Symptom Dimension Breakpoints for the Obsessive-Compulsive Inventory-Child Version (OCI-CV).

Pediatric obsessive-compulsive disorder (OCD) clusters around three major symptom dimensions: contamination/cleaning, symmetry/ordering, and disturbing thoughts/checking. The Obsessive-Compulsive Inventory-Child Version (OCI-CV) is a self-report questionnaire that provides scores along six theory-based OCD dimensions, but no study has evaluated how well OCI-CV identifies clinically significant symptoms within each of the three major symptom dimensions of OCD. We examined this question using data from 197 Swedish and Spanish youth with OCD. All youth completed the OCI-CV and clinically significant symptom severity within each major OCD dimension was established with a validated interview-based measure. Results showed that a score ≥ 3 on the OCI-CV washing scale excellently captured those with clinically significant contamination/cleaning symptoms (AUC = 0.85 [0.80-0.90], 79% accuracy). A score ≥ 4 on the obsessing scale adequately captured those with disturbing thoughts/checking symptoms (AUC = 0.71 [0.64-0.78], 67% accuracy) and a score ≥ 3 on the ordering scale adequately captured those with symmetry/ordering symptoms (AUC = 0.72 [0.65-0.79], 70% accuracy). Similar accuracy of the breakpoints was found in the Swedish and Spanish samples. OCI-CV works well to identify youth with pediatric OCD that have clinically significant contamination/cleaning symptoms. The measure can also with adequate precision identify those with clinically significant disturbing thoughts/checking and symmetry/ordering symptoms. The breakpoints provided in this study can be used to examine differences in clinical presentation and treatment outcome for youth with different types of OCD.

Right Prefrontal Cortical Thickness Is Associated With Response to Cognitive-Behavioral Therapy in Children With Obsessive-Compulsive Disorder.

OBJECTIVE: Cognitive-behavioral therapy (CBT) is considered a first-line treatment for obsessive-compulsive disorder (OCD) in pediatric and adult populations. Nevertheless, some patients show partial or null response. The identification of predictors of CBT response may improve clinical management of patients with OCD. Here, we aimed to identify structural magnetic resonance imaging (MRI) predictors of CBT response in 2 large series of children and adults with OCD from the worldwide ENIGMA-OCD consortium. METHOD: Data from 16 datasets from 13 international sites were included in the study. We assessed which variations in baseline cortical thickness, cortical surface area, and subcortical volume predicted response to CBT (percentage of baseline to post-treatment symptom reduction) in 2 samples totaling 168 children and adolescents (age range 5-17.5 years) and 318 adult patients (age range 18-63 years) with OCD. Mixed linear models with random intercept were used to account for potential cross-site differences in imaging values. RESULTS: Significant results were observed exclusively in the pediatric sample. Right prefrontal cortex thickness was positively associated with the percentage of CBT response. In a post hoc analysis, we observed that the specific changes accounting for this relationship were a higher thickness of the frontal pole and the rostral middle frontal gyrus. We observed no significant effects of age, sex, or medication on our findings. CONCLUSION: Higher cortical thickness in specific right prefrontal cortex regions may be important for CBT response in children with OCD. Our findings suggest that the right prefrontal cortex plays a relevant role in the mechanisms of action of CBT in children.

Functional impairment in a Spanish Sample of Children and Adolescents with Obsessive-Compulsive Disorder.

The Child Obsessive-Compulsive Impact Scale (COIS-R) is a parent- and self-report measure of the impairment related to Obsessive-Compulsive Disorder (OCD) symptoms. Previous research has demonstrated the reliability and validity of the original version of the COIS-R; to date, however, the scale has not been validated for use in Spanish samples of pediatric OCD. The present study aimed to assess the psychometric properties of this in a clinical sample of pediatric OCD (n = 91). Analyses of internal consistency, convergent and divergent validity were conducted. For both the COIS-R report scales estimates similar to those in the original instrument were obtained for internal consistency, test-retest reliability, and convergent validity. Thus, the Spanish version of the COIS-R seems to retain sound psychometric properties of its original version; it appears to be a reliable instrument for the assessment of obsessive-compulsive impairment and the effects of treatment, and can be used in other cultural contexts.

Gene expression study in monocytes: evidence of inflammatory dysregulation in early-onset obsessive-compulsive disorder.

Obsessive-compulsive disorder (OCD) has a complex etiology that seems to include immune dysfunction and alterations in circulating monocytes. To investigate the immune basis and the functional dysregulation of monocytes in this disease, we analyzed gene expression in the peripheral monocytes of pediatric patients with OCD (N = 102) compared to controls (N = 47). We examined gene expression in primary cultures of peripheral monocytes from participants, under basal conditions and under exposure to lipopolysaccharide (LPS) to stimulate immune response. Whole-genome expression was assessed in 8 patients and 8 controls. Differentially expressed genes were identified followed by protein-protein interaction network construction and functional annotation analysis to identify the genes and biological processes that are altered in the monocytes of OCD patients. We also explored the expression levels of selected genes in monocytes from the other participants using qPCR. Several changes in gene expression were observed in the monocytes of OCD patients, with several immune processes involved under basal conditions (antigen processing and presentation, regulation of immune system and leukocyte cell adhesion) and after LPS stimulation (immune and inflammatory response, cytokine production and leukocyte activation). Despite the qPCR analysis provided no significant differences between patients and controls, high correlations were observed between the expression levels of some of the genes and inflammatory markers (i.e., T helper 17 and regulatory T cell levels, total monocyte and proinflammatory monocyte subset levels, and the cytokine production by resting and stimulated monocytes) of the study participants. Our findings provide more evidence of the involvement of monocyte dysregulation in early-onset OCD, indicating a proinflammatory predisposition and an enhanced immune response to environmental triggers.

Genetic Associations of Serotoninergic and GABAergic Genes in an Extended Collection of Early-Onset Obsessive-Compulsive Disorder Trios.

OBJECTIVE: Obsessive-compulsive disorder (OCD) is a debilitating neuropsychiatric disorder whose etiology includes important genetic contributions. In a previous transmission disequilibrium study in which 75 complete trios were included, single-nucleotide polymorphisms (SNPs) in serotoninergic and GABAergic genes were associated with early-onset OCD. Our aim was to assess those findings in an extended collection of early-onset OCD trios. METHODS: A transmission disequilibrium test for SNPs in HTR1B (rs2000292), SLC18A1 (rs6586896), GAD1 (rs3791860), and GAD2 (rs8190748) was performed in a total of 101 early-onset OCD trios, from which 26 trios were newly recruited for the purpose of the present analysis. RESULTS: All the SNPs were overtransmitted from parents to OCD probands (p < 0.012, significant after Bonferroni correction). CONCLUSIONS: These results are consistent with the previous findings and constitute more evidence of the role of genetic factors related to serotoninergic and GABAergic pathways in the pathophysiology of early-onset OCD.

Five-year diagnostic stability among adolescents in an inpatient psychiatric unit.

INTRODUCTION: In childhood, diagnoses made at the first admission to a psychiatric unit are frequently unstable and temporary. In this study, we examined the stability of DSM-IV-TR disorders and groups of disorders among adolescents followed-up for 5 years after hospitalization. METHOD: All inpatients admitted for the first time between 2007 and 2008 were included and contacted after 5 years for re-evaluation. The final sample comprised 72 patients. At admission, diagnoses were based on the DSM-IV-TR criteria, Fourth Edition. At five years, diagnoses were made using structured clinical interviews for DSM-IV axis I Disorders and for axis II (SCID-I and SCID-II) as well as the Personality Diagnostic Questionnaire, Fourth Edition (PDQ-4). We also evaluated and collected information on the global assessment of functioning using the World Health Organization Quality of Life-BREF (WHOQOL-BREF) instrument. Depending on the distribution of variables, we used the chi-squared and Fisher exact tests or the Student t and McNemar tests for statistical analyses. RESULTS: The most stable diagnoses were schizophrenia spectrum disorders, bipolar disorder, generalized anxiety disorder, obsessive-compulsive disorder, attention deficit hyperactivity disorder, Tourette syndrome, and pervasive developmental disorder. The most unstable diagnoses were disruptive disorders. Participants were satisfied with their quality of life and the global outcomes of the sample were positive. CONCLUSION: Major psychiatric disorders, including mood and schizophrenia spectrum disorders, were significantly more stable than other diagnoses and tended to continue into adulthood. In the case of study participants, suffering a mental disorder during adolescence did not appear to affect global functioning outcomes.

Association between genetic variants of serotonergic and glutamatergic pathways and the concentration of neurometabolites of the anterior cingulate cortex in paediatric patients with obsessive-compulsive disorder.

OBJECTIVES: The present study aimed to assess the relationship between variability in genes related to the pathophysiology of obsessive-compulsive disorder (OCD) and the concentration of different neurometabolites in the anterior cingulate cortex (ACC). METHODS: We concomitantly assessed neurometabolite concentrations using 3-T (1)H-MRS and 262 single nucleotide polymorphism (SNPs) in 35 genes in 41 paediatric OCD patients. RESULTS: There were significant associations, after Bonferroni correction, between the concentration of inositol, glutamate and glutamine, and total choline and five polymorphisms located in genes related to serotonin and glutamate (i.e., the vesicular monoamine transporter 1 gene, SLC18A1 [rs6586896]; the serotonin receptor 1B gene, HTR1B [rs6296 and rs6298]; and the glutamate receptor, ionotropic, AMPA1 gene, GRIA1 [rs707176 and rs2963944]). CONCLUSIONS: The association observed between these polymorphisms and the neurometabolite concentrations could indicate the presence of a biological interaction between the serotonin and the glutamate pathways that could be involved in the pathophysiology of OCD. More studies with this methodology could increase our understanding of the aetiology and pathophysiology of OCD in children.

Association between genetic variants related to glutamatergic, dopaminergic and neurodevelopment pathways and white matter microstructure in child and adolescent patients with obsessive-compulsive disorder.

BACKGROUND: Alterations in white matter (WM) integrity observed in patients with obsessive-compulsive disorder (OCD) may be at least partly determined genetically. Neuroimaging measures of WM microstructure could serve as promising intermediate phenotypes for genetic analysis of the disorder. The objective of the present study was to explore the association between variability in genes related to the pathophysiology of OCD and altered WM microstructure previously identified in child and adolescent patients with the disease. METHODS: Fractional anisotropy (FA) and mean diffusivity (MD) measured by diffusion tensor imaging (DTI) and 262 single nucleotide polymorphisms (SNPs) in 35 candidate genes were assessed concomitantly in 54 child and adolescent OCD patients. RESULTS: Six polymorphisms located in the glutamate transporter gene (SLC1A1 rs3087879), dopamine transporter gene (SLC6A3 rs4975646), dopamine receptor D3 (DRD3 rs3773679), nerve growth factor receptor gene (NGFR rs734194 and rs2072446), and cadherin 9 gene (CDH9 rs6885387) showed significant p-values after Bonferroni correction (p≤0.00019). More specifically, the vast majority of these associations were detected with MD in the right and left anterior and posterior cerebellar lobes. LIMITATIONS: Patients were under pharmacological treatment at the time of the DTI examination. Sample size is limited. CONCLUSIONS: The results provide the first evidence of the involvement of genetic variants related to glutamatergic, dopaminergic, and neurodevelopmental pathways in determining the WM microstructure of child and adolescent patients with OCD, which could be related to the neurobiology of the disorder.

Microstructural brain abnormalities and symptom dimensions in child and adolescent patients with obsessive-compulsive disorder: a diffusion tensor imaging study.

BACKGROUND: The aims of this study were to determine white matter (WM) microstructure abnormalities in obsessive-compulsive disorder (OCD) using diffusion tensor imaging, and to investigate whether these abnormalities differ according to OCD symptom dimensions. METHODS: Sixty-three child and adolescent OCD patients (11-18 years old) and 37 healthy subjects matched for gender, age, and estimated intelligence quotient were assessed by means of psychopathology scales and diffusion tensor magnetic resonance imaging. RESULTS: Compared with healthy controls OCD patients showed a significant decrease (t = 3.79, P = .049 FDR-corrected) in fractional anisotropy (FA) in the anterior region of the corpus callosum (CC). In addition, mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) values were significantly increased in OCD compared with controls in the CC and in several WM regions of the cingulate, frontal and occipital lobes, basal ganglia, cerebellum, and pons. Compared with healthy controls, OCD patients presenting the harm/checking dimension showed decreased FA in the CC and in the left anterior cingulate gyrus and caudate nucleus, whereas patients with a predominant contamination/washing symptom dimension presented significantly decreased FA in the left midbrain, lentiform nucleus, insula, and thalamus, and increased MD, AD, and RD in both the anterior lobes of cerebellum and in the pons. CONCLUSIONS: The findings suggest WM abnormalities at the microstructural level in the pathogenesis of OCD. Moreover, WM abnormalities in OCD may vary according to the specific OCD symptom dimensions, thus indicating the clinical heterogeneity of the condition.