Are neurologic examination abnormalities heritable? A preliminary study

Background: Neurologic examination abnormalities (NEA) are more prevalent among patients with schizophrenia as well as their unaffected relatives when compared with healthy controls, suggesting that NEA may be endophenotypes for schizophrenia. We estimated the heritability of NEA in moderately sized pedigrees. We also evaluated correlations between NEA and cognitive performance in order to examine their construct validity. Methods: Members of eight extended families, each consisting of two first degree relatives with schizophrenia/schizoaffective disorders, as well as available first- to fifth-degree relatives were examined (n = 96 participants). A modification of the Neurological Evaluation Scale (NES) was employed, augmented with localizing signs. Where feasible, we used untransformed data such as error counts and completion time, rather than ordinal measures. Heritability was estimated using the variance component method, implemented in SOLAR. Results: Statistically significant heritability (h²) estimates were obtained for several measures (p < 0.05, h² ± standard error: rapid alternating movements, right-sided completion time, 0.99 ± 0.19; alternating fist-palm test, completion time, 0.77 ± 0.19 s, errors, 0.70 ± 0.32; fist-ring test, right-sided completion time, 0.53 ± 0.23 s, left-sided completion time, 0.70 ± 0.21 s; go-no go task, correct responses, 0.93 ± 0.33; audio-visual integration, correct responses, 0.79 ± 0.54). For most items, heritability analysis was hampered by insufficient data variability (infrequent errors). Correlational analyses show some degree of divergence among types of NEA, repetitive motor tasks being associated with most domains of cognitive functioning other than executive functioning, and cognitive-perceptual tasks being associated with memory and executive functioning. Conclusions: Significant familial influences on certain aspects of neurologic performance were detected. These heritable measures were also correlated with heritable neurocognitive measures.