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.

ADHD is associated with migraine: a systematic review and meta-analysis.

An association between primary headaches and attention-deficit/hyperactivity disorder (ADHD) has long been suggested. Moreover, headache is regarded as a common side effect of stimulants, the most effective treatment for ADHD. So far, no systematic review has evaluated the potential association between ADHD and headache. We performed a systematic review of the literature and a meta-analysis of all reported studies on ADHD and primary headaches. Our analysis showed a positive association between ADHD and migraine (OR 1.322, 95% CI 1.018-1717, p value 0.036), but not with tension-type headache. There is a significant association between migraine and ADHD. The mechanisms underlying this association remain to be elucidated, warranting further studies.

The Greater Houston Area Bipolar Registry-Clinical and Neurobiological Trajectories of Children and Adolescents With Bipolar Disorders and High-Risk Unaffected Offspring.

The aims of this article are to discuss the rationale, design, and procedures of the Greater Houston Area Bipolar Registry (HBR), which aims at contributing to the effort involved in the investigation of neurobiological mechanisms underlying bipolar disorder (BD) as well as to identify clinical and neurobiological markers able to predict BD clinical course. The article will also briefly discuss examples of other initiatives that have made fundamental contributions to the field. This will be a longitudinal study with participants aged 6-17 at the time of enrollment. Participants will be required to meet diagnostic criteria for BD, or to be offspring of a parent with BD. We will also enroll healthy controls. Besides clinical information, which includes neurocognitive performance, participants will be asked to provide blood and saliva samples as well as to perform neuroimaging exams at baseline and follow-ups. Several studies point to the existence of genetic, inflammatory, and brain imaging alterations between individuals at higher genetic risk for BD compared with healthy controls. Longitudinal designs have shown high conversion rates to BD among high-risk offspring, with attempts to identify clinical predictors of disease onset, as well as clarifying the burden associated with environmental stressors. The HBR will help in the worldwide effort investigating the clinical course and neurobiological mechanisms of affected and high-risk children and adolescents with BD.

Interpersonal Trust and Suicide Ideation Among Adolescent Psychiatric Inpatients: An Indirect Effect via Perceived Burdensomeness.

The identification of theoretically and empirically supported correlates of suicide ideation is important to improve treatment approaches to suicide. This study sought to examine the association between interpersonal trust (theoretically conceptualized as a distal risk marker) and suicide ideation in adolescence. Specifically, it was hypothesized that interpersonal trust would be negatively associated with suicide ideation via perceived burdensomeness and thwarted belongingness (conceptualized as more proximal risk markers). Data were drawn from a cross-sectional sample of 387 adolescent inpatients between the ages of 12 and 17 years (M = 14.72, SD = 1.49). The sample was 63.6% female, 37.5% Hispanic, 26.9% African American/Black, and 25.8% Caucasian. Adolescents completed a series of self-report measures to assess thwarted belongingness, perceived burdensomeness, interpersonal trust, depressive symptoms, and suicide ideation. A structural equation model was fit to the data, and results demonstrated a significant indirect path from interpersonal trust to suicide ideation via perceived burdensomeness, but not thwarted belongingness. Results suggest that interpersonal trust may be a distal risk marker for suicide ideation and that interventions to increase interpersonal trust may help prevent the development of thwarted belongingness, perceived burdensomeness, and suicide ideation.

Measurement invariance of depression symptom ratings across African American, Hispanic/Latino, and Caucasian adolescent psychiatric inpatients.

The Beck Depression Inventory-II (BDI-II) is widely used to assess adolescent depressive symptom severity. Psychometric investigations, including factor-analytic studies, with adolescents support the reliability and validity of the BDI-II. However, a major limitation of this research is that samples have been predominantly Caucasian/White. This is critical because depressive illness is highly prevalent across race and ethnicity, and the extent to which reliability and findings generalize to non-Caucasian populations is in question. The present study recruited African American/Black (n = 96), Hispanic/Latino(a) (n = 151), and Caucasian/White (n = 97) adolescent psychiatric inpatients (Mage = 14.73) to test the measurement invariance of the BDI-II, using Osman and colleagues' two-factor solution while also assessing within-group reliability and concurrent validity by examining associations with other symptom measures. Across groups, the two-factor solution, factor loadings, and indicator thresholds were invariant. Within-group reliability estimates were adequate, and the concurrent validity was supported. This suggests BDI-II symptom comparisons between African American/Black, Hispanic/Latino(a), and Caucasian/White adolescent inpatients are valid. Critical extensions of this work may include the examination of potential invariance across depressive symptom clusters via network analysis and invariance testing of depression symptom ratings over time in ethnoracially diverse children and adolescents. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Correlates of childhood trauma in children and adolescents with bipolar disorder spectrum: A preliminary study.

OBJECTIVE: Histories of childhood trauma (CT) are risk factors for affect dysregulation and poor clinical outcomes in women with bipolar disorder (BD). While much is known about the link between BD and CT in adult patients, there is limited data on this research topic in pediatric BD (PBD). The present study aims to investigate the impact of CT on irritability, aggressive and suicidal behaviors in PBD patients across gender types. METHODS: From 2013 to 2015, 59 PBD patients Aged 6-17 (30 female) were administered the Childhood Trauma Questionnaire (CTQ) along with scales assessing irritability (Affective Reactivity Index), aggression (Modified Overt Aggression Scale) and suicidal thoughts and behaviors (Columbia-Suicide Severity Rating Scale). We examined the severity of these behaviors across types of CT and gender using univariate regression analyses. Findings were adjusted for age, number of traumas, and CTQ denial score. RESULTS: In PBD patients, analyses showed that the effect of physical abuse depended on gender, whereby females were more likely than males to engage in suicidal thoughts and behaviors (p < 0.05). Male gender and CT were strong determinants of irritability (p < 0.05). Violence against property and people was found to be reduced in females, and increased in males with a history of emotional and sexual abuse, respectively (p < 0.05). CONCLUSION: These preliminary findings highlight the significant impact of CT in PBD and suggest that gender may predict the risk for dysfunctional behaviors in PBD patients with CT. Future large scale, longitudinal, investigations focusing on fear processing and extinction may provide a deeper understanding of these gender differences, and their role in the course of BD.

Hippocampal subfield volumes in children and adolescents with mood disorders.

The hippocampus has been implicated in various mood disorders, with global volume deficits consistently found in patient populations. The hippocampus, however, consists of anatomically distinct subfields, and examination of specific subfield differences may elucidate the possible molecular mechanisms behind psychiatric pathologies. Indeed, adult studies have reported smaller hippocampal subfield volumes in regions within the cornu ammonis (CA1 and CA4), dentate gyrus (DG), and hippocampal tails in both patients with Major Depressive Disorder (MDD) and Bipolar Disorder (BD) compared to healthy controls. Subfield differences in pediatric patients with mood disorders, on the other hand, have not been extensively investigated. In the current study, magnetic resonance imaging scans were acquired for 141 children and adolescents between the ages of eight and eighteen (57 with BD, 30 with MDD, and 54 healthy controls). An automated segmentation method was then used to assess differences in hippocampal subfield volumes. Children and adolescents with BD were found to have significantly smaller volumes in the right CA1, CA4, and right subiculum, as well as the bilateral granule cell layer (GCL), molecular layer (ML), and hippocampal tails. The volume of the right subiculum in BD patients was also found to be negatively correlated with illness duration. Overall, the findings from this cross-sectional study provide evidence for specific hippocampal subfield volume differences in children and adolescents with BD compared to healthy controls and suggest progressive reductions with increased illness duration.

The Columbia-Suicide Severity Rating Scale: Associations between interrupted, aborted, and actual suicide attempts among adolescent inpatients.

The Columbia-Suicide Severity Rating Scale divides suicide attempt behaviors into actual, interrupted, and aborted attempts, but limited data have been reported regarding associations between interrupted, aborted, and actual attempts. This study provided initial data on the ability of interrupted and aborted attempts to estimate the frequency of actual suicide attempts. Participants were adolescent psychiatric inpatients (59.9% female), 12-17 years (mean = 14.73, SD = 1.62). Results suggest that interrupted and aborted suicide attempts are associated with the frequency of actual suicide attempts, controlling for suicidal ideation and depressive symptoms. Future research should evaluate whether interrupted and aborted attempts prospectively predicting actual suicide attempts.

Accelerated epigenetic aging and mitochondrial DNA copy number in bipolar disorder.

Bipolar disorder (BD) has been previously associated with accelerated aging; yet, the mechanisms underlying this association are largely unknown. The epigenetic clock has been increasingly recognized as a valuable aging marker, although its association with other biological clocks in BD patients and high-risk subjects, such as telomere length and mitochondrial DNA (mtDNA) copy number, has never been investigated. We included 22 patients with BD I, 16 siblings of BD patients, and 20 healthy controls in this analysis. DNA was isolated from peripheral blood and interrogated for genome-wide DNA methylation, mtDNA copy number, and telomere length. DNA methylation age (DNAm age) and accelerated aging were calculated using the Horvath age estimation algorithm in blood and in postmortem brain from BD patients and nonpsychiatric controls using publicly available data. Older BD patients presented significantly accelerated epigenetic aging compared to controls, whereas no difference was detected among the younger subjects. Patients showed higher levels of mtDNA copy number, while no difference was found between controls and siblings. mtDNA significantly correlated with epigenetic age acceleration among older subjects, as well and with global functioning in our sample. Telomere length did not show significant differences between groups, nor did it correlate with epigenetic aging or mtDNA copy number. These results suggest that BD may involve an accelerated epigenetic aging, which might represent a novel target for treating BD and subjects at risk. In particular, our results suggest a complex interplay between biological clocks to determine the accelerated aging and its consequences in BD.