A diffusion tensor MRI study of white matter integrity in subjects at high genetic risk of schizophrenia

Maniega, Susana Muñoz; Lymer, G. Katherine S.; Bastin, Mark E.; Marjoram, Dominic; Job, Dominic; Moorhead, T. William J.; Owens, David C.; Johnstone, Eve C.; McIntosh, Andrew M.; Lawrie, Stephen M.

doi:10.1016/j.schres.2008.09.016

Cited by 98 publications

(90 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…There were no significant differences between the groups in terms of age (age: mean Based on the results above, we restricted the search volume to the bilateral ALIC. Subjects homozygous for the T allele showed reduced FA in the right ALIC compared to C allele homozygotes ( Figures 3 and 4, peak MNI coordinates = (22,14,8), t = 2.65, P = 0.006, search volume = 0.7 resels; Figure 2). Reductions were also found in the genu of the left ALIC and in cerebellar white matter, although these did not reach statistical significance.…”

Section: Diffusion Tensor Imagingmentioning

confidence: 98%

“…Subjects with the TT genotype also had significantly reduced white matter density as assessed by voxelbased morphometry compared to the C allele carriers at the tip of the right anterior capsule (peak 1: MNI coordinates = (29, 30, 7), t = 4.41, P-corrected = 0.028; peak 2: MNI coordinates = (29,26,8), t = 4.38, Pcorrected = 0.016; peak 3: MNI coordinates = (29,23,12), t = 4.26, P-corrected = 0.023). The associated cluster extended both medially and laterally into frontal white matter (Figure 1).…”

Section: T 1 -Weighted Imagingmentioning

confidence: 99%

“…6 Deficits in the ALIC and frontal white matter have been confirmed in both schizophrenia and bipolar disorder by studying patients within the same study, 7 supporting the idea that these deficits may be related to the shared pathophysiology of both conditions. These deficits are also found in individuals at high risk of schizophrenia for genetic reasons, 8 suggesting that they are likely to be associated with genetic factors potentially related to the aetiology of psychosis.…”

Section: Introductionmentioning

confidence: 98%

See 2 more Smart Citations

The effects of a neuregulin 1 variant on white matter density and integrity

et al. 2007

Self Cite

View full text Add to dashboard Cite

Theories of abnormal anatomical and functional connectivity in schizophrenia and bipolar disorder are supported by evidence from functional magnetic resonance imaging (MRI), structural MRI and diffusion tensor imaging (DTI). The presence of similar abnormalities in unaffected relatives suggests such disconnectivity is genetically mediated, albeit through unspecified loci. Neuregulin 1 (NRG1) is a psychosis susceptibility gene with effects on neuronal migration, axon guidance and myelination that could potentially explain these findings. In the current study, unaffected subjects were genotyped at the NRG1 single nucleotide polymorphism (SNP) rs6994992 (SNP8NRG243177) locus, previously associated with increased risk for psychosis, and the effect of genetic variation at this locus on white matter density (T 1 -weighted MRI) and integrity (DTI) was ascertained. Subjects with the riskassociated TT genotype had reduced white matter density in the anterior limb of the internal capsule and evidence of reduced structural connectivity in the same region using DTI. We therefore provide the first imaging evidence that genetic variation in NRG1 is associated with reduced white matter density and integrity in human subjects. This finding is discussed in the context of NRG1 effects on neuronal migration, axon guidance and myelination.

show abstract

Section: Diffusion Tensor Imagingmentioning

confidence: 98%

Section: T 1 -Weighted Imagingmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 98%

See 1 more Smart Citation

The effects of a neuregulin 1 variant on white matter density and integrity

et al. 2007

Self Cite

View full text Add to dashboard Cite

show abstract

“…While the majority of studies investigating first-degree relatives of schizophrenia patients have revealed decreasing FA in tracts compared to controls (Camchong et al, 2009;Hao et al, 2009;Hoptman et al, 2008;Munoz Maniega et al, 2008), there have been a few studies that have demonstrated increased FA (Boos et al, 2013;Hoptman et al, 2008). One possible explanation for the difference is that previous studies have examined adult relatives of patients with schizophrenia, while the present study tested adolescent relatives.…”

Section: Discussionmentioning

confidence: 74%

“…diffusion) by applying many diffusion-encoding gradients in different orientations (Beaulieu, 2002). DTI studies have demonstrated decreased white matter fractional anisotropy (FA) in adult onset schizophrenia (AOS) patients compared to healthy subjects (Camchong et al, 2009;Ellison-Wright and Bullmore, 2009;Hao et al, 2009;Hoptman et al, 2008;Munoz Maniega et al, 2008), though one study (Hoptman et al, 2008) showed an increase in FA.…”

Section: Introductionmentioning

confidence: 99%

DTI microstructural abnormalities in adolescent siblings of patients with childhood-onset schizophrenia

Waltzman

Knowlton

Cohen

et al. 2016

Psychiatry Research: Neuroimaging

View full text Add to dashboard Cite

Structural Brain Connectivity as a Genetic Marker for Schizophrenia

et al. 2016

View full text Add to dashboard Cite

IMPORTANCE Schizophrenia is accompanied by a loss of integrity of white matter connections that compose the structural brain network, which is believed to diminish the efficiency of information transfer among brain regions. However, it is unclear to what extent these abnormalities are influenced by the genetic liability for developing the disease. OBJECTIVE To determine whether white matter integrity is associated with the genetic liability for developing schizophrenia. DESIGN, SETTING, AND PARTICIPANTS In 70 individual twins discordant for schizophrenia and 130 matched individual healthy control twins, structural equation modeling was applied to quantify unique contributions of genetic and environmental factors on brain connectivity and disease liability. The data for this study were collected from October 1, 2008, to September 30, 2013. The data analysis was performed between November 1, 2013, and March 30, 2015. MAIN OUTCOME MEASURES Structural connectivity and network efficiency were assessed through diffusion-weighted imaging, measuring fractional anisotropy (FA) and streamlines. RESULTS The sample included 30 monozygotic twins matched to 72 control participants and 40 dizygotic twins matched to 58 control participants. Lower global FA was significantly correlated with increased schizophrenia liability (phenotypic correlation, −0.25; 95% CI, −0.38 to −0.10; P = .001), with 83.4% explained by common genes. In total, 8.1% of genetic variation in global FA was shared with genetic variance in schizophrenia liability. Local reductions in network connectivity (as defined by FA-weighted local efficiency) of frontal, striatal, and thalamic regions encompassed 85.7% of genetically affected areas. Multivariate genetic modeling revealed that global FA contributed independently of other genetic markers, such as white matter volume and cortical thickness, to schizophrenia liability. CONCLUSIONS AND RELEVANCE Global reductions in white matter integrity in schizophrenia are largely explained by the genetic risk of developing the disease. Network analysis revealed that genetic liability for schizophrenia is primarily associated with reductions in connectivity of frontal and subcortical regions, indicating a loss of integrity along the white matter fibers in these regions. The reported reductions in white matter integrity likely represent a separate and novel genetic vulnerability marker for schizophrenia.

show abstract

A diffusion tensor MRI study of white matter integrity in subjects at high genetic risk of schizophrenia

Cited by 98 publications

References 38 publications

The effects of a neuregulin 1 variant on white matter density and integrity

The effects of a neuregulin 1 variant on white matter density and integrity

DTI microstructural abnormalities in adolescent siblings of patients with childhood-onset schizophrenia

Structural Brain Connectivity as a Genetic Marker for Schizophrenia

Contact Info

Product

Resources

About