Familiality of symptom dimensions in schizophrenia.
ABSTRACT The division of schizophrenic symptoms into three core dimensions - psychomotor poverty, reality distortion, and disorganisation - is well established. When factor analytic studies have included affective symptoms they have identified two additional dimensions - manic and depressive. Whether these five dimensions represent underlying psychopathology of a genetic or environmental aetiology remains unclear. The aims of this study were to perform factor analysis of symptoms in a group of familial schizophrenic patients and to investigate the familiality of the symptom dimensions identified, and their relationship to clinical characteristics. Symptoms were recorded, using the Operational Criteria Checklist for Psychotic Illness, for 155 Caucasian subjects with an RDC diagnosis of schizophrenia, schizoaffective disorder, or psychosis of unknown origin, from 61 families multiply affected with schizophrenia. Factor analysis indicated five symptom dimensions: depressive, manic, reality distortion, disorganisation, and psychomotor poverty. The psychomotor poverty, disorganisation, and manic dimensions were shown to be familial. Psychomotor poverty, disorganisation, and reality distortion were all associated with deterioration from premorbid functioning and chronic course of the disorder. In addition, psychomotor poverty was significantly related to poor premorbid functioning, as well as to single marital status and unemployment at onset. Disorganisation was significantly related to single marital status and unemployment at onset. The familiality of the psychomotor poverty, disorganisation, and manic dimensions supports their use in the delineation of homogeneous subsets for genetic studies.
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ABSTRACT: The power of SNP association studies to detect valid relationships with clinical phenotypes in schizophrenia is largely limited by the number of SNPs selected and non-specificity of phenotypes. To address this, we first assessed performance on two visual perceptual organization tasks designed to avoid many generalized deficit confounds, Kanizsa shape perception and contour integration, in a schizophrenia patient sample. Then, to reduce the total number of candidate SNPs analyzed in association with perceptual organization phenotypes, we employed a two-stage strategy: first a priori SNPs from three candidate genes were selected (GAD1, NRG1 and DTNBP1); then a Hierarchical Classes Analysis (HICLAS) was performed to reduce the total number of SNPs, based on statistically related SNP clusters. HICLAS reduced the total number of candidate SNPs for subsequent phenotype association analyses from 6 to 3. MANCOVAs indicated that rs10503929 and rs1978340 were associated with the Kanizsa shape perception filling in metric but not the global shape detection metric. rs10503929 was also associated with altered contour integration performance. SNPs not selected by the HICLAS model were unrelated to perceptual phenotype indices. While the contribution of candidate SNPs to perceptual impairments requires further clarification, this study reports the first application of HICLAS as a hypothesis-independent mathematical method for SNP data reduction. HICLAS may be useful for future larger scale genotype-phenotype association studies.04/2015; 8. DOI:10.1016/j.scog.2015.03.003
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ABSTRACT: Given that schizophrenia is a heterogeneous disorder, the analysis of clinical characteristics could help to identify homogeneous phenotypes that may be of relevance in genetic studies. Linkage and association studies have suggested that a locus predisposing to schizophrenia may reside within Xp11. We analyzed uVNTR and rs1137070, polymorphisms from MAOA and rs1799836 of MAOB genes to perform single SNP case-control association study in a sample of 344 schizophrenia patients and 124 control subjects. Single polymorphism analysis of uVNTR, rs1137070 and rs1799836 SNPs did not show statistical differences between cases and controls. Multivariate ANOVA analysis of clinical characteristics showed statistical differences between MAOB/rs1799836 and affective flattening scores (F = 4.852, P = 0.009), and significant association between MAOA/uVNTR and affective flattening in female schizophrenia patients (F = 4.236, P = 0.016) after Bonferroni's correction. Our preliminary findings could suggest that severity of affective flattening may be associated by modifier variants of MAOA and MAOB genes in female Mexican patients with schizophrenia. However, further large-scale studies using quantitative symptom-based phenotypes and several candidate variants should be analyzed to obtain a final conclusion.04/2012; 2012:852949. DOI:10.5402/2012/852949
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ABSTRACT: There is good evidence that psychotic symptoms segregate into symptom dimensions. However, it is still unclear how these dimensions are associated with risk indicators and other clinical variables, and whether they have advantages over categorical diagnosis in clinical practice. We investigated symptom dimensions in a first-onset psychosis sample and examined their associations with risk indicators and clinical variables. We then examined the relationship of categorical diagnoses to the same variables. We recruited 536 patients as part of a population-based, incidence study of psychosis. Psychopathology was assessed using the Schedules for Clinical Assessment in Neuropsychiatry (SCAN). A principal axis factor analysis was performed on symptom scores. The relationship of dimension scores with risk indicators and with clinical variables was then examined employing regression analyses. Finally, regression models were compared to assess the contribution of dimensions versus diagnosis in explaining these variables. Factor analysis gave rise to a five-factor solution of manic, reality distortion, negative, depressive and disorganization symptom dimensions. The scores of identified dimensions were differentially associated with specific variables. The manic dimension had the highest number of significant associations; strong correlations were observed with shorter duration of untreated psychosis, acute mode of onset and compulsory admission. Adding dimensional scores to diagnostic categories significantly increased the amount of variability explained in predicting these variables; the reverse was also true but to a lesser extent. Categorical and dimensional representations of psychosis are complementary. Using both appears to be a promising strategy in conceptualising psychotic illnesses.Psychological Medicine 08/2009; 39(12):1943-55. DOI:10.1017/S0033291709990651 · 5.43 Impact Factor