CLINICAL HANDBOOK OF SCHIZOPHRENIA

46 I. CORE SCIENCE AND BACKGROUND INFORMATIONTABLE 5.2. Limitations on Neuropathological InvestigationLimitation Affects postmortem studies Affects imaging studiesPostmortem index + –Variations in sample selection or+ +delineation of region of interestDiffering methodologies for analysis + +Small sample sizes + +brain development across the lifespan), then little doubt exists that schizophrenia is atleast partly neurodevelopmental.Decreased Brain VolumeGLOBAL BRAIN FINDINGSEarly research into brain volumes in schizophrenia, at least partially driven by theoriesthat brain volume was related to mental illness, cognitive deficits, and low socioeconomicstatus, reach as far back as the early 1800s. Using postmortem tissue, the brains of patientswith schizophrenia have been found to be reduced in length, volume, and weight.In imaging studies, schizophrenia has been found to be associated with reduced globalbrain volumes; however, the majority of studies have not found significant differences betweenpatients with schizophrenia and controls. There are several explanations for thesediscrepant findings, and it is likely that each plays a part in this inconsistency. First,global brain volume is a somewhat imprecise and gross measure in and of itself. Second,controlling for brain size differences related to variations in head size rather than toschizophrenia is difficult to do. Third, sample sizes in schizophrenia studies are typicallysmall, and the volume changes themselves are likely to be small, thus increasing the likelihoodthat subtle brain volume differences will be missed. Fourth, many of these studiesdid not separate patients by differences in symptom severity, age, or disease course, and itis possible, if not likely, that patients whose disease has a particularly severe progressionwould have more profound brain changes than those who have a relatively good outcome.When these heterogeneous groups are examined together, those with good outcome—who might have less brain pathology—may wash out the findings that would be seen ifpatients with poor outcome were examined separately. Last, and perhaps most important,schizophrenia may be better characterized as a disorder with regional aberrations. Itis important to note that few diseases that have a profound effect on global brain volumeare not only consistent with life but also allow those afflicted to function in society. Eventhough the schizophrenia symptom picture is devastating and debilitating, one must keepin mind that these changes are subtle in the grand scheme of self-maintenance and selfpreservation;consequently, they might be better explained by regional neuropathology ordysconnectivity (both discussed below). All this having been said, meta-analyses havedemonstrated small but significant reductions in total brain volume in schizophrenia.Ventricular EnlargementThere is enlargement of the ventricles in schizophrenia. Data come from both imagingand postmortem investigations. Areas typically noted to be enlarged in patients with