Iron deficiency and internalizing symptom severity in unmedicated adolescents: a pilot study.

BACKGROUND: Iron plays a key role in a broad set of metabolic processes. Iron deficiency is the most common nutritional deficiency in the world, but its neuropsychiatric implications in adolescents have not been examined. METHODS: Twelve- to 17-year-old unmedicated females with major depressive or anxiety disorders or with no psychopathology underwent a comprehensive psychiatric assessment for this pilot study. A T1-weighted magnetic resonance imaging scan was obtained, segmented using Freesurfer. Serum ferritin concentration (sF) was measured. Correlational analyses examined the association between body iron stores, psychiatric symptom severity, and basal ganglia volumes, accounting for confounding variables. RESULTS: Forty females were enrolled, 73% having a major depressive and/or anxiety disorder, 35% with sF < 15 ng/mL, and 50% with sF < 20 ng/mL. Serum ferritin was inversely correlated with both anxiety and depressive symptom severity (r = -0.34, p < 0.04 and r = -0.30, p < 0.06, respectively). Participants with sF < 15 ng/mL exhibited more severe depressive and anxiety symptoms as did those with sF < 20 ng/mL. Moreover, after adjusting for age and total intracranial volume, sF was inversely associated with left caudate (Spearman's r = -0.46, p < 0.04), left putamen (r = -0.58, p < 0.005), and right putamen (r = -0.53, p < 0.01) volume. CONCLUSIONS: Brain iron may become depleted at a sF concentration higher than the established threshold to diagnose iron deficiency (i.e. 15 ng/mL), potentially disrupting brain maturation and contributing to the emergence of internalizing disorders in adolescents.

Machine Learning-Based Aggression Detection in Children with ADHD Using Sensor-Based Physical Activity Monitoring.

Aggression in children is highly prevalent and can have devastating consequences, yet there is currently no objective method to track its frequency in daily life. This study aims to investigate the use of wearable-sensor-derived physical activity data and machine learning to objectively identify physical-aggressive incidents in children. Participants (n = 39) aged 7 to 16 years, with and without ADHD, wore a waist-worn activity monitor (ActiGraph, GT3X+) for up to one week, three times over 12 months, while demographic, anthropometric, and clinical data were collected. Machine learning techniques, specifically random forest, were used to analyze patterns that identify physical-aggressive incident with 1-min time resolution. A total of 119 aggression episodes, lasting 7.3 ± 13.1 min for a total of 872 1-min epochs including 132 physical aggression epochs, were collected. The model achieved high precision (80.2%), accuracy (82.0%), recall (85.0%), F1 score (82.4%), and area under the curve (89.3%) to distinguish physical aggression epochs. The sensor-derived feature of vector magnitude (faster triaxial acceleration) was the second contributing feature in the model, and significantly distinguished aggression and non-aggression epochs. If validated in larger samples, this model could provide a practical and efficient solution for remotely detecting and managing aggressive incidents in children.

Predictors of depressive symptom trajectories in a prospective follow-up of late adolescents.

BACKGROUND: Group-based trajectory modeling holds promise for the study of prognostic indicators in the mood disorders because the courses that the individuals with these disorders follow are so highly variable. However, trajectory analyses of major depressive disorder have so far not included some of the more robust predictors of mood disorder outcome, nor have they described interactions between these predictors. METHODS: A group of 186 individuals aged 15-20 years with past or current depressive symptoms, who had recently begun taking a serotonin reuptake inhibitors antidepressant, underwent extensive baseline evaluations and were then followed for up to 2 years. Trajectory analyses used weekly ratings of depressive symptoms and the resulting groups were compared by the risk factors of sex, psychiatric comorbidity, negative emotionality, and childhood adversity. RESULTS: A three-group solution provided the best statistical fit to the 2-year symptom trajectory. Negative emotionality and childhood adversity, though correlated, independently predicted membership in higher-morbidity groups. Female sex and comorbidity with generalized anxiety disorder (GAD) were also significantly more likely in the trajectory groups with higher symptom levels. However, the presence of GAD, rather than female sex, was the most important determinant of group membership. Negative emotionality was predictive of group membership only among women. CONCLUSIONS: Trajectory analyses indicated that week-to-week variations in depressive symptoms across individuals could best be condensed into low, remitting and persistent symptom patterns. Female sex, anxiety symptoms, negative emotionality and childhood adversity were each independently associated with trajectories of higher morbidity but negative emotionality may be prognostically important only among women.

First known case of catatonia due to cyclosporine A-related neurotoxicity in a pediatric patient with steroid-resistant nephrotic syndrome.

BACKGROUND: Catatonia is a neuropsychiatric syndrome characterized by diverse psychomotor abnormalities, including motor dysregulation and behavioral and affective disturbances. Once thought to occur primarily in the context of schizophrenia, recent data suggest most cases of catatonia develop in individuals with depressive or bipolar disorders. Moreover, catatonia may ensue in general medical and neurological conditions, as well as due to a variety of pharmaceuticals, drugs of abuse, and toxic agents. At one time considered rare in pediatric patients, evidence now suggests catatonia is both underrecognized and undertreated in this population, where it carries an elevated risk of morbidity and mortality. Here we present the case of a child with steroid-resistant nephrotic syndrome who developed catatonia due to cyclosporine A-related neurotoxicity. CASE PRESENTATION: A 9-year-old African-American boy with no psychiatric history and a 9-month history of nephrotic syndrome due to focal segmental glomerulosclerosis was admitted to the local children's hospital for management of mutism, posturing, insomnia, gait abnormalities, and somatic delusions. Seven days prior to admission, his cyclosporine plasma concentration was elevated at 1224 ng/mL (therapeutic range: 100-200 ng/mL). Upon admission, cyclosporine was discontinued and psychiatry was consulted, diagnosing catatonia. The patient subsequently received propofol 80 mg IV resulting in a transient lysis of catatonia. Over a lengthy hospitalization, the patient's catatonia was initially treated with lorazepam, quetiapine being added later to target psychosis. All signs and symptoms of catatonia resolved, and the patient was eventually tapered off both lorazepam and quetiapine with no return of symptoms more than 6 months later. CONCLUSIONS: To our knowledge, this case represents the first reported instance of cyclosporine A-induced catatonia in a patient with steroid-resistant nephrotic syndrome. It illustrates the importance of maintaining vigilance for signs and symptoms of cyclosporine A-related neurotoxicity (including catatonia) in patients with steroid-resistant nephrotic syndrome. In addition, it highlights the challenges faced by clinicians in jurisdictions that prohibit the use of electroconvulsive therapy in pediatric patients.

Selective Serotonin Reuptake Inhibitors Reduce Longitudinal Growth in Risperidone-Treated Boys.

OBJECTIVES: To examine whether selective serotonin reuptake inhibitors (SSRIs) inhibit longitudinal growth in children and adolescents, particularly in the early stages of puberty, using a sample of convenience comprising risperidone-treated boys. STUDY DESIGN: Data from four clinic-based studies in risperidone-treated 5- to 17-year-old boys with no general medical conditions were combined for this analysis. Anthropometric measurements and psychotropic treatment history were extracted from the medical and pharmacy records. Linear mixed effects regression analyses examined the association between SSRI use and change in age-sex-specific height and body mass index z scores, after adjusting for relevant confounders. RESULTS: Risperidone-treated boys (n = 267; age: 12.7 ± 2.7 years), 71% of whom had ever taken an SSRI, contributed to the analysis. After adjusting for age, psychostimulant and antipsychotic use, and time in the study, both the duration of SSRI use as well as the cumulative dose were inversely associated with height z score after age 11 years (P < .0001). After adjusting for baseline height, duration of SSRI use was most strongly inversely associated with height z score in Tanner stages 3 and 4 boys who took SSRIs continuously (r = -0.69, P < .009). No association was observed with body mass index z score. CONCLUSIONS: In risperidone-treated boys, SSRI use is associated with reduced longitudinal growth, particularly in those undergoing puberty. Whether adult height or other metabolic or psychological outcomes are affected remains to be determined.

Comorbidity of Migraine, Major Depressive Disorder, and Generalized Anxiety Disorder in Adolescents and Young Adults.

PURPOSE: Depression and anxiety are highly comorbid psychiatric conditions and both are common in adult patients with migraine. This study aims to examine the unique associations between major depressive disorder (MDD) and generalized anxiety disorder (GAD) in a well-characterized group of older adolescents and college-age individuals with migraine. METHOD: Participants (N =  227), between 15 and 20 years old, who were unmedicated or within 1 month of beginning antidepressant treatment underwent a comprehensive psychiatric assessment to establish the presence of MDD and GAD, according to the Diagnostic and Statistical Manual, Fourth Edition, Text Revision, and to rate their symptom severity using the Longitudinal Interval Follow-up Evaluation for Adolescents (A-LIFE). They then completed the ID-Migraine. The Student's t test and chi-square test were used to compare continuous and categorical variables, respectively, across participants with vs. without migraine. Logistic regression analysis examined the association between the presence of migraine and psychopathology. RESULTS: A diagnosis of MDD was associated with significantly increased risk of having migraine. Moreover, more severe and persistent ratings of depression were associated with an even higher likelihood of having migraine. A diagnosis of GAD was also significantly associated with the presence of migraine. The prevalence of comorbid MDD and GAD was significantly higher in participants with migraine than those without migraine (55 vs. 22%, p < 0.0001). When examined concurrently, GAD remained significantly associated with migraine, with a statistical trend for MDD to be associated with it. CONCLUSION: The comorbidity of migraine, MDD, and GAD has important clinical and research implications. Patients who suffer from any of these problems should be screened for all three in order to receive comprehensive care. Shared psychological and biological vulnerabilities may be involved in the three conditions. Greater understanding of the shared vulnerabilities can lead to unified treatments.

The effect of psychostimulants on skeletal health in boys co-treated with risperidone.

OBJECTIVES: To examine the skeletal effects of chronic psychostimulant treatment in children and adolescents. STUDY DESIGN: Medically healthy 5- to 17-year-old males from 4 different clinic-based studies were combined for this analysis. They were divided by psychostimulant use into 3 groups: none to negligible, intermittent, and continuous use. Most (95%) had also received risperidone for 6 months or more. Treatment history was extracted from medical and pharmacy records. Anthropometric and bone measurements, using dual-energy x-ray absorptiometry and peripheral quantitative computed tomography, were obtained at each research visit. Multivariable linear regression analysis models examined whether age-sex-specific height Z-score and skeletal outcomes differed among the 3 psychostimulant-use groups. RESULTS: The sample consisted of 194 males with a mean age of 11.7 ± 2.8 years at study entry. The majority had an externalizing disorder. There was no significant difference across the 3 treatment groups in height Z-score or in skeletal outcomes at the radius, lumbar spine, or whole body. One hundred forty-four boys had valid follow-up skeletal data 1.4 ± 0.7 years after study entry. Again, neither height Z-score nor the skeletal outcomes were different among those who remained on psychostimulants between the 2 visits, started psychostimulants anew, or had not taken psychostimulants. CONCLUSIONS: Following chronic treatment, psychostimulants did not appear to significantly affect bone mass accrual in children and adolescents taking risperidone. There was a small, but statistically not significant, negative impact on longitudinal growth.

Rapid adipose deposition with mood disorders.

BACKGROUND: Persons with bipolar disorder represent a high-risk group for obesity, but little is known about the time course by which weight gain occurs in bipolar disorder. METHODS: We prospectively studied changes in fat distribution using dual-energy x-ray absorptiometry in relationship to medication exposure and mood symptom burden in 36 participants with bipolar disorder. We assessed the relationship between prior medication exposure and course of illness with adiposity measures at baseline (N = 36) and at 6-month follow-up (N = 22). RESULTS: At baseline, greater adiposity was associated with advanced age and female sex, not retrospectively assessed symptom course or medication exposure (past 2 years). Over 6 months of prospective follow-up, participants developed greater adiposity (fat mass index +0.82 kg/m(²), P = .007; visceral fat area +8.6 cm(²), P = .02; total percent fat +1.6%, P = .02). Manic symptomatology, not antipsychotic exposure, was related to the increased adiposity. CONCLUSIONS: Acute exacerbations of mood disorders appear to represent high-risk periods for adipose deposition. Obesity prevention efforts may be necessary during acute exacerbations.

Adherence to Recommended Metabolic Monitoring of Children and Adolescents Taking Second-Generation Antipsychotics.

OBJECTIVE: Clinical guidelines recommend periodic monitoring for adverse metabolic effects associated with second-generation antipsychotic medications. The authors sought to evaluate adherence to the guideline-recommended metabolic monitoring schedule for children and adolescents prescribed second-generation antipsychotics. METHODS: The authors used a national electronic medical records database for a retrospective study of children and adolescents ages 1-17 years (N=9,620) who were prescribed second-generation antipsychotics in January 2010-December 2018. Adherence to guideline-recommended monitoring of body mass index (BMI), blood glucose, and cholesterol was categorized as full, partial, and no monitoring. Full monitoring of patients was defined as strict metabolic monitoring, following the guideline-recommended schedule. Patients who received any monitoring, but not meeting the full monitoring criteria, were considered partially monitored. Three multinomial logistic regression models were fitted for each metabolic parameter to identify predictors associated with monitoring status. RESULTS: BMI was the metabolic parameter with the highest adherence to guideline-recommended monitoring (full monitoring, 4.7% of patients; partial monitoring, 44.8%), followed by blood glucose (full monitoring, 6.5%; partial monitoring, 29.4%) and cholesterol (full monitoring, 0.8%; partial monitoring, 22.4%). Being Black (vs. non-Black), having a comorbid mood disorder (vs. none), receiving olanzapine as the index second-generation antipsychotic (vs. aripiprazole), and receiving an antidepressant as a concurrent medication (vs. none) were associated with a higher likelihood of receiving both full and partial monitoring of all three metabolic parameters. CONCLUSIONS: Both full and partial adherence to guideline-recommended monitoring of children and adolescents prescribed second-generation antipsychotics were poor. However, children and adolescents at increased metabolic risk tended to be more closely monitored.

Iron Deficiency in Attention-Deficit Hyperactivity Disorder, Autism Spectrum Disorder, Internalizing and Externalizing Disorders, and Movement Disorders.

This article reviews the role of iron in brain development and function, with a focus on the association between iron deficiency (ID) and neuropsychiatric conditions. First, we describe how ID is defined and diagnosed. Second, the role of iron in brain development and function is summarized. Third, we review current findings implicating ID in a number of neuropsychiatric conditions in children and adolescents, including attention deficit hyperactivity disorder and other disruptive behavior disorders, depressive and anxiety disorders, autism spectrum disorder, movement disorders, and other situations relevant to mental health providers. Last, we discuss the impact of psychotropic medication on iron homeostasis.

Utilization and Predictors of Adjuvant Metformin for Children and Adolescents on Mixed Receptor Antagonists (Second-Generation Antipsychotics).

OBJECTIVE: To examine utilization and predictors of adjuvant metformin among pediatric recipients of second-generation antipsychotics (SGAs) (mixed receptor antagonist). METHOD: This study used 2016-2021 data of a national electronic medical record database. Eligible participants were children aged 6 to 17 with a new SGA prescription for at least 90 days. Predictors of prescribing adjuvant metformin in general and to nonobese pediatric SGA recipients in particular were assessed using conditional logistic regression and logistic regression analyses, respectively. RESULTS: Of 30,009 pediatric SGA recipients identified, 2.3% (n = 785) received adjuvant metformin. Among 597 participants with a body mass index z score documented during the 6-month period before metformin initiation, 83% were obese, and 34% had either hyperglycemia or diabetes. Significant predictors for metformin prescribing were high baseline body mass index z score (odds ratio [OR] 3.5, 95% CI 2.8-4.5, p < .0001), having hyperglycemia or diabetes (OR 5.3, 95% CI 3.4-8.3, p < .0001), and undergoing a switch from a higher metabolic risk SGA to a lower risk one (OR 9.9, 95% CI 3.5-27.5, p = .0025) or a switch in the opposite direction (OR 4.1, 95% CI 2.1-7.9, p = .0051) compared with no switch. Nonobese metformin users were more likely to have a positive body mass index z score velocity before metformin initiation than their obese counterparts. Receiving the index SGA prescribed by a mental health specialist was associated with higher likelihood of receiving adjuvant metformin and receiving metformin before the development of obesity. CONCLUSION: Utilization of adjuvant metformin among pediatric SGA recipients is uncommon, and early introduction of the medication among nonobese children is rare.

Impact of antidepressant use on the autonomic nervous system: A meta-analysis and systematic review.

Changes in cardiac autonomic nervous system (ANS) regulation observed in psychiatric disorders may be mitigated by antidepressants. We meta-analyzed and systematically reviewed studies examining antidepressants' effects on ANS outcomes, including heart rate variability (HRV). We conducted a PRISMA/MOOSE-compliant search of PubMed and Scopus until March 28th, 2022. We included randomized placebo-controlled trials (RCTs) and pre-post studies, regardless of diagnosis. We pooled results in random-effects meta-analyses, pooling homogeneous study designs and outcomes. We conducted sensitivity analyses and assessed quality of included studies. Thirty studies could be meta-analyzed. Selective serotonin reuptake inhibitors (SSRIs) were significantly associated with a reduction in the square root of the mean-squared difference between successive R-R intervals (RMSSD) (SMD= -0.48) and skin conductance response (SMD= -0.55) in RCTs and with a significant increase in RMSSD in pre-post studies (SMD=0.27). In pre-post studies, tricyclic antidepressants (TCAs) were associated with a significant decrease in several HRV outcomes while agomelatine was associated with a significant increase in high frequency power (SMD= 0.14). In conclusion, SSRIs reduce skin conductance response but have no or inconclusive effects on other ANS outcomes, depending on study design. TCAs reduce markers of parasympathetic function while agomelatine might have the opposite effect. Studies are needed to investigate the impact of SSRIs on the recovery of cardiac ANS regulation after acute myocardial infarction, and the effects of newer antidepressants.

The Effectiveness of Metformin in Managing Second Generation Antipsychotic-Induced Weight Gain in Children and Adolescents.

Objective: This study aimed to assess the effectiveness of metformin for antipsychotic-induced weight gain (AIWG) and determine whether the timing of metformin initiation and premorbid obesity moderated metformin effectiveness in children and adolescents on treatment with second-generation antipsychotics (SGAs).Methods: A cohort of individuals 6 to 17 years of age, from 2016 to 2021, initiating a new SGA treatment and receiving a subsequent metformin prescription during SGA treatment were identified from the IQVIA Ambulatory EMR-US database. The changes in body mass index (BMI) z score before and after metformin initiation were assessed using the piecewise linear mixed-effects regression model.Results: The results showed that the initiation of metformin was associated with a flattening out of the prior-metformin BMI z score trend. Relative to those who did not use metformin, metformin users had an additional monthly decrease in BMI z score of -0.053 (P = .0008) during the 6-month period after metformin initiation. Specifically, users who were non-obese before the intervention experienced a greater reduction in the BMI z score slope compared to those who were mildly-to-moderately obese and severely obese (non-obese - mildly-to-moderately obese: -0.07631, P = .0001; non-obese - severely obese: -0.09613, P < .0001). A different effect was not observed between patients who initiated metformin within versus beyond 90 days of SGA initiation. Extending the observation period to 12 months yielded comparable findings.Conclusions: Adjuvant metformin helps manage AIWG in children and adolescents by flattening the upward AIWG trend rather than reversing it. The effect was more prominent before the development of obesity, suggesting that the early introduction of metformin for AIWG management may be warranted.

Examining Whether Genetic Variants Moderate the Skeletal Effects of Selective Serotonin Reuptake Inhibitors in Older Adolescents and Young Adults.

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 (ß = 0.18, p = <0.0001). Female SSRI users with the combination of rs6295 CC+GC and rs6311 GG genotypes had greater LS BMD than female SSRI nonusers (ß = 0.29, p < 0.0001). SSRI users with the rs6295 GG genotype had higher trabecular BMD compared to nonusers (ß = 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.

Impact of the AACAP practice parameters on the metabolic adverse event monitoring for second-generation antipsychotics (SGAs) in children and adolescents.

INTRODUCTION: The objective of our study was to evaluate the impact of the publication of the American Academy of Child and Adolescent Psychiatry (AACAP) practice parameters for SGA metabolic monitoring in 2011 on SGA metabolic monitoring uptake among pediatric SGA recipients. METHODS: This was a retrospective study of children 1-17 years of age who initiated SGA treatment from Jan 2010 to December 2018 using a national Electronic Medical Records database. A segmented regression of interrupted time-series (ITS) analysis was conducted to analyze the change of metabolic monitoring rates for Body Mass Index (BMI), Blood Glucose (BG), and Total Cholesterol (CHL) 9 quarters pre- and 26 quarters post-the publication of the AACAP practice parameters. RESULTS: The analytical cohort included 9620 children and adolescents who initiated SGA treatment during the study period. The ITS results showed that the publication of the AACAP practice parameter for SGA metabolic monitoring was associated with a 12.61 percentage points (p < 0.0002) immediate increase in BMI monitoring rate, (increased from 29.10% in Q4 2011 to 40.10% in Q3 2012). There was a positive trend of BMI monitoring rate prior to the publication of AACAP practice parameters, which continued during the post-publication period. Neither immediate nor sustained changes in the association of monitoring rates for BG and CHL were observed after the issuance of the guidelines. CONCLUSION: The publication of AACAP practice parameters for SGA monitoring was associated with a significant improvement in the monitoring for BMI, but not for BG and CHL in children and adolescents.

Association Between Abnormal Metabolic Parameters and Receiving Subsequent Interventions in Children and Adolescents Initiating Second-Generation Antipsychotics.

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.

Common Variable Immunodeficiency Patient Fecal Microbiota Transplant Recapitulates Gut Dysbiosis.

Purpose: Patients with non-infectious complications have worse clinical outcomes in common variable immunodeficiency (CVID) than those with infections-only. Non-infectious complications are associated with gut microbiome aberrations, but there are no reductionist animal models that emulate CVID. Our aim in this study was to uncover potential microbiome roles in the development of non-infectious complications in CVID. Methods: We examined fecal whole genome shotgun sequencing from patients CVID, and non-infectious complications, infections-only, and their household controls. We also performed Fecal Microbiota transplant from CVID patients to Germ-Free Mice. Results: We found potentially pathogenic microbes Streptococcus parasanguinis and Erysipelatoclostridium ramosum were enriched in gut microbiomes of CVID patients with non-infectious complications. In contrast, Fusicatenibacter saccharivorans and Anaerostipes hadrus, known to suppress inflammation and promote healthy metabolism, were enriched in gut microbiomes of infections-only CVID patients. Fecal microbiota transplant from non-infectious complications, infections-only, and their household controls into germ-free mice revealed gut dysbiosis patterns in recipients from CVID patients with non-infectious complications, but not infections-only CVID, or household controls recipients. Conclusion: Our findings provide a proof of concept that fecal microbiota transplant from CVID patients with non-infectious complications to Germ-Free mice recapitulates microbiome alterations observed in the donors.

Rate of weight gain and cardiometabolic abnormalities in children and adolescents.

OBJECTIVE: To investigate whether the rate of weight gain is associated with cardiometabolic risk, independent of weight measured concurrently. STUDY DESIGN: Healthy 7- to 17-year-old risperidone-treated patients (N = 105, 88% were boys) had blood pressure, anthropometry, and laboratory tests performed. Growth history was extracted from medical records. The rate of change in age- and sex-adjusted weight and body mass index (BMI) z score after the initiation of risperidone was individually modeled. Multivariable linear regression analyses explored the association of the rate of weight or BMI z score change with cardiometabolic outcomes, independent of last measured weight or BMI z score, respectively. RESULTS: Following a mean of 1.9 years (SD = 1.0) of risperidone treatment, the absolute increase in weight and BMI z scores was 0.61 (SD = 0.61) and 0.62 (SD = 0.73), respectively. After controlling for the final weight z score, the rate of change in weight z score was significantly associated with final glucose (P < .04), C-peptide (P < .004), the homeostasis model assessment insulin resistance index (P < .02), high-density lipoprotein (HDL) cholesterol (P < .0001), a metabolic syndrome score (P < .005), adiponectin (P < .04), and high-sensitivity C-reactive protein (P < .04). After controlling for the final BMI z score, the rate of change in BMI z score was associated with final HDL cholesterol (P < .04), leptin (P < .03), and adiponectin (P < .04), with a suggestion of an association with the final homeostasis model assessment insulin resistance index (P < .08). CONCLUSIONS: Compared with weight measured concurrently, the rate of weight gain in risperidone-treated children accounts for an equal or larger share of the variance in certain cardiometabolic outcomes (eg, HDL cholesterol [ΔR(2) = 8% vs ΔR(2) = 11%] and high-sensitivity C-reactive protein [ΔR(2) = 5% vs ΔR(2) = 9%]) and may serve as a treatment target.

Psychological and Psychiatric Comorbidities in Youth with Serious Physical Illness.

An estimated one in six children in the United States suffers from a mental disorder, including mood, anxiety, or behavioral disorders. This rate is even higher in children with chronic medical illness. This manuscript provides a concise review of the symptoms that comprise mental conditions often observed in children with chronic illness or at the end of life. It further provides some guidance to help clinicians distinguish normative from pathological presentations. Evidence-based psychotherapy interventions, potentially applicable to the acute inpatient setting, are briefly summarized. Broad recommendations are made regarding both psychotherapeutic as well as pharmacotherapeutic interventions, with a review of common or serious medication side effects. Finally, delirium recognition and management are summarized.

An open-label trial of aripiprazole in the treatment of aggression in male adolescents diagnosed with conduct disorder.

BACKGROUND: The adverse effect profiles of typical and atypical antipsychotics are problematic because of their extrapyramidal and endocrine adverse effects, respectively. METHODS: Ten adolescent male patients diagnosed with conduct disorder received aripiprazole in doses of ≤20 mg/d in an open-label, intent-to-treat design to establish and characterize the efficacy of the drug in reducing aggressive behavior. RESULTS: Based on clinician and parent observations, aripiprazole was effective in reducing aggressive behavior in adolescent boys. The change in clinician-observed aggression ratings appears to have been driven by a decrease in physical aggression, whereas the change in parent-observed aggression ratings appears to have been driven by a decrease in verbal aggression and aggression against objects and animals. CONCLUSIONS: Aripiprazole was an effective and relatively well-tolerated treatment for overall aggression in adolescent males with conduct disorder, in the view of both clinicians and parents. Depending on the observer, aripiprazole improved aggression categorized as physical aggression, verbal aggression, and aggression against objects and animals.