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Co-occurring Psychopathology in Children With and Without Autism Spectrum Disorder (ASD): Differences by Sex in the ECHO Cohorts

Volk, Heather E; Fortes, Diogo; Musci, Rashelle; Kim, Amanda; Bastain, Theresa M; Camargo, Carlos A; Croen, Lisa A; Dabelea, Dana; Duarte, Cristiane S; Dunlop, Anne L; Gachigi, Kennedy; Ghassabian, Akhgar; Hertz-Picciotto, Irva; Huddleston, Kathi C; Joseph, Robert M; Keating, Daniel; Kelly, Rachel S; Kim, Young Shin; Landa, Rebecca J; Leve, Leslie D; Lyall, Kristen; Northrup, Jessie B; O'Connor, Thomas; Ozonoff, Sally; Ross, Anna; Schmidt, Rebecca J; Schweitzer, Julie B; Shuffrey, Lauren C; Shuster, Coral; Vance, Emily; Weiss, Scott T; Wilkening, Greta; Wright, Robert O
PURPOSE/OBJECTIVE:Our goals were to: 1) examine the occurrence of behavioral and emotional symptoms in children on the autism spectrum in a large national sample, stratifying by sex, and 2) evaluate whether children with increased autism-related social communication deficits also experience more behavioral and emotional problems. METHODS: Participants (n = 7,998) were from 37 cohorts from the Environmental influences on Child Health Outcomes (ECHO) Program. Cross-sectional information on demographic factors, parent-report of an ASD diagnosis by clinician, Social Responsiveness Scale (SRS) scores, and Child Behavior Checklist (CBCL) scores were obtained for children aged 2.5-18 years by surveys. We examined mean differences in CBCL Total Problems and DSM-oriented subscale scores by autism diagnosis and by child sex. Analyses using logistic regression were conducted to examine whether autism was associated with higher CBCL scores. We further examined if these relationships differed by child age category (< 6 years, 6-11 years, 12 + years). The relationships between SRS score and CBCL total and subscale scores were examined using quantile regression models, with analyses adjusted for child sex and age. RESULTS: In ECHO, 553 youth were reported by a parent to have a clinician diagnosis of autism spectrum disorder (ASD) (432 [78%] boys and 121 [22%] girls). Youth on the spectrum had higher mean CBCL raw scores on Total Problems and all DSM-oriented subscales compared to those not on the spectrum (all p < 0.0001). Analyses adjusted for sex and stratified by age group indicated that higher odds of autism diagnosis were associated with total, depression, anxiety, and attention-deficit/hyperactivity disorder (ADHD) scales in the top 30% of the CBCL score distribution. Autistic girls were more likely to have parent-reported depression and anxiety compared to autistic boys. In quantile regression analyses, we observed evidence of stronger associations between SRS and CBCL for those in higher quantiles of CBCL total problems scale score (beta representing 1-unit change in SRS associated with 1-unit increase in CBCL total problems scale score), among children in the 70-90th percentile (β = 1.60, p < 0.01), or top 10th percentile (β = 2.43, p < 0.01) of the CBCL total problems scale score distribution. Similar findings were seen for the DSM-oriented depression, anxiety, and ADHD subscales. CONCLUSION/CONCLUSIONS: Results from this large national sample suggest increased behavioral and emotional problems among autistic children compared to non-autistic children throughout early life. Among children on the spectrum this may warrant increased monitoring for co-occurring behavioral and emotional problems.
PMID: 39762643
ISSN: 1573-3432
CID: 5804942

Mental Health Care Utilization and Prescription Rates Among Children, Adolescents, and Young Adults in France

Fond, Guillaume; Pauly, Vanessa; Brousse, Yann; Llorca, Pierre-Michel; Cortese, Samuele; Rahmati, Masoud; Correll, Christoph U; Gosling, Corentin J; Fornaro, Michele; Solmi, Marco; Smith, Lee; Veronese, Nicola; Yon, Dong Keon; Auquier, Pascal; Duclos, Antoine; Boyer, Laurent
IMPORTANCE/UNASSIGNED:Amid escalating mental health challenges among young individuals, intensified by the COVID-19 pandemic, analyzing postpandemic trends is critical. OBJECTIVE/UNASSIGNED:To examine mental health care utilization and prescription rates for children, adolescents, and young adults before and after the COVID-19 pandemic. DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:This population-based time trend study used an interrupted time series analysis to examine mental health care and prescription patterns among the French population 25 years and younger. Aggregated data from the French national health insurance database from January 2016 to June 2023. Data were analyzed from September 2023 to February 2024. MAIN OUTCOMES AND MEASURES/UNASSIGNED:The number of individuals with at least 1 outpatient psychiatric consultation, those admitted for full-time psychiatric hospitalization, those with a suicide attempt, and those receiving psychotropic medication was computed. Data were stratified by age groups and sex. Quasi-Poisson regression modeled deseasonalized data, estimating the relative risk (RR) and 95% CI for differences in slopes before and after the pandemic. RESULTS/UNASSIGNED:This study included approximately 20 million individuals 25 years and younger (20 829 566 individuals in 2016 and 20 697 169 individuals in 2022). In 2016, the population consisted of 10 208 277 of 20 829 566 female participants (49.0%) and 6 091 959 (29.2%) aged 18 to 25 years. Proportions were similar in 2022. Significant increases in mental health care utilization were observed postpandemic compared with the prepandemic period, especially among females and young people aged 13 years and older. Outpatient psychiatric consultations increased among women (RR, 1.13; 95% CI, 1.07-1.20), individuals aged 13 to 17 years (RR, 1.15; 95% CI, 1.06-1.23), and individuals aged 18 to 25 years (RR, 1.08; 95% CI, 1.03-1.14). Hospitalizations for suicide attempt increased among women (RR, 1.14; 95% CI, 1.02-1.27) and individuals aged 18 to 25 years (RR, 1.07; 95% CI, 1.03-1.12). Regarding psychotropic medications, almost all classes, except hypnotics, increased in prescriptions between 2016 and 2022 for females, with a particularly marked rise in the postpandemic period. For men, only increases in the prescriptions of antidepressants (RR, 1.03; 95% CI, 1.01-1.06), methylphenidate (RR, 1.09; 95% CI, 1.06-1.12), and medications prescribed for alcohol use disorders (RR, 1.08; 95% CI, 1.04-1.13) were observed, and these increases were less pronounced than for women (antidepressant: RR, 1.13, 95% CI, 1.09-1.16; methylphenidate: RR, 1.15; 95% CI, 1.13-1.18; alcohol use dependence: RR, 1.12; 95% CI, 1.08-1.16). Medications reserved for severe mental health situations, such as lithium or clozapine, were prescribed more frequently starting at the age of 6 years. CONCLUSIONS AND RELEVANCE/UNASSIGNED:In this study, an interrupted time-series analysis found a marked deterioration in the mental health of young women in France in the after the COVID-19 pandemic, accentuating a trend of deterioration that was already observed in the prepandemic period.
PMCID:11707635
PMID: 39777444
ISSN: 2574-3805
CID: 5779342

Race and Ethnicity and Diffusion of Telemedicine in Medicaid for Schizophrenia Care After Onset of the COVID-19 Pandemic

Normand, Sharon-Lise; Leckman-Westin, Emily; Finnerty, Molly; Jeong, Junghye; Tsuei, Jeannette; Zelevinsky, Katya; Chen, Qingxian; Horvitz-Lennon, Marcela
IMPORTANCE/UNASSIGNED:Delivery of mental health care through telehealth (telemental health care) increased after the onset of the COVID-19 pandemic. Little is known about the speed of adoption (diffusion) of telemental health in the care in the care of individuals with schizophrenia. OBJECTIVES/UNASSIGNED:To characterize telemental health care diffusion in mental health agencies serving Medicaid beneficiaries with schizophrenia and the beneficiary-level association of telemental health care use with race and ethnicity. DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:This retrospective cohort study used New York State Medicaid data from March 1, 2019, to February 29, 2020 (prepandemic period), and from March 11, 2020, to March 31, 2021 (pandemic period), from 261 agencies serving 30 990 beneficiaries with schizophrenia with 1 or more mental health visits during the pandemic period. Statistical analysis was performed from November 2021 through September 2024. EXPOSURE/UNASSIGNED:Agency percentage of patients belonging to racial and ethnic minority groups among all Medicaid-covered patients between March 2019 and February 2020; agency type, categorized as freestanding, hospital affiliated, or state operated; beneficiary-level race and ethnicity, categorized as Asian or other (American Indian or Alaska Native; Native Hawaiian or Other Pacific Islander), Black, Latinx, White, and unknown; and pandemic severity, operationalized as COVID-19 hospitalization rates per 10 000 population in administratively defined catchment areas. MAIN OUTCOMES AND MEASURES/UNASSIGNED:Days to 10% cumulative telemental health care use within agencies, as well as beneficiary-level time to first telemental health care visit and any telemental health care visit in catchment areas in times of varying pandemic severity. RESULTS/UNASSIGNED:In this cohort study of 261 agencies (18 [7%] state operated, 79 [30%] hospital affiliated, and 164 [63%] free standing) and 30 990 beneficiaries with schizophrenia (mean [SD] age, 43 [13] years; 59% male; 7% Asian or other, 38% Black, 20% Latinx, and 25% White), 6 agencies (2%) never adopted telemental health care, and 248 (95%) reached 10% cumulative telemental health care visits in a mean of 18 days. Mean (SD) agency prepandemic shares of beneficiaries belonging to racial or ethnic minority groups (56% [23%]) were not associated with telemental health care diffusion. Diffusion was faster in state-operated vs free-standing agencies (hazard ratio [HR], 2.44 [95% CI, 1.21-4.95]). Relative to White beneficiaries, time to first telemental health care visit was slower in every racial and ethnic minority group (Asian or other: HR, 0.93 [95% CI, 0.88-0.98]; Black: HR, 0.90 [95% CI, 0.87-0.93]; Latinx: HR, 0.95 [95% CI, 0.91-0.99]). Beneficiaries from at least 1 racial or ethnic minority group were less likely than White beneficiaries to have a telemental health care visit regardless of pandemic severity and area; differences narrowed when pandemic severity was higher (eg, in New York City, the odds ratio of Black beneficiaries having a telemental health care visit relative to White beneficiaries when the pandemic severity was high was 0.70 [95% CI, 0.63-0.79] but decreased to 0.59 [95% CI, 0.53-0.67] when the pandemic severity was low). CONCLUSIONS AND RELEVANCE/UNASSIGNED:In this cohort study of Medicaid beneficiaries with schizophrenia, telemental health care diffused rapidly after the onset of the COVID-19 pandemic, particularly in state-operated agencies. Together, agency-level and beneficiary-level race and ethnicity findings suggest within-agency racial and ethnic differences in diffusion of telemental health care. States should monitor the diffusion of innovations across vulnerable populations.
PMCID:11739993
PMID: 39820692
ISSN: 2574-3805
CID: 5777362

Multidimensional Personality Changes Following Psilocybin-Assisted Therapy in Patients With Alcohol Use Disorder: Results From a Double-Blind, Placebo-Controlled Clinical Trial

Pagni, Broc A; Zeifman, Richard J; Mennenga, Sarah E; Carrithers, Brennan M; Goldway, Noam; Bhatt, Snehal; O'Donnell, Kelley C; Ross, Stephen; Bogenschutz, Michael P
OBJECTIVE/UNASSIGNED:Evidence suggests that psilocybin-assisted therapy (PAT) leads to durable shifts in personality structure. However, such changes have yet to be characterized in disorders of addiction. In this secondary analysis from a randomized controlled trial, the authors examined the effect of PAT on personality dimensions in patients with alcohol use disorder (AUD), hypothesizing that PAT would attenuate personality abnormalities in AUD and that reductions in trait impulsiveness would be associated with lower drinking. METHODS/UNASSIGNED:Eighty-four adults with AUD were randomized to two medication sessions of either psilocybin (N=44) or active placebo (diphenhydramine; N=40), received 12 weekly psychotherapy sessions, and completed follow-up for an additional 24 weeks. Changes in personality traits (week 36 vs. baseline) were assessed with the revised NEO Personality Inventory; daily alcohol consumption was quantified using the timeline followback. RESULTS/UNASSIGNED:Relative to the placebo group, the psilocybin group showed significant reductions in neuroticism and increases in extraversion and openness. Secondary analyses showed that reductions in neuroticism were driven by decreases in the facets depression, impulsiveness, and vulnerability; increases in openness were driven by increases in the facets openness toward feelings and fantasy. Across all participants, decreases in impulsiveness were associated with lower posttreatment alcohol consumption, and an exploratory analysis revealed that these associations were strongest among psilocybin-treated participants who continued moderate- or high-risk drinking prior to the first medication session. CONCLUSIONS/UNASSIGNED:PAT elicited durable shifts in personality, suggesting normalization of abnormal personality trait expression in AUD. Further study is needed to clarify whether PAT exerts its beneficial effects by reducing impulsiveness or whether impulsive individuals inherently respond better to PAT.
PMID: 39741446
ISSN: 1535-7228
CID: 5779242

Acute and long-term effects of COVID-19 on brain and mental health: A narrative review

Bremner, J Douglas; Russo, Scott J; Gallagher, Richard; Simon, Naomi M
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.
PMID: 39500417
ISSN: 1090-2139
CID: 5761312

First evidence on a general disease ("d") factor underlying psychopathology and physical illness in adolescents

Stevanovic, Dejan; Cirovic, Nikola; Cortese, Samuele; Knez, Rajna; Kerekes, Nóra
The coexistence of mental and physical health illnesses could be accounted for by an underlying general disease factor (termed d-factor), reflecting theoretical underpinnings based on possible genetic and pathophysiological overlapping mechanisms. This study evaluated whether the d-factor underlies mental and physical health illnesses in adolescents. A series of confirmatory factor analyses were conducted using data from 1120 adolescents. The proposed common underlying factor, we believe is the d-factor, was consistently present across different modeling approaches, including unidimensional, correlated-factor, and bifactor models. The best model fit was achieved with the bifactor model represented by mental, neurological, and psychical conditions tested. The first compelling evidence was provided supporting the existence of the transdiagnostic d-factor in youth, opening the door to innovative research of comorbid mental and physical health conditions.
PMID: 38849671
ISSN: 1435-165x
CID: 5665912

Pulmonary Overcirculation Requiring Surgical and Pulmonary Flow Restrictor Device Intervention in Critical Coarctation of the Aorta-A Case Series [Case Report]

Medar, Shivanand S; Kumar, T K Susheel; Choi, Esther Yewoon; Cha, Christine; Saharan, Sunil; Argilla, Michael; Mosca, Ralph S; Chakravarti, Sujata B
The use of prostaglandin infusion to maintain patency of the ductus arteriosus in patients with critical coarctation of the aorta (CoA) to support systemic circulation is the standard of care. However, pulmonary overcirculation resulting from a patent ductus arteriosus in patients with critical CoA is not well described in the literature. We report two cases of critical CoA that required invasive measures to control pulmonary blood flow before surgical repair of the CoA. Both patients had signs of decreased oxygen delivery, hyperlactatemia, and systemic to pulmonary flow via the ductus arteriosus. One patient required surgical pulmonary artery banding and the second patient underwent pulmonary flow restrictor device placement for the control of pulmonary blood flow. A rapid improvement in oxygen delivery and normalization of lactate levels were observed after control of pulmonary overcirculation. Both patients underwent successful surgical repair of the coarctation A and were discharged home.
PMID: 39328166
ISSN: 2150-136x
CID: 5762082

Towards an Understanding of the Dentate Gyrus Hilus [Historical Article]

Scharfman, Helen E
For many years, the hilus of the dentate gyrus (DG) was a mystery because anatomical data suggested a bewildering array of cells without clear organization. Moreover, some of the anatomical information led to more questions than answers. For example, it had been identified that one of the major cell types in the hilus, the mossy cell, innervates granule cells (GCs). However, mossy cells also targeted local GABAergic neurons. Furthermore, it was not yet clear if mossy cells were glutamatergic or GABAergic. This led to many debates about the role of mossy cells. However, it was clear that hilar neurons, including mossy cells, were likely to have very important functions because they provided strong input to GCs. Hilar neurons also attracted attention in epilepsy because pathological studies showed that hilar neurons were often lost, but GCs remained. Vulnerability of hilar neurons also occurred after traumatic brain injury and ischemia. These observations fueled an interest to understand hilar neurons and protect them, an interest that continues to this day. This article provides a historical and personal perspective into the ways that I sought to contribute to resolving some of the debates and moving the field forward. Despite several technical challenges the outcomes of the studies have been worth the effort with some surprising findings along the way. Given the growing interest in the hilus, and the advent of multiple techniques to selectively manipulate hilar neurons, there is a great opportunity for future research.
PMCID:11673923
PMID: 39721944
ISSN: 1098-1063
CID: 5767562

Safety of psychotropic medications in pregnancy: an umbrella review

Fabiano, Nicholas; Wong, Stanley; Gupta, Arnav; Tran, Jason; Bhambra, Nishaant; Min, Kevin K; Dragioti, Elena; Barbui, Corrado; Fiedorowicz, Jess G; Gosling, Corentin J; Cortese, Samuele; Gandhi, Jasmine; Saraf, Gayatri; Shorr, Risa; Vigod, Simone N; Frey, Benicio N; Delorme, Richard; Solmi, Marco
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.
PMID: 39266712
ISSN: 1476-5578
CID: 5690682

Combining developmental and sleep health measures for autism spectrum disorder screening: an ECHO study

Shuffrey, Lauren C; Rennie, Brandon; Li, Xiuhong; Galai, Noya; Pini, Nicolò; Akbaryan, Anahid; Alshawabkeh, Akram; Aschner, Judy; Vargas, Julianna Collazo; Costello, Lauren; D'Sa, Viren; Deoni, Sean; Dunlop, Anne; Elliott, Amy J; Fifer, William P; Hash, Jonica; Koinis-Mitchell, Daphne; Lai, Jin-Shei; Leventhal, Bennett L; Lewis, Johnnye; Lucchini, Maristella; McArthur, Kristen L; Morales, Santiago; Nozadi, Sara S; O'Connor, Thomas G; O'Shea, T Michael; Page, Grier P; Propper, Cathi; Sania, Ayesha; Shuster, Coral; Zimmerman, Emily; Margolis, Amy E; ,
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.
PMID: 38867029
ISSN: 1530-0447
CID: 5669182