Clinic-Based Characterization of Adolescents and Young Adults With Migraine: Psychological Functioning, Headache Days, and Disability.

Background and Objectives: This cross-sectional observational study retrospectively examined clinical data collected from adolescents and young adults (AYAs) seeking care in a specialty headache clinic. We characterized participants' headache characteristics and psychological functioning and examined the association between self-reported anxiety and depressive symptoms and headache frequency, severity, and disability. Methods: During their clinic visit, AYAs (M age = 18.36; range = 14-32, 79.5% female) completed an intake questionnaire and reported about their headache characteristics (i.e., frequency, severity, and duration of symptoms in months), mental health history (i.e., previous diagnosis of an anxiety or depressive disorder), and utilization of emergency department (ED) services for migraine. AYAs also completed psychometrically validated screening tools for anxiety and depressive symptoms (i.e., the GAD-7 and PHQ-9). We computed descriptive statistics and examined associations among scores on psychological measures and headache characteristics, including migraine-related disability. We also tested whether individuals with clinically elevated GAD-7 and PHQ-9 scores had higher levels of disability relative to those with fewer/subclinical levels of anxiety and depressive symptoms. Results: Participants (N = 283) reported more than 19 headache days per month on average, with more than 90% describing their average headache intensity as moderate or severe. Nearly half of AYAs reported severe headache-related disability. Approximately one-quarter of AYAs reported a previous diagnosis anxiety or depressive disorder diagnosis, and more than one-third scored above clinical cutoffs on the PHQ-9 and GAD-7. Higher scores on both psychological screening instruments were associated with greater headache frequency. More than 10% of patients endorsed current suicidal ideation; this was not related to headache-related disability. Participants reported a high degree of ED utilization for headache; these rates were unrelated to endorsement of psychological comorbidities. Discussion: In this sample of AYAs, headache characteristics were generally unrelated to scores on measures on psychological functioning. However, the observed rates of clinically elevated anxiety/depressive symptoms and suicidality in this sample of AYAs underscore the importance of screening for psychological comorbidities in neurology clinics that serve this age group, irrespective of self-reported disability. Results also emphasize the need to expand access to behavioral health services for AYAs with headache disorders and the importance of incorporating a biopsychosocial perspective to the transition of health care from pediatrics to adult neurology practice.

Biopsychosocial treatment response among youth with continuous headache: A retrospective, clinic-based study.

BACKGROUND: Youth with continuous (always present) headache are vastly understudied; much remains to be understood regarding treatment response in this population. OBJECTIVE: To describe and explore biopsychosocial factors related to initial clinical outcomes among treatment-seeking youth with continuous headache. METHODS: This retrospective cohort study extracted data of 782 pediatric patients (i.e., aged <18 years) with continuous headache from a large clinical repository. Youth in this study had experienced continuous headache for ≥1 month before presenting to a multidisciplinary headache specialty clinic appointment. Extracted data from this appointment included patients' headache history, clinical diagnoses, and headache-related disability, as well as information about biopsychosocial factors implicated in headache management and/or maintenance (e.g., healthy lifestyle habits, history of feeling anxious or depressed). Additional data regarding patient headache characteristics, disability, and lifestyle habits were extracted from a subset of 529 youth who returned to clinic 4-16 weeks after their initial follow-up visit. After characterizing initial treatment response, exploratory analyses compared youth with the best and worst treatment outcomes on several potentially influential factors. RESULTS: Approximately half of youth (280/526; 53.2%) continued to have continuous headache at follow-up, ~20% of youth (51/526) reported a significant (≥50%) reduction in headache frequency. Improvements in average headache severity (e.g., percentage with severe headaches at initial visit: 45.3% [354/771]; percentage with severe headaches at follow-up visit: 29.8% [156/524]) and headache-related disability were also observed (e.g., percentage severe disability at initial visit: 62.9% [490/779]; percentage severe disability at initial follow-up visit: 34.2% [181/529]). Individuals with the worst headache frequency and disability had a longer history of continuous headache (mean difference estimate = 5.76, p = 0.013) and worse initial disability than the best responders (χ2 [3, 264] = 23.49, p < 0.001). They were also more likely to have new daily persistent headache (χ2 [2, 264] = 12.61, p = 0.002), and were more likely to endorse feeling depressed (χ2 [1, 260] = 11.46, p < 0.001). CONCLUSION: A notable percentage of youth with continuous headache show initial improvements in headache status. Prospective, longitudinal research is needed to rigorously examine factors associated with continuous headache treatment response.

Impact of preventive pill-based treatment on migraine days: A secondary outcome study of the Childhood and Adolescent Migraine Prevention (CHAMP) trial and a comparison of self-report to nosology-derived assessments.

OBJECTIVE: To examine group differences in self-reported migraine days among youth who completed the Childhood and Adolescent Migraine Prevention (CHAMP) trial prior to its closure and explore the relationship between self-reported and "nosology-derived" (i.e., International Classification of Headache Disorders, 3rd edition [ICHD-3]) migraine days. BACKGROUND: The CHAMP trial compared amitriptyline and topiramate to placebo for migraine prevention in youth and proposed to analyze change in migraine days as a secondary outcome. There is considerable variability in the field regarding what constitutes a "migraine day," how this is determined and reported in trials, and how consistent these measures are with diagnostic nosology. METHODS: CHAMP trial completers (N = 175) were randomized to receive amitriptyline (n = 77), topiramate (n = 63), or placebo (n = 35). Participants maintained daily headache diaries where they reported each day with headache and if they considered that headache to be a migraine. For each headache day, participants completed a symptom record and reported about symptoms such as pain location(s) and presence of nausea/vomiting or photophobia and phonophobia. We examined group differences in self-reported migraine days at trial completion (summed from trial weeks 20-24) compared to baseline. We also used an algorithm to determine whether participants' symptom reports met ICHD-3 criteria for migraine without aura, and examined the association between self-reported and "nosology-derived" migraine days. RESULTS: Results showed no significant differences between groups in self-reported migraine days over the course of the trial. Self-reported and "nosology-derived" migraine days during the baseline and treatment phases were strongly associated (r's = 0.73 and 0.83, respectively; p's < 0.001). CONCLUSION: Regardless of treatment, CHAMP trial completers showed clinically important reductions in self-reported migraine days over the course of the trial (about 3.8 days less). The strong association between self-reported and "nosology-derived" migraine days suggests youth with migraine can recognize a day with migraine and reliably report their headache features and symptoms. Greater rigor and transparency in the calculation and reporting of migraine days in trials is needed.

Management of Chronic Migraine in Children and Adolescents: Where are We in 2022?

Migraine is a neurological disorder that affects millions of children and adolescents worldwide. Chronic migraine is a subtype of migraine in which patients experience headaches for more days than not each month, with accompanying symptoms of phonophobia, photophobia, nausea or vomiting for most of these headaches. The burden and impact of chronic migraine in the daily lives of children and adolescents is substantial, requiring a holistic, multidisciplinary, and biopsychosocial approach to conceptualization and treatment. The purpose of this review is to provide a comprehensive "2022" overview of acute and preventive treatments for the management of chronic migraine in youth. We first describe diagnostic criteria for chronic migraine and highlight the state of evidence for acute and preventive treatment in children and adolescents. We then discuss emerging treatments currently receiving rigorous clinical research effort, special considerations for the treatment of chronic migraine in children and adolescents, and avenues for improving existing treatments and expanding access to evidence-based care.

Psychological Interventions for Pediatric Headache Disorders: A 2021 Update on Research Progress and Needs.

PURPOSE OF REVIEW: This review summarizes key findings from recent investigations of psychological interventions for pediatric headache disorders and discusses important avenues for future research. RECENT FINDINGS: Cognitive Behavioral Therapy (CBT) is effective in reducing headache days among youth with chronic headache. There is mixed evidence for the benefit of CBT on reducing disability associated with migraine, suggesting that there is room to optimize CBT by leveraging complementary or alternative psychological interventions, such as Acceptance and Commitment Therapy (ACT) and mindfulness-based approaches. Tailoring CBT may be especially important for youth with more impairing or complex clinical presentations, such as those with continuous headache. Using eHealth and novel study designs to expand access to and dissemination of psychological interventions is promising. Although CBT is the gold standard psychological treatment for youth with migraine, we are only beginning to understand how and why it is effective. Other promising psychological treatments are available, and studies are beginning to examine how CBT can be optimized to fit the unique needs of each patient. Improving access and equitability of care for youth with migraine will require tailoring psychological treatments for patients with varying headache presentations and youth from a variety of cultural, racial, ethnic, and linguistic backgrounds.

Trajectory of treatment response in the child and adolescent migraine prevention (CHAMP) study: A randomized clinical trial.

OBJECTIVE: Identify preventive medication treatment response trajectories among youth participating in the Childhood and Adolescent Migraine Prevention study. METHODS: Data were evaluated from 328 youth (ages 8-17). Childhood and Adolescent Migraine Prevention study participants completed headache diaries during a 28-day baseline period and a 168-day active treatment period during which youth took amitriptyline, topiramate, or placebo. Daily headache occurrence trajectories were established across baseline and active treatment periods using longitudinal hierarchical linear modeling. We tested potential treatment group differences. We also compared final models to trajectory findings from a clinical trial of cognitive behavioral therapy plus amitriptyline for youth with chronic migraine to test for reproducibility. RESULTS: Daily headache occurrence showed stability across baseline. Active treatment models revealed decreases in headache frequency that were most notable early in the trial period. Baseline and active treatment models did not differ by treatment group and replicated trajectory cognitive behavioral therapy plus amitriptyline trial findings. CONCLUSIONS: Replicating headache frequency trajectories across clinical trials provides strong evidence that youth can improve quickly. Given no effect for medication, we need to better understand what drives this clinically meaningful improvement. Results also suggest an expected trajectory of treatment response for use in designing and determining endpoints for future clinical trials.Trial Registration. ClinicalTrials.gov Identifier: NCT01581281.

Multimodal Assessment of Medication Adherence Among Youth With Migraine: An Ancillary Study of the CHAMP Trial.

OBJECTIVE: Examine preventive medication adherence among youth with migraine. METHODS: Adherence (self-report, pill count, and blood serum drug levels) was assessed as an ancillary study that utilized data from 328 CHAMP Study participants (ages 8-17). CHAMP was a multisite trial of preventive medications. Participants completed a prospective headache diary during a six-month active treatment period during which youth took amitriptyline, topiramate, or placebo pill twice daily. Self-reported medication adherence was collected via daily diary. At monthly study visits, pill count measures were captured. At trial month 3 (trial midpoint) and 6 (end of active trial), blood serum drug levels were obtained. Self-report and pill count adherence percentages were calculated for the active trial period, at each monthly study visit, and in the days prior to participants' mid-trial blood draw. Percentages of nonzero drug levels were calculated to assess blood serum drug level data. Adherence measures were compared and assessed in context of several sociodemographic factors. Multiple regression analyses investigated medication adherence as a predictor of headache outcomes. RESULTS: Self-report and pill count adherence rates were high (over 90%) and sustained over the course of the trial period. Serum drug level adherence rates were somewhat lower and decreased significantly (from 84% to 76%) across the trial period [t (198) = 3.23, p = .001]. Adherence measures did not predict headache days at trial end; trial midpoint serum drug levels predicted headache-related disability. CONCLUSIONS: Youth with migraine can demonstrate and sustain relatively high levels of medication adherence over the course of a clinical trial.

Prevalence of Headache Days and Disability 3 Years After Participation in the Childhood and Adolescent Migraine Prevention Medication Trial.

Importance: Migraine is a common neurological disease that often begins in childhood and continues into adulthood; approximately 6 million children and adolescents in the United States cope with migraine, and many frequently experience significant disability and multiple headache days per week. Although pharmacological preventive treatments have been shown to offer some benefit to youth with migraine, additional research is needed to understand whether and how these benefits are sustained. Objective: To survey clinical status of youth with migraine who participated in the 24-week Childhood and Adolescent Migraine Prevention (CHAMP) trial over a 3-year follow-up period. Design, Setting, and Participants: This survey study used internet-based surveys collected from youth ages 8 to 17 years at 3, 6, 12, 18, 24, and 36 months after completion of the CHAMP trial, which randomized participants to amitriptyline, topiramate, or placebo. At the end of the trial, the study drug was stopped, and participants received clinical care of their choice thereafter. The CHAMP trial was conducted between May 2012 and November 2015, and survey follow-up was conducted June 2013 to June 2018. Participants in this survey study were representative of those randomized in the trial. Data were analyzed from March 2020 to April 2021. Exposures: Survey completion. Main Outcomes and Measures: Headache days, disability (assessed using the Pediatric Migraine Disability Scale [PedMIDAS]), and self-report of ongoing use of prescription preventive medication. Results: A total of 205 youth (mean [SD] age, 14.2 [2.3] years; 139 [68%] girls; mean [SD] history of migraine, 5.7 [3.1] years) participated in the survey. Retention of participants was 189 participants (92%) at month 6, 182 participants (88%) at month 12, 163 participants (80%) at month 18, 165 participants (80%) at month 24, and 155 participants (76%) at month 36. Over the course of the 3-year follow-up, participants consistently maintained meaningful reductions in headache days (mean [SD] headache days per 28 days: CHAMP baseline, 11.1 [6.0] days; CHAMP completion, 5.0 [5.7] days; 3-year follow-up, 6.1 [6.1] days) and disability (mean [SD] score: CHAMP baseline, 40.9 [26.4]; CHAMP completion, 17.9 [22.1]; 3-year follow-up, 12.3 [20.0]). At 3 years after completion of the CHAMP trial, headache days were approximately 1.5 per week (changed from about 3 per week at trial baseline) and disability had improved from the moderate range to the low mild range on the PedMIDAS. Longitudinal analyses showed that amitriptyline and topiramate did not explain intercept random effects for either mean rate of headache days per week (amitriptyline: estimate [SE], 0.07 [0.05]; P = .16; topiramate: estimate [SE], 0.04 [0.05]; P = .50) or headache disability PedMIDAS total score (amitriptyline: estimate [SE], 0.25 [0.38]; P = .52; topiramate: estimate [SE], -0.09 [0.39]; P = .82) changes over time. Of 153 participants who reported on prescription drug use at 3 years, only 1 participant (1%) reported using prevention medication, and most participants reported no medication use at most time points. Conclusions and Relevance: These findings suggest that children and adolescents with longer than 5 years history of migraine who participated in the CHAMP trial may sustain positive clinical outcomes over time, even after discontinuing preventive pill-based treatment. This survey study could inform use and discontinuation timing of pharmacological preventive therapies for migraine in youth ages 8 to 17 years. Research is needed to examine mechanisms of treatment improvement and maintenance for preventive therapies, as well as placebo, in the pediatric population.

Clinic-based characterization of continuous headache in children and adolescents: Comparing youth with chronic migraine to those with new daily persistent headache.

OBJECTIVE: To describe the headache characteristics and functional disability of a large sample of treatment-seeking youth with continuous headache and compare these factors across diagnostic subgroups of chronic migraine and new daily persistent headache. METHODS: This retrospective study utilized clinical information (e.g. diagnosis, headache features, medication overuse, functional disability) from a large data repository of patients initially presenting to a multidisciplinary headache center with continuous headache. Patient inclusion in subgroup analyses for chronic migraine and new daily persistent headache was based on clinician diagnosis using International Classification of Headache Disorders (ICHD) criteria. RESULTS: The current sample included 1170 youth (mean age = 13.95 years, 78.8% female) with continuous headache. The overwhelming majority of these youth had headaches with migrainous features, regardless of their clinical diagnosis. Youth with chronic migraine reported a longer history of continuous headache symptoms and earlier age of headache onset than youth with new daily persistent headache and were more likely to have medication overuse. Most youth with continuous headache experienced severe migraine-related functional disability, regardless of diagnostic subgroup. CONCLUSIONS: Overall, youth with continuous chronic migraine and new daily persistent headache did not have clinically meaningful differences in headache features and associated disability. Findings suggest that chronic migraine and new daily persistent headache may be variants of the same underlying disease.

Early-Life Somatic Complaints: Longitudinal Associations with Maternal and Child Psychopathology.

OBJECTIVE: Somatic complaints, often associated with concurrent and future internalizing symptoms and disorders in adult samples, were examined longitudinally from preschool to school age in a sample of children at an increased familial risk for psychopathology. The behavioral correlates and sex differences of somatic complaints and the persistence of these complaints across early childhood were examined. METHOD: A longitudinal sample of 185 mothers completed a laboratory visit when children were preschool aged and an online follow-up when children were school aged. Mothers were assessed for psychopathology, and mothers and secondary caregivers reported on children's somatic complaints, anxiety, and depression at both time points. RESULTS: A high rate of child's somatic complaints was noted in this sample, with similar rates in males and females. Regression analyses revealed that somatic complaints at preschool predicted somatic complaints, anxiety, and depression at school age, and sex did not moderate these relationships. Overall, maternal psychopathology predicted somatic complaints, but findings were inconsistent across reporters, time points, and types of maternal psychopathology. Evidence for maternal reporting bias was mixed. CONCLUSION: The association between preschool-age somatic complaints and school-age internalizing symptoms suggests the potential utility of early detection and treatment of somatic complaints, particularly for young children at an increased familial risk for developing internalizing disorders. Pediatric primary care is an ideal setting for these early intervention efforts.

Decreased sleep duration is associated with increased fMRI responses to emotional faces in children.

In adults and children, sleep loss is associated with affective dysregulation and increased responsivity to negative stimuli. Adult functional neuroimaging (fMRI) studies have demonstrated associations between restricted sleep and neural alterations in the amygdala and reward circuitry when viewing emotional picture and face stimuli. Despite this, few studies have examined the associations between short sleep duration and emotional responsivity in typically developing children, and no studies have investigated this relationship using fMRI. The current study examined the relationship between sleep duration and fMRI activation to emotional facial expressions in 15 male children (ages 7-11 years). During fMRI scanning, subjects viewed and made perceptual judgments regarding negative, neutral, and positive emotional faces. Maternal reported child sleep duration was negatively associated with (a) activation in the bilateral amygdala, left insula, and left temporal pole activation when viewing negative (i.e., fearful, disgust) vs. neutral faces, (b) right orbitofrontal and bilateral prefrontal activation when viewing disgust vs. neutral faces, and (c) bilateral orbitofrontal, right anterior cingulate, and left amygdala activation when viewing happy vs. neutral faces. Consistent with our prediction, we also noted that emotion-dependent functional connectivity between the bilateral amygdala and prefrontal cortex, cingulate, fusiform, and occipital cortex was positively associated with sleep duration. Paralleling similar studies in adults, these findings collectively suggest that decreased sleep duration in school-aged children may contribute to enhanced reactivity of brain regions involved in emotion and reward processing, as well as decreased emotion-dependent functional connectivity between the amygdala and brain regions associated with emotion regulation.

Prospective associations between chronic youth sleep problems and young adult health.

OBJECTIVES: The current study investigated prospective associations between youth sleep problems across childhood and adolescence, as well as the relationship between chronic youth sleep problems and young adult health. Exploratory analyses investigated this sleep-health relationship in the context of several established risk factors, including youth depression and environmental stress. DESIGN: This project is an extension of the Mater-University Study of Pregnancy, a longitudinal study that followed more than 7000 children across early development. SETTING: Brisbane, Australia. PARTICIPANTS: Seven hundred ten mother-child dyads assessed from birth to age 20. MEASUREMENTS: We used maternal report measures to assess the persistence of youth sleep problems. We used structural equation modeling to explore the relationship between chronic maternal-reported youth sleep problems and subjective reports of young adult health quality and to assess whether associations remained when other potential health risks were included in the model. RESULTS: Path analyses revealed that sleep problems in early childhood predicted sleep problems in middle adolescence, which predicted sleep problems at age 20. Structural equation models showed that chronic youth sleep problems predicted youth health quality at age 20 (ß = .263, P < .001) over and above the effects of early adversity, chronic childhood illness, maternal depression, lifetime youth depression, and chronic youth stress. CONCLUSIONS: Chronic sleep problems can emerge in childhood and may contribute to negative health outcomes in young adulthood. Chronic youth sleep problems remain a significant predictor of poor health when tested against other known health risk factors, suggesting that sleep may be an important health intervention target.

Family functioning deficits in bipolar disorder and ADHD in youth.

BACKGROUND: Rates of diagnosis and treatment for bipolar disorder (BD) in youth continue to rise. Researchers and clinicians experience difficulty differentiating between BD in youth and other conditions that are commonly comorbid or share similar clinical features with BD, especially attention-deficit/hyperactivity disorder (ADHD). Comparative studies of the phenomenology and psychosocial correlates of these conditions help to address this. Family functioning is an important topic for both BD and ADHD since both are associated with numerous family-related deficits. One previous study suggested that manic/hypomanic youths'family functioning differed from ADHD and typically developing control (TDC) groups. However, many family functioning studies with BD and ADHD youth have methodological limitations or fail to use comprehensive, validated measures. METHODS: This investigation used adolescent report on the Family Assessment Device (FAD), based on the McMaster Model of family functioning. Youth were recruited in BD (n=30), ADHD (n=36), and TDC (n=41) groups. RESULTS: Groups were similar on most demographic variables, but The TDC group scored somewhat higher than the others on IQ and socioeconomic status. FAD results indicated that BD and ADHD groups scored worse than TDC on the General Functioning and Roles scales of the FAD. In addition, the BD group showed impairment on the Problem Solving scale relative to TDC. LIMITATIONS: sample size, lack of parent report, ADHD comorbidity in BD group. CONCLUSIONS: Family functioning deficits distinguish both clinical groups from TDC, and problem-solving dysfunction may be specific to BD. These findings may apply to treatment models for both conditions.

Emotional face identification in youths with primary bipolar disorder or primary attention-deficit/hyperactivity disorder.

OBJECTIVE: Bipolar disorder (BD) and attention-deficit/hyperactivity disorder (ADHD) are often comorbid or confounded; therefore, we evaluated emotional face identification to better understand brain/behavior interactions in children and adolescents with either primary BD, primary ADHD, or typically developing controls (TDC). METHOD: Participants included individuals 7 to 17 years of age (overall sample mean age 12.40 ± 3.01 years), with "narrow-phenotype" pediatric BD (n = 30) or ADHD (n = 38), or typically developing controls (TDC) with no psychiatric disorders themselves or in their first-degree relatives (n = 41). In the BD group, comorbid diagnoses were allowed; however, youth in the ADHD group were excluded for comorbid mood or anxiety disorders. Patient groups were not excluded for psychotropic medication use. Emotional face identification was assessed using the computerized Diagnostic Analysis of Non-Verbal Accuracy (DANVA). RESULTS: Participants with BD made significantly more identification errors on child happy faces than either TDCs (p = .03) or participants with ADHD (p = .01). Furthermore, youth with BD (0.33 ± 0.55) were more likely than youth with ADHD (0.11 ± 0.31) to make errors on low-intensity child happy faces (p = .05) but not high-intensity happy faces (p = NS). Participants with BD and ADHD made significantly more total errors in child face labeling than did TDCs, although participants with BD and ADHD did not differ from one another. CONCLUSION: Our data suggest that youths with BD have specific alterations in emotional face identification of happy faces, an important finding that supports theories that response to positively valenced emotional stimuli may be especially salient in BD. Clinical trial registration information-Brain Imaging and Computer Games in Children With Either Bipolar Disorder, ADHD, Anxiety or Healthy Controls (BBPP); http://clinicaltrials.gov/; NCT01570426.

Developmental meta-analysis of the functional neural correlates of autism spectrum disorders.

OBJECTIVE: There is a pressing need to elucidate the brain-behavior interactions underlying autism spectrum disorders (ASD) given the marked rise in ASD diagnosis over the past decade. Functional magnetic resonance imaging (fMRI) has begun to address this need, but few fMRI studies have evaluated age-related changes in ASD. Therefore, we conducted a developmental analysis of activation likelihood estimation (ALE) meta-analysis to compare child versus adult ASD fMRI studies. We hypothesized that children and adolescents with ASD (<18 years old) would rely less on prefrontal cortex structures than adults (≥18 years old). METHOD: PubMed and PsycInfo literature searches were conducted to identify task-dependent fMRI studies of children or adults with ASD. Then recent GingerALE software improvements were leveraged to perform direct comparisons of child (n = 18) versus adult (n = 24) studies. RESULTS: ALE meta-analyses of social tasks showed that children and adolescents with ASD versus adults had significantly greater hyperactivation in the left post-central gyrus, and greater hypoactivation in the right hippocampus and right superior temporal gyrus. ALE meta-analyses of nonsocial tasks showed that children with ASD versus adults had significantly greater hyperactivation in the right insula and left cingulate gyrus, and hypoactivation in the right middle frontal gyrus. CONCLUSION: Our data suggest that the neural alterations associated with ASD are not static, occurring only in early childhood. Instead, children with ASD have altered neural activity compared to adults during both social and nonsocial tasks, especially in fronto-temporal structures. Longitudinal neuroimaging studies are required to examine these changes prospectively, as potential targets for brain-based treatments for ASD.

Translational neuroscience in pediatric bipolar disorder.

While controversial and often confounded with other forms of psychopathology, recent studies have shown that bipolar disorder (BD) is on the rise in children and adolescents. Research has made important strides in advancing our understanding of the phenomenology, neural underpinnings and treatment outcomes for BD youths. However, there is an increasing need to unite these domains to identify potential neural effects and predictors of treatment outcome. Pavuluri et al. have conducted such a study, evaluating the neural effects of divalproex or risperidone for pediatric BD. The future is likely to bring more of such studies, potentially resulting in a biomarker augmented approach to the diagnosis and treatment of pediatric BD.