Faculty Bibliography

BACKGROUND:Preexposure prophylaxis (PrEP) reduces risk of human immunodeficiency virus infection for many gay and bisexual men (GBM); however, bacterial sexually transmitted infections associated with decreasing condom use among users is of concern. Center for Disease Control and Prevention's guidelines for PrEP use recommend bacterial sexually transmitted infection screening every 6 months. We sought to investigate comprehensive PrEP care, defined as: (1) discussion of sexual behavior, (2) blood sample, (3) urine sample, (4) rectal sample (rectal swab), and (5) throat sample (throat swab), provided at the user's last PrEP appointment. METHODS:The PrEP-using GBM in New York City (n = 104) were asked about their last PrEP care visit. We examined associations of demographics (age, race/ethnicity, and education), recent number of condomless anal sex events, time on PrEP, and health care provider type on receiving comprehensive care at last visit using fully adjusted binary logistic regression. RESULTS:At their last visit, nearly all men (94%) gave blood for testing, 88% provided a urine sample, and 77% discussed sexual behavior with their provider. However, only 51% reported having a rectal swab, and 48% an oral swab. Only 32% of men received comprehensive PrEP care at their last PrEP visit. Odds of receiving comprehensive care were significantly higher among younger men, men with a bachelor's degree or more education, and those who reported more condomless anal sex. CONCLUSIONS:Less than one third of GBM received comprehensive human immunodeficiency virus/sexually transmitted infection counseling and testing at their last visit. These findings indicate further efforts are needed to prepare health care providers for prescribing and managing patients on PrEP.

Early life stress in humans (i.e. maltreatment, violence exposure, loss of a loved one) and in rodents (i.e. disrupted attachment or nesting, electric shock, restraint, predator odor) occurs during critical steps of neural circuit formation. ELS in humans is associated with increased risk for developmental psychopathology, including anxious and depressive phenotypes. The biological mechanisms underlying these potentially persistent maladaptive changes involve long-term epigenetic modifications, which have been suggested to be potentially transmissible to subsequent generations. DNA methylation is an epigenetic mechanism that modifies gene expression patterns in response to environmental challenges and influences mutation rates. It remains to be seen whether a functionally relevant fraction of DNA methylation marks can escape genome-wide erasures that occur in primordial germ cells and after fertilization within the zygote. Early life-stress-triggered changes in epigenetic mediated transmission of acquired behavioral traits among humans have been assessed mainly by targeting genes involved in the hypothalamic-pituitary-adrenal (HPA) axis, such as NR3C1 and FKBP5. Recently, researchers examining epigenetic transmission have begun to apply genome-wide approaches. In humans, reduced representation bisulfite sequencing (RRBS) was performed on peripheral samples that were obtained from individuals who were prenatally exposed to the "Dutch Hunger Winter", resulting in two Differentially Methylated Regions (DMRs) in INSR and CPTIA genes that were functionally, biologically and technically validated, and significantly associated with birth weights and LDL cholesterol levels in offspring. In rodents, non-genomic intergenerational transmission of anxiety which was associated with differentially methylated enhancers that were putatively involved in lipid signaling and synaptic/neurotransmission in hippocampal granule cells, was discovered also using RRBS. Finally, transgenerational transmission of altered behaviors was associated with sperm-derived microRNAs produced by ELS male mice. The field of epigenetic transmission is just beginning to enter the epigenomic era by using genome-wide analyses. Such approaches remain of strong interest to human studies, first in order to help to assess the relevance of the previous targeted studies, and second to discover new important epigenetic modifications of potential clinical importance. New discoveries may help to assess how transmittable the negative impact of stress may be to offspring. The latter may open doors for future treatments and resilience-promoting interventions, as well as new approaches to treat the effects of childhood trauma before the onset of psychiatric disorder.

Future orientation (FO) has received increasing attention for its positive effects on adolescent well-being and successful transition to adulthood. Although numerous measures of FO exist, most are not developmentally appropriate for diverse populations of adolescents, do not assess all theoretical components of FO, and/or were not developed for administration in schools. Additionally, the invariance of existing measures across racial/ethnic groups has not been examined using appropriately rigorous procedures. Using data from 2575 students in grades 6-9, this study examined the psychometric quality and measurement invariance of the FO scale on the School Success Profile (SSP) across African American (34.8%), Latino (27.0%), and European American (38.1%) subsamples. A one-factor model fit the data well in all three groups. Analyses identified only a small number of noninvariant parameters, supporting the conclusion that the scale has partial measurement invariance across the three groups. On average, African Americans had significantly higher levels of FO than the other two groups; mean scores for Latinos and European Americans were lower and statistically equivalent to each other. Construct validity of the SSP FO scale was also supported by findings of medium-sized relationships of FO scores to scores on five other constructs: low grades, school engagement, parent educational support, psychological distress, and school behavior. Multiple group tests of the magnitude and direction of the validity relationships indicated statistical equivalence across the three groups. Results support the use of the SSP FO scale by school psychologists to assess FO and to evaluate the effects of interventions targeting FO as a promoter of well-being and school success.

Faces are often used in psychological and neuroimaging research to assess perceptual and emotional processes. Most available stimulus sets, however, represent minimal diversity in both race and ethnicity, which may confound understanding of these processes in diverse/racially heterogeneous samples. Having a diverse stimulus set of faces and emotional expressions could mitigate these biases and may also be useful in research that specifically examines the effects of race and ethnicity on perceptual, emotional and social processes. The racially diverse affective expression (RADIATE) face stimulus set is designed to provide an open-access set of 1,721 facial expressions of Black, White, Hispanic and Asian adult models. Moreover, the diversity of this stimulus set reflects census data showing a change in demographics in the United States from a white majority to a nonwhite majority by 2020. Psychometric results are provided describing the initial validity and reliability of the stimuli based on judgments of the emotional expressions.

RATIONALE/BACKGROUND:Weight gain during treatment with antipsychotics is a prominent side-effect, especially with some second-generation antipsychotics, such as olanzapine and clozapine, and pharmacological treatments which ameliorate this side-effect are important to investigate. Decreases in histaminergic transmission in the brain induced by antipsychotics may be one of the mechanisms contributing to weight gain. Since betahistine is a histaminergic agonist, it may potentially counteract the weight gain effects of antipsychotics. METHOD/METHODS:We conducted a double-blind placebo-controlled study to evaluate the effects of 12 weeks of treatment with betahistine (N = 29) or placebo (N = 22) in adolescents and adults on anthropomorphically measured weight-related parameters, appetite, and fasting glucose-lipid and leptin levels in 51 patients treated with first and/or second-generation antipsychotics who had gained weight during treatment or had high body-mass-index (BMI). Psychopathology and side-effects were also assessed with relevant scales. RESULTS:In a sub-group of patients being treated with olanzapine or clozapine (n = 26), betahistine was significantly (P < .05) better than placebo in preventing increases in weight (3.1 kg less weight gain than placebo), BMI, and waist circumference. Betahistine did not decrease weight or BMI in patients treated with other antipsychotics. There was also no effect of betahistine on preventing weight or BMI gain in the total combined sample of all subjects. Betahistine did not significantly improve appetite or glucose-lipid measures in either subgroup. There were no significant differences in side-effects or psychopathology changes in the betahistine- vs. placebo-treated patients. CONCLUSIONS:These results suggest that betahistine may potentially be a useful adjunctive drug for decreasing weight gain in patients treated with antipsychotics that are potent histamine antagonists, such as olanzapine or clozapine, but may not be useful for this purpose in patients on other antipsychotic medications. The results justify larger placebo-controlled studies to further confirm these effects before specific recommendations can be made for routine use.

BACKGROUND:Weight gain is a potentially concerning side effect of second-generation antipsychotics (SGAs). Metformin, a biguanide with antihyperglycemic effects, is used to manage weight gain in adults treated with SGAs. OBJECTIVE:The objective of this study was to perform the first systematic review and meta-analysis of randomized controlled trials (RCTs) assessing the effects of metformin on weight gain in children and adolescents treated with SGAs. METHODS:Based on a pre-registered protocol (PROSPERO-CRD42017074839), we searched the PubMed, EMBASE, PsychoINFO, BIOSIS, Science Direct, Cochrane Central, and ClinicalTrials.gov electronic databases through March 2018 (with no restrictions on language, date, or type of publication) for RCTs that assessed the effect of metformin or placebo on body weight in children or adolescents (< 18 years of age) treated with selected SGAs (risperidone, aripiprazole, olanzapine, and clozapine) for any psychiatric disorder. We also contacted relevant drug manufacturers for possible additional pertinent studies/data. A random effects model was used and the quality of the included RCTs was assessed using the Cochrane Risk of Bias tool. RESULTS:Five RCTs (205 participants in total) were included in the meta-analysis. We found a significant weight decrease in the metformin group compared with placebo after 4, 12, and 16 weeks of treatment {mean difference - 0.98 kg (95% confidence interval [CI] - 1.26, - 0.69); - 1.83 kg (95% CI - 2.47, - 1.18); and - 3.23 kg (95% CI - 5.59, - 0.86), respectively}. A weight decrease at weeks 2 and 8 did not reach statistical significance. The decrease in body mass index (BMI) paralleled that of weight, with a significant effect at weeks 4, 12, and 16. Overall, four studies were rated as unclear, and one study was rated as high, risk of bias. CONCLUSION/CONCLUSIONS:Meta-analytical evidence shows that metformin might decrease weight in children/adolescents treated with SGAs but additional high-quality evidence is needed. Clinicians need to be aware that this use of metformin is currently off-label.

Earlier this year, we shared with you our commitment to supporting the dissemination of research that is well designed, carefully conducted, and properly interpreted, and our belief that authors, reviewers, editors, publishers, and readers should jointly strive to ensure the integrity of the science that we publish.¹ Toward this end, we are pleased to announce a new submission type beginning in 2019: Registered Reports.

The use of movie-watching as an acquisition state for functional connectivity (FC) MRI has recently enabled multiple groups to obtain rich data sets in younger children with both substantial sample sizes and scan durations. Using naturalistic paradigms such as movies has also provided analytic flexibility for these developmental studies that extends beyond conventional resting state approaches. This review highlights the advantages and challenges of using movies for developmental neuroimaging and explores some of the methodological issues involved in designing pediatric studies with movies. Emerging themes from movie-watching studies are discussed, including an emphasis on intersubject correlations, developmental changes in network interactions under complex naturalistic conditions, and dynamic age-related changes in both sensory and higher-order network FC even in narrow age ranges. Converging evidence suggests an enhanced ability to identify brain-behavior correlations in children when using movie-watching data relative to both resting state and conventional tasks. Future directions and cautionary notes highlight the potential and the limitations of using movies to study FC in pediatric populations.

Sleep is critical for proper memory consolidation. The locus coeruleus (LC) releases norepinephrine throughout the brain except when the LC falls silent throughout rapid eye movement (REM) sleep and prior to each non-REM (NREM) sleep spindle. We hypothesize that these transient LC silences allow the synaptic plasticity that is necessary to incorporate new information into pre-existing memory circuits. We found that spontaneous LC activity within sleep spindles triggers a decrease in spindle power. By optogenetically stimulating norepinephrine-containing LC neurons at 2 Hz during sleep, we reduced sleep spindle occurrence, as well as NREM delta power and REM theta power, without causing arousals or changing sleep amounts. Stimulating the LC during sleep following a hippocampus-dependent food location learning task interfered with consolidation of newly learned locations and reconsolidation of previous locations, disrupting next-day place cell activity. The LC stimulation-induced reduction in NREM sleep spindles, delta, and REM theta and reduced ripple-spindle coupling all correlated with decreased hippocampus-dependent performance on the task. Thus, periods of LC silence during sleep following learning are essential for normal spindle generation, delta and theta power, and consolidation of spatial memories.