Brain changes associated with negative symptoms in clinical high risk for psychosis: A systematic review

•Negative symptoms of schizophrenia often occur early in those at clinical high risk.•The biological basis of negative symptoms are poorly understood in those at risk.•Some evidence for inverse relationship between negative symptoms and grey matter.•Negative symptoms are associated with changes in reward response in those at risk.•Greater consistency in clinical and neuroimaging methods would clarify relationship. The negative symptoms of schizophrenia are linked to poorer functional outcomes and decreases in quality of life, and are often the first to develop in individuals who are at clinical high risk (CHR) for psychosis. However, the accompanying neurobiological changes are poorly understood. Therefore, we conducted a systematic review of the studies that have examined the brain metrics associated with negative symptoms in those at CHR. Electronic databases were searched from inception to August 2019. Studies were selected if they mentioned negative symptoms in youth at CHR for psychosis, and brain imaging. Of 261 citations, 43 studies with 2144 CHR participants met inclusion criteria. Too few studies were focused on the same brain regions using similar neuroimaging methods to perform a meta-analysis, however, the results of this systematic review suggest a relationship between negative symptom increases and decreases in grey matter. The paucity of studies linking changes in brain structure and function with negative symptoms in those at CHR suggests that future work should focus on examining these relationships.