Intensified electrical stimulation targeting lateral and medial prefrontal cortices for the treatment of social anxiety disorder: A randomized, double-blind, parallel-group, dose-comparison study

Eisa Jafari,Jaber Alizadehgoradel,Fereshteh Pourmohseni Koluri,Ezzatollah Nikoozadehkordmirza,Meysam Refahi,Mina Taherifard,Vahid Nejati,Amir-Homayun Hallajian,Elham Ghanavati,Carmelo M Vicario,Michael A Nitsche,Mohammad Ali Salehinejad

doi:10.1016/j.brs.2021.06.005

Abstract

BackgroundSocial Anxiety Disorder (SAD) is the most common anxiety disorder while remains largely untreated. Disturbed amygdala-frontal network functions are central to the pathophysiology of SAD, marked by hypoactivity of the lateral prefrontal cortex (PFC), and hypersensitivity of the medial PFC and the amygdala. The objective of this study was to determine whether modulation of the dorsolateral and medial PFC activity with a novel intensified stimulation protocol reduces SAD core symptoms, improves treatment-related variables, and reduces attention bias to threatening stimuli. MethodsIn this randomized, sham-controlled, double-blind trial, we assessed the efficacy of an intensified stimulation protocol (20 min, twice-daily sessions with 20 min intervals, 5 consecutive days) in two intensities (1 vs 2 mA) compared to sham stimulations. 45 patients with SAD were randomized in three tDCS arms (1-mA, 2-mA, sham). SAD symptoms, treatment-related variables (worries, depressive state, emotion regulation, quality of life), and attention bias to threatening stimuli (dot-probe paradigm) were assessed before and right after the intervention. SAD symptoms were also assessed at 2-month follow-up. ResultsBoth 1-mA and 2-mA protocols significantly reduced fear/avoidance symptoms, worries and improved, emotion regulation and quality of life after the intervention compared to the sham group. Improving effect of the 2-mA protocol on avoidance symptoms, worries and depressive state was significantly larger than the 1-mA group. Only the 2-mA protocol reduced attention bias to threat-related stimuli, the avoidance symptom at follow-up, and depressive states, as compared to the sham group. ConclusionsModulation of lateral-medial PFC activity with intensified stimulation can improve cognitive control, motivation and emotion networks in SAD and might thereby result in therapeutic effects. These effects can be larger with 2-mA vs 1-mA intensities, though a linear relationship between intensity and efficacy should not be concluded. Our results need replication in larger trials.

Highlights

With a lifetime prevalence of 13% [1], Social Anxiety Disorder (SAD), known as social phobia, is the most common anxiety disorder with an early onset age and a risk factor for subsequent depression, substance abuse, and cardiovascular disease [1,2]
In this randomized, sham-controlled, double-blind trial, we assessed the efficacy of an intensified stimulation protocol (20 min, twice-daily sessions with 20 min intervals, 5 consecutive days) in two intensities (1 vs 2 mA) compared to sham stimulations. 45 patients with SAD were randomized in three Transcranial direct current stimulation (tDCS) arms (1-mA, 2-mA, sham)
SAD is usually associated with other mental health problems elevated anxiety and depressive states [6], decreased quality of life [7], and disturbed emotion regulation [8] leading to disabling consequences such as social isolation and functional impairment

Summary

Introduction

With a lifetime prevalence of 13% [1], Social Anxiety Disorder (SAD), known as social phobia, is the most common anxiety disorder with an early onset age and a risk factor for subsequent depression, substance abuse, and cardiovascular disease [1,2]. The objective of this study was to determine whether modulation of the dorsolateral and medial PFC activity with a novel intensified stimulation protocol reduces SAD core symptoms, improves treatment-related variables, and reduces attention bias to threatening stimuli. Results: Both 1-mA and 2-mA protocols significantly reduced fear/avoidance symptoms, worries and improved, emotion regulation and quality of life after the intervention compared to the sham group. Conclusions: Modulation of lateral-medial PFC activity with intensified stimulation can improve cognitive control, motivation and emotion networks in SAD and might thereby result in therapeutic effects. These effects can be larger with 2-mA vs 1-mA intensities, though a linear relationship between intensity and efficacy should not be concluded.

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