IMPLICATIONS OF COMORBIDITY FOR GENETIC-STUDIES OF BIPOLAR DISORDER -P300 AND EYE TRACKING AS BIOLOGICAL MARKERS FOR ILLNESS

In large families with affective illness, identification of a biologic al variable is needed that reflects brain dysfunction at an earlier po int than symptom development. Eye movement disorder, a possible vulner ability marker in schizophrenia, is less clearly associated with affec tive illness, although a subgroup of affective disorders shows smooth- pursuit eye movement disorder. The auditory P300 event-related potenti al may be a useful marker for risk to schizophrenia, but a role in bip olar illness is less certain. The distribution of these two biological variables and their association with symptoms in two multiply affecte d bipolar families is described. In a single, five-generation family i dentified for linkage studies through two bipolar I (BPI) probands, 12 8 members (including 20 spouses) were interviewed. The 108 related ind ividuals had diagnoses of BPI (7), bipolar II (2), cyclothymia (3), or major depressive disorder (19). Eight others had generalised anxiety (1), minor depression (5), intermittent depression (1), or alcoholism (1). Sixty-nine subjects had no psychiatric diagnosis. P300 latency (8 1) and eye tracking (71) were recorded from a subgroup of relatives wi thin the pedigree. Eye tracking was abnormal in 11 of 71 relatives (15 .5%) and was bimodally distributed. In these 11 relatives, clinical di agnoses included minor depression (1), alcoholism (1) and generalised anxiety disorder (1). P300 latency was normally distributed and did no t differ from controls. In a second family in which five of seven sibl ings have BPI illness, P300 latency and eye movement disorder were fou nd in affected relatives and in some unaffected offspring. In these la rge families, clinical diagnoses of general anxiety, alcoholism and mi nor depression, when associated with eye tracking abnormality, may be considered alternative clinical manifestations of the same trait that in other relatives is expressed as bipolar illness.