Clinical Health Outcomes of Siblings of Children with Chronic Conditions: A Systematic Review and Meta-Analysis.

OBJECTIVE: The objective of the study was to assess clinical mental and physical health outcomes of siblings of children with chronic health condition(s) compared with siblings of healthy children or normative data. STUDY DESIGN: We searched Ovid MEDLINE, Embase, Cochrane Central Register of Controlled Trials, PsycINFO, and CINAHL through August 9, 2021. We included English-language studies that reported clinically diagnosable mental or physical health outcomes among siblings of children (<18 years old) with a chronic health condition, included a comparison group, and used an experimental or observational study design. Two reviewers extracted data and independently assessed risk of bias using the Newcastle Ottawa Scale. RESULTS: Of 9899 screened studies, 34 were included; 28 studies reported on mental health, 3 reported on physical health, and 3 reported on mortality. Siblings of children with chronic conditions had greater depression rating scale scores than their comparison groups (standardized mean difference = 0.53; 95% CI = 0.38-0.68; P < .001 [6 studies]), whereas anxiety scores were not substantially increased (standardized mean difference = 0.21; 95% CI = -0.02 to 0.43; P = .07 [7 studies]). The effects for confirmed psychiatric diagnoses (7 studies), mortality (3 studies), or physical health outcomes (3 studies) could not be meta-analyzed given the limited number of studies and between-study heterogeneity. CONCLUSION: Siblings of children with chronic health conditions may be at an increased risk of depression. Our findings suggest the need for targeted interventions to support the psychological well-being of siblings of children with chronic health conditions.

Dietary patterns and internalizing symptoms in children and adolescents: A meta-analysis.

CONTEXT: Studies of child and adolescent internalizing symptoms and dietary pattern have produced mixed results. OBJECTIVES: To quantify the association between dietary patterns and internalizing symptoms, including depression, in children and adolescents. DATA SOURCES: Embase, PsycINFO, MEDLINE, Web of Science and Cochrane up to March 2021. STUDY SELECTION: Observational studies and randomized controlled trials with mean age ⩽ 18 years, reporting associations between diet patterns and internalizing symptoms. DATA EXTRACTION: Mean effect sizes and 95% confidence intervals were determined under a random-effects model. RESULTS: Twenty-six studies were cross-sectional, 12 were prospective, and 1 used a case-control design. The total number of participants enrolled ranged from 73,726 to 116,546. Healthy dietary patterns were negatively associated with internalizing (r = -0.07, p < 0.001, 95% confidence interval [-0.12, 0.06]) and depressive symptoms (r = -0.10, p < 0.001, 95% confidence interval [-0.18, -0.08]). Effect sizes were larger for studies of healthy dietary patterns and internalizing and depressive symptoms using self-report versus parent-report measures, as well as in cross-sectional studies of healthy dietary patterns and depression compared to prospective studies. Unhealthy dietary patterns were positively associated with internalizing (r = 0.09, p < 0.001, 95% confidence interval [0.06, 0.14]) and depressive symptoms (r = 0.10, p < 0.01, 95% CI [0.05, 0.17]). Larger effect sizes were observed for studies of unhealthy dietary patterns and internalizing and depressive symptoms using self-report versus parent-report measures. LIMITATIONS: A lack of studies including clinical samples and/or physician diagnosis, and a paucity of studies in which anxiety symptoms were the primary mental health outcome. CONCLUSION: Greater depression and internalizing symptoms are associated with greater unhealthy dietary patterns and with lower healthy dietary intake among children and adolescents.

The longitudinal association between temperament and physical activity in young children.

OBJECTIVE: To examine the longitudinal association of negative affect and physical activity in a population of preschool children. STUDY DESIGN: Participants included 763 children (53% male) attending scheduled health supervision visits in their primary care physicians' offices. Data were collected at two time points at mean ages 27 (SD=5.4) and 47 (SD=6.2) months. Negative affect (NA) was measured using the Negative Affectivity (frustration/anger, decreased soothability) domain of the Children's Behavior Questionnaire. Physical Activity (PA) was assessed using a parent-report questionnaire. Multiple regression analyses tested the association between NA and PA, adjusting for child age, sex, z-BMI, PA at Time 1, maternal education, household income, and season, and examined for sex differences in the relationship between NA and PA. RESULTS: The longitudinal association between NA at Time 1 and PA at Time 2 was moderated by sex (p<0.001). After adjusting for covariates, females with greater NA at Time 1 had decreased PA at Time 2 (p=0.01), whereas males with greater NA at Time 1 had increased PA at Time 2 (p=0.01). Specifically, among females, every 1 unit increase in NA at Time 1 was associated with a 9.9min/day decrease in PA at Time 2 (95% CI: -17.1, -2.8). CONCLUSIONS: NA and PA were associated early in childhood and the effects of NA on PA were gender specific. These findings underscore the importance of longitudinal and gender-specific analyses in mood-obesity research.

The Effects of Stigma on Recovery Attitudes in People With Anorexia Nervosa in Intensive Treatment.

Self-stigma in individuals with anorexia nervosa (AN) may affect engagement in intensive treatment. The objective of this study was to test a Model of Self-Stigma to identify the influence of public stigma, internalized stigma, self-esteem, and self-efficacy on recovery attitudes in individuals in inpatient treatment for AN. Using a cross-sectional design, 36 female participants with AN completed questionnaires during the first week of intensive inpatient treatment. Better attitude towards recovery was positively correlated with higher self-esteem and self-efficacy and negatively correlated with greater internalized stigma and perceptions of others devaluing families of individuals with AN. Together, these factors accounted for 63% of the variance in recovery attitudes. Findings demonstrate the adverse effects perceived stigma towards families, self-stigma, and self-esteem have on recovery attitudes in individuals with AN. Clinical interventions are needed to challenge internalized stigma and bolster self-esteem to enhance individuals' recovery efforts.

Preliminary Observations of Resting-State Magnetoencephalography in Nonmedicated Children with Obsessive-Compulsive Disorder.

Background: Cortico-striato-thalamo-cortical (CSTC) network alterations are hypothesized to contribute to symptoms of obsessive-compulsive disorder (OCD). To date, very few studies have examined whether CSTC network alterations are present in children with OCD, who are medication naive. Medication-naive pediatric imaging samples may be optimal to study neural correlates of illness and identify brain-based markers, given the proximity to illness onset. Methods: Magnetoencephalography (MEG) data were analyzed at rest, in 18 medication-naive children with OCD (M = 12.1 years ±2.0 standard deviation [SD]; 10 M/8 F) and 13 typically developing children (M = 12.3 years ±2.2 SD; 6 M/7 F). Whole-brain MEG-derived resting-state functional connectivity (rs-fc), for alpha- and gamma-band frequencies were compared between OCD and typically developing (control) groups. Results: Increased MEG-derived rs-fc across alpha- and gamma-band frequencies was found in the OCD group compared to the control group. Increased MEG-derived rs-fc at alpha-band frequencies was evident across a number of regions within the CSTC circuitry and beyond, including the cerebellum and limbic regions. Increased MEG-derived rs-fc at gamma-band frequencies was restricted to the frontal and temporal cortices. Conclusions: This MEG study provides preliminary evidence of altered alpha and gamma networks, at rest, in medication-naive children with OCD. These results support prior findings pointing to the relevance of CSTC circuitry in pediatric OCD and further support accumulating evidence of altered connectivity between regions that extend beyond this network, including the cerebellum and limbic regions. Given the substantial portion of children and youth whose OCD symptoms do not respond to conventional treatments, our findings have implications for future treatment innovation research aiming to target and track whether brain patterns associated with having OCD may change with treatment and/or predict treatment response.

Depression and inflammation among children and adolescents: A meta-analysis.

BACKGROUND: Increasing evidence suggests that youth with Major Depressive Disorder (MDD) exhibit early indicators of cardiovascular disease. A leading hypothesized mechanism of this association is via inflammatory pathways, however, results examining this direct association are mixed. Our objective was to synthesize and quantify observational studies examining the association of depression and inflammation among children and adolescents. METHODS: Electronic searches were conducted in MEDLINE, Embase, PsycINFO, and Scopus, yielding 2,757 non-duplicate records from 1946 to 2019. The included studies measured depression or depressive symptoms and examined its association with inflammation in participants younger than 18 years. All relevant articles were reviewed and data extracted by two independent coders. Estimates were examined by using random-effects meta-analysis. RESULTS: Twenty-two studies (20,791 participants) were included. Significant associations were observed between concurrent depression and CRP (n = 7; r = 0.12; 95% confidence interval [CI] = 0.04 to 0.19), and IL-6 (n = 7; r = 0.17; 95% CI= 0.10 to 0.24). Longitudinal analyses revealed that depression is a significant predictor of IL-6 (n = 3; r = 0.29; 95% CI= 0.04 to 0.50) and conversely, that inflammation (measured by CRP or IL-6) predicts future depression (n = 4; r = 0.04; 95% CI= 0.00 to 0.08). LIMITATIONS: Results are limited by the small number of studies preventing examination of some moderator variables. Findings are correlational, not causal. CONCLUSION: Depression is positively associated with concurrent and future inflammation among children and adolescents. Results suggest that bidirectional associations may exist between depression and a pro-inflammatory state.

Children's Physical Activity and Depression: A Meta-analysis.

CONTEXT: Research regarding the protective effects of early physical activity on depression has yielded conflicting results. OBJECTIVE: Our objective was to synthesize observational studies examining the association of physical activity in childhood and adolescence with depression. DATA SOURCES: Studies (from 2005 to 2015) were identified by using a comprehensive search strategy. STUDY SELECTION: The included studies measured physical activity in childhood or adolescence and examined its association with depression. DATA EXTRACTION: Data were extracted by 2 independent coders. Estimates were examined by using random-effects meta-analysis. RESULTS: Fifty independent samples (89 894 participants) were included, and the mean effect size was significant (r = -0.14; 95% confidence interval [CI] = -0.19 to -0.10). Moderator analyses revealed stronger effect sizes in studies with cross-sectional versus longitudinal designs (k = 36, r = -0.17; 95% CI = -0.23 to -0.10 vs k = 14, r = -0.07; 95% CI = -0.10 to -0.04); using depression self-report versus interview (k = 46, r = -0.15; 95% CI = -0.20 to -0.10 vs k = 4, r = -0.05; 95% CI = -0.09 to -0.01); using validated versus nonvalidated physical activity measures (k = 29, r = -0.18; 95% CI = -0.26 to -0.09 vs k = 21, r = -0.08; 95% CI = -0.11 to -0.05); and using measures of frequency and intensity of physical activity versus intensity alone (k = 27, r = -0.17; 95% CI = -0.25 to -0.09 vs k = 7, r = -0.05; 95% CI = -0.09 to -0.01). LIMITATIONS: Limitations included a lack of standardized measures of physical activity; use of self-report of depression in majority of studies; and a small number of longitudinal studies. CONCLUSIONS: Physical activity is associated with decreased concurrent depressive symptoms; the association with future depressive symptoms is weak.

Uncovering obsessive-compulsive disorder risk genes in a pediatric cohort by high-resolution analysis of copy number variation.

BACKGROUND: Obsessive-compulsive disorder (OCD) is a heterogeneous neuropsychiatric condition, thought to have a significant genetic component. When onset occurs in childhood, affected individuals generally exhibit different characteristics from adult-onset OCD, including higher prevalence in males and increased heritability. Since neuropsychiatric conditions are associated with copy number variations (CNVs), we considered their potential role in the etiology of OCD. METHODS: We genotyped 307 unrelated pediatric probands with idiopathic OCD (including 174 that were part of complete parent-child trios) and compared their genotypes with those of 3861 population controls, to identify rare CNVs (<0.5 % frequency) of at least 15 kb in size that might contribute to OCD. RESULTS: We uncovered de novo CNVs in 4/174 probands (2.3 %). Our case cohort was enriched for CNVs in genes that encode targets of the fragile X mental retardation protein (nominal p = 1.85 × 10-03; FDR=0.09), similar to previous findings in autism and schizophrenia. These results also identified deletions or duplications of exons in genes involved in neuronal migration (ASTN2), synapse formation (NLGN1 and PTPRD), and postsynaptic scaffolding (DLGAP1 and DLGAP2), which may be relevant to the pathogenesis of OCD. Four cases had CNVs involving known genomic disorder loci (1q21.1-21.2, 15q11.2-q13.1, 16p13.11, and 17p12). Further, we identified BTBD9 as a candidate gene for OCD. We also sequenced exomes of ten "CNV positive" trios and identified in one an additional plausibly relevant mutation: a 13 bp exonic deletion in DRD4. CONCLUSIONS: Our findings suggest that rare CNVs may contribute to the etiology of OCD.