Faculty Bibliography

Early-life stress has been linked to multiple neurodevelopmental and neuropsychiatric deficits. Our previous studies have linked maternal presence/absence from the nest in developing rat pups to changes in prefrontal cortex (PFC) activity. Furthermore, we have shown that these changes are modulated by serotonergic signaling. Here we test whether changes in PFC activity during early life affect the developing cortex leading to behavioral alterations in the adult. We show that inhibiting the PFC of mouse pups leads to cognitive deficits in the adult comparable to those seen following maternal separation. Moreover, we show that activating the PFC during maternal separation can prevent these behavioral deficits. To test how maternal separation affects the transcriptional profile of the PFC we performed single-nucleus RNA-sequencing. Maternal separation led to differential gene expression almost exclusively in inhibitory neurons. Among others, we found changes in GABAergic and serotonergic pathways in these interneurons. Interestingly, both maternal separation and early-life PFC inhibition led to changes in physiological responses in prefrontal activity to GABAergic and serotonergic antagonists that were similar to the responses of more immature brains. Prefrontal activation during maternal separation prevented these changes. These data point to a crucial role of PFC activity during early life in behavioral expression in adulthood.

BACKGROUND:Despite a large body of evidence linking the impact of trauma, parenting, and child maltreatment recidivism, current child welfare services often do not target maternal trauma and post-traumatic stress disorder (PTSD). Moreover, there is little evidence that traditional family preservation services (FPS) lower the rates of repeat incidences of child abuse and neglect. The novel intervention, Parenting-STAIR (P-STAIR), seeks to address maternal mental health and parenting skills in order to reduce punitive parenting behaviors. OBJECTIVE:This study analyzes the effects of P-STAIR on child maltreatment risk. PARTICIPANTS AND SETTING/METHODS:P-STAIR was administered to 112 child welfare-involved mothers in New York City (NYC). The mothers were between 18 and 52 years old (M = 31.1, SD = 6.6) and were referred from 4 child welfare preventive service agencies in NYC. METHODS:To evaluate change over time in indicators of maltreatment risk, two-tailed paired sample t-tests compared 1) pre- and post-treatment scores and 2) pre-treatment and 3-month follow-up scores. RESULTS:Among the 71 mothers who completed treatment, significant improvements from baseline to post-assessment and pre- to 3-month follow-up were observed across total scores on the CTSPC and the AAPI-2. Improvements were evident in nonviolent disciple, psychological aggression, expectations, empathy, and parent-child family roles at both the post-assessment and 3-month follow-up which are proximal outcomes of P-STAIR (CTSPC: pre-post nonviolent disciple d = 0.70; pre-post psychological aggression d = 0.34; pre-follow-up nonviolent disciple d = 0.42; pre-follow-up psychological aggression d = 0.36; AAPI-2; pre-post expectations d = 0.31; pre-post empathy d = 0.39; pre-post parent-child roles d = 0.47; pre-follow-up expectations d = 0.33; pre-follow-up empathy d = 0.42; pre-follow-up parent-child roles d = 0.66). CONCLUSIONS:The improvement in indicators of maltreatment risk demonstrates promising support for the utility of P-STAIR within the child welfare system.

When patients seek professional help for mental disorders, they often do so because of troubling subjective affective experiences. While these subjective states are at the center of the patient's symptomatology, scientific tools for studying them and their cognitive antecedents are limited. Here, we explore the use of concepts and analytic tools from the science of consciousness, a field of research that has faced similar challenges in having to develop robust empirical methods for addressing a phenomenon that has been considered difficult to pin down experimentally. One important strand is the operationalization of some relevant processes in terms of metacognition and confidence ratings, which can be rigorously studied in both humans and animals. By assessing subjective experience with similar approaches, we hope to develop new scientific approaches for studying affective processes and promoting psychological resilience in the face of debilitating emotional experiences.

We investigated whether SARS-CoV-2 infection is associated with short- and long-term neuropsychiatric sequelae. We used population-based cohorts from the Korean nationwide cohort (discovery; n = 10,027,506) and the Japanese claims-based cohort (validation; n = 12,218,680) to estimate the short-term (<30 days) and long-term (≥30 days) risks of neuropsychiatric outcomes after SARS-CoV-2 infection compared with general population groups or external comparators (people with another respiratory infection). Using exposure-driven propensity score matching, we found that both the short- and long-term risks of developing neuropsychiatric sequelae were elevated in the discovery cohort compared with the general population and those with another respiratory infection. A range of conditions including Guillain-Barré syndrome, cognitive deficit, insomnia, anxiety disorder, encephalitis, ischaemic stroke and mood disorder exhibited a pronounced increase in long-term risk. Factors such as mild severity of COVID-19, increased vaccination against COVID-19 and heterologous vaccination were associated with reduced long-term risk of adverse neuropsychiatric outcomes. The time attenuation effect was the strongest during the first six months after SARS-CoV-2 infection, and this risk remained statistically significant for up to one year in Korea but beyond one year in Japan. The associations observed were replicated in the validation cohort. Our findings contribute to the growing evidence base on long COVID by considering ethnic diversity.

INTRODUCTION/BACKGROUND:Access to care for children and adolescents affected by ADHD in France remains below the levels attained in most industrialised countries. To contribute to improving ADHD care in France, we assessed existing ADHD knowledge among medical doctors (MDs) and described associated care pathways in two large French regions in 2021. We produced tools to evaluate the regional impact of implementing a stepped-care pathway for ADHD. METHODS:A SurveyMonkey® study was sent to professionals from two regions in France accounting for 14 million inhabitants, allowing them to describe their role in child/adolescent ADHD, as well as their representations and knowledge about the disorder. RESULTS:Around 9.4% of all MDs potentially involved with children took part in the study; 34.9% considered themselves untrained, 40.5% were involved in ADHD care at a first-tier level, and 19.6% at a second-tier level. Access to a second or third-tier service for ADHD was associated with mean waiting times of 5.7 and 8.5 months, respectively. Initiation of stimulant therapy remained mainly restricted to second or third-tier MDs, and adaptation of dosage or change in the galenic formulation was rarely performed by first-tier MDs (27.2% and 18%, respectively). Training in neurodevelopmental disorders and tier-level were the strongest determinants of knowledge, attitudes and self-assessed expertise about ADHD. CONCLUSIONS:This study provides insight into training needs for MDs regarding healthcare pathways in ADHD and should support the implementation of health policies, such as a stepped healthcare access for ADHD. The study design and dissemination have been validated and will be available in France and other countries facing similar obstacles in care pathways for ADHD. Official recommendations on ADHD in children and adults are being updated in France, and our data and the survey design will be a starting point for their implementation.

Adolescence is a critical developmental period of biological and social change during which 1 in 3 youth experience significant anxiety symptoms. The social-emotional lives of the majority of adolescents are largely conducted via digital media use (DMU; e.g., social media, text messaging). Yet the past decade of research on DMU and anxiety has yielded mixed results (e.g., Keles et al., 2020 review), leaving the complex role that DMU might play in the emergence and maintenance of anxiety poorly understood. A key step forward is to leverage psychophysiology to identify individual differences in cognitive and emotional processes that confer vulnerability to potential negative effects of DMU. Further, given the ubiquity of DMU, a greater focus is needed on measurements that move beyond sheer frequency to capture DMU in comparison to face-to-face (FTF) social interactions. This study examined attention bias (AB), characterized by selective and exaggerated attention toward or away from threat, as a moderator of the link between DMU and anxiety in adolescents (N = 75; 42 female) aged 12-14 years (M = 13.28, SD = 0.87). AB was indexed during a dot probe task using reaction time metrics (i.e., trial-level bias) and via ERPs capturing attentional selection and discrimination (N170) and cognitive control (N2) to threat compared to neutral faces. AB moderated associations between DMU and anxiety. A greater preference to use DMU vs FTF predicted greater anxiety among those with a greater behavioral bias away from threat, blunted N170, and blunted N2 in the presence of threat. Future research should examine potential causal and bidirectional links between DMU and anxiety and explore whether preferences for technology-mediated interactions and individual differences in threat processing increase risk.

To provide an overview of treatments in the pipeline for adults with attention-deficit/hyperactivity disorder (ADHD), we searched https://clinicaltrials.gov/and and https://www.clinicaltrialsregister.eu/ from 01/01/2010-10/18/2023 for ongoing or completed phase 2 or 3 randomised controlled trials (RCTs), assessing pharmacological or non-pharmacological interventions for adults with ADHD with no current regulatory approval. We found 90 eligible RCTs. Of these, 24 (27 %) reported results with statistical analysis for primary efficacy endpoints. While several pharmacological and non-pharmacological interventions had evidence of superiority compared to the control condition from a single RCT, centanafadine (norepinephrine, dopamine, and serotonin re-uptake inhibitor) was the only treatment with evidence of efficacy on ADHD core symptoms (small effect size=0.28-0.40) replicated in at least one additional RCT, alongside reasonable tolerability. Overall, the body of ongoing RCTs in adults with ADHD is insufficient, without any intervention on the horizon to match the efficacy of stimulant treatment or atomoxetine and with better tolerability profile. Additional effective and well tolerated treatments for adults with ADHD require development and testing.