Schizophrenia is a brain disorder presenting with a wide range of symptoms affecting everyday life. Genetic factors are known to confer risk to schizophrenia, as well as many aspects of mental health and brain structure. However, we do not know why some patients show prominent reality distortion while others suffer more from losing motivation and pleasure in life. In this study, we ask how genetic factors relate to the interindividual differences in symptom manifestation in schizophrenia (or “clinical heterogeneity”). We propose to investigate this clinical heterogeneity using 1) genomic data and symptom ratings from patients, and 2) genomic data, brain image, and mental-health questionnaire from the general population in the UK Biobank. We have previously collected genomic data and symptom ratings in over 2,000 patients in Taiwan, which hinted on genomic factors that may relate to symptom dimensions. The enormous scale of the UK Biobank can help us elucidate how these genetic factors may contribute to brain features and mental-health traits in the general population. The findings of this study will be useful for researchers to better understand the biological basis of clinical heterogeneity in schizophrenia. Existing medicine for schizophrenia is more effective in treating positive symptoms (such as hallucinations and delusions) than negative symptoms (such as lack of motivation and pleasure). The findings of this research will also bring researchers one step closer to developing future drugs aimed at addressing the difficult-to-treat symptoms that persist in patients’ everyday lives.
