Single-dose serotonergic stimulation shows widespread effects on functional brain connectivity.
The serotonergic system is widely distributed throughout the central nervous system. It is well known as a mood regulating system, although it also contributes to many other functions. With resting state functional magnetic resonance imaging (RS-fMRI) it is possible to investigate whole brain functional connectivity. We used this non-invasive neuroimaging technique to measure acute pharmacological effects of the selective serotonin reuptake inhibitor sertraline (75 mg) in 12 healthy volunteers. In this randomized, double blind, placebo-controlled, crossover study, RS-fMRI scans were repeatedly acquired during both visits (at baseline and 3, 5, 7 and 9h after administering sertraline or placebo). Within-group comparisons of voxelwise functional connectivity with ten functional networks were examined (p<0.005, corrected) using a mixed effects model with cerebrospinal fluid, white matter, motion parameters, heart rate and respiration as covariates. Sertraline induced widespread effects on functional connectivity with multiple networks; the default mode network, the executive control network, visual networks, the sensorimotor network and the auditory network. A common factor among these networks was the involvement of the precuneus and posterior cingulate cortex. Cognitive and subjective measures were taken as well, but yielded no significant treatment effects, emphasizing the sensitivity of RS-fMRI to pharmacological challenges. The results are consistent with the existence of an extensive serotonergic system relating to multiple brain functions with a possible key role for the precuneus and cingulate.
Leiden University, Institute of Psychology, Leiden, The Netherlands; Leiden University Medical Center, Department of Radiology, Leiden, The Netherlands; Leiden University, Leiden Institute for Brain and Cognition, Leiden, The Netherlands. Electronic address: b.klaassens@lumc.nl.
Bernadet L
BL
Klaassens
Centre for Human Drug Research, Leiden, The Netherlands.
Helene C
HC
van Gorsel
McGill University, Montreal Neurological Institute, Montreal, QC, Canada.
Najmeh
N
Khalili-Mahani
Leiden University Medical Center, Department of Radiology, Leiden, The Netherlands.
Jeroen
J
van der Grond
Pfizer Inc., Cambridge, MA, USA.
Bradley T
BT
Wyman
Pfizer Inc., Cambridge, MA, USA.
Brandon
B
Whitcher
Leiden University, Institute of Psychology, Leiden, The Netherlands; Leiden University Medical Center, Department of Radiology, Leiden, The Netherlands; Leiden University, Leiden Institute for Brain and Cognition, Leiden, The Netherlands.
Serge A R B
SA
Rombouts
Centre for Human Drug Research, Leiden, The Netherlands.
Joop M A
JM
van Gerven
D000328:Adult; D001921:Brain / Q000187:drug effects / Q000502:physiology*; D001931:Brain Mapping; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D008279:Magnetic Resonance Imaging; D008297:Male; D009483:Neuropsychological Tests; D011388:Prolactin / Q000097:blood; D012701:Serotonin / Q000502:physiology*; D017367:Selective Serotonin Reuptake Inhibitors / Q000493:pharmacokinetics / Q000494:pharmacology; D020280:Sertraline / Q000493:pharmacokinetics / Q000494:pharmacology; D055815:Young Adult
D006854:Hydrocortisone; D011388:Prolactin; D012701:Serotonin; D017367:Selective Serotonin Reuptake Inhibitors; D020280:Sertraline
FMRI; Functional connectivity; Neuropharmacology; Resting state networks; SSRI; Serotonin