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SSRI administration reduces resting state functional connectivity in dorso-medial prefrontal cortex

Molecular Psychiatry volume 16, pages 592–594 (2011)Cite this article

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Recent evidence suggests that an area in the dorsal medial prefrontal cortex (dorsal nexus) shows dramatic increases in connectivity across a network of brain regions in depressed patients during the resting state;1 this increase in connectivity is suggested to represent hotwiring of areas involved in disparate cognitive and emotional functions.1, 2, 3 Sheline et al.1 concluded that antidepressant action may involve normalisation of the elevated resting state functional connectivity seen in depressed patients. However, the effects of conventional pharmacotherapy for depression on this resting state functional connectivity is not known and the effects of antidepressant treatment in depressed patients may be confounded by change in symptoms following treatment.

To test the hypothesis that decreasing the activity of the ‘dorsal nexus’ might be a potential therapeutic target for depression, we examined the effects of an SSRI (citalopram, 20 mg daily) given for 7 days to 30 healthy (mean age 25 and range±5 years) volunteers, matched for age and gender, with no previous psychiatric history, in a double-blind placebo-controlled design. Resting state data were available for 12 healthy volunteers in the citalopram group and 15 healthy volunteers in the placebo group. We used resting-state functional magnetic resonance imaging and seed-based connectivity analysis, in which we selected the right and left dorsal medial prefrontal cortex from Sheline et al.1 study as seed regions (see Supplementary Material for details). Such an approach allowed us to examine changes in connectivity early on in treatment and in the absence of changes in subjective state.

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Authors and Affiliations

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

    C McCabe, Z Mishor, P J Cowen, M J Taylor & C J Harmer

  2. Department of Clinical Neurology, Centre for Functional MRI of the Brain, University of Oxford, Oxford, UK

    N Filippini

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  1. C McCabe
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  2. Z Mishor
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  3. N Filippini
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  4. P J Cowen
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  5. M J Taylor
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  6. C J Harmer
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Correspondence to C McCabe.

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Competing interests

Dr McCabe has received consultancy from P1vital. Dr Harmer is on the advisory board of P1vital and holds shares in the same company. She is also company director of Oxford Psychologists. Dr Harmer has received fees for consultancy from Servier, GlaxoSmithKline, Astra Zeneca, Johnson & Johnson, P1vital, Roche and EiSai. Professor Cowen has been a paid member of advisory boards of Eli Lilly, Servier and Lundbeck and has been a paid lecturer for Eli Lilly, Servier, GlaxoSmithKline and AstraZeneca. Dr Taylor's spouse is an employee of GlaxoSmithKline. Mr Mishor and Dr Filippini report no biomedical financial interests or potential conflict of interest.

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McCabe, C., Mishor, Z., Filippini, N. et al. SSRI administration reduces resting state functional connectivity in dorso-medial prefrontal cortex. Mol Psychiatry 16, 592–594 (2011). https://doi.org/10.1038/mp.2010.138

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