Antioxidative Defense Genes and Brain Structure in Youth Bipolar Disorder

Abstract Background Oxidative stress is implicated in the neuropathology of bipolar disorder (BD). We investigated the association of single-nucleotide polymorphisms (SNPs) in the antioxidative genes superoxide dismutase 2 (SOD2) and glutathione peroxidase 3 (GPX3) with structural neuroimaging phenotypes in youth BD. Methods SOD2 rs4880 and GPX3 rs3792797 SNP genotypes, along with structural magnetic resonance imaging, were obtained from 147 youth (BD=75; healthy controls (HC)=72). Images were processed using FreeSurfer, yielding surface area, volume, and thickness values for regions of interest (ROI; prefrontal cortex (PFC), caudal anterior cingulate cortex (cACC), hippocampus) and for vertex-wise whole brain analysis. Analyses controlled for age, sex, race, and intracranial volume for volume area, and thickness analyses. Result ROI analyses revealed diagnosis-by-SOD2 rs4880 interaction effects for cACC volume and surface area, and PFC volume; in each case, there was lower volume/area in the BD GG genotype group vs. the HC GG genotype group. There was a significant BD diagnosis x GPX3 rs3793797 interaction effect for PFC surface area, where area was lower in the BD A-allele carrier group vs. the other genotype groups. Vertex-wise analyses revealed significant interaction effects in frontal, temporal, and parietal regions, related to smaller brain structure in the BD SOD2 rs4880 GG group and BD GPX3 rs3793797 A-allele carrier group. Conclusion We found preliminary evidence that SOD2 rs4880 and GPX3 rs3792797 are differentially associated with brain structure in youth with BD, in regions that are relevant to BD. Further studies incorporating additional neuroimaging phenotypes and blood levels of oxidative stress markers are warranted.

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Neurostructural Correlates of Cannabis Use in Adolescent Bipolar Disorder

The International Journal of Neuropsychopharmacology ◽

10.1093/ijnp/pyaa077 ◽

2020 ◽

Author(s):

Alysha A Sultan ◽

Kody G Kennedy ◽

Lisa Fiksenbaum ◽

Bradley J MacIntosh ◽

Benjamin I Goldstein

Keyword(s):

Bipolar Disorder ◽

Prefrontal Cortex ◽

Brain Structure ◽

Social Acceptance ◽

Region Of Interest ◽

Cannabis Use ◽

Anterior Cingulate ◽

Intracranial Volume ◽

Significant Group ◽

Healthy Control

Abstract Objective Little is known regarding the association of cannabis use with brain structure in adolescents with bipolar disorder (BD). This subject is timely, given expanded availability of cannabis contemporaneously with increased social acceptance and diminished societal constraints to access. Therefore, we set out to examine this topic in a sample of adolescents with BD and healthy control (HC) adolescents. Methods Participants included 144 adolescents (47 BD with cannabis use [BDCB+; including 13 with cannabis use disorder], 34 BD without cannabis use [BDCB-], 63 HC without cannabis use) ages 13-20 years. FreeSurfer-processed 3T MRI with T1-weighted contrast, yielded measures of cortical thickness, surface area (SA), and volume. Region of interest (ROI; amygdala, hippocampus, ventrolateral prefrontal cortex [vlPFC], ventromedial prefrontal cortex [vmPFC], and anterior cingulate cortex [ACC]), analyses and exploratory vertex-wise analysis were undertaken. A general linear model tested for between-group differences, accounting for age, sex, and intracranial volume. Results Vertex-wise analysis revealed significant group effects in frontal and parietal regions. In post-hoc analyses, BDCB+ exhibited larger volume and SA in parietal regions, and smaller thickness in frontal regions, relative to HC and BDCB-. BDCB- had smaller volume, SA and thickness in parietal and frontal regions relative to HC. There were no significant ROI findings after correcting for multiple comparisons. Conclusion This study found that cannabis use is associated with differences in regional brain structure among adolescents with BD. Future prospective studies are necessary to determine the direction of the observed association and to assess for dose effects.

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Brain Cortical Thickness and Surface Area Correlates of Neurocognitive Performance in Patients with Schizophrenia, Bipolar Disorder, and Healthy Adults

Journal of the International Neuropsychological Society ◽

10.1017/s1355617711001081 ◽

2011 ◽

Vol 17 (6) ◽

pp. 1080-1093 ◽

Cited By ~ 52

Author(s):

C.B. Hartberg ◽

K. Sundet ◽

L.M. Rimol ◽

U.K. Haukvik ◽

E.H. Lange ◽

...

Keyword(s):

Bipolar Disorder ◽

Working Memory ◽

Surface Area ◽

Cortical Thickness ◽

Negative Relationship ◽

Anterior Cingulate ◽

Neurocognitive Functioning ◽

Healthy Controls ◽

Neurocognitive Performance ◽

Mri Scans

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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Increased oxidative stress in the anterior cingulate cortex of subjects with bipolar disorder and schizophrenia

Bipolar Disorders ◽

10.1111/j.1399-5618.2009.00717.x ◽

2009 ◽

Vol 11 (5) ◽

pp. 523-529 ◽

Cited By ~ 159

Author(s):

Jun-Feng Wang ◽

Li Shao ◽

Xiujun Sun ◽

L Trevor Young

Keyword(s):

Oxidative Stress ◽

Bipolar Disorder ◽

Anterior Cingulate Cortex ◽

Cingulate Cortex ◽

Anterior Cingulate

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The protective impact of education on brain structure and function in Alzheimer’s Disease

10.21203/rs.3.rs-73112/v2 ◽

2020 ◽

Author(s):

Wanqiu Zhu ◽

Xiaoshu Li ◽

Xiaohu Li ◽

Haibao Wang ◽

Meiqin Li ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Frontal Cortex ◽

Brain Structure ◽

Structure And Function ◽

Anterior Cingulate ◽

Angular Gyrus ◽

Intracranial Volume ◽

Brain Structure And Function ◽

And Function

Abstract Background: The Cognitive Reserve (CR) theory posits that brains with higher reserve can cope with more cerebral damage to minimize clinical manifestations. The aim of this study was to examine the effect of education (CR proxy) on brain structure and function in Alzheimer’s disease (AD) and amnestic mild cognitive impairment (aMCI) patients and in cognitively healthy elderly (HC) individuals.Methods: Fifty-seven AD patients, 57 aMCI patients and 48 HCs were included to investigate the relationships between education years and gray matter volume (GMV), regional homogeneity (ReHo) and functional connectivity (FC) in brain regions to show associations with both structure and function. Taking the severity of the disease into account, we further assessed the relationships in AD stratified analyses.Results: In AD group, the GMV of the dorsal anterior cingulate cortex (dACC) and ReHo in the left inferior temporal cortex (ITC) were inversely associated with education years, after adjustment for age, sex, Mini-Mental State Examination (MMSE), and total intracranial volume or head motion parameters. Seed-based FC analyses revealed that education years were negatively correlated with the FC between the left anterior ITC and left mid frontal cortex as well as right superior frontal cortex and right angular gyrus. Stratified analyses results indicated that this negative relation between education and GMV, ReHo, FC was mainly present in mild AD, which was attenuated in moderate AD and aMCI groups.Conclusions: Our results support the CR theory, and suggest that CR may be protective against AD related brain pathology at the early stage of clinical dementia. These findings could provide the locus of CR-related functional brain mechanisms and a specific time-window for therapeutic interventions to help AD patients to cope better with the brain pathological damage by increasing CR.

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The protective impact of education on brain structure and function in Alzheimer’s disease

BMC Neurology ◽

10.1186/s12883-021-02445-9 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Wanqiu Zhu ◽

Xiaoshu Li ◽

Xiaohu Li ◽

Haibao Wang ◽

Meiqin Li ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Frontal Cortex ◽

Brain Structure ◽

Structure And Function ◽

Anterior Cingulate ◽

Angular Gyrus ◽

Intracranial Volume ◽

Brain Structure And Function ◽

And Function

Abstract Background The Cognitive Reserve (CR) theory posits that brains with higher reserve can cope with more cerebral damage to minimize clinical manifestations. The aim of this study was to examine the effect of education (CR proxy) on brain structure and function in Alzheimer’s disease (AD) and amnestic mild cognitive impairment (aMCI) patients and in cognitively healthy elderly (HC) individuals. Methods Fifty-seven AD patients, 57 aMCI patients and 48 HCs were included to investigate the relationships between education years and gray matter volume (GMV), regional homogeneity (ReHo) and functional connectivity (FC) in brain regions to show associations with both structure and function. Taking the severity of the disease into account, we further assessed the relationships in AD stratified analyses. Results In AD group, the GMV of the dorsal anterior cingulate cortex (dACC) and ReHo in the left inferior temporal cortex (ITC) were inversely associated with education years, after adjustment for age, sex, Mini-Mental State Examination (MMSE), and total intracranial volume or head motion parameters. Seed-based FC analyses revealed that education years were negatively correlated with the FC between the left anterior ITC and left mid frontal cortex as well as right superior frontal cortex and right angular gyrus. Stratified analyses results indicated that this negative relation between education and GMV, ReHo, FC was mainly present in mild AD, which was attenuated in moderate AD and aMCI groups. Conclusions Our results support the CR theory, and suggest that CR may be protective against AD related brain pathology at the early stage of clinical dementia. These findings could provide the locus of CR-related functional brain mechanisms and a specific time-window for therapeutic interventions to help AD patients to cope better with the brain pathological damage by increasing CR.

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Neuroanatomical markers of familial risk in adolescents with conduct disorder and their unaffected relatives

Psychological Medicine ◽

10.1017/s0033291721003202 ◽

2021 ◽

pp. 1-11

Author(s):

Graeme Fairchild ◽

Kate Sully ◽

Luca Passamonti ◽

Marlene Staginnus ◽

Angela Darekar ◽

...

Keyword(s):

Conduct Disorder ◽

Surface Area ◽

Brain Structure ◽

Structural Changes ◽

Familial Risk ◽

Temporal Cortex ◽

Lower Surface ◽

Anterior Cingulate ◽

Inferior Temporal Cortex ◽

Group Differences

Abstract Background Previous studies have reported brain structure abnormalities in conduct disorder (CD), but it is unclear whether these neuroanatomical alterations mediate the effects of familial (genetic and environmental) risk for CD. We investigated brain structure in adolescents with CD and their unaffected relatives (URs) to identify neuroanatomical markers of familial risk for CD. Methods Forty-one adolescents with CD, 24 URs of CD probands, and 38 healthy controls (aged 12–18), underwent structural magnetic resonance imaging. We performed surface-based morphometry analyses, testing for group differences in cortical volume, thickness, surface area, and folding. We also assessed the volume of key subcortical structures. Results The CD and UR groups both displayed structural alterations (lower surface area and folding) in left inferior parietal cortex compared with controls. In contrast, CD participants showed lower insula and pars opercularis volume than controls, and lower surface area and folding in these regions than controls and URs. The URs showed greater folding in rostral anterior cingulate and inferior temporal cortex than controls and greater medial orbitofrontal folding than CD participants. The surface area and volume differences were not significant when controlling for attention-deficit/hyperactivity disorder comorbidity. There were no group differences in subcortical volumes. Conclusions These findings suggest that alterations in inferior parietal cortical structure partly mediate the effects of familial risk for CD. These structural changes merit investigation as candidate endophenotypes for CD. Neuroanatomical changes in medial orbitofrontal and anterior cingulate cortex differentiated between URs and the other groups, potentially reflecting neural mechanisms of resilience to CD.

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Cortical thickness, cortical surface area and subcortical volumes in schizophrenia and bipolar disorder patients with cannabis use

10.26226/morressier.5971be84d462b80290b52671 ◽

2017 ◽

Author(s):

Cecilie Bhandari Hartberg

Keyword(s):

Bipolar Disorder ◽

Surface Area ◽

Cortical Thickness ◽

Cannabis Use ◽

Cortical Surface ◽

Cortical Surface Area ◽

Subcortical Volumes

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The relationship between brain structure and general psychopathology in preadolescents

10.31234/osf.io/r4pxy ◽

2020 ◽

Author(s):

Louise Mewton ◽

Briana Lees ◽

Lindsay Squeglia ◽

Miriam K. Forbes ◽

Matthew Sunderland ◽

...

Keyword(s):

Mental Disorders ◽

Surface Area ◽

Brain Structure ◽

Parental Education ◽

Mental Illnesses ◽

General Psychopathology ◽

Control Approach ◽

Cortical Volume ◽

Subcortical Regions ◽

The Relationship

Categorical mental disorders are being recognized as suboptimal targets in clinical neuroscience due to poor reliability as well as high rates of heterogeneity within, and comorbidity between, mental disorders. As an alternative to the case-control approach, recent studies have focused on the relationship between neurobiology and latent dimensions of psychopathology. The current study aimed to investigate the relationship between brain structure and psychopathology in the critical preadolescent period when psychopathology is emerging. This study included baseline data from the Adolescent Brain and Cognitive Development (ABCD) Study® (n = 11,721; age range = 9-10 years; male = 52.2%). General psychopathology, externalizing, internalizing, and thought disorder dimensions were based on a higher-order model of psychopathology and estimated using Bayesian plausible values. Outcome variables included global and regional cortical volume, thickness, and surface area. Higher levels of psychopathology across all dimensions were associated with lower volume and surface area globally, as well as widespread and pervasive alterations across the majority of cortical and subcortical regions studied, after adjusting for sex, race/ethnicity, and parental education. The relationships between general psychopathology and brain structure were attenuated when adjusting for cognitive functioning. There was evidence of a relationship between externalizing psychopathology and frontal regions of the cortex that was independent of general psychopathology. The current study identified lower cortical volume and surface area as transdiagnostic biomarkers for general psychopathology in preadolescence. The widespread and pervasive relationships between general psychopathology and brain structure may reflect cognitive dysfunction that is a feature across a range of mental illnesses.

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