CLINICAL HANDBOOK OF SCHIZOPHRENIA

5. Neuropathology 45TABLE 5.1. Summary of Major Findings in the Brains of Patients with SchizophreniaRegionGlobalCorticalSubcorticalWhite matterFindings• Decreased brain volume• Increased ventricular volume• Frontal lobe volume reduced, particularly in• Dorsolateral prefrontal cortex• Orbitofrontal and dorsomedial regions• Increased frontal lobe neuronal packing density• Temporal lobe volume reduced, particularly in• Medial temporal lobe• Superior temporal gyrus• Decreased asymmetry of planum temporale• Parietal lobe potentially with volume reduction• Cerebellar findings inconsistent• Thalamic volume decreased• Decreased organization of thalamocortical pathways• Basal ganglia volume increased with typical antipsychotic medication treatment• Basal ganglia volume potentially decreased pretreatment• Oligodendrocyte number reduced in schizophrenia• Coherence of white matter in various brain regions decreased, including• Temporal lobe• Frontal lobe• Corpus callosum• White matter tracts in schizophrenia decreased in organization, including• Thalamocortical tracts• Uncinate fasciculus• Arcuate fasciculus• Cingulum bundleTHE NEURODEVELOPMENTAL MODEL OF SCHIZOPHRENIAThat schizophrenia has a neurodevelopmental component is essentially established. Variousstructural and functional abnormalities that are present at first break—that is, whenan individual has his or her first formal psychotic episode—along with the absence of anygross neurodegenerative markers (i.e., gliosis), have led to the suggestion that at leastsome of the processes that predispose individuals to the disease are prenatal. However,this often accepted position, when considered in light of the evidence, may at best be onlypartially true. For example, the idea that gliosis must be present for there to be aneurodegenerative process taking place is an incomplete notion, probably limited by ourknowledge of pathophysiology at the time of its inception. Several other insults that maybe active and ongoing in the brains of patients who have or will develop schizophrenia,such as excessive pruning, inadequate supply of trophic factors to neurons, or poor functioningor even death of oligodendrocytes, could cause the loss of neurons over time withoutnecessarily causing gliosis. Furthermore, any of these types of insults could predatethe illness, yet not occur during intrauterine life. So the question becomes, what exactly ismeant by the term neurodevelopmental? If one intends to suggest that this requires anintrauterine event, then this conclusion remains somewhat speculative. If however, onemeans a process that involves any aberration in the typical pattern of brain development,including not only neuronal development but also glial development (not to mention thehitherto unknown factors that regulate the timing of specific developmental milestones in