Longitudinal Volume Reductions in People at High Genetic Risk of Schizophrenia as They Develop Psychosis

McIntosh, Andrew M.; Owens, David C.; Moorhead, William J.; Whalley, Heather C.; Stanfield, Andrew C.; Hall, Jérémy; Johnstone, Eve C.; Lawrie, Stephen M.

doi:10.1016/j.biopsych.2010.11.003

Cited by 105 publications

(87 citation statements)

References 24 publications

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“…For this reason, we controlled for total surface area in our analysis of thickness. PSE factors, as used in McIntosh et al (17), including increasing severity of hallucinations, delusional construction, and disorder of possession of thought, were obtained and correlated with structural brain parameters in the HR cohort. Logistic regressions were also performed to assess the correlation between area and thickness and how this differed across groups both at baseline and longitudinally.…”

Section: Discussionmentioning

confidence: 99%

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Cortical Surface Area Differentiates Familial High Risk Individuals Who Go on to Develop Schizophrenia

Bois

Ronan

Levita

et al. 2015

Biological Psychiatry

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ReuseThis article is distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs (CC BY-NC-ND) licence. This licence only allows you to download this work and share it with others as long as you credit the authors, but you can't change the article in any way or use it commercially. More information and the full terms of the licence here: https://creativecommons.org/licenses/ Takedown If you consider content in White Rose Research Online to be in breach of UK law, please notify us by emailing eprints@whiterose.ac.uk including the URL of the record and the reason for the withdrawal request. Archival Report Cortical Surface Area Differentiates Familial High Risk Individuals Who Go on to Develop SchizophreniaCatherine Bois, Lisa Ronan, Liat Levita, Heather C. Whalley, Stephen Giles, Andrew M. McIntosh, Paul C. Fletcher, David C. Owens, Eve C. Johnstone, and Stephen M. Lawrie ABSTRACT BACKGROUND: Schizophrenia is associated with structural brain abnormalities that may be present before disease onset. It remains unclear whether these represent general vulnerability indicators or are associated with the clinical state itself. METHODS: To investigate this, structural brain scans were acquired at two time points (mean scan interval 1.87 years) in a cohort of individuals at high familial risk of schizophrenia (n 5 142) and control subjects (n 5 36). Cortical reconstructions were generated using FreeSurfer. The high-risk cohort was subdivided into individuals that remained well during the study, individuals that had transient psychotic symptoms, and individuals that subsequently became ill. Baseline measures and longitudinal change in global estimates of thickness and surface area and lobar values were compared, focusing on overall differences between high-risk individuals and control subjects and then on group differences within the high-risk cohort. RESULTS: Longitudinally, control subjects showed a significantly greater reduction in cortical surface area compared with the high-risk group. Within the high-risk group, differences in surface area at baseline predicted clinical course, with individuals that subsequently became ill having significantly larger surface area than individuals that remained well during the study. For thickness, longitudinal reductions were most prominent in the frontal, cingulate, and occipital lobes in all high-risk individuals compared with control subjects. CONCLUSIONS: Our results suggest that larger surface areas at baseline may be associated with mechanisms that go above and beyond a general familial disposition. A relative preservation over time of surface area, coupled with a thinning of the cortex compared with control subjects, may serve as vulnerability markers of schizophrenia.

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Section: Discussionmentioning

confidence: 99%

“…Most studies that investigate familial HR cohorts have been cross-sectional; however, some have shown that dynamic changes occur before disorder onset in those at HR for familial or clinical reasons (14)(15)(16)(17). This suggests that a vulnerability to schizophrenia entails both initial structural abnormalities coupled with aberrant development.…”

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confidence: 99%

Cortical Surface Area Differentiates Familial High Risk Individuals Who Go on to Develop Schizophrenia

Bois

Ronan

Levita

et al. 2015

Biological Psychiatry

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“…Three studies included the G-HR population with either no transition to psychosis [30] or with a relative low transition rate (10.5% [15] and 12% [31]). Data from overlapping C-HR studies from Melbourne showed 35% to 47% transition rate [23][24][25][26]87].…”

Section: Longitudinal Structural Neuroimaging Studies Of Individuals mentioning

confidence: 99%

“…We extracted longitudinal studies comprising structural results among all high-risk groups starting with C-HR studies from the centers Melbourne, Basel, Bonn [23][24][25][26][27][28][29] and continuing with G-HR studies from Edinburgh and Pittsburgh [15,30,31] (Table 1). …”

Section: Data Analysis: Subjects At Genetic Risk (G-hr) and Clinical mentioning

confidence: 99%

Do Subjects at Clinical High Risk for Psychosis Differ from those with a Genetic High Risk? - A Systematic Review of Structural and Functional Brain Abnormalities

Smieskova¹,

Marmy²,

Schmidt³

et al. 2013

Current Medicinal Chemistry

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“…Studies of at-risk youth with a family history of schizophrenia indicate that these individuals are characterized by progressive GM loss in the prefrontal and temporal lobes. 5 However, because two-thirds of individuals with schizophrenia have no affected relatives, 6 findings from studies examining these genetic high-risk youth may not generalize to the majority of patients with schizophrenia. Investigations of (prodromal) youth considered at ultra high risk (UHR) of psychosis due to their clinical presentation (attenuated psychotic symptoms; brief, limited intermittent psychotic symptoms; or genetic risk plus functional decline) 7 indicate relative GM reductions in the hippocampus, insula, superior temporal gyrus (STG), and prefrontal cortex, 8 and WM reductions in the superior temporal lobe 9 relative to healthy youth.…”

Section: Introductionmentioning

confidence: 99%

Temporal Lobe Volume Abnormalities Precede the Prodrome: A Study of Children Presenting Antecedents of Schizophrenia

Cullen¹,

Brito²,

Gregory³

et al. 2012

Schizophrenia Bulletin

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Distributed abnormalities of gray matter (GM) and white matter (WM) volume characterize individuals experiencing their first episode of schizophrenia. Regions of abnormality are present already, albeit less extensively, during the prodromal phase of illness. This study aimed to determine whether putatively at-risk children, aged 9-12 years, who present multiple antecedents of schizophrenia (ASz), display GM and WM volume abnormalities relative to typically developing (TD) children presenting no antecedents. Structural magnetic resonance images were acquired for 20 ASz children and 20 TD children matched on age, sex, and IQ. Whole-brain differences in GM and WM volume were determined using voxel-based morphometry. Relative to the TD group, ASz children showed significantly decreased GM volume in the right middle temporal gyrus (MTG) and increased GM volume in the left superior-middle temporal gyri (P < 0.05, cluster correction). WM volume was significantly increased in ASz children relative to TD children in a cluster encompassing the left inferior parietal lobe, occipital lobe, and superior temporal gyrus. Post-hoc analyses indicated that these abnormalities were not limited to ASz children who selfreported auditory hallucinations on questionnaire. Our findings suggest that children aged 9-12 years who present multiple ASz are characterized by abnormalities of GM and WM volume in the temporal lobes, comprising a subset of the regions affected in first-episode schizophrenia and in the prodromal phase of illness. These preliminary findings indicate that structural brain abnormalities associated with schizophrenia may be detected in putatively at-risk, preprodromal children. Prospective studies following the brain development of at-risk children are needed.

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Longitudinal Volume Reductions in People at High Genetic Risk of Schizophrenia as They Develop Psychosis

Cited by 105 publications

References 24 publications

Cortical Surface Area Differentiates Familial High Risk Individuals Who Go on to Develop Schizophrenia

Cortical Surface Area Differentiates Familial High Risk Individuals Who Go on to Develop Schizophrenia

Do Subjects at Clinical High Risk for Psychosis Differ from those with a Genetic High Risk? - A Systematic Review of Structural and Functional Brain Abnormalities

Temporal Lobe Volume Abnormalities Precede the Prodrome: A Study of Children Presenting Antecedents of Schizophrenia

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