Structural brain abnormalities in first episode schizophrenia. Is it just illness?

Abstract

Although neuroimaging studies consistently demonstrated brain volume alterations in patients with schizophrenia, confounding factors like age, IQ, duration of the illness, use of antipsychotic medication and drug (ab-)use might partly explain these results. Therefore, the relation between confounding factors and brain morphology (together with white matter integrity) was investigated in patients with first-episode schizophrenia. To investigate the effects of cannabis (ab-)use on brain morphology, changes in brain volume and cortical thickness were measured over a 5-year interval in 19 cannabis-using first-episode schizophrenia patients, 32 non-using patients, and 31 cannabis-naive healthy subjects. Cannabis-using patients show a more pronounced brain volume reduction (as expressed by a more pronounced grey matter volume loss and increased vericular volume) over a 5-year follow-up as compared to non-using patients and healthy subjects. Moreover, although schizophrenia patients showed widespread cortical thinning along the cerebral cortex, cannabis-using patients showed additional thinning in the left dorsolateral prefrontal cortex, left anterior cingulate cortex and left occipital lobe. Interestingly, these areas are known for their high density of CB1 receptors particularly in schizophrenia patients. These results suggest that in first-episode patients with schizophrenia who continue to use cannabis after illness onset, it is particularly those cortical regions that are rich in CB1 receptors that are vulnerable to excessive cortical thinning. Numerous structural MRI studies and diffusion tensor imaging (DTI) studies have implicated brain tissue abnormalities in schizophrenia. However, the majority of these studies included patient populations that use anti-psychotic medication. To what extent the reported aberrations can be attributed to the disease rather than to the use of medication is still debated. Therefore, global brain volumes and white matter structure were investigated in antipsychotic naive patients. Ia a cross-sectional study, we compared global brain volumes and cortical thickness between 20 first-episode medication-naive schizophrenia patients and 26 healthy comparison subjects. Moreover DTI techniques were used to study white matter structure in a subgroup of the same sample with 16 medication-naive patients as compared to 23 healthy controls. Medication-naive patients showed smaller whole brain volume (as expressed by smaller grey and white matter volume) together with enlarged lateral ventricles. Moreover, a relationship between IQ and brain volume, irrespective of diagnosis, was found. Furthermore white matter microstructure, was altered particularly in the left arcuate fasciculus and the right uncinate fasciculus. These processes took place early in the disease process and cannot be attributed to the effects of antipsychotic medication. Finally, to investigate the relation between progressive brain volume changes and duration of psychosis in patients with schizophrenia, changes in global brain volumes were measured over a 5-year interval in 48 first-episode patients. This study shows that, in the first five years of schizophrenia, brain volume is related to the time patients are actively psychotic with more pronounced brain volume loss associated with longer duration of psychosis. This suggests that the progressive brain volume changes in schizophrenia are intrinsic to the illness and, more specifically, are related to the psychotic aspects of it.