title: Functional effects of chronic paroxetine versus placebo on the fear, stress and anxiety brain circuit in Social Anxiety Disorder: initial validation of an imaging protocol for drug discovery.
abstract: Recent studies suggest that pharmacologic effects of anxiolytic agents can be mapped as functional changes in the fear, stress and anxiety brain circuit. In this work we investigated the effects of a standard treatment, paroxetine (20mg/day), in subjects with Social Anxiety Disorder (SAD) versus placebo using different fMRI paradigms. The fMRI sessions, performed before and after the treatment, consisted of a public exposition of recorded performance task (PERPT), an emotional face processing task (EFPT) and a 6-min resting state followed by an off-scanner public speaking test. Paroxetine significantly improved the clinical conditions of SAD patients (n=17) vs. placebo (n=16) as measured with Clinical Global Inventory - Improvement (CGI-I) while no change was seen when using Liebowitz Social Anxiety Scale, as expected given the small size of the study population. Paroxetine reduced the activation of insula, thalamus and subgenual/anterior cingulate cortex (ACC) in PERPT. Resting-state fMRI assessment using Independent Component Analysis indicated that paroxetine reduced functional connectivity in insula, thalamus and ACC when compared with placebo. Both paradigms showed significant correlation with CGI-I in rostral prefrontal cortex. Conversely, paroxetine compared to placebo produced activation of right amygdala and bilateral insula and no effects in ACC when tested with EFPT. No treatment effects on distress scores were observed in the off-scanner Public Speaking Test. Overall this study supports the use of fMRI as sensitive approach to explore the neurobiological substrate of the effects of pharmacologic treatments and, in particular, of resting state fMRI given its simplicity and task independence.
authors: MRI Research Unit, CRC-Mar, Hospital del Mar, Barcelona, Spain.
authors: Mónica
authors: M
authors: Giménez
authors: MRI Research Unit, CRC-Mar, Hospital del Mar, Barcelona, Spain.
authors: Hector
authors: H
authors: Ortiz
authors: Bellvitge Biomedical Research Institute-IDIBELL, Psychiatry Department, Bellvitge University Hospital, CIBERSAM, Barcelona, Spain.
authors: Carles
authors: C
authors: Soriano-Mas
authors: MRI Research Unit, CRC-Mar, Hospital del Mar, Barcelona, Spain; Bellvitge Biomedical Research Institute-IDIBELL, Psychiatry Department, Bellvitge University Hospital, CIBERSAM, Barcelona, Spain.
authors: Marina
authors: M
authors: López-Solà
authors: Human Pharmacology and Neurosciences, IMIM-Hospital del Mar, Red RTA, Barcelona, Spain; Clinical Pharmacology, Autonomous University of Barcelona, Barcelona, Spain.
authors: Magí
authors: M
authors: Farré
authors: MRI Research Unit, CRC-Mar, Hospital del Mar, Barcelona, Spain; Department of Clinical and Health Psychology, Autonomous University of Barcelona, Spain.
authors: Joan
authors: J
authors: Deus
authors: Human Pharmacology and Neurosciences, IMIM-Hospital del Mar, Red RTA, Barcelona, Spain; Clinical Institute of Neuroscience, Hospital Clínic-IDIBAPS, CIBERSAM, Barcelona and Department of Psychiatry and Clinical Psychobiology, University of Barcelona, Spain.
authors: Rocio
authors: R
authors: Martín-Santos
authors: Neurosciences Centre of Excellence for Drug Discovery, GlaxoSmithKline R&D, Verona, Italy.
authors: Sofia
authors: S
authors: Fernandes
authors: Neurosciences Centre of Excellence for Drug Discovery, GlaxoSmithKline R&D, Verona, Italy.
authors: Paolo
authors: P
authors: Fina
authors: Neurosciences Centre of Excellence for Drug Discovery, GlaxoSmithKline R&D, Verona, Italy.
authors: Massimo
authors: M
authors: Bani
authors: Neurosciences Centre of Excellence for Drug Discovery, GlaxoSmithKline R&D, Verona, Italy.
authors: Stefano
authors: S
authors: Zancan
authors: MRI Research Unit, CRC-Mar, Hospital del Mar, Barcelona, Spain.
authors: Jesús
authors: J
authors: Pujol
authors: Neurosciences Centre of Excellence for Drug Discovery, GlaxoSmithKline R&D, Verona, Italy. Electronic address: emilio.merlopich@gmail.com.
authors: Emilio
authors: E
authors: Merlo-Pich
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D018687:Antidepressive Agents, Second-Generation / Q000097:blood / Q000627:therapeutic use*; D001007:Anxiety / Q000188:drug therapy / Q000209:etiology; D001921:Brain / Q000098:blood supply / Q000187:drug effects*; D001931:Brain Mapping; D005239:Fear / Q000187:drug effects*; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D017374:Paroxetine / Q000097:blood / Q000627:therapeutic use*; D010698:Phobic Disorders / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D013060:Speech; D013315:Stress, Psychological / Q000188:drug therapy* / Q000209:etiology; D013997:Time Factors; D064232:Visual Analog Scale; D014796:Visual Perception / Q000187:drug effects; D055815:Young Adult
chemical_list: D018687:Antidepressive Agents, Second-Generation; D017374:Paroxetine
keywords: Anxiety; Placebo; Public speaking test; Randomized clinical trial; Resting state; Social emotional stimuli; fMRI