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Palm, Ulrich; Keeser, Daniel; Hasan, Alkomiet; Kupka, Michael J.; Blautzik, Janusch; Sarubin, Nina; Kaymakanova, Filipa; Unger, Ina; Falkai, Peter ORCID logoORCID: https://orcid.org/0000-0003-2873-8667; Meindl, Thomas; Ertl-Wagner, Birgit and Padberg, Frank (2016): Prefrontal Transcranial Direct Current Stimulation for Treatment of Schizophrenia With Predominant Negative Symptoms: A Double-Blind, Sham-Controlled Proof-of-Concept Study. In: Schizophrenia Bulletin, Vol. 42, No. 5: pp. 1253-1261

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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, 20 min) 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.

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