Running in the family? : structural brain abnormalities in first-degree relatives of patients with schizophrenia

Abstract

The studies conducted in this thesis explored brain structures in first-degree relatives of patients with schizophrenia. The meta-analysis that Boos and colleagues performed showed that relatives of patients with schizophrenia had smaller hippocampal volumes, smaller gray matter volumes and larger third ventricle volumes compared to controls. These volumetric differences are similar to the areas that are affected in patients with schizophrenia and parallel findings of neuropsychological impairments. Boos suggested that this finding may reflect a vulnerability to develop schizophrenia but that it is still unclear how and to what extent genetic and/or environmental influences are involved. In a large cross-sectional MRI study Boos and colleagues examined brain structures in patients with schizophrenia, their non-psychotic siblings and controls, using global and focal brain measurements. Global brain volumes of non-psychotic siblings were not different from those of controls, nor did siblings differ in cortical thickness or gray matter density, using a voxel-based morphometry approach. Their findings were consistent with those from another large sibling sample, but contrast with those of smaller imaging studies. Boos suggested that the structural brain abnormalities observed in patients are (for the largest part) explained by disease-related factors. Boos further examined mean fractional anisotropy (FA) in multiple white matter tracts in patients with schizophrenia, their non-psychotic siblings and controls using tract-based analysis. This was the first tract-based study in siblings of patients with schizophrenia. Mean FA was higher in the left and right arcuate fasciculus for siblings compared to patients and controls, but no differences were found in mean FA for other WM tracts. They suggested that an increased familial risk for schizophrenia may be associated with higher FA for the arcuate fasciculus bilaterally. They found a decrease in FA with increasing age in patients compared to siblings and controls, suggesting a possible progressive loss of WM microstructure over time in schizophrenia. In their final study, Boos and colleagues examined brain structures in both the healthy parents of patients with schizophrenia compared to control couples, in relation to cognitive function. The association between brain measures and cognitive measures of psychomotor function, verbal memory and IQ were investigated. Parents of patients showed smaller total brain volumes as compared to control couples, but no differences were found for other global volumes or gray matter density. In the total sample, total brain volume was associated with faster performance on the motor task. The findings in the parents of patients mirror (to a lesser extent) the decrease of brain volume that has consistently been reported in patients with this illness. Together, the studies of Boos and colleagues show that indeed there are structural brain abnormalities in the first-degree relatives of patients with schizophrenia. However, using multiple brain imaging measurements, Boos and colleagues have not found brain differences in the non-psychotic siblings compared to healthy controls. There is evidence that genes play an important role in the development of schizophrenia and that siblings of patients with schizophrenia are at high risk to developing this illness. However, Boos and colleagues do not clearly suggest that structural brain abnormalities are present in this group at risk for schizophrenia. It remains to be elucidated to what extent genetic and/or environmental influences are involved in the cause of brain abnormalities in schizophreni