Running in the Family? Structural Brain Abnormalities and IQ in Offspring, Siblings, Parents, and Co-twins of Patients with Schizophrenia

Zwarte, Sonja M C de; Brouwer, Rachel M.; Tsouli, Andromachi; Cahn, Wiepke; Hillegers, Manon H. J.; Pol, Hilleke E. Hulshoff; Kahn, René S.; Haren, Neeltje E.M. van

doi:10.1093/schbul/sby182

Cited by 22 publications

(28 citation statements)

References 45 publications

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“…(2) cortical surface area alterations being only present in a specific subgroup (subtype) of adult patients with adolescent-onset MDD, which we were unable to detect; or (3) those with cortical surface area alterations in early adolescence may be at higher risk for transitioning from MDD to other mental disorders over time. This latter possibility is consistent with reports of lower cortical surface area in adolescents and adults with psychosis or schizophrenia 80,81 , and in individuals at high risk for and/ or transitioning to psychosis 82,83 . Longitudinal studies are required to test the hypothesis that cortical surface area alteration is a pre-existing risk factor for the development of MDD, and to investigate the subsequent clinical course of these depressed young people with global surface area reductions.…”

Section: Cortical Thickness and Surface Areasupporting

confidence: 91%

ENIGMA MDD: seven years of global neuroimaging studies of major depression through worldwide data sharing

et al. 2020

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A key objective in the field of translational psychiatry over the past few decades has been to identify the brain correlates of major depressive disorder (MDD). Identifying measurable indicators of brain processes associated with MDD could facilitate the detection of individuals at risk, and the development of novel treatments, the monitoring of treatment effects, and predicting who might benefit most from treatments that target specific brain mechanisms. However, despite intensive neuroimaging research towards this effort, underpowered studies and a lack of reproducible findings have hindered progress. Here, we discuss the work of the ENIGMA Major Depressive Disorder (MDD) Consortium, which was established to address issues of poor replication, unreliable results, and overestimation of effect sizes in previous studies. The ENIGMA MDD Consortium currently includes data from 45 MDD study cohorts from 14 countries across six continents. The primary aim of ENIGMA MDD is to identify structural and functional brain alterations associated with MDD that can be reliably detected and replicated across cohorts worldwide. A secondary goal is to investigate how demographic, genetic, clinical, psychological, and environmental factors affect these associations. In this review, we summarize findings of the ENIGMA MDD disease working group to date and discuss future directions. We also highlight the challenges and benefits of largescale data sharing for mental health research.

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Section: Cortical Thickness and Surface Areasupporting

confidence: 91%

ENIGMA MDD: seven years of global neuroimaging studies of major depression through worldwide data sharing

et al. 2020

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“…This might be explained by (1) normalization of cortical surface area when transitioning into adulthood; (2) cortical surface area alterations being only present in a specific subgroup (subtype) of adult patients with adolescent-onset MDD, which we were unable to detect; or (3) those with cortical surface area alterations in early adolescence may be at higher risk for transitioning from MDD to other mental disorders over time. This latter possibility is consistent with reports of lower cortical surface area in adolescents and adults with psychosis or schizophrenia 82,83 , and in individuals at high risk for and/or transitioning to psychosis 84,85 . Longitudinal studies are required to test the hypothesis that cortical surface area alteration is a pre-existing risk factor for the development of MDD, and to investigate the subsequent clinical course of these young people with MDD and global surface area reductions.…”

Section: Subcortical Brain Regionssupporting

confidence: 91%

ENIGMA MDD: Seven Years of Global Neuroimaging Studies of Major Depression through Worldwide Data Sharing

Schmaal¹,

Pozzi²,

Ho³

et al. 2019

Preprint

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A key objective in the field of translational psychiatry over the past few decades has been to identify the brain correlates common to individuals with major depressive disorder (MDD). Identifying measurable indicators of brain processes associated with MDD could facilitate the detection of individuals at risk, and the development of novel treatments, the monitoring of treatment effects, and predicting who might benefit most from treatments that target specific brain mechanisms. However, despite intensive neuroimaging research towards this effort, underpowered studies and a lack of reproducible findings have hindered progress. Here we discuss the work of the ENIGMA Major Depressive Disorder (MDD) Consortium, which was established to address issues of poor replication, unreliable results, and overestimation of effect sizes in previous studies. The ENIGMA MDD Consortium currently includes data from 45 MDD study cohorts from 14 countries across 6 continents. The primary aim of ENIGMA MDD is to identify structural and functional brain alterations associated with MDD that can be reliably detected and replicated across cohorts worldwide. A secondary goal is to investigate how demographic, genetic, clinical, psychological, and environmental factors affect these associations. In this review, we summarize findings of the ENIGMA-MDD disease working group to date and discuss future directions. We also highlight the challenges and benefits of large-scale data-sharing for mental health research.

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“…The question remains how these measures interact with brain development in individuals at familial risk. As recently reported in a study that included only FDRs-SZ from one site (Utrecht, The Netherlands), current IQ was intertwined with most of the brain abnormalities (15). However, in FDRs-BD, it still remains unclear how IQ and risk for bipolar disorder act on the brain.…”

Section: Discussionmentioning

confidence: 91%

“…Multiple imaging studies have investigated individuals at high familial risk for schizophrenia and/or bipolar disorder, but results of these often small studies have been variable. First-degree relatives of patients with schizophrenia (FDRs-SZ) tend to show smaller brain volumes and larger ventricle volumes compared with control subjects (14,15). In contrast, first-degree relatives of patients with bipolar disorder (FDRs-BD) show regionally larger volumes (16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26).…”

mentioning

confidence: 99%

The Association Between Familial Risk and Brain Abnormalities Is Disease Specific: An ENIGMA-Relatives Study of Schizophrenia and Bipolar Disorder

Zwarte¹,

Brouwer²,

Agartz³

et al. 2019

Biological Psychiatry

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BACKGROUND: Schizophrenia and bipolar disorder share genetic liability, and some structural brain abnormalities are common to both conditions. First-degree relatives of patients with schizophrenia (FDRs-SZ) show similar brain abnormalities to patients, albeit with smaller effect sizes. Imaging findings in first-degree relatives of patients with bipolar disorder (FDRs-BD) have been inconsistent in the past, but recent studies report regionally greater volumes compared with control subjects. METHODS: We performed a meta-analysis of global and subcortical brain measures of 6008 individuals (1228 FDRs-SZ, 852 FDRs-BD, 2246 control subjects, 1016 patients with schizophrenia, 666 patients with bipolar disorder) from 34 schizophrenia and/or bipolar disorder family cohorts with standardized methods. Analyses were repeated with a correction for intracranial volume (ICV) and for the presence of any psychopathology in the relatives and control subjects. RESULTS: FDRs-BD had significantly larger ICV (d = 10.16, q , .05 corrected), whereas FDRs-SZ showed smaller thalamic volumes than control subjects (d = 20.12, q , .05 corrected). ICV explained the enlargements in the brain measures in FDRs-BD. In FDRs-SZ, after correction for ICV, total brain, cortical gray matter, cerebral white matter, cerebellar gray and white matter, and thalamus volumes were significantly smaller; the cortex was thinner (d , 20.09, q , .05 corrected); and third ventricle was larger (d = 10.15, q , .05 corrected). The findings were not explained by psychopathology in the relatives or control subjects. CONCLUSIONS: Despite shared genetic liability, FDRs-SZ and FDRs-BD show a differential pattern of structural brain abnormalities, specifically a divergent effect in ICV. This may imply that the neurodevelopmental trajectories leading to brain anomalies in schizophrenia or bipolar disorder are distinct.

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Running in the Family? Structural Brain Abnormalities and IQ in Offspring, Siblings, Parents, and Co-twins of Patients with Schizophrenia

Cited by 22 publications

References 45 publications

ENIGMA MDD: seven years of global neuroimaging studies of major depression through worldwide data sharing

ENIGMA MDD: seven years of global neuroimaging studies of major depression through worldwide data sharing

ENIGMA MDD: Seven Years of Global Neuroimaging Studies of Major Depression through Worldwide Data Sharing

The Association Between Familial Risk and Brain Abnormalities Is Disease Specific: An ENIGMA-Relatives Study of Schizophrenia and Bipolar Disorder

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