Long-term outcomes of deep brain stimulation for treatment-resistant schizophrenia: Exploring potential targets

Abstract

Background: Schizophrenia is a complex and disabling disorder. Around 30% of patients have treatment-resistant schizophrenia (TRS).

Objective: This study summarizes the outcomes after three years follow-up of the first series of patients with TRS treated with deep brain stimulation (DBS) and discuss surgical, clinical and imaging analysis.

Methods: Eight patients with TRS treated with DBS in the nucleus accumbens (NAcc) or the subgenual cingulate gyrus (SCG) were included. Symptoms were rated with the PANSS scale and normalized using the illness density index (IDI). A reduction in IDI-PANSS of ≥25% compared to baseline was the criterion of good response. The volume of activated tissue was calculated to perform a connectomic analysis for each patient. An estimation of the tracts and cortical areas modulated was generated.

Results: Five women and three men were analyzed. After 3 years' follow-up, positive symptoms improved in 50% of the SCG group and 75% of the NAcc group (p = 0.06), and general symptoms improved in 25% and 50% respectively (p = 0.06). The SCG group showed activation of the cingulate bundle and modulation of orbitofrontal and frontomesial regions; in contrast, the NAcc group showed activation of the ventral tegmental area projections pathway and modulation of regions associated with the "default mode network" (precuneus) and Brodmann areas 19 and 20.

Conclusions: These results showed a trend toward improvement for positive and general symptoms in patients with TRS treated with DBS. The connectomic analysis will help us understand the interaction of this treatment with the disease to pursue future trial designs.

Keywords: Deep brain stimulation; Nucleus accumbens; Subgenual cingulate gyrus; Tractography-activation model; Treatment-resistant schizophrenia.