Faculty Bibliography

Background: The brain contains interconnected circuits which are neither completed at birth or invariant across life. This neuronal plasticity is essential for life-long adaptive features like continuous learning and memory. However, this plasticity, especially when associated with severe adverse factors during early-life, can lead to the derailment of normative brain development and contribute to the etiology of behavioral deficits and psychiatric disorders. One of the most influential environmental factors during early-life is parental/caregiver care. Childhood adversity has been estimated to account for a significant percentage of adult-onset mental health disorders. In extreme cases of childhood adversity, institutional rearing where the infants were deprived of caregiver contact, cognitive deficits and dysregulated prefrontal cortex (PFC) function were found. In this study we hypothesize that earlylife adversity, in the form of maternal separation, leads to longlasting changes in the transcriptome of specific PFC cell populations leading to a dysregulation of PFC function.
Method(s): Here, we use a mouse model of maternal separation. The brains of pups and adults of normal reared or maternal separated (MS) animals were collected. In one set, we performed single-nucleus RNAseq with hashing to contrast the PFC transcriptome of these groups. In a separate cohort, we recorded whole slice voltage dye (VSD) responses to explore how changes in receptors identified by snRNAseq altered PFC responses.
Result(s): Using snRNAseq, as expected, we observed that the changes between ages were much more accentuated than changes between treatments. We also observed that the proportion of oligodendrocytes in adult-MS animals was similar to infant animals. Furthermore, we found that most of the differential gene expression between MS and standard reared animals was in interneurons, affecting pathways related to GABAergic, glutamatergic, and serotonergic functions. Using VSD we observed that adult-MS responses to GABAergic and serotonergic agonists were similar to the responses of more immature normal-reared animals.
Conclusion(s): This study suggests that MS leads to an immature PFC that may be linked to the behavioral deficits observed in animals and humans exposed to poor early-life care

Digital messaging programs have the potential to be a powerful, low-cost, technological tool to support multiple facets of caregivers' knowledge, and implementation of developmentally appropriate caregiver-child activities among diverse immigrant populations. However, involving caregivers and community stakeholders in the cultural and linguistic tailoring of interventions to optimize utilization and engagement may be critical to ensuring messaging programs' usability and acceptability. The purpose of this mixed-method study was to use the dynamic adaptation process (DAP) within an Exploration, Preparation, Implementation, Sustainment (EPIS) framework to examine the implementation of a digital messaging program, developed at the beginning of the COVID-19 pandemic, aimed at providing Spanish-, English-, and Mandarin-speaking immigrant caregivers with caregiver-child activities that supported children's development and caregivers' knowledge. Building upon the EPIS framework, using DAP, we assessed the feasibility and acceptability of a messaging program via short message service or multimedia message service, WeChat, and Remind and webinar program during the COVID-19 pandemic. The study illustrated how a digital messaging program is a feasible mechanism for sharing developmentally and culturally appropriate information with immigrant caregivers. In addition, the use of the DAP and the EPIS framework allowed us to continuously track the process of cultural adaptation, identify barriers and facilitators of the outreach program, and examine how implementation unfolded across all three groups of caregivers.

In this Editorial Perspective, we take a systematic look at the overall nature of the Covid-19 related research on mental health in children and young people, to gain insight into the major trends in this area of research and inform future lines of investigation, clinical practices, and policies. By means of state-of-the-art scientometric approaches, we identified 3,692 relevant research outputs, mainly clustering around the following themes: (a) mental health consequences of the Covid-19 pandemic in children and young people; (b) impact of the pandemic on pre-existing psychiatric disorders; (c) family outcomes (i.e., family violence and parental mental health); and (d) link between physical and mental conditions. Only 23% of the retrieved publications reported new data, the remaining ones being reviews, editorials, opinion papers, and other nonempirical reports. The majority of the empirical studies used a cross-sectional design. We suggest that future research efforts should prioritise: (a) longitudinal follow-up of existing cohorts; (b) quasi-experimental studies to gain insight into causal mechanisms underlying pandemic-related psychopathology in children and young people; (c) pragmatic randomised controlled trials (RCTs) to test evidence-based intervention strategies; and (d) evidence-based guidelines for clinicians and policymakers.

We carried out a systematic review and meta-analysis to investigate the effects of stimulant and non-stimulant medications on autonomic functioning in people with ADHD (PROSPERO: CRD42020212439). We searched (9th August 2021) PsycInfo, MEDLINE, EMBASE, Web of Science and The Cochrane Library, for randomised and non-randomised studies reporting indices of autonomic activity, (electrodermal, pupillometry and cardiac), pre- and post-medication exposure in people meeting DSM/ICD criteria for ADHD. In the narrative syntheses, we included 5 electrodermal studies, 1 pupillometry study and 57 studies investigating heart rate and blood pressure. In the meta-analyses, 29 studies were included on blood pressure and 32 on heart rate. Administration of stimulants, and to a lesser degree, non-stimulants increased heart rate and blood pressure in people with ADHD. Similarly, an upregulation of arousal, reflected in increased electrodermal activity and pupil diameter was observed following stimulant use. Yet, the methodological diversity of studies presented in this review reinforces the need for more standardised and rigorous research to fully understand the relationship between arousal, medication, and behaviour in ADHD.

AIM/OBJECTIVE:Adolescents in low-and-middle-income countries (LMICs) are facing numerous developmental, sexual and reproductive health (SRH) challenges including exposure to multidimensional violence. Gender-based violence (GBV) specifically intimate partner violence (IPV) are both highly prevalent in LMICs and are strongly linked with poor SRH outcomes. However, GBV and IPV interventions have not yet been adequately integrated in SRH due to individual, social, cultural, service, and resource barriers. To promote long-term SRH, a more holistic approach that integrates GBV and IPV, and adolescent development needs is imperative. Digital health has the potential to address multiple service setup, provision, and addressing access barriers through designing and providing integrated SRH care. However, there are no guidelines for an integrated digital SRH and development promotion for adolescents in LMICs. METHODS:An umbrella review was conducted to synthesize evidence in three inter-related areas of digital health intervention literature: (i) SRH, (ii) GBV specifically IPV as a subset, and (iii) adolescent development and health promotion. We first synthesize findings for each area of research, then further analyze the implications and opportunities to inform approaches to develop an integrated intervention that can holistically address multiple SRH needs of adolescents in LMICs. Articles published in English, between 2010 and 2020, and from PubMed were included. RESULTS:Seventeen review articles met our review inclusion criterion. Our primary finding is that application of digital health strategies for adolescent SRH promotion is highly feasible and acceptable. Although effectiveness evidence is insufficient to make strong recommendations for interventions and best practices suggestions, some user-centered design guidelines have been proposed for web-based health information and health application design for adolescent use. Additionally, several digital health strategies have also been identified that can be used to further develop integrated GBV-IPV-SRH-informed services to improve adolescent health outcomes. We generated several recommendations and strategies to guide future digital based SRH promotion research from our review. CONCLUSIONS:Rigorous research that focuses on intervention effectiveness testing using a combination of digital health strategies and standardized albeit contextualized outcome measures would be important. Methodological improvement such as adoption of longitudinal experimental design will be crucial in generating evidence-based intervention and practice guidelines for adolescents in LMICs.

OBJECTIVE:To assess the prevalence of early trauma in individuals with onset of schizophrenia at early (≤ 18 years) and adult (> 18 years) ages (EOP and AOP, respectively). and explore relationship between the onset of disease and clinical variables, including traumatic events, psychotic and mood symptoms. METHODS:Subjects with SZ (n=71) and EOP and AOP were compared for the history of psychological trauma, sexual abuse, and physical punishment through the Early Trauma Inventory Self Report - Short Form (ETISR-SF); a history of comorbidities and affective disorders through the Diagnostic Interview for Psychosis and Affective Disorders, Positive and Negative Syndrome Scale, Liebowitz Social Anxiety Scale and the Calgary Depression Scale for Schizophrenia was correlated with the disease duration. RESULTS:Early trauma was significantly associated with an early onset psychotic episode (r = -0.315, p < 0.01). General trauma and depressive symptoms in adulthood were also associated (r = 0.442, p < 0.01), as well as social anxiety symptoms and early trauma (r = 0.319, p < 0.01). ETISR-SF global scores and the psychical abuse item were significantly higher in the EOP than in the AOP. In the hierarchical regression, PANSS scores were better predicted by the duration of disease and age of first psychotic episode (R=0.303). CONCLUSIONS:Our results support the hypothesis that early trauma, including physical abuse, may play a relevant role in schizophrenia symptoms, such as an earlier psychotic occurrence, as well as features of other psychiatric disorders, such as greater severity of social anxiety and depression.

INTRODUCTION/UNASSIGNED:Clinical information regarding selective mutism (SM), a persistent and debilitating psychiatric disorder, in children is extremely limited. We aimed to examine sociodemographic characteristics and comorbid psychiatric conditions and identify clinical variables associated with sex and SM severity among children with SM. METHODS/UNASSIGNED:We analyzed the medical records of 49 children who received treatment for SM in four different tertiary hospitals in Turkey between 2016 and 2021. Children's charts were reviewed to examine clinical characteristics, comorbidities, and response to treatment. RESULTS/UNASSIGNED:= 0.039) than males. The vast majority of children received two or more psychiatric diagnoses. Children in the severe group had a longer duration of illness, higher rates of psychiatric comorbidity, speech delay, and treatment resistance. CONCLUSION/UNASSIGNED:Our study suggests that SM may have different clinical features according to sex and symptom severity of SM. More information about children with SM is needed to understand the development and maintenance of SM.

UNLABELLED:Maternal psychopathology given a history of maltreatment and domestic violence exposure increases the risk for child psychopathology. Infant social withdrawal is one warning sign of adverse developmental outcomes including child anxiety and depression. It remains unclear how maternal trauma-related psychopathology might affect infant social withdrawal six-months postpartum. METHODS:One-hundred ninety-five women and their six-month-old infants were studied in an at-risk community sample. Maternal trauma history, posttraumatic stress (PTSD) and major depressive (MDD) disorders were assessed. Maternal and infant behaviors were coded from videotaped interactions. RESULTS:Maternal trauma was correlated with atypical maternal behavior (AMB) and infant social withdrawal (p ≤ .001). PTSD and MDD, and comorbid PTSD/MDD predicted increased AMB (p ≤ .001) but only maternal MDD was predictive of infant social withdrawal (p ≤ .001). Effects of maternal MDD on infant withdrawal were mediated by AMB. CONCLUSIONS:At six-months postpartum, maternal MDD was associated with infant withdrawal. AMB is an important target for early intervention.

BACKGROUND:Digital technology has the potential to transform psychiatry, but its adoption has been limited. The proliferation of telepsychiatry during the COVID-19 pandemic has increased the urgency of optimizing technology for clinical practice. Understanding clinician attitudes and preferences is crucial to effective implementation and patient benefit. OBJECTIVE:Our objective was to elicit clinician perspectives on emerging digital technology. METHODS:Clinicians in a large psychiatry department (inpatient and outpatient) were invited to complete a web-based survey about their attitudes toward digital technology in practice, focusing on implementation, clinical benefits, and expectations about patients' attitudes. The survey consisted of 23 questions that could be answered on either a 3-point or 5-point Likert scale. We report the frequencies and percentages of responses. RESULTS:In total, 139 clinicians completed the survey-they represent a variety of years of experience, credentials, and diagnostic subspecialties (response rate 69.5%). Overall, 83.4% (n=116) of them stated that digital data could improve their practice, and 23.0% (n=32) of responders reported that they had viewed patients' profiles on social media. Among anticipated benefits, clinicians rated symptom self-tracking (n=101, 72.7%) as well as clinical intervention support (n=90, 64.7%) as most promising. Among anticipated challenges, clinicians mostly expressed concerns over greater time demand (n=123, 88.5%) and whether digital data would be actionable (n=107, 77%). Furthermore, 95.0% (n=132) of clinicians expected their patients to share digital data. CONCLUSIONS:Overall, clinicians reported a positive attitude toward the use of digital data to not only improve patient outcomes but also highlight significant barriers that implementation would need to overcome. Although clinicians' self-reported attitudes about digital technology may not necessarily translate into behavior, our results suggest that technologies that reduce clinician burden and are easily interpretable have the greatest likelihood of uptake.

Several lines of evidence suggest that classic psychedelics (5-HT_2A receptor agonists or partial agonists) such as psilocybin might facilitate behavior change in individuals with substance use disorders. We conducted a multi-site, double-blind, randomized controlled trial (RCT) to assess the effects of psilocybin-assisted psychotherapy in alcohol-dependent volunteers. In addition to a structured 12-week psychotherapy platform, participants (n = 96) were randomly assigned (1:1) to receive either oral psilocybin or an active placebo (oral diphenhydramine) in each of two dosing sessions (at weeks 4 and 8). Initial doses were 25 mg/70 kg psilocybin or 50 mg diphenhydramine, which could be increased in the second session depending on initial response. The psychotherapy platform combined evidence-based, manualized therapy for alcohol dependence with a supportive context for the dosing sessions. All participants were followed in the RCT through week 36. At the end of the RCT, participants who still met safety criteria were offered an open-label psilocybin session. Data collected at screening, baseline and throughout the study included: demographics, measures of alcohol use, subjective response to psilocybin and diphenhydramine, and safety measures. The primary outcome was the proportion of heavy drinking days during the 32 weeks after the first dosing session (i.e., between week 4 and week 36). Secondary outcomes included safety, additional measures of drinking (e.g., abstinence, drinking days, etc.), craving, self-efficacy, and acute effects. We will also explore moderators and mediators of the primary outcome. The primary outcomes will be published elsewhere. In this paper, we describe the protocol and rationale for our design decisions.