Faculty Bibliography

Monosodium glutamate (MSG) has become one of the most widely used food additives in the global food supply. Although it has been classified for decades as a food ingredient that is generally recognized as safe, concerns about the health impacts of chronic MSG use, especially its potential effect on weight, are still ongoing. This comprehensive review summarizes the available human and animal evidence, highlighting potential mechanisms linking MSG use to weight gain or obesity, and discusses challenges and future research directions. Because of MSG intake worldwide as well as hidden MSG in food labeling, there is a pressing need for a mechanistic understanding of the health impacts of MSG use especially on weight. To generate robust scientific evidence and to clarify public concerns, rigorous mechanistic studies and randomized controlled clinical trials are warranted.

IMPORTANCE/UNASSIGNED:General trauma is the leading cause of nonobstetric maternal morbidity and mortality, affecting approximately 8% of all pregnancies. Pregnant women with traumatic brain injury (TBI) face high morbidity and mortality rates, requiring complex management due to physiological changes, teratogenic risks of treatments, and the need for fetal monitoring. OBJECTIVES/UNASSIGNED:To assess the consequences of TBI during pregnancy on maternal and fetal outcomes and to evaluate management strategies to inform clinical decision-making. EVIDENCE REVIEW/UNASSIGNED:A systematic literature search was conducted on January 12, 2024, in PubMed, Web of Science, and PsycInfo to identify articles published in English, German, or Spanish between January 1, 1990, and December 31, 2023, that included at least 1 pregnant individual with TBI. Peer-reviewed, human-based studies with original data on maternal and fetal outcomes were included. Reviews, meta-analyses, and nonhuman studies were excluded. Two independent reviewers screened abstracts and full-text articles. Study characteristics, pregnancy outcomes (maternal and fetal), management methods, and authors' conclusions were extracted. Risk of bias was assessed by 2 reviewers, with interrater agreement measured using Cohen κ. Disagreements were resolved through discussion. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guideline was followed. FINDINGS/UNASSIGNED:This systematic review included 16 articles involving a total of 4112 individuals (mean maternal age, 26.9 years; range, 16-47 years) who experienced TBI during pregnancy (mean gestational age at injury, 24 weeks; range, 3-38 weeks). The articles comprised 10 case reports, 2 case series, and 4 cohort studies. Motor vehicle crashes were the most common cause of injury, reported in 12 articles. The average Glasgow Coma Scale score ranged from 3 to 15 across all individuals. Conservative management was reported in 7 case patients, whereas surgery was performed in 6 case patients. Maternal outcomes ranged from functional recovery to severe cognitive impairment, and fetal outcomes varied from stable to severe adverse outcomes, including stillbirth and death. Risk of bias assessment indicated moderate to good methodological validity overall, but most articles demonstrated poor quality of evidence. CONCLUSIONS AND RELEVANCE/UNASSIGNED:In this review, no definitive association between TBI during pregnancy and maternal or fetal outcomes was found owing to conflicting findings, poor to moderate study quality, and limited evidence. Although some articles suggested increased risks such as placental abruption and cesarean delivery, the findings remained inconclusive. The findings of this review underscore the need for high-quality research, standardized reporting, and rigorous methodology to improve data reliability. Future research should focus on developing consensus-driven, multidisciplinary management strategies to improve maternal and fetal outcomes.

IMPORTANCE/UNASSIGNED:Neurofeedback has been proposed for the treatment of attention-deficit/hyperactivity disorder (ADHD) but the efficacy of this intervention remains unclear. OBJECTIVE/UNASSIGNED:To conduct a meta-analysis of randomized clinical trials (RCTs) using probably blinded (ie, rated by individuals probably or certainly unaware of treatment allocation) or neuropsychological outcomes to test the efficacy of neurofeedback as a treatment for ADHD in terms of core symptom reduction and improved neuropsychological outcomes. DATA SOURCES/UNASSIGNED:PubMed (MEDLINE), Ovid (PsycInfo, MEDLINE, Embase + Embase Classic), and Web of Science, as well as the reference lists of eligible records and relevant systematic reviews, were searched until July 25, 2023, with no language limits. STUDY SELECTION/UNASSIGNED:Parallel-arm RCTs investigating neurofeedback in participants of any age with a clinical ADHD or hyperkinetic syndrome diagnosis were included. DATA EXTRACTION AND SYNTHESIS/UNASSIGNED:Standardized mean differences (SMDs) with Hedges g correction were pooled in random effects meta-analyses for all eligible outcomes. MAIN OUTCOMES AND MEASURES/UNASSIGNED:The primary outcome was ADHD total symptom severity assessed at the first postintervention time point, focusing on reports by individuals judged probably or certainly unaware of treatment allocation (probably blinded). Secondary outcomes were inattention and/or hyperactivity-impulsivity symptoms and neuropsychological outcomes postintervention and at a longer-term follow-up (ie, after the last follow-up time point). RCTs were assessed with the Cochrane risk of bias tool version 2.0. RESULTS/UNASSIGNED:A total of 38 RCTs (2472 participants aged 5 to 40 years) were included. Probably blinded reports of ADHD total symptoms showed no significant improvement with neurofeedback (k = 20; n = 1214; SMD, 0.04; 95% CI, -0.10 to 0.18). A small significant improvement was seen when analyses were restricted to RCTs using established standard protocols (k = 9; n = 681; SMD, 0.21; 95% CI, 0.02 to 0.40). Results remained similar with adults excluded or when analyses were restricted to RCTs where cortical learning or self-regulation was established. Of the 5 neuropsychological outcomes analyzed, a significant but small improvement was observed only for processing speed (k = 15; n = 909; SMD, 0.35; 95% CI, 0.01 to 0.69). Heterogeneity was generally low to moderate. CONCLUSIONS AND RELEVANCE/UNASSIGNED:Overall, neurofeedback did not appear to meaningfully benefit individuals with ADHD, clinically or neuropsychologically, at the group level. Future studies seeking to identify individuals with ADHD who may benefit from neurofeedback could focus on using standard neurofeedback protocols, measuring processing speed, and leveraging advances in precision medicine, including neuroimaging technology.

Iron in the brain is essential to neurodevelopmental processes, as it supports neural functions, including processes of oxygen delivery, electron transport, and enzymatic activity. However, the development of brain iron before birth is scarcely understood. By estimating R2* (1/T2*) relaxometry from a sizable sample of fetal multiecho echo-planar imaging (EPI) scans, which is the standard sequence for functional magnetic resonance imaging (fMRI), across gestation, this study investigates age and sex-related changes in iron, across regions and tissue segments. Our findings reveal that brain R2* levels significantly increase throughout gestation spanning many different regions, except the frontal lobe. Furthermore, females exhibit a faster rate of R2* increase compared to males, in both gray matter and white matter. This sex effect is particularly notable within the left insula. This work represents the first MRI examination of iron accumulation and sex differences in developing fetal brains. This is also the first study to establish R2* estimation methodology in fetal multiecho functional MRI.

Although parenting interventions are recommended by major clinical guidelines for managing children's behavioral challenges, including ADHD, their uptake in clinical practice remains limited. Building on the contributions of Hodson et al. and Nijboer et al. in the current issue of this journal, we here explore solutions to enhance this uptake. We first summarize the usual suspects: solutions that could be implemented in our current mental healthcare systems. Digital and brief interventions could remove obstacles that are often experienced with traditional parenting interventions, and nudges inspired by behavioral economic theories can help remove dynamic, time-varying barriers experienced by parents that may arise during the course of the intervention. We then zoom out and present a paradigmatic challenge. The current narrative surrounding behavioral problems like ADHD is predominantly biomedical, which tends to elevate expectations for treatments such as medication while simultaneously diminishing confidence in parenting interventions. From this perspective, it is unsurprising that engagement issues arise when a context-focused intervention such as parent training is proposed as a solution to a decontextualized problem like ADHD. Adopting a truly balanced biopsychosocial-societal perspective on behavioral problems like ADHD would better reflect their complex and heterogeneous etiology, and would broaden the scope for interventions, such as parenting programs, that focus on optimizing children's contextual environments.

We aimed to examine the role of shared decision-making (SDM) in family participation in the treatment of adolescents and young adults with first-episode psychosis (FEP). Based on responses of 144 family members of OnTrackNY (OTNY) participants, we divided the sample into low participators and high participators. We calculated the total SDM score for each participant by summing the ratings across items inquiring about SDM and assessed the extent to which loved ones encouraged family participation in their care. Our results indicated that the level of loved ones' encouragement was significantly related to family participation. When controlling for loved ones' encouragement, we found that the total SDM score was significantly higher in the high participator group. These findings suggest that SDM may be influenced by loved ones' attitudes towards family involvement in treatment and SDM may play a role in promoting family participation in care for individuals with FEP.

OBJECTIVE:To better understand the value of DNR orders for critically ill infants in the NICU. METHODS:A prospective mixed-methods approach was utilized including chart review of infants who died in a regional NICU over a twenty-six-month period and surveys of their neonatologists, neonatal fellows, and nurses. RESULTS:40 infants died during the study period and 120 staff surveys were completed. Infants with DNR orders were of a higher gestational age at birth and a higher chronological age at death. Nurses were more likely to perceive benefit from DNR orders than physicians. Medical staff recollection of the existence of DNR orders was not always accurate. Time and fear of adding unnecessary emotional burden to parents were identified as barriers to DNR order implementation. An advanced care planning model built on open communication instead of DNR order documentation was deemed the best approach. CONCLUSION/CONCLUSIONS:Though DNR orders are beneficial for a subset of infants, DNR orders are likely not applicable for all infants who die in the NICU. More important is supportive, individualized communication between families and the medical team to ensure quality end-of-life care. IMPACT/CONCLUSIONS:In the adult and pediatric ICU literature, DNR orders are associated with improved qualitative "good death" assessments and decreased familial decision regret. In the NICU, rates of DNR usage aren't well reported and their overall utility is unclear. Though DNR orders can help guide clinical decision making in the NICU and may be associated with higher quality ethical discussion, our data suggest that they are not applicable in all patient cases. We hope that this work will help guide approaches to end-of-life care in the NICU and underscore the importance of frequent, open communication between families and their medical team.

Parental depression is a risk factor for children's cognitive and psychological development. Literature has found reciprocal relations between parental depression and child psychopathology and effects of parental depression on children's cognition. The present study is the first to examine reciprocity among parental depression and child cognition, and pathways to child psychopathology. Structural equation models were conducted using data from the Early Head Start Research and Evaluation Project, a nationally representative sample of 3,001 economically marginalized families. Measures were collected in four waves from 14 months to 10-11 years. Reciprocal associations emerged between maternal and paternal depression at from 14 months to 5 years. Reciprocal parental depression was associated with greater psychopathology at age 10-11. Maternal depression predicted poorer child cognition, which indirectly predicted increased depression in mothers of children aged 3-5 through paternal depression, and in fathers at age 3, through earlier paternal depression. This study was unable to parse within- and between-person effects. Additionally, data for paternal depression was limited to ages 2 and 3. Findings emphasize the transactional nature of child cognition and child and parent psychopathology, supporting family focused intervention and prevention efforts that target parent psychopathology and child cognition.

BACKGROUND:Randomised controlled trials (RCTs) evaluating ADHD medications often use strict eligibility criteria, potentially limiting generalisability to patients in real-world clinical settings. We aimed to identify the proportion of individuals with ADHD who would be ineligible for medication RCTs and evaluate differences in treatment patterns and clinical and functional outcomes between RCT-eligible and RCT-ineligible individuals. METHODS:We used multiple Swedish national registries to identify individuals with ADHD, aged at least 4 years at the age of diagnosis, initiating pharmacological treatment between Jan 1, 2007, and Dec 31, 2019, with follow-up up to Dec 31, 2020. Hypothetical RCT ineligibility was established using exclusion criteria from the international MED-ADHD dataset, including 164 RCTs of ADHD medications. Cox models evaluated differences in medication switching and discontinuation within 1 year between eligible and ineligible individuals. Quasi-Poisson models compared eligible and ineligible individuals on rates of psychiatric hospitalisations, injuries or accidents, and substance use disorder within 1 year of initiating ADHD medications. People with lived experience of ADHD were not involved in the research and writing process. FINDINGS/RESULTS:Of 189 699 individuals included in the study cohort (112 153 men and boys [59%] and 77 546 women and girls [41%]; mean age 21·52 years [SD 12·83; range 4-68]) initiating ADHD medication, 53% (76 477 [74%] of 103 023 adults [aged >17 years], 12 658 [35%] of 35 681 adolescents [aged 13-17 years], and 10 643 [21%] of 50 995 children [aged <13 years]) would have been ineligible for RCT participation. Ethnicity data were not available. Ineligible individuals had a higher likelihood of treatment switching (hazard ratio 1·14, 95% CI 1·12-1·16) and a decreased likelihood of medication discontinuation (0·96, 0·94-0·98) compared with eligible individuals. Individuals ineligible for RCTs had significantly higher rates of psychiatric hospitalisations (ncidence rate ratio 9·68, 95% CI 9·57-9·78) and specialist care visits related to substance use disorder (14·78, 14·64-14·91), depression (6·00, 5·94-6·06), and anxiety (11·63, 11·56-11·69). INTERPRETATION/CONCLUSIONS:Individuals ineligible for ADHD medication trials face higher risks of adverse outcomes. This study provides the first empirical evidence for the limited generalisability of ADHD RCTs to real-world clinical populations, by applying eligibility criteria extracted from a comprehensive dataset of RCTs to a large real-world cohort. Triangulating evidence from RCTs and real-world studies is crucial to inform rigorous evidence-based treatment guidelines. FUNDING/BACKGROUND:National Institute of Healthcare and Research, European Union's Horizon 2020, and Swedish Research Council.

PURPOSE OF REVIEW/OBJECTIVE:There is a mental health crisis affecting youth, and the utility of existing treatments is often limited by lack of effectiveness and tolerability. The aim of this review is to report on outcomes of clinical trials for psilocybin-assisted psychotherapy for adults with depression and MDMA-assisted psychotherapy for adults with post-traumatic stress disorder (PTSD) and discuss recommendations for exploring these treatments in adolescent populations. RECENT FINDINGS/RESULTS:There have been encouraging data supporting the use of psilocybin-assisted psychotherapy for depression, including previously treatment-resistant symptoms. MDMA-assisted psychotherapy is showing similar promise in treating PTSD, with excellent response and remission rates that appear durable. However, no studies have looked at the use of these treatments in younger patients. The safety and efficacy of psychedelic- and MDMA-assisted psychotherapies should be investigated in adolescents, especially considering the burden of untreated and undertreated psychiatric illness in youth, and the benefits of a potentially earlier, more effective, and more tolerable recovery process. Research and implementation should be tailored to the needs of this population, and equity and access should be considered at every stage. In this novel and rapidly evolving landscape, the psychiatric community is encouraged to advocate for safe, appropriate, and inclusive inquiry into, and application and scaling of these treatment models in adolescent patients.