Faculty Bibliography

OBJECTIVE:The habenula is a small region in the epithalamus that contributes to the regulation of midbrain dopaminergic circuits implicated in attention-deficit hyperactivity disorder (ADHD). This investigation aims to evaluate the intrinsic functional connectivity (iFC) of the habenula in children with ADHD. METHOD/METHODS:A total of 112 children (5-9 years; 75 ADHD, 37 healthy comparisons) completed anatomical and resting-state functional magnetic resonance imaging (MRI) scans. Habenula regions of interest (ROIs) were identified individually on normalized T1-weighted anatomical images. Seed-based iFC analyses and group comparisons were conducted for habenula ROIs, as well as thalamic ROIs to test the specificity of habenula findings. RESULTS:Children with ADHD exhibited reduced habenula-putamen iFC compared with healthy comparisons. Group differences in thalamic iFC showed no overlap with habenular findings. CONCLUSION/CONCLUSIONS:These preliminary findings suggest that habenula-putamen iFC may be disrupted in children with ADHD. Further work is needed to confirm and elucidate the role of this circuit in ADHD pathophysiology.

OBJECTIVE:There is no standard method for assessing symptoms of the prodrome to bipolar disorder (BD), which has limited progress toward early identification and intervention. We aimed to validate the Bipolar Prodrome Symptom Scale-Abbreviated Screen for Patients (BPSS-AS-P), a brief self-report derived from the validated, clinician-rated Bipolar Prodrome Symptom Interview and Scale-Full Prospective (BPSS-FP), as a means to screen and identify people for whom further evaluation is indicated. METHOD/METHODS:Altogether, 134 participants (aged 12-18 years) were drawn from a study of the pre-syndromal stage of mood and psychotic disorders. All participants had chart diagnoses of a mood- or psychosis-spectrum disorder. Participants were interviewed with the BPSS-FP and completed measures of mania and non-mood psychopathology. Prior to being interviewed, patients completed the BPSS-AS-P. Scores on the BPSS-AS-P were determined by summing the severity and frequency ratings for each item. RESULTS:BPSS-AS-P scores were highly reliable (Cronbach's alpha = 0.94) and correlated with the interview-based BPSS-FP Mania Symptom Index (r = 0.55, p < .0001). BPSS-AS-P scores had good convergent validity, correlating with the General Behavior Inventory-10M (r = 0.65, p < .0001) and Young Mania Rating Scale; r = 0.48, p < .0001). The BPSS-AS-P had good discriminant validity, not being correlated with scales measuring positive and negative symptoms of psychotic disorders (p-values = 0.072-0.667). LIMITATIONS/CONCLUSIONS:Findings are limited by the cross-sectional nature of the study by the fact that the participants were all treatment-seeking. Future studies need to evaluate the predictive validity of the BPSS-AS-P for identifying those who develop BD in a community sample. CONCLUSION/CONCLUSIONS:BPSS-AS-P has promise as a screening tool for people at risk for BD. Adopting the BPSS-AS-P would support the goal of characterizing the prodrome systematically in order to facilitate research and clinical care.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder associated with social communication deficits and restricted/repetitive behaviors and is characterized by large-scale atypical subcortical-cortical connectivity, including impaired resting-state functional connectivity between thalamic and sensory regions. Previous studies have typically focused on the abnormal static connectivity in ASD and overlooked potential valuable dynamic patterns in brain connectivity. However, resting-state brain connectivity is indeed highly dynamic, and abnormalities in dynamic brain connectivity have been widely identified in psychiatric disorders. In this study, we investigated the dynamic functional network connectivity (dFNC) between 51 intrinsic connectivity networks in 170 individuals with ASD and 195 age-matched typically developing (TD) controls using independent component analysis and a sliding window approach. A hard clustering state analysis and a fuzzy meta-state analysis were conducted respectively, for the exploration of local and global aberrant dynamic connectivity patterns in ASD. We examined the group difference in dFNC between thalamic and sensory networks in each functional state and group differences in four high-dimensional dynamic measures. The results showed that compared with TD controls, individuals with ASD show an increase in transient connectivity between hypothalamus/subthalamus and some sensory networks (right postcentral gyrus, bi paracentral lobule, and lingual gyrus) in certain functional states, and diminished global meta-state dynamics of the whole-brain functional network. In addition, these atypical dynamic patterns are significantly associated with autistic symptoms indexed by the Autism Diagnostic Observation Schedule. These converging results support and extend previous observations regarding hyperconnectivity between thalamic and sensory regions and stable whole-brain functional configuration in ASD. Dynamic brain connectivity may serve as a potential biomarker of ASD and further investigation of these dynamic patterns might help to advance our understanding of behavioral differences in this complex neurodevelopmental disorder.

We report the first experimental results on spin-dependent elastic weakly interacting massive particle (WIMP) nucleon scattering from the XENON1T dark matter search experiment. The analysis uses the full ton year exposure of XENON1T to constrain the spin-dependent proton-only and neutron-only cases. No significant signal excess is observed, and a profile likelihood ratio analysis is used to set exclusion limits on the WIMP-nucleon interactions. This includes the most stringent constraint to date on the WIMP-neutron cross section, with a minimum of 6.3×10^{-42}  cm^{2} at 30  GeV/c^{2} and 90% confidence level. The results are compared with those from collider searches and used to exclude new parameter space in an isoscalar theory with an axial-vector mediator.

OBJECTIVES/OBJECTIVE:Recent magnetic resonance imaging (MRI) studies implicate structural alterations of amygdala, a brain region responsible for processing and experiencing negative emotions, in adolescents with attention-deficit/hyperactivity disorder (ADHD). Here we examined ADHD-related structural correlates of amygdala functional activity elicited during a functional MRI task designed to test behavioural and brain responses to the imposition of delay - an event known to both elicit amygdala hyperactivation and aversity in ADHD. METHODS:Structural MRI scans from 28 right-handed male adolescents with combined type ADHD and 32 age-matched controls were analysed. Regional grey matter volumes of ADHD and control participants (P[FWE] < 0.05) were correlated with delay aversion self-ratings and neural activity in response to delay-related cues on the Escape Delay Incentive fMRI task. RESULTS:ADHD was associated with significantly reduced volumes in bilateral amygdala, parahippocampal and temporal gyrus (P[FWE] < 0.05), greater basolateral amygdala activation to delay-related cues (P[FWE] < 0.05) and higher delay aversion self-ratings. Amygdala volume reductions were significantly correlated with, and statistically mediated the pathway from ADHD to, delay-cue-related amygdala hyperactivity (P < 0.01) and self-reported delay aversion (P < 0.01). CONCLUSIONS:We provide the first evidence of the functional significance of reduced amygdala volumes in adolescents with ADHD by highlighting its relation to delay-induced brain activity that is linked to delay aversion.

BACKGROUND:Disruptive Behavioral Disorders (DBDs) and Attention Deficit/Hyperactivity Disorder (ADHD) are chronic, impairing, and costly child and adolescent mental health challenges which, when untreated, can result in disruptions in school performance, friendships and family relations. Yet, there is dearth of prevalence data on child and adolescent behavioral challenges within sub-Saharan Africa, including Uganda. This study aims to estimate the prevalence rate of behavioral challenges and ADHD among young school going children and early adolescents (ages 8-13 at study enrollment), utilizing a school-based sample in southwest Uganda. METHODS:We present screening results from a 5-year scale-up study titled SMART Africa-Uganda (2016-2021), set across 30 public primary schools located in the greater Masaka region in Uganda, a region heavily impacted by poverty and HIV/AIDS. Specifically, we draw on screening data from caregivers of 2434 children that used well-established standardized measures that had been pre-tested in the region. These were: 1) oppositional defiant disorder (ODD) and conduct disorder (CD) subscales of the Disruptive Behavior Disorders (DBD) scale; and 2) the Iowa Connors and Impairment scales. Slightly over half of the children in the sample were female (52%), with a mean age of 10.27 years. RESULTS:Of the 2434 participants screened for disruptive behaviors: 1) 6% (n = 136) scored positive on ODD and 2% (n = 42) scored positive on CD subscales of the DBD scale; 2) 9.61% (n = 234), and 2.67% (n = 65) were reported to have elevated symptoms of ODD and ADHD on the Iowa Connors caregiver report scale respectively. Twenty-five percent (n = 586) of children were described by their caregivers as having experienced some form of impairment in at least four domains of the Impairment scale. CONCLUSION/CONCLUSIONS:The results indicate the presence of behavioral challenges and ADHD among school going children, aged 8-13 years, in Uganda. Given the negative outcomes associated with behavioral challenges as children transition to adolescence and adulthood, detecting these emerging behavioral challenges early is critical in developing appropriate interventions. School settings could be considered as one of the contextually-relevant, culturally-appropriate, and non-stigmatizing venues to implement screening procedures and to detect emerging behavioral challenges and to make necessary referrals.

OBJECTIVE:Research on pediatric bipolar disorder (PBD) has grown substantially in the past 7 years; updating a 2011 meta-analysis of PBD prevalence could improve understanding of factors that influence prevalence. DATA SOURCES:A literature review of papers published in English was updated in 2018 using PubMed and PsycINFO. Search terms included pediatric, child, "bipolar disorder," bipolar, mania, prevalence, epidemiology, community, adolescent, and youth. STUDY SELECTION:Inclusion criteria were (1) youth epidemiologic sample, (2) number of youth with bipolar spectrum disorders reported, and (3) prevalence rates for youth differentiated from prevalence for those over age 21 years (if both included). Of 2,400 articles retrieved, 44 were evaluated and 8 new were included. DATA EXTRACTION:Prevalence rates for each bipolar subtype were recorded as reported; hypothesized moderators (eg, study characteristics, environmental factors) were also coded. RESULTS:Eight additional studies resulted in a total sample of 19 studies, tripling the sample size to N = 56,103 and n = 1,383 with bipolar disorder. Seven studies were from the United States, and 12 were from South America, Central America, or Europe. Weighted average prevalence of bipolar spectrum disorders was 3.9% (95% CI, 2.6%-5.8%). There was significant heterogeneity across studies (Q = 759.82, df = 32, P < .0005). The pooled rate of bipolar I was 0.6% (95% CI, 0.3%-1.2%); these rates were also heterogeneous (Q = 154.27, df = 13, P < .0001). Predictors of higher bipolar spectrum disorder prevalence were the use of broad bipolar criteria (P < .0001), older minimum age (P = .005), and lifetime prevalence (P = .002). Newer studies were associated with lower rates (P < .0001). CONCLUSIONS:The updated meta-analysis confirms that rates of bipolar spectrum disorders are not higher in the United States than in other Western countries, nor are rates increasing over time. Nonstandard diagnostic criteria result in highly variable prevalence rates, as does focusing on narrow definitions of PBD to the exclusion of the full spectrum. Consistent application of validated criteria could help to settle questions regarding PBD prevalence. Studies from non-Western countries are needed to refine understanding of international prevalence and risk factors.

CONTEXT/BACKGROUND:Dual-energy X-ray absorptiometry (DXA) is a cornerstone of pediatric bone health assessment, yet differences in height-for-age confound the interpretation of areal bone mineral density (aBMD) measures. To reduce the confounding of short stature on spine bone density, use of bone mineral apparent density (BMAD) and height-for-age Z-score (HAZ)‒adjusted aBMD (aBMDHAZ) are recommended. However, spine BMAD reference data are sparse, and the degree to which BMAD and aBMDHAZ account for height-related artifacts in bone density remains unclear. OBJECTIVE:We developed age-, sex-, and population ancestry‒specific spine BMAD reference ranges; compared height-adjustment methods in accounting for shorter stature; and assessed the stability of these measures over time. DESIGN/METHODS:Secondary analysis of data from a previous longitudinal study. PARTICIPANTS/METHODS:Children and adolescents aged 5 to 19 years at baseline (n = 2014; 922 males; 22% black) from the Bone Mineral Density in Childhood Study. MAIN OUTCOME MEASURES/METHODS:Lumbar spine BMAD and aBMDHAZ from DXA. RESULTS:Spine BMAD increased nonlinearly with age and was greater in blacks and females (all P < 0.001). Age-specific spine BMAD z-score reference curves were constructed for black and non‒black males and females. Overall, both BMAD and aBMDHAZz scores reduced the confounding influence of shorter stature, but neither was consistently unbiased across all age ranges. Both BMAD and aBMDHAZz scores tracked strongly over 6 years (r = 0.70 to 0.80; all P < 0.001). CONCLUSION/CONCLUSIONS:This study provided robust spine BMAD reference ranges and demonstrated that BMAD and aBMDHAZ partially reduced the confounding influence of shorter stature on bone density.

OBJECTIVE:Behavioral intervention technologies (BITs) stand as a promising delivery mechanism that overcomes multiple condition-specific and access barriers for self-management interventions for adolescents and young adults with spina bifida (AYA-SB). The purpose of the current review was to synthesize the behavioral and self-management intervention literature in conditions that have overlapping symptoms with youth with SB and to develop a model of likely user needs for AYA-SB that promotes self-management. METHOD:The search strategy was conducted by a medical research librarian in the following databases: MEDLINE (Ovid), EMBASE (Elsevier), PsycINFO (EbscoHost), the Cochrane Library (Wiley), and Web of Science (Thomson Reuters) databases. The review was based on a systematic narrative synthesis framework and adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (registration number CRD42018092342). RESULTS:In total, 18 articles were included in the current BIT review. The majority of included studies (1) targeted the management of chronic health conditions, (2) were informed by evidence-based approaches, (3) relied on content delivery, (4) were Web-based, (5) used linear or user-driven workflows, (6) included professional human support, and (7) included a control condition. CONCLUSIONS:Many of the evaluated BITs resulted in acceptable usage and maintained or improved targeted symptoms. A user needs model for AYA-SB is proposed with the intention that future research will promote further refinement and ultimate deployment of a BIT for AYA-SB to promote self-management.

Human brain anatomical and resting-state functional connectivity have been comprehensively portrayed using MRI, which are termed anatomical and functional connectomes. A systematic examination of tasks modulated whole brain functional connectivity, which we term as task connectome, is still lacking. We analyzed 6 block-designed and 1 event-related designed functional MRI data, and examined whole-brain task modulated connectivity in various task domains, including emotion, reward, language, relation, social cognition, working memory, and inhibition. By using psychophysiological interaction between pairs of regions from the whole brain, we identified statistically significant task modulated connectivity in 4 tasks between their experimental and respective control conditions. Task modulated connectivity was found not only between regions that were activated during the task but also regions that were not activated or deactivated, suggesting a broader involvement of brain regions in a task than indicated by simple regional activations. Decreased functional connectivity was observed in all the 4 tasks and sometimes reduced connectivity was even between regions that were both activated during the task. This suggests that brain regions that are activated together do not necessarily work together. The current study demonstrates the comprehensive task connectomes of 4 tasks, and suggested complex relationships between regional activations and connectivity changes.