Faculty Bibliography

BACKGROUND:Previous studies are inconclusive concerning the association between maternal pre-pregnancy overweight/obesity and risk of attention-deficit/hyperactivity disorder (ADHD) in offspring. We therefore conducted a systematic review and meta-analysis to clarify this association. To address the variation in confounding adjustment between studies, especially inadequate adjustment of unmeasured familial confounding in most studies, we further performed cousin and sibling comparisons in a nationwide population-based cohort in Sweden. METHODS:We searched PubMed, Embase and PsycINFO during 1975-2018. We used random-effects models to calculate pooled risk ratios (RRs) with 95% confidence interval. In the population-based study, Cox proportional hazard models were used to calculate the unadjusted hazard ratios (HRs) and HRs adjusted for all confounders identified in previous studies. Stratified Cox models were applied to data on full cousins and full siblings to further control for unmeasured familial confounding. RESULTS:Eight cohorts with a total of 784 804 mother-child pairs were included in the meta-analysis. Maternal overweight [RRoverweight = 1.31 (1.25-1.38), I2 = 6.80%] and obesity [RRobesity = 1.92 (1.84-2.00), I2 = 0.00%] were both associated with an increased risk of ADHD in offspring. In the population-based cohort of 971 501 individuals born between 1992 and 2004, unadjusted Cox models revealed similar associations [HRoverweight = 1.30 (1.28-1.34), HRobesity = 1.92 (1.87-1.98)]. These associations gradually attenuated towards the null when adjusted for measured confounders [HRoverweight = 1.21 (1.19-1.25), HRobesity = 1.60 (1.55-1.65)], unmeasured factors shared by cousins [HRoverweight = 1.10 (0.98-1.23), HRobesity = 1.44 (1.22-1.70)] and unmeasured factors shared by siblings [HRoverweight = 1.01 (0.92-1.11), HRobesity = 1.10 (0.94-1.27)]. CONCLUSION/CONCLUSIONS:Pre-pregnancy overweight/obesity is associated with an increased risk of ADHD in offspring. The observed association is largely due to unmeasured familial confounding.

BACKGROUND:Antidepressants may be used to manage a number of conditions in children and young people including depression, anxiety, and obsessive-compulsive disorder. UK guidelines for the treatment of depression in children and young people recommend that antidepressants should only be initiated following assessment and diagnosis by a child and adolescent psychiatrist. The aim of this study was to summarise visits to mental health specialists and indications recorded around the time of antidepressant initiation in children and young people in UK primary care. METHODS:The study used linked English primary care electronic health records and Hospital Episode Statistics secondary care data. The study included 5-17-year-olds first prescribed antidepressants between January 2006 and December 2017. Records of visits to paediatric or psychiatric specialists and potential indications (from a pre-specified list) were extracted. Events were counted if recorded less than 12 months before or 6 months after the first antidepressant prescription. Results were stratified by first antidepressant type (all, selective serotonin reuptake inhibitors (SSRIs), tricyclic and related antidepressants) and by age group (5-11 years, 12-17 years). RESULTS:In total, 33,031 5-17-year-olds were included. Of these, 12,149 (37%) had a record of visiting a paediatrician or a psychiatric specialist in the specified time window. The majority of recorded visits (7154, 22%) were to paediatricians. Of those prescribed SSRIs, 5463/22,130 (25%) had a record of visiting a child and adolescent psychiatrist. Overall, 17,972 (54%) patients had a record of at least one of the pre-specified indications. Depression was the most frequently recorded indication (12,501, 38%), followed by anxiety (4155, 13%). CONCLUSIONS:The results suggest many children and young people are being prescribed antidepressants without the recommended involvement of a relevant specialist. These findings may justify both greater training for GPs in child and adolescent mental health and greater access to specialist care and non-pharmacological treatments. Further research is needed to explore factors that influence how and why GPs prescribe antidepressants to children and young people and the real-world practice barriers to adherence to clinical guidelines.

Drawing on data from the Clinical Practice Research Datalink, Price et al reported UK regional variations in primary care prescribing and referral rates to adult mental health services for young people with attention-deficit hyperactivity disorder (ADHD) in transition from child and adolescent mental health services. Overall, considering that around 65% of young adults with childhood ADHD present with impairing ADHD symptoms and up to 90% of individuals with ADHD may benefit from ADHD medications, the study by Price et al shows that the rate of appropriate treatment for youngsters in the transition period varies from low to very low across the UK. As such, there is a continuous need for education and training for patients, their families, mental health professionals and commissioners, to eradicate the misconception that, in the majority of the cases, ADHD remits during adolescence and to support the devolvement of appropriate services for the evidence-based management of adult ADHD across the UK.

INTRODUCTION/BACKGROUND:Affirmative health care is imperative to address health and mental health disparities faced by transgender communities. Yet, transgender help-seekers experience discrimination that precludes their access to and participation in care. This study uses latent class analysis to examine patterns of healthcare discrimination among transgender help-seekers. Predictors of class membership are investigated to identify subpopulations at highest risk for healthcare discrimination. METHODS:Data were obtained from the 2015 U.S. Transgender Survey and analyzed in 2019. Ten healthcare experiences were included as latent class indicators. Latent class analysis and regression were performed in Mplus, version 8 to identify latent subgroups and examine the relationship between respondent characteristics and the latent classes. RESULTS:The final sample included 23,541 respondents. A 3-class model fit best: Class 1 experienced overt discrimination and interfaced with providers with limited trans-competence; Class 2 did not experience healthcare discrimination or report issues related to providers' trans-competence; and Class 3 did not experience discrimination but had providers with low trans-competence. Transmen and respondents who were out as trans to their providers and reported psychological distress, suicidal thoughts, and disabilities were more likely to be members of Class 1 or 3 than Class 2. CONCLUSIONS:Experiences of healthcare discrimination are not homogeneous across transgender help-seekers. Predictors of the latent classes indicated that transgender help-seekers holding an additional marginalized identity may be at higher risk for healthcare discrimination or care from providers with limited trans-competence. Targeted engagement and education interventions might improve these transgender help-seekers' access to and connections with care.

OBJECTIVE:Randomized clinical trials of augmentation strategies for youth with treatment-resistant anxiety disorders do not exist. This report presents findings from an efficacy trial of attention bias modification treatment (ABMT) as an augment for this population compared with attention control training (ACT). METHOD/METHODS:Sixty-four youths (34 boys; mean age 11.7 years) who continued to meet for anxiety diagnoses after completing cognitive-behavioral therapy were randomized to ABMT or ACT. ABMT and ACT consisted of dot-probe attention training trials presenting angry and neutral faces; probes appeared in the location of neutral faces on 100% of trials in ABMT and 50% of trials in ACT. Independent evaluators, youths, and parents completed ratings of youth anxiety severity, and youths completed measures of attention bias to threat and attention control at pretreatment, post-treatment, and 2-month follow-up. RESULTS:The 2 arms showed significant decreases in anxiety severity, with no differences between arms. Specifically, across informants, anxiety severity was significantly decreased at post-treatment and decreases were maintained at follow-up. Primary anxiety disorder diagnostic recovery combined across arms was 50% at post-treatment and 58% at follow-up. Attention control, but not attention bias to threat, was significantly improved at post-treatment in the 2 arms. CONCLUSION/CONCLUSIONS:This is the first study to show anxiety can be decreased in youth who did not respond to cognitive-behaviorial therapy, and that the anxiety-decreasing effect is found using these 2 attention training contingency schedules. These findings and increases in attention control in the 2 arms raise intriguing questions about mechanisms of decreasing anxiety in treatment-resistant youth with attention training that require further research. CLINICAL TRIAL REGISTRATION INFORMATION/BACKGROUND:Attention Bias Modification Training for Child Anxiety CBT Nonresponders; https://clinicaltrials.gov/; NCT01819311.

Residential mobility is hypothesized to impact health through changes to the built environment and disruptions in social networks, and may vary by neighborhood deprivation exposure. However, there are few longitudinal investigations of residential mobility in relation to health outcomes. This study examined enrollees from the World Trade Center Health Registry, a longitudinal cohort of first responders and community members in lower Manhattan on September 11, 2001. Enrollees who completed ≥2 health surveys between 2004 and 2016 and did not have diabetes (N = 44,089) or hypertension (N = 35,065) at baseline (i.e., 2004) were included. Using geocoded annual home addresses, residential mobility was examined using two indicators: moving frequency and displacement. Moving frequency was defined as the number of times someone was recorded as living in a different neighborhood; displacement as any moving to a more disadvantaged neighborhood. We fit adjusted Cox proportional hazards models with time-dependent exposures (moving frequency and displacement) and covariates to evaluate associations with incident diabetes and hypertension. From 2004 to 2016, the majority of enrollees never moved (54.5%); 6.5% moved ≥3 times. Those who moved ≥3 times had a similar hazard of diabetes (hazard ratio (HR) = 0.78; 95% Confidence Interval (CI): 0.40, 1.53) and hypertension (HR = 0.99; 95% CI: 0.68, 1.43) compared with those who never moved. Similarly, displacement was not associated with diabetes or hypertension. Residential mobility was not associated with diabetes or hypertension among a cohort of primarily urban-dwelling adults.

The precuneus (PreC; Brodmann area 7), a key hub within the default mode network (DMN) displays amyloid and tau-containing neurofibrillary tangle (NFT) pathology during the onset of Alzheimer's disease (AD). PreC layer III projection neurons contain lysosomal hydrolase cathepsin D (CatD), 14)a marker of neurons vulnerable to NFT pathology. Here we applied single population laser capture microdissection coupled with custom-designed microarray profiling to determine the genetic signature of PreC CatD-positive-layer III neurons accrued from postmortem tissue obtained from the Rush Religious Orders Study (RROS) cases with a premortem clinical diagnosis of no cognitive impairment (NCI), mild cognitive impairment (MCI) and AD. Expression profiling revealed significant differential expression of key transcripts in MCI and AD compared to NCI that underlie signaling defects, including dysregulation of genes within the endosomal-lysosomal and autophagy pathways, cytoskeletal elements, AD-related genes, ionotropic and metabotropic glutamate receptors, cholinergic enzyme and receptors, markers of monoamine neurotransmission as well as steroid-related transcripts. Pervasive defects in both MCI and AD were found in select transcripts within these key gene ontology categories, underscoring the vulnerability of these corticocortical neurons during the onset and progression of dementia. Select PreC dysregulated genes detected via custom-designed microarray analysis were validated using qPCR. In summary, expression profiling of CatD positive PreC layer III neurons revealed significant dysregulation of a mosaic of genes in MCI and AD that were not previously appreciated in terms of their indication of systems-wide signaling defects in a key hub of the DMN. This article is protected by copyright. All rights reserved.

Magnetic resonance imaging, histological, and gene analysis approaches in living and nonliving human fetuses and in prematurely born neonates have provided insight into the staged processes of prenatal brain development. Increased understanding of micro- and macroscale brain network development before birth has spurred interest in understanding the relevance of prenatal brain development to common neurological diseases. Questions abound as to the sensitivity of the intrauterine brain to environmental programming, to windows of plasticity, and to the prenatal origin of disorders of childhood that involve disruptions in large-scale network connectivity. Much of the available literature on human prenatal neural development comes from cross-sectional or case studies that are not able to resolve the longitudinal consequences of individual variation in brain development before birth. This review will 1) detail specific methodologies for studying the human prenatal brain, 2) summarize large-scale human prenatal neural network development, integrating findings from across a variety of experimental approaches, 3) explore the plasticity of the early developing brain as well as potential sex differences in prenatal susceptibility, and 4) evaluate opportunities to link specific prenatal brain developmental processes to the forms of aberrant neural connectivity that underlie common neurological disorders of childhood.