Official announcement: Disputas: Kjetil Nordbø Jørgensen
Thesis summary
Structural magnetic resonance imaging (MRI) studies have demonstrated global and regional brain structure alterations in severe mental disorders. These are often assumed to reflect illness pathophysiology, but awareness of potential confounders has increased. The aim of the thesis was to examine the influence of cigarette smoking, antipsychotic medication, and weight gain (a common side effect), and to examine a novel MRI measure, the cortical gray/white matter intensity contrast.
The studies were based on two independent clinical cohorts from the TOP project (University of Oslo, Norway) and the HUBIN project (Karolinska Institutet, Stockholm, Sweden), respectively. Patients with schizophrenia, other psychotic disorders, and bipolar disorders as well as healthy control subjects were examined with clinical interviews and 1.5T MRI of the brain. T1-weighted images were processed using FreeSurfer and FSL. Statistical analyses were performed using linear models.
Cigarette smoking was associated with thinner cortex in the left cingulum and insula among patients; but not among healthy controls. Patients with schizophrenia using antipsychotic medications long-term, with the exception of clozapine, showed increased basal ganglia volumes. In first episode psychosis (FEP) patients, higher medication dosage was associated with greater brain volume reductions over one year; weight change did not explain this. Increased gray/white matter intensity contrast was found in sensory and motor regions of the cortex in schizophrenia.
Future studies of brain structure in severe mental disorders should consider these variables as potential confounders. Causality could, however, not be determined, and effects of antipsychotic dosage on brain volume change should be interpreted cautiously, as illness severity is an alternative explanation. Altered gray/white matter contrast could reflect cortical myelination and should be further examined in psychotic disorders.