The early findings of Kraepelin and of Bleuler, that many schizophrenic patients will, on detailed examination, show some neurologic abnormalities, have been substantiated by Stevens, Kennard, Hertzig and Birch, Tucker and colleagues, and Woods. They all found a higher frequency of “soft neurologic signs” in schizophrenic patients than they did in a healthy population. The signs to which they refer include impersistence in assigned motor and mental tasks, astereognosis and graphesthesia, sensory extinction, hyperreflexia and hyporeflexia, slight tendency to grasping, mild impairment of coordination and disturbances of balance, abnormal (choreiform) movements, abnormalities of motor activity, adventitious and overflow movements, anisocoria, slight esotropia, and faults in visual auditory integration. Features of this type were noted in 50 percent of patients and correlated with the degree of cognitive disorder. Also evident in about half of schizophrenic patients are subtle defects in ocular tracking movements (Levin et al). These take the form mainly of slowed smooth pursuit and intrusions of saccades during pursuit; some relatives of schizophrenic patients also show these eye signs when carefully tested. In contrast, “hard neurologic signs” (such as unilateral motor or sensory defects) are not seen unless they are the result of an engrafted neurologic disease. Electroencephalographic (EEG) abnormalities have been detected in about one-third of patients, but are generally minor; their meaning is uncertain, especially if they have occurred after long-standing gestational period and birth of schizophrenic patients. Also consistent with an early adverse environmental factor is the observation by several groups that in the northern latitudes, more schizophrenic persons are born in the winter months and to women who were exposed to influenza during midpregnancy—inviting speculation that a viral infection may have damaged the fetal brain. Mortensen and colleagues found that being born in an urban region, particularly in February or March, carried with it a higher risk for developing the disease than having an affected parent or sibling. They suggested that these inexplicable demographic features accounted for more cases than did inheritance. Among 5,362 infants who were followed prospectively since their birth in 1946 by Jones and colleagues, the 30 individuals who later developed schizophrenia had been delayed in the attainment of motor milestones and speech and exhibited greater social withdrawal and schoolroom anxiety as well as lower scholastic achievement. Thus it appears that schizophrenic patients are not entirely normal in early childhood, but whether their abnormalities are already early manifestations of schizophrenia or risk factors for the disease has not been determined.
Neuropathologic, Brain Imaging, and Neurophysiologic Findings
Notably lacking in reports of developmental changes in schizophrenia, are neuropathologic data. Dunlap, in 1928, in a critical analysis, repudiated all earlier interpretations of cellular alterations that had been reported in the brains of schizophrenic patients. He pointed out that many of them, such as dark “sclerotic” nerve cells, were artifacts and that the presence of lipofuscin was a nonspecific age change. He also asserted that the neuronal loss described by Alzheimer was based on impression and could not be corroborated by quantitative methods. Similarly, the claim of Oscar Vogt of neuronal loss in the cortex was rejected by his contemporaries, Spielmeyer and Scholz, who were unable to find any consistent cellular abnormality in schizophrenia. Spielmeyer, in a critical study of the problem in 1930, concluded that such changes as had been described up to that time could not be clearly distinguished from the normal, and that the more marked changes in some cases were due to coincidental causes. Corsellis, on the basis of yet another thorough review of the neuropathologic data in 1976, found no reason to deviate from Spielmeyer’s view. The uncertain neuropathologic findings were responsible for the enigmatic categorization of schizophrenia as a “functional” disorder, that is, a disorder with no structural basis.