Faculty Bibliography

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.

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.

Reduction in parvalbumin-positive (PV+) interneurons is observed in adult mice exposed to ethanol at postnatal day 7 (P7), a late gestation fetal alcohol spectrum disorder model. To evaluate whether PV+ cells are lost, or PV expression is reduced, we quantified PV+ and associated perineuronal net (PNN)+ cell densities in barrel cortex. While PNN+ cell density was not reduced by P7 ethanol, PV cell density decreased by 25% at P90 with no decrease at P14. PNN+ cells in controls were virtually all PV+, whereas more than 20% lacked PV in ethanol-treated adult animals. P7 ethanol caused immediate apoptosis in 10% of GFP+ cells in G42 mice, which express GFP in a subset of PV+ cells, and GFP+ cell density decreased by 60% at P90 without reduction at P14. The ethanol effect on PV+ cell density was attenuated by lithium treatment at P7 or at P14-28. Thus, reduced PV+ cell density may be caused by disrupted cell maturation, in addition to acute apoptosis. This effect may be regionally specific: in the dentate gyrus, P7 ethanol reduced PV+ cell density by 70% at P14 and both PV+ and PNN+ cell densities by 50% at P90, and delayed lithium did not alleviate ethanol's effect.

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.

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.

Sézary syndrome (SS) is the leukemic form of cutaneous T-cell lymphoma (CTCL) and can be associated with various nail irregularities, though they are infrequently reported. In this retrospective study, we reviewed medical records from a CTCL clinic database at the University of Texas MD Anderson Cancer Center (Houston, Texas) for reported nail abnormalities in patients with a diagnosis of SS. Findings for 2 select cases are described in more detail and are compared to prior case reports to establish a comprehensive list of nail irregularities that have been associated with SS.

Social support can buffer against stressors often associated with having family members with autism spectrum disorder. This study included 112 parents and typically developing siblings of children with autism spectrum disorder. Relations between self-reported typically developing sibling emotional and behavioral problems and discrepancy between social support frequency and importance were examined via polynomial regression with response surface analysis. Typically developing siblings who described social support as frequent and important reported relatively few problems. Typically developing siblings who reported social support as highly important but infrequent exhibited the highest emotional and behavioral difficulties. Thus, typically developing siblings with little support who view support as highly important may be particularly responsive to social support improvement efforts.

We conducted a systematic review of studies that have evaluated invariance of the construct of posttraumatic stress disorder (PTSD) to summarize their conclusions related to invariance/noninvariance and sources of noninvariance. In November 2017, we searched Pubmed, PSYCINFO, PILOTS Web of Science, CINAHL, Medline, and Psychological and Behavioral Science Collection for abstracts and articles with these inclusionary criteria: peer-reviewed, including DSM-IV or DSM-5 PTSD invariance as a main study aim, use of multigroup confirmatory factor analyses, and use of an independent PTSD instrument or module. In total, 45 articles out of 1,169 initially identified abstracts met inclusion criteria. Research assistants then followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to complete a secondary search and independently extract data. Results indicated that DSM-IV dysphoric arousal and DSM-5 hybrid model factors demonstrated the most stability; sources of instability were some intrusion (distress to trauma cues), dysphoria/numbing (traumatic amnesia, foreshortened future, emotional numbness, detachment), and arousal (hypervigilance) items. The PTSD Checklist and PTSD Reaction Index were most often used to assess PTSD in studies investigating its invariance; however, these measures demonstrated partial conceptual equivalence of PTSD across subgroups. Instead, clinician-administered measures demonstrated more conceptual equivalence across subgroups. Age, gender, cultural/linguistic factors, and sample diversity had the least moderating effect on PTSD's symptom structure. Our review demonstrates the need to examine invariance of the PTSD construct following recommended guidelines for each empirical and clinical trial study to draw meaningful multigroup comparative conclusions.

Over the past two decades, a low frequency variant (rs1800012) within the first intron of the type I collagen alpha 1 (COLIA1) gene has been implicated in lower areal BMD (aBMD) and increased risk of osteoporotic fracture. This association is particularly strong in postmenopausal women, in whom net bone loss arises in the context of high bone turnover. High bone turnover also accompanies childhood linear growth; however, the role of rs1800012 in this stage of net bone accretion is less well understood. Thus, we assessed the association between rs1800012 and aBMD and bone mineral content (BMC) Z-scores for the 1/3 distal radius, lumbar spine, total hip, and femoral neck total body less head in the Bone Mineral Density in Childhood Study, a mixed-longitudinal cohort of children and adolescents (total n = 804 girls and 771 boys; n = 19 girls and 22 boys with the TT genotype). Mixed effects modeling, stratified by sex, was used to test for associations between rs1800012 and aBMD or BMC Z-scores and for pubertal stage interactions. Separately, SITAR growth modeling of aBMD and BMC in subjects with longitudinal data reduced the complex longitudinal bone accrual curves into three parameters representing a-size, b-timing, and c-velocity. We tested for differences in these three parameters by rs1800012 genotype using t-tests. Girls with the TT genotype had significantly lower aBMD and BMC Z-scores prior to puberty completion (e.g. spine aBMD-Z P-interaction = 1.0 × 10^-6), but this association was attenuated post-puberty. SITAR models revealed that TT girls began pubertal bone accrual later (b-timing; e.g. total hip BMC, P = 0.03). BMC and aBMD Z-scores also increased across puberty in TT homozygous boys. Our data, along with previous findings in post-menopausal women, suggest that rs1800012 principally affects female bone density during periods of high turnover. Insights into the genetics of bone gain and loss may be masked during the relatively quiescent state in mid-adulthood, and discovery efforts should focus on early and late life.