Neural and Cognitive Predictors of Stimulant Treatment Efficacy in Medication-Naïve ADHD Adults: A Pilot Diffusion Tensor Imaging Study.

OBJECTIVE: Stimulant medications are the main treatment for Attention Deficit Hyperactivity Disorder (ADHD), but overall treatment efficacy in adults has less than a 60% response rate. This study aimed to identify neural and cognitive markers predictive of longitudinal improvement in response to stimulant treatment in drug-naïve adults with ADHD. METHOD: We used diffusion tensor imaging (DTI) and executive function measures with 36 drug-naïve adult ADHD patients in a prospective study design. RESULTS: Structural connectivity (measured by fractional anisotropy, FA) in striatal regions correlated with ADHD clinical symptom improvement following stimulant treatment (amphetamine or methylphenidate) in better medication responders. A significant positive correlation was also found between working memory performance and stimulant-related symptom improvement. Higher pre-treatment working memory scores correlated with greater response. CONCLUSION: These findings provide evidence of pre-treatment neural and behavioral markers predictive of longitudinal treatment response to stimulant medications in adults with ADHD.

Decline in Partner-Accompanied Births during the COVID-19 Pandemic in Japan: A Nationwide Cross-Sectional Internet-Based Study.

The study objective was to describe trends in partner-accompanied birth between January 2019 and August 2021 and examine the associations of partner-accompanied birth with women's psychological distress and partners' housework and parenting. A total of 5605 women who had a live singleton birth between January 2019 and August 2021 and had a partner participated in this nationwide internet-based survey between July and August 2021 in Japan. The percentages of women's intentions and actual experience of partner-accompanied births were calculated per month. Associations of partner-accompanied birth with scores on the Kessler Psychological Distress Scale (K6) ≥10, partners' participation in housework and parenting, and factors associated with having a partner-accompanied birth were examined using a multivariable Poisson regression model. The proportion of women who had partner-accompanied births was 65.7% between January 2019 and March 2020, dropping to 32.1% between April 2020 and August 2021. Partner-accompanied birth was not associated with a K6 score ≥10, but was significantly associated with the partner's daily housework and parenting (adjusted prevalence ratio 1.08, 95% CI 1.02-1.14). Partner-accompanied births have been substantially restricted since the beginning of the COVID-19 pandemic. The right to a birth partner should be protected, while addressing infection control.

Protease-Independent Production of Poliovirus Virus-like Particles in Pichia pastoris: Implications for Efficient Vaccine Development and Insights into Capsid Assembly.

The production of enterovirus virus-like particles (VLPs) that lack the viral genome have great potential as vaccines for a number of diseases, such as poliomyelitis and hand, foot, and mouth disease. These VLPs can mimic empty capsids, which are antigenically indistinguishable from mature virions, produced naturally during viral infection. Both in infection and in vitro, capsids and VLPs are generated by the cleavage of the P1 precursor protein by a viral protease. Here, using a stabilized poliovirus 1 (PV-1) P1 sequence as an exemplar, we show the production of PV-1 VLPs in Pichia pastoris in the absence of the potentially cytotoxic protease, 3CD, instead using the porcine teschovirus 2A (P2A) peptide sequence to terminate translation between individual capsid proteins. We compare this to protease-dependent production of PV-1 VLPs. Analysis of all permutations of the order of the capsid protein sequences revealed that only VP3 could be tagged with P2A and maintain native antigenicity. Transmission electron microscopy of these VLPs reveals the classic picornaviral icosahedral structure. Furthermore, these particles were thermostable above 37°C, demonstrating their potential as next generation vaccine candidates for PV. Finally, we believe the demonstration that native antigenic VLPs can be produced using protease-independent methods opens the possibility for future enteroviral vaccines to take advantage of recent vaccine technological advances, such as adenovirus-vectored vaccines and mRNA vaccines, circumventing the potential problems of cytotoxicity associated with 3CD, allowing for the production of immunogenic enterovirus VLPs in vivo. IMPORTANCE The widespread use of vaccines has dramatically reduced global incidence of poliovirus infections over a period of several decades and now the wild-type virus is only endemic in Pakistan and Afghanistan. However, current vaccines require the culture of large quantities of replication-competent virus for their manufacture, thus presenting a potential risk of reintroduction into the environment. It is now widely accepted that vaccination will need to be extended posteradication into the foreseeable future to prevent the potentially catastrophic reintroduction of poliovirus into an immunologically naive population. It is, therefore, imperative that novel vaccines are developed which are not dependent on the growth of live virus for their manufacture. We have expressed stabilized virus-like particles in yeast, from constructs that do not require coexpression of the protease. This is an important step in the development of environmentally safe and commercially viable vaccines against polio, which also provides some intriguing insights into the viral assembly process.

The Heritability of ADHD in Children of ADHD Parents: A Post-hoc Analysis of Longitudinal Data.

OBJECTIVE: A growing literature suggests attention-deficit/hyperactivity disorder (ADHD) is a heritable disorder. We evaluated children at risk for ADHD by virtue of having parents with ADHD and compared them with children of parents without ADHD to assess the degree of heritability of ADHD. METHOD: The sample for this study was derived from three longitudinal studies that tracked families with various disorders, including ADHD. Children were stratified based on presence of parental ADHD, and clinical assessments were taken to evaluate presence of ADHD and related psychiatric and functional outcomes in children. RESULTS: Children with parental ADHD had significantly more full or subthreshold psychiatric disorders (including ADHD) as well as functional impairments compared to children without parental ADHD. CONCLUSION: Our findings suggest that offspring of parents with ADHD are at significant risk for ADHD and its associated psychiatric, cognitive, and educational impairments. These findings aid in identifying early manifestations of ADHD in young children at risk.

A Randomized, Double-Blind, Controlled Clinical Trial of Omega-3 Fatty Acids and Inositol as Monotherapies and in Combination for the Treatment of Pediatric Bipolar Spectrum Disorder in Children Age 5-12.

Objectives: The aim of this study was to assess the efficacy and tolerability of omega-3 fatty acids (FAs) and inositol alone and in combination for the treatment of pediatric bipolar (BP) spectrum disorder in young children. Methods: Participants were male and female children ages 5-12 meeting DSM-IV diagnostic criteria for a BP spectrum disorder and displaying mixed, manic, or hypomanic symptoms without psychotic features at the time of evaluation. Results: Participants concomitantly taking psychotropic medication were excluded from efficacy analyses. There were significant reductions in YMRS and HDRS mean scores in the inositol and combination treatment groups (all p < 0.05) and in CDRS mean scores in the combination treatment group (p < 0.001), with the largest changes seen in the combination group. Those receiving the combination treatment had the highest rates of antimanic and antidepressant response. The odds ratios for the combination group compared to the omega-3 FAs and inositol groups were clinically meaningful (ORs ≥2) for 50% improvement on the YMRS, normalization of the YMRS (score <12) (vs. inositol group only), 50% improvement on the HDRS, 50% improvement on CDRS (vs. omega-3 FAs group only), and CGI-I Mania, CGI-I MDD, and CGI-I Anxiety scores <2. Conclusion: The antimanic and antidepressant effects of the combination treatment of omega-3 FAs and inositol were consistently superior to either treatment used alone. This combination may offer a safe and effective alternative or augmenting treatment for youth with BP spectrum disorder, but more work is needed to confirm the statistical significance of this finding.

Can machine learning identify childhood characteristics that predict future development of bipolar disorder a decade later?

Early identification of bipolar disorder may provide appropriate support and treatment, however there is no current evidence for statistically predicting whether a child will develop bipolar disorder. Machine learning methods offer an opportunity for developing empirically-based predictors of bipolar disorder. This study examined whether bipolar disorder can be predicted using clinical data and machine learning algorithms. 492 children, ages 6-18 at baseline, were recruited from longitudinal case-control family studies. Participants were assessed at baseline, then followed-up after 10 years. In addition to sociodemographic data, children were assessed with psychometric scales, structured diagnostic interviews, and cognitive and social functioning assessments. Using the Balanced Random Forest algorithm, we examined whether the diagnostic outcome of full or subsyndromal bipolar disorder could be predicted from baseline data. 45 children (10%) developed bipolar disorder at follow-up. The model predicted subsequent bipolar disorder with 75% sensitivity, 76% specificity, and an Area Under the Receiver Operating Characteristics of 75%. Predictors best differentiating between children who did or did not develop bipolar disorder were the Child Behavioral Checklist Externalizing and Internalizing behaviors, the Child Behavioral Checklist Total t-score, problematic school functions indexed through the Child Behavioral Checklist School Competence scale, and the Child Behavioral Checklist Anxiety/Depression and Aggression scales. Our study provides the first quantitative model to predict bipolar disorder. Longitudinal prediction may help clinicians assess children with emergent psychopathology for future risk of bipolar disorder, an area of clinical and scientific importance. Machine learning algorithms could be implemented to alert clinicians to risk for bipolar disorder.

Long term outcomes of pediatric Bipolar-I disorder: A prospective follow-up analysis attending to full syndomatic, subsyndromal and functional types of remission.

OBJECTIVE: To examine patterns of remission of pediatric bipolar I (BP-I) disorder attending to syndromatic, symptomatic, and functional outcomes from childhood to adolescent and young adult years. METHODS: We analyzed data from a six-year prospective follow-up study of youths aged 6-17 years with BP-I disorder. Subjects were comprehensively assessed at baseline and subsequently at four, five, and six years thereafter. Assessments included structured diagnostic interviews and measures of psychosocial and educational functioning. Patterns of remission were calculated attending to whether syndromatic, symptomatic, and functional remission were achieved. RESULTS: Kaplan-Meier failure functions revealed that the probability of functional recovery from pediatric BP-I disorder was very low. Of the 88 youths assessed, only 6% (N = 5) of the sample were euthymic with normal functioning during the year prior to their last follow-up assessment (average follow-up time = 5.8 ± 1.8 years). CONCLUSIONS: These results provide compelling evidence of the high level of persistence of pediatric BP-I disorder. Symptomatic and functional remission were uncommon and most subjects continued to demonstrate high morbidity into late adolescence and early adulthood.

Findings from a pilot open-label trial of N-acetylcysteine for the treatment of pediatric mania and hypomania.

BACKGROUND: Pediatric bipolar disorder is a highly prevalent and morbid disorder and is considered a prevalent public health concern. Currently approved treatments often pose the risk of serious side effects. Therefore, this study assessed the efficacy and tolerability of N-acetylcysteine (NAC), in children and adolescents with bipolar spectrum disorder. METHODS: We conducted a 12-week open-label trial of NAC for treatment of mania and hypomania in children and adolescents ages 5-17 with bipolar spectrum disorder including participants with full and subthreshold manic symptoms, accepting those with and without mixed states with co-occurring depression, and Young Mania Rating Scale scores ≥ 20 and < 40. Symptoms of mania and depression were assessed using the Young Mania Rating Scale (YMRS), Hamilton Depression Rating Scale (HDRS), Children's Depression Rating Scale (CDRS), and Clinical Global Impression (CGI) Severity (CGI-S) and Improvement (CGI-I) scales for mania and depression. RESULTS: This study had a high drop-out rate with only 53% completing all 12 weeks. There was a significant reduction in YMRS, HDRS, and CDRS mean scores from baseline to endpoint. Of the 24 exposed participants, 54% had an anti-manic response measured by a reduction in YMRS ≥ 30% and 46% had a CGI-I mania score ≤ 2 at endpoint. Additionally, 62% of participants had an anti-depressive response measured by a reduction in HDRS ≥ 30%, 31% had an anti-depressive response measured by a reduction in CDRS ≥ 30%, and 38% had a CGI-I depression score ≤ 2 at endpoint. CONCLUSIONS: These pilot open-label findings in a small sample provide preliminary data supporting the tolerability and safety of NAC in a pediatric population. The findings of this pilot scale study indicating improvement in mania and depression are promising, but require replication with a monotherapy randomized placebo controlled clinical trial and larger sample. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02357290 . First Registration 06/02/2015.

Disentangling the heterogeneity of emotional dysregulation in referred youth using the Child Behavior Checklist attending to age and sex effects.

PURPOSE: To assess the utility of the Child Behavior Checklist (CBCL) to identify meaningful subtypes of emotional dysregulation in an outpatient pediatric psychiatry clinic. METHODS: The sample consisted of 417 newly referred youth 6-18 years of age. Parents completed the CBCL and rating scales measuring executive function deficits, social functioning, and quality of life. Patients were stratified into subtypes of emotional dysregulation and compared on clinical correlates based on the A-A-A profile consisting of the CBCL Anxious/Depressed, Aggressive Behavior, and Attention Problems (A-A-A) scales. RESULTS: 67% of youth had emotional dysregulation (CBCL A-A-A T-score ≥ 180) and of these, 39% had a positive CBCL-Bipolar (BP) profile (A-A-A T-score ≥ 210), 24% had depression without the BP profile (CBCL Anxious/Depressed and/or Withdrawn/Depressed T-scores ≥70 and A-A-A T-score ≥ 180 and ã€ˆ210), and 37% had emotional impulsivity (A-A-A T-score ≥ 180 and <210) with normal CBCL Anxious/Depressed and Withdrawn/Depressed T-scores. Patients with the CBCL-BP profile were significantly more impaired on all measures of social and executive functioning compared to the other two groups. LIMITATIONS: Since our findings relied on the CBCL, other instruments may have led to different results. Because we included youth from a single clinic, largely Caucasian and referred, our findings may not generalize to other ethnic groups or settings. CONCLUSIONS: The CBCL can aid in the identification of subtypes of emotional dysregulation affecting youth seeking mental health services.

Review: Adult Outcome as Seen Through Controlled Prospective Follow-up Studies of Children With Attention-Deficit/Hyperactivity Disorder Followed Into Adulthood.

OBJECTIVE: To describe adult outcome of people with attention-deficit/hyperactivity disorder (ADHD) diagnosed in childhood and its several key predictors via a review of 7 North American controlled prospective follow-up studies: Montreal, New York, Milwaukee, Pittsburgh, Massachusetts General Hospital (MGH), Berkeley, and 7-site Multimodal Treatment Study of Children With ADHD (MTA). METHOD: All studies were prospective and followed children with a diagnosis of ADHD and an age- and gender-matched control group at regular intervals from childhood (6-12 years of age) through adolescence into adulthood (20-40 years of age), evaluating symptom and syndrome persistence, functional outcomes, and predictors of these outcomes. RESULTS: The rates of ADHD syndrome persistence ranged from 5.7% to 77%, likely owing to varying diagnostic criteria and the source of information (self-report vs informant report) across the studies. However, all studies observed high rates of symptomatic persistence ranging from 60% to 86%. The 7 studies were largely consistent in finding that relative to control groups, research participants with childhood-diagnosed ADHD had significant impairments in the areas of educational functioning, occupational functioning, mental health, and physical health as well as higher rates of substance misuse, antisocial behavior, and unsafe driving. The most consistently observed predictors of functional outcomes included ADHD persistence and comorbidity, especially with disruptive behavior disorders. CONCLUSION: Childhood ADHD has high rates of symptomatic persistence, which is associated with negative functional outcomes. Characteristics that predict these negative outcomes, such as comorbid disruptive behavior disorders, may be important targets for intervention.

The Efficacy and Cognitive Effects of Acute Course Electroconvulsive Therapy Are Equal in Adolescents, Transitional Age Youth, and Young Adults.

Objective: Electroconvulsive therapy (ECT) is the most effective acute treatment for depression, but its use in younger patients is rare and heavily regulated in many U.S. states. It is unclear whether age modifies treatment response or tolerability in adolescents, transitional age youth, and young adults. We examined the effects of ECT on depression and cognition in patients aged 16-30 years. Methods: A retrospective cohort study of patients aged 16-30 years receiving ECT between 2011 and 2020 who were evaluated with the Quick Inventory of Depressive Symptomatology (QIDS), the Behavior and Symptom Identification Scale-24 (BASIS-24), and the Montreal Cognitive Assessment (MoCA) at baseline and following treatment #10. Results: Among the 424 patients who met the inclusion criteria, ECT was associated with a decrease in depression symptoms (ΔQIDS -6.7; Kruskal-Wallis rank sum test; χ2 = 293.37; df = 2; p < 0.0001) and improvement in overall self-reported mental health status (ΔBASIS-24 - 0.70; Kruskal-Wallis rank sum test; χ2 = 258.5; df = 2; p < 0.0001) during the first 10 treatments, with a slight reduction in cognition as measured by the MoCA (ΔMoCA -1.1; Kruskal-Wallis rank sum test; χ2 = 33.7; df = 1; p < 0.0001). Age was not a significant predictor of QIDS, BASIS-24, or MoCA changes. Conclusions: Among 424 patients aged 16-30 years receiving acute course ECT, age was not a significant predictor of improvement in depression, change in overall self-reported mental health status, or change in cognition. These results support the utility of ECT in the treatment of adolescents and young adults.

Association between frontal cortico-limbic white-matter microstructure and risk for pediatric depression.

This study aimed to identify white-matter microstructural characteristics associated with risk for pediatric major depressive disorder (MDD) measured by the Child Behavior Checklist (CBCL) Anxiety/Depression scores. Children (N = 32) of both sexes, aged 6-12, underwent T1-weighted whole-head anatomical and diffusion-weighted imaging. Each participant's mean diffusion measure image was generated and thinned to create an alignment-invariant tract representation. Voxel-wise analysis on the resulting map was carried out in Track Based Spatial Statistics (TBSS) using general linear models by regressing the CBCL-Anxiety/Depression score against measures of diffusion tensor imaging (DTI). We also compared these results with prior DTI findings from the same children associated with CBCL-Emotion Dysregulation profile, an indicator for bipolar disorder. TBSS voxel-wise analysis showed a significant negative correlation between fractional anisotropy (FA) and CBCL-Anxiety/Depression scores localized in the right anterior cingulum and connected corpus callosal region. The negative FA correlations in these regions were greater in CBCL-Anxiety/ Depression scores compared to CBCL-Emotional Dysregulation scores. Reduced white-matter connectivity in the anterior cingulum and connected corpus callosal region may represent a biomarker of risk for pediatric MDD. These results may help identify brain differences associated with the development of MDD, and assist with earlier clinical identification of pediatric MDD.

The child behavior checklist can aid in characterizing suspected comorbid psychopathology in clinically referred youth with ADHD.

OBJECTIVE: To examine the utility of the Child Behavior Checklist (CBCL) to aid in the identification of comorbid psychopathological conditions affecting referred youth with suspected ADHD prior to the evaluation. The CBCL is an easy-to-use assessment tool that may provide invaluable information regarding the severity and characteristics of the presenting complaints. METHODS: The sample included 332 youths consecutively referred to an ADHD program for the assessment of suspected ADHD. Parents completed the CBCL, parent-rated ADHD Self-Report Scale (ASRS), Social Responsiveness Scale (SRS), and Behavior Rating Inventory of Executive Function (BRIEF). Because of the established association between the CBCL Attention Problems scale and a structured diagnostic interview of ADHD, all youths analyzed had abnormal Attention Problems T-scores (≥60). RESULTS: Seventy-six percent of youths with elevated Attention Problems T-scores had ≥3 additional abnormal CBCL scales, suggesting they were likely affected with multiple comorbid psychopathological conditions. Moreover, 44% had ≥1 CBCL clinical scale with a T-score more severe than their Attention Problems T-score, suggesting the putative comorbid condition was more severe than the ADHD symptoms. Additional CBCL scale elevations were associated with more severe functional impairments as assessed by the ASRS, SRS, BRIEF, and CBCL competence scales. CONCLUSION: The CBCL obtained before the clinical assessment identified high rates of comorbid psychopathology in youths referred for the assessment of ADHD. It provided detailed information about the types and severity of suspected psychopathological conditions impacting a particular youth, which is critical to guide the assessing clinician on likely differing needs of the affected child.

Prediction of stimulus-independent and task-unrelated thought from functional brain networks.

Neural substrates of "mind wandering" have been widely reported, yet experiments have varied in their contexts and their definitions of this psychological phenomenon, limiting generalizability. We aimed to develop and test the generalizability, specificity, and clinical relevance of a functional brain network-based marker for a well-defined feature of mind wandering-stimulus-independent, task-unrelated thought (SITUT). Combining functional MRI (fMRI) with online experience sampling in healthy adults, we defined a connectome-wide model of inter-regional coupling-dominated by default-frontoparietal control subnetwork interactions-that predicted trial-by-trial SITUT fluctuations within novel individuals. Model predictions generalized in an independent sample of adults with attention-deficit/hyperactivity disorder (ADHD). In three additional resting-state fMRI studies (total n = 1115), including healthy individuals and individuals with ADHD, we demonstrated further prediction of SITUT (at modest effect sizes) defined using multiple trait-level and in-scanner measures. Our findings suggest that SITUT is represented within a common pattern of brain network interactions across time scales and contexts.

Further Evidence that Subsyndromal Manifestations of Depression in Childhood Predict the Subsequent Development of Major Depression: A Replication Study in a 10 Year Longitudinally Assessed Sample.

BACKGROUND: We have previously shown that subsyndromal scores on the Child Behavior Checklist (CBCL)-Anxiety/Depression (Anx/Dep) scale at baseline predicted the subsequent development of Major Depressive Disorder (MDD) in youth with ADHD. The present study aimed to replicate these findings in a separate, long-term, longitudinal sample of children at high- and low- risk for depression. METHODS: 219 children of parents with and without depression and/or anxiety, ages 2-25, were stratified into 3 groups: 1) children with familial risk for depression (by presence of parental MDD) plus subsyndromal scores on the CBCL-Anx/Dep scale, 2) children with familial risk for depression without subsyndromal scores, and 3) children with neither familial risk for depression nor subsyndromal scores. Subjects were reassessed at both 5 and 10 year follow-ups. RESULTS: Children with both subsyndromal scores on the CBCL-Anx/Dep plus a familial risk for depression were at greater risk for developing MDD at the 10 year follow-up when compared with all other groups. Those with familial risk but no subsyndromal scores had an intermediate risk that was greater than the controls, who had the lowest risk. LIMITATIONS: The recruitment of the study included families with parental panic disorder, so the sample likely included more families with anxiety disorders than the general population. CONCLUSIONS: Our results showed that subsyndromal scores of the CBCL-Anx/Dep scale increased the risk for the subsequent development of MDD, particularly in children at high risk for depression. These results confirm the CBCL-Anx/Dep scale's utility in identifying children at high risk for developing MDD.

Assessing the Magnitude of Risk for ADHD in Offspring of Parents with ADHD: A Systematic Literature Review and Meta-Analysis.

The main aim of this study was to examine the body of knowledge on the prevalence of Attention Deficit Hyperactivity Disorder (ADHD) in "high-risk" children whose parents are diagnosed with ADHD. This knowledge could aid early identification for children presenting with ADHD symptoms at a young age. We conducted a systematic search of the literature assessing high-risk children. Included were original articles published in English with the main aim to assess prevalence of ADHD in high risk children. In addition, a meta-analysis was conducted to examine this prevalence. Four articles met our inclusion and exclusion criteria all suggesting an increased prevalence of ADHD in children of parents with ADHD. The meta-analysis also confirmed the increased prevalence of ADHD in high-risk children. The literature indicates that children of ADHD parents have an increased risk of developing ADHD compared to control children.

Differentiating bipolar disorder from unipolar depression in youth: A systematic literature review of neuroimaging research studies.

Differentiating bipolar disorder from unipolar depression is one of the most difficult clinical questions posed in pediatric psychiatric practices, as misdiagnosis can lead to severe repercussions for the affected child. This study aimed to examine the existing literature that investigates brain differences between bipolar and unipolar mood disorders in children directly, across all neuroimaging modalities. We performed a systematic literature search through PubMed, PsycINFO, Embase, and Medline databases with defined inclusion and exclusion criteria. Nine research studies were included in the systematic qualitative review, including three structural MRI studies, five functional MRI studies, and one MR spectroscopy study. Relevant variables were extracted and brain differences between bipolar and unipolar mood disorders in children as well as healthy controls were qualitatively analyzed. Across the nine studies, our review included 228 subjects diagnosed with bipolar disorder, 268 diagnosed with major depressive disorder, and 299 healthy controls. Six of the reviewed studies differentiated between bipolar and unipolar mood disorders. Differentiation was most commonly found in the anterior cingulate cortex (ACC), insula, and dorsal striatum (putamen and caudate) brain areas. Despite its importance, the current neuroimaging literature on this topic is scarce and presents minimal generalizability.

Cingulum-Callosal white-matter microstructure associated with emotional dysregulation in children: A diffusion tensor imaging study.

Emotional dysregulation symptoms in youth frequently predispose individuals to increased risk for mood disorders and other mental health difficulties. These symptoms are also known as a behavioral risk marker in predicting pediatric mood disorders. The underlying neural mechanism of emotional dysregulation, however, remains unclear. This study used the diffusion tensor imaging (DTI) technique to identify anatomically specific variation in white-matter microstructure that is associated with pediatric emotional dysregulation severity. Thirty-two children (mean age 9.53 years) with varying levels of emotional dysregulation symptoms were recruited by the Massachusetts General Hospital and underwent the DTI scans at Massachusetts Institute of Technology. Emotional dysregulation severity was measured by the empirically-derived Child Behavior Checklist Emotional Dysregulation Profile that includes the Attention, Aggression, and Anxiety/Depression subscales. Whole-brain voxel-wise regression tests revealed significantly increased radial diffusivity (RD) and decreased fractional anisotropy (FA) in the cingulum-callosal regions linked to greater emotional dysregulation in the children. The results suggest that microstructural differences in cingulum-callosal white-matter pathways may manifest as a neurodevelopmental vulnerability for pediatric mood disorders as implicated in the clinical phenotype of pediatric emotional dysregulation. These findings may offer clinically and biologically relevant neural targets for early identification and prevention efforts for pediatric mood disorders.