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  • Kochunov, Peter  (3)
  • Pharmacy  (3)
  • 1
    In: Schizophrenia Bulletin, Oxford University Press (OUP), Vol. 48, No. 6 ( 2022-11-18), p. 1306-1317
    Abstract: Schizophrenia (SZ) and bipolar disorder (BD) share genetic risk factors, yet patients display differential levels of cognitive impairment. We hypothesized a genome-transcriptome-functional connectivity (frontoparietal)-cognition pathway linked to SZ-versus-BD differences, and conducted a multiscale study to delineate this pathway. Study Designs Large genome-wide studies provided single nucleotide polymorphisms (SNPs) conferring more risk for SZ than BD, and we identified their regulated genes, namely SZ-biased SNPs and genes. We then (a) computed the polygenic risk score for SZ (PRSSZ) of SZ-biased SNPs and examined its associations with imaging-based frontoparietal functional connectivity (FC) and cognitive performances; (b) examined the spatial correlation between ex vivo postmortem expressions of SZ-biased genes and in vivo, SZ-related FC disruptions across frontoparietal regions; (c) investigated SZ-versus-BD differences in frontoparietal FC; and (d) assessed the associations of frontoparietal FC with cognitive performances. Study Results PRSSZ of SZ-biased SNPs was significantly associated with frontoparietal FC and working memory test scores. SZ-biased genes’ expressions significantly correlated with SZ-versus-BD differences in FC across frontoparietal regions. SZ patients showed more reductions in frontoparietal FC than BD patients compared to controls. Frontoparietal FC was significantly associated with test scores of multiple cognitive domains including working memory, and with the composite scores of all cognitive domains. Conclusions Collectively, these multiscale findings support the hypothesis that SZ-biased genetic risk, through transcriptome regulation, is linked to frontoparietal dysconnectivity, which in turn contributes to differential cognitive deficits in SZ-versus BD, suggesting that potential biomarkers for more precise patient stratification and treatment.
    Type of Medium: Online Resource
    ISSN: 0586-7614 , 1745-1701
    RVK:
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2022
    detail.hit.zdb_id: 2180196-4
    SSG: 15,3
    Library Location Call Number Volume/Issue/Year Availability
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  • 2
    In: Schizophrenia Bulletin, Oxford University Press (OUP), Vol. 49, No. 1 ( 2023-01-03), p. 172-184
    Abstract: Schizophrenia (SZ), schizoaffective disorder (SAD), and psychotic bipolar disorder share substantial overlap in clinical phenotypes, associated brain abnormalities and risk genes, making reliable diagnosis among the three illness challenging, especially in the absence of distinguishing biomarkers. This investigation aims to identify multimodal brain networks related to psychotic symptom, mood, and cognition through reference-guided fusion to discriminate among SZ, SAD, and BP. Psychotic symptom, mood, and cognition were used as references to supervise functional and structural magnetic resonance imaging (MRI) fusion to identify multimodal brain networks for SZ, SAD, and BP individually. These features were then used to assess the ability in discriminating among SZ, SAD, and BP. We observed shared links to functional and structural covariation in prefrontal, medial temporal, anterior cingulate, and insular cortices among SZ, SAD, and BP, although they were linked with different clinical domains. The salience (SAN), default mode (DMN), and fronto-limbic (FLN) networks were the three identified multimodal MRI features within the psychosis spectrum disorders from psychotic symptom, mood, and cognition associations. In addition, using these networks, we can classify patients and controls and distinguish among SZ, SAD, and BP, including their first-degree relatives. The identified multimodal SAN may be informative regarding neural mechanisms of comorbidity for psychosis spectrum disorders, along with DMN and FLN may serve as potential biomarkers in discriminating among SZ, SAD, and BP, which may help investigators better understand the underlying mechanisms of psychotic comorbidity from three different disorders via a multimodal neuroimaging perspective.
    Type of Medium: Online Resource
    ISSN: 0586-7614 , 1745-1701
    RVK:
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2023
    detail.hit.zdb_id: 2180196-4
    SSG: 15,3
    Library Location Call Number Volume/Issue/Year Availability
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  • 3
    In: Schizophrenia Bulletin, Oxford University Press (OUP), Vol. 45, No. 4 ( 2019-06-18), p. 859-870
    Abstract: Auditory encoding abnormalities, gray-matter loss, and cognitive deficits are all candidate schizophrenia (SZ) endophenotypes. This study evaluated associations between and heritability of auditory network attributes (function and structure) and attention in healthy controls (HC), SZ patients, and unaffected relatives (UR). Methods Whole-brain maps of M100 auditory activity from magnetoencephalography recordings, cortical thickness (CT), and a measure of attention were obtained from 70 HC, 69 SZ patients, and 35 UR. Heritability estimates (h2r) were obtained for M100, CT at each group-difference region, and the attention measure. Results SZ patients had weaker bilateral superior temporal gyrus (STG) M100 responses than HC and a weaker right frontal M100 response than UR. Abnormally large M100 responses in left superior frontal gyrus were observed in UR and SZ patients. SZ patients showed smaller CT in bilateral STG and right frontal regions. Interrelatedness between 3 putative SZ endophenotypes was demonstrated, although in the left STG the M100 and CT function−structure associations observed in HC and UR were absent in SZ patients. Heritability analyses also showed that right frontal M100 and bilateral STG CT measures are significantly heritable. Conclusions Present findings indicated that the 3 SZ endophenotypes examined are not isolated markers of pathology but instead are connected. The pattern of auditory encoding group differences and the pattern of brain function−structure associations differ as a function of brain region, indicating the need for regional specificity when studying these endophenotypes, and with the presence of left STG function−structure associations in HC and UR but not in SZ perhaps reflecting disease-associated damage to gray matter that disrupts function−structure relationships in SZ.
    Type of Medium: Online Resource
    ISSN: 0586-7614 , 1745-1701
    RVK:
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2019
    detail.hit.zdb_id: 2180196-4
    SSG: 15,3
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
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