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Altered cognitive response to serotonin challenge as a candidate endophenotype for obsessive-compulsive disorder

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Abstract

Rationale

Obsessive-compulsive disorder (OCD) implicates dysfunction of orbitofrontal and insula-related circuitry and of the serotonin system. There is an on-going search in psychiatry for intermediate biological markers, termed ‘endophenotypes’, that exist not only in patients with a given disorder but also in their clinically unaffected first-degree relatives.

Objective

Pharmacological challenge is recognized as a means of eliciting an endophenotype, but this strategy has yet to be used in OCD.

Methods

Twenty-three OCD patients without comorbidities (12 [52.2 %] female), 13 clinically asymptomatic first-degree relatives of OCD patients (11 [84.6 %] female) and 27 healthy controls (16 [59.3 %] female) received single-dose escitalopram (20 mg) and placebo in a randomized double-blind crossover design. Effects of treatment on decision-making were quantified using the Cambridge Gamble Task (CGT) in conjunction with a mixed model analysis of covariance (ANCOVA).

Results

There was a significant interaction between serotonergic challenge and group for risk adjustment on the CGT (F = 4.1406; p = 0.02). Only controls showed a significant placebo-drug change in risk adjustment (p = 0.02; versus p > 0.10). Numerically, escitalopram was associated with increase in risk adjustment in controls and reductions in the other groups. Change in risk adjustment was similar in OCD patients and relatives (p = 0.806) and differed significantly from controls (p = 0.007; p = 0.041, respectively).

Conclusions

Individuals with OCD, and first-degree relatives, showed an altered cognitive response to serotonin challenge. This is the first demonstration of a candidate pharmacological challenge endophenotype for the disorder. Future work should confirm these findings in a larger sample size and ideally extend them to other cognitive paradigms, utilizing functional neuroimaging.

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Acknowledgments

This work was supported by the Medical Research Council of South Africa, the Obsessive-Compulsive Foundation (Prof Stein), the National Research Foundation of South Africa (Prof Lochner), an unrestricted grant from Lundbeck H/S and by a Starter Grant for Clinical Lecturers from the Academy of Medical Sciences UK (Dr Chamberlain). Dr Chamberlain consults for Cambridge Cognition. We would like to acknowledge the contribution of our research assistants.

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Authors and Affiliations

  1. US/UCT MRC Unit on Anxiety & Stress Disorders, Department of Psychiatry, University of Stellenbosch, PO Box 241, Cape Town, 8000, South Africa

    Christine Lochner

  2. Department of Psychiatry, University of Cambridge School of Clinical Medicine and Cambridge and Peterborough NHS Foundation Trust (CPFT), Cambridge, UK

    Samuel R. Chamberlain & Naomi A. Fineberg

  3. Centre for Statistical Consultation, Department of Statistics and Actuarial Sciences, University of Stellenbosch, Stellenbosch, South Africa

    Martin Kidd

  4. US/UCT MRC Unit on Anxiety & Stress Disorders, Department of Psychiatry and Mental Health, University of Cape Town, Cape Town, South Africa

    Dan J. Stein

  5. Hertfordshire Partnership University NHS Foundation Trust and University Of Hertfordshire, Hatfield, UK

    Naomi A. Fineberg

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  1. Christine Lochner
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  2. Samuel R. Chamberlain
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Correspondence to Christine Lochner.

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Lochner, C., Chamberlain, S.R., Kidd, M. et al. Altered cognitive response to serotonin challenge as a candidate endophenotype for obsessive-compulsive disorder. Psychopharmacology 233, 883–891 (2016). https://doi.org/10.1007/s00213-015-4172-y

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