| 1. |
- Demichev, Vadim, et al.
(author)
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A time-resolved proteomic and prognostic map of COVID-19
- 2021
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In: Cell Systems. - : Elsevier BV. - 2405-4712 .- 2405-4720. ; 12:8, s. 780-794.e7
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Journal article (peer-reviewed)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.
(author)
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Aberrant callosal morphology in ex-smokers
- 2022
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In: Journal of Integrative Neuroscience. - : IMR Press. - 0219-6352 .- 1757-448X. ; 21:4
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Journal article (peer-reviewed)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.
(author)
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Corpus callosum morphology and relationships to illness phenotypes in individuals with anorexia nervosa
- 2024
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In: Scientific Reports. - : Springer Nature. - 2045-2322. ; 14:1
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Journal article (peer-reviewed)abstract
- Anorexia nervosa is an often-severe psychiatric illness characterized by significantly low body weight, fear of gaining weight, and distorted body image. Multiple neuroimaging studies have shown abnormalities in cortical morphology, mostly associated with the starvation state. Investigations of white matter, while more limited in number, have suggested global and regional volume reductions, as well as abnormal diffusivity in multiple regions including the corpus callosum. Yet, no study has specifically examined thickness of the corpus callosum, a large white matter tract instrumental in the inter-hemispheric integration of sensory, motor, and cognitive information. We analyzed MRI data from 48 adolescents and adults with anorexia nervosa and 50 healthy controls, all girls/women, to compare corpus callosum thickness and examined relationships with body mass index (BMI), illness duration, and eating disorder symptoms (controlling for BMI). There were no significant group differences in corpus callosum thickness. In the anorexia nervosa group, severity of body shape concerns was significantly, positively correlated with callosal thickness in the rostrum, genu, rostral body, isthmus, and splenium. In addition, there were significant positive correlations between eating disorder-related obsessions and compulsions and thickness of the anterior midbody, rostral body, and splenium. There were no significant associations between callosal thickness and BMI or illness duration. In sum, those with AN with worse concerns about bodily appearance and worse eating disorder-related obsessive thought patterns and compulsive behaviours have regionally thicker corpus callosum, independent of current weight status. These findings provide important neurobiological links to key, specific eating disorder behavioural phenotypes.
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| 4. |
- Feusner, Jamie D., et al.
(author)
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Cytoarchitectonically Defined Volumes of Early Extrastriate Visual Cortex in Unmedicated Adults With Body Dysmorphic Disorder
- 2023
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In: Biological Psychiatry. - : Elsevier BV. - 2451-9022. ; 8:9, s. 909-917
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Journal article (peer-reviewed)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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| 5. |
- Kleeman, Sam O, et al.
(author)
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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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In: Cell genomics. - 2666-979X. ; 3:8
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Journal article (peer-reviewed)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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| 6. |
- Kurth, Florian, et al.
(author)
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Brain Sex in Transgender Women Is Shifted towards Gender Identity
- 2022
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In: Journal of Clinical Medicine. - : MDPI. - 2077-0383. ; 11:6
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Journal article (peer-reviewed)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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| 7. |
- Kurth, Florian, et al.
(author)
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Preliminary evidence for a lower brain age in children with attention-deficit/hyperactivity disorder
- 2022
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In: Frontiers in Psychiatry. - : Frontiers Media S.A.. - 1664-0640. ; 13
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Journal article (peer-reviewed)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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| 8. |
- Kurth, Florian, et al.
(author)
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Reduced Age-Related Gray Matter Loss in the Orbitofrontal Cortex in Long-Term Meditators
- 2023
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In: Brain Sciences. - : MDPI. - 2076-3425. ; 13:12
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Journal article (peer-reviewed)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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| 9. |
- Luders, Eileen, et al.
(author)
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Cortical gyrification in women and men and the (missing) link to prenatal androgens
- 2024
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In: European Journal of Neuroscience. - : John Wiley & Sons. - 0953-816X .- 1460-9568.
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Journal article (peer-reviewed)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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| 10. |
- Luders, Eileen, et al.
(author)
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Effects of Congenital Adrenal Hyperplasia (CAH) and Biological Sex on Brain Size
- 2024
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In: Anatomia. - Basel : MDPI. - 2813-0545. ; 3:3, s. 155-162
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Journal article (peer-reviewed)abstract
- Congenital Adrenal Hyperplasia (CAH) has been reported to involve structural alterations in some brain regions. However, it remains to be established whether there is also an impact on the size of the brain as a whole. Here, we compiled the largest CAH sample to date (n = 53), matched pair-wise to a control group (n = 53) on sex, age, and verbal intelligence. Using T1-weighted brain scans, we calculated intracranial volume (ICV) as well as total brain volume (TBV), which are both common estimates for brain size. The statistical analysis was performed using a general linear model assessing the effects of CAH (CAH vs. controls), sex (women vs. men), and any CAH-by-sex interaction. The outcomes were comparable for ICV and TBV, i.e., there was no significant main effect of CAH and no significant CAH-by-sex interaction. However, there was a significant main effect of sex, with larger ICVs and TBVs in men than in women. Our findings contribute to an understudied field of research exploring brain anatomy in CAH. In contrast to some existing studies suggesting a smaller brain size in CAH, we did not observe such an effect. In other words, ICV and TBV in women and men with CAH did not differ significantly from those in controls. Notwithstanding, we observed the well-known sex difference in brain size (12.69% for ICV and 12.50% for TBV), with larger volumes in men than in women, which is in agreement with the existing literature.
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