Chadi Albert Calarge

Children diagnosed with intellectual and developmental disability (IDD), including autism spectrum disorder (ASD), often present to pediatric acute care hospitals for behavioral crises or medical care. Board Certified Behavior Analysts (BCBAs) and Registered Behavior Technicians (RBTs) have important skill sets and can partner with multidisciplinary teams to advance the care of hospitalized patients with ASD or IDD. We describe the care model used by our Behavior Analysis and ASD/IDD Team (BAAT) in an inpatient medical setting. Components of the BAAT approach include: (1) consultation triage, (2) direct behavior analytic services (including assessment, intervention, and caregiver training), (3) staff training, (4) crisis response, (5) behavioral data collection, and (6) multidisciplinary collaboration. We include representative data from 2 years of the BAAT service to demonstrate the individualized and innovative application of our approach, as well as preliminary outcome data to show the potential impact of the program. This study highlights the key role of BCBAs and RBTs in acute inpatient medical settings, particularly in optimizing the care of children with ASD or IDD and behavioral health needs, while disseminating behavior analytic practice.

Importance: Although brain iron is necessary for neurogenesis, myelination, and neurotransmitter synthesis, iron deficiency (ID) is defined solely based on hematological outcomes.Objective: To examine the association of ID without anemia with basal ganglia (BG) iron content and its structural and functional sequelae in adolescents.Design, Setting, and Participants: This cross-sectional study enrolled participants using the electronic medical record system from a large network of pediatrics clinics between December 2020 and April 2024. Otherwise healthy, unmedicated participants aged 10 to 17 years with a depressive or anxiety disorder or with no psychopathology were consecutively enrolled. Anemia and acute inflammation led to exclusion, and ID without anemia status was identified after procedure completion. Data were analyzed from May to November 2024.Exposure: Following the World Health Organization’s guidelines, ID without anemia was defined as a serum ferritin concentration less than 15 ng/mL.Main Outcomes and Measures: Participants underwent a brain magnetic resonance imaging scan to measure BG susceptibility and structures volume, a clinical interview to rate psychiatric symptoms severity, and neuropsychological testing. Multivariable regression and correlational partial least-squares analyses examined the association of ID without anemia status and BG susceptibility with each other and with BG structures volume, psychiatric symptom severity, and neuropsychological performance.Results: Among a total of 209 participants (122 [58%] female; mean [SD] age, 13.5 [2.2] years; 62 participants [30%] with ID without anemia), ID without anemia was associated with a significantly lower susceptibility in the caudate (Cohen d = −0.41; 95% CI, −0.72 to −0.10; P = .01) and putamen (d = −0.38; 95% CI, −0.69 to −0.07; P = .02), after accounting for age and sex. Notably, in females, the age by ID without anemia status had a significant 2-way interaction, indicating larger difference in caudate (β = 1.11; 95% CI, 0.08 to 2.15; P = .04) and putamen susceptibility (β = 0.95; 95% CI, 0.18 to 1.71; P = .02) with increasing age, favoring those without ID without anemia. None of the 2-way interactions were significant in males. Moreover, BG susceptibility was inversely associated with BG structures volume and psychiatric symptom severity and positively associated with neuropsychological performance, particularly in female adolescents.Conclusions and Relevance: In this cross-sectional study, ID without anemia was associated with lower striatal iron content and disrupted structure and function during adolescence, a critical period when the brain develops and accrues iron, particularly in females.

Patients with common variable immunodeficiency (CVID) who develop noninfectious complications (NIC) have worse clinical outcomes than those with infections only (INF). While gut microbiome aberrations have been linked to NIC, reductionist animal models that accurately recapitulate CVID are lacking. Our aim in this study was to uncover potential microbiome roles in the development of NIC in CVID. We performed whole-genome shotgun sequencing on fecal samples from CVID patients with NIC, INF, and their household controls. We also performed fecal microbiota transplants from CVID patients to germ-free mice. We found potentially pathogenic microbes Streptococcus parasanguinis and Erysipelatoclostridium ramosum were enriched in gut microbiomes of CVID patients with NIC. In contrast, Fusicatenibacter saccharivorans and Anaerostipes hadrus, known to suppress inflammation and promote healthy metabolism, were enriched in gut microbiomes of INF CVID patients. Fecal microbiota transplant from NIC, INF, and their household controls into germ-free mice revealed gut dysbiosis patterns only in recipients from CVID patients with NIC, but not in those from INF CVID or household controls recipients. Our findings provide a proof of concept that fecal microbiota transplant from CVID patients with NIC to germ-free mice recapitulates microbiome alterations observed in the donors.

Background: Iron Deficiency (ID) affects two billion people worldwide, predominantly adolescent girls, and may be associated with increased psychopathology. The associations between ID and symptoms of depression and anxiety in adolescents were examined using data from the National Health and Nutrition Examination Survey (NHANES), a cross-sectional survey of a nationally representative sample of non-institutionalized Americans. Methods: The current analysis included survey cycles where both iron-related markers and mental health-related outcomes were collected in adolescents 12 to 17 years old. Acute and serious medical conditions, acute inflammation, and abnormal birth weight led to exclusion. Linear multivariable regression analyses examined the association between ID status (defined based on the total body iron model) and (1) total Patient Health Questionnaire (PHQ-9) score, (2) one item examining anxiety severity, and (3) one item examining overall mental well-being. Covariates included age, sex, race and ethnicity, body mass index, household income, head-of-household marital status, and psychotropic medication use. Sensitivity analyses examined the robustness of the findings when ID was defined based on the ferritin model. Results: In 1990 adolescents (age [mean ± SD]: 14.5 ± 1.7 years; 85.7% females), ID with and without anemia was significantly associated with a higher PHQ-9 score in multiracial adolescents (Cohen’s d = 1.09, p = 0.0005 for ID without anemia; d = 0.92, p = 0.0395 for ID with anemia). Moreover, ID with anemia was associated with more severe anxiety (d = 3.00, p = 0.0130) and worse mental well-being (d = 2.75, p = 0.0059) in multiracial adolescents. The findings remained significant after adjusting for psychotropic use and in the sensitivity analyses. Conclusions: Iron deficiency is associated with poorer mental health in adolescents of multiracial background. Future studies should confirm these findings prospectively and examine the underlying mechanism.

Purpose: The aim of this study was to examine the effect of fluoxetine and sertraline on height growth and insulin-like growth factor-1 (IGF-1) during puberty. Methods: In this 6-month cohort study, electronic medical records were used to identify 8- to 15-year-old participants, within 1 month of starting fluoxetine (n = 39) or sertraline (n = 27), and sexual maturation stages 2 to 4 were confirmed. Conditions that interfere with height growth led to exclusion. Participants underwent anthropometric assessments and phlebotomy. Healthy, unmedicated children (n = 36) also provided anthropometric data. Results: After the baseline height Z-score, sex, Tanner stage, daily selective serotonin reuptake inhibitor (SSRI) dose, and time were accounted for, the interaction effect of dose by time was inversely associated with height Z-score in SSRI-treated participants (β = −0.18; 95% confidence interval [CI]: −0.35, −0.02). Sertraline and fluoxetine did not differ in their effect on height growth. Compared with being unmedicated, SSRI treatment was associated with a smaller growth in height (time × dose 2-way interaction effect β = −1.30; 95% CI: −2.52, −0.09). The interaction effect of dose by time was significant for body mass index Z-score (β = 0.35; 95% CI: 0.06, 0.64) but not weight Z-score (β = 0.24; 95% CI: −0.01, 0.49). Body mass index Z-score increased more with sertraline compared with fluoxetine (time × dose × SSRI type 3-way interaction effect P < 0.05). SSRI dose was inversely associated with IGF-1 (β = −63.5; 95% CI: −112.2, −14.7) but not insulin growth factor binding protein-3 concentration (β = −207.3; 95% CI: −536.2, 121.5). Conclusions: Fluoxetine and sertraline reduce height gain and IGF-1 concentration, in a dose-dependent manner. Longer-term studies are necessary.

Introduction: Professional guidelines recommend that providers routinely monitor children prescribed second-generation antipsychotics (SGA) to reduce the risk of adverse metabolic events associated with the medication. Despite this guidance, many studies show low rates of monitoring compliance. In this study, we interviewed child psychiatrists for their views of possible barriers to monitoring. Methods: Semi-structured qualitative interviews, developed according to the Regehr model of influences upon patient–provider decision making, were conducted with child and adolescent psychiatrists in current practice and recruited by convenience and snowball sampling. Interviews were conducted through internet video meetings and were recorded. Interview data were analyzed following Framework Analysis qualitative methods. Results: We recruited and completed interviews with 17 psychiatrists. Patient-level barriers included travel difficulties, limited family time for health care appointments, patient fear of blood draws, and more. Provider-level barriers included professional judgment versus guideline guidance, perceived family burden, assumption of low-risk, short-term SGA use, and more. Organizational level barriers included lack of organizational mandates or incentives, limited appointment time per patient, lack of care coordination, lack of co-located labs, personnel turnover, and more. Barriers at the social and cultural level include stigma and low health literacy. Conclusion: These practicing prescribers provided a wide range of possible barriers to metabolic monitoring in children and adolescents prescribed SGAs. The next step is to explore which may be present in certain settings, and to pilot quality improvement interventions. Addressing barriers can reduce risk of metabolic disorders arising from long-term use of SGAs in children and adolescents.

Objectives: This study aimed to examine the association between abnormal readings of metabolic parameters detected during second-generation antipsychotic (SGA) treatment and the likelihood of receiving subsequent adverse drug event interventions. Methods: This was a nested case–control study conducted on patients 1–17 years of age with at least two prescriptions of SGAs between January 2010 and January 2019 using TriNetX EMR data. Following an incident density sampling procedure, patients who received the SGA metabolic adverse event intervention (mAEI) (case) were matched with three nonrecipients (controls). The abnormal readings of metabolic parameters within 30 days before the initiation of mAIEs were further identified. These metabolic parameters include body mass index (BMI) and laboratory parameters such as cholesterol, high-density lipoprotein, low-density lipoprotein, triglycerides, blood glucose, HbA1c, thyroid hormones, liver enzymes, and prolactin. The association of abnormal metabolic parameters with subsequent mAEIs was assessed using a conditional logistic regression model, after adjusting for demographic and other clinical risk factors. Results: One thousand eight hundred eighty-four children and adolescents met the inclusion criteria and were prescribed SGA mAEIs. The most common types of mAEIs prescribed were weight management pharmacotherapy (40.6%), switching from a high or medium metabolic risk profile SGA to a low-risk one (30.9%), nonpharmacological treatment (25.4%), and switching from SGA polytherapy to monotherapy (11.7%). The conditional logistic regression analysis on matched mAEI recipients and nonrecipients showed that patients with an abnormal BMI had 43% higher odds of receiving mAEI (odds ratio [95% confidence interval]: 1.43 [1.13–1.79]). However, the presence of an abnormal laboratory reading was not associated with the initiation of mAEIs. Conclusions: The prescribing of mAEIs were associated with the presence of obesity, but not with abnormal readings of other metabolic parameters, suggesting that additional data are needed to clarify the long-term implication of SGA metabolic adverse events other than weight gain and to inform the appropriate timing for interventions.

Objective: To examine whether serotonin (5-HT) related genetic variants moderate the effects of selective serotonin reuptake inhibitors (SSRIs) on skeletal outcomes. Methods: Trabecular bone mineral density (BMD) at the radius, lumbar spine (LS) BMD, total body less head (TBLH) bone mineral content (BMC) and markers of bone metabolism (osteocalcin, C-terminal telopeptide of type I collagen [CTX-1], and bone specific alkaline phosphatase to CTX-1 ratio) were examined in an observational study, enrolling 15- to 20-year-old participants, unmedicated or within a month of SSRI initiation. Variants in HTR1A (rs6295), HTR1B (rs6296), HTR1D (rs6300), HTR2A (rs6311 and rs6314), HTR2B (rs6736017), and the serotonin transporter intron 2 variable number tandem repeat (STin2 VNTR) were genotyped. Linear mixed-effects regression analysis examined associations between SSRI use, genetic variants, and skeletal outcomes. Results: After adjusting for relevant covariates, rs6295 CC and GC genotypes in 262 participants (60% female, mean ± SD age = 18.9 ± 1.6 years) were significantly associated with higher LS BMD compared to the GG genotype. Rs6311 GG SSRI users had greater LS BMD compared to nonusers (β = 0.18, p = β = 0.29, p < 0.0001). SSRI users with the rs6295 GG genotype had higher trabecular BMD compared to nonusers (β = 3.60, p = 0.05). No significant interactions were found for TBLH BMC or bone turnover markers. After correcting for multiple comparisons, none of the results retained significance. Conclusions: In older adolescents and young adults, HTR1A (rs6295) and HTR2A (rs6311) variants may moderate the effect of SSRIs on BMD. Sex differences may exist and require further examination. Further research with larger sample sizes is needed to confirm our preliminary findings. Clinical Trial Registration: clinicaltrials.gov NCT02147184.