Neurite Orientation Dispersion and Density Imaging (NODDI) and duration of untreated psychosis in antipsychotic medication-naïve first episode psychosis patients

Kraguljac, Nina; Monroe, William S.; Anthony, Thomas; Jindal, Ripu D.; Hill, Harrison; Lahti, Adrienne C.

doi:10.1016/j.ynirp.2021.100005

Cited by 8 publications

(8 citation statements)

References 49 publications

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“…Case-control studies of schizophrenia have increasingly reported significant differences in grey matter microstructure [26], such as increased mean diffusivity (MD) [28][29][30], decreased fractional anisotropy (FA) [31], decreased neurite density index (NDI) [26] and orientation dispersion index (ODI) [32]. Significant microstructural abnormalities of white matter tracts have also been reported, including decreased FA [13,33] and NDI [34,35], and increased MD [13], in schizophrenia case-control studies.…”

Section: Introductionmentioning

confidence: 99%

Grey and white matter microstructure is associated with polygenic risk for schizophrenia

et al. 2021

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Recent discovery of approximately 270 common genetic variants associated with schizophrenia has enabled polygenic risk scores (PRS) to be measured in the population. We hypothesized that normal variation in PRS would be associated with magnetic resonance imaging (MRI) phenotypes of brain morphometry and tissue composition. We used the largest extant genome-wide association dataset (N = 69,369 cases and N = 236,642 healthy controls) to measure PRS for schizophrenia in a large sample of adults from the UK Biobank (Nmax = 29,878) who had multiple micro- and macrostructural MRI metrics measured at each of 180 cortical areas, seven subcortical structures, and 15 major white matter tracts. Linear mixed-effect models were used to investigate associations between PRS and brain structure at global and regional scales, controlled for multiple comparisons. Polygenic risk was significantly associated with reduced neurite density index (NDI) at global brain scale, at 149 cortical regions, five subcortical structures, and 14 white matter tracts. Other microstructural parameters, e.g., fractional anisotropy, that were correlated with NDI were also significantly associated with PRS. Genetic effects on multiple MRI phenotypes were co-located in temporal, cingulate, and prefrontal cortical areas, insula, and hippocampus. Post-hoc bidirectional Mendelian randomization analyses provided preliminary evidence in support of a causal relationship between (reduced) thalamic NDI and (increased) risk of schizophrenia. Risk-related reduction in NDI is plausibly indicative of reduced density of myelinated axons and dendritic arborization in large-scale cortico-subcortical networks. Cortical, subcortical, and white matter microstructure may be linked to the genetic mechanisms of schizophrenia.

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Section: Introductionmentioning

confidence: 99%

Grey and white matter microstructure is associated with polygenic risk for schizophrenia

et al. 2021

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“…The dataset here has subject overlap with our recent reports ( Briend et al, 2020 , Kraguljac et al, 2020 , Kraguljac et al, 2021 , Maximo et al, 2020 , Nelson et al, 2020 ). Data for NCT 034420101 is deposited to the NDA data archive and shared per NIMH agreement.…”

Section: Introductionmentioning

confidence: 99%

Salience network glutamate and brain connectivity in medication-naïve first episode patients – A multimodal magnetic resonance spectroscopy and resting state functional connectivity MRI study

Máximo

Briend

Armstrong

et al. 2021

NeuroImage: Clinical

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Highlights The pathophysiology of salience network in schizophrenia remains poorly understood. We found reduced connectivity, but no Glx alterations in psychosis patients. The relationship between Glx and connectivity was abnormal in psychosis patients. Findings suggest altered glutamatergic neurometabolism and connectivity in psychosis.

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“…Case-control studies of schizophrenia have increasingly reported significant differences in grey matter micro-structure (26), such as increased mean diffusivity (MD) [28, 29, 30], decreased fractional anisotropy (FA) [31], decreased neurite density index (NDI) [26] and orientation dispersion index (ODI) [32]. Significant micro-structural abnormalities of white matter tracts have also been reported, including decreased FA [14, 33] and NDI [34, 35], and increased MD [14], in schizophrenia case-control studies.…”

Section: Introductionmentioning

confidence: 99%

Grey and white matter micro-structure is associated with polygenic risk for schizophrenia

Stauffer

Bethlehem

Warrier

et al. 2021

Preprint

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Background Recent discovery of hundreds of common gene variants associated with schizophrenia has enabled polygenic risk scores (PRS) to be measured in the population. It is hypothesized that normal variation in genetic risk of schizophrenia should be associated with MRI changes in brain morphometry and tissue composition. Methods We used the largest extant genome-wide association dataset (N = 69,369 cases and N = 236,642 healthy controls) to measure PRS for schizophrenia in a large sample of adults from the UK Biobank (Nmax = 29,878) who had multiple micro- and macro-structural MRI metrics measured at each of 180 cortical areas and seven subcortical structures. Linear mixed effect models were used to investigate associations between schizophrenia PRS and brain structure at global and regional scales, controlled for multiple comparisons. Results Micro-structural phenotypes were more robustly associated with schizophrenia PRS than macro-structural phenotypes. Polygenic risk was significantly associated with reduced neurite density index (NDI) at global brain scale, at 149 cortical regions, and five subcortical structures. Other micro-structural parameters, e.g., fractional anisotropy, that were correlated with NDI were also significantly associated with schizophrenia PRS. Genetic effects on multiple MRI phenotypes were co-located in temporal, cingulate and prefrontal cortical areas, insula, and hippocampus. Conclusions We show widespread cortical and subcortical grey matter micro-structure associations with schizophrenia PRS. Across all investigated phenotypes NDI, a measure of the density of myelinated axons and dendrites, showed the most robust associations with schizophrenia PRS. We interpret these results as indicative of reduced density of myelinated axons and dendritic arborization in large-scale cortico-subcortical networks mediating the genetic risk for schizophrenia.

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Neurite Orientation Dispersion and Density Imaging (NODDI) and duration of untreated psychosis in antipsychotic medication-naïve first episode psychosis patients

Cited by 8 publications

References 49 publications

Grey and white matter microstructure is associated with polygenic risk for schizophrenia

Grey and white matter microstructure is associated with polygenic risk for schizophrenia

Salience network glutamate and brain connectivity in medication-naïve first episode patients – A multimodal magnetic resonance spectroscopy and resting state functional connectivity MRI study

Grey and white matter micro-structure is associated with polygenic risk for schizophrenia

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