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Short-term antidepressant administration reduces negative self-referential processing in the medial prefrontal cortex in subjects at risk for depression

Molecular Psychiatry volume 17, pages 503–510 (2012)Cite this article

Abstract

Depression has been associated with changes in responses within the medial prefrontal cortex (mPFC) during emotional information processing. Antidepressant drug treatment has been shown to modify neural responses in healthy volunteers early in treatment within similar circuitry. It is unclear, however, whether the same early effect occurs in depressed patients, before changes in mood. The current study therefore investigated the effects of 7-days administration of the selective serotonin-uptake inhibitor citalopram vs placebo in volunteers (n=29) at a high risk for the development of depression, using the personality phenotype of high neuroticism in a double-blind, between-groups design. On the last day of treatment, resting haemoperfusion and functional magnetic resonance imaging (MRI) data were acquired during a self-referential words categorisation task. A significant activation in a cluster of mPFC areas, including dorsal anterior cingulate and right orbitofrontal cortex was revealed, driven by decreased responses to the negative self-descriptors following citalopram compared with placebo, in the absence of any mood differences. These findings show a normalisation of neural abnormalities in- and at-risk population early in treatment, supporting the theory that antidepressants may indeed act by modifying specific neural dysfunctions correlated to negative cognitive biases.

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Acknowledgements

The study was supported by a Medical Research Council grant to Dr Catherine Harmer.

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  1. University Department of Psychiatry, Warneford Hospital, Oxford, UK

    M Di Simplicio, R Norbury & C J Harmer

  2. Neuroscience Department, Psychiatry Section, University of Siena, Siena, Italy

    M Di Simplicio

  3. University of Oxford Centre for Clinical Magnetic Resonance Research (OCMR), John Radcliffe Hospital, Oxfordshire, UK

    R Norbury

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  1. M Di Simplicio
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Correspondence to M Di Simplicio.

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MD and RN report no conflicts of interest. CJH has served as a consultant for P1vital, GlaxoSmithKline, Servier, Astra Zeneca, Johnson & Johnson, Lundbeck and is on the advisory board and holds shares of P1vital.

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Di Simplicio, M., Norbury, R. & Harmer, C. Short-term antidepressant administration reduces negative self-referential processing in the medial prefrontal cortex in subjects at risk for depression. Mol Psychiatry 17, 503–510 (2012). https://doi.org/10.1038/mp.2011.16

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