Neuroanatomical Correlates of the Late Positive Potential in Youth with Pediatric Bipolar Disorder.

BACKGROUND: The late positive potential (LPP) could be a marker of emotion dysregulation in youth with pediatric bipolar disorder (PBD). However, the neuroanatomical correlates of the LPP are still not clarified. OBJECTIVE: To provide cortical and deep gray matter correlates of the LPP in youth, specifically, youth with PBD. METHODS: Twenty-four 7 to 17 years-old children with PBD and 28 healthy controls (HC) underwent cortical thickness and deep gray matter volumes measurements through magnetic resonance imaging and LPP measurement elicited by passively viewing emotional faces through electroencephalography. T-tests compared group differences in LPP, cortical thickness, and deep gray matter volumes. Linear regressions tested the relationship between LPP amplitude and cortical thickness/deep gray matter volumes. RESULTS: PBD had a more pronounced LPP amplitude for happy faces and a thinner cortex in prefrontal areas than HC. While considering both groups, a higher LPP amplitude was associated with a thicker cortex across occipital and frontal lobes, and with a smaller right globus pallidus volume. In addition, a higher LPP amplitude for happy faces was associated with smaller left caudate and left globus pallidus volumes across both groups. Finally, the LPP amplitude correlated negatively with right precentral gyrus thickness across youth with PBD, but positively across HC. CONCLUSION: Neural correlates of LPP in youth included fronto-occipital areas that have been associated also with emotion processing and control. The opposite relationship between BPD and HC of LPP amplitude and right precentral gyrus thickness might explain the inefficacy of the emotional control system in PBD.

Disrupted white matter microstructure correlates with impulsivity in children and adolescents with bipolar disorder.

Altered white matter (WM) microstructure likely occurs in children with bipolar disorder (BD) with impulsivity representing one of the core features. However, altered WM microstructures and their age-related trendlines in children with BD and those at high-risk of developing BD, as well as correlations of WM microstructures with impulsivity, have been poorly investigated. In this study, diffusion MRI, cognitive, and impulsivity assessments were obtained from children/adolescents diagnosed with BD, offspring of individuals with BD (high-risk BD) and age-matched healthy controls. A novel atlas-based WM skeleton measurement approach was used to quantify WM microstructural integrity with all diffusion-tensor-imaging (DTI) metrics including fractional anisotropy, axial, mean and radial diffusivity to survey entire WM tracts and ameliorate partial volume effects. Among all DTI-derived metric measures, radial diffusivity quantifying WM myelination was found significantly higher primarily in corpus callosum and in the corona radiata in children with BD compared to controls. Distinguished from age-related progressively decreasing diffusivities and increasing fractional anisotropy in healthy controls, flattened age-related trendlines were found in BD group, and intermediate developmental rates were observed in high-risk group. Larger radial diffusivity in the corpus callosum and corona radiata significantly correlated with shorter response times to affective words that indicate higher impulsivity in the BD group, whereas no such correlation was found in the healthy control group. This work corroborates the progressive nature of pediatric BD and suggests that WM microstructural disruption involved in affective regulation and sensitive to impulsivity may serve as a biomarker of pediatric BD progression.

Neurocognitive Correlates of Cerebellar Volumetric Alterations in Youth with Pediatric Bipolar Spectrum Disorders and Bipolar Offspring.

BACKGROUND: Emerging evidence points towards the involvement of the cerebellum in the processing of emotions and pathophysiology of mood disorders. However, cerebellar and related cognitive alterations in youth with pediatric bipolar disorder (PBD) and those at high risk to develop the disorder, such as bipolar offspring (BD-OFF) are not clearly defined. OBJECTIVE: To investigate cerebellar gray and white matter volumes, cognition, and their relationship in youth with PBD and BD-OFF. METHODS: Thirty youth (7 to 17 years, inclusive) with PBD, 30 BD-OFF and 40 healthy controls (HC) were recruited. Study participants underwent a computer-based cognitive battery assessing affective processing, executive function, attention, psychomotor speed, and learning. Three-tesla MRI scan was performed to assess cerebellar white and gray matter volumes. Cerebellar segmentation was performed with FreeSurfer. Statistical analyses include between-group differences in cognitive domains, cerebellar gray, and white matter volumes. Relationships between cerebellar volumes and cognitive domains were examined. RESULTS: Youth with PBD showed greater cerebellar gray matter volumes than both BD-OFF and HC, whereas no differences were present between BD-OFF and HC. Both youth with PBD and BD-OFF showed altered processing of negative emotions and a bias towards positive emotions. In youth with PBD and BD-OFF, greater impairment in the processing of emotions correlated with greater cerebellar gray matter volumes. CONCLUSION: The present findings corroborate hypotheses on cerebellar involvement in the processing of emotions and the pathophysiology of PBD. The presence of cerebellar dysfunction in BD-OFF is unclear.

Suicide Screening in a Large Pediatric Emergency Department: Results, Feasibility, and Lessons Learned.

OBJECTIVE: This study examined the feasibility of screening all patients entering the ED using the Columbia-Suicide Severity Rating Scale as well as examining the rates of suicide ideation and attempts endorsed by adolescents who present at the ED. METHODS: This study used a sample of 12,113 patients between the ages of 11 and 19 years. RESULTS: Results revealed that 13.5% of the participants endorsed passive suicide ideation in the month leading up to their ED visit and 11.3% of the participants reported active ideation in the prior month. Results also revealed that patients whose chief complaints were coded as psychiatric or medical trauma were more likely to endorse either active or passive suicidal ideation than other presenting problems. Patients with a psychiatric or medical trauma chief complaint were also more likely to report lifetime suicidal behavior and suicidal behavior 3 months before the ED visit. CONCLUSIONS: In addition to findings, implications, feasibility, and lessons learned are discussed for other institutions or departments considering implementation of a widespread screening.Highlights:• Suicide screenings were implemented in a large pediatric emergency department.• One in 5 endorsed suicidal ideation or behavior regardless of presenting problem.• Feasibility and lessons learned are discussed for others hoping to implement a widespread screening.

Cortical Correlates of Impulsive Aggressive Behavior in Pediatric Bipolar Disorder.

Background: Impulsive aggression represents a frequent characteristic of pediatric bipolar disorder (PBD). Cortical alterations associated with impulsive aggression and its multiple facets have not been investigated yet in youth with bipolar disorder. Aim: To investigate the relationship between cortical thickness and facets of impulsive aggression in youth with PBD. Materials and Methods: Twenty-three youth with PBD and 23 healthy controls (HC) were administered the aggression questionnaire (AQ) and underwent 3T magnetic resonance imaging scan. Cortical thickness was assessed with FreeSurfer. Canonical correlation analyses were used to investigate the relationship between AQ total and subscale scores and cortical thickness in youth with PBD. Results: Youth with PBD had increased scores in the subscales of AQ-anger and AQ-hostility and cortical thinning in in areas belonging to the affective network (AN), frontoparietal network (FPN) and cingulo-opercular network (CON), i.e., right rostral anterior cingulate, right caudal anterior cingulate, right lateral orbitofrontal, right medial orbitofrontal, left and right inferior parietal, left posterior cingulate, left and right supramarginal left lingual cortices. Greater thickness in these networks positively correlated with the AQ-hostility subscale and negatively correlated with AQ-anger subscale. Conclusions: The opposite patterns observed between areas belonging to AN, FPN, CON, and the two facets of IA, namely anger and hostility, corroborate clinical findings supporting the different nature of these two constructs.

Cognitive correlates of impulsive aggression in youth with pediatric bipolar disorder and bipolar offspring.

BACKGROUND: Youth with bipolar disorder (BD) and offspring of individuals with BD (BD-OFF) are characterized by higher levels of impulsive and overt aggression. The cognitive basis underlying these aggressive behaviors are not clarified in this population. The aim of this study was to investigate the relationship between cognitive alterations and aggressive behavior in youth with BD and BD-OFF. METHODS: Forty-two youth with BD, 17 BD-OFF and 57 healthy controls (HCs) were administered the Modified Overt Aggression Scale (MOAS), the Cambridge Neuropsychological Test Automated Battery (CANTAB), the Young Mania Rating Scale (YMRS) and the Children's Depression Rating Scale (CDRS). Multiple linear regression analyses were performed in the three groups separately. In each group, tests scores from the CANTAB were predictors. MOAS subscale scores and MOAS total scores were dependent variables. Results are corrected for age, IQ and mood state. RESULTS: Both youth with BD and BD-OFF showed positive correlations between impairment in executive functions and levels of verbal aggression. In youth with BD, altered processing of either positive and negative stimuli positively correlated with MOAS total scores, whereas in BD-OFF, such relationship was negative. CONCLUSIONS: Impulsive aggressive behaviors in youth with BD arise from a combination of altered affective processing and executive dysfunction. The negative relationship between affective processing and aggression in BD-OFF suggested the presence of possible mechanisms of resilience in this population.

Geospatial identification of high youth suicide risk areas via electronic health records: Avenues for research and prevention efforts.

OBJECTIVE: As suicide risk screening becomes more common in healthcare settings, geospatial coding of behavioral health data may offer a means for identifying areas of elevated suicide risk for use in public health prevention efforts. The present study demonstrates an analytic approach for using universal suicide risk screening data to identify areas of elevated suicide risk. METHOD: Data were drawn from standard suicide risk screens recorded in electronic health records of a large pediatric emergency department. A total of 12,400 suicide risk screening responses were recorded, among youth aged 11-19 years (mean = 14.60, SD = 2.16; 57.2% girls, 47.8% Hispanic/Latinx, 72.1% White). A total of 86 unique ZIP codes had at least 50 completed screens, representing 9139 respondents. RESULTS: Rates of positive screens ranged from 6.17% to 31.03% (mean = 18.33, SD = 5.14) for any suicide-related behavior and from 0.0% to 19.61% (mean = 9.14, SD = 3.43) for suicide attempt. Rates of positive screens approximated a normal distribution. CONCLUSIONS: Results demonstrated several areas with elevated rates of positive suicide risk screens, within the hospital catchment area. The proposed method capitalizes on large-scale screening data, provides an estimate of areas of relative increased risk, and may be used to inform public health responses to suicide prevention.

Suicide Ideation and Attempts in a Pediatric Emergency Department Before and During COVID-19.

OBJECTIVES: Elevated rates of mental health concerns have been identified during the coronavirus disease 2019 (COVID-19) pandemic. In this study, we sought to evaluate whether youth reported a greater frequency of suicide-related behaviors during the 2020 COVID-19 pandemic as compared with 2019. We hypothesized that rates of suicide-related behaviors would be elevated between the months of March and July 2020 as compared with 2019, corresponding to the onset of the COVID-19 pandemic. METHODS: Routine suicide-risk screening was completed with youth aged 11 to 21 in a pediatric emergency department. Electronic health records data for suicide-risk screens completed between January and July 2019 and January and July 2020 were evaluated. A total of 9092 completed screens were examined (mean age 14.72 years, 47.7% Hispanic and/or Latinx, 26.7% non-Hispanic white, 18.7% non-Hispanic Black). RESULTS: Rates of positive suicide-risk screen results from January to July 2020 were compared with corresponding rates from January to July 2019. Results indicated a significantly higher rate of suicide ideation in March and July 2020 and higher rates of suicide attempts in February, March, April, and July 2020 as compared with the same months in 2019. CONCLUSIONS: Rates of suicide ideation and attempts were higher during some months of 2020 as compared with 2019 but were not universally higher across this period. Months with significantly higher rates of suicide-related behaviors appear to correspond to times when COVID-19-related stressors and community responses were heightened, indicating that youth experienced elevated distress during these periods.

Alterations in plasma kynurenine pathway metabolites in children and adolescents with bipolar disorder and unaffected offspring of bipolar parents: A preliminary study.

BACKGROUND: There has been growing scientific evidence in recent years that bipolar disorder (BD) is associated with alterations in the kynurenine (KYN) pathway. However, many of these studies have been limited by their focus on adults. Thus, this preliminary study investigated differences in the peripheral levels of KYN metabolites in children and adolescents with BD, unaffected offspring of parents with BD, and healthy controls (HCs). METHODS: Plasma samples were collected from 49 youths with BD, 19 bipolar offspring, and 31 HCs. Tryptophan (TRP), KYN, and kynurenic acid (KYNA) were separated using electrospray ionization. RESULTS: One-Way ANCOVA after controlling for age, gender, race, BMI-for-age, and smoking status showed that BD had lower levels of KYN, while unaffected high-risk offspring subjects had lower levels of TRP, KYN, and KYNA when compared to HCs. Moreover, we found that KYN, KYN/TRP, and KYNA/KYN levels predicted the severity of depressive symptoms, while the YMRS score was not associated with any metabolite. CONCLUSIONS: In summary, this preliminary study has shown that KYN metabolites are decreased in both affected and unaffected subjects, strengthening the idea that the KYN pathway might underlie the familial risk of BD shown by high-risk offspring individuals. However, longitudinal studies are needed to examine whether the alterations observed in this study represent early markers of risk for later developing BD.

An Evaluation of Yoga and Meditation to Improve Attention, Hyperactivity, and Stress in High-School Students.

Objective: Problems with attention and stress are common in children and predict academic difficulties and other behavioral and emotional problems. Mind-body interventions such as yoga and meditation improve attention and reduce stress. In this study, we examined the impact of Hatha yoga on attention and stress in ninth graders. Design: A total of 174 ninth graders from a Texas high school were enrolled in the study. Teachers assigned students to a yoga group (YG) or control group (CG) based on their class schedule. The YG participated in 25-min Hatha yoga classes twice weekly over 12 weeks (n = 123). The CG included 51 students. Student self-reports on measures of inattention and hyperactivity (the strengths and weaknesses of ADHD [attention-deficit/hyperactivity disorder] symptoms and normal behavior rating scale for ADHD) and stress (perceived stress scale) were obtained at baseline and at 12 weeks. Results: There were no significant differences in baseline levels of inattention (p = 0.86), hyperactivity (p = 0.25), and perceived stress (p = 0.28) between the YG and CG. Regarding inattention scores, there was a significant interaction of group and time (b = -1.09, standard error [SE] = 0.30, p < 0.001). Pairwise t-tests showed a significant reduction in inattention for the YG (d = 0.27) but a significant increase in inattention for the CG. Regarding hyperactivity, there was no significant interaction of group and time (b = -0.43, SE = 0.26, p = 0.1). Pairwise t-tests demonstrated a significant reduction in hyperactivity for the YG (d = 0.22), but not the CG. The interaction of group and time was not significant in predicting the slope of change in perceived distress (b = -0.93, SE = 1.19, p = 0.43). Pairwise t-tests did not show a significant reduction in perceived distress for either group. Conclusion: These findings suggest that Hatha yoga may improve attention and hyperactivity in high school students.

Mixed States in Early-Onset Bipolar Disorder.

Pediatric bipolar disorder (PBD) is a severe and chronic illness. The occurrence of mixed symptoms might add further risk of recurrence of treatment resistance and suicidality. Early recognition and treatment of mixed symptoms might prevent illness progression and development of suicide attempts. This article provides an update on the epidemiology, clinical profile, and treatment of youth with PBD with mixed states. Mixed states in PBD are characterized by higher rates of suicide and more chronic symptoms, and are associated with younger age of onset and greater comorbidity. A careful assessment for mixed states using standardized criteria is essential.