Faculty Bibliography

Gestational diabetes mellitus (GDM) affects around 10% of pregnancies in the United States and has been linked to neurodevelopmental sequelae in children. However, there is a paucity of studies investigating early-life neural markers in GDM-exposed infants. This study examined the association of GDM with relative EEG power among healthy term-age neonates collected during natural sleep. Participants included a diverse cohort of 101 mothers (45% multiracial, 25% Black, and 69% Hispanic or Latina) and their infants (gestational age at birth M_age = 39.0 ± 0.95; 46.5% female). We did not observe the main effect of GDM on infant relative EEG power. Our post hoc analyses revealed a significant interaction effect between GDM and infant birth weight on relative EEG power in active sleep. Among GDM-exposed neonates, increased birth weight was associated with increased relative theta EEG power and decreased relative beta and gamma EEG power across multiple electrode regions. Among non-GDM-exposed infants, increased birth weight was associated with decreased relative theta EEG power and increased relative beta and gamma EEG power across multiple electrode regions. Our findings suggest that alterations in fetal growth may serve as either an indirect marker or pathway through which GDM influences the developing fetal brain.

Weighing risks and benefits of the use of psychotropic medications during pregnancy remains a challenge worldwide. We systematically assessed the strength of associations between psychotropic medication use in pregnant people with mental disorders and various adverse health outcomes in both pregnant people and foetuses. Systematic reviews with meta-analyses of observational studies investigating the association between exposure to psychotropic medication in pregnancy and any adverse health outcomes were included. Credibility was graded into convincing, highly suggestive, suggestive, weak or not significant. Quality of the meta-analyses and of individual studies were assessed with A Measurement Tool to Assess Systematic Reviews 2 (AMSTAR 2) the Newcastle-Ottawa Scale (NOS), respectively. We considered 21 meta-analyses encompassing 17,290,755 participants (AMSTAR 2 high = 1, low = 12, or critically low = 8). Evidence was suggestive for: (1) preterm birth in pregnant people with either any mental disorder (equivalent odds ratio 1.62 (95% confidence interval 1.24-2.12) or depression (1.65 [1.34-2.02]) receiving antidepressants during any trimester of pregnancy; (2) small for gestational age for pregnant people with depression receiving a SSRI during any trimester of pregnancy (1.50 [1.19-1.90]); and (3) major congenital malformation (1.24 [1.09-1.40]) or cardiac malformations (1.28 [1.11-1.47]) in babies for pregnant people with depression or anxiety receiving paroxetine during first trimester of pregnancy. Additional associations were supported by weak evidence, or were not statistically significant. This umbrella review found no convincing or highly suggestive level of evidence of adverse health outcomes associated with psychotropic medication use in pregnant people with mental disorders.

BACKGROUND:COVID infection has been associated with long term sequalae (Long COVID) which include neurological and behavioral effects in thousands of patients, but the etiology and scope of symptoms is not well understood. This paper reviews long term sequelae of COVID on brain and mental health in patients with the Long COVID syndrome. METHODS:This was a literature review which queried databases for Pubmed, Psychinfo, and Medline for the following topics for January 1, 2020-July 15, 2023: Long COVID, PASC, brain, brain imaging, neurological, neurobiology, mental health, anxiety, depression. RESULTS:Tens of thousands of patients have developed Long COVID, with the most common neurobehavioral symptoms anosmia (loss of smell) and fatigue. Anxiety and mood disorders are elevated and seen in about 25% of Long COVID patients. Neuropsychological testing studies show a correlation between symptom severity and cognitive dysfunction, while brain imaging studies show global decreases in gray matter and alterations in olfactory and other brain areas. CONCLUSIONS:Studies to date show an increase in neurobehavioral disturbances in patients with Long COVID. Future research is needed to determine mechanisms.

BACKGROUND:Sleep problems are reported for up to 80% of autistic individuals. We examined whether parsimonious sets of items derived from the Modified Checklist for Autism in Toddlers, Revised (M-CHAT-R) and the Brief Infant Sleep Questionnaire (BISQ) are superior to the standard M-CHAT-R in predicting subsequent autism spectrum disorder (ASD) diagnoses. METHODS:Participants from 11 Environmental influences on Child Health Outcomes (ECHO) cohorts were included. We performed logistic LASSO regression models with 10-fold cross-validation to identify whether a combination of items derived from the M-CHAT-R and BISQ are superior to the standard M-CHAT-R in predicting ASD diagnoses. RESULTS:The final sample comprised 1552 children. The standard M-CHAT-R had a sensitivity of 44% (95% CI: 34, 55), specificity of 92% (95% CI: 91, 94), and AUROC of 0.726 (95% CI: 0.663, 0.790). A higher proportion of children with ASD had difficulty falling asleep or resisted bedtime during infancy/toddlerhood. However, LASSO models revealed parental reports of sleep problems did not improve the accuracy of the M-CHAT-R in predicting ASD diagnosis. CONCLUSION/CONCLUSIONS:While children with ASD had higher rates of sleep problems during infancy/toddlerhood, there was no improvement in ASD developmental screening through the incorporation of parent-report sleep metrics. IMPACT/CONCLUSIONS:Parental-reported sleep problems are common in autism spectrum disorder (ASD). We investigated whether the inclusion of parental-reports of infant/toddler sleep patterns enhanced the effectiveness of developmental screening for autism. We reported higher rates of difficulty falling asleep and resisting bedtime during infancy and toddlerhood among children later diagnosed with ASD; however, we did not find an improvement in ASD developmental screening through the incorporation of parent-report sleep metrics. In our sample, the standard M-CHAT-R had a sensitivity of 39% among children of mothers with government insurance compared with a sensitivity of 53% among children of mothers with employer-based insurance.

Generative artificial intelligence (genAI) has potential to improve healthcare by reducing clinician burden and expanding services, among other uses. There is a significant gap between the need for mental health care and available clinicians in the United States-this makes it an attractive target for improved efficiency through genAI. Among the most sensitive mental health topics is suicide, and demand for crisis intervention has grown in recent years. We aimed to evaluate the quality of genAI tool responses to suicide-related queries. We entered 10 suicide-related queries into five genAI tools-ChatGPT 3.5, GPT-4, a version of GPT-4 safe for protected health information, Gemini, and Bing Copilot. The response to each query was coded on seven metrics including presence of a suicide hotline number, content related to evidence-based suicide interventions, supportive content, harmful content. Pooling across tools, most of the responses (79%) were supportive. Only 24% of responses included a crisis hotline number and only 4% included content consistent with evidence-based suicide prevention interventions. Harmful content was rare (5%); all such instances were delivered by Bing Copilot. Our results suggest that genAI developers have taken a very conservative approach to suicide-related content and constrained their models' responses to suggest support-seeking, but little else. Finding balance between providing much needed evidence-based mental health information without introducing excessive risk is within the capabilities of genAI developers. At this nascent stage of integrating genAI tools into healthcare systems, ensuring mental health parity should be the goal of genAI developers and healthcare organizations.

BACKGROUND:The comparative benefits and harms of available interventions for ADHD in adults remain unclear. We aimed to address these important knowledge gaps. METHODS:In this systematic review and component network meta-analysis (NMA), we searched multiple databases for published and unpublished randomised controlled trials (RCTs) investigating pharmacological and non-pharmacological interventions for ADHD in adults from database inception to Sept 6, 2023. We included aggregate data from RCTs comparing interventions against controls or any other eligible active intervention for the treatment of symptoms in adults (ages ≥18 years) with a formal diagnosis of ADHD. Pharmacological therapies were included only if their maximum planned doses were considered eligible according to international guidelines. We included RCTs of at least 1-week duration for medications, of at least four sessions for psychological therapies, and of any length deemed appropriate for neurostimulation. For RCTs of medications, cognitive training, or neurostimulation alone, we included only double-blind RCTs. At least two authors independently screened the identified records and extracted data from eligible RCTs. Our primary outcomes were efficacy (change in ADHD core symptom severity on self-rated and clinician-rated scales at timepoints closest to 12 weeks) and acceptability (all-cause discontinuation). We estimated standardised mean differences (SMDs) and odds ratios (ORs) using random effects pairwise and component NMA, dismantling interventions into specific therapeutic components. This study was registered with PROSPERO (CRD42021265576). People with relevant lived experience were involved in the conduct of the research and writing process. FINDINGS/RESULTS:Of 32 416 records, 113 unique RCTs encompassing 14 887 participants were eligible for analysis (6787 [45·6%] females, 7638 [51·3%] males, 462 [3·1%] sex not reported). The RCTs encompassed pharmacological therapies (63 [55·8%] of 113 RCTs; 6875 participants), psychological therapies (28 [24·8%] of 113 RCTs; 1116 participants), neurostimulatory therapy and neurofeedback (ten [8·8%] of 113 RCTs; 194 participants), and control conditions (97 [85·8%] of 113 RCTs; 5770 participants). For reduction of ADHD core symptoms at 12 weeks on both self-reported and clinician-reported rating scales, atomoxetine (self-reported scale SMD -0·38, 95% CI -0·56 to -0·21; clinician-reported scale -0·51, -0·64 to -0·37) and stimulants (0·39, -0·52 to -0·26; -0·61, -0·71 to -0·51) had higher efficacy than placebo (Confidence in Network Meta-Analysis [CINeMA] ranging between very low and moderate). Cognitive behavioural therapy (-0·76, -1·26 to -0·26), cognitive remediation (-1·35, -2·42 to -0·27), mindfulness (-0·79, -1·29 to -0·29), psychoeducation (-0·77, -1·35 to -0·18), and transcranial direct current stimulation (-0·78; -1·13 to -0·43) were better than placebo only on clinician-reported measures. Regarding acceptability, all therapeutic components were similar to placebo other than atomoxetine (OR 1·43, 95% CI 1·14 to 1·80; CINeMA moderate) and guanfacine (3·70, 1·22 to 11·19; high), which had lower acceptability compared with placebo. Baseline severity of self-reported ADHD core symptoms, year of publication, percentage of male individuals, and percentage of individuals with ADHD and another mental health condition did not explain the heterogeneity observed in unadjusted non-component models of self-reported ADHD core symptoms. Treatment length had little effect on heterogeneity. INTERPRETATION/CONCLUSIONS:Stimulants and atomoxetine were the only interventions with evidence of beneficial effects in terms of reducing ADHD core symptoms in the short term, supported by both self-reported and clinician-reported ratings. However, atomoxetine was less acceptable than placebo. Medications for ADHD were not efficacious on additional relevant outcomes, such as quality of life, and evidence in the longer term is underinvestigated. The effects of non-pharmacological strategies were inconsistent across different raters. Our network meta-analysis represents the most comprehensive synthesis of available evidence to inform future guidelines in the field. FUNDING/BACKGROUND:UK National Institute for Health and Care Research.

Glutamatergic dentate gyrus (DG) mossy cells (MCs) innervate the primary DG cell type, granule cells (GCs). Numerous MC synapses are on GC proximal dendrites in the inner molecular layer (IML). However, field recordings of the GC excitatory postsynaptic potential (fEPSPs) have not been used to study this pathway selectively. Here we describe methods to selectively activate MC axons in the IML using mice with Cre recombinase expressed in MCs. Slices were made after injecting adeno-associated virus (AAV) encoding channelrhodopsin (ChR2) in the DG. In these slices, we show that fEPSPs could be recorded reliably in the IML in response to optogenetic stimulation of MC axons. Furthermore, fEPSPs were widespread across the septotemporal axis. However, fEPSPs were relatively weak because they were small in amplitude and did not elicit a significant population spike in GCs. They also showed little paired pulse facilitation. We confirmed the extracellular findings with patch clamp recordings of GCs despite different recording chambers and other differences in methods. Together the results provide a simple method for studying MC activation of GCs and add to the evidence that this input is normally weak but widespread across the GC population.

Firesetting behaviors are extremely dangerous not only to the individual but to society as one fire has the potential to destroy property and lead to serious injury or death. Youth firesetting behaviors are often under-assessed in psychiatric care settings intakes due to their relatively low base-rate and only are a part of a practitioner’s conceptualization when these behaviors are part of their presentation to an emergency room. Acute psychiatric care settings are well-equipped to assess and treat many highly dangerous behaviors such as active suicidal and homicidal ideation, as well as non-suicidal self-injury. However, youth firesetting is without a formal and directed plan on how to assess the risk of these behaviors, conceptualize, and intervene effectively. A case study of a 16-year-old multiracial male named “Luis”, who was psychiatrically hospitalized on an adolescent inpatient unit following multiple firesetting behaviors in the community, is used is to show the importance of multiinterdisciplinary collaboration between mental health providers and local fire safety programs. In addition, we will offer several recommendations to providers in the assessment and treatment related to juvenile who fireset

This pilot study aimed to understand the moderating role of context processing (i.e. encoding and memorizing) when mothers are confronted with threatening stimuli and undergo physiologic monitoring in order to understand a possible mechanism favoring intergenerational transmission of posttraumatic stress. Thirty-one mothers (M age = 33.87 years, SD = 4.14) and their toddlers (M age = 22.66 months, SD = 7.01) participated in the study. Mothers reported adverse life events (ALE), their current posttraumatic stress symptoms (PTSS), as well as regulatory problems of their toddler. Mothers performed a context-encoding and -memory (CEM) task including emotional facial expressions (especially angry faces considered as threatening stimuli) embedded into photo-backgrounds, after which they were asked to recognize both the faces and contexts. Maternal heart rate variability (HRV) was measured during resting state. Maternal current PTSS, but not ALE, had impact on child dysregulation only for mothers with poor context processing (β = 0.014, p = .017). Baseline HRV was negatively correlated with the recognition of contexts previously associated with angry faces (ρ = -.53, p = .006), and marginally with the recognition of angry faces (ρ = -.37, p = .059). This pilot study identifies psychophysiological markers (i.e. CEM, HRV) that may influence the intergenerational transmission of posttraumatic stress. This may open new avenues in early identification and intervention with traumatized mothers and their toddlers.