Our study provides further evidence for the presence of qualitatively different SAD subgroups and the propensity of a subset of people with SAD to exhibit impulsive, high-risk behaviors.

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.

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One of the leading biological models of obsessivecompulsive disorder (OCD) is the frontal-striatal-thalamic model. This study undertakes an extensive exploration of the variability in genes related to the regulation of the frontal-striatal-thalamic system in a sample of early-onset OCD trios. To this end, we genotyped 266 single nucleotide polymorphisms (SNPs) in 35 genes in 84 OCD probands and their parents. Finally, 75 complete trios were included in the analysis. Twenty SNPs were overtransmitted from parents to early-onset OCD probands and presented nominal pointwise P < 0.05 values. Three of these polymorphisms achieved P < 2 × 10 −4 , the significant P-value after Bonferroni corrections: rs8190748 and rs992990 localized in GAD2 and rs2000292 in HTR1B. When we stratified our sample according to gender, different trends were observed between males and females. In males, SNP rs2000292 (HTR1B) showed the lowest P-value (P = 0.0006), whereas the SNPs in GAD2 were only marginally significant (P = 0.01). In contrast, in females HTR1B polymorphisms were not significant, whereas rs8190748 (GAD2) showed the lowest P-value (P = 0.0006). These results are in agreement with several lines of evidence that indicate a role for the serotonin and -Aminobutyric acid (GABA) pathways in the risk of early-onset OCD and with the gender differences in OCD pathophysiology reported elsewhere. However, our results need to be replicated in studies with larger cohorts in order to confirm these associations.

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A promising approach in relation to reducing phenotypic heterogeneity involves the identification of homogeneous subtypes of OCD based on age of onset, gender, clinical course and comorbidity. This study aims to assess the sociodemographic characteristics and clinical features of OCD patients in relation to gender and the presence or absence of another comorbid disorder. The sample comprised 112 children and adolescents of both sexes and aged 8-18 years, all of whom had a diagnosis of OCD. Overall, 67 % of OCD patients had one comorbid diagnosis, 20.5 % had two such diagnoses and 2.6 % had three comorbid diagnoses. The group of OCD patients with a comorbid neurodevelopmental disorder had significantly more family history of OCD in parents (p = .049), as compared with the no comorbidity group and the group with a comorbid internalizing disorder, and they also showed a greater predominance of males (p = .013) than did the group with a comorbid internalizing disorder. The group of OCD patients with internalizing comorbidity had a later age of onset of OCD (p = .001) compared with both the other groups. Although the initial severity was similar in all three groups, the need for pharmacological treatment and for hospitalization due to OCD symptomatology was greater in the groups with a comorbid neurodevelopmental disorder (p = .038 and p = .009, respectively) and a comorbid internalizing disorder (p = .008 and p = .004, respectively) than in the group without comorbidity. Our findings suggest that two subtypes of OCD can be defined on the basis of the comorbid pathology presented. The identification of different subtypes according to comorbidity is potentially useful in terms of understanding clinical variations, as well as in relation to treatment management and the use of therapeutic resources.

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