From the Group to the Individual in Schizophrenia Spectrum Disorders: Biomarkers of Social Cognitive Impairments and Therapeutic Translation

Abstract

People with schizophrenia spectrum disorders (SSDs) often experience persistent social cognitive impairments, associated with poor functional outcome. There are currently no approved treatment options for these debilitating symptoms, highlighting the need for novel therapeutic strategies. Work to date has elucidated differential social processes and underlying neural circuitry affected in SSDs, which may be amenable to modulation using neurostimulation. Further, advances in functional connectivity mapping and electric field modeling may be used to identify individualized treatment targets to maximize the impact of brain stimulation on social cognitive networks. Here, we review literature supporting a roadmap for translating functional connectivity biomarker discovery to individualized treatment development for social cognitive impairments in SSDs. First, we outline the relevance of social cognitive impairments in SSDs. We review machine learning approaches for dimensional brain-behavior biomarker discovery, emphasizing the importance of individual differences. We synthesize research showing that brain stimulation techniques, such as repetitive transcranial magnetic stimulation, can be used to target relevant networks. Further, functional connectivity-based individualized targeting may enhance treatment response. We then outline recent approaches to account for neuroanatomical variability and optimize coil positioning to individually maximize target engagement. Overall, the synthesized literature provides support for the utility and feasibility of this translational approach to precision treatment. The proposed roadmap to translate biomarkers of social cognitive impairments to individualized treatment is currently under evaluation in precision-guided trials. Such a translational approach may also be applicable across conditions and generalizable for the development of individualized neurostimulation targeting other behavioral deficits.

Keywords: Biomarkers; Functional connectivity; Machine learning; Schizophrenia spectrum disorders; Social cognition; Transcranial magnetic stimulation.