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Abstract #0796

How Antidepressants Work: SSRI Treatment Induces Adaptive Changes in Brain 5-HT PhMRI Responses

Darragh Downey1,2, Karen E. Davies1, Shane McKie2, Gabriella Juhasz2, Ian M. Anderson2, Mark A. Smith3, John-Francis William Deakin2, Steve R. Williams1

1Imaging Science and Biomedical Engineering, University of Manchester, Manchester, UK; 2Neuroscience and Psychiatry Unit, University of Manchester, Manchester, UK; 3 Astra Zeneca R&D, Astra Zeneca U.S., Wilmington, DE, USA

The delayed therapeutic effect of SSRIs may be mediated by adaptive changes to the 5-HT system following chronic treatment. Desensitisation of the 5-HT system may be observed by BOLD signal changes directly at the site of reuptake inhibition or upstream on integrated networks. Using citalopram challenge phMRI we examined BOLD responses to the acute and chronic effects of citalopram. Significant signal decreases following chronic treatment were found in brain areas implicated in depression and its treatment. We observed adaptive changes to an acute pharmacological challenge suggesting down regulation of receptor expression or enhanced post synaptic signalling following chronic SSRI treatment.