Schizophrenia Twins Research Articles

T198. Evidence for Cerebello-Thalamo-Cortical Hyperconnectivity as a Heritable Trait for Schizophrenia

Our recent study revealed that cerebello-thalamo-cortical (CTC) hyperconnectivity is a state-independent “trait” alteration for psychosis prediction. One possible cause of such change would be genetic predisposition. Here we tested this hypothesis using two independent twin datasets: the Human Connectome Project (HCP) twin sample and the Swedish Schizophrenia Twin Study (STAR).

Cellular analysis of a discordant schizophrenia twin using iPS cell technology

Cellular analysis of a discordant schizophrenia twin using iPS cell technology

Reciprocal causation models of cognitive vs volumetric cerebral intermediate phenotypes for schizophrenia in a pan-European twin cohort.

In aetiologically complex illnesses such as schizophrenia, there is no direct link between genotype and phenotype. Intermediate phenotypes could help clarify the underlying biology and assist in the hunt for genetic vulnerability variants. We have previously shown that cognition shares substantial genetic variance with schizophrenia; however, it is unknown if this reflects pleiotropic effects, direct causality or some shared third factor that links both, for example, brain volume (BV) changes. We quantified the degree of net genetic overlap and tested the direction of causation between schizophrenia liability, brain structure and cognition in a pan-European schizophrenia twin cohort consisting of 1243 members from 626 pairs. Cognitive deficits lie upstream of the liability for schizophrenia with about a quarter of the variance in liability to schizophrenia explained by variation in cognitive function. BV changes lay downstream of schizophrenia liability, with 4% of BV variation explained directly by variation in liability. However, our power to determine the nature of the relationship between BV deviation and schizophrenia liability was more limited. Thus, while there was strong evidence that cognitive impairment is causal to schizophrenia liability, we are not in a position to make a similar statement about the relationship between liability and BV. This is the first study to demonstrate that schizophrenia liability is expressed partially through cognitive deficits. One prediction of the finding that BV changes lie downstream of the disease liability is that the risk loci that influence schizophrenia liability will thereafter influence BV and to a lesser extent. By way of contrast, cognitive function lies upstream of schizophrenia, thus the relevant loci will actually have a larger effect size on cognitive function than on schizophrenia. These are testable predictions.

The Genetic and Environmental Determinants of the Association Between Brain Abnormalities and Schizophrenia: The Schizophrenia Twins and Relatives Consortium

BackgroundStructural brain abnormalities are consistently found in schizophrenia (Sz) and have been associated with the familial risk for the disorder. We aim to define the relative contributions of genetic and nongenetic factors to the association between structural brain abnormalities and Sz in a uniquely powered cohort (Schizophrenia Twins and Relatives consortium).MethodsAn international multicenter magnetic resonance imaging collaboration was set up to pool magnetic resonance imaging scans from twin pairs in Utrecht (The Netherlands), Helsinki (Finland), London (United Kingdom), and Jena (Germany). A sample of 684 subjects took part, consisting of monozygotic twins (n = 410, with 51 patients from concordant and 52 from discordant pairs) and dizygotic twins (n = 274, with 39 patients from discordant pairs). The additive genetic, common, and unique environmental contributions to the association between brain volumes and risk for Sz were estimated by structural equation modeling.ResultsThe heritabilities of most brain volumes were significant and ranged between 52% (temporal cortical gray matter) and 76% (cerebrum). Heritability of cerebral gray matter did not reach significance (34%). Significant phenotypic correlations were found between Sz and reduced volumes of the cerebrum (−.22 [−.30/−.14]) and white matter (−.17 [−.25/−.09]) and increased volume of the third ventricle (.18 [.08/.28]). These were predominantly due to overlapping genetic effects (77%, 94%, and 83%, respectively).ConclusionsSome of the genes that transmit the risk for Sz also influence cerebral (white matter) volume.

The importance of systematic genetic approach to familial schizophrenia cases and discussion of cryptic mosaic X chromosome aneuploidies in schizophrenia pathogenesis

Objective. The aim of this study is to contribute to the understanding of schizophrenia genetics by using efficient algorithmic examination techniques including dysmorphic examination, karyotyping, and Fluoresence in situ hybridization (FISH). Methods. In this study we have investigated 20 familial schizophrenia patients from Turkey who had an affected first-degree relative. Dysmorphic examination of the schizophrenia cases and their relatives have been performed. High resolution banding (HRB), specific centromeric, subtelomeric and 22q11.2 region FISH probes were used for genotyping of patients. Results. Dysmorphic examination revealed ear, palate, nose, columella anomalies, and obesity in contributing patients, and the pale skin was noticed. The medical histories and clinical findings of two schizophrenia twins were almost identical. HRB study demonstrated the presence of 46,XX[55]/47,XXX[4]/48,XXXX[1] constitution in a paranoid schizophrenia case and 46,XX[67]/45,X[5] karyotype in her mother. FISH studies aiming subtelomeric chromosomal regions revealed no rearrangements and 22q11.2 regions were intact in all of the patients. Conclusions. The parental gonadal mosaicism lying at the origin of the mitotic aneuploidy may be the reason for mosaic X chromosome aneuploidies in our mother–daughter schizophrenia couple. Mosaic X chromosome aneuploidies may accompany schizophrenia cases and may contribute to pathogenesis of familial schizophrenia.

Open Forum: Evolution of the Antipsychiatry Movement Into Mental Health Consumerism

Open Forum: Evolution of the Antipsychiatry Movement Into Mental Health Consumerism

Metabolic Profiling of Plasma from Discordant Schizophrenia Twins: Correlation between Lipid Signals and Global Functioning in Female Schizophrenia Patients

(1)H NMR spectroscopy-based metabonomic analysis was employed to investigate plasma samples from 21 pairs of monozygotic twins discordant for schizophrenia and 8 pairs of age-matched healthy twins in an effort to disentangle genetic and epigenetic components of schizophrenia. We identified alterations in the lipid profile of both affected and unaffected schizophrenia twins. Additionally, there is a close association of VLDL/LDL signals and Global Functioning Scores in female twins suffering from schizophrenia. Our results further support a link between metabolic disturbances and the etiopathology of schizophrenia.

When assessing twin concordance, use the probandwise not the pairwise rate.

Geneticists and twin researchers have long debated the relative merits of two alternative measures of twin concordance: the pairwise and probandwise concordance rates. The results of this debate are now quite clear, for almost every application the probandwise rate is preferred over the pairwise rate. In a recent review of schizophrenia twin studies, however, Torrey (1992) chose to analyze pairwise rather than probandwise rates. Torrey's use of pairwise rates led him to conclude that the monozygotic twin concordance for schizophrenia is weaker than what is widely accepted, and that, by implication, the magnitude of the genetic contribution to schizophrenia has been overestimated. In this brief commentary, we review the relative strengths and weaknesses of the pairwise and probandwise rates and show that Torrey's conclusion is based upon his incorrect use of pairwise rates. Twin studies of schizophrenia continue to support the existence of a strong genetic influence on the development of schizophrenia.