Differential Targeting of the CA1 Subfield of the Hippocampal Formation by Schizophrenia and Related Psychotic Disorders

Abstract

The frontal cortex, basal ganglia, amygdala, and hippocampal formation—all brain areas implicated in schizophrenia¹—are subdivided into functionally distinct subregions (Figure 1). Each subregion is unique in its molecular expression profile² so that select regions are differentially vulnerable to mechanisms of disease.³ Nevertheless, pinpointing regions differentially targeted by schizophrenia is difficult. By the time patients are clinically diagnosed with schizophrenia, multiple brain sites are affected,⁴ making the task of dissociating primary from secondary sites of dysfunction challenging. Further confounding the problem is the absence of pathognomonic histological markers or florid neurodegeneration.⁴ Thus, because schizophrenia is primarily a disease of neuronal dysfunction, not neuronal cell death, cross-sectional comparisons of postmortem samples do not necessarily reveal patterns of anatomical progression.