| 51. |
- Johansson, Martin M., et al.
(författare)
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Microarray Analysis of Copy Number Variants on the Human Y Chromosome Reveals Novel and Frequent Duplications Overrepresented in Specific Haplogroups
- 2015
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 10:8
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND:The human Y chromosome is almost always excluded from genome-wide investigations of copy number variants (CNVs) due to its highly repetitive structure. This chromosome should not be forgotten, not only for its well-known relevance in male fertility, but also for its involvement in clinical phenotypes such as cancers, heart failure and sex specific effects on brain and behaviour.RESULTS:We analysed Y chromosome data from Affymetrix 6.0 SNP arrays and found that the signal intensities for most of 8179 SNP/CN probes in the male specific region (MSY) discriminated between a male, background signals in a female and an isodicentric male containing a large deletion of the q-arm and a duplication of the p-arm of the Y chromosome. Therefore, this SNP/CN platform is suitable for identification of gain and loss of Y chromosome sequences. In a set of 1718 males, we found 25 different CNV patterns, many of which are novel. We confirmed some of these variants by PCR or qPCR. The total frequency of individuals with CNVs was 14.7%, including 9.5% with duplications, 4.5% with deletions and 0.7% exhibiting both. Hence, a novel observation is that the frequency of duplications was more than twice the frequency of deletions. Another striking result was that 10 of the 25 detected variants were significantly overrepresented in one or more haplogroups, demonstrating the importance to control for haplogroups in genome-wide investigations to avoid stratification. NO-M214(xM175) individuals presented the highest percentage (95%) of CNVs. If they were not counted, 12.4% of the rest included CNVs, and the difference between duplications (8.9%) and deletions (2.8%) was even larger.CONCLUSIONS:Our results demonstrate that currently available genome-wide SNP platforms can be used to identify duplications and deletions in the human Y chromosome. Future association studies of the full spectrum of Y chromosome variants will demonstrate the potential involvement of gain or loss of Y chromosome sequence in different human phenotypes.
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| 52. |
- Jönsson, Erik G., et al.
(författare)
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Two methylenetetrahydrofolate reductase gene (MTHFR) polymorphisms, schizophrenia and bipolar disorder : An association study
- 2008
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Ingår i: American journal of medical genetics. Part B, Neuropsychiatric genetics. - : Wiley. - 1552-4841. ; 147B:6, s. 976-982
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Tidskriftsartikel (refereegranskat)abstract
- Recent meta-analyses of the methylenetetrahydrofolate reductase gene (MTHFR) have suggested association between two of its functional single gene polymorphisms (SNPs, C677T and A1298C) and schizophrenia. Studies have also suggested association between MTHFR C677T and A1298C variation and bipolar disorder. In a replication attempt the MTHFR C677T and A1298C SNPs were analyzed in three Scandinavian schizophrenia case-control samples. In addition, Norwegian patients with bipolar disorder were investigated. There were no statistically significant allele or genotype case-control differences. The present Scandinavian results do not verify previous associations between the putative functional MTHFR gene polymorphisms and schizophrenia or bipolar disorder. However, when combined with previous studies in meta-analyses there is still evidence for association between the MTHFR C677T polymorphism. and schizophrenia. Additional studies are warranted to shed further light on these relationships. (c) 2007 Wiley-Liss, Inc.
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| 53. |
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| 54. |
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| 55. |
- Koenig, Julian, et al.
(författare)
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Cortical thickness and resting-state cardiac function across the lifespan : A cross-sectional pooled mega-analysis
- 2021
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Ingår i: Psychophysiology. - : Wiley. - 0048-5772 .- 1469-8986 .- 1540-5958. ; 58:7
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Tidskriftsartikel (refereegranskat)abstract
- Understanding the association between autonomic nervous system [ANS] function and brain morphology across the lifespan provides important insights into neurovisceral mechanisms underlying health and disease. Resting-state ANS activity, indexed by measures of heart rate [HR] and its variability [HRV] has been associated with brain morphology, particularly cortical thickness [CT]. While findings have been mixed regarding the anatomical distribution and direction of the associations, these inconsistencies may be due to sex and age differences in HR/HRV and CT. Previous studies have been limited by small sample sizes, which impede the assessment of sex differences and aging effects on the association between ANS function and CT. To overcome these limitations, 20 groups worldwide contributed data collected under similar protocols of CT assessment and HR/HRV recording to be pooled in a mega-analysis (N = 1,218 (50.5% female), mean age 36.7 years (range: 12–87)). Findings suggest a decline in HRV as well as CT with increasing age. CT, particularly in the orbitofrontal cortex, explained additional variance in HRV, beyond the effects of aging. This pattern of results may suggest that the decline in HRV with increasing age is related to a decline in orbitofrontal CT. These effects were independent of sex and specific to HRV; with no significant association between CT and HR. Greater CT across the adult lifespan may be vital for the maintenance of healthy cardiac regulation via the ANS—or greater cardiac vagal activity as indirectly reflected in HRV may slow brain atrophy. Findings reveal an important association between CT and cardiac parasympathetic activity with implications for healthy aging and longevity that should be studied further in longitudinal research.
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| 56. |
- Lawyer, Glenn, et al.
(författare)
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Morphological correlates to cognitive dysfunction in schizophrenia as studied with Bayesian regression
- 2006
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Ingår i: BMC Psychiatry. - 1471-244X. ; 6, s. 31-
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Tidskriftsartikel (refereegranskat)abstract
- Background: Relationships between cognitive deficits and brain morphological changes observed in schizophrenia are alternately explained by less gray matter in the brain cerebral cortex, by alterations in neural circuitry involving the basal ganglia, and by alteration in cerebellar structures and related neural circuitry. This work explored a model encompassing all of these possibilities to identify the strongest morphological relationships to cognitive skill in schizophrenia. Methods: Seventy-one patients with schizophrenia and sixty-five healthy control subjects were characterized by neuropsychological tests covering six functional domains. Measures of sixteen brain morphological structures were taken using semi-automatic and fully manual tracing of MRI images, with the full set of measures completed on thirty of the patients and twenty controls. Group differences were calculated. A Bayesian decision-theoretic method identified those morphological features, which best explained neuropsychological test scores in the context of a multivariate response linear model with interactions. Results: Patients performed significantly worse on all neuropsychological tests except some regarding executive function. The most prominent morphological observations were enlarged ventricles, reduced posterior superior vermis gray matter volumes, and increased putamen gray matter volumes in the patients. The Bayesian method associated putamen volumes with verbal learning, vigilance, and (to a lesser extent) executive function, while caudate volumes were associated with working memory. Vermis regions were associated with vigilance, executive function, and, less strongly, visuo-motor speed. Ventricular volume was strongly associated with visuo-motor speed, vocabulary, and executive function. Those neuropsychological tests, which were strongly associated to ventricular volume, showed only weak association to diagnosis, possibly because ventricular volume was regarded a proxy for diagnosis. Diagnosis was strongly associated with the other neuropsychological tests, implying that the morphological associations for these tasks reflected morphological effects and not merely group volumetric differences. Interaction effects were rarely associated, indicating that volumetric relationships to neuropsychological performance were similar for both patients and controls. Conclusion: The association of subcortical and cerebellar structures to verbal learning, vigilance, and working memory supports the importance of neural connectivity to these functions. The finding that a morphological indicator of diagnosis (ventricular volume) provided more explanatory power than diagnosis itself for visuo-motor speed, vocabulary, and executive function suggests that volumetric abnormalities in the disease are more important for cognition than non-morphological features.
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| 57. |
- Lundberg, Mathias, et al.
(författare)
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Clozapine protects adult neural stem cells from ketamine-induced cell death in correlation with decreased apoptosis and autophagy
- 2020
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Ingår i: Bioscience Reports. - : Portland Press Ltd.. - 0144-8463 .- 1573-4935. ; 40:1
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Tidskriftsartikel (refereegranskat)abstract
- Adult neurogenesis, the production of newborn neurons from neural stem cells (NSCs) has been suggested to be decreased in patients with schizophrenia. A similar finding was observed in an animal model of schizophrenia, as indicated by decreased bromodeoxyuridine (BrdU) labelling cells in response to a non-competitive N-methyl-d-aspartate (NMDA) receptor antagonist. The antipsychotic drug clozapine was shown to counteract the observed decrease in BrdU-labelled cells in hippocampal dentate gyrus (DG). However, phenotypic determination by immunohistochemistry analysis could not reveal whether BrdU-positive cells were indeed NSCs. Using a previously established cell model for analysing NSC protection in vitro, we investigated a protective effect of clozapine on NSCs.Primary NSCs were isolated from the mouse subventricular zone (SVZ), we show that clozapine had a NSC protective activity alone, as evident by employing an ATP cell viability assay. In contrast, haloperidol did not show any NSC protective properties. Subsequently, cells were exposed to the non-competitive NMDA-receptor antagonist ketamine. Clozapine, but not haloperidol, had a NSC protective/anti-apoptotic activity against ketamine-induced cytotoxicity. The observed NSC protective activity of clozapine was associated with increased expression of the anti-apoptotic marker Bcl-2, decreased expression of the pro-apoptotic cleaved form of caspase-3 and associated with decreased expression of the autophagosome marker 1A/1B-light chain 3 (LC3-II).Collectively, our findings suggest that clozapine may have a protective/anti-apoptotic effect on NSCs, supporting previous in vivo observations, indicating a neurogenesis-promoting activity for clozapine. If the data are further confirmed in vivo, the results may encourage an expanded use of clozapine to restore impaired neurogenesis in schizophrenia.
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| 58. |
- Lundberg, Mathias, et al.
(författare)
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Development of an ELISA displaying similar reactivity with reduced and oxidized human Thioredoxin-1 (Trx1) : The plasma level of Trx1 in early onset psychosis disorders
- 2022
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Ingår i: JIM - Journal of Immunological Methods. - : Elsevier. - 0022-1759 .- 1872-7905. ; 510
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Tidskriftsartikel (refereegranskat)abstract
- The plasma level of human thioredoxin-1 (Trx1) has been shown to be increased in various somatic diseases and psychiatric disorders. However, when comparing the reported plasma levels of Trx1, a great inter-study vari-ability, as well as variability in study outcomes of differences between patients and control subjects has been observed, ultimately limiting the possibility to make comparative analyses. Trx1 is a highly redox active protein prone to form various redox forms, e.g. dimers, oligomers or Trx1-protein complexes. We have recently shown that ELISA systems may vary in reactivity to various Trx1 redox forms. The primary aim of the present study was to develop an ELISA system with similar reactivity to various Trx1 redox forms. By evaluating a panel of novel monoclonal antibodies (mAbs), in various paired combinations, three ELISA systems were generated, with observed large variability in reactivity to various Trx1 redox forms. Importantly, an ELISA system (capture mAb MT17R6 and detection mAb MT13X3-biotin), was identified that displayed similar reactivity to oxidized and DTT reduced Trx1. The ELISA system (MT17R6/MT13X3-biotin), was subsequently used to analyze the level of Trx1 in plasma from patients (< 18 years) with early onset psychosis disorders (EOP). However, no significant (p > 0.7) difference in plasma Trx1 levels between patients with EOP (n = 23) and healthy age matched controls (HC) (n = 20) were observed. Furthermore, reliable measurement was shown to be dependent on the estab-lishment of platelet poor plasma samples, enabled by rigorous blood sample centrifugation and by efficient blocking of potentially interfering heterophilic antibodies. In conclusion, we report the design and character-ization of a Trx1 ELISA system with similar reactivity to various Trx1 redox forms. Importantly, data indicated that generated ELISA systems show large variability in reactivity to various redox forms with ultimate impact on measured levels of Trx1. Overall, results from this study suggests that future studies may be strongly improved by the use of Trx1 ELISA systems with characterized specificity to various redox forms.
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| 59. |
- Mørch-Johnsen, Lynn, et al.
(författare)
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The neural correlates of negative symptoms in schizophrenia : examples from MRI literature
- 2018
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Ingår i: Clinical EEG and Neuroscience. - : SAGE Publications Inc.. - 1550-0594 .- 2169-5202. ; 49:1, s. 12-17
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Tidskriftsartikel (refereegranskat)abstract
- Negative symptoms of schizophrenia have a negative impact on psychosocial functioning and disease outcome. It is therefore important to investigate the pathophysiology underlying negative symptoms as this may aid the development of better treatment. In the current article, examples from studies investigating neural correlates of negative symptoms in schizophrenia are given. Investigations using both structural and functional magnetic resonance imaging are presented at different levels of symptomatology descriptions, from the more heterogenous construct of negative symptoms to more single discrete symptoms. Some methods to improve imaging studies of negative symptoms in schizophrenia are also suggested.
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| 60. |
- Petrov, Dmitry, et al.
(författare)
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Machine Learning for Large-Scale Quality Control of 3D Shape Models in Neuroimaging
- 2017
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Ingår i: Machine learning in medical imaging. MLMI (Workshop). - Cham : Springer International Publishing. ; 10541, s. 371-378
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Tidskriftsartikel (refereegranskat)abstract
- As very large studies of complex neuroimaging phenotypes become more common, human quality assessment of MRI-derived data remains one of the last major bottlenecks. Few attempts have so far been made to address this issue with machine learning. In this work, we optimize predictive models of quality for meshes representing deep brain structure shapes. We use standard vertex-wise and global shape features computed homologously across 19 cohorts and over 7500 human-rated subjects, training kernelized Support Vector Machine and Gradient Boosted Decision Trees classifiers to detect meshes of failing quality. Our models generalize across datasets and diseases, reducing human workload by 30-70%, or equivalently hundreds of human rater hours for datasets of comparable size, with recall rates approaching inter-rater reliability.
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