Right orbitofrontal cortex rTMS targets anxiety, not depressive, symptoms in first-episode schizophrenia

Anxiety is highly prevalent and undertreated in first-episode schizophrenia(FES), but repetitive transcranial magnetic stimulation(rTMS) data for this comorbidity are scarce. The orbitofrontal cortex(OFC) is a key anxiety-regulating node, supporting its potential as a target. This study aimed to explore 1-Hz right OFC-rTMS's symptom-specific effects on FES mood.

This is a secondary analysis of a randomized controlled trial. Participants were drug-naive FES patients randomized to the active rTMS group(n = 51) or sham group(n = 45). All completed 20 intervention sessions, 20 sessions of active OFC-rTMS or sham, with 4-week follow-up, initiating oral olanzapine(10-20 mg/day) concurrently with the first rTMS session. Mood symptoms were assessed using the 24-item Hamilton Depression Rating Scale(HAMD) and the 14-item Hamilton Anxiety Rating Scale(HAMA). Psychopathological symptoms were assessed using the Positive and Negative Syndrome Scale(PANSS). The main outcome was the changes in HAMD and HAMA scores from baseline to 2 weeks and 4 weeks.

The active group showed greater PANSS total(t = -3.260, p = 0.002; Cohen's d = 0.672) and subscale improvements vs. the sham group. Repeated-measures ANOVA(controlling for covariates) revealed significant Time×Group interactions for HAMA total(F = 4.698, p = 0.010; partial η² = 0.059) and psychic anxiety(F = 5.735, p = 0.004; partial η² = 0.072), but not somatic anxiety. For HAMD, only anxiety/somatization(F = 8.397, p = 0.031; partial η² = 0.099) and cognitive impairment(F = 6.240, p = 0.002; partial η² = 0.076) showed interactions, with no specific effects on overall depressive symptoms. In the sham group, HAMD anxiety/somatization correlated with all PANSS subscales(r = 0.311-0.477, p < 0.05), but this correlation was absent in the active group(all p > 0.05).

Right OFC-rTMS improves FES anxiety (not depression), supporting it as a targeted non-pharmacological option.