aspects of the program), and changes needed in the CBGT intervention (things wished for and barriers that interfered with the program). The two diagnostic groups differed in their responses, although both groups identified content and delivery gaps they wished would be addressed. Specifically related to their diagnosis, women most commonly talked about problems with worsening mood and mood instability and multiple stressors interfering with their ability to follow through with the intervention. Conclusions: These findings can help refine existing CBGT protocols for women diagnosed on the BD and MDD spectrum seeking help for menopause symptoms. Trial Registry: Parent study ClinicalTrials.gov [identifier: NCT02860910].

Primary care pediatrician perceptions towards mental health within the primary care setting.

BACKGROUND: Mental health (MH) conditions are highly prevalent, yet only marginal portions of children receive adequate services. Access to specialized mental healthcare is limited and, consequently, pediatricians remain the source of management and care of children with MH disorders. Despite this, research suggests that pediatricians report lack of access to training and support regarding MH care of youth, leading to discomfort with managing the population they are asked to treat. An additional barrier to care that has less research is perceptions regarding MH disorders among pediatricians. This scoping review aims to describe the state of science regarding perceptions and possible stigma towards MH in pediatric primary care. METHODS: PsychInfo, PubMed Medline, Ovid Medline, CINAHL, and Embase were searched with terms related to stigma, pediatricians, and MH disorders. New research articles were included after review, which addressed stigma in pediatricians treating youth with MH disorders. RESULTS: Our initial search produced 457 titles, with 23 selected for full-text review, and 8 meeting inclusion criteria, N = 1571 pediatricians. CONCLUSIONS: While a limited number of studies focus on physician-based perceptions/stigma, and even less data on pediatrician stigma towards MH, more studies are needed to explore how this impacts patient care. IMPACT: In this scoping review, we sought to shed light on the limitations regarding MH care access, especially with the increasing need for care and not enough MH specialists, adding to an already tremendous burden pediatric primary care providers face daily. We also reviewed barriers to said care within pediatric primary care, including the potential for physician stigma towards MH diagnosis, treatment, and management. This review adds a concise summary of the current limited studies on stigma towards MH within primary care pediatricians and the importance of continued research into how perception and stigma affect patient care. This material is an original project and has not been previously published. This work is not submitted for publication or consideration elsewhere.

Medication Adherence in Pediatric Patients with Bipolar Disorder: A Systematic Review.

Objectives: Pediatric bipolar disorder is a severe disabling condition affecting 1%-3% of youth worldwide. Both acute and maintenance treatment with medications are mainstays of treatment. It is well established in adult literature that adherence to medications improves outcomes and many adult studies have examined factors impacting adherence. This systematic review set out to identify the current state of research examining adherence to medications and characteristics influencing adherence in pediatric bipolar disorder. Methods: We performed a systematic literature review in the Medline, PsycINFO, CINAHL, EMBASE, Wiley Clinical Trials, and Cochrane databases. New research regarding characteristics and measurement of adherence to psychotropic medication for bipolar disorder (I, II, or not otherwise specified) in patients ≤18 years old were included for review. Exclusion criteria included no bipolar diagnosis, inclusion of patients >18 years old, no pharmacologic treatment, and lack of adherence measurements. Results: Initial search generated 439 articles after duplicate removal. One hundred thirty-three full-text articles were reviewed, 16 underwent additional review and 6 were selected for final inclusion. The majority of articles were excluded for patients >18 years old. Included articles were extremely heterogeneous for multiple measures, including methodology, determination of adherence, adherence rates, and characteristics influencing adherence. Of medications evaluated, 6/6 studies included mood stabilizers, 4/6 antidepressants, 3/6 antipsychotics, and 2/6 psychostimulants. Three out of six articles included patients <12 years old. Some significant factors affecting adherence included polypharmacy, comorbid psychiatric diagnoses, socioeconomic status, sex, family history and functioning, side effects, race, stability of bipolar diagnosis, and number of follow-up visits attended. Conclusions: Pediatric-specific information on medication adherence in bipolar disorder is very limited. Information on patient characteristics that may influence adherence rates is critical to target interventions to improve adherence. No articles reported on interventions to improve adherence. Given the different psychosocial situations of pediatric patients versus adults, it is likely that targets for improving adherence differ in pediatric patients.

Understanding Chronic Aggression and Its Treatment in Children and Adolescents.

PURPOSE OF REVIEW: Youth aggression is common and has a significant burden on individuals, families, and society. However, its treatment is often a challenge for clinicians. Thus, this review will examine the current understanding of youth aggression, conceptualize aggression as a symptom rather than its own disorder, and provide an overview of treatment strategies. RECENT FINDINGS: Youth aggression is associated with complex genetic, neurobiological, and environmental risks. Prevention strategies are of the utmost importance for at-risk families and youth. Psychosocial interventions are the first line treatment. But if not fully effective, then pharmacologic interventions-including psychostimulants, alpha-2 agonists, atomoxetine, and risperidone-have shown benefits. Other medications, such as SSRIs, can be useful in certain scenarios. It is important to conceptualize youth aggression as being a trans-diagnostic symptom in psychopathology. Determining the underlying cause of aggression will help to guide treatment.

A systematic review of quantitative EEG as a possible biomarker in child psychiatric disorders.

Quantitative EEG (qEEG) has emerged as a potential intermediate biomarker for diagnostic clarification in mental illness. This systematic review examines published studies that used qEEG in youth with psychiatric illness between 1996 and 2017. We conducted a comprehensive database search of CINAHL, PubMed, and Cochrane using the following keywords: "quantitative EEG" and depression (MDD), anxiety, attention-deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD), eating disorder, conduct, substance use, schizophrenia, post-traumatic stress disorder, and panic disorder. Our search yielded 516 titles; 33 met final inclusion criteria, producing a total of 2268 youth aged 4-18. qEEG was most frequently studied as a potential diagnostic tool in pediatric mental illness; few studies assessed treatment response. Studies show higher theta/beta ratio in ADHD vs healthy controls (HC). The most consistent finding in ASD was decreased coherence in ASD vs HC. Studies show MDD has lower temporal coherence and interhemispheric coherence in sleep EEGs than HC. Further research is needed in the areas of mood, anxiety, ASD, and relationship to treatment. It remains unknown if abnormalities in qEEG are nonspecific markers of pediatric psychiatric illness or if they have the potential to differentiate types of psychopathology.

Resting-State Quantitative Electroencephalography Demonstrates Differential Connectivity in Adolescents with Major Depressive Disorder.

Background: Biomarkers for psychiatric disorders in children and adolescents are urgently needed. This cross-sectional pilot study investigated quantitative electroencephalogram (qEEG), a promising intermediate biomarker, in pediatric patients with major depressive disorder (MDD) compared with healthy controls (HCs). We hypothesized that youth with MDD would have increased coherence (connectivity) and absolute alpha power in the frontal cortex compared with HC. Methods: qEEG was obtained in adolescents aged 14-17 years with MDD (n = 25) and age- and gender-matched HCs (n = 14). The primary outcome was overall coherence on qEEG in the four frequency bands (alpha, beta, theta, and delta). Other outcomes included frontal-only coherence, overall and frontal-only qEEG power, and clinician-rated measures of anhedonia and anxiety. Results: Average coherence in the theta band was significantly lower in MDD patients versus HCs, and also lower in frontal cortex among MDD patients. Seven node pairs were significantly different or trending toward significance between MDD and HC; all had lower coherence in MDD patients. Average frontal delta power was significantly higher in MDD versus HCs. Conclusions: Brain connectivity measured by qEEG differs significantly between adolescents with MDD and HCs. Compared with HCs, youth with MDD showed decreased connectivity, yet no differences in power in any frequency bands. In the frontal cortex, youth with MDD showed decreased resting connectivity in the alpha and theta frequency bands. Impaired development of a resting-state brain network (e.g., default mode network) in adolescents with MDD may represent an intermediate phenotype that can be assessed with qEEG.