Focal And Global Brain Measurements in Siblings of Patients With Schizophrenia

Boos, Heleen B. M.; Cahn, Wiepke; Haren, Neeltje E.M. van; Derks, Eske M.; Brouwer, Rachel M.; Schnack, Hugo G.; Pol, Hilleke E. Hulshoff; Kahn, René S.

doi:10.1093/schbul/sbq147

Cited by 52 publications

(36 citation statements)

References 93 publications

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“…One important aspect of an endophenotype is that it should be present in unaffected relatives of patients. The present study and previous reports [12][13][14] question the idea that grey matter abnormalities are present in relatives of patients with schizophrenia. However, our ROI analysis did reveal significantly higher grey matter volume in the ACC in siblings of patients with schizophrenia.…”

Section: Discussioncontrasting

confidence: 54%

“…The finding of nonsignificant grey matter differences between siblings and controls is in accordance with results of 3 previous large studies on grey matter in relatives of patients with schizophrenia. [12][13][14] This agreement suggests that enhanced genetic risk for schizophrenia might not be related to substantial differences in grey matter. Although large studies have been unable to find grey matter alterations in relatives of patients with schizophrenia, smaller studies with lower thresholds have often reported grey matter differences between relatives and controls, 23,37 which may explain the positive (albeit inconsistent) effects found in previous metaanalyses.…”

Section: Discussionmentioning

confidence: 77%

“…We therefore performed a voxel-based morphometry (VBM) analysis on a large group of siblings and controls (n = 170) -a larger group than in most grey matter studies reporting significant differences between relatives and controls (for example, see the studies by Hu and colleagues, 21 Tian and colleagues 22 and Oertel-Knöchel and colleagues 23 ). Based on previous large VBM studies [12][13][14] we did not expect to find grey matter differences between the general group of siblings and controls. However, we did expect that selecting siblings younger than 30 years with high genetic loading or high schizotypy scores would reveal significant grey matter abnormalities because of their higher risk profile.…”

Section: J Psychiatry Neurosci 2015;40(3)mentioning

confidence: 71%

“…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][13][14] did not report any significant differences in whole brain grey matter between siblings and controls.…”

Section: Introductionmentioning

confidence: 99%

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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: Discussioncontrasting

confidence: 54%

Section: Discussionmentioning

confidence: 77%

Section: J Psychiatry Neurosci 2015;40(3)mentioning

confidence: 71%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

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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“…In vivo MR imaging measurements have shown regional differences in cortical thickness (22) and have revealed focal differences in cortical thickness between healthy control subjects and patients with schizophrenia (23,24), Alzheimer disease (25) or autism (26). The ability to distinguish multiple cortical layers might yield more insight into where cortical thinning mainly takes place, be it in the superficial or deep layers or diffuse in all layers.…”

Section: Discussionmentioning

confidence: 99%

Generalized Multiple-Layer Appearance of the Cerebral Cortex with 3D FLAIR 7.0-T MR Imaging

Zwanenburg¹,

Hendrikse²,

Luijten³

2012

Radiology

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Delayed White Matter Growth Trajectory in Young Nonpsychotic Siblings of Patients With Childhood-Onset Schizophrenia

Gogtay

Hou²,

Stidd³

et al. 2012

Arch Gen Psychiatry

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Context Nonpsychotic siblings of patients with childhood-onset schizophrenia (COS) share cortical gray matter abnormalities with their probands at an early age; these normalize by the time the siblings are aged 18 years, suggesting that the gray matter abnormalities in schizophrenia could be an age-specific endophenotype. Patients with COS also show significant white matter (WM) growth deficits, which have not yet been explored in nonpsychotic siblings. Objective To study WM growth differences in non-psychotic siblings of patients with COS. Design Longitudinal (5-year) anatomic magnetic resonance imaging study mapping WM growth using a novel tensor-based morphometry analysis. Setting National Institutes of Health Clinical Center, Bethesda, Maryland. Participants Forty-nine healthy siblings of patients with COS (mean [SD] age, 16.1[5.3] years; 19 male, 30 female) and 57 healthy persons serving as controls (age, 16.9[5.3] years; 29 male, 28 female). Intervention Magnetic resonance imaging. Main Outcome Measure White matter growth rates. Results We compared the WM growth rates in 3 age ranges. In the youngest age group (7 to <14 years), we found a significant difference in growth rates, with siblings of patients with COS showing slower WM growth rates in the parietal lobes of the brain than age-matched healthy controls (false discovery rate, q = 0.05; critical P = .001 in the bilateral parietal WM; a post hoc analysis identified growth rate differences only on the left side, critical P =.004). A growth rate difference was not detectable at older ages. In 3-dimensional maps, growth rates in the siblings even appeared to surpass those of healthy individuals at later ages, at least locally in the brain, but this effect did not survive a multiple comparisons correction. Conclusions In this first longitudinal study of nonpsychotic siblings of patients with COS, the siblings showed early WM growth deficits, which normalized with age. As reported before for gray matter, WM growth may also be an age-specific endophenotype that shows compensatory normalization with age.

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Focal And Global Brain Measurements in Siblings of Patients With Schizophrenia

Cited by 52 publications

References 93 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

Generalized Multiple-Layer Appearance of the Cerebral Cortex with 3D FLAIR 7.0-T MR Imaging

Delayed White Matter Growth Trajectory in Young Nonpsychotic Siblings of Patients With Childhood-Onset Schizophrenia

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