Abnormalities in left inferior frontal gyral thickness and parahippocampal gyral volume in young people at high genetic risk for bipolar disorder

2016 ◽  
Vol 46 (10) ◽  
pp. 2083-2096 ◽  
Author(s):  
G. Roberts ◽  
R. Lenroot ◽  
A. Frankland ◽  
P. K. Yeung ◽  
N. Gale ◽  
...  

BackgroundFronto-limbic structural brain abnormalities have been reported in patients with bipolar disorder (BD), but findings in individuals at increased genetic risk of developing BD have been inconsistent. We conducted a study in adolescents and young adults (12–30 years) comparing measures of fronto-limbic cortical and subcortical brain structure between individuals at increased familial risk of BD (at risk; AR), subjects with BD and controls (CON). We separately examined cortical volume, thickness and surface area as these have distinct neurodevelopmental origins and thus may reflect differential effects of genetic risk.MethodWe compared fronto-limbic measures of grey and white matter volume, cortical thickness and surface area in 72 unaffected-risk individuals with at least one first-degree relative with bipolar disorder (AR), 38 BD subjects and 72 participants with no family history of mental illness (CON).ResultsThe AR group had significantly reduced cortical thickness in the left pars orbitalis of the inferior frontal gyrus (IFG) compared with the CON group, and significantly increased left parahippocampal gyral volume compared with those with BD.ConclusionsThe finding of reduced cortical thickness of the left pars orbitalis in AR subjects is consistent with other evidence supporting the IFG as a key region associated with genetic liability for BD. The greater volume of the left parahippocampal gyrus in those at high risk is in line with some prior reports of regional increases in grey matter volume in at-risk subjects. Assessing multiple complementary morphometric measures may assist in the better understanding of abnormal developmental processes in BD.

2018 ◽  
Vol 49 (08) ◽  
pp. 1308-1315 ◽  
Author(s):  
V. Drobinin ◽  
C. Slaney ◽  
J. Garnham ◽  
L. Propper ◽  
R. Uher ◽  
...  

AbstractBackgroundLarger grey matter volume of the inferior frontal gyrus (IFG) is among the most replicated biomarkers of genetic risk for bipolar disorders (BD). However, the IFG is a heterogeneous prefrontal region, and volumetric findings can be attributable to changes in cortical thickness (CT), surface area (SA) or gyrification. Here, we investigated the morphometry of IFG in participants at genetic risk for BD.MethodsWe quantified the IFG cortical grey matter volume in 29 affected, 32 unaffected relatives of BD probands, and 42 controls. We then examined SA, CT, and cortical folding in subregions of the IFG.ResultsWe found volumetric group differences in the right IFG, with the largest volumes in unaffected high-risk and smallest in control participants (F2,192 = 3.07, p = 0.01). The volume alterations were localized to the pars triangularis of the IFG (F2,97 = 4.05, p = 0.02), with no differences in pars opercularis or pars orbitalis. Pars triangularis volume was highly correlated with its SA [Pearson r(101) = 0.88, p < 0.001], which significantly differed between the groups (F2,97 = 4.45, p = 0.01). As with volume, the mean SA of the pars triangularis was greater in unaffected (corrected p = 0.02) and affected relatives (corrected p = 0.05) compared with controls. We did not find group differences in pars triangularis CT or gyrification.ConclusionsThese findings strengthen prior knowledge about the volumetric findings in this region and provide a new insight into the localization and topology of IFG alterations. The unique nature of rIFG morphology in BD, with larger volume and SA early in the course of illness, could have practical implications for detection of participants at risk for BD.


2021 ◽  
pp. 1-12
Author(s):  
Simon Schmitt ◽  
Tina Meller ◽  
Frederike Stein ◽  
Katharina Brosch ◽  
Kai Ringwald ◽  
...  

Abstract Background MRI-derived cortical folding measures are an indicator of largely genetically driven early developmental processes. However, the effects of genetic risk for major mental disorders on early brain development are not well understood. Methods We extracted cortical complexity values from structural MRI data of 580 healthy participants using the CAT12 toolbox. Polygenic risk scores (PRS) for schizophrenia, bipolar disorder, major depression, and cross-disorder (incorporating cumulative genetic risk for depression, schizophrenia, bipolar disorder, autism spectrum disorder, and attention-deficit hyperactivity disorder) were computed and used in separate general linear models with cortical complexity as the regressand. In brain regions that showed a significant association between polygenic risk for mental disorders and cortical complexity, volume of interest (VOI)/region of interest (ROI) analyses were conducted to investigate additional changes in their volume and cortical thickness. Results The PRS for depression was associated with cortical complexity in the right orbitofrontal cortex (right hemisphere: p = 0.006). A subsequent VOI/ROI analysis showed no association between polygenic risk for depression and either grey matter volume or cortical thickness. We found no associations between cortical complexity and polygenic risk for either schizophrenia, bipolar disorder or psychiatric cross-disorder when correcting for multiple testing. Conclusions Changes in cortical complexity associated with polygenic risk for depression might facilitate well-established volume changes in orbitofrontal cortices in depression. Despite the absence of psychopathology, changed cortical complexity that parallels polygenic risk for depression might also change reward systems, which are also structurally affected in patients with depressive syndrome.


2018 ◽  
Vol 115 (22) ◽  
pp. E5154-E5163 ◽  
Author(s):  
Xiang-Zhen Kong ◽  
Samuel R. Mathias ◽  
Tulio Guadalupe ◽  
David C. Glahn ◽  
Barbara Franke ◽  
...  

Hemispheric asymmetry is a cardinal feature of human brain organization. Altered brain asymmetry has also been linked to some cognitive and neuropsychiatric disorders. Here, the ENIGMA (Enhancing NeuroImaging Genetics through Meta-Analysis) Consortium presents the largest-ever analysis of cerebral cortical asymmetry and its variability across individuals. Cortical thickness and surface area were assessed in MRI scans of 17,141 healthy individuals from 99 datasets worldwide. Results revealed widespread asymmetries at both hemispheric and regional levels, with a generally thicker cortex but smaller surface area in the left hemisphere relative to the right. Regionally, asymmetries of cortical thickness and/or surface area were found in the inferior frontal gyrus, transverse temporal gyrus, parahippocampal gyrus, and entorhinal cortex. These regions are involved in lateralized functions, including language and visuospatial processing. In addition to population-level asymmetries, variability in brain asymmetry was related to sex, age, and intracranial volume. Interestingly, we did not find significant associations between asymmetries and handedness. Finally, with two independent pedigree datasets (n = 1,443 and 1,113, respectively), we found several asymmetries showing significant, replicable heritability. The structural asymmetries identified and their variabilities and heritability provide a reference resource for future studies on the genetic basis of brain asymmetry and altered laterality in cognitive, neurological, and psychiatric disorders.


2010 ◽  
Vol 196 (2) ◽  
pp. 150-157 ◽  
Author(s):  
Michael P. Harms ◽  
Lei Wang ◽  
Carolina Campanella ◽  
Kristina Aldridge ◽  
Amanda J. Moffitt ◽  
...  

BackgroundThe relatives of individuals with schizophrenia exhibit deficits of overall frontal lobe volume, consistent with a genetic contribution to these deficits.AimsTo quantify the structure of gyral-defined subregions of prefrontal cortex in individuals with schizophrenia and their siblings.MethodGrey matter volume, cortical thickness, and surface area of the superior, middle and inferior frontal gyri were measured in participants with schizophrenia and their unaffected (non-psychotic) siblings (n = 26 pairs), and controls and their siblings (n = 40 pairs).ResultsGrey matter volume was reduced in the middle and inferior frontal gyri of individuals with schizophrenia, relative to controls. However, only inferior frontal gyrus volume was also reduced in the unaffected siblings of those with schizophrenia, yielding a volume intermediate between their affected siblings and controls.ConclusionsThe structure of subregions of the prefrontal cortex may be differentially influenced by genetic factors in schizophrenia, with inferior frontal gyrus volume being most related to familial risk.


2013 ◽  
Vol 44 (3) ◽  
pp. 489-498 ◽  
Author(s):  
S. Tognin ◽  
A. Riecher-Rössler ◽  
E. M. Meisenzahl ◽  
S. J. Wood ◽  
C. Hutton ◽  
...  

BackgroundGrey matter volume and cortical thickness represent two complementary aspects of brain structure. Several studies have described reductions in grey matter volume in people at ultra-high risk (UHR) of psychosis; however, little is known about cortical thickness in this group. The aim of the present study was to investigate cortical thickness alterations in UHR subjects and compare individuals who subsequently did and did not develop psychosis.MethodWe examined magnetic resonance imaging data collected at four different scanning sites. The UHR subjects were followed up for at least 2 years. Subsequent to scanning, 50 UHR subjects developed psychosis and 117 did not. Cortical thickness was examined in regions previously identified as sites of neuroanatomical alterations in UHR subjects, using voxel-based cortical thickness.ResultsAt baseline UHR subjects, compared with controls, showed reduced cortical thickness in the right parahippocampal gyrus (p < 0.05, familywise error corrected). There were no significant differences in cortical thickness between the UHR subjects who later developed psychosis and those who did not.ConclusionsThese data suggest that UHR symptomatology is characterized by alterations in the thickness of the medial temporal cortex. We did not find evidence that the later progression to psychosis was linked to additional alterations in cortical thickness, although we cannot exclude the possibility that the study lacked sufficient power to detect such differences.


2019 ◽  
Vol 22 ◽  
pp. 101695
Author(s):  
Nefize Yalin ◽  
Aybala Saricicek ◽  
Ceren Hidiroglu ◽  
Andre Zugman ◽  
Nese Direk ◽  
...  

2019 ◽  
Vol 90 (10) ◽  
pp. 1124-1130 ◽  
Author(s):  
Stefano Gazzina ◽  
Mario Grassi ◽  
Enrico Premi ◽  
Maura Cosseddu ◽  
Antonella Alberici ◽  
...  

ObjectiveCognitively engaging lifestyles have been associated with reduced risk of conversion to dementia. Multiple mechanisms have been advocated, including increased brain volumes (ie, brain reserve) and reduced disease progression (ie, brain maintenance). In cross-sectional studies of presymptomatic frontotemporal dementia (FTD), higher education has been related to increased grey matter volume. Here, we examine the effect of education on grey matter loss over time.MethodsTwo-hundred twenty-nine subjects at-risk of carrying a pathogenic mutation leading to FTD underwent longitudinal cognitive assessment and T1-weighted MRI at baseline and at 1 year follow-up. The first principal component score of the graph-Laplacian Principal Component Analysis on 112 grey matter region-of-interest volumes was used to summarise the grey matter volume (GMV). The effects of education on cognitive performances and GMV at baseline and on the change between 1 year follow-up and baseline (slope) were tested by Structural Equation Modelling.ResultsHighly educated at-risk subjects had better cognition and higher grey matter volume at baseline; moreover, higher educational attainment was associated with slower loss of grey matter over time in mutation carriers.ConclusionsThis longitudinal study demonstrates that even in presence of ongoing pathological processes, education may facilitate both brain reserve and brain maintenance in the presymptomatic phase of genetic FTD.


2009 ◽  
Vol 195 (3) ◽  
pp. 218-226 ◽  
Author(s):  
Nikolaos Koutsouleris ◽  
Gisela J. E. Schmitt ◽  
Christian Gaser ◽  
Ronald Bottlender ◽  
Johanna Scheuerecker ◽  
...  

BackgroundStructural brain abnormalities have been described in individuals with an at-risk mental state for psychosis. However, the neuroanatomical underpinnings of the early and late at-risk mental state relative to clinical outcome remain unclear.AimsTo investigate grey matter volume abnormalities in participants in a putatively early or late at-risk mental state relative to their prospective clinical outcome.MethodVoxel-based morphometry of magnetic resonance imaging data from 20 people with a putatively early at-risk mental state (ARMS–E group) and 26 people with a late at-risk mental state (ARMS–L group) as well as from 15 participants with at-risk mental states with subsequent disease transition (ARMS–T group) and 18 participants without subsequent disease transition (ARMS–NT group) were compared with 75 healthy volunteers.ResultsCompared with healthy controls, ARMS–L participants had grey matter volume losses in frontotemporolimbic structures. Participants in the ARMS–E group showed bilateral temporolimbic alterations and subtle prefrontal abnormalities. Participants in the ARMS–T group had prefrontal alterations relative to those in the ARMS–NT group and in the healthy controls that overlapped with the findings in the ARMS–L group.ConclusionsBrain alterations associated with the early at-risk mental state may relate to an elevated susceptibility to psychosis, whereas alterations underlying the late at-risk mental state may indicate a subsequent transition to psychosis.


2011 ◽  
Vol 17 (6) ◽  
pp. 1080-1093 ◽  
Author(s):  
C.B. Hartberg ◽  
K. Sundet ◽  
L.M. Rimol ◽  
U.K. Haukvik ◽  
E.H. Lange ◽  
...  

AbstractRelationships between cortical brain structure and neurocognitive functioning have been reported in schizophrenia, but findings are inconclusive, and only a few studies in bipolar disorder have addressed this issue. This is the first study to directly compare relationships between cortical thickness and surface area with neurocognitive functioning in patients with schizophrenia (n = 117) and bipolar disorder (n = 121) and healthy controls (n = 192). MRI scans were obtained, and regional cortical thickness and surface area measurements were analyzed for relationships with test scores from 6 neurocognitive domains. In the combined sample, cortical thickness in the right rostral anterior cingulate was inversely related to working memory, and cortical surface area in four frontal and temporal regions were positively related to neurocognitive functioning. A positive relationship between left transverse temporal thickness and processing speed was specific to schizophrenia. A negative relationship between right temporal pole thickness and working memory was specific to bipolar disorder. In conclusion, significant cortical structure/function relationships were found in a large sample of healthy controls and patients with schizophrenia or bipolar disorder. The differences that were found between schizophrenia and bipolar may indicate differential relationship patterns in the two disorders, which may be of relevance for understanding the underlying pathophysiology. (JINS, 2011, 17, 1080–1093)


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