COMT and bipolar disorder: Our findings of a detrimental effect of high proline in combination with the COMT Met allele, on schizophrenia and bipolar disorder negative symptoms, is in part supported by studies of 22q11DS patients, who have an increased risk of psychosis (albeit exhibiting positive symptoms20) plus a neurophysiological visual sensory deficit,28 when carrying the Met allele in the presence of high proline.