Neurophysiological and autonomic effects of Cognitive Remediation Therapy in schizophrenia: a randomized controlled...

Cognitive impairment and emotion dysregulation are core features of schizophrenia and remain insufficiently addressed by pharmacological treatment. Cognitive Remediation Therapy (CRT) has demonstrated efficacy in improving neurocognitive performance; however, evidence linking behavioral improvements to neurophysiological and autonomic mechanisms remains limited. The present randomized controlled trial examined the effects of CRT on electrophysiological, autonomic, cognitive, and clinical outcomes in clinically stable individuals with schizophrenia.

Fifty-seven outpatients with schizophrenia were randomized to a 12-week CRT program (24 sessions) or control condition. Forty-eight participants completed the protocol (CRT: n = 26; control: n = 22). Primary outcome was change in P300 amplitude during a visual oddball task. Secondary outcomes included N200 amplitude, frontal midline theta power during a 2-back task, skin conductance responses (SCR) to negative emotional stimuli, working memory performance, emotion recognition, symptom severity (PANSS), global cognition (MoCA, BACS), emotion regulation (Difficulties in Emotion Regulation Scale (DERS)), and quality of life (QLS). Repeated-measures ANOVA tested Group × Time interactions.

CRT produced a significant increase in P300 amplitude relative to control (F(1,46) = 18.72, p < .001, η²p = .29). Significant Group × Time interactions were also observed for N200 amplitude (η²p = .18) and frontal midline theta power (η²p = .26). SCR to negative stimuli decreased in the CRT group (η²p = .16), whereas tonic baseline arousal showed no significant interaction. Behavioral improvements were observed in 2-back accuracy (η²p = .24) and backward digit span (η²p = .19), alongside gains in facial emotion recognition. Psychometric analyses revealed significant improvements in PANSS total and subscales, MoCA, BACS composite, DERS, and QLS scores. Correlation analyses demonstrated that increases in P300 and theta power were associated with improvements in working memory and global cognition, while reductions in SCR were associated with improvements in emotion regulation.

CRT induced convergent improvements across neural, cognitive, autonomic, and clinical domains. Enhanced P300 amplitude and frontal midline theta power suggest strengthened attentional allocation and executive control mechanisms, while reduced stimulus-evoked autonomic reactivity indicates improved emotional regulation. These findings support CRT as a mechanistically informed intervention capable of modifying core cognitive-control processes and promoting functional recovery in schizophrenia.

This randomized controlled trial was prospectively registered at ClinicalTrials.gov (Identifier: NCT06936397; registration date: 20.04.2025).