A Systematic Review of the Magnetic Resonance Imaging (MRI) Literature Investigating the Deficit Syndrome in Schizophrenia

Abstract Background and Hypotheses Heterogeneity in schizophrenia is significant but remains poorly understood. Treatment strategies have not evolved beyond one-size-fits-all approaches, often delaying the discovery of effective treatments and better outcomes. The deficit syndrome was proposed as a more homogenous subtype of the illness that is characterized by primary and enduring negative symptoms. We reviewed Magnetic Resonance Imaging (MRI) studies examining brain structure, function, and neurometabolism in deficit syndrome with the goal of identifying unique brain signatures for this subtype of schizophrenia. Study Design Systematic Review of MRI studies published between 1999 and 2024 on the deficit syndrome. Study Results Potentially unique features of the deficit syndrome include nucleus accumbens and cerebellar gray matter volume deficits, reduced uncinate fasciculus fractional anisotropy, fronto-parietal and default mode network dysconnectivity, altered global efficiency, and shortest path-length in brain network organization. Further, abnormalities in cerebellar culmen volume and cerebellar spontaneous activation may differ only in degree between patient groups. Many findings warrant replication and must be interpreted with caution. Conclusions The deficit syndrome is hypothesized to be different from other forms of schizophrenia and more homogenous in its pathophysiology. MRI studies examining neurobiological group differences show conflicting results; some report that the deficit syndrome may be distinct, while others find that brain pathology is more severe or shared across subtypes. No MRI studies have directly tested if inter-individual heterogeneity in brain pathology is lower in the deficit syndrome, which would be necessary to determine if this clinically more homogenous subtype is also neurobiologically more homogenous.