Faculty Bibliography
Searched for:
school:SOM
Department/Unit:Child and Adolescent Psychiatry
Total Results:
11507
Effects of Short Chain Fatty Acid Supplementation in Modulation of Gut Microbiome and T-Regulatory Cells in Health and New Onset Rheumatoid Arthritis [Meeting Abstract]
Background/Purpose: The gut microbiome and its metabolites are dysregulated in rheumatoid arthritis. Short chain fatty acids (SCFAs), microbial fermentation byproducts of certain gut microbes, induce regulatory T cells (Treg) that exhibit antiinflammatory properties. Unsurprisingly, SCFA are found at reduced levels in both murine models of RA and patients. The SCFA butyrate has been shown to increase levels of gut and circulating Treg and ameliorate inflammatory arthritis in murine models. Additionally, we previously noted that SCFA supplementation in WT mice led to significant perturbations in gut bacterial composition with a significant increase in SCFA-producing commensals. Similarly, others have shown that a high-fiber diet increases circulating levels of SCFAs and decreases pro-arthritogenic cytokines (Durholz et al. Nutrients. 2020). We therefore hypothesized that butyrate supplementation may promote favorable gut microbial changes and increase tolerogenic adaptive immune response in RA patients.
Method(s): We designed an ongoing, prospective, proof-of-principle study to determine the effects of butyrate supplementation in new-onset RA (NORA) patients. First, we evaluated the effects of butyrate supplementation in healthy subjects (n=7; 1 gm 3 times daily for 14 days). Next, we evaluated the effects of butyrate on new-onset RA (n=5; 1 gm 3 times daily for 30 days) compared to methotrexate (n=20). Clinical history and joint exam were performed at baseline and follow up. Peripheral blood and fecal samples were collected at baseline and follow up for flow cytometric analysis of Treg and 16s rRNA sequencing, respectively. Wilcoxon signed-rank test was used to compare differences in Treg before and after butyrate administration.
Result(s): Although butyrate supplementation in healthy subjects did not lead to significant community changes by 7 days, it did lead to a significant increase in the percentage of circulating CD4+CD25+FoxP3+ Treg (p=0.02) followed by a significant increase in highly activated CD39+ Treg by 14 days (p < 0.0001). Gut bacterial alpha diversity (Shannon index) was significantly lower in NORA patients compared to healthy subjects at baseline (p=0.04; wilcox-test). After butyrate supplementation, NORA alpha diversity increased to levels approaching those of healthy subjects, with a modest increase in abundance of both Firmicutes and Bacteroidetes. LDA Effect Size analysis recapitulated previous studies where healthy subjects had greater abundance of SCFA producing commensals compared to NORA.
Conclusion(s): In both health and new-onset RA, butyrate supplementation is associated with changes in human gut microbiota composition and in peripheral Treg abundance and markers of Treg activation. In preliminary analyses of this ongoing prospective study, butyrate increased gut microbial diversity in NORA, suggesting that gut microbial composition may shift towards a healthier level of diversity. As seen in murine models, butyrate also increased Treg in healthy subjects. We hypothesize that, in patients, butyrate will induce modifications in gut microbial communities that favor a regulatory adaptive immune response that may ultimately lead to better clinical response
Method(s): We designed an ongoing, prospective, proof-of-principle study to determine the effects of butyrate supplementation in new-onset RA (NORA) patients. First, we evaluated the effects of butyrate supplementation in healthy subjects (n=7; 1 gm 3 times daily for 14 days). Next, we evaluated the effects of butyrate on new-onset RA (n=5; 1 gm 3 times daily for 30 days) compared to methotrexate (n=20). Clinical history and joint exam were performed at baseline and follow up. Peripheral blood and fecal samples were collected at baseline and follow up for flow cytometric analysis of Treg and 16s rRNA sequencing, respectively. Wilcoxon signed-rank test was used to compare differences in Treg before and after butyrate administration.
Result(s): Although butyrate supplementation in healthy subjects did not lead to significant community changes by 7 days, it did lead to a significant increase in the percentage of circulating CD4+CD25+FoxP3+ Treg (p=0.02) followed by a significant increase in highly activated CD39+ Treg by 14 days (p < 0.0001). Gut bacterial alpha diversity (Shannon index) was significantly lower in NORA patients compared to healthy subjects at baseline (p=0.04; wilcox-test). After butyrate supplementation, NORA alpha diversity increased to levels approaching those of healthy subjects, with a modest increase in abundance of both Firmicutes and Bacteroidetes. LDA Effect Size analysis recapitulated previous studies where healthy subjects had greater abundance of SCFA producing commensals compared to NORA.
Conclusion(s): In both health and new-onset RA, butyrate supplementation is associated with changes in human gut microbiota composition and in peripheral Treg abundance and markers of Treg activation. In preliminary analyses of this ongoing prospective study, butyrate increased gut microbial diversity in NORA, suggesting that gut microbial composition may shift towards a healthier level of diversity. As seen in murine models, butyrate also increased Treg in healthy subjects. We hypothesize that, in patients, butyrate will induce modifications in gut microbial communities that favor a regulatory adaptive immune response that may ultimately lead to better clinical response
EMBASE:639965609
ISSN: 2326-5205
CID: 5513092
Short Research Article: Impact of a prolonged lockdown on the symptoms of paediatric ADHD and common associated disorders
OBJECTIVE:Our objective is to explore the change in the severity of ADHD, ODD and anxiety during a two-month lockdown among children in France and the moderating role of behavioural regulation. METHOD:In 235 children with ADHD, the symptom severity of ADHD, ODD and anxiety was investigated one and two months after the beginning of lockdown, and one month after its end. Behavioural regulation skills were estimated with the Behaviour Regulation Index. RESULTS:ADHD, ODD and anxiety scores were increasing or decreasing depending on BRI. CONCLUSION:Baseline behavioural regulation skills may act as a moderating factor for the persistence of ADHD, ODD and anxiety symptoms related to the lockdown.
PMID: 34983079
ISSN: 1475-357x
CID: 5470382
Reprint of: Advanced paternal age and risk of schizophrenia in offspring - Review of epidemiological findings and potential mechanisms
A large number of studies have examined the association between advanced paternal age (APA) and risk of schizophrenia in offspring. Here we present an overview of epidemiological studies on this subject published since 2000, and systematically summarize their methodologies and results. Next, we discuss evidence to elucidate the potential mechanisms contributing to the association between APA and offspring schizophrenia, considering paternal psychiatric morbidity and genetic liability, maternal factors, and findings from family design studies. We propose that multiple mechanisms, including causal and non-causal pathways, contribute to the observed relationship between APA and schizophrenia in offspring, and conclude by highlighting the need for multi-disciplinary studies in disentangling these complex, non-mutually exclusive mechanisms.
PMID: 36085274
ISSN: 1573-2509
CID: 5681802
State Policies that Impact the Design of Children's Mental Health Services: A Modified Delphi Study
To identify the state-level policies and policy domains that state policymakers and advocates perceive as most important for positively impacting the use of children's mental health services (CMHS). We used a modified Delphi technique (i.e., two rounds of questionnaires and an interview) during Spring 2021 to elicit perceptions among state mental health agency officials and advocates (n = 28) from twelve states on state policies that impact the use of CMHS. Participants rated a list of pre-specified policies on a 7-point Likert scale (1 = not important, 7 = extremely important) in the following policy domains: insurance coverage and limits, mental health services, school and social. Participants added nine policies to the initial list of 24 policies. The "school" policy domain was perceived as the most important, while the "social" policy domain was perceived as the least important after the first questionnaire and the second most important policy domain after the second questionnaire. The individual policies perceived as most important were school-based mental health services, state mental health parity, and Medicaid reimbursement rates. Key stakeholders in CMHS should leverage this group of policies to understand the current policy landscape in their state and to identify gaps in policy domains and potential policy opportunities to create a more comprehensive system to address children's mental health from a holistic, evidence-based policymaking perspective.
PMCID:9219374
PMID: 35737191
ISSN: 1573-3289
CID: 5282072
Research on child & adolescent psychopathology. 2022:50(9):1107-1119.DOI: 10.1007/s10802-022-00919-z
Secret Agent Society: A Randomized Controlled Trial of a Transdiagnostic Youth Social Skills Group Treatment
Group programs are key for targeting social skills (SS) for children with developmental disorders and/or mental illness. Despite promising evidence regarding efficacy of group treatments, there are several limitations to current research regarding generalizability and effectiveness across diagnoses. This randomized control trial assessed whether the Secret Agent Society (SAS) group program was superior to treatment as usual (TAU) in improving social-emotional functioning for children with Attention Deficit-Hyperactivity Disorder (ADHD), Autism Spectrum Disorder (ASD), and/or anxiety. Eighty-nine youth (8-12) with ADHD, ASD, and/or an anxiety disorder receiving treatment at hospital-based outpatient clinics were randomized to receive SAS (n = 47) or TAU (n = 42) over a three-month period, at which point TAU participants were offered the SAS intervention. Parent report showed significant improvement in Emotion Regulation (ER) and Social Skills (SS) for youth in SAS vs. TAU (Fs ≥ 6.79, ps ≤ 01). Gains for the SAS condition were maintained at 6-months. Intent-to-treat analysis of teacher report indicated youth in SAS had positive gains in SS (F = 0.41, p = 0.475) and ER (F = 0.99, p = 0.322), though not significantly better than youth in TAU. Clinically reliable improvement rates were significantly higher for SAS participants than TAU for parent and teacher reported SS and ER. Improvements were significant for youth with single and comorbid diagnoses. Results suggest that SAS was superior to TAU in improving SS and ER for youth aged 8-12 with ADHD, ASD, and/or anxiety. Gains maintained in the medium-term. Trial registration number NCT02574273, registered 10/12/2015.
PMID: 35441908
ISSN: 2730-7174
CID: 5981832
Recognizing and treating the emotional and behavioral effects of child maltreatment
[S.l.] : Nova Science Publishers, Inc., 2022
pp. 33-59
ISBN: 9798886970609
CID: 5369012
Advocacy for a coordinated and safe response for the mental health and psychosocial needs of children affected by the conflict in Ukraine [Letter]
PMCID:9395799
PMID: 35997819
ISSN: 1435-165x
CID: 5331572
Virtual Ontogeny of Cortical Growth Preceding Mental Illness
BACKGROUND:Morphology of the human cerebral cortex differs across psychiatric disorders, with neurobiology and developmental origins mostly undetermined. Deviations in the tangential growth of the cerebral cortex during pre/perinatal periods may be reflected in individual variations in cortical surface area later in life. METHODS:Interregional profiles of group differences in surface area between cases and controls were generated using T1-weighted magnetic resonance imaging from 27,359 individuals including those with attention-deficit/hyperactivity disorder, autism spectrum disorder, bipolar disorder, major depressive disorder, schizophrenia, and high general psychopathology (through the Child Behavior Checklist). Similarity of interregional profiles of group differences in surface area and prenatal cell-specific gene expression was assessed. RESULTS:Across the 11 cortical regions, group differences in cortical area for attention-deficit/hyperactivity disorder, schizophrenia, and Child Behavior Checklist were dominant in multimodal association cortices. The same interregional profiles were also associated with interregional profiles of (prenatal) gene expression specific to proliferative cells, namely radial glia and intermediate progenitor cells (greater expression, larger difference), as well as differentiated cells, namely excitatory neurons and endothelial and mural cells (greater expression, smaller difference). Finally, these cell types were implicated in known pre/perinatal risk factors for psychosis. Genes coexpressed with radial glia were enriched with genes implicated in congenital abnormalities, birth weight, hypoxia, and starvation. Genes coexpressed with endothelial and mural genes were enriched with genes associated with maternal hypertension and preterm birth. CONCLUSIONS:Our findings support a neurodevelopmental model of vulnerability to mental illness whereby prenatal risk factors acting through cell-specific processes lead to deviations from typical brain development during pregnancy.
PMID: 35489875
ISSN: 1873-2402
CID: 5217792
Longitudinal characterization of EEG power spectra during eyes open and eyes closed conditions in children
This study is the first to examine spectrum-wide (1 to 250 Hz) differences in electroencephalogram (EEG) power between eyes open (EO) and eyes closed (EC) resting state conditions in 486 children. The results extend the findings of previous studies by characterizing EEG power differences from 30 to 250 Hz between EO and EC across childhood. Developmental changes in EEG power showed spatial and frequency band differences as a function of age and EO/EC condition. A 64-electrode system was used to record EEG at 4, 5, 7, 9, and 11 years of age. Specific findings were: (1) the alpha peak shifts from 8 Hz at 4 years to 9 Hz at 11 years, (2) EC results in increased EEG power (compared to EO) at lower frequencies but decreased EEG power at higher frequencies for all ages, (3) the EEG power difference between EO and EC changes from positive to negative within a narrow frequency band which shifts toward higher frequencies with age, from 9 to 12 Hz at 4 years to 32 Hz at 11 years, (4) at all ages EC is characterized by an increase in lower frequency EEG power most prominently over posterior regions, (5) at all ages, during EC, decreases in EEG power above 30 Hz are mostly over anterior regions of the scalp. This report demonstrates that the simple challenge of opening and closing the eyes offers the potential to provide quantitative biomarkers of phenotypic variation in brain maturation by employing a brief, minimally invasive protocol throughout childhood.
PMID: 35968705
ISSN: 1540-5958
CID: 5340642
The day I told Karim Nader, "Don't do the study"
Karim Nader changed the course of memory research by reviving interest in the mostly forgotten topic of post-retrieval manipulations of memory. In this paper I summarize the events leading up to his ground-breaking study in my lab on so-called memory reconsolidation, and the effects of that study on the field.
PMID: 35981628
ISSN: 1873-2747
CID: 5300192
