| 1. |
- Demichev, Vadim, et al.
(författare)
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A time-resolved proteomic and prognostic map of COVID-19
- 2021
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Ingår i: Cell Systems. - : Elsevier BV. - 2405-4712 .- 2405-4720. ; 12:8, s. 780-794.e7
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Tidskriftsartikel (refereegranskat)abstract
- COVID-19 is highly variable in its clinical presentation, ranging from asymptomatic infection to severe organ damage and death. We characterized the time-dependent progression of the disease in 139 COVID-19 inpatients by measuring 86 accredited diagnostic parameters, such as blood cell counts and enzyme activities, as well as untargeted plasma proteomes at 687 sampling points. We report an initial spike in a systemic inflammatory response, which is gradually alleviated and followed by a protein signature indicative of tissue repair, metabolic reconstitution, and immunomodulation. We identify prognostic marker signatures for devising risk-adapted treatment strategies and use machine learning to classify therapeutic needs. We show that the machine learning models based on the proteome are transferable to an independent cohort. Our study presents a map linking routinely used clinical diagnostic parameters to plasma proteomes and their dynamics in an infectious disease.
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| 2. |
- Dale, Caitlin, et al.
(författare)
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Aberrant callosal morphology in ex-smokers
- 2022
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Ingår i: Journal of Integrative Neuroscience. - : IMR Press. - 0219-6352 .- 1757-448X. ; 21:4
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Tidskriftsartikel (refereegranskat)abstract
- Background: Cigarette smoking is associated with widespread structural alterations in both brain hemispheres as well as of the corpus callosum (i.e., the brain???s main interhemispheric white matter pathway). While similar hemispheric alterations have also been reported in ex-smokers, no study has yet examined the corpus callosum in ex-smokers.Methods: We compared callosal morphology in a sample of 107 ex-smokers (57 males/50 females) and 193 non-smokers (73 males/120 females), aged between 42 and 97 years. More specifically, we measured the total callosal area as well as seven callosal subregions using the Witelson parcellation scheme.Results: At uncorrected levels, we detected significantly smaller callosal areas in ex-smokers than in non-smokers within the posterior midbody, genu, and isthmus (albeit the latter only on a trend level). When applying corrections for multiple comparisons, only the effect within the posterior midbody remained significant.Conclusions: Our findings suggest a weaker interhemispheric connectivity in ex-smokers compared to non-smokers, specifically between frontal and temporal areas.
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| 3. |
- Feusner, Jamie D., et al.
(författare)
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Cytoarchitectonically Defined Volumes of Early Extrastriate Visual Cortex in Unmedicated Adults With Body Dysmorphic Disorder
- 2023
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Ingår i: Biological Psychiatry. - : Elsevier BV. - 2451-9022. ; 8:9, s. 909-917
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Individuals with body dysmorphic disorder (BDD) misperceive that they have prominent defects in their appearance, resulting in preoccupations, time-consuming rituals, and distress. Previous neuroimaging studies have found abnormal activation patterns in the extrastriate visual cortex, which may underlie experiences of distorted perception of appearance. Correspondingly, we investigated gray matter volumes in individuals with BDD in the early extrastriate visual cortex using cytoarchitectonically defined maps that were previously derived from postmortem brains.METHODS: We analyzed T1-weighted magnetic resonance imaging data from 133 unmedicated male and female participants (BDD: n = 65; healthy control subjects: n = 68). We used cytoarchitectonically defined probability maps for the early extrastriate cortex, consisting of areas corresponding to V2, V3d, V3v/VP, V3a, and V4v. Gray matter volumes were compared between groups, supplemented by testing associations with clinical symptoms.RESULTS: The BDD group exhibited significantly larger gray matter volumes in the left and right early extrastriate cortex. Region-specific follow-up analyses revealed multiple subregions showing larger volumes in BDD, significant in the left V4v. There were no significant associations after corrections for multiple comparisons between gray matter volumes in early extrastriate cortex and BDD symptoms, comorbid symptoms, or duration of illness.CONCLUSIONS: Greater volumes of the early extrastriate visual cortex were evident in those with BDD, which aligns with outcomes of prior studies revealing BDD-specific functional abnormalities in these regions. Enlarged volumes of the extrastriate cortex in BDD might manifest during neurodevelopment, which could predispose individuals to aberrant visual perception and contribute to the core phenotype of distortion of perception for appearance.
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| 4. |
- Kleeman, Sam O, et al.
(författare)
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Cystatin C is glucocorticoid responsive, directs recruitment of Trem2+ macrophages, and predicts failure of cancer immunotherapy.
- 2023
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Ingår i: Cell genomics. - 2666-979X. ; 3:8
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Tidskriftsartikel (refereegranskat)abstract
- Cystatin C (CyC), a secreted cysteine protease inhibitor, has unclear biological functions. Many patients exhibit elevated plasma CyC levels, particularly during glucocorticoid (GC) treatment. This study links GCs with CyC's systemic regulation by utilizing genome-wide association and structural equation modeling to determine CyC production genetics in the UK Biobank. Both CyC production and a polygenic score (PGS) capturing predisposition to CyC production were associated with increased all-cause and cancer-specific mortality. We found that the GC receptor directly targets CyC, leading to GC-responsive CyC secretion in macrophages and cancer cells. CyC-knockout tumors displayed significantly reduced growth and diminished recruitment of TREM2+ macrophages, which have been connected to cancer immunotherapy failure. Furthermore, the CyC-production PGS predicted checkpoint immunotherapy failure in 685 patients with metastatic cancer from combined clinical trial cohorts. In conclusion, CyC may act as a GC effector pathway via TREM2+ macrophage recruitment and may be a potential target for combination cancer immunotherapy.
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| 5. |
- Kurth, Florian, et al.
(författare)
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Brain Sex in Transgender Women Is Shifted towards Gender Identity
- 2022
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Ingår i: Journal of Clinical Medicine. - : MDPI AG. - 2077-0383. ; 11:6
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Tidskriftsartikel (refereegranskat)abstract
- Transgender people report discomfort with their birth sex and a strong identification with the opposite sex. The current study was designed to shed further light on the question of whether the brains of transgender people resemble their birth sex or their gender identity. For this purpose, we analyzed a sample of 24 cisgender men, 24 cisgender women, and 24 transgender women before gender-affirming hormone therapy. We employed a recently developed multivariate classifier that yields a continuous probabilistic (rather than a binary) estimate for brains to be male or female. The brains of transgender women ranged between cisgender men and cisgender women (albeit still closer to cisgender men), and the differences to both cisgender men and to cisgender women were significant (p = 0.016 and p < 0.001, respectively). These findings add support to the notion that the underlying brain anatomy in transgender people is shifted away from their biological sex towards their gender identity.
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| 6. |
- Kurth, Florian, et al.
(författare)
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Preliminary evidence for a lower brain age in children with attention-deficit/hyperactivity disorder
- 2022
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Ingår i: Frontiers in Psychiatry. - : Frontiers Media S.A.. - 1664-0640. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- Attention-deficit hyperactivity disorder (ADHD) is a debilitating disorder with apparent roots in abnormal brain development. Here, we quantified the level of individual brain maturation in children with ADHD using structural neuroimaging and a recently developed machine learning algorithm. More specifically, we compared the BrainAGE index between three groups matched for chronological age (mean +/- SD: 11.86 +/- 3.25 years): 89 children diagnosed with ADHD, 34 asymptomatic siblings of those children with ADHD, and 21 unrelated healthy control children. Brains of children with ADHD were estimated significantly younger (-0.85 years) than brains of healthy controls (Cohen's d = -0.33; p = 0.028, one-tailed), while there were no significant differences between unaffected siblings and healthy controls. In addition, more severe ADHD symptoms were significantly associated with younger appearing brains. Altogether, these results are in line with the proposed delay of individual brain maturation in children with ADHD. However, given the relatively small sample size (N = 144), the findings should be considered preliminary and need to be confirmed in future studies.
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| 7. |
- Kurth, Florian, et al.
(författare)
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Reduced Age-Related Gray Matter Loss in the Orbitofrontal Cortex in Long-Term Meditators
- 2023
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Ingår i: Brain Sciences. - : MDPI. - 2076-3425 .- 2076-3425. ; 13:12
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Tidskriftsartikel (refereegranskat)abstract
- The orbitofrontal cortex (OFC) is a functionally heterogeneous brain region contributing to mental processes relating to meditation practices. The OFC has been reported to decline in volume with increasing age and differs in volume between meditation practitioners and non-practitioners. We hypothesized that the age-related decline of the OFC is diminished in meditation practitioners. We tested this hypothesis in a sample of 50 long-term meditators and 50 matched controls by correlating chronological age with regional gray matter volumes of the left and right OFC, as well as in seven left and right cytoarchitectonically defined subregions of the OFC (Fo1-Fo7). In both meditators and controls, we observed a negative relationship between age and OFC (sub)volumes, indicating that older participants have smaller OFC volumes. However, in meditators, the age-related decline was less steep compared to controls. These age-related differences reached significance for left and right Fo2, Fo3, Fo4, and Fo7, as well as left Fo5 and right Fo6. Since different subregions of the OFC are associated with distinct brain functions, further investigations are required to explore the functional implications of these findings in the context of meditation and the aging brain.
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| 8. |
- Luders, Eileen, et al.
(författare)
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Cortical gyrification in women and men and the (missing) link to prenatal androgens
- 2024
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Ingår i: European Journal of Neuroscience. - 0953-816X .- 1460-9568.
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Tidskriftsartikel (refereegranskat)abstract
- Previous studies have reported sex differences in cortical gyrification. Since most cortical folding is principally defined in utero, sex chromosomes as well as gonadal hormones are likely to influence sex-specific aspects of local gyrification. Classic congenital adrenal hyperplasia (CAH) causes high levels of androgens during gestation in females, whereas levels in males are largely within the typical male range. Therefore, CAH provides an opportunity to study the possible effects of prenatal androgens on cortical gyrification. Here, we examined the vertex-wise absolute mean curvature—a common estimate for cortical gyrification—in individuals with CAH (33 women and 20 men) and pair-wise matched controls (33 women and 20 men). There was no significant main effect of CAH and no significant CAH-by-sex interaction. However, there was a significant main effect of sex in five cortical regions, where gyrification was increased in women compared to men. These regions were located on the lateral surface of the brain, specifically left middle frontal (rostral and caudal), right inferior frontal, left inferior parietal, and right occipital. There was no cortical region where gyrification was increased in men compared to women. Our findings do not only confirm prior reports of increased cortical gyrification in female brains but also suggest that cortical gyrification is not significantly affected by prenatal androgen exposure. Instead, cortical gyrification might be determined by sex chromosomes either directly or indirectly—the latter potentially by affecting the underlying architecture of the cortex or the size of the intracranial cavity, which is smaller in women.
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| 9. |
- Luders, Eileen, et al.
(författare)
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From baby brain to mommy brain : Widespread gray matter gain after giving birth
- 2020
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Ingår i: Cortex. - : ELSEVIER MASSON, CORP OFF. - 0010-9452 .- 1973-8102. ; 126, s. 334-342
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Tidskriftsartikel (refereegranskat)abstract
- Pregnancy results in obvious physiological changes to the female body, but data as to what happens to the maternal brain after giving birth are sparse as well as inconsistent. The overall goal of this study is to determine the nature of cerebral change in the postpartum period. For this purpose, we analyzed T1-weighted brain images of 14 healthy women (age range: 25-38 years) at two time points, specifically within 1-2 days of childbirth (immediate postpartum) and at 4-6 weeks after childbirth (late postpartum). When comparing voxel-wise gray matter between these two time points, there was no evidence of any significant decrease. Instead, we detected a pronounced gray matter increase involving both cortical and subcortical regions, such as the pre- and postcentral gyrus, the frontal and central operculum, the inferior frontal gyrus, the precuneus, and the middle occipital gyrus, as well as the thalamus and caudate. These structural changes occurring within only 4-6 weeks after delivery are reflective of a high degree of neuroplasticity and massive adaptations in the maternal brain. They may suggest a restoration of brain tissue following pregnancy and/or a substantial brain reorganization, possibly to accommodate a multifaceted repertoire of complex behaviors associated with being a mother.
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| 10. |
- Luders, Eileen, et al.
(författare)
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Gray matter increases within subregions of the hippocampal complex after pregnancy
- 2021
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Ingår i: Brain Imaging and Behavior. - : Springer Nature. - 1931-7557 .- 1931-7565. ; 15:6, s. 2790-2794
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Tidskriftsartikel (refereegranskat)abstract
- Neuroimaging findings - although still relatively sparse in the realm of postpartum research - suggest significant tissue increases within the hippocampus or its vicinity after giving birth. Given that the hippocampus is not a homogenous structure, effects may manifest differently across the hippocampal complex. Thus, the goal of this study was to determine the presence, magnitude, and direction of postpartum gray matter changes within five hippocampal subregions, specifically the dentate gyrus, the subiculum, and the subfields of the cornu ammonis (CA1, CA2 and CA3). For this purpose, we analyzed brain images of 14 healthy women acquired at immediate postpartum (within 1-2 days of childbirth) and at late postpartum (at 4-6 weeks after childbirth). Changes in hippocampal gray matter between both time points were calculated for all subregions as well as the hippocampal complex as a whole by integrating imaging-based intensity information with microscopically defined cytoarchitectonic probabilities. Hippocampal gray matter increased significantly within the right subiculum, right CA2, and right CA3. These findings may suggest that brain tissue lost during pregnancy is being restored after giving birth, perhaps even expanded compared to before pregnancy. Possible events on the microanatomical level include dendritic branching as well as the generation of new synapses, glia cells, and blood vessels. Altogether, the outcomes of our study confirm that hippocampal gray matter increases in the female human brain after giving birth, with differential effects across the hippocampal complex.
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