Genetic modelling of childhood social development and personality in twins and siblings with schizophrenia

Picchioni, Marco; Walshe, Muriel; Toulopoulou, Timothea; McDonald, Colm; Taylor, Mark; Waters-Metenier, Sheena; Bramon, Elvira; Regojo, A; Murray, Robin M.; Rijsdijk, Frühling

doi:10.1017/s0033291709991425

Cited by 16 publications

(15 citation statements)

References 90 publications

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“…Crucially, the risk for Sz is increased in those with a lower IQ score, in particular in the presence of impaired nonverbal reasoning (49). Furthermore, recent work has shown that there are significant common genetic influences acting on the covariance between IQ, schizotypy, abnormal social functioning, and schizophrenia (50). This suggests that the same genetic factors that impair intelligence, increase schizotypy, impede social development, and decrease BV in childhood also determine the liability to Sz (39,50).…”

Section: Discussionmentioning

confidence: 99%

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

Haren

Rijsdijk

Schnack

et al. 2012

Biological Psychiatry

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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.

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Section: Discussionmentioning

confidence: 99%

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

Haren

Rijsdijk

Schnack

et al. 2012

Biological Psychiatry

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“…Premorbid dysfunction is strongly associated with postonset illness characteristics including severity of negative symptoms, cognitive deficits, motor slowing, and treatment refraction (e.g., Addington, van Mastrigt, & Addington, 2003; Haim, Rabinowitz, & Bromet, 2006; Larsen, McGlashan, Johannessen, & Vibe-Hansen, 1996; Levitt, O'Donnell, McCarley, Nestor, & Shenton, 1996; Silverstein, Mavrolefteros, & Turnbull, 2003). Furthermore, a history of poor functioning in childhood and adolescence in nonpsychotic adult relatives of schizophrenia patients (Shapiro et al, 2009; Walshe et al, 2007), including monozygotic twins (Picchioni et al, 2010), suggests a genetic component to this association.…”

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confidence: 99%

Premorbid functional development and conversion to psychosis in clinical high-risk youths

et al. 2013

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Deterioration in premorbid functioning is a common feature of schizophrenia, but sensitivity to psychosis conversion among clinical high-risk samples has not been examined. This study evaluates premorbid functioning as a predictor of psychosis conversion among a clinical high-risk sample, controlling for effects of prior developmental periods. Participants were 270 clinical high-risk individuals in the North American Prodrome Longitudinal Study—I, 78 of whom converted to psychosis over the next 2.5 years. Social, academic, and total maladjustment in childhood, early adolescence, and late adolescence were rated using the Cannon–Spoor Premorbid Adjustment Scale. Early adolescent social dysfunction significantly predicted conversion to psychosis (hazard ratio = 1.30, p = .014), independently of childhood social maladjustment and independently of severity of most baseline positive and negative prodromal symptoms. Baseline prodromal symptoms of disorganized communication, social anhedonia, suspiciousness, and diminished ideational richness mediated this association. Early adolescent social maladjustment and baseline suspiciousness together demonstrated moderate positive predictive power (59%) and high specificity (92.1%) in predicting conversion. Deterioration of academic and total functioning, although observed, did not predict conversion to psychosis. Results indicate early adolescent social dysfunction to be an important early predictor of conversion. As such, it may be a good candidate for inclusion in prediction algorithms and could represent an advantageous target for early intervention.

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“…Group effects were analyzed using a regression model with standard errors that are robust against familial correlations (Binder, 1983, Picchioni et al, 2010). Regression and logistic regression with the Huber–White sandwich standard error were used to compare demographic, clinical, and behavioral variables while taking account of family clusters.…”

Section: Methodsmentioning

confidence: 99%

“…Regression and logistic regression with the Huber–White sandwich standard error were used to compare demographic, clinical, and behavioral variables while taking account of family clusters. We carried out overall group comparisons followed by post-hoc pair-wise comparisons where the initial test was significant using established testing models (Picchioni et al, 2006, Picchioni et al, 2010) in STATA 10.1.…”

Section: Methodsmentioning

confidence: 99%

Effects of risk for bipolar disorder on brain function: A twin and family study

Sugihara

Kane

Picchioni

et al. 2017

European Neuropsychopharmacology

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Bipolar disorder (BPD) is associated with altered regional brain function during the performance of cognitive tasks. The relative contribution of genetic and environmental risk factors for BPD to these changes has not yet been quantified. We sought to address this issue in a functional neuroimaging study of people who varied in their risk for BPD. Functional magnetic resonance imaging was used to study 124 subjects (29 twin and 9 sibling pairs with at least one member with BPD, and 24 healthy twin pairs) performing a working memory task. We assessed the influence of risk for BPD on regional brain function during the task in a two stage process. Firstly, we identified areas where there were group differences in activation. Secondly, we estimated the heritability and phenotypic correlation of activation and BPD using genetic modeling. BPD was associated with increased activation in the anterior cingulate, orbitofrontal, medial prefrontal, and left precentral cortices, and in the precuneus. Within these regions, activation in the orbitofrontal cortex rendered the most significant heritability estimate (h2=0.40), and was significantly correlated with BPD phenotype (rph=0.29). A moderate proportion of the genetic influences (rg=0.69) acting on both BPD and on the degree of orbitofrontal activation were shared. These findings suggest that genetic factors that confer vulnerability to BPD alter brain function in BPD.

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Genetic modelling of childhood social development and personality in twins and siblings with schizophrenia

Abstract: Abnormalities of social adjustment and personality are present in children and adolescents who later develop schizophrenia, reflecting the influence of common genetic risk.

Cited by 16 publications

References 90 publications

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

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

Premorbid functional development and conversion to psychosis in clinical high-risk youths

Effects of risk for bipolar disorder on brain function: A twin and family study

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