The relationship between genetic loading for schizophrenia, sustained attention deficits, schizotypy, and handedness
Date Issued
2007
Date
2007
Author(s)
Tsuang, Hui-Chun
DOI
en-US
Abstract
Three studies were conducted to investigate the relationship between sustained attention deficits, genetic loading for schizophrenia, schizotypy, and handedness in non-psychotic first-degree relatives of schizophrenic patients.
Study 1. More severe sustained attention deficits in nonpsychotic siblings of multiplex schizophrenia families than in those of simplex ones
Sustained attention deficits measured by the Continuous Performance Test (CPT) have been proposed as an endophenotype of schizophrenia. However, little is known about whether sustained attention deficits in first-degree relatives of schizophrenic patients are associated with familial loading for schizophrenia. We examined 107 parents and 84 siblings of simplex schizophrenia families as well as 72 parents and 56 siblings of multiplex schizophrenia families, all nonpsychotic, using the Diagnostic Interview for Genetic Studies and two sessions of the CPT (undegraded and degraded). The effect of perceptual load was assessed using the residual of the regression of the degraded score on the undegraded one. Statistical models that can adjust for familial correlations were used to compare the CPT performance of relatives between the two types of families. Siblings from multiplex families exhibited worse performance on the degraded CPT and less proficiency in processing the perceptual load than those from simplex families. No such difference was observed for the parents on either CPT version. We concluded that sustained attention along with perceptual load processing is more impaired in the siblings of schizophrenic patients with high familial loading and that this finding might be useful for future genetic dissection of schizophrenia.
Study 2. The Multidimensionality of Schizotypy in Nonpsychotic Relatives of Patients with Schizophrenia and Its Relations with Sustained Attention
Objective. To examine the multidimensionality of schizotypy in relatives from families with different genetic loading and to validate the structure using sustained attention deficits measured by the Continuous Performance Test (CPT).
Method. A total of 203 and 1,310 nonpsychotic first-degree relatives from simplex and multiplex schizophrenia families, respectively, were interviewed with the Diagnostic Interview for Genetic Studies, which contains a section of the modified Structured Interview for Schizotypy, and completed two sessions on the CPT. Both exploratory and confirmatory factor analyses were performed using the Mplus program with categorical factor indicators. The relationship between sustained attention performance and schizotypal factors was assessed by means of linear mixed effect regression analysis to adjust for within-family correlation.
Results. A four-factor model, containing Negative Schizotypy, Positive Schizotypy, Interpersonal Sensitivity, and Social Isolation/Introversion, was extracted by exploratory factor analysis from relatives of simplex families and the results of confirmatory factor analysis in relatives of multiplex families indicated a good fit. Among the four factors, only the Negative Schizotypy factor consistently discriminated relatives of the simplex families from those of the multiplex ones. The four factors further displayed differential relations to performance indexes on the CPT, with Positive Schizotypy and Interpersonal Sensitivity positively associated with false alarm rate, whereas Negative Schizotypy and Social Isolation/Introversion inversely associated with hit rate and sensitivity.
Conclusions. A consistent four-factor model of schizotypy could be derived in non-psychotic relatives across families of different genetic loadings, and their differential relations to CPT indexes have etiological implications.
Study 3. Handedness and schizotypy in nonpsychotic first-degree relatives of schizophrenic patient
Convincing evidence showed excess of non-right handedness in schizophrenic patients. However, existing studies have found the relationship between handedness and schizotypy to be inconsistent and were limited regarding to generalization since only highly homogeneous groups have been investigated. This study examined the relation between handedness and the four schizotypal factors identified in a previous confirmatory factor analysis in 850 parents and 334 siblings of schizophrenic patients. All participants were interviewed with the Diagnostic Interview for Genetic Studies, which contains a section of the modified Structured Interview for Schizotypy, and the 12-item Annett handedness questionnaire. Both categorical and continuous indicators for handedness were examined. Non-right handed siblings of schizophrenic patients displayed more positive schizotypal features than their right handed counterparts when the two-way Annett’s handedness classification was adopted. No association was found when handedness was treated as continuous or when the Briggs-Nebes’ classification was used. The relationship between handedness and schizotypy was insignificant for parents probably due to the strong social pressure against left-handedness in that generation. In conclusion, the relationship between handedness and positive schizotypy has been confirmed in siblings of schizophrenic patients. Additionally, the study highlights the importance of taking into account the effect of handedness indicators on relating studies. Whether categorical or continuous approach of handedness better identify people with high positive schizotypy warrants further investigation.
Subjects
精神分裂症
持續注意力缺失
連續性表現測驗
內在表現型
遺傳負荷
精神分裂性人格特質
慣用手側
Schizophrenia
Sustained attention deficits
Continuous Performance Test (CPT)
Endophenotypes
Genetic loading
Schizotypy
Handedness
Type
thesis
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