Age effects on cerebral grey matter and their associations with psychopathology, cognition and treatment response in previously untreated schizophrenia patients

The diagnosis of schizophrenia lacks a broadly accepted biological basis and its heterogeneity may well represent a group of disorders with different etiologies. Even so, brain imaging can map and quantify structural brain abnormalities in vivo as an intermediate (or endo-) phenotype of the disorder. Brain structural abnormalities occur in the prodromal phase and progress in the course of illness, and patterns of grey matter deficits appear to determine the clinical phenotype, thus addressing some of the diagnostic heterogeneity. Here we examined cerebral grey matter with cortical pattern matching in MRI scans from 18 previously untreated patients meeting DSM-IV diagnostic criteria for schizophrenia by employing a three-dimensional spoiled gradient recalled (SPGR) pulse sequence at 1.5 T. Data were compared to 18 pair-wise age and sex-matched healthy volunteers from the patient communities. We found widespread cerebral grey matter deficits in schizophrenia. Grey matter deficits in the right dorsolateral prefrontal cortex were the strongest predictor of diagnosis. Symptom severity and treatment response were associated with regional grey matter deficits in older patients with a longer history of untreated illness, while significant structure/function associations with cognitive impairment in prefrontal and temporal cortices were found across all ages. Quantitative brain maps are useful for assessing disease burden in schizophrenia, and for understanding its heterogeneity, including its changing clinical characteristics as the illness progresses