Faculty Bibliography

IMPORTANCE:Psilocybin shows promise as a treatment for major depressive disorder (MDD). OBJECTIVE:To evaluate the magnitude, timing, and durability of antidepressant effects and safety of a single dose of psilocybin in patients with MDD. DESIGN, SETTING, AND PARTICIPANTS:In this phase 2 trial conducted between December 2019 and June 2022 at 11 research sites in the US, participants were randomized in a 1:1 ratio to receive a single dose of psilocybin vs niacin placebo administered with psychological support. Participants were adults aged 21 to 65 years with a Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition diagnosis of MDD of at least 60 days' duration and moderate or greater symptom severity. Exclusion criteria included history of psychosis or mania, active substance use disorder, and active suicidal ideation with intent. Participants taking psychotropic agents who otherwise met inclusion/exclusion criteria were eligible following medication taper. Primary and secondary outcomes and adverse events (AEs) were assessed at baseline (conducted within 7 days before dosing) and at 2, 8, 15, 29, and 43 days after dosing. INTERVENTIONS:Interventions were a 25-mg dose of synthetic psilocybin or a 100-mg dose of niacin in identical-appearing capsules, each administered with psychological support. MAIN OUTCOMES AND MEASURES:The primary outcome was change in central rater-assessed Montgomery-Asberg Depression Rating Scale (MADRS) score (range, 0-60; higher scores indicate more severe depression) from baseline to day 43. The key secondary outcome measure was change in MADRS score from baseline to day 8. Other secondary outcomes were change in Sheehan Disability Scale score from baseline to day 43 and MADRS-defined sustained response and remission. Participants, study site personnel, study sponsor, outcome assessors (raters), and statisticians were blinded to treatment assignment. RESULTS:A total of 104 participants (mean [SD] age, 41.1 [11.3] years; 52 [50%] women) were randomized (51 to the psilocybin group and 53 to the niacin group). Psilocybin treatment was associated with significantly reduced MADRS scores compared with niacin from baseline to day 43 (mean difference,-12.3 [95% CI, -17.5 to -7.2]; P <.001) and from baseline to day 8 (mean difference, -12.0 [95% CI, -16.6 to -7.4]; P < .001). Psilocybin treatment was also associated with significantly reduced Sheehan Disability Scale scores compared with niacin (mean difference, -2.31 [95% CI, 3.50-1.11]; P < .001) from baseline to day 43. More participants receiving psilocybin had sustained response (but not remission) than those receiving niacin. There were no serious treatment-emergent AEs; however, psilocybin treatment was associated with a higher rate of overall AEs and a higher rate of severe AEs. CONCLUSIONS AND RELEVANCE:Psilocybin treatment was associated with a clinically significant sustained reduction in depressive symptoms and functional disability, without serious adverse events. These findings add to increasing evidence that psilocybin-when administered with psychological support-may hold promise as a novel intervention for MDD. TRIAL REGISTRATION:ClinicalTrials.gov Identifier: NCT03866174.

Although evidence-based psychological treatments such as cognitive behavioral therapy (CBT) have strong empirical support for reducing anxiety and depression symptoms, CBT outcome research often does not report race and ethnicity variables, or assess how well CBT works for people from historically excluded racial and ethnic groups. This study presents post hoc analyses comparing treatment retention and symptom outcomes for participants of color ( n = 43) and White participants ( n = 136) from a randomized controlled efficacy trial of CBT. χ 2 tests and one-way ANCOVA showed no observable differences between the two samples on attrition or on clinician-rated measures of anxiety and depression at posttreatment and follow-up. Moderate to large within-group effect sizes on anxiety and depression were found for Black, Latinx, and Asian American participants at almost all time points. These preliminary findings suggest that CBT for anxiety and comorbid depression may be efficacious for Black, Asian American, and Latinx individuals.

It has been suggested that autistic traits are associated with less frequent alcohol use in adolescence. Our study seeks to examine the relationship between autistic traits and alcohol use in a large adolescent population. Leveraging data from the IMAGEN cohort, including 2045 14-year-old adolescents that were followed-up to age 18, we selected items on social preference/skills and rigidity from different questionnaires. We used linear regression models to (1) test the effect of the sum scores on the prevalence of alcohol use (AUDIT-C) over time, (2) explore the relationship between autistic traits and alcohol use patterns, and (3) explore the specific effect of each autistic trait on alcohol use. Higher scores on the selected items were associated with trajectories of less alcohol use from the ages between 14 and 18 (b = - 0.030; CI 95% = - 0.042, - 0.017; p < 0.001). Among adolescents who used alcohol, those who reported more autistic traits were also drinking less per occasion than their peers and were less likely to engage in binge drinking. We found significant associations between alcohol use and social preference (p < 0.001), nervousness for new situations (p = 0.001), and detail orientation (p < 0.001). Autistic traits (social impairment, detail orientation, and anxiety) may buffer against alcohol use in adolescence.

We examined relationships among sleep quality and forms of social interaction (in-person vs. online) as predictors of change in affect and interpersonal needs (perceived burdensomeness, thwarted belongingness) - correlates of suicidal thoughts and behaviors - during the early COVID-19 pandemic lockdown. New York City undergraduates (N = 58) from four public colleges completed a baseline survey and daily diaries up to 30 days in April-June 2020. Adjusting for relevant covariates, better sleep quality and in-person communication predicted greater positive affect and lower negative affect over time, but online social interaction only predicted greater positive affect and did not predict negative affect. Better sleep quality predicted lower perceived burdensomeness but not thwarted belongingness. Both in-person and online social interaction - but not total hours on social media - predicted lower thwarted belonging and perceived burdensomeness. Greater hours spent on social media each day lessened the relationship between in-person interaction and positive affect and lessened the buffering effect of in-person interaction on perceived burdensomeness. Improving sleep quality and increasing in-person interaction may ameliorate psychological variables that increase risk for suicidal thoughts and behaviors. However, when in-person interaction is limited, such as during the COVID-19 pandemic, online social interaction might be encouraged - depending on the nature of the interactions - to increase positive affect and buffer against suicide-related factors.

A maternal history of major depressive disorder (MDD) is a well-known risk factor for depression in offspring. However, the mechanism through which familial risk is transmitted remains unclear. Cognitive control alterations are common in MDD, and thus, the current study investigated whether altered control capacity is transmitted intergenerationally, and whether it then contributes to the developmental pathways through which depression is passed from mothers to children. We recruited children (N = 65) ages 4-10-years-old, of which 47.7 % (n = 31) reported a maternal history of MDD, and their biological mother (N = 65). Children performed a child-friendly Go/NoGo task while electroencephalography (EEG) data were recorded, and mothers performed a Flanker task. Children exhibited heightened sensitivity to error versus correct responses, which was characterized by an error-related negativity (ERN), error positivity (Pe) as well as prominent delta and frontal midline theta (FMT) oscillations. Interestingly, worse maternal performance on the Flanker task associated with an increased Go/NoGo error rate and a smaller ERN and Pe in children. However, there was no association between maternal or child control indices with child depression symptoms. Our results suggest a familial influence of cognitive control capacity in mother-child dyads, but it remains unclear whether this confers risk for depressive symptoms in children. Further research is necessary to determine whether alterations in cognitive control over time may influence symptom development in at-risk children.

Ring chromosome 20 or r(20) syndrome is a rare chromosomal disorder, mainly characterized by childhood-onset drug-resistant epilepsy with typical electroencephalographic findings, followed by mild to severe cognitive-behavioral decline. Recent studies support a possible role of the dopaminergic system in the epileptogenesis of this syndrome. We report the case of a 13-year-old female with mosaic r(20) who showed typical disease onset and evolution and a remarkable electroclinical improvement with zonisamide. Epilepsy related to r(20) is often medically intractable. When valproate and lamotrigine are not effective, zonisamide could be further investigated as a therapeutic option, since it acts as antifocal and it has a potential role in the prevention of dopamine depletion.

OBJECTIVE:Globally, rates of youth suicide vary considerably. Suicidal thoughts and behaviors (STB) are consistently associated with risk of death by suicide. However, international trends in STB have not yet been compared. To address this gap, an international meta-analysis of epidemiological and school-based studies that report on STB in youth was conducted. METHOD/METHODS:Systematic searches were conducted in PubMed and PsycINFO through April 2022. Eligible studies included prevalence of active suicidal ideation (SI) or suicide attempts (SA) in community youth younger than age 22. All studies were coded by 2 authors. Mixed models accounting for shared methods and including hypothesized moderators were conducted using the metafor package in R. RESULTS:There were 371 effect sizes for SI, 94 for SI with a plan, and 316 for SA, representing 149 regions. Year of data collection ranged from 1981 to 2021. Participants were 6 to 21 years old. The prevalence of SI ranged across regions from 14.3% to 22.6%; the prevalence of SA ranged from 4.6% to 15.8%. Year was not associated with increasing STB prevalence except for studies from the United States, which showed increasing rates of SI and SA since 2007. CONCLUSION/CONCLUSIONS:This is the most comprehensive meta-analysis of STB in youth, providing valuable data about how risk factors most commonly associated with suicide vary internationally and over time. International rates of STB among youth are not improving and may be getting worse in the United States, despite efforts to reduce suicide risk. Most studies did not report rates of SI or SA separately for LGBTQIA+ (lesbian, gay, bisexual, transgender, queer, intersex, asexual, and others) youth and youth of color. A better understanding of proximal risk at the individual level will be important to informing future prevention efforts, especially for high-risk groups.

BACKGROUND/UNASSIGNED:Adolescence is characterized by an increase in the rate of sleep problems, which might be even more pronounced in adolescents with ADHD. This systematic review with meta-analysis aimed to compare sleep in adolescents with and without ADHD, including sleep parameters, both subjectively and objectively measured, sleep problems and sleep hygiene. METHODS/UNASSIGNED:Medline, CINAHL, PsycINFO, EMBASE, ERIC, Web of Science, and PubMed databases were searched for studies with case-control designs (published between 1980 and 2022) directly comparing sleep in adolescents (12-25 years) with ADHD to typically developing controls. Standardized mean differences were calculated and a random-effects model was implemented using RevMan. RESULTS/UNASSIGNED: = 3) in any parameter. Differences in sleep hygiene could not be examined due to a limited number of studies. CONCLUSIONS/UNASSIGNED:Adolescents with ADHD report significantly worsened subjectively sleep parameters and more sleep problems compared to controls. These findings are still preliminary as a limited number of studies was identified. Nevertheless, it is advised to routinely include sleep assessment in the ADHD diagnostic process. More research is needed with a focus on objective measurement and sleep hygiene in ADHD.

OBJECTIVES/OBJECTIVE:Mental health care clinicians' training in treating sleep problems was investigated. We examined clinicians' (1) prior training in providing treatment for sleep problems, (2) interest in receiving training in treatment for sleep problems, and (3) perceptions of the importance of treating sleep problems and interest in incorporating sleep treatments into their practices. METHODS:An online survey was completed by 137 clinicians. RESULTS:The majority of clinicians (61.31%) reported receiving prior training in treating sleep problems, most commonly in the form of a workshop and after receiving a graduate degree. Most clinicians reported interest in receiving further training in treating sleep problems. Clinicians reported that the majority (66.67%) of their clients experience sleep problems, yet reported that they address sleep with fewer than half of clients. Addressing sleep in treatment was rated as "somewhat" to "very" important and most clinicians indicated further interest in receiving training in treating sleep. CONCLUSIONS:Mental health care clinicians receive limited training in treating sleep problems. As clinicians are interested in gaining further training to address sleep concerns within their clinical practice, training programs and continuing education programs should consider increasing the amount of programming in sleep treatment and assessment.

Adverse Events (AEs) are defined as any unfavorable and unintended sign or symptom, that may occur during or after receipt of any intervention. The principle of non-maleficence requires careful consideration to ensure that existing or new psychological interventions are not harmful before they can be considered beneficial. In this context, the safety of psychological interventions, including the possible occurrence of AEs, is increasingly important for patients, families, and clinicians. The evaluation of AEs is crucial to obtain a complete understanding of the risk/benefit balance of psychological interventions. There is a need for researchers and clinicians to assess and report AEs comprehensively and in a coordinated manner. It is necessary to have more accurate data on the recording of AEs in protocols to enhance transparency and consistency, as well as to improve practice. Finally, and to facilitate this process, there is a need for standards for data collection.