Anatomy of Schizophrenia Revisited

Abstract

The search for an anatomy of schizophrenia has engendered an enormous, almost indigestible mass of data. In no studies do all patients show the same deviations from control samples. No morphological or microscopic abnormality has been found that is either necessary or sufficient for the diagnosis. In contrast to epilepsy, in which a proliferation of excitatory pathways or inadequate inhibitory factors are paramount, schizophrenia may represent a genetically and age-determined elaboration of one or more inhibitory networks in response to specific physiological events (e.g., the increased neuronal activity in limbic and hypothalamic structures during the physiological events of puberty) or to brain injury or defect. Current diagnostic classifications, including the positive-negative categories, have not led to separation of the disorder into etiologically or pathologically similar subgroups. Analysis of morphological and other biological pathology by a different nosological principle, such as trajectory of the illness, and separate correlation of anatomical and other biological outliers with clinical and demographic factors may be more successful strategies than pooling and averaging results from a mixture of patients diagnosed with schizophrenia.

Schizophrenia and viral infection during neurodevelopment: a focus on mechanisms

“…These paradigms should be designed with the recognition that schizophrenia is a heterogeneous disease, and clinical subtypes of the disease may be reflections of sub-mechanisms of pathogenesis. [49][50][51][52] The first step in refining these paradigms of pathogenesis is to ask what type of data can be reasonably expected if viruses are involved in the etiology of schizophrenia. The human host is constantly confronted with emerging and undefined viral pathogens.…”

Neurodevelopmental risk factors in schizophrenia

“…Although most prospective studies that have looked for neurodevelopmental abnormalities in schizophrenia before diagnosis report negative results, some did detect subtle behavior and intellectual abnormalities as possible predictors of risk for the development of schizophrenia (4). These findings, however, are inconsistent, raising doubts about the neurodevelopmental theory (3,4).…”

“…A possible explanation is the occurrence of some maturational processes throughout adolescence that modulate psychosis (2). It is known that the human brain reaches approximately adult size during the early school years, and that this growth seems to be affected by the increase of gray matter volume as opposed to white matter volume (2,3,5). It is also known that the fine tuning of neuronal connections and the selective reduction of cerebral structures occurs during early cerebral maturation.…”

“…An important issue for the neurodevelopmental theory is the failure of major early studies to detect gliosis (considering gliosis as the evidence of a brain reaction to afterbirth insults, producing glial scars) (3). Cerebral abnormalities in the absence of gliosis may probably indicate abnormalities of fetal cerebral development instead of neurodegeneration (3).…”

“…Cerebral abnormalities in the absence of gliosis may probably indicate abnormalities of fetal cerebral development instead of neurodegeneration (3). Some neuropathological studies have failed to detect evidence of gliosis (1), but others have described it in subcortical and periventricular areas.…”