Frontal Transcranial Direct Current Stimulation Improves Schizophrenia Symptoms

Negative symptoms, including avolition-apathy (AA) and expressive deficit (EXP) domains, are improved in individuals with schizophrenia following treatment with bilateral bipolar-nonbalanced frontal transcranial direct current stimulation (tDCS), according to study findings published in Journal of Psychiatric Research.

Researchers conducted a randomized, double-blind, sham-controlled study that included 50 adult outpatients at least 18 years of age (mean age, 42.50±12.63 years) with clinically stabilized schizophrenia (active-tDCS [N=25]; sham-tDCS [N=25]). Participants were attending the Department of Mental Health and Addiction Services of ASST Spedali Civili Brescia, Italy, from January 2019 to September 2021 and enrolled consecutively. Exclusion criteria included recent brain surgery, moderate or severe intellectual disability, active substance use disorders, organic brain comorbidities, pregnancy, and use of implant medical devices.

The primary endpoints included PANSS-Negative subscale, Negative Factor (Neg-PANSS), and AA and EXP domains; neurocognitive performance at Brief Assessment of Cognition in Schizophrenia. The researchers used analysis of covariance to evaluate between-group changes across time. Clinical global impression (CGI) scores, disorganized/concrete (DiscC-PANSS) and positive factors, PANSS subscales and total score, and clinical insight at scale to assess unawareness of mental disorder (SUMD) represented the secondary endpoints.

Participants (5 left-handed; 11 women) were randomly assigned to the treatment or control groups and were blinded to treatment conditions along with tDCS operators and raters. Patients received first- or second-generation antipsychotics, but dosage changes were not permitted during the study. Baseline group differences were observed only for sex distribution (P =.037), but an independent t-test showed no clinical and neurocognitive sex between-group differences except for verbal fluency (t=3.17; P =.003).

Significant improvements were observed following active-tDCS for all negative symptom (NS) measures (Cohen d [d]>0.8; all P <.001), and for working memory (d=0.31; P =.025). Improvements were also shown among this group for PANSS-general psychopathology subscale (d=0.54; P <.001), CGI indexes (d>0.6; all P <.001), DiscC-PANSS (d=0.80; P <.001), PANSS total score (d=0.69; P <.001), and SUMD-general unawareness index (d=0.15; P =.005). Such improvements were not observed for positive symptoms and other insight measures.

There were no between-group differences for adverse events (AEs; P =.30), with 10 patients reporting 1 or more mild-intensity AEs.

Limitations of the study include the lack of neurobiological correlates to support cortico-subcortical networks modulation by tDCS, underpowered sample size, the unbalanced sex distribution, and the lack of a follow-up period.

Researchers concluded, “Along with working memory, disorganization and clinical severity improvements, we demonstrated that bilateral bipolar-nonbalanced frontal-tDCS is a safe and well-tolerated nonpharmacological approach to effectively improve negative symptoms in patients with schizophrenia, particularly influencing the AA and EXP domains.”