Acute effects of selective serotonin reuptake inhibitors on cerebral glucose metabolism and blood flow

TL;DR

This study investigates how SSRIs, a type of antidepressant, affect brain glucose metabolism and blood flow in healthy volunteers.

Contribution

The study introduces a novel multimodal neuroimaging approach combining fPET and pcASL to assess acute SSRI effects on brain energy demands.

Findings

SSRIs acutely altered glucose metabolism in serotonergic brain regions like the striatum and occipital cortex.

No corresponding changes in cerebral blood flow were observed, indicating SSRI effects are specific to energy demands.

Exploratory analysis showed acute effects in the dorsal raphe nucleus.

Abstract

Selective serotonin reuptake inhibitors (SSRIs) are widely prescribed antidepressants, though their mechanisms of action beyond serotonin transporter (SERT) blockade remain unclear [1]. As previous work on BOLD signal changes remain equivocal, pharmacological multimodal neuroimaging of energy demands and blood flow (CBF) holds promise due to increased specificity of these signals. This may advance the understanding of the involved pharmacodynamic mechanisms and guide treatment strategies of highly prevalent neuropsychiatric disorders. We combine new techniques of functional positron emission tomography (fPET) with high temporal resolution (3 seconds) using [18F]FDG and simultaneously acquired pseudo-continuous arterial spin labelling (pcASL). Thus, we aimed for a highly quantitative assessment of changes in brain activation following an intravenous SSRI challenge using a randomized, placebo-controlled, double-blind study design. We demonstrate acute drug induced changes in glucose metabolism (Ki) in serotonergic projections, i.e. the striatum and the occipital cortex in 16 healthy volunteers (7 females). In an exploratory analysis, acute effects were observed in the dorsal raphe nucleus. We did not observe corresponding changes in CBF, which suggests that observed SSRI effects are specific to brain energy demands. Our results complement the existing literature on the acute pharmacological effects of SSRIs by providing insights in specific aspects of neuronal activation. Moreover, our findings expand upon the results of existing BOLD fMRI studies and, thus, support the application of this pharmacological neuroimaging protocol in psychopharmacological research.

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