A controlled study of brain structure in monozygotic twins concordant and discordant for schizophrenia

Haren, Neeltje E.M. van; Picchioni, Marco; McDonald, Colm; Marshall, Nicolette; Davis, Nadia; Ribchester, Tracey; Pol, Hilleke E. Hulshoff; Sharma, Tonmoy; Sham, Pak C.; Kahn, René S.; Murray, Robin M.

doi:10.1016/j.biopsych.2004.06.033

Cited by 79 publications

(56 citation statements)

References 33 publications

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“…Our results showed that even when comparing a high genetic risk group of siblings and a low genetic risk group of controls, no grey matter volume or concentration differences were found. This finding is in line with those of studies that were unable to find grey matter differences in unaffected monozygotic twins of patients with schizophrenia, 38,39 who are at the highest possible genetic risk for schizophrenia.…”

Section: Discussionsupporting

confidence: 91%

Grey matter, an endophenotype for schizophrenia? A voxel-based morphometry study in siblings of patients with schizophrenia

Velde

Gromann

Swart

et al. 2015

jpn

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IntroductionThe liability for schizophrenia is heritable, 1 with siblings of patients with schizophrenia being at increased risk (about a 10-fold increase) for the disorder.2 Structural brain abnormalities in patients with schizophrenia have been consistently reported. For example, patients show reduced grey matter in the frontal, temporal and thalamic regions (see the meta-analyses by Fornito and colleagues 3 and Haijma and colleagues 4 ). Previous studies have suggested that part of these grey matter abnormalities might not be related to the illness state, but rather to the genetic risk, and have proposed these abnormalities to be an endophenotype for schizophrenia. [5][6][7] Consistent with this proposal, 4 recent meta-analyses reported grey matter reductions in relatives of patients compared with controls. [8][9][10][11] Although the aims of these meta-analyses differed, all of them compared individuals at genetic high risk with controls. However, the results of these meta-analyses differed substantially, and the thresholds applied were rather low (p < 0.05, p < 0.005 and p < 0.001, uncorrected). Two meta-analyses showed grey matter reductions in relatives compared with controls in the lentiform nucleus 9,11 and medial prefrontal cortex, 9 whereas another meta-analysis reported higher levels of grey matter in the medial prefrontal cortex in siblings.11 Furthermore, reductions in the parahippompal gyrus and anterior cingulate have been reported, 8 while others reported reductions in the amygdala and hippocampus.10 Besides these contradictory reports, the 3 largest voxel-based morphometry (VBM) studies in siblings 12-14 did not report any significant differences in whole brain grey matter between siblings and controls.In a recent review, several hypotheses were proposed to explain these differences. 5 The first explanation was that many studies included participants who were already past the critical ages for schizophrenia developing. The onset of Background: Grey matter, both volume and concentration, has been proposed as an endophenotype for schizophrenia given a number of reports of grey matter abnormalities in relatives of patients with schizophrenia. However, previous studies on grey matter abnormalities in relatives have produced inconsistent results. The aim of the present study was to examine grey matter differences between controls and siblings of patients with schizophrenia and to examine whether the age, genetic loading or subclinical psychotic symptoms of selected individuals could explain the previously reported inconsistencies. Methods: We compared the grey matter volume and grey matter concentration of healthy siblings of patients with schizophrenia and healthy controls matched for age, sex and education using voxel-based morphometry (VBM). Furthermore, we selected subsamples based on age (< 30 yr), genetic loading and subclinical psychotic symptoms to examine whether this would lead to different results. Results: We included 89 siblings and 69 controls in our study. The results showed that sibl...

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Section: Discussionsupporting

confidence: 91%

Grey matter, an endophenotype for schizophrenia? A voxel-based morphometry study in siblings of patients with schizophrenia

Velde

Gromann

Swart

et al. 2015

jpn

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“…Together, these findings indicate that while hippocampal volume in healthy subjects is under substantial genetic control, hippocampal volume in SZ patients and their relatives appears to be influenced to a greater extent by unique and shared environmental factors . A similar pattern of results was observed in a Dutch twin sample [van Haren et al, 2004]. These results extend those of prior studies demonstrating medial temporal abnormalities in the unaffected relatives of schizophrenia patients [Seidman et al, 2003;Tepest et al, 2003].…”

Section: Heritability Of Brain Structure In Twins Discordant For Schisupporting

confidence: 90%

Cortical mapping of genotype–phenotype relationships in schizophrenia

Bearden

Erp

Thompson

et al. 2007

Human Brain Mapping

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Although schizophrenia is highly heritable, the search for susceptibility genes has been challenging. The "endophenotype" approach is an alternative method for measuring phenotypic variation that may make it easier to identify susceptibility genes in the context of complexly inherited traits. Neuroimaging methods in particular offer a powerful way to bridge the neurobiology of genes and behavior. Such investigations may be further empowered by complementary strategies involving chromosomal abnormalities associated with schizophrenia, which can help to localize causative genes and better understand the genetic complexity of the illness. Here, we illustrate our use of these convergent approaches, with a focus on neuroimaging studies using novel computational brain mapping algorithms, to investigate genetic influences on brain structure in the development of psychosis. These studies provide compelling evidence that specific genetic loci suspected to predispose to schizophrenia may affect quantitative variation in neural indicators underlying the neurobehavioral phenotype, and illustrate how geneticneuroimaging paradigms can improve our understanding of the pathogenesis of this highly disabling mental illness.

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“…Data from subsets of this cohort have been published previously. 18,23 We obtained local and South East (UK) multicentre ethics approval for our study, and all participants gave their written informed consent.…”

Section: Participantsmentioning

confidence: 99%

Familial and environmental influences on brain volumes in twins with schizophrenia

Picchioni

Rijsdijk²,

Toulopoulou

et al. 2017

JPN

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A controlled study of brain structure in monozygotic twins concordant and discordant for schizophrenia

Cited by 79 publications

References 33 publications

Grey matter, an endophenotype for schizophrenia? A voxel-based morphometry study in siblings of patients with schizophrenia

Grey matter, an endophenotype for schizophrenia? A voxel-based morphometry study in siblings of patients with schizophrenia

Cortical mapping of genotype–phenotype relationships in schizophrenia

Familial and environmental influences on brain volumes in twins with schizophrenia

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