Searching for endophenotypes: negative symptoms and schizophrenia

Schizophrenia is a disorder affecting millions of individuals, with a prevalence rate over one percent. Although the diagnosis of schizophrenia has a high heritability, identification of individual risk variants has been difficult, due to their small individual effects on the diagnosis. Identification of useful endophenotypes - that is, features more sensitive to genetic effects than the diagnosis itself - should aid in detecting genetic variants that contribute to the disorder. The current study examined negative symptoms as a possible endophenotype for schizophrenia. Specifically, the study examined the genetic correlations between the Scale for the Assessment of Negative Symptoms (SANS) and schizophrenia among multigenerational, multiplex schizophrenia families. To examine diagnostic specificity, major depressive disorder and substance abuse were also tested for genetic correlations with negative symptoms. The total sample (493) included 43 families, 90 schizophrenia patients, 359 of their relatives, and 44 controls. The majority of SANS scales were significantly heritable (average h2 = 0.48). Results suggested that even among relatives without any diagnoses, the prevalence of negative symptoms increased significantly with the degree of genetic relationship to schizophrenia (average RG = 0.76) but not depression or substance abuse. This suggests the potential utility of negative symptoms as a candidate endophenotype with some diagnostic specificity in studies seeking to identify genetic risk variants contributing to schizophrenia