Prefrontal Transcranial Direct Current Stimulation for Treatment of Schizophrenia With Predominant Negative Symptoms: A Double-Blind, Sham-Controlled Proof-of-Concept Study.
Negative symptoms are highly relevant in the long-term course of schizophrenia and are an important target domain for the development of novel interventions. Recently, transcranial direct current stimulation (tDCS) of the prefrontal cortex has been investigated as a treatment option in schizophrenia. In this proof-of-concept study, 20 schizophrenia patients with predominantly negative symptoms were randomized to either 10 sessions of add-on active (2 mA, 20min) or sham tDCS (anode: left DLPFC/F3; cathode: right supraorbital/F4). Primary outcome measure was the change in the Scale for the Assessment of Negative Symptoms (SANS) sum score; secondary outcomes included reduction in Positive and Negative Syndrome Scale (PANSS) scores and improvement of depressive symptoms, cognitive processing speed, and executive functioning. Sixteen patients underwent 4 functional connectivity magnetic resonance imaging (fcMRI) scans (pre and post 1st and pre and post 10th tDCS) to investigate changes in resting state network connectivity after tDCS. Per-protocol analysis showed a significantly greater decrease in SANS score after active (-36.1%) than after sham tDCS (-0.7%). PANSS sum scores decreased significantly more with active (-23.4%) than with sham stimulation (-2.2%). Explorative analysis of fcMRI data indicated changes in subgenual cortex and dorsolateral prefrontal cortex (DLPFC) connectivity within frontal-thalamic-temporo-parietal networks. The results of this first proof-of-concept study indicate that prefrontal tDCS may be a promising intervention for treatment of schizophrenia with predominant negative symptoms. Large-scale randomized controlled studies are needed to further establish prefrontal tDCS as novel treatment for negative symptoms in schizophrenia.
Department of Psychiatry and Psychotherapy, Ludwig Maximilian University Munich, Munich, Germany; ulrich.palm@med.uni-muenchen.de.
Ulrich
U
Palm
Institute for Clinical Radiology, Ludwig Maximilian University Munich, Munich, Germany;
Daniel
D
Keeser
Alkomiet
A
Hasan
Institute for Clinical Radiology, Ludwig Maximilian University Munich, Munich, Germany;
Michael J
MJ
Kupka
Institute for Clinical Radiology, Ludwig Maximilian University Munich, Munich, Germany;
Janusch
J
Blautzik
Hochschule Fresenius, University of Applied Sciences, Psychology School, Munich, Germany.
Nina
N
Sarubin
Filipa
F
Kaymakanova
Ina
I
Unger
Peter
P
Falkai
Institute for Clinical Radiology, Ludwig Maximilian University Munich, Munich, Germany;
Thomas
T
Meindl
Institute for Clinical Radiology, Ludwig Maximilian University Munich, Munich, Germany;
Birgit
B
Ertl-Wagner
Frank
F
Padberg
D000328:Adult; D063132:Connectome / Q000379:methods*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009415:Nerve Net / Q000503:physiopathology*; D017063:Outcome Assessment, Health Care; D017397:Prefrontal Cortex / Q000503:physiopathology*; D012559:Schizophrenia / Q000503:physiopathology*; D065908:Transcranial Direct Current Stimulation / Q000379:methods*; D055815:Young Adult
functional connectivity MRI—fcMRI; negative symptoms; resting-state networks; schizophrenia; transcranial direct current stimulation—tDCS