How does personality affect mental illness? Investigations into the Cloninger personality model as a predictor and factor in mental illness have found that significant relationships exist. The relationship between personality and symptoms of depression in a sample of depressed patients before and after treatment is investigated. Utilising the modern brain imaging technique of SPECT the relationship between brain function and personality types in normal males is studied. Independent component analysis and confirmatory factor analysis are used to investigate new component variables that reduce the data dimensionality and describe response to depression treatment. Two symptom components are found that significantly predict depression outcome. Significant linear and non-linear relationships are found between personality and depression symptoms both before and after treatment using general additive models. As part of the study, gender differences in personality and symptoms of depression are investigated, using multigroup analysis, leading to a combined symptom structure before treatment. Personality is found to significantly correlate with specific brain regions. In particular the personality trait cooperativeness has significant relationships with brain function in a large number of regions. These results support previous work showing a biological basis for the Cloninger personality model. Overall the character personality traits appear important in both the relationship with depression symptoms and in the relationship with brain function in normal males. This study has relevance to future randomised clinical trials to assess optimal treatment for depression.