Background: We present a case-control study of single nucleotide polymorphisms of NTNG1 in affective Psychosis. In this paper we examine the occurrence of this isoform variation in cases of psychotic mania compared to a population with nonpsychotic bipolar disorder. Our previous work found NTNG1 variations to be more common among subjects with schizophrenia than in healthy controls. Our current study detected a significant increase in this genetic variation (p < 0.001) for psychosis in a group that excluded subjects with schizophrenia. This new study is further confirmation of the association between netrin anomalies and severe neuropsychiatric illness. It also supports the hypothesis that there is a genetic contribution to psychosis that is not unique to the syndrome of schizophrenia.