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Objective Activation changes at the interface of affective and cognitive systems are examined over a 3 year period in pediatric bipolar disorder (PBD). Methods Thirteen participants with PBD and 10 healthy controls (HC) matched on demographics and IQ were scanned at baseline, at 16 weeks, and after 3 years. All patients received pharmacotherapy based on a medication algorithm. A pediatric affective color matching paradigm was used to probe cognitive processing under emotional challenge. Results At baseline, in response to emotional vs. neutral words, patients with PBD showed greater activation than HC in the right dorsal lateral prefrontal cortex (DLPFC) and amygdala, ventral lateral prefrontal cortex (VLPFC), bilateral anterior cingulate cortex (ACC), and ventral striatum. Increased activation in DLPFC in the PBD group normalized by 16 weeks. By 3 years, normalization was observed in VLPFC, ACC, amygdala, and striatum. Limitations Small sample size renders the present findings preliminary. Conclusions Greater activation in fronto-striatal and fronto-limbic circuits were observed in unmedicated patients with PBD. Present findings suggest the possibility that DLPFC is most malleable to pharmacological intervention with systematic pharmacotherapy leading to immediate response, which extended to amygdalostriatal and ventral cortical regions at 3 years. The seminal observation from this study is the prolonged length of recovery time in the normalization of subcortical activity along with their interfacing cortical regions. Findings from this proof of concept study need to be replicated in a larger sample.

Background The development of valid parent-report measures of symptom change in pediatric bipolar disorder (PBD) is imperative to evaluate the effectiveness of different treatment approaches; yet, few studies have tested the sensitivity of symptom measures. The current study evaluated the sensitivity of the Child Mania Rating Scale (CMRS-P) to detect symptom change over time in a treatment study for PBD. Methods Data on symptom change were drawn from a prospective six-week, double-blind, placebo-controlled, randomized outpatient medication treatment trial of risperidone versus divalproex. The sample included 66 children with Bipolar type I disorder. Measures were administered every week for six weeks of treatment. Results The CMRS-P demonstrated statistically (p ≤ .05) and clinically significant change in symptom report from pre to post-test. Growth curve modeling indicated that the CMRS-P demonstrated overall similarity to the YMRS in the magnitude and trajectory of change over time. Finally, results indicate that the CMRS-P is able to detect response rates with moderate levels of agreement with other measures. Limitations Limitations of this study include a relatively small sample size and uncertain generalizability beyond treatment trials. Conclusions The CMRS-P is short, easy to administer, and represents parent's report of symptoms, all strengths which make it a compelling treatment outcome tool. This preliminary evidence of its validity as a treatment outcome measure makes it applicable in other research settings and suggests its potential use in clinical settings.

Background: There is under-recognition or misdiagnosis of pediatric bipolar disorder with psychotic features. It is of major public health importance to recognize psychosis in bipolar disorder. Method: Original research on phenomenological description of psychosis and external validators including family history, longitudinal course and treatment effects are systematically reviewed. Age differences, sampling, and interview methods of the studies on pediatric bipolar disorder that reported psychotic features are compared. Critical differentiating features between pediatric bipolar disorder and pediatric schizophrenia are summarized given the presence of overlapping psychotic features. Results: Prevalence of psychotic features in pediatric bipolar disorder ranged from 16 to 87.5% based on age and methodological differences. The most common psychotic features are mood congruent delusions, mainly grandiose delusions. Psychotic features appear in the context of affective symptoms in pediatric bipolar disorder as opposed to schizophrenia where psychotic symptoms are independent of them. Family history of affective psychosis aggregated in probands with bipolar disorder. Limitations: There is discrepancy in clinical appraisal of what constitutes psychosis and pediatric bipolar disorder, apart from the differences in methodology and nature of the samples. Conclusion: Clinicians must be vigilant in identifying psychosis in pediatric bipolar disorder, especially when there is a positive family history of psychosis.

Background: In response to emotional faces, patients with adolescent bipolar disorder (ABD) exhibit increased neural activity in subcortical emotional processing regions (e.g., amygdala, ventral striatum) and variable prefrontal activity. We extend previous research by identifying cortical and subcortical regions showing altered hemodynamic response shapes in ABD relative to healthy controls (HC). Methods: ABD (N¼ 65) and matched HC (N ¼ 79) completed a slow event-related affective hemodynamic probe task that required indicating the gender of fearful and neutral faces. An informed basis set in SPM8 evaluated shape variations of the hemodynamic responses to these faces. Results: Patients with ABD showed higher activity for fearful relative to neutral faces in the amygdala and prefrontal cortex and a delayed hemodynamic response to fearful faces in dorsolateral and ventrolateral prefrontal cortices (PFC), as well as bilateral amygdala and caudate. Furthermore, the ABD group, relative to HC, showed a prolonged response to fearful faces in right dorsolateral PFC. Clinical measures of mania and depression severity correlated with increased processing delays in the amygdala and striatum. Limitations: By design, the task contained fewer, more widely-spaced stimuli, possibly reducing its power to detect group differences. The use of fearful faces makes comparisons with prior literature in ABD somewhat more difficult. Conclusions: The ABD group engaged in enhanced neural processing of the fearful faces which was associated with increasingly severe manic/mixed mood states. These exploratory findings could help elucidate a ‘‘biosignature’’ of emotion–attention interactions in ABD and present a potential target for reversal with medication treatment.

Pediatric Bipolar Disorder (PBD) is a debilitating condition associated with impairment in many domains. Social functioning is one of the disorder's most notable areas of impairment and this deficit may be in part due to difficulties recognizing affect in others.In the present study, medication naïve youth with PBD were compared to age-matched healthy controls on their ability to (a) distinguish between categorical emotions, such as happiness, anger, and sadness on the Emotion Recognition Test (ER-40) and (b) differentiate between levels of emotional intensity on an adapted version of the Penn Emotional Acuity Task (Chicago-PEAT).Results indicated that PBD youth misidentified sad, fearful, and neutral faces more often than controls, and PBD girls mislabeled 'very angry' faces more often than healthy girls. A mediation analyses indicated that these diagnostic group differences on emotion recognition were significantly mediated by irritability.The Chicago-PEAT only examined variations in emotional intensity for the emotions happy and anger. Additionally, all results are correlational; therefore causal inferences cannot be made.Supporting previous literature, the present findings highlight the importance of emotion recognition deficits in PBD individuals. Additionally, the irritability associated with PBD may be an important mechanism of this deficit and may thus represent an important target for treatment.

Objective: This prospective 6-month open trial examined the safety and efficacy of two combination therapies for manic or mixed episodes of pediatric bipolar disorder: (1) divalproex sodium plus risperidone (DVPX+Risp), or (2) lithium plus risperidone (Li+Risp). Methods: Thirty-seven (37) subjects aged 5 and 18 (age=12.1±3.5 years) with DSM IV current mixed or manic episode and Young Mania Rating Scale (YMRS) score >20 were sequentially assigned to either DVPX+Risp or Li+Risp in a 6-month, prospective open-label trial. Outcome measures included the YMRS, Clinical Global Impression Scale for Bipolar Disorder (CGI-BP), Child Depression Rating Scale-Revised (CDRS-R) as well as measures of safety and tolerability. Results: Effect sizes (Cohen's d) based on change of YMRS scores from baseline were 4.36 for DVPX+Risp and 2.82 for Li+Risp. Response rates (≥50% change from baseline YMRS score at the end of study) were 80% for DVPX+Risp and 82.4% for Li+Risp. Both combination treatments were well tolerated. Significant improvements (p

This paper explores the unifying aetiopathology between disorders of the immune system and the CNS, using a case example. An adolescent had a 2-year history of chronic-active Epstein-Barr virus infection and recurrent acute pancreatitis that resolved following a course of immunotherapy. Subsequently, she redeveloped acute symptoms of infectious mononucleosis and pancreatitis, along with manic depression, and then made a complete recovery with combination of lithium carbonate and electroconvulsive therapy. On follow-up, lithium carbonate effectively controlled the previous neuroimmune dysfunction.