CLINICAL HANDBOOK OF SCHIZOPHRENIA

CHAPTER 5NEUROPATHOLOGYDANIEL G. STEWARTKENNETH L. DAVISSchizophrenia is a brain disease. Regardless of the theoretical stance from which onewants to view the terrain of schizophrenia symptomatology, etiology, and course, thereremains little question that part of that terrain contains alterations to brain structure andbrain function. Although arguments still persist as to the individual contributions of geneticsand environment to the structural and functional pathology present in schizophrenia,our ever-increasing sophistication as a field has led us to begin to embrace the notionthat neuropathology is both causal and resultant—that a neuroanatomical or neurochemicalfinding can be an upstream effect in one instance and a downstream effect in another,even within the same disease. The neuropathological findings and the symptom picturethat emerge then, are the result of a complex interplay of genetic, environmental, andeven stochastic forces that occur over time and within a context. The neuropathologicalfindings in schizophrenia are often subtle, span brain regions and processes, share overlapwith control populations, and are typically difficult to replicate in different samples ofpatients. These findings currently may be best seen in light of the endophenotype model.In other words, several different aberrations of brain structure and function likely convergein the symptom picture we call schizophrenia. And even if we ignore the divergentneuropathological and genetic findings, an examination of the myriad clinical presentationsof the disease certainly suggests that multiple processes may be at work. Theneuropathological data on schizophrenia are pieces of an explanation, awaiting assemblyby what has been proven to be a rather elusive set of principles.Because an exhaustive description of all the findings in the brains of patients withschizophrenia could easily be the topic of a book rather than a chapter, this chapter focuseson the major findings in schizophrenia brain research that are either well replicatedor have particular importance for a basic understanding of schizophrenia. We begin witha brief discussion of the neurodevelopmental model of schizophrenia, then go on to discussglobal and regional findings (summarized in Table 5.1). Other overarching issues arethen examined briefly, including the disconnectivity model of schizophrenia, limitationsof neuropathological investigation (summarized in Table 5.2), and the progressive versusstatic nature of some neuropathological findings.44