Chromosome 15q 13.3 after CNV and qPCR procedures.

<p><b>A</b>. The microdeletion identified in the <i>FMN1</i> region of chromosome 15q13.3 using Genomic Workbench software (Agilent Technologies, Santa Clara, CA, USA). <b>B</b>. Genome browser image of the region containing the <i>FMN1</i> gene. One rare deletion was identified in the male proband (64 kb loss in OCD case 222_3). <b>C</b>. Rare CNVs were validated by SYBR Green-based real time PCR, and it was found that the father and son had only one copy of the exon while the gender-matched control had two copies.</p

Frequency of copy number variants of different sizes in patients with obsessive-compulsive disorder (OCD) and controls.

<p><i>P</i>-values were calculated using Pearson's Chi-square test; Bonferroni-adjusted significance of 0.025.</p><p>Frequency of copy number variants of different sizes in patients with obsessive-compulsive disorder (OCD) and controls.</p

Socioeconomic Disadvantage Moderates the Association between Peripheral Biomarkers and Childhood Psychopathology

<div><p>Background</p><p>Socioeconomic disadvantage (SED) has been consistently associated with early life mental health problems. SED has been shown to impact multiple biological systems, including the regulation of neurotrophic proteins, immune-inflammatory and oxidative stress markers, which, conversely, have been reported to be relevant to physiological and pathological neurodevelopment This study investigated the relationship between SED, different domains of psychopathology, serum levels of interleukin-6 (IL6), thiobarbituric acid-reactive substance (TBARS) and brain-derived neurotrophic factor (BDNF). We hypothesized that a composite of socioeconomic risk would be associated with psychopathology and altered levels of peripheral biomarkers. In addition, we hypothesized that SED would moderate the associations between mental health problems, IL6, TBARS and BDNF.</p><p>Methods and Findings</p><p>Using a cross-sectional design, we measured the serum levels of IL6, TBARS and BDNF in 495 children aged 6 to 12. We also investigated socio-demographic characteristics and mental health problems using the Child Behaviour Checklist (CBCL) DSM-oriented scales. SED was evaluated using a cumulative risk model. Generalized linear models were used to assess associations between SED, biomarkers levels and psychopathology. SED was significantly associated with serum levels of IL6 (RR = 1.026, 95% CI 1.004; 1.049, p = 0.020) and TBARS (RR = 1.077, 95% CI 1.028; 1.127, p = 0.002). The association between SED and BDNF was not statistically significant (RR = 1.031, 95% CI 0.997; 1.066, p = 0.077). SED was also significantly associated with all CBCL DSM-oriented scales (all p < 0.05), whereas serum biomarkers (i.e. IL6, TBARS, BDNF) were associated with specific subscales. Moreover, the associations between serum biomarkers and domains of psychopathology were moderated by SED, with stronger correlations between mental health problems, IL6, TBARS, and BDNF being observed in children with high SED.</p><p>Conclusions</p><p>In children, SED is highly associated with mental health problems. Our findings suggest that this association may be moderated via effects on multiple interacting neurobiological systems.</p></div

Effects of interactions between high socioeconomic disadvantage and peripheral biomarkers on CBCL scales.

<p>All analyses included age, gender and ethnicity as covariates.</p

Mental health problems and peripheral biomarkers within socioeconomic disadvantage exposure subgroups.

<p>Correlations between (A) somatic problems and serum IL6; (B) attention deficit/hyperactivity problems and serum TBARS and (C) depressive problems and serum BDNF; within socioeconomic disadvantage exposure subgroups. SED: socioeconomic disadvantage; IL6: interlukin-6; TBARS: thiobarbituric acid-reactive substance; BDNF: brain-derived neurotrophic factor.</p

Definitions and descriptive statistics.

<p>Definitions and descriptive statistics.</p

Associations between socioeconomic disadvantage, IL6, TBARS and BDNF; considered separately (Model 1) and together (Model 2).

<p>All analyses included age, gender and ethnicity as covariates.</p

Heritability by minor allele frequency.

<p>The x-axis represents all minor allele frequency bins tested while the y-axis represents resultant heritability in a given bin. Blue bars indicate TS and red bars indicate OCD. Error bars are shown.</p

GWAS and imputed heritability partitioned by minor allele frequency.

<p>Legend: MAF: minor allele frequency; GWAS: genome-wide association study; se: standard error; SNPs: single nucleotide polymorphisms.</p

Overall heritability analysis of obsessive-compulsive disorder and Tourette syndrome.

<p>Legend: se: standard error; SNPs: single nucleotide polymorphisms; TS: Tourette syndrome; OCD: Obsessive-compulsive disorder;</p>*<p>Average of 10 analyses of permuted phenotypes.</p>**<p>Sample size reduced to match size of TS sample.</p