- Email: [email protected]
743. Brain Network Resilience and Accelerated Brain Aging in Schizophrenia
Biological Psychiatry
Saturday Abstracts
Martin Styner2, Amanda Thompson2, Xiujuan Geng3, Barbara Goldman2, John Gilmore2, and Rebecca Santelli2
1
Cedars-Sinai Medical Center, 2University of North Carolina at Chapel Hill, 3University of Hong Kong
Background: Age-related trajectories of gray matter and white matter changes in schizophrenia remain unclear. We sought to measure whether these changes remain stable, are accelerated, or are diminished with age. We also sought to examine whether brain networks in schizophrenia are resilient to any accelerated changes associated with aging. Methods: Gray matter volume, fractional anisotropy and whole-brain white matter networks were mapped in 326 individuals diagnosed with schizophrenia and in 197 healthy comparison subjects of age 20–65 years. Polynomial regression was used to model the influence of age on gray matter volume and fractional anisotropy at a whole-brain and voxel level. Brain network resilience was measured within each network module and compared between patients and controls using permutation testing. Results: While more than 50% of cortico-cortical and corticosubcortical white matter fiber bundles were disrupted in schizophrenia, network modules were more resilient to these disruptions in patients compared to healthy comparison subjects. Significant loss of gray matter volume was evident in schizophrenia, progressively worsening with age to a maximal loss of 8% in the seventh decade of life. The inferred rate of gray matter volume loss was significantly accelerated in schizophrenia up to middle age and plateaued thereafter. In contrast, significant reductions in fractional anisotropy emerged in schizophrenia only after age 35. Conclusions: The findings suggest that schizophrenia is characterized by an initial, rapid rate of gray matter loss that slows in middle life, followed by the emergence of a deficit in white matter that progressively worsens with age at a constant rate. Supported By: National Health and Medical Research Council of Australia Keywords: Schizophrenia, Resilience, Brain Aging, Connectivity, Diffusion Tensor Imaging (DTI)
1
Background: There has been a recent surge of interest in the possibility that the gut microbiome influence brain development and associated risks for mental disorders. However, to date, there have been no studies on the relationship between the gut microbiome and functional brain organization during human infancy. Methods: Resting-state functional magnetic resonance imaging (rsfMRI) was conducted on 39 1-year-old infants who had donated fecal samples for the identification and quantification of bacterial taxa (i.e. enterostate, alpha diversity). Seed-based functional connectivity analysis centered on the amygdala was first conducted given its high relevance in emotional/social behaviors that are documented to be mostly affected by gut microbiome. Independent component analysis (ICA) was also conducted to explore potential network-level effects. Results: Functional connectivity between the right amygdala and bilateral anterior insula significantly (cluster-level P,0.05) differed across three infant groups characterized by distinct microbiome compositions (E1-E3). Consistently, two functional networks overlapped on the detected anterior insula clusters and demonstrated similar profiles across the three groups. Importantly, the interaction strength between the two networks significantly predicted performance on the Mullen scales at 2 years of age (r5 20.51 P 5 0.0036). In addition, there was a superior temporal cluster showing significant connectivity differences with the left amygdala and two other clusters showing significant correlations with alpha diversity. Conclusions: We have demonstrated associations between infant gut microbiome and amygdala-insula functional connectivity, as well as related functional networks and behavior. Future studies should determine whether microbiome–associated changes in neurocircuitry influence later risk for psychopathology, particularly in the realm of anxiety-related behaviors. Supported By: R33MH104330 Keywords: Gut Microbiome, Resting state fMRI, Infants, Amygdala, Insula
Melbourne Neuropsychiatry Centre, 2CHUV, Switzerland, Australia
3
744. Linking Macroscale Connectivity Disruptions with Microscale Measures of Spine Density and Gene Expression Martijn van den Heuvel
SYMPOSIUM Disease Connectomics: From Gene Expression to Large-Scale Brain Networks Saturday, May 20, 2017 - 3:00 PM - 5:00 PM Sapphire AB Chair: Andrew Zalesky Co-Chair: Christos Pantelis 743. Brain Network Resilience and Accelerated Brain Aging in Schizophrenia Andrew Zalesky1, Vanessa Cropley1, Paul Klauser2, Christos Pantelis1, and ASRB Working Group3
University Medical Center Utrecht Background: Schizophrenia is well known to involve changes at both the microscale cellular and macroscale level of brain disconnectivity. At the cellular microscale, schizophrenia has been reported to include pronounced reductions in pyramidal spine density. In parallel, at the macroscale whole-brain level MRI studies have reported disruptions in structural and functional connectivity networks and connectome organization. Heritability and GWAS studies have further shown a strong genetic component of both effects. Here, I will discuss findings of changes at different levels of brain connectivity to be related Methods: Changes in microscale spine density as collated from 201 studies using Golgi staining in post-mortem material were
Biological Psychiatry May 15, 2017; 81:S277–S413 www.sobp.org/journal
S301
Saturday Abstracts
Martin Styner2, Amanda Thompson2, Xiujuan Geng3, Barbara Goldman2, John Gilmore2, and Rebecca Santelli2
1
Cedars-Sinai Medical Center, 2University of North Carolina at Chapel Hill, 3University of Hong Kong
Background: Age-related trajectories of gray matter and white matter changes in schizophrenia remain unclear. We sought to measure whether these changes remain stable, are accelerated, or are diminished with age. We also sought to examine whether brain networks in schizophrenia are resilient to any accelerated changes associated with aging. Methods: Gray matter volume, fractional anisotropy and whole-brain white matter networks were mapped in 326 individuals diagnosed with schizophrenia and in 197 healthy comparison subjects of age 20–65 years. Polynomial regression was used to model the influence of age on gray matter volume and fractional anisotropy at a whole-brain and voxel level. Brain network resilience was measured within each network module and compared between patients and controls using permutation testing. Results: While more than 50% of cortico-cortical and corticosubcortical white matter fiber bundles were disrupted in schizophrenia, network modules were more resilient to these disruptions in patients compared to healthy comparison subjects. Significant loss of gray matter volume was evident in schizophrenia, progressively worsening with age to a maximal loss of 8% in the seventh decade of life. The inferred rate of gray matter volume loss was significantly accelerated in schizophrenia up to middle age and plateaued thereafter. In contrast, significant reductions in fractional anisotropy emerged in schizophrenia only after age 35. Conclusions: The findings suggest that schizophrenia is characterized by an initial, rapid rate of gray matter loss that slows in middle life, followed by the emergence of a deficit in white matter that progressively worsens with age at a constant rate. Supported By: National Health and Medical Research Council of Australia Keywords: Schizophrenia, Resilience, Brain Aging, Connectivity, Diffusion Tensor Imaging (DTI)
1
Background: There has been a recent surge of interest in the possibility that the gut microbiome influence brain development and associated risks for mental disorders. However, to date, there have been no studies on the relationship between the gut microbiome and functional brain organization during human infancy. Methods: Resting-state functional magnetic resonance imaging (rsfMRI) was conducted on 39 1-year-old infants who had donated fecal samples for the identification and quantification of bacterial taxa (i.e. enterostate, alpha diversity). Seed-based functional connectivity analysis centered on the amygdala was first conducted given its high relevance in emotional/social behaviors that are documented to be mostly affected by gut microbiome. Independent component analysis (ICA) was also conducted to explore potential network-level effects. Results: Functional connectivity between the right amygdala and bilateral anterior insula significantly (cluster-level P,0.05) differed across three infant groups characterized by distinct microbiome compositions (E1-E3). Consistently, two functional networks overlapped on the detected anterior insula clusters and demonstrated similar profiles across the three groups. Importantly, the interaction strength between the two networks significantly predicted performance on the Mullen scales at 2 years of age (r5 20.51 P 5 0.0036). In addition, there was a superior temporal cluster showing significant connectivity differences with the left amygdala and two other clusters showing significant correlations with alpha diversity. Conclusions: We have demonstrated associations between infant gut microbiome and amygdala-insula functional connectivity, as well as related functional networks and behavior. Future studies should determine whether microbiome–associated changes in neurocircuitry influence later risk for psychopathology, particularly in the realm of anxiety-related behaviors. Supported By: R33MH104330 Keywords: Gut Microbiome, Resting state fMRI, Infants, Amygdala, Insula
Melbourne Neuropsychiatry Centre, 2CHUV, Switzerland, Australia
3
744. Linking Macroscale Connectivity Disruptions with Microscale Measures of Spine Density and Gene Expression Martijn van den Heuvel
SYMPOSIUM Disease Connectomics: From Gene Expression to Large-Scale Brain Networks Saturday, May 20, 2017 - 3:00 PM - 5:00 PM Sapphire AB Chair: Andrew Zalesky Co-Chair: Christos Pantelis 743. Brain Network Resilience and Accelerated Brain Aging in Schizophrenia Andrew Zalesky1, Vanessa Cropley1, Paul Klauser2, Christos Pantelis1, and ASRB Working Group3
University Medical Center Utrecht Background: Schizophrenia is well known to involve changes at both the microscale cellular and macroscale level of brain disconnectivity. At the cellular microscale, schizophrenia has been reported to include pronounced reductions in pyramidal spine density. In parallel, at the macroscale whole-brain level MRI studies have reported disruptions in structural and functional connectivity networks and connectome organization. Heritability and GWAS studies have further shown a strong genetic component of both effects. Here, I will discuss findings of changes at different levels of brain connectivity to be related Methods: Changes in microscale spine density as collated from 201 studies using Golgi staining in post-mortem material were
Biological Psychiatry May 15, 2017; 81:S277–S413 www.sobp.org/journal
S301