Effect of illness expression and liability on familial associations of clinical and subclinical psychosis phenotypes

Given the familial influences on schizophrenia, it may be hypothesized that specific symptom domains also cluster within families, and that this applies to both clinical and subclinical levels of expression. This hypothesis was put to the test in a group of patients with a DSM-IV diagnosis of psychotic disorder together with their unaffected siblings, and a group of healthy sib-pairs. Subclinical positive, negative and depressive symptoms in relatives and healthy controls were assessed with the Community Assessment of Psychic Experiences (CAPE). Positive and negative schizotypy in relatives and controls was measured with the Structured Interview for Schizotypy-Revised. Multilevel linear regression analyses were conducted to investigate clustering of symptom dimensions within patient-relative sib-pairs (N = 811 pairs), healthy sib-pairs of affected families (N = 136 pairs) and healthy control sib-pairs (N = 58 pairs). Familial clustering of symptoms was found in all three groups. Effect sizes were largest in healthy control sib-pairs, smallest in patient-relative sib-pairs and intermediate in healthy sib-pairs of affected families. Studies of sibling associations in genetic studies of psychometric expression of psychosis liability need to take into account the fact that the higher levels of background genetic risk and presence of diagnosed illness are inversely associated with sibling associations