Transcranial Direct Current Stimulation Improves Paranoia and Social Functioning in Schizophrenia: A Randomized Clinical Trial

BACKGROUND: Innovative treatments for paranoia, which significantly impairs social functioning in schizophrenia spectrum disorders (SSDs), are urgently needed. The pathophysiology of paranoia implicates the amygdala–prefrontal cortex (PFC) circuits; thus, in this study, we systematically investigated whether transcranial direct current stimulation (tDCS) to the ventrolateral PFC can attenuate paranoia and improve social functioning in SSDs.
METHODS:  A double-blind, within-subjects, crossover design was used to compare active versus sham tDCS effects in 50 participants with SSDs (ClinicalTrials.gov identifier: NCT05746494). Participants completed 2 stimulation visits, each including 2 tDCS sessions about 1 week apart, with active (2 mA for 20 minutes) and sham conditions counterbalanced across the 2 visits. Alongside laboratory-based measurements of state paranoia and its associated social cognitive biases, ecological momentary assessment (EMA) was used. This involved daily evaluations of paranoia and social functioning administered 3 times per day for 7 days during each EMA period (EMA-baseline, EMA-active, EMA-sham).
RESULTS:  For laboratory-based assessments, participants showed greater reductions in state paranoia and improvements in paranoia-related social cognitive biases after active stimulation compared with sham, including lower self-reported hostility and hostile attributions in ambiguous situations post active versus post sham. Similarly, in the EMA-active period, participants had lower daily paranoia than in the EMA-sham period and higher social interaction motivation with better attitudes compared with baseline and the EMA-sham period.
CONCLUSIONS:  Extending our pilot study, the current findings further supported the efficacy of tDCS in mitigating paranoia and enhancing social functioning in patients with SSDs. This work sheds light on the neuropathology of paranoia and identifies a promising avenue for future large-scale interventions.
© 2025 Society of Biological Psychiatry.