Larger right inferior frontal gyrus volume and surface area in participants at genetic risk for bipolar disorders

Drobinin, Vladislav; Slaney, Claire; Garnham, Julie; Propper, Lukáš; Uher, Rudolf; Alda, Martin; Hájek, Tomáš

doi:10.1017/s0033291718001903

Cited by 23 publications

(38 citation statements)

References 79 publications

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“…In contrast to smaller brain volumes in patients with bipolar disorder (7,8), we found larger brain volumes in their relatives. This is in keeping with other studies, which have reported larger regional gray matter volumes in participants at genetic risk (16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26). As expected, FDRs-SZ had smaller brain volumes, similar to findings in patients with schizophrenia (6,(10)(11)(12), but with smaller effect sizes, in line with a previous retrospective meta-analysis and a review (14,36).…”

Section: Discussionsupporting

confidence: 91%

“…Interestingly, in contrast to FDRs-BD, patients with bipolar disorder did not show an ICV enlargement, confirming previous findings in a large meta-analysis (7). In the early stages of the disease, however, regional increases have been reported (21,22,24,26,56,57). Given the positive relationship between genetic risk for bipolar disorder and ICV reported in twins (13), one could argue that the genetic liability for bipolar disorder leads to a larger ICV as represented in our findings of larger ICV in FDRs-BD.…”

Section: Discussionsupporting

confidence: 86%

“…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). Many of these schizophrenia and bipolar disorder family studies grouped all FDRs together regardless of kinship.…”

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confidence: 99%

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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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Section: Discussionsupporting

confidence: 91%

Section: Discussionsupporting

confidence: 86%

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confidence: 99%

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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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“…The neural substrate of predisposition, which is associated with the genetic load for the disorder, is consistent in RELs and patients, and may include altered activation in parietal cortex across all fMRI tasks and in OFC during reward, and the amygdala during emotional processing together with increased brain volume in rIFG and STG. Most interestingly, a recent report on the volumetric changes in BD indicated that, within the rIFG, the surface area of the pars triangularis, which is strongly modulated by the genetic variants associated with the risk for BD, showed the greatest increase in both RELs and patients with BD . Previous studies in other psychiatric disorders (eg, schizophrenia, autism, etc.)…”

Section: Discussionmentioning

confidence: 95%

“…Previous studies in other psychiatric disorders (eg, schizophrenia, autism, etc.) have suggested that cortical volume increases may reflect aberrant neurodevelopment with altered synaptic remodeling (eg, reduced synaptic pruning) …”

Section: Discussionmentioning

confidence: 99%

Neural signatures of the risk for bipolar disorder: A meta‐analysis of structural and functional neuroimaging studies

et al. 2018

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Objective: Widespread functional and structural alterations in the brain have been extensively reported in unaffected relatives (RELs) of patients with bipolar disorder (BD) who are at genetic risk for BD. A sufficiently powered meta-analysis of structural (sMRI) and functional magnetic resonance imaging (fMRI) alterations in RELs is still lacking.Methods: Functional and structural magnetic resonance imaging studies investigating RELs and healthy controls (HCs) published by July 2017 were included in the meta-analyses. Study procedures were conducted in accordance with the Meta-analysis Of Observational Studies in Epidemiology (MOOSE) guidelines. Random-effects coordinate-based meta-analyses were performed across all the studies per imaging modality using Seed-based d Mapping (SDM). For fMRI studies, meta-analyses were calculated for each task type. For sMRI studies, regional volumetric changes-analyses were estimated using R. Finally, multimodal meta-analyses of structural and functional abnormalities were performed. Results:Sixty-nine imaging studies (2195 RELs and 3169 HCs) were included in the meta-analyses. RELs showed hyperactivation in the fronto-striatal regions as well as parietal hypoactivation during cognition. Also, activation was increased in the amygdala during emotional processing and in the orbitofrontal cortex during reward, respectively. Frontal and superior temporal cortex were hypertrophic in RELs. The right inferior frontal gyrus (rIFG) showed both increased activation during cognitive tasks and greater volume in RELs. Conclusions:Our findings demonstrate that increased brain volume and activation are present in RELs and may represent intermediate phenotypes for the disorder.Furthermore, some neural changes including increased rIFG volume may be associated with the resilience to BD. K E Y W O R D Sbipolar disorders, functional magnetic resonance imaging, intermediate phenotype, metaanalysis, relatives, structural magnetic resonance imaging

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Aberrant brain network topology in the frontoparietal-limbic circuit in bipolar disorder: a graph-theory study

Zhang

et al. 2021

Eur Arch Psychiatry Clin Neurosci

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Larger right inferior frontal gyrus volume and surface area in participants at genetic risk for bipolar disorders

Cited by 23 publications

References 79 publications

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

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

Neural signatures of the risk for bipolar disorder: A meta‐analysis of structural and functional neuroimaging studies

Aberrant brain network topology in the frontoparietal-limbic circuit in bipolar disorder: a graph-theory study

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