Brain imaging studies showed that total brain volume, especially prefrontal and temporal brain volume, was significantly reduced in patients with first-episode schizophrenia compared to healthy subjects with normal brain volume. The above findings further corroborate the hypothesis that structural brain abnormalities are part of the pathogenesis of schizophrenia. However, when do brain abnormalities begin to occur in schizophrenia patients? And how do these abnormalities progress? This is not yet clear. A recent study from Scotland may help us answer some of these questions. This study shows that the total brain volume, as well as prefrontal and temporal lobe volumes, have decreased in schizophrenia patients years before their first episode, with significant reductions in prefrontal volume. The new study, known as the Edinburgh High Risk Study, included 162 subjects at high genetic risk of schizophrenia (the study group) and 36 subjects without risk factors for schizophrenia (the control group), according to Professor McIntosh (Department of Psychiatry, University of Edinburgh) and his colleagues. All subjects had at least 2 cases of first- or second-degree schizophrenia within their families and were aged 16 to 25 years. The socio-demographic characteristics of the control group were consistent with the study group, but there was no family history of psychiatric disorders. All subjects underwent clinical and psychological assessments as well as structural MRI brain scans. The study was a 10-year follow-up study, with subjects assessed at follow-up every 2 years. Of the 162 subjects at high genetic risk for schizophrenia, 17 developed schizophrenia during the follow-up period. There were no subjects in the control group who developed schizophrenia. Brain scans were performed on control subjects, those at high genetic risk of developing schizophrenia, and those at high genetic risk of not developing schizophrenia, respectively. The total brain volume and prefrontal volume were significantly reduced in those at high genetic risk of developing schizophrenia and those who did not develop schizophrenia compared to controls, and the prefrontal lobe was significantly reduced in those who developed schizophrenia during follow-up compared to those who did not develop schizophrenia (P<0.05). At the same time, there was a significant increase in the number of hallucinations and delusions and a significant decrease in prefrontal and temporal lobe volume among those at high genetic risk of developing schizophrenia. In conclusion, the researchers concluded that this study shows that the neurological development of patients at high genetic risk for schizophrenia is significantly different from that of healthy subjects, that specific, longitudinal changes are present in the brains of these subjects for several years prior to definitive diagnosis, and that clinical symptoms are more severe in this population and eventually lead to the development of schizophrenia.