Nevertheless, there has been a general sense that while the number of neurons in the gray matter is normal, the pyramidal cells are smaller and more densely packed, resulting in a thinning of laminae II and III. These cytoarchitectonic changes have been the most difficult to interpret and to confirm. Capricious methods such as the rapid Golgi stain indicate that density of dendritic spines is decreased in the frontal and temporal cortex of chronic schizophrenic patients.
A number of more contemporary reports using special cell-labeling studies have found cytoarchitectonic abnormalities in the brains of schizophrenic patients. For example, Akbarian and colleagues, following previous similar findings, have described an aberrant distribution of interstitial neurons in the frontal lobe white matter. These cells have their origin in the embryologic subplate that guides neuronal migration, and the inference is that the abnormally migrating cells have formed aberrant neuronal connections. Benes and colleagues observed that the number of small neurons was reduced in at least 1 layer (usually layer II) of the anterior cingulate cortex. These are gamma-aminobutyric acid (GABA)–releasing (inhibitory) neurons. Benes and colleagues also noted that the arrays of macrocolumns of cortical neurons were smaller in the occipital lobes (vertical axons increased in number). Newer studies also describe a paucity of gabanergic, inhibitory interneurons (so-called chandelier cells) in the prefrontal cortex (Woo et al). These observations suggest a developmental rather than an acquired lesion. The absence of gliosis supports but does not prove that the developmental disorder occurs prenatally.
The advent of CT and subsequently of MRI of the brain provided a new stimulus to the anatomic study of schizophrenia. Johnstone and coworkers were the first to describe ventricular enlargement and sulcal widening in 18 patients and correlate these findings with dulling of intellect and affect. In a study of 58 chronic schizophrenics younger than age 50 years, Weinberger and colleagues (1979) found enlargement of the lateral ventricles in 40 percent. In 9 of 11 CT studies, the third ventricle was found to be enlarged, and in 14 of 17 the sulci were widened. In 15 pairs of monozygotic twins, one of whom had schizophrenia, the anterior hippocampi were found to be smaller and the lateral and third ventricles larger in the affected twin (Suddath et al). Shenton and colleagues demonstrated a reduction in the volume of gray matter in the posterior part of the left superior temporal gyrus, which includes Heschl gyri and the planum temporale. The degree of volumetric reduction correlated roughly with the severity of the thought disorder. A reduction in volume of the superior temporal gyrus has also been associated with the occurrence of auditory hallucinations (Barta et al). Other MRI studies have shown a volumetric change in the gray matter of the left hippocampus, parahippocampal gyrus, and amygdala (in right-handed patients). Equally compelling is the finding that young individuals having 2 or more relatives with the disease, and therefore being at risk for developing schizophrenia, have certain volumetric brain changes detected by imaging studies (Lawrie et al). In unaffected relatives, the left hippocampal–amygdaloid region was smaller than in healthy people, but slightly larger than in affected relatives.