Heritability of Trail Making Test performance in multiplex schizophrenia families: implications for the search for an endophenotype

The impairment of the Trail Making Test (TMT) performance as a measure of executive function deficits has been found both in patients with schizophrenia and in their unaffected first-degree relatives, suggesting that it might be considered as a familial vulnerability marker, but its heritability estimates are not well known. This study investigated the genetic heritability of impairments in TMT performance using a sample of 80 schizophrenia patients, 145 unaffected first-degree relatives and 127 healthy controls from families with multiple members with schizophrenia. Consistent with previous reports in the literature, relatives performed in between healthy controls and schizophrenia patients. Based on these results, a variance component-analysis provided small, but significant additive heritability estimates for performance indices relating performance in TMT-version A to TMT-version B. These results showed that this significant but small evidence of heritability on the one hand suggests an association with genetic predisposition to schizophrenia, but that TMT performance is also associated with epigenetic or environmental factors.