Neurocognitive impairment was found to be heritable in individuals with schizophrenia
and their relatives. However, the heritability of neurocognitive measures in families
with and without schizophrenia has not been directly compared. In this study, we examined
the genetic structure of clinical and neurocognitive measures in sibling pairs with
and without schizophrenia to test the hypothesis that the familial aggregation of
such measures may be altered by having schizophrenia.
A total of 278 subjects including patients with schizophrenia and their non-psychotic
full siblings, healthy controls, and their full siblings were recruited. Heritability
was estimated for working memory, episodic memory, executive function and attention,
as well as clinical features, such as positive, negative and disorganization symptoms.
Many clinical and cognitive domains were impaired in subjects with schizophrenia and
their non psychotic siblings. Negative symptoms, working memory, episodic memory and
executive function, but not positive, disorganization symptoms and attention, were
found to be significantly heritable in all sibling pairs. However, the heritability
of working memory function was significantly (chi(2)((d.f.=6))=13.9, p=.031) decreased
in proband sibling pairs (h(2)=.38) as compared to control sibling pairs (h(2)=.95).
Significant genetic correlations were observed between negative symptoms and the cluster
of working memory, episodic memory and executive function.
Several neurocognitive measures were heritable in sibling pairs with and without schizophrenia.
However, schizophrenia reduced the heritability of working memory, perhaps due to
disease-related environmental or genetic factors. Evidence for potential pleiotropy
will inform future phenotypic studies.