Monozygotic twins discordant for schizophrenia differ in maturation and synaptic transmission.

Schizophrenia affects approximately 1% of the world population. Genetics, epigenetics, and environmental factors are known to play a role in this psychiatric disorder. While there is a high concordance in monozygotic twins, about half of twin pairs are discordant for schizophrenia. To address the question of how and when concordance in monozygotic twins occur, we have obtained fibroblasts from two pairs of schizophrenia discordant twins (one sibling with schizophrenia while the second one is unaffected by schizophrenia) and three pairs of healthy twins (both of the siblings are healthy). We have prepared iPSC models for these 3 groups of patients with schizophrenia, unaffected co-twins, and the healthy twins. When the study started the co-twins were considered healthy and unaffected but both the co-twins were later diagnosed with a depressive disorder. The reprogrammed iPSCs were differentiated into hippocampal neurons to measure the neurophysiological abnormalities in the patients. We found that the neurons derived from the schizophrenia patients were less arborized, were hypoexcitable with immature spike features, and exhibited a significant reduction in synaptic activity with dysregulation in synapse-related genes. Interestingly, the neurons derived from the co-twin siblings who did not have schizophrenia formed another distinct group that was different from the neurons in the group of the affected twin siblings but also different from the neurons in the group of the control twins. Importantly, their synaptic activity was not affected. Our measurements that were obtained from schizophrenia patients and their monozygotic twin and compared also to control healthy twins point to hippocampal synaptic deficits as a central mechanism in schizophrenia.

Trajectories and correlates of mental health among urban, school-age children during the COVID-19 pandemic: a longitudinal study.

BACKGROUND: The COVID-19 pandemic posed numerous obstacles to psychosocial wellbeing for children. We conducted a longitudinal study to evaluate child mental health and social risks during the pandemic. METHODS: Participants were 172 caregivers of children aged 6-11 years old who attended well child visits within 6 months before pandemic onset at an urban safety net hospital in the US. Prepandemic data was extracted from the electronic medical record, and surveys were administered at three time points between August 2020 and July 2021. We measured mental health symptoms with the Pediatric Symptom Checklist-17, social risks (e.g., food and housing insecurity) with the THRIVE questionnaire, and school modality (in-person, hybrid, remote). RESULTS: Compared to pre-pandemic, children had significantly higher PSC-17 total scores (overall mental health symptoms) and THRIVE total scores (total burden of social risks) at all three mid-pandemic waves. Using longitudinal mixed models accounting for time, social risks, and school modality, both social risks (B = 0.37, SE = 0.14, p < 0.01) and school modality were significantly associated with PSC-17 scores (B = - 1.95, SE = 0.63, p < 0.01). Children attending in-person school had fewer mental health symptoms than those attending remote or hybrid school. CONCLUSION: Mental health symptoms and social risks remained significantly higher fifteen months after the onset of the COVID-19 pandemic compared to prepandemic. In-person attendance at school appeared protective against persistently elevated mental health symptoms.

A Quality Improvement Initiative for Detection of Attention-Deficit/Hyperactivity Disorder in an Urban, Academic Safety Net Hospital.

OBJECTIVE: Improve detection of Attention Deficit/Hyperactivity Disorder (ADHD) in a safety net, hospital-based, academic pediatric practice by optimizing screening with the Pediatric Symptom Checklist attention score (PSC-AS) and further evaluation with the Vanderbilt ADHD Diagnostic Rating Scale (VADRS). METHODS: We implemented a multi-component intervention by (1) optimizing electronic medical record (EMR) features; (2) adjusting clinic operational workflow; and (3) creating a decision-making algorithm for pediatric primary care clinicians (PPCCs). We extracted 4 outcomes manually from the EMR (pediatrician acknowledgment of a positive PSC-AS, documentation of a plan for further evaluation, distribution of VADRS, and completion of at least 1 VADRS). Outcomes were measured monthly in run charts compared to the pre-intervention control period, and implementation was optimized with Plan-Do-Study-Act cycles. RESULTS: PPCCs were significantly more likely to acknowledge a positive PSC-AS in the intervention versus control (65.3% vs 41.5%; p < 0.001), although this did not change documentation of a plan (70% vs 67.1%; p -value = 0.565). Significantly more children with a positive PSC-AS were distributed a parent or teacher VADRS in the intervention versus control (30.6% vs 17.7%; p -value = 0.0059), but the percentage of returned VADRS rating scales did not improve (12.9% vs 9.2%; p -value = 0.269). CONCLUSION: Our ADHD detection quality improvement initiative improved use of the PSC-AS to identify attention problems and distribution of VADRS diagnostic rating scales, but additional interventions are needed to improve the completion of ADHD evaluations in primary care to ensure that children are appropriately identified and offered evidence-based care.

Trends in Attention-Deficit Hyperactivity Disorder Diagnosis and Pharmacotherapy Among Adults With Opioid Use Disorder.

OBJECTIVE: This study aimed to assess nationwide trends in attention-deficit hyperactivity disorder (ADHD) diagnoses and pharmacotherapy among patients with opioid use disorder and ADHD and to examine factors predicting receipt of stimulant medications among patients receiving medications for opioid use disorder (MOUDs). METHODS: A claims-based database of commercially insured patients ages 13-64 was used to conduct two analyses: an annual cross-sectional study of 387,980 patients diagnosed as having opioid use disorder (2007-2017) to estimate the prevalence of ADHD diagnoses and pharmacotherapy, and a retrospective cohort study of 158,591 patients receiving MOUDs to test, with multivariable regression, the association between patient characteristics and receipt of stimulant medication. RESULTS: From 2007 to 2017, the prevalence of ADHD diagnoses increased from 4.6% to 15.1% and the rate of ADHD pharmacotherapy increased from 42.6% to 51.8% among patients with opioid use disorder. Among all patients receiving MOUDs, 10.5% received at least one prescription stimulant during the study period. Female sex; residence in the southern United States; and ADHD, mood, and anxiety disorder diagnoses were associated with increased likelihood of stimulant receipt. Stimulant use disorder and other substance use disorder diagnoses were associated with decreased likelihood of stimulant receipt. CONCLUSIONS: ADHD diagnoses and pharmacotherapy among patients with opioid use disorder have increased. A minority of patients with ADHD and taking MOUDs received a stimulant. Further study is needed of the benefits and risks of ADHD pharmacotherapy for patients with opioid use disorder.

Written exposure therapy for treatment of perinatal PTSD among women with comorbid PTSD and SUD: A pilot study examining feasibility, acceptability, and preliminary effectiveness.

OBJECTIVE: This pilot open trial examined the feasibility, acceptability, and preliminary effectiveness of Written Exposure Therapy (WET), a 5-session evidence-based intervention for posttraumatic stress disorder (PTSD) during pregnancy. Participants were pregnant women with comorbid PTSD and substance use disorder (SUD) receiving prenatal care in a high risk obstetrics-addictions clinic. METHODS: A total of 18 participants with probable PTSD engaged in the intervention, and 10 completed the intervention and were included in outcome analyses. Wilcoxon's Signed-Rank analyses were used to evaluate PTSD and depression symptoms and craving at pre-intervention to post-intervention and pre-intervention to the 6-month postpartum follow-up. Engagement and retention in WET and therapist fidelity to the intervention manual were used to assess feasibility. Quantitative and qualitative measures of patient satisfaction were used to assess acceptability. RESULTS: PTSD symptoms significantly decreased from pre-intervention to post-intervention (S = 26.6, p = 0.006), which sustained at the 6-month postpartum follow-up (S = 10.5, p = 0.031). Participant satisfaction at post-intervention was high. Therapists demonstrated high adherence to the intervention and excellent competence. CONCLUSIONS: WET was a feasible and acceptable treatment for PTSD in this sample. Randomized clinical trial studies with a general group of pregnant women are needed to expand upon these findings and perform a full-scale test of effectiveness of this intervention.

"If he doesn't buy in, it's a waste of time": Perspectives from diverse parents and adolescents on engaging children in ADHD treatment.

Engaging children and adolescents in ADHD care is critical for future independent disease management. However, there is a lack of evidence guiding health professionals and parents on how best to engage their children and adolescents in ADHD care. We recruited 41 diverse parents of children and adolescents with ADHD and 11 adolescents with ADHD from an urban, safety-net hospital to participate in in-depth, semi-structured qualitative interviews and then analyzed this data using thematic analysis. Children's level of illness insight about ADHD and self-esteem emerged as two major contributors to engagement of children and adolescents in ADHD care, and their intersection created four styles of engagement: proactive (high insight, high self-esteem), anxious (high insight, low self-esteem), apathetic (low insight, high self-esteem), and resistant (low insight, low self-esteem). This framework can help health professionals engage children and adolescents in care for ADHD and guide development of interventions to improve engagement in care.

Linguistic Inequities in ADHD Diagnosis among School-age Children Screened for Attention Problems in Primary Care.

INTRODUCTION: Attention deficit/hyperactivity disorder (ADHD) remains underidentified among racial/ethnic minoritized populations. We examined whether parent reported screening questionnaires for attention problems in primary care mitigated these ADHD diagnostic inequities and identified contributing sociodemographic and clinical factors. METHODS: We conducted a cross-sectional electronic medical record (EMR) study in an urban, hospital-based primary care pediatric clinic of school age children (N=2212) with a completed Pediatric Symptom Checklist (PSC-17). We examined differences between children with vs. without ADHD diagnoses, adjusting for positive PSC-17 attention score. RESULTS: Adjusting for positive PSC attention score, children had higher odds of an ADHD diagnosis if they were English-speaking and had a documented Vanderbilt ADHD Diagnostic Rating Scale in their medical record. CONCLUSION: Multilingual, parent-report screening for attention problems in pediatric primary care does not mitigate linguistic inequities in ADHD diagnosis.

Factors Affecting Compliance With Myringotomy Tube Follow-up Care.

OBJECTIVE: Myringotomy and tube insertion is a commonly practiced procedure within pediatric otolaryngology. Though relatively safe, follow-up appointments are critical in preventing further complications and monitoring for improvement. This study sought to evaluate the factors associated with compliance of post-myringotomy follow-up visits in an urban safety-net tertiary care setting. METHODS: This study is a retrospective chart review conducted in outpatient otolaryngology clinic at an urban, safety-net, tertiary-care, academic medical center. All patients from ages 0 to 18 who received myringotomy and tube placement between February 3, 2012, to May 30, 2018 at the aforementioned clinic were included. RESULTS: A total of 806 patients had myringotomy tubes placed during this period; 190 patients were excluded due to no visits being scheduled within 1 and 6 month visit windows post-operatively, leaving 616 patients included for analysis. Of 616 patients, 574 patients were seen for the 1-month visit, (42 patients did not have follow-up visits within the 1-month window), and 356 patients were examined for the 6-month visit (260 patients did not schedule follow-up visits within the 6-month window). For the 1-month follow-up visits post-procedure, only race/ethnicity type "Other" was associated with lower no-show rates (OR = 0.330, 95% CI: 0.093-0.968). With the 6-month follow-up visits, having private insurance (OR = 0.446, 95% CI: 0.229-0.867) and not having a 1-month visit scheduled (OR = 0.404, 95% CI: 0.174-0.937) predicted lower no-show rates. CONCLUSION: No meaningful factors studied were significantly associated with compliance of short-term, 1-month visits post-myringotomy. Compliance of longer-term, 6-month post-operative visits was associated with insurance type and previous visit status.

Changes in psychosocial functioning among urban, school-age children during the COVID-19 pandemic.

BACKGROUND: There is concern about the effect of the COVID-19 pandemic on psychosocial functioning among school-age children, who have faced unusual stressors during this time. Our goal was to assess mental health symptoms and social risks during COVID-19, compared to before the pandemic, for urban, racial and ethnic minority school-age children, and investigate the relationship between mental health and social risks. METHODS: We conducted a cohort study from September 2019 until January 2021 of children age 5-11 years old recruited from an urban safety net hospital-based pediatric primary care practice. We measured emotional and behavioral symptoms (including attention, internalizing, and externalizing symptoms) before and during the pandemic with the Pediatric Symptom Checklist (PSC-17). We measured social risks (including food and housing insecurity) before and during the pandemic with the THRIVE screener. We measured additional mid-pandemic COVID-related stressors with items on school participation, screens/media use, illness exposure, and caregiver mental health. We compared pre- and mid-pandemic PSC-17 symptom scores across 4 domains (total, attention, internalizing, and externalizing) and used path analysis to examine the relationship between mental health and social risks pre- and mid-pandemic. RESULTS: Caregivers of 168 children (54% non-Hispanic Black, 29% Hispanic, and 22% non-English speaking) completed the study. Children had significantly higher levels of emotional and behavioral symptoms midpandemic- vs. pre-pandemic in all domains. Significantly more children had a positive PSC-17 total score (18% vs. 8%, p < 0.01) and internalizing (depression and anxiety) score (18% vs. 5%, p < 0.001) during the pandemic vs. before, indicating clinical concerns in these areas. Caregivers reported significantly more social risks during vs. before the pandemic (p < 0.001). Mental health symptoms significantly correlated with number of social risks before the pandemic, but not during the pandemic. Less school assignment completion, increased screen time, and caregiver depression were all significantly associated with worse mid-pandemic mental health in children. CONCLUSION: The COVID-19 pandemic has led to a dramatic increase in depression/anxiety problems and social risks among urban, racial and ethnic minority school-age children compared to before the pandemic. More research is needed to understand if these changes will persist.

Six Stages of Engagement in ADHD Treatment Described by Diverse, Urban Parents.

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental condition in children. Although ADHD is treatable, barriers remain to engagement in treatment, especially among socioeconomically disadvantaged and racial and ethnic minority families. Our goal was to examine the process by which families engage in ADHD treatment and to identify targets for an intervention to improve engagement in care. METHODS: We conducted in-depth semistructured qualitative interviews with 41 parents of diverse youth aged 3 to 17 years old in treatment of ADHD at an urban safety net hospital. Parents were asked about their journey through diagnosis and treatment, community attitudes about ADHD, and other factors influencing treatment access and decision-making. Transcripts were analyzed by using thematic analysis. RESULTS: Of children with ADHD, 69.2% were male, 57.7% were Black or African American, and 38.5% were of Hispanic, Latino, or Spanish origin. Parents were 92.7% female, were 75.6% English speaking, and had a median income of $20 000. Parents described 6 stages to the process of engaging in care for their child's ADHD, which unfolded like a developmental process: (1) normalization and hesitation, (2) fear and stigmatization, (3) action and advocacy, (4) communication and navigation, (5) care and validation, and (6) preparation and transition. Barriers often occurred at points of stage mismatch between parents and providers and/or systems. Difficulty resolving an earlier stage interfered with the progression through subsequent stages. CONCLUSIONS: The 6 stages framework could be used to develop new strategies to measure engagement and to design family-centered interventions to facilitate engagement in ADHD treatment.

Low sports participation is associated with withdrawn and depressed symptoms in urban, school-age children.

BACKGROUND: The association between sports participation and mental health has not been studied in primary care samples of school-age children, nor in underrepresented minority children. We assessed the relationship between number of sports played and psychiatric symptoms in children ages 6-11 at well-child visits in an urban clinic. METHODS: Guardians of 206 children (85% Latinx) ages 6-11 completed Child Behavior Checklists (CBCL) in Spanish (66.5%) or English at well-child visits at an urban community health center. We performed linear regression between number of sports played and individual CBCL syndrome scores, and multiple logistic regression with normal (T-score <60) vs. elevated (T-score ≥60) CBCL syndrome scale score as the outcome. We conducted bivariate, multiple logistic regression, and linear regression analyses between low (1 or fewer) vs. high (2 or more) sports participators and subscales of interest. RESULTS: Fewer sports played was associated with higher Withdrawn/Depressed CBCL syndrome scale T-scores (p = 0.019), but not with other CBCL syndrome scale scores nor number of syndrome scale elevations (p = 0.638). Low participators had higher odds of an elevated Withdrawn/Depressed T-score (p = 0.033) than high participators. LIMITATIONS: Our dataset did not contain certain details about sports played, nor information about income and insurance, and our results may not generalize to other populations. CONCLUSIONS: Playing fewer sports is associated with higher withdrawn/depressed symptoms in urban, predominantly Latinx, school-age children. Therefore, urban school-age children with low sports participation may be at risk for depression, and sports participation might protect against depressive symptoms in childhood.

Peer delivery of a brief cognitive-behavioral treatment for posttraumatic stress disorder: A hybrid effectiveness-implementation pilot study.

OBJECTIVE: Posttraumatic stress disorder (PTSD) treatment delivery by peer specialist providers could increase access to and engagement with PTSD treatment in low resource settings. The current pilot study tested the feasibility, acceptability, and initial effectiveness of a peer-delivered, brief cognitive-behavioral therapy for PTSD. METHOD: Four certified peer specialists delivered the intervention to 18 participants with probable PTSD. We assessed PTSD symptoms weekly and administered surveys and interviews at baseline and posttreatment. RESULTS: Our mixed-methods approach suggests that the intervention was feasible and acceptable, demonstrating high client satisfaction. We also found significant improvements in PTSD, depressive, anxiety, and general stress symptoms. CONCLUSIONS: Peer-delivered interventions may be a good fit for addressing posttraumatic stress symptoms for people accessing care in low resource settings. Future research should evaluate peer-delivered PTSD treatment as a strategy for both reducing symptoms and improving access and engagement in professional care.

The Relationship Between Social Risks and the Mental Health of School-Age Children in Primary Care.

BACKGROUND AND OBJECTIVE: The study's goal was to measure the association between social risks and the mental health of school-age children in primary care. METHODS: We conducted a cross-sectional study in an urban safety-net hospital-based pediatric clinic using data collected from 2 standardized screening tools administered at well-child care visits for children age 6 to 11. Psychosocial dysfunction was measured with the Pediatric Symptom Checklist-17 (PSC-17), and 6 social risks (caregiver education, employment, child care, housing, food security, and household heat) were measured with the WE CARE screener. Multivariable linear and logistic regression analyses were conducted to measure the association between scores while controlling for sociodemographic characteristics. RESULTS: Among N = 943 patients, cumulative social risks were significantly associated with a positive PSC-17 total score (adjusted odds ratio [aOR] 1.2; 95% confidence interval [CI] 1.1-1.5; P = .02), indicating psychosocial dysfunction. Children with ≥3 social risks were 2.4 times more likely to have a positive PSC-17 total score compared to children with <3 social risks (95% CI 1.5-3.9; P < .001). Of the individual social risks measured, only food insecurity significantly predicted a positive PSC-17 total score (aOR 1.9; 95% CI 1.1-3.2; P = .02) and attention score (aOR 1.9; 95% CI 1.1-3.4; P = .03). CONCLUSION: Number of risks on a social risk screener was associated with psychosocial dysfunction in school-age children. Food insecurity was the only individual risk associated with psychosocial dysfunction, in particular attention problems. Screening tools for social risks could be used to identify at-risk children whose mental health may be adversely impacted by their social conditions.

Gender-specific experiences of serious mental illness in rural Ethiopia: A qualitative study.

Considerable variation in the gender-specific prevalence of serious mental illness (SMI) has been reported in low- and middle-income countries (LMICs). In the rural setting of Butajira, Ethiopia, the male-to-female prevalence ratio of schizophrenia was reported to be 5:1. This qualitative study explores gender-specific experiences of SMI and the extent to which sociocultural factors may explain the observed difference in prevalence estimates. Using purposive sampling, 39 in-depth interviews were conducted with community members from Butajira, a rural district in South Central Ethiopia. Transcripts were analysed using thematic analysis to elicit community perspectives on cultural explanatory models of SMI and experiences in this region. Gender-specific experiences were reported to differ due to visibility of symptoms, community responses, and varying levels of family support towards individuals with SMI. Overall, respondents described how various sociocultural factors subject women with SMI to higher levels of physical and social isolation compared to men, greatly affecting community health workers' ability to identify and provide care to women with mental illness. Future case detection methods should involve family members as they interact with women with SMI early on in the development of their symptoms and play an essential role in their path to mental health care.

"He can send her to her parents": The interaction between marriageability, gender and serious mental illness in rural Ethiopia.

BACKGROUND: For women in most low- and middle-income countries, the diagnosis with serious mental illness (SMI) leads to stigma and challenges related to starting or maintaining marriages. The purpose of this qualitative study was to explore perspectives on marriage, divorce and family roles of women with SMI in rural Ethiopia. METHODS: A qualitative study was conducted in a rural setting of Butajira, South Central Ethiopia. A total of 39 in-depth interviews were carried out with service users (n = 11), caregivers (n = 12), religious leaders (n = 6), health extension workers (n = 4), police officers (n = 2), teachers (n = 2) and government officials (n = 2). Data were analyzed using a thematic approach. RESULTS: Three themes emerged. (1) Marriage and SMI: Chances of getting married for individuals with SMI in general was perceived to be lower: Individuals with SMI experienced various challenges including difficulty finding romantic partner, starting family and getting into a long-term relationship due to perceived dangerousness and the widespread stigma of mental illness. (2) Gendered experiences of marriageability: Compared to men, women with SMI experienced disproportionate levels of stigma which often continued after recovery. SMI affects marriageability for men with SMI, but mens' chances of finding a marital partner increases following treatment. For women in particular, impaired functioning negatively affects marriageability as ability to cook, care and clean was taken as the measure of suitability. (3) Acceptability of divorce and separation from a partner with SMI: Divorce or separation from a partner with SMI was considered mostly acceptable for men while women were mostly expected to stay married and care for a partner with SMI. For men, the transition from provider to dependent was often acceptable. However, women who fail to execute their domestic roles successfully were considered inept and would be sent back to their family of origin. CONCLUSION: Women with SMI or those married to partners with SMI are at greater disadvantage. Reducing vulnerabilities through stigma reduction efforts such as community outreach and mental health awareness raising programs might contribute for better social outcomes for women with SMI.

REST Regulates Non-Cell-Autonomous Neuronal Differentiation and Maturation of Neural Progenitor Cells via Secretogranin II.

RE-1 silencing transcription factor (REST), a master negative regulator of neuronal differentiation, controls neurogenesis by preventing the differentiation of neural stem cells. Here we focused on the role of REST in the early steps of differentiation and maturation of adult hippocampal progenitors (AHPs). REST knockdown promoted differentiation and affected the maturation of rat AHPs. Surprisingly, REST knockdown cells enhanced the differentiation of neighboring wild-type AHPs, suggesting that REST may play a non-cell-autonomous role. Gene expression analysis identified Secretogranin II (Scg2) as the major secreted REST target responsible for the non-cell-autonomous phenotype. Loss-of-function of Scg2 inhibited differentiation in vitro, and exogenous SCG2 partially rescued this phenotype. Knockdown of REST in neural progenitors in mice led to precocious maturation into neurons at the expense of mushroom spines in vivo. In summary, we found that, in addition to its cell-autonomous function, REST regulates differentiation and maturation of AHPs non-cell-autonomously via SCG2. SIGNIFICANCE STATEMENT: Our results reveal that REST regulates differentiation and maturation of neural progenitor cells in vitro by orchestrating both cell-intrinsic and non-cell-autonomous factors and that Scg2 is a major secretory target of REST with a differentiation-enhancing activity in a paracrine manner. In vivo, REST depletion causes accelerated differentiation of newborn neurons at the expense of spine defects, suggesting a potential role for REST in the timing of the maturation of granule neurons.