Altered fear learning processes could be mechanistically linked to the development and/or maintenance of obsessive-compulsive disorder (OCD). From a clinical perspective, the first-line psychological treatment for OCD is cognitive-behavioral therapy (CBT), which is based on the principles of fear learning. However, no previous functional magnetic resonance imaging (fMRI) studies have evaluated the predictive capacity of regional brain activations during fear learning on CBT response in patients with OCD.

We aimed at exploring whether brain activation during fear learning in patients with OCD are associated with CBT outcome.

We assessed 18 patients with OCD and 18 healthy participants during a 2-day experimental protocol where brain activation and skin conductance responses (SCR) where assessed during fear conditioning, extinction learning, and extinction recall within the fMRI scanner. Following the protocol, patients with OCD received CBT.

We found non-significant between-group differences in SCR during fear learning. Patients with OCD showed significantly diminished activation of the dorsal anterior cingulate cortex and the right insula during fear conditioning. Importantly, our analyses revealed a significant negative association between clinical improvement after CBT and activity at the right insula during fear conditioning (x = 39, y = 12, z = -11; t = 5.64; p<0.001; k = 928). This finding is displayed in Figure 1 below.

Patients with OCD may require less fear-conditioned brain responses to achieve the same level of psychophysiological fear conditioning as healthy participants. Interestingly, insula activations during fear-conditioned responses may represent a potential predictor biomarker of response to CBT for OCD.

No significant relationships.

Contemporary cognitive models emphasize the importance of certain dysfunctional beliefs in the development and maintenance of Obsessive-Compulsive Disorder (OCD): overimportance of thoughts, need to control thoughts, perfectionism, intolerance of uncertainty, inflated responsibility, and overestimation of threat. Although a recent twin study suggests that these dysfunctional beliefs are significantly heritable, there have been no previous attempts to analyze candidate genes associated with them.

Our study aimed to investigate the possible association between OC-related dysfunctional beliefs and variants of two functional polymorphisms of the COMT (Val158Met) and BDNF (Val66Met) genes in 141 OCD patients.

The non-synonymous mutation Val158Met (rs4680) in the COMT gene and the Val66Met functional variant (rs6265) in the BDNF gene were genotyped with the KASPar assay system. The validated Spanish short version of the Obsessive Beliefs Questionnaire, (OBQ-44), was used to assess dysfunctional beliefs. Multivariate analysis of covariance (MANCOVA) and a post hoc one-way analysis of covariance (ANCOVA) were perfomed.

Variability in dysfunctional beliefs was not affected by the COMT or BDNF genotype when examining the two genes in isolation, but we detected a significant COMT x BDNF interaction effect on responsibility and overestimation of threat scores. These cognitive distortions were significantly higher among OCD subjects with the BDNF Met-present genotype who were also carriers of the COMT Val/Met and Met/Met genotypes.

Our data suggest that an interaction between dopaminergic and neurotrophic functional gene variants influences some of the dysfunctional belief domains hypothesized to contribute to the etiology of OCD.

Recent research suggests that the brain-derived neurotrophic factor (BDNF) may play a role in extinction learning. The goal of this study was to test whether variation in the BDNF Val66Met polymorphism is related to treatment response to exposure-based cognitive-behavior therapy (CBT), a form of extinction learning, in obsessive-compulsive disorder (OCD).

One hundred and six OCD patients from a specialized clinic, who underwent a standardized CBT treatment after partial or non-response to a 12-week pharmacological trial, were genotyped for the BDNF Val66Met and the relationship between genotype and treatment response was analyzed.

Among 98 CBT completers, 36% of those carrying the BDNF Met allele were rated as CBT responders compared to 60% of nonMet allele carriers (P = 0.027). When analyzing the different obsessive-compulsive symptom dimensions, in patients with contamination/cleaning symptoms, the Met allele was associated with a significantly worse CBT response (P<0.0001) and a lower obsessions severity decrease from pre- to posttreatment (P = 0.046).

Genetic variation in BDNF may be associated with treatment response in exposure-based CBT in OCD, especially in those patients exhibiting contamination/cleaning symptoms.

Impaired social functioning is a hallmark characteristic of several mental disorders including those characterized by paranoid ideation (P) and social anxiety (SA). Social deficits have been related to impaired social cognition.

To investigate the neurofunctional basis of social cognition in people with subclinical P and SA.

13 healthy participants with high paranoid ideation; 12 healthy participants with high social anxiety. Procedures and Instruments: Paranoid Thoughts Scale, Liebowitz Social Anxiety Scale, Cardiff Anomalous Perceptions Scale. Brain response to social stimuli was investigated with two event-related fMRI experiments with implicit processing of facial. expressions of happiness and anger in two different intensities, and with faces expressing no emotion.

People with P recruit differentially and positively the Left Lingual (p < 0,05 FWEcorr), and close to significant (p < 0,06 FWEcorr) the Right Caudate when processing neutral faces. People with SA only showed significant positive differences (p < 0,05 FWEcorr) in the Right Inferior frontal gyrus when processing anger stimuli at 100%. When comparing both groups, we did not find significant differences.

The preliminary results indicate a stronger recruitment of emotional and visual areas in P subjects when processing neutral faces and a stronger recruitment of cognitive processing areas in SA subjects when processing angry faces.