Christine Lochner1, Samuel R Chamberlain2,3, Martin Kidd4, Lian Taljaard5, Naomi A Fineberg6,7, Trevor W Robbins2, Dan J Stein8. 1. SAMRC Unit on Risk and Resilience in Mental Disorders, Department of Psychiatry, Stellenbosch University, Stellenbosch, South Africa. cl2@sun.ac.za. 2. Department of Psychiatry, University of Cambridge, Cambridge, UK. 3. Cambridgeshire & Peterborough NHS Foundation Trust, Cambridge, UK. 4. Centre for Statistical Consultation, Department of Statistics and Actuarial Sciences, University of Stellenbosch, Stellenbosch, South Africa. 5. SAMRC Unit on Risk and Resilience in Mental Disorders, Department of Psychiatry, Stellenbosch University, Stellenbosch, South Africa. 6. National Treatment Service for OCD, Hertfordshire, UK. 7. University of Hertfordshire, Hertfordshire, UK. 8. SAMRC Unit on Risk & Resilience in Mental Disorders, Department of Psychiatry & Neuroscience Institute, University of Cape Town, Cape Town, South Africa.
Abstract
RATIONALE: Obsessive-compulsive disorder (OCD) is characterized by executive function impairment and by clinical responsivity to selective serotonin reuptake inhibitors (SSRIs). Executive planning deficits constitute a candidate endophenotype for OCD. It is not known whether this endophenotype is responsive to acute serotonin manipulation. OBJECTIVE: The study aimed to investigate the effects of acute SSRI administration on executive function in patients with OCD, first-degree relatives of patients with OCD, and healthy controls. METHODS: A randomized double-blind cross-over study assessed the effects of single-dose escitalopram (20 mg) and placebo on executive planning in 24 patients with OCD, 13 clinically unaffected first-degree relatives of patients with OCD, and 28 healthy controls. Performance on a Tower of London task measuring executive planning was assessed 4 h after oral administration of the pharmacological challenge/placebo and compared across and within groups using a mixed model analysis of variance. RESULTS: On the outcome measure of interest, i.e., the mean number of choices to obtain the correct solution, there was a marginally significant effect of group (F(2, 59) = 3.1; p = 0.052), with patients (least square (LS) mean 1.43; standard error [SE] 0.06; 95% confidence interval (CI), 1.31-1.55) and their relatives (LS mean 1.46; SE 0.08; 95% CI, 1.30-1.62) performing worse than matched healthy controls (LS mean 1.26; SE 0.05; 95% CI, 1.15-1.37) on placebo. There was a trend towards a significant group × treatment interaction (F(2, 58) = 2.8, p = 0.069), with post hoc tests showing (i) patients (p = 0.009; LS mean difference 0.23; SE 0.08) and relatives (p = 0.03; LS mean difference 0.22; SE 0.10) were more impaired compared to controls and (ii) escitalopram was associated with improved executive planning in patients with OCD (p = 0.013; LS mean difference 0.1; SE 0.04), but not other groups (both p > 0.1; controls: LS mean difference - 0.03; SE 0.04; relatives: LS mean difference 0.02; SE 0.05). CONCLUSION: Our findings are consistent with a view that there is impaired executive planning in OCD and that this constitutes a behavioural endophenotype. In patients with OCD, but not in relatives, acute SSRI administration ameliorated this deficit. Further investigation is needed to understand common and differential involvement of neurochemical systems in patients with OCD and their relatives.
RCT Entities:
RATIONALE: Obsessive-compulsive disorder (OCD) is characterized by executive function impairment and by clinical responsivity to selective serotonin reuptake inhibitors (SSRIs). Executive planning deficits constitute a candidate endophenotype for OCD. It is not known whether this endophenotype is responsive to acute serotonin manipulation. OBJECTIVE: The study aimed to investigate the effects of acute SSRI administration on executive function in patients with OCD, first-degree relatives of patients with OCD, and healthy controls. METHODS: A randomized double-blind cross-over study assessed the effects of single-dose escitalopram (20 mg) and placebo on executive planning in 24 patients with OCD, 13 clinically unaffected first-degree relatives of patients with OCD, and 28 healthy controls. Performance on a Tower of London task measuring executive planning was assessed 4 h after oral administration of the pharmacological challenge/placebo and compared across and within groups using a mixed model analysis of variance. RESULTS: On the outcome measure of interest, i.e., the mean number of choices to obtain the correct solution, there was a marginally significant effect of group (F(2, 59) = 3.1; p = 0.052), with patients (least square (LS) mean 1.43; standard error [SE] 0.06; 95% confidence interval (CI), 1.31-1.55) and their relatives (LS mean 1.46; SE 0.08; 95% CI, 1.30-1.62) performing worse than matched healthy controls (LS mean 1.26; SE 0.05; 95% CI, 1.15-1.37) on placebo. There was a trend towards a significant group × treatment interaction (F(2, 58) = 2.8, p = 0.069), with post hoc tests showing (i) patients (p = 0.009; LS mean difference 0.23; SE 0.08) and relatives (p = 0.03; LS mean difference 0.22; SE 0.10) were more impaired compared to controls and (ii) escitalopram was associated with improved executive planning in patients with OCD (p = 0.013; LS mean difference 0.1; SE 0.04), but not other groups (both p > 0.1; controls: LS mean difference - 0.03; SE 0.04; relatives: LS mean difference 0.02; SE 0.05). CONCLUSION: Our findings are consistent with a view that there is impaired executive planning in OCD and that this constitutes a behavioural endophenotype. In patients with OCD, but not in relatives, acute SSRI administration ameliorated this deficit. Further investigation is needed to understand common and differential involvement of neurochemical systems in patients with OCD and their relatives.
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