Schizophrenia is viewed increasingly as a neurodevelopmental (ndev.) disorder. As indications of a ndev. hypothesis are debated premorbid personality and behaviour anomalies, premorbid somatic signs, deviations shown by brain imaging methods, neuropathological findings or also neuropsychological deficits. With regard to these indications we discuss, proceeding from Stevens' contributions to the topic [120], the arguments in favour of and against a ndev. hypothesis. Premorbid personality and behaviour anomalies have to be distinguished from precursor syndromes [prodromes and outpost syndromes -38, 39, 82], preceding the first psychotic episode many years, and, moreover, only a minority of later schizophrenics reveal abnormal premorbid personality traits. Explanations why clinical expression of the disorder is delayed until adult life or at least adolescence, e.g. because relevant developmental milestones must be reached, remain speculative. The findings of neocortical and limbic maldevelopment, e.g. in parahippocampal cortex [86], are hitherto not vet conclusive, though the cumulative evidence of cortical maldevelopment seems to be compelling and the data suggest [130] that neuronal connections and circuits are to some degree anomalous and cortical laminae and regions may be "dysconnected". As an argument for the ndev. hypothesis is claimed that ventricular enlargement is already present at the onset of positive symptoms and does not progress on follow-up. But, if a ndev. disorder would have caused the ventricular enlargement, cranial volume and head size must be decreased, what is not the case in schizophrenia. Furtheron, there are findings of progressive increase in ventricular size and also of gliosis, especially in subcortical and periventricular areas [120]. Anomalies of cerebral asymmetry in schizophrenia, speaking for a ndev. arrest [21], could be found only in some patients; also distinct ndev. brain anomalies as cavum septi pellucidi or dysgenesis of corpus callosum do not occur more frequently than expected in schizophrenia [57]. As to the rate of obstetric complications (O.Cs.) and viral infections as influenza pandemics, sufficiently reliable data are missing; the great majority of schizophrenics have no O.Cs. and it is also controversial. whether patients with O.Cs. show a more chronic form and an earlier onset or if there exists an association of O.Cs. and brain imaging findings. No single abnormality has been found in all schizophrenics, but only in more or less small subgroups, that could not be associated to clinical subgroups hitherto raised. Altogether, the attempts to correlate the brain findings, regarded as expression of an aberrant brain development with clinical subgroups of schizophrenia, were not very successful. This is also valid for ndev. concepts confined to male, early onset or sporadic schizophrenics. Only a distinct psychopathological remission type with the component of an irreversible pure dynamic-cognitive deficiency can be correlated with distinct brain imaging changes [42, 55, 74, 80, 81, 82]. It has been shown [25, 53, 55, 57] that there are associations between brain imaging and psychopathological findings and also between the progression of neuroradiological and psychopathological changes, data confirmed by newer brain imaging techniques. The longterm course with progress to different residual syndromes provides hints that schizophrenia certainly is not a neurodegenerative process in the usual sense, but maybe a special neuroregressive illness in the majority of cases. Data. relevant for this assumption are. that the disorder in 78% shows no full remitting course: that the progression concerns only 5 until 10 years after onset: that chronic defect psychoses can remit still after decades of course to non-psychotic pure deficiency-syndromes. that some cases (15%) can progress even after years and decades of remitting course and, finally, that altogether no correlation exists between the duration of course and outcome [82]. The data prove that schizophrenia cannot be an over the whole lifelong course continuously progressing illness in the sense of a primary neurodegenerative process as M. Alzheimer or M. Pick. but rather a disorder. progressing transiently in brief stages and afterwards coming to a standstill of the process [57. 120]. That schizophrenia is not neurodegenerative in the traditional sense. does not mean that it is a ndev. disorder. This applies only to a small subgroup. while the assumption of a non-ndev. subgroup with an only transitory. in short periods advancing special regressive brain process seems to be plausible. There are analogies in organic brain disorders, e.g. the "premature failure states" [6]. Hence ensues the interpretation of the brain findings in a subgroup of schizophrenia as "premature. locally accentuated involution of advanced age" [114]. The argument that at the time of the first psychotic episode the brain changes had already developed without progressing in the further course, can be refuted by neuropsychiatric observations in brain atrophic processes and the knowledge of the true onset of schizophrenia several years before the first positive symptoms.
