Anatomy of schizophrenia revisited

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.