Brain structure, genetic liability, and psychotic symptoms in subjects at high risk of developing schizophrenia

Background: Structural magnetic resonance imaging (MRI) of the brain in pat ients with schizophrenia has consistently demonstrated several abnormalitie s. These are thought to be neurodevelopmental in origin, as they have also been described in first episode cases, although there may be a progressive component. It is not known at which point in development these abnormalitie s are evident, nor to what extent they are genetically or environmentally m ediated. Methods: One hundred forty-seven high-risk subjects (with at least two affe cted first or second degree relatives), 34 patients in their first episode, and 36 healthy control subjects received an MRI scan covering the whole br ain. After inhomogeneity correction, regions of interest were traced by thr ee group-blind raters with good inter-rater reliability. Regional brain vol umes were related to measures of genetic liability to schizophrenia and to psychotic symptoms elicited at structured psychiatric interviews. Results: High-risk subjects had statistically significantly reduced mean vo lumes of the left and right amygdalo-hippocampus and thalamus, as compared to healthy control subjects. They also had bilaterally larger amygdalo-hipp ocampi and bilaterally smaller lenticular nuclei than the schizophrenics. H igh-risk subjects with symptoms had smaller brains than those without. The volumes of the prefrontal lobes and the thalamus were the only consistent a ssociates of genetic liability. Conclusions: Subjects at high risk of developing schizophrenia have abnorma lities of brain structure similar to but not identical to those found in sc hizophrenia. Our results suggest that some structural abnormalities are gen etic trait or vulnerability markers, others are environmentally mediated, a nd that the development of symptoms is associated with a third overlapping group of structural changes. Particular risk factors for schizophrenia may interact at discrete time points of neurodevelopment with different effects on specific brain regions and may represent relatively distinct disease pr ocesses.