Pediatric Bipolar Disorder Research Articles

Alterations of subcortical structure volume in pediatric bipolar disorder patients with manic or depressive first-episode

BackgroundBipolar disorder may begin as depression or mania, which can affect the treatment and prognosis. The physiological and pathological differences among pediatric bipolar disorder (PBD) patients with different onset symptoms are not clear. The aims of the present study were to investigate subcortical structural alterations in PBD patients with first-episode depressive (PBD-FED) and first-episode manic (PBD-FEM).MethodsA total of 59 individuals including 28 PBD-FED, 13 PBD-FEM, and 18 healthy controls (HCs) underwent high-resolution structural magnetic resonance scans. FreeSurfer 7.2 was used to detect changes in subcortical volumes. Simultaneously, thalamic, hippocampal, and amygdala subregion volumes were compared between the three groups.ResultsAnalysis of covariance controlling for age, sex, education, and estimated intracranial volume shows third and fourth ventricle enlargement in patients with PBD. Compared with the PBD-FED and HCs, the PBD-FEM group had reduced gray matter volume in the left thalamus, bilateral hippocampus, and right amygdala. Subsequent subregion analyses showed right cortico-amygdaloid transient, bilateral accessory-basal nucleus, left hippocampal tail, right hippocampal head, and body volume reduction in the PBD-FEM group.ConclusionsThe present findings provided evidence of decreased subcortical structure in PBD-FEM patients, which might present its trait feature.

Discriminant diagnostic validity of paediatric bipolar disorder screening tests: A systematic review and meta-analysis.

Bipolar disorders (BD) are among the most significantly impairing of childhood and adolescent psychiatric disorders. Although BD symptoms may begin in adolescence, they are frequently not diagnosed until adulthood, and accordingly BD scales could aid diagnostic assessment in paediatric populations. This review aims to synthesis the evidence for the accuracy of BD symptom index tests for discriminating BD from non-BD (other diagnoses or healthy controls) in paediatric population. Additionally, several theoretically relevant moderators of diagnostic accuracy were evaluated. A systematic search across three databases were conducted from 1980 to 2022, augmented by grey literature database searches, citation chaining and contacting authors. Data from eligible studies were synthesized using meta-analysis. A multilevel model was fitted to account for nested effect sizes, with 31 potential moderators examined in univariate and multivariate models. Twenty-Eight studies were eligible, yielding 115 effect sizes for analysis. Meta-analytic modelling indicated BD symptom index tests have a high diagnostic accuracy (g = 1.300; 95% CI: 0.982 - 1.619; p < .001) in paediatric population. Accuracy was relative to the type of comparison group, index test content, index test informant and index test's scale or subscale. Screening tests based on mania content, caregiver report and non-healthy comparison groups have clinical utility in identifying paediatric BD. Other informant-and-content combination may not accurately identify paediatric BD. Unlike healthy controls, tests derived from studies using non-healthy comparison groups, represent BD symptom non-specificity and BD symptom overlap with other disorders, providing external validity and clinical utility.

Risk of Pediatric Bipolar Disorder After General Anesthesia in Infants and Toddlers: A Propensity Score-Matched Population-Based Cohort Study.

The potential role of anesthesia as an independent risk factor for childhood bipolar disorder (BD) remains unclear. To address this, we conducted a population-based cohort study employing propensity score matching to compare BD incidence between pediatric patients undergoing surgery with and without general anesthesia. Our study included patients aged 0-3 years who received at least 1 episode of general anesthesia and were hospitalized for over 1 day in Taiwan between January 2004 and December 2014. They were matched 1:1 with a population not receiving general anesthesia to assess pediatric BD incidence. The study cohort comprised 15 070 patients, equally distributed between the general anesthesia and nongeneral anesthesia groups (7535 each). Multivariate Cox regression analysis revealed adjusted hazard ratios (aHRs; 95% CIs) for pediatric BD in the general anesthesia group as 1.26 (1.04-1.54; P = .021) compared to the nongeneral anesthesia group. Moreover, the incidence rate ratio (95% CI) for the general anesthesia group was 1.26 (1.03-1.53) compared to the nongeneral anesthesia group. Early childhood exposure to general anesthesia is significantly associated with an increased risk of pediatric BD. This expands understanding of pediatric BD's complex development, informing preventive strategies, and enhancing mental health outcomes for vulnerable young patients and global pediatric healthcare.

Structural and functional disruption of subcortical limbic structures related with executive function in pediatric bipolar disorder

BackgroundImpaired cognition has been demonstrated in pediatric bipolar disorder (PBD). The subcortical limbic structures play a key role in PBD. However, alternations of anatomical and functional characteristics of subcortical limbic structures and their relationship with neurocognition of PBD remain unclear. MethodsThirty-six PBD type I (PBD-I) (15.36 ± 0.32 years old), twenty PBD type II (PBD-II) (14.80 ± 0.32 years old) and nineteen age-gender matched healthy controls (HCs) (14.16 ± 0.36 years old) were enlisted. Primarily, the volumes of the subcortical limbic structures were obtained and differences in the volumes were evaluated. Then, these structures served as seeds of regions of interest to calculate the voxel-wised functional connectivity (FC). After that, correlation analysis was completed between volumes and FC of brain regions showing significant differences and neuropsychological tests. ResultsCompared to HCs, both PBD-I and PBD-II patients showed a decrease in the Stroop color word test (SCWT) and digit span backward test scores. Compared with HCs, PBD-II patients exhibited a significantly increased volume of right septal nuclei, and PBD-I patients presented increased FC of right nucleus accumbens and bilateral pallidum, of right basal forebrain with right putamen and left pallidum. Both the significantly altered volumes and FC were negatively correlated with SCWT scores. SignificanceThe study revealed the role of subcortical limbic structural and functional abnormalities on cognitive impairments in PBD patients. These may have far-reaching significance for the etiology of PBD and provide neuroimaging clues for the differential diagnosis of PBD subtypes. ConclusionsDistinctive features of neural structure and function in PBD subtypes may contribute to better comprehending the potential mechanisms of PBD.

Evidence-based Psychopharmacological Treatments for Pediatric Bipolar Disorder

Evidence-based Psychopharmacological Treatments for Pediatric Bipolar Disorder

Evaluation of Neurocognitive Functions of Children and Adolescents Diagnosed with Pediatric Bipolar Disorder and Disruptive Mood Dysregulation and at High Risk for Bipolar Disorder

IntroductionPediatric Bipolar Disorder (BPD) is a chronic psychiatric disorder that alters normal and psychological development processes among patients. Although cognitive deficits in BPD have identified in recent studies, little is known about the developmental trajectory of these deficits. DMDD is a newly defined diagnosis included in the DSM-V. Since it added a new dimension to the clinical spectrum but few studies conducted on DMDD, there are some conflicting discussions in the literature about how to distinguish this disorder from other childhood psychiatric disorders and how to treat it.ObjectivesThe aim of this study was to determine the phenomenological and neuropsychological differences between children and adolescents with a diagnosis of BPD (Pediatric Bipolar Disorder), DMDD (Disruptive Mood Dysregulation Disorder), and children and adolescents who are genetically at high risk for Bipolar Disorder (BD), and healthy controls (HCs) who do not have any psychiatric diagnosis, to investigate endophenotypes that may be predictive for BD.MethodsOur study sample consists of four groups, the BPD group (n=30), the Risk group (n=25), the DMDD group (n=36), and the Healthy Control group (n=29). All participants were evaluated by the “Kiddie Schedule for Affective Disorders and Schizophrenia for School-Age Children—Now and Lifetime Pattern (K-SADS-PL)”. “Young Mania Rating Scale/Parent Form (YMRS-ABF), Conner’s Parent Rating Scale (CPRS-48), Child and Adolescent Behavior Rating Scale (CBCL)” scales were filled by parents, and “Child Depression Inventory (CDI), Youth Self-Report Form for 11-18 Years Olds (YSR)” scales were filled by children and adolescents. Neurocognitive test battery was applied to each participant: Continuous Performance Test (CPT), Wisconsin Card Sorting Test (WCST), Stroop Color and Word Test (SCWT), Trait Making Test A and B sections (TMT-A/B), California Verbal Learning Test-Child version (CVLT-C).ResultsWhile it was determined that the cases in the BPD and DMDD groups performed significantly worse in CPT, SCWT, CVLT-C, TMT A/B tests compared to healthy controls, it was found that the subjects in the Risk group performed worse at the CPT test than healthy controls. In addition, the cases in the BPD, Risk and DMDD groups reported more clinical and behavioral problems than the healthy controls.ConclusionsThere is a significant deterioration in the areas of continuous attention, processing speed, cognitive flexibility, response prevention, verbal memory and working memory in the BPD and DMDD groups, and in the continuous attention area in the Risk group compared to healthy controls. Prospective follow-up and imaging studies using larger samples and a larger neurocognitive test battery in the future will better reveal the neuropsychological characteristics of the BPD, Risk and DMDD groups.Disclosure of InterestNone Declared

In Memoriam: Professor Joseph Biederman’s Contributions to Child and Adolescent Psychiatry

Objective: To provide an overview of Joe Biederman’s contributions to child and adolescent psychiatry. Method: Nine colleagues described his contributions to: psychopharmacology, comorbidity and genetics, pediatric bipolar disorder, autism spectrum disorders, Tourette’s and tic disorders, clinical and neuro biomarkers for pediatric mood disorders, executive functioning, and adult ADHD. Results: Joe Biederman left us with many concrete indicators of his contributions to child and adolescent psychiatry. He set up the world’s first pediatric psychopharmacology clinic and clinical research program in child adolescent psychiatry. As a young faculty member he began a research program that led to many awards and eventual promotion to full professor at Harvard Medical School. He was for many years the most highly cited researcher in ADHD. He achieved this while maintaining a full clinical load and was widely respected for his clinical acumen. Conclusion: The world is a better place because Joe Biederman was here.

A Systematic Review of Misdiagnosis of Pediatric Bipolar Disorder: Assessments and Recommendations.

Bipolar disorders (BP) are a class of psychiatric disorders with a complex symptom presentation. This systematic review aims to summarize literature pertaining to the misdiagnosis of pediatric BP using the DSM-IV and DSM-5 criteria, while emphasizing the negative impact that untreated BP has on life outcomes. This paper also attempts to outline and summarize available recommendations which may aid in improving diagnostic accuracy of pediatric BP. Scholars Portal Journals, PsychINFO, and MEDLINE databases were used to search articles until March 21, 2023. Inclusion criteria limited this review to articles published between 1995 and 2022 using a pediatric (age < 18) sample. Exclusion criteria omitted articles containing samples with self-reported diagnoses. A total of 15 articles are included in this review; study results were synthesized using a narrative summary. Youth with BP are most frequently misdiagnosed with attention-deficit hyperactive disorder (ADHD), schizophrenia, and major depressive disorder (MDD). Misdiagnosis can lead to inappropriate intervention plans and a delay in proper treatment, negatively impacting a child's quality of life by contributing to social, occupational, and economic adversity. Finally, this review addresses the need for future quantitative research on the implications of false negative diagnoses of pediatric BP.

Study on the correlation between suicidal ideation and ABI3BP gene、DPYSL2 gene methylation in pediatric bipolar disorder with depressive episode

Patients with bipolar disorder have a higher risk of suicide than the general population. This study aimed to explore the correlation between suicide and gene methylation, as screened by genome-wide scanning, in children and adolescents with bipolar disorder. A total of 45 children and adolescents with bipolar disorder were divided into a suicidal ideation group (n = 41), a non-suicidal ideation group (n = 4), a low-risk group (n = 12), and a middle-to-high-risk group (n = 33). A pre-experiment was conducted on the suicidal ideation (n = 6) and non-suicidal ideation groups (n = 4). Blood samples were scanned using an Illumina HD 850K microarray, and methylation levels were analysed. Differential methylation sites among the sample groups were screened from the original data, and genes related to suicide were identified. Methylation of the ABI3BP and DPYSL2 genes was detected by pyrophosphate sequencing and statistically analysed. There was a significant difference in age between the low- and middle-risk groups. The results of GO analysis for the suicidal ideation and non-suicidal ideation groups showed that the differential methylation sites were mainly involved in the interferon-γ-mediated signalling pathway, with the main signalling pathways being the inflammatory bowel disease (IBD) pathway and type 1 diabetes mellitus (T1DM) pathway. There were significant differences in the methylation of ABI3BP, HLA-DQB1, HLA-DRB1, AUTS2, SP3, NINJ2, DPYSL2, and other genes between the suicidal and non-suicidal ideation groups. There was also a statistically significant difference in the gene methylation levels between the two groups. However, there was no significant difference in the degree of methylation of the ABI3BP and DPYSL2 genes between the low- and middle-to-high-risk groups. These results suggest that suicidal ideation is correlated with the methylation levels of differentially methylated genes in children with bipolar disorder. However, the severity of suicide risk in paediatric patients with bipolar disorder may not be correlated with the degree of methylation of the ABI3BP and DPYSL2 genes. Therefore, further validation was required.

Shared and Distinct Neurobiological Bases of Bipolar Disorder and Attention-Deficit/Hyperactivity Disorder in Children and Adolescents: A Comparative Meta-Analysis of Structural Abnormalities

Pediatric bipolar disorder (PBD) and attention-deficit/hyperactivity disorder (ADHD) frequently co-occur and share dysfunctions in affective and cognitive domains. As the neural substrates underlying their overlapping and dissociable symptomatology have not been well delineated, a meta-analysis of whole-brain voxel-based morphometry studies in PBD and ADHD was conducted. A systematic literature search was performed in PubMed, Web of Science, and Embase. The seed-based d mapping toolbox was used to identify altered clusters of PBD or ADHD and obtain their conjunctive and comparative abnormalities. Suprathreshold patterns were subjected to large-scale network analysis to identify affected brain networks. The search revealed 10 PBD studies (268 patients) and 32 ADHD studies (1,333 patients). Decreased gray matter volumes in the right insula and anterior cingulate cortex relative to typically developing individuals were conjunctive in PBD and ADHD. Reduced volumes in the right inferior frontal gyrus, left orbitofrontal cortex, and hippocampus were more substantial in PBD, while decreased volumes in the left precentral gyrus, left inferior frontal gyrus, and right superior frontal gyrus were more pronounced in ADHD. Neurodevelopmental effects modulated patterns of the left hippocampus in PBD and those of the left inferior frontal gyrus in ADHD. These findings suggest that PBD and ADHD are characterized by both common and distinct patterns of gray matter volume alterations. Their overlapping abnormalities may represent a transdiagnostic problem of attention and emotion regulation shared by PBD and ADHD, whereas the disorder-differentiating substrates may contribute to the relative differences in cognitive and affective features that define the 2 disorders. Pediatric bipolar disorder (BD) and attention-deficit/hyperactivity disorder (ADHD) frequently co-occur, with overlapping changes in emotional and cognitive functioning. This meta-analysis summarizes findings from 10 articles on BD and 32 articles on ADHD to identify similarities and differences in brain structure between youth with BD and youth with ADHD. The authors found that both disorders share decreased gray matter volumes in the right insula and anterior cingulate cortex, which play important roles in emotion processing and attention, respectively. Youth with BD had decreased gray matter volume in the right inferior frontal gyrus, left orbitofrontal gyrus, and left hippocampus, while youth with ADHD had decreased volumes in the left precentral gyrus, left inferior frontal gyrus, and right superior frontal gyrus. Structural Brain Abnormalities of Attention-Deficit/Hyperactivity Disorder and Bipolar Disorder in Children/Adolescents: An Overlapping Meta-analysis; https://osf.io; trg4m.

Distinct functional patterns in child and adolescent bipolar and unipolar depression during emotional processing.

Accumulating evidence from functional magnetic resonance imaging studies supported brain dysfunction during emotional processing in bipolar disorder (BD) and major depressive disorder (MDD). However, child and adolescent BD and MDD could display different activation patterns, which have not been fully understood. This study aimed to investigate common and distinct activation patterns of pediatric BD (PBD) and MDD (p-MDD) during emotion processing using meta-analytic approaches. Literature search identified 25 studies, contrasting 252 PBD patients, and 253 healthy controls (HCs) as well as 311 p-MDD patients and 263 HCs. A total of nine meta-analyses were conducted pulling PBD and p-MDD experiments together and separately. The results revealed that PBD and p-MDD showed distinct patterns during negative processing. PBD patients exhibited activity changes in bilateral precuneus, left inferior parietal gyrus, left angular gyrus, and right posterior cingulate cortex while p-MDD patients showed functional disruptions in the left rectus, left triangular part of the inferior frontal gyrus, left orbital frontal cortex, left insula, and left putamen. In conclusion, the activity changes in PBD patients were mainly in regions correlated with emotion perception while the dysfunction among p-MDD patients was in the fronto-limbic circuit and reward-related regions in charge of emotion appraisal and regulation.

Increased regional Hurst exponent reflects response inhibition related neural complexity alterations in pediatric bipolar disorder patients during an emotional Go-Nogo task.

Fractal patterns have been shown to change in resting- and task-state blood oxygen level-dependent signals in bipolar disorder patients. However, fractal characteristics of brain blood oxygen level-dependent signals when responding to external emotional stimuli in pediatric bipolar disorder remain unclear. Blood oxygen level-dependent signals of 20 PBD-I patients and 17 age- and sex-matched healthy controls were extracted while performing an emotional Go-Nogo task. Neural responses relevant to the task and Hurst exponent of the blood oxygen level-dependent signals were assessed. Correlations between clinical indices and Hurst exponent were estimated. Significantly increased activations were found in regions covering the frontal lobe, parietal lobe, temporal lobe, insula, and subcortical nuclei in PBD-I patients compared to healthy controls in contrast of emotional versus neutral distractors. PBD-I patients exhibited higher Hurst exponent in regions that involved in action control, such as superior frontal gyrus, inferior frontal gyrus, inferior temporal gyrus, and insula, with Hurst exponent of frontal orbital gyrus correlated with onset age. The present study exhibited overactivation, increased self-similarity and decreased complexity in cortical regions during emotional Go-Nogo task in patients relative to healthy controls, which provides evidence of an altered emotional modulation of cognitive control in pediatric bipolar disorder patients. Hurst exponent may be a fractal biomarker of neural activity in pediatric bipolar disorder.

Development of a Korean Version of the Child Mania Rating Scale: Korean Validity and Reliability Study.

Clinical rating scales are essential in psychiatry. The Young Mania Rating Scale is the gold standard for assessing mania. However, increased attention to pediatric bipolar disorder has led to the development of the Child Mania Rating Scale (CMRS), which is a parent-reported rating scale designed to assess mania in children and adolescents. This study aimed to translate the CMRS into Korean and assess the validity and reliability of the Korean version of the CMRS (K-CMRS). The original English version of the CMRS has been translated into Korean. We enrolled 33 patients with bipolar disorder and 26 patients with attention-deficit hyperactivity disorder (ADHD). All participants were evaluated using the translated K-CMRS, Mood Disorder Questionnaire (MDQ), and ADHD Rating Scale. The Cronbach's α was 0.907. Correlation analyses between K-CMRS and MDQ scores yielded significant positive correlations (r=0.529, p=0.009). However, the factor analysis was unsuccessful. The total K-CMRS scores of bipolar disorder and ADHD patients were compared. However, the differences were not statistically significant. The K-CMRS showed good internal consistency and reliability. The correlation between the K-CMRS and MDQ scores verifies its validity. The K-CMRS was designed to assess and score manic symptoms in children and adolescents but had difficulties in differentiating between bipolar disorder and ADHD. It is a valuable tool for evaluating the presence and severity of manic symptoms in pediatric patients with bipolar disorder.

3.7 Neuroanatomical Correlates of Altered Decision-Making Processes in Children and Adolescents With Pediatric Bipolar Disorder and Bipolar Offspring

3.7 Neuroanatomical Correlates of Altered Decision-Making Processes in Children and Adolescents With Pediatric Bipolar Disorder and Bipolar Offspring

Addressing Severely Impairing Comorbidity in Pediatric Bipolar Disorder

Addressing Severely Impairing Comorbidity in Pediatric Bipolar Disorder

3.1 Multimodal Assessment in Children and Adolescents With Pediatric Bipolar Disorder: Preliminary Findings

3.1 Multimodal Assessment in Children and Adolescents With Pediatric Bipolar Disorder: Preliminary Findings

3.6 Cognitive Correlates With Borderline Features in Youth With Pediatric Bipolar Disorder and Bipolar Offspring

3.6 Cognitive Correlates With Borderline Features in Youth With Pediatric Bipolar Disorder and Bipolar Offspring

Altered white matter integrity in euthymic children with bipolar disorder: A tract-based spatial statistical analysis of diffusion tensor imaging

Pediatric Bipolar Disorder (BD) is a serious mental illness that affects children and adolescents, characterized by episodes of mania, depression, and mixed episodes. Recent studies have suggested that abnormalities in the white matter (WM) may be a contributing factor. The neuropathogenesis of BD in children is not well-described, and research in this area is limited. Euthymic phase is a period in which clinical symptoms are present but not severe enough to significantly impact mood and daily behavior. In order to better understand the WM changes associated with BD in children, this study utilized Diffusion Tensor Imaging (DTI), to investigate alterations in WM microstructure. 20 confirmed euthymic BD children (aged 7–16) and 20 typically developing children were included in the study. DTI scans were obtained using a 3 T Magnetom Skyra and were analyzed using tract-based spatial statistics (TBSS) to examine changes in fractional anisotropy (FA), axial diffusivity (AD), radial diffusivity (RD), and mean diffusivity (MD). Results showed that compared to the healthy control group, the euthymic BD group exhibited increased FA, AD, RD, and MD values in several brain regions, including the thalamus, precentral corticospinal tract, and superior longitudinal fasciculus. Conversely, decreased values were observed in the body of the corpus callosum and inferior fronto-occipital fasciculus. These findings suggest that alterations in WM microstructure are a hallmark of pediatric bipolar disorder. These findings provide important insights into the brain changes associated with pediatric bipolar disorder and open the door for new avenues of research.

Misconceptions about Paediatric Bipolar Disorder.

Misconceptions about Paediatric Bipolar Disorder.

The diagnosis of bipolar disorder in children and adolescents: Past, present and future.

This article examines the ongoing debate concerning the diagnosis of bipolar disorder in children and adolescents. This contentious issue has generated robust discussion over the past two decades without consensus, and as such the true prevalence of so-called paediatric bipolar disorder (PBD) remains unknown. In this article we offer a solution to break this deadlock. Recent meta-analyses and additional literature concerning the definition and prevalence of PBD was critically reviewed with a view to understanding the perspectives of those developing the taxonomy of PBD, and those engaged in research and clinical practice. A key finding is the lack of iteration and meaningful communication between the various groups interested in PBD that stems from deep-seated problems within our classificatory systems. This undermines our research efforts and complicates clinical practice. These problems make the already difficult diagnosis of bipolar disorder in adults even more challenging to transpose to younger populations, and additional complexities arise when parsing clinical phenomenology from normative developmental changes in youth. Therefore, in those manifesting bipolar symptoms post-puberty, we argue for the use of adolescent bipolar disorder to describe bipolar symptoms whereas in pre-pubertal children, we propose a reconceptualisation that allows symptomatic treatment to be advanced whilst requiring critical review of these symptoms over time. Significant changes in our current taxonomy are necessary and to be clinically meaningful, these revisions to our diagnoses need to be developmentally-informed.