White matter microstructure and the clinical risk for psychosis: A diffusion tensor imaging study of individuals with basic symptoms and at ultra-high risk

Smigielski, Lukasz; Stämpfli, Philipp; Wotruba, Diana; Buechler, Roman; Sommer, Stefan; Theodoridou, Anastasia; Walitza, Susanne; Rössler, Wulf

doi:10.1016/j.nicl.2022.103067

Cited by 11 publications

(11 citation statements)

References 138 publications

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“…22 OCD has been previously linked to increased intra-frontoparietal network connectivity 23,24 , as in the present study, and may reflect over control and excessive monitoring tendencies typical of compulsive disorders. Psychotic PRS was associated with lower par orbitalis thickness, lower ventral diencephalon volume, and lower fractional anisotropy of the corpus callosum, consistent with previous research on clinical high risk for psychosis (though pars orbitalis thickness may be associated especially with more chronic diseases stages) [25][26][27] . Neurodevelopmental PRS was negatively associated with global gray matter volume, as well as right cortical thickness, whereas Internalizing PRS showed no significant associations with neural metrics.…”

Section: Discussionsupporting

confidence: 87%

Phenome-wide Investigation of Behavioral, Environmental, and Neural Associations with Cross-Disorder Genetic Liability in Youth of European Ancestry

Paul

Colbert

Gorelik

et al. 2023

Preprint

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Etiologic insights into psychopathology may be gained by using hypothesis-free methods to identify associations between genetic risk for broad psychopathology and phenotypes measured during adolescence, including both markers of child psychopathology and intermediate phenotypes such as neural structure that may link genetic risk with outcomes. We conducted a phenome-wide association study (phenotype n=1,269-1,694) of polygenic risk scores (PRS) for broad spectrum psychopathology (i.e., Compulsive, Psychotic, Neurodevelopmental, and Internalizing) in youth of PCA-selected European ancestry (n=5,556; ages 9-13) who completed the baseline and/or two-year follow-up of the ongoing Adolescent Brain Cognitive DevelopmentSM (ABCD) Study. We found that Neurodevelopmental and Internalizing PRS were significantly associated with a host of proximal as well as distal phenotypes (Neurodevelopmental: 187 and 211; Internalizing: 122 and 173 phenotypes at baseline and two-year follow-up, respectively), whereas Compulsive and Psychotic PRS showed zero and one significant associations, respectively, after Bonferroni correction. Neurodevelopmental PRS were further associated with brain structure metrics (e.g., total volume, mean right hemisphere cortical thickness), with only cortical volume indirectly linking Neurodevelopmental PRS to grades in school. Genetic variation influencing risk to psychopathology manifests broadly as behaviors, psychopathology symptoms, and related risk factors in middle childhood and early adolescence. Keywords: Phenome-wide Association Study (PheWAS), polygenic risk scores, Neurodevelopmental, Internalizing

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Section: Discussionsupporting

confidence: 87%

Phenome-wide Investigation of Behavioral, Environmental, and Neural Associations with Cross-Disorder Genetic Liability in Youth of European Ancestry

Paul

Colbert

Gorelik

et al. 2023

Preprint

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“…We found that levels of all kynurenine metabolites, with the exception of XA, were increased in the white matter, and levels of KYN, 3-HK, ANA, and 3-HANA were increased in the gray matter of the DLPFC of individuals affected by schizophenia. The homogenous activation of the kynurenine pathway in the white matter is in line with a large body of evidence suggesting that white matter abnomalities are associated with schizophrenia 48 – 54 . Fractional anisotropy MI analysis exploring age-related white matter trajectories in a large cohort of patients affected by schizophrenia and healthy controls demonstrates that white matter is affected in all stages of schizophrenia in a tract-specific manner since the early phases of myelin maturation 50 .…”

Section: Discussionsupporting

confidence: 82%

Changes in kynurenine metabolites in the gray and white matter of the dorsolateral prefrontal cortex of individuals affected by schizophrenia

Antenucci,

D’Errico,

Fazio

et al. 2024

Schizophr

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Alterations in the kynurenine pathway of tryptophan metabolism have been implicated in the pathophysiology of schizophrenia. Here, we performed an in-depth analysis of all metabolites of the kynurenine pathway, i.e., tryptophan (TRY), kynurenic acid (KYNA), L-kynurenine (KYN), 3-hydroxykynurenine (3-HK), anthranylic acid (ANA), 3-hydroxyanthranylic acid (3-HANA), xanthurenic acid (XA) and quinolinic acid (QUINA), in postmortem samples of the dorsolateral prefrontal cortex (DLPFC, Brodmann area 46, 9) of individuals affected by schizophrenia and non-schizophrenic controls. The analysis was carried out in the gray and white matter. Levels of KYN, 3-HK, ANA, and 3-HANA were significantly increased in both the gray and white matter of the DLPFC of individuals affected by schizophrenia, whereas levels of TRY, KYNA, and QUINA were increased exclusively in the white matter and remained unchanged in the gray matter. These increases in kynurenine metabolites did not correlate with age, sex, duration of the disease, and duration and type of antipsychotic medication. These findings suggest that the two major branches of the kynurenine pathway, i.e., the transamination of KYN into KYNA, and hydroxylation of KYN into 3-HK are activated in the white matter of individuals affected by schizophrenia, perhaps as a result of neuroinflammation, and support the evidence that abnormalities of the white matter are consistenly associated with schizophrenia.

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“…Fractional anisotropy values were reduced across all regions of the corpus callosum although similar findings are found in bipolar patients ( Li et al, 2014 ). When patients at risk for schizophrenia (based on various surveys and examinations) were divided into those that progressed to schizophrenia versus those that did not, one group found more severe fractional anisotropy and radial diffusivity changes in the corpus callosum in at risk subjects who progressed to schizophrenia versus those who did not progress ( Smigielski et al, 2022 ).…”

Section: Imagingmentioning

confidence: 99%

Neuroimaging in schizophrenia: A review article

et al. 2022

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In this review article we have consolidated the imaging literature of patients with schizophrenia across the full spectrum of modalities in radiology including computed tomography (CT), morphologic magnetic resonance imaging (MRI), functional magnetic resonance imaging (fMRI), magnetic resonance spectroscopy (MRS), positron emission tomography (PET), and magnetoencephalography (MEG). We look at the impact of various subtypes of schizophrenia on imaging findings and the changes that occur with medical and transcranial magnetic stimulation (TMS) therapy. Our goal was a comprehensive multimodality summary of the findings of state-of-the-art imaging in untreated and treated patients with schizophrenia. Clinical imaging in schizophrenia is used to exclude structural lesions which may produce symptoms that may mimic those of patients with schizophrenia. Nonetheless one finds global volume loss in the brains of patients with schizophrenia with associated increased cerebrospinal fluid (CSF) volume and decreased gray matter volume. These features may be influenced by the duration of disease and or medication use. For functional studies, be they fluorodeoxyglucose positron emission tomography (FDG PET), rs-fMRI, task-based fMRI, diffusion tensor imaging (DTI) or MEG there generally is hypoactivation and disconnection between brain regions. However, these findings may vary depending upon the negative or positive symptomatology manifested in the patients. MR spectroscopy generally shows low N-acetylaspartate from neuronal loss and low glutamine (a neuroexcitatory marker) but glutathione may be elevated, particularly in non-treatment responders. The literature in schizophrenia is difficult to evaluate because age, gender, symptomatology, comorbidities, therapy use, disease duration, substance abuse, and coexisting other psychiatric disorders have not been adequately controlled for, even in large studies and meta-analyses.

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White matter microstructure and the clinical risk for psychosis: A diffusion tensor imaging study of individuals with basic symptoms and at ultra-high risk

Cited by 11 publications

References 138 publications

Phenome-wide Investigation of Behavioral, Environmental, and Neural Associations with Cross-Disorder Genetic Liability in Youth of European Ancestry

Phenome-wide Investigation of Behavioral, Environmental, and Neural Associations with Cross-Disorder Genetic Liability in Youth of European Ancestry

Changes in kynurenine metabolites in the gray and white matter of the dorsolateral prefrontal cortex of individuals affected by schizophrenia

Neuroimaging in schizophrenia: A review article

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