Faculty Bibliography

BACKGROUND:The Structured E-Parenting Support (STEPS) app provides support for parents of children with elevated hyperactivity, impulsivity, inattention, and conduct problems who are awaiting clinical assessment. STEPS will be evaluated in a randomized controlled trial (RCT) within the Online Parent Training for the Initial Management of ADHD Referrals (OPTIMA) research program in the United Kingdom. Phase 1 of the OPTIMA tested the feasibility of participants' recruitment and the app's usability. OBJECTIVE:This study aimed to adapt a digital routine clinical monitoring system, myHealthE, for research purposes to facilitate waitlist recruitment; test using remote methods to screen and identify participants quickly and systematically; pilot the acceptability of the recruitment and assessment protocol; and explore the usability of STEPS. METHODS:myHealthE was adapted to screen patients' data. Parents' and clinicians' feedback on myHealthE was collected, and information governance reviews were conducted in clinical services planning to host the RCT. Potential participants for the observational feasibility study were identified from new referrals using myHealthE and non-myHealthE methods. Descriptive statistics were used to summarize the demographic and outcome variables. We estimated whether the recruitment rate would meet the planned RCT sample size requirement (n=352). In addition to the feasibility study participants, another group of parents was recruited to assess the STEPS usability. They completed the adapted System Usability Scale and responded to open-ended questions about the app, which were coded using the Enlight quality construct template. RESULTS:Overall, 124 potential participants were identified as eligible: 121 (97.6%) via myHealthE and 3 (2.4%) via non-myHealthE methods. In total, 107 parents were contacted, and 48 (44.9%) consented and were asked if, hypothetically, they would be willing to participate in the OPTIMA RCT. Of the 28 feasibility study participants who provided demographic data, 21 (75%) identified as White. Their children had an average age of 8.4 (SD 1.7) years and 65% (31/48) were male. During the primary recruitment period (June to July 2021) when 45 participants had consented, 38 (84%) participants agreed hypothetically to take part in the RCT (rate of 19/mo, 95% CI 13.5-26.1), meeting the stop-go criterion of 18 participants per month to proceed with the RCT. All parents were satisfied or very satisfied with the study procedures. Parents (n=12) recruited to assess STEPS' usability described it as easy to navigate and use and as having an attractive combination of colors and visual design. They described the content as useful, pitched at the right level, and sensitively presented. Suggested improvements included adding captions to videos or making the recorded reflections editable. CONCLUSIONS:Remote recruitment and study procedures for testing a parenting intervention app are feasible and acceptable for parents. The parents felt that STEPS was a useful and easy-to-use digital parenting support tool. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID)/UNASSIGNED:RR2-10.1186/s40814-021-00959-0.

There has been rapid growth in gene therapy development with an expanding list of approved clinical products. Several therapies are particularly relevant to patients in low- and middle-income countries. Moreover, investing in research and manufacturing presents an opportunity for economic development. To increase awareness of gene therapy, the American Society of Gene and Cell Therapy partnered with the Muhimbili University of Health and Allied Sciences, Tanzania, to create a certificate-bearing course. The goal was to provide faculty teaching in graduate and medical schools with the tools needed to add gene therapy to the university curriculum. The first virtual course was held in October of 2022, and 45 individuals from 9 countries in Africa completed the training. The content was new to approximately two-thirds of participants, with the remaining third indicating that the course increased their knowledge base. The program was well received and will be adapted for other under-resourced regions.

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.

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.

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.

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.

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.

We aimed to identify diagnosis-specific/transdiagnostic/transoutcome multivariable candidate predictors (MCPs) of key outcomes in mental disorders. We conducted an umbrella review (protocol  link ), searching MEDLINE/Embase (19/07/2022), including systematic reviews of studies reporting on MCPs of response, remission, recovery, or relapse, in DSM/ICD-defined mental disorders. From published predictors, we filtered MCPs, validating MCP criteria. AMSTAR2/PROBAST measured quality/risk of bias of systematic reviews/individual studies. We included 117 systematic reviews, 403 studies, 299,888 individuals with mental disorders, testing 796 prediction models. Only 4.3%/1.2% of the systematic reviews/individual studies were at low risk of bias. The most frequently targeted outcome was remission (36.9%), the least frequent was recovery (2.5%). Studies mainly focused on depressive (39.4%), substance-use (17.9%), and schizophrenia-spectrum (11.9%) disorders. We identified numerous MCPs within disorders for response, remission and relapse, but none for recovery. Transdiagnostic MCPs of remission included lower disease-specific symptoms (disorders = 5), female sex/higher education (disorders = 3), and quality of life/functioning (disorders = 2). Transdiagnostic MCPs of relapse included higher disease-specific symptoms (disorders = 5), higher depressive symptoms (disorders = 3), and younger age/higher anxiety symptoms/global illness severity/ number of previous episodes/negative life events (disorders = 2). Finally, positive trans-outcome MCPs for depression included less negative life events/depressive symptoms (response, remission, less relapse), female sex (response, remission) and better functioning (response, less relapse); for schizophrenia, less positive symptoms/higher depressive symptoms (remission, less relapse); for substance use disorder, marital status/higher education (remission, less relapse). Male sex, younger age, more clinical symptoms and comorbid mental/physical symptoms/disorders were poor prognostic factors, while positive factors included social contacts and employment, absent negative life events, higher education, early access/intervention, lower disease-specific and comorbid mental and physical symptoms/conditions, across mental disorders. Current data limitations include high risk of bias of studies and extraction of single predictors from multivariable models. Identified MCPs can inform future development, validation or refinement of prediction models of key outcomes in mental disorders.