Differential effects of sertraline and cognitive behavioural therapy on behavioural inhibition in patients with obsessive compulsive disorder.

Patients with obsessive compulsive disorder (OCD) randomised to sertraline, manualised cognitive behavioural therapy (CBT), or combination (sertraline + CBT), underwent cognitive assessment. Cognitive testing was conducted at baseline and at week 16. The stop signal reaction time task (SSRT) was used to evaluate motor impulsivity and attentional flexibility was evaluated using the intra/extra-dimensional set shifting task. Paired-samples t -tests or nonparametric variants were used to compare baseline and posttreatment scores within each treatment group. Forty-five patients were tested at baseline (sertraline n  = 14; CBT n  = 14; sertraline + CBT n  = 17) and 23 patients at week 16 (sertraline n  = 6; CBT n  = 7; sertraline + CBT n  = 10). The mean dosage of sertraline was numerically higher in those taking sertraline as a monotherapy (166.67 mg) compared with those taking sertraline in combination with CBT (100 mg). Analysis of pre-post treatment scores using an intent-to-treat-analysis found a significant reduction in the SSRT in those treated with sertraline, whilst there was no significant change on this task for those treated with CBT or the combination. This study found that motor inhibition improved significantly following sertraline monotherapy. Suboptimal sertraline dosing might explain the failure to detect an effect on motor inhibition in the group receiving combination of sertraline + CBT. Higher dose sertraline may have broader cognitive effects than CBT for OCD, motor impulsivity may have value as a measure of treatment outcome and, by extension, the SSRT could serve as a biomarker for personalising care.

Optimal treatment for obsessive compulsive disorder: a randomized controlled feasibility study of the clinical-effectiveness and cost-effectiveness of cognitive-behavioural therapy, selective serotonin reuptake inhibitors and their combination in the management of obsessive compulsive disorder.

Established treatments for obsessive compulsive disorder (OCD) include cognitive behaviour therapy (CBT) and selective serotonin reuptake inhibitor (SSRI) medication. Combined treatment may outperform monotherapy, but few studies have investigated this. A total of 49 community-based adults with OCD were randomly assigned to CBT, SSRI, or SSRI+CBT. Sertraline (50-200 mg/day) was given as the SSRI for 52 weeks. A 16-h-manualized individual CBT was delivered over 8 weeks with four follow-up sessions. Assessors were 'blinded' to treatment allocation. A preliminary health economic evaluation was conducted. At week 16, combined treatment (n=13) was associated with the largest improvement, sertraline (n=7) the next largest and CBT (n=9) the smallest on the observed case analysis. The effect size (Cohen's d) comparing the improvement in Yale Brown Obsessive Compulsive Scale on CBT versus combined treatment was -0.39 and versus sertraline was -0.27. Between 16 and 52 weeks, the greatest clinical improvement was seen with sertraline, but participant discontinuation prevented reliable analysis. Compared with sertraline, the mean costs were higher for CBT and for combined treatment. The mean Quality Adjusted Life Year scores for sertraline were 0.1823 (95% confidence interval: 0.0447-0.3199) greater than for CBT and 0.1135 (95% confidence interval: -0.0290-0.2560), greater than for combined treatment. Combined treatment appeared the most clinically effective option, especially over CBT, but the advantages over SSRI monotherapy were not sustained beyond 16 weeks. SSRI monotherapy was the most cost-effective. A definitive study can and should be conducted.

Free operant observing in humans: a translational approach to compulsive certainty seeking.

Excessive checking is reported in non-clinical populations and is a pervasive symptom in obsessive compulsive disorder (OCD). We implemented a free-operant task in humans, previously used in rats, wherein participants can "check" to reduce uncertainty. Participants can press an observing key to ascertain which of two main keys will, if pressed, currently lead to rewards. Over a series of experiments, we found that punishment robustly increased observing in non-clinical participants and that observing persisted long after punishment was removed. Moreover, participants appeared insensitive to the initial costs of checking, and a threefold increase in the effort required to observe served to deter participants only to a limited degree. We also assessed observing in OCD patients with no known comorbidities. The patients observed more than control participants and were abnormally insensitive to the introduction of punishment. These findings support the translational value of the task, with similar behaviours in humans and rodents. This paradigm may serve as a unifying platform, promoting interaction between different approaches to analyse adaptive and maladaptive certainty seeking behaviours. Specifically, we demonstrate how seemingly disparate theoretical and empirical approaches can be reconciled synergistically to promote a combined behavioural and cognitive account of certainty seeking.

Mapping Compulsivity in the DSM-5 Obsessive Compulsive and Related Disorders: Cognitive Domains, Neural Circuitry, and Treatment.

Compulsions are repetitive, stereotyped thoughts and behaviors designed to reduce harm. Growing evidence suggests that the neurocognitive mechanisms mediating behavioral inhibition (motor inhibition, cognitive inflexibility) reversal learning and habit formation (shift from goal-directed to habitual responding) contribute toward compulsive activity in a broad range of disorders. In obsessive compulsive disorder, distributed network perturbation appears focused around the prefrontal cortex, caudate, putamen, and associated neuro-circuitry. Obsessive compulsive disorder-related attentional set-shifting deficits correlated with reduced resting state functional connectivity between the dorsal caudate and the ventrolateral prefrontal cortex on neuroimaging. In contrast, experimental provocation of obsessive compulsive disorder symptoms reduced neural activation in brain regions implicated in goal-directed behavioral control (ventromedial prefrontal cortex, caudate) with concordant increased activation in regions implicated in habit learning (presupplementary motor area, putamen). The ventromedial prefrontal cortex plays a multifaceted role, integrating affective evaluative processes, flexible behavior, and fear learning. Findings from a neuroimaging study of Pavlovian fear reversal, in which obsessive compulsive disorder patients failed to flexibly update fear responses despite normal initial fear conditioning, suggest there is an absence of ventromedial prefrontal cortex safety signaling in obsessive compulsive disorder, which potentially undermines explicit contingency knowledge and may help to explain the link between cognitive inflexibility, fear, and anxiety processing in compulsive disorders such as obsessive compulsive disorder.

Autism spectrum disorders in adult outpatients with obsessive compulsive disorder in the UK.

OBJECTIVES: Patients with obsessive compulsive disorder (OCD) frequently show traits of autism spectrum disorders (ASD). This is one of the first studies to explore the clinical impact of the overlap between OCD and ASD as a categorical diagnosis. METHODS: A cross-sectional survey in 73 adult outpatients with DSM-IV OCD. Autistic traits were measured using the Autism-Spectrum Quotient (AQ). A clinical estimate ASD diagnosis was made by interview using DSM-IV-TR criteria. OCD patients with and without autistic traits or ASD were compared on demographic and clinical parameters and level of OCD treatment-resistance based on treatment history. RESULTS: Thirty-four (47%) patients scored above the clinical threshold on the AQ (≥26) and 21 (27.8%) met diagnostic criteria for ASD. These diagnoses had not been made before. Patients with autistic traits showed a borderline significant increase in OCD symptom-severity (Yale-Brown Obsessive Compulsive Scale (Y-BOCS); p = .054) and significantly increased impairment of insight (Brown Assessment of Beliefs Scale; p = .01). There was a positive correlation between AQ and Y-BOCS scores (p = .04), but not with OCD treatment resistance. CONCLUSION: There is a high prevalence of previously undiagnosed ASD in patients with OCD. ASD traits are associated with greater OCD symptom-severity and poor insight.