| 1. |
- Witt, S. H., et al.
(author)
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Genome-wide association study of borderline personality disorder reveals genetic overlap with bipolar disorder, major depression and schizophrenia
- 2017
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In: Translational Psychiatry. - : Springer Science and Business Media LLC. - 2158-3188. ; 7
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Journal article (peer-reviewed)abstract
- Borderline personality disorder (BOR) is determined by environmental and genetic factors, and characterized by affective instability and impulsivity, diagnostic symptoms also observed in manic phases of bipolar disorder (BIP). Up to 20% of BIP patients show comorbidity with BOR. This report describes the first case-control genome-wide association study (GWAS) of BOR, performed in one of the largest BOR patient samples worldwide. The focus of our analysis was (i) to detect genes and gene sets involved in BOR and (ii) to investigate the genetic overlap with BIP. As there is considerable genetic overlap between BIP, major depression (MDD) and schizophrenia (SCZ) and a high comorbidity of BOR and MDD, we also analyzed the genetic overlap of BOR with SCZ and MDD. GWAS, gene-based tests and gene-set analyses were performed in 998 BOR patients and 1545 controls. Linkage disequilibrium score regression was used to detect the genetic overlap between BOR and these disorders. Single marker analysis revealed no significant association after correction for multiple testing. Gene-based analysis yielded two significant genes: DPYD (P = 4.42 x 10(-7)) and PKP4 (P = 8.67 x 10(-7)); and gene-set analysis yielded a significant finding for exocytosis (GO: 0006887, PFDR = 0.019; FDR, false discovery rate). Prior studies have implicated DPYD, PKP4 and exocytosis in BIP and SCZ. The most notable finding of the present study was the genetic overlap of BOR with BIP (r(g) = 0.28 [P = 2.99 x 10(-3)]), SCZ (r(g) = 0.34 [P = 4.37 x 10(-5)]) and MDD (r(g) = 0.57 [P = 1.04 x 10(-3)]). We believe our study is the first to demonstrate that BOR overlaps with BIP, MDD and SCZ on the genetic level. Whether this is confined to transdiagnostic clinical symptoms should be examined in future studies.
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| 2. |
- Chacko, L. Johnson, et al.
(author)
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Role of BDNF and neurotrophic receptors in human inner ear development
- 2017
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In: Cell and Tissue Research. - : SPRINGER. - 0302-766X .- 1432-0878. ; 370:3, s. 347-363
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Journal article (peer-reviewed)abstract
- The expression patterns of the neurotrophin, brain-derived neurotrophic factor, BDNF, and the neurotrophic receptors-p75NTR and Trk receptors-in the developing human fetal inner ear between the gestational weeks (GW) 9 to 12 are examined via in situ hybridization and immunohistochemistry. BDNF mRNA expression was highest in the cochlea at GW 9 but declined in the course of development. In contrast to embryonic murine specimens, a decline in BDNF expression from the apical to the basal turn of the cochlea could not be observed. p75NTR immunostaining was most prominent in the nerve fibers that penetrate into the sensory epithelia of the cochlea, the urticule and the saccule as gestational age progresses. TrkB and TrkC expression intensified towards GW 12, at which point the BDNF mRNA localization was at its lowest. TrkA expression was limited to fiber subpopulations of the facial nerve at GW 10. In the adult human inner ear, we observed BDNF mRNA expression in the apical poles of the cochlear hair cells and supporting cells, while in the adult human utricle, the expression was localized in the vestibular hair cells. We demonstrate the highly specific staining patterns of BDNF mRNA and its putative receptors over a developmental period in which multiple hearing disorders are manifested. Our findings suggest that BDNF and neurotrophin receptors are important players during early human inner ear development. In particular, they seem to be important for the survival of the afferent sensory neurons.
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| 3. |
- Sawicki, M., et al.
(author)
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Cubic anisotropy in (Ga,Mn) As layers : Experiment and theory
- 2018
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In: Physical Review B. - : American Physical Society. - 2469-9950 .- 2469-9969. ; 97:18
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Journal article (peer-reviewed)abstract
- Historically, comprehensive studies of dilute ferromagnetic semiconductors, e.g., p-type (Cd,Mn) Te and (Ga,Mn) As, paved the way for a quantitative theoretical description of effects associated with spin-orbit interactions in solids, such as crystalline magnetic anisotropy. In particular, the theory was successful in explaining uniaxial magnetic anisotropies associated with biaxial strain and nonrandom formation of magnetic dimers in epitaxial (Ga,Mn) As layers. However, the situation appears much less settled in the case of the cubic term: the theory predicts switchings of the easy axis between in-plane < 100 > and < 110 > directions as a function of the hole concentration, whereas only the < 100 > orientation has been found experimentally. Here, we report on the observation of such switchings by magnetization and ferromagnetic resonance studies on a series of high-crystalline quality (Ga,Mn) As films. We describe our findings by themean-field p-d Zener model augmented with three new ingredients. The first one is a scattering broadening of the hole density of states, which reduces significantly the amplitude of the alternating carrier-induced contribution. This opens the way for the two other ingredients, namely the so-far disregarded single-ion magnetic anisotropy and disorder-driven nonuniformities of the carrier density, both favoring the < 100 > direction of the apparent easy axis. However, according to our results, when the disorder gets reduced, a switching to the < 110 > orientation is possible in a certain temperature and hole concentration range.
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