Abstract
Intermediate endophenotypes emerge as an important concept in the study of schizophrenia. Although research on phenotypes mainly investigated cognitive, metabolic or neurophysiological markers so far, some authors also examined the motor behavior anomalies as a potential trait-marker of the disease. However, no research has investigated social motor coordination despite the possible importance of its anomalies in schizophrenia. The aim of this study was thus to determine whether coordination modifications previously demonstrated in schizophrenia are trait-markers that might be associated with the risk for this pathology. Interpersonal motor coordination in 27 unaffected first-degree relatives of schizophrenia patients and 27 healthy controls was assessed using a hand-held pendulum task to examine the presence of interpersonal coordination impairments in individuals at risk for the disorder. Measures of neurologic soft signs, clinical variables and neurocognitive functions were collected to assess the cognitive and clinical correlates of social coordination impairments in at-risk relatives. After controlling for potential confounding variables, unaffected relatives of schizophrenia patients had impaired intentional interpersonal coordination compared to healthy controls while unintentional interpersonal coordination was preserved. More specifically, in intentional coordination, the unaffected relatives of schizophrenia patients exhibited coordination patterns that had greater variability and in which relatives did not lead the coordination. These results show that unaffected relatives of schizophrenia patients, like the patients themselves, also present deficits in intentional interpersonal coordination. For the first time, these results suggest that intentional interpersonal coordination impairments might be a potential motor intermediate endophenotype of schizophrenia opening new perspectives for early diagnosis.
Highlights
Schizophrenia is a highly heritable condition, with complex genetic susceptibility likely arising from the combined effects of multiple susceptibility alleles of individually weak effect, and environmental factors
The results showed that schizophrenia patients had unimpaired unintentional interpersonal motor coordination (UIMC) but impaired intentional interpersonal motor coordination (IIMC) compared to healthy controls
As integrative modeling of multivariate data from familial, neurobiological, socio-environmental, cognitive, and clinical domains represents a powerful approach to prediction of psychosis development (Shah et al, 2012), our results suggest that IIMC could be used as complementary measure to the existing ones in the early diagnosis of individuals with high risk of developing schizophrenia
Summary
Schizophrenia is a highly heritable condition, with complex genetic susceptibility likely arising from the combined effects of multiple susceptibility alleles of individually weak effect, and environmental factors. This complicates the search for susceptibility genes with traditional linkage approaches (Gottesman and Shields, 1973). An alternative approach is based on the identification of so-called intermediate phenotypes that are detectable both in schizophrenia patients and in a higher proportion of their unaffected relatives than in the population at large (Pearlson and Folley, 2008) The advantage of such intermediate phenotypes stems from their greater penetrance at the level of vulnerability markers, increasing statistical power (Egan et al, 2001). To be useful an intermediate phenotype must be: (1) associated with the illness; (2) heritable to some degree; (3) observed in unaffected family members to a greater extent than the general population, Frontiers in Behavioral Neuroscience www.frontiersin.org
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