Faculty Bibliography

Fragile X Syndrome (FXS) is a neurodevelopmental disorder and the most common monogenic cause of intellectual disability, autism spectrum disorders (ASDs) and anxiety disorders. Loss of fragile x mental retardation protein (FMRP) results in disruptions of synaptic development during a critical period (CP) of circuit formation in the basolateral amygdala (BLA). However, it is unknown how these alterations impact microcircuit development and function. Using a combination of electrophysiologic and behavioral approaches in both male (Fmr1-/y) and female (Fmr1-/-) mice, we demonstrate that principal neurons (PNs) in the Fmr1KO BLA exhibit hyperexcitability during a sensitive period in amygdala development. This hyperexcitability contributes to increased excitatory gain in fear-learning circuits. Further, synaptic plasticity is enhanced in the BLA of Fmr1KO mice. Behavioral correlation demonstrates that fear-learning emerges precociously in the Fmr1KO mouse. Early life THIP intervention ameliorates fear-learning in Fmr1KO mice. These results suggest that CP plasticity in the amygdala of the Fmr1KO mouse may be shifted to earlier developmental timepoints.SIGNIFICANCE STATEMENTIn these studies we identify early developmental alterations in principal neurons in the FXS BLA. We show that as early as P14, excitability and feed-forward excitation, and synaptic plasticity is enhanced in Fmr1KO lateral amygdala. This correlates with precocious emergence of fear-learning in the Fmr1KO mouse. Early life THIP intervention restores CP plasticity in WT mice and ameliorates fear-learning in the Fmr1KO mouse.

Our study examines the acceptability and feasibility of Moshi, an audio-based mobile application, among children 3-8 years old using a parent-child dyadic approach. Our 10-day within-subject pre-post study design consisted of five nights of a normal bedtime routine and a subsequent five nights exposed to one story on the Moshi application during the intervention. Each five-night period spanned three weeknights and two weekend nights. The Short-Form Children's Sleep Habits Questionnaire (SF-CSHQ) was used to measure children's sleep at baseline and post-intervention. The PROMIS, Epworth Sleepiness Scale and Pittsburgh Sleep Quality Index were used to assess parents' sleep. Among the 25 child-parent dyads, the mean child age was 4 (SD = 1.23) and 63% were male (n = 15). Mean parent age was 35 (SD = 5.83), 84% were female (n = 21), and 48.0% were Black (n = 12). For child-only comparisons, mean post-SF-CSHQ measures were lower compared to baseline. A trend in parent sleep is reported. This study shows the potential of an audio-based mobile sleep aid to improve sleep health in a racially diverse parent and child dyad sample.

BACKGROUND:Overdose education and naloxone distribution (OEND) trains people who use opioids (PWUO) in how to intervene in cases of opioid overdose but best practices have not been assessed empirically. METHODS:PWUO along with a significant other (SO) were randomized to one of three training conditions. In the Treatment-as-Usual (TAU) condition, participants were randomized to receive minimal overdose-related education. In the extended training (ET) condition, PWUO received an extended training, while their SO received no overdose training. In the final condition, both the participant and SO received the extended overdose training (ETwSO). Outcome measures were naloxone use and overdose knowledge and competency assessed immediately before and after training, and at 1-, 3-, 6-, and 12-month timepoints following training. RESULTS:Three hundred and twenty-one PWUO (w/ a SO) were randomized. All intensities of OD training were associated with sustained increases in OD knowledge/ competency (versus pre-training baseline p's < 0.01). PWUO intervened in 166 ODs. The 12-month incidence of naloxone use did not significantly differ between groups. Extended training (ET + ETwSO) compared to TAU resulted in significantly greater naloxone utilization by: 30 days (10.1% vs 4.1%, p = 0.041), 60 days (16.4% vs 5.2%, p<0.001) and 90 days (17.9% vs 9.5%, p = 0.039). CONCLUSIONS:All intensities of OD training were associated with sustained increases in OD knowledge and competency, and equivalent rates of successful naloxone use. More extensive training increased naloxone utilization during the first 3 months. However, the benefits of more comprehensive training should be balanced against feasibility.

This article explores the role of formal and informal supports for women with intellectual and developmental disabilities (IDD) throughout their pregnancy, childbirth, and postpartum experiences. Data from qualitative interviews with women with IDD (n = 16) were analyzed. Results showed that formal supports aided in planning, transportation, advocacy, and providing emotional support throughout pregnancy. Informal supports helped with errands, comfort, and emotional encouragement. The community surrounding these women facilitated communication with providers, self-empowerment regarding health choices, and increased preparedness for parenthood. Findings indicate the importance of encouraging and sustaining both formal and informal supports during pregnancy, childbirth, and postpartum to improve pregnancy and parenting experiences for women with IDD.

BACKGROUND AND OBJECTIVES:Concerns about early childhood social transitions among transgender youth include that these youth may later change their gender identification (ie, retransition), a process that could be distressing. The current study aimed to provide the first estimate of retransitioning and to report the current gender identities of youth an average of 5 years after their initial social transitions. METHODS:The current study examined the rate of retransition and current gender identities of 317 initially transgender youth (208 transgender girls, 109 transgender boys; M = 8.1 years at start of study) participating in a longitudinal study, the Trans Youth Project. Data were reported by youth and their parents through in-person or online visits or via e-mail or phone correspondence. RESULTS:We found that an average of 5 years after their initial social transition, 7.3% of youth had retransitioned at least once. At the end of this period, most youth identified as binary transgender youth (94%), including 1.3% who retransitioned to another identity before returning to their binary transgender identity. A total of 2.5% of youth identified as cisgender and 3.5% as nonbinary. Later cisgender identities were more common among youth whose initial social transition occurred before age 6 years; their retransitions often occurred before age 10 years. CONCLUSIONS:These results suggest that retransitions are infrequent. More commonly, transgender youth who socially transitioned at early ages continued to identify that way. Nonetheless, understanding retransitions is crucial for clinicians and families to help make retransitions as smooth as possible for youth.

OBJECTIVE:This systematic review and meta-analysis aimed to determine the accuracies of a broad range of screening tools for attention-deficit/hyperactivity disorder (ADHD) in children and adolescents, and to compare the diagnostic accuracy of tools between population-based and clinical/high-risk samples, and across reporters. METHOD:MEDLINE, PsycINFO, EMBASE, and PubMed were searched up until February 20, 2020, with no language restrictions. Studies reporting diagnostic accuracy of a screening tool against a diagnosis of ADHD in children and adolescents <18 years of age were eligible for inclusion. Meta-analyses were undertaken to provide pooled estimates of the area under the curve (AUC), and sensitivity and specificity of groups of measures. RESULTS:A total of 75 studies published between 1985 and 2021 reporting on 41 screening tools that were grouped into 4 categories (Achenbach System of Empirically Based Assessment [ASEBA], DSM-IV symptom scales, SDQ, and Other Scales) were retained. The pooled AUC for studies using a combined ADHD symptoms score was 0.82 (95% CI = 0.78-0.86), although this varied considerably across reporters (0.67-0.92) and populations (CI = 0.60-0.95). None of the measures met minimal standards for acceptable sensitivity (0.8) and specificity (0.8). CONCLUSION:Most tools have excellent overall diagnostic accuracy as indicated by the AUC. However, a single measure completed by a single reporter is unlikely to have sufficient sensitivity and specificity for clinical use or population screening.

Across Western countries, approximately 15% to 20% of school-aged children and adolescents have a health-related disorder, with incidence rates of childhood chronic health conditions (CHCs) increasing. This contribution comprehensively reviews disease-level, school-level, and systems-level issues related to effectively supporting children with CHCs succeed from both psychosocial and educational perspectives. This article also delineates training needs as they pertain to graduate preparation and/or professional development to equip school personnel to appropriately address students' needs. The article concludes with recommendations for evidence-based prevention and intervention strategies and potential avenues for interdisciplinary collaboration and models of coordinated care for these medically compromised youth.

BACKGROUND:Antipsychotic-induced weight gain (AIWG) is a clinically relevant and concerning adverse effect of contemporary antipsychotic medications. Lumateperone is a novel antipsychotic, which became commercially available in 2020 and received Food and Drug Administration approval for schizophrenia and bipolar disorder in 2019 and 2021, respectively. To date, no comprehensive review exists on its AIWG profile. This systematic review aims to assess the association between lumateperone and AIWG. METHODS:Data Sources: A comprehensive search of published studies on "lumateperone" OR "ITI-007" OR "Caplyta" was conducted on PubMed, CINAHL Complete, APA PsychInfo, Cochrane Library, and Embase databases until January 2022.Study Selection: A total of 149 articles in English were collected. After removing duplicates, all human trials on lumateperone were screened for the inclusion criteria.Data Extraction: Two reviewers conducted an independent screening followed by full-text analysis of extracted studies adhering to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Third reviewer resolved the conflicts as tiebreaker. RESULTS:Primary search generated 77 articles, excluding 72 duplicates, of which 51 were deemed appropriate for exclusion. Full-text analysis of the remaining 26 articles concluded with 5 studies for finalized review per inclusion criteria. Excluded studies were manually reviewed for relevant citation of studies per inclusion criteria. Three randomized, double-blinded, placebo-controlled clinical trials and 2 open-label trials were derived from this systematic review. Lumateperone showed a favorable weight profile compared with placebo and alternate antipsychotics. CONCLUSIONS:Lumateperone displays minimal to no weight gain among participants in the studies reviewed.

BACKGROUND:The degree of efficacy, safety, quality, and certainty of meta-analytic evidence of biological non-pharmacological treatments in mental disorders is unclear. METHODS:We conducted an umbrella review (PubMed/Cochrane Library/PsycINFO-04-Jul-2021, PROSPERO/CRD42020158827) for meta-analyses of randomized controlled trials (RCTs) on deep brain stimulation (DBS), transcranial magnetic stimulation (TMS), transcranial direct current stimulation (tDCS), electro-convulsive therapy (ECT), and others. Co-primary outcomes were standardized mean differences (SMD) of disease-specific symptoms, and acceptability (for all-cause discontinuation). Evidence was assessed with AMSTAR/AMSTAR-Content/GRADE. RESULTS:We selected 102 meta-analyses. Effective interventions compared to sham were in depressive disorders: ECT (SMD=0.91/GRADE=moderate), TMS (SMD=0.51/GRADE=moderate), tDCS (SMD=0.46/GRADE=low), DBS (SMD=0.42/GRADE=very low), light therapy (SMD=0.41/GRADE=low); schizophrenia: ECT (SMD=0.88/GRADE=moderate), tDCS (SMD=0.45/GRADE=very low), TMS (prefrontal theta-burst, SMD=0.58/GRADE=low; left-temporoparietal, SMD=0.42/GRADE=low); substance use disorder: TMS (high frequency-dorsolateral-prefrontal-deep (SMD=1.16/GRADE=moderate), high frequency-left dorsolateral-prefrontal (SMD=0.77/GRADE=very low); OCD: DBS (SMD=0.89/GRADE=moderate), TMS (SMD=0.64/GRADE=very low); PTSD: TMS (SMD=0.46/GRADE=moderate); generalized anxiety disorder: TMS (SMD=0.68/GRADE=low); ADHD: tDCS (SMD=0.23/GRADE=moderate); autism: tDCS (SMD=0.97/GRADE=very low). No significant differences for acceptability emerged. Median AMSTAR/AMSTAR-Content was 8/2 (suggesting high-quality meta-analyses/low-quality RCTs), GRADE low. DISCUSSION/CONCLUSIONS:Despite limited certainty, biological non-pharmacological interventions are effective and safe for numerous mental conditions. Results inform future research, and guidelines. FUNDING/BACKGROUND:None.

The year 2020 brought unprecedented challenges and renewed focus on racial disparities and inequities in the United States. For racial and ethnic minority groups, and in particular African Americans, racial disparities have been a constant presence and threat from the time of slavery through the present day. These racial disparities, sanctioned and maintained by institutional racism, manifest in all aspects of life for African Americans-segregated and unequal education and housing systems, health and mental health care disparities, disproportionally elevated incarceration rates, and, as painfully highlighted this past year, continued vulnerability to acts of violence at the hands of law enforcement. In addition, most recently, there has been a renewed focus on the increased suicide rate for Black youth and its relationship to these racial disparities.¹ In a large urban environment, our academic Child Psychiatry Department recognized that progress toward addressing racial disparities would be impeded without raising awareness and taking individual and collective action to identify implicit bias, power, and privilege differentials, and systemic racism inherent within academic medicine and our own lived experiences. This letter describes the development of such examination through facilitated dialogues on race and antiracism in our department.