Kilian Vomstein

Reduced cortical thickness and its association with social reactivity in children with autism spectrum disorder.

Symptomatology and behavioral characteristics in autism spectrum disorders (ASD) have increasingly been linked to abnormalities in early brain growth patterns of affected children. Studies investigating specific components of gray matter structure, such as cortical thickness (CT), have produced conflicting results, and have rarely included additional measures of social impairment. In the present study, we applied a surface-based whole brain analysis to investigate CT in a sample of 36 pre-adolescent children [18 subjects with ASD (IQ mean: 111) and 18 healthy controls (IQ mean: 112.8), age range 6-12 years]. The CT analysis revealed widespread, but mostly left-hemispheric thinning in frontal, temporal, parietal and occipital brain areas related to the theory-of-mind network and the heteromodal association cortex. In an exploratory analysis, CT was observed to be differently associated with social impairment in children with ASD compared with typically developing children. The affected neuroanatomical regions are related to characteristic deficits in language, cognition and behavior that are often observed in the disorder. The relationship between social impairment and CT in children with ASD and controls seems to indicate aberrant developmental trajectories in ASD emerging early in life.

The “killer cell story” in recurrent miscarriage: Association between activated peripheral lymphocytes and uterine natural killer cells

Peripheral and uterine NK cells (pNK, uNK) can be distinguished according to their receptor expression. Recent studies indicate an association of elevated pNK and uNK with recurrent miscarriage (RM). This study aimed to analyze pNK and uNK in patients with RM and healthy controls. Out of n=590 RM patients screened according to a standard diagnostic protocol, n=268 couples with ≥3 consecutive RM were identified. Subgroups consisted of n=151 primary RM (pRM), n=85 secondary RM (sRM), n=32 tertiary RM (tRM) and n=42 healthy controls. Finally, n=147 idiopathic RM (iRM) and n=121 non-iRM patients were identified. Peripheral blood levels of CD45+CD3-CD56+CD16+ NK cells were determined in non-pregnant patients and controls in the mid-luteal phase by FACS. In n=129 RM patients a uterine biopsy was taken to evaluate CD56+ NK cells by immunohistochemistry. PRM showed higher absolute pNK than sRM (median/μl (Q1;Q3): 234 (147;306) vs 176 (128;245), p=0.02). Further a trend towards higher pNK percentages in pRM was detected. UNK numbers did not differ between RM subgroups and did not correlate with pNK. However, the rate of highly elevated uNK was increased in iRM compared to non-iRM patients (p=0.04). Further, higher numbers of CD45+CD3-DR+ (p<0.01) and CD45+CD3+CD8+DR+ (p=0.04) peripheral lymphocytes were associated with higher uNK numbers. In conclusion, elevated pNK were present in pRM patients. Although pNK and uNK numbers did not correlate, the association between high CD45+CD3-DR+ and CD45+CD3+CD8+DR+ peripheral lymphocytes and uNK might indicate that activated NK, B and T cells provide cytokines for the differentiation of uNK.

Uterine natural killer cells in patients with idiopathic recurrent miscarriage

Uterine natural killer (uNK) cells are major players during implantation and early pregnancy. The aim of our study was to analyze uNK cell concentration in the endometrium of idiopathic recurrent miscarriage (iRM) patients and fertile controls.

Volumetric alterations in the heteromodal association cortex in children with autism spectrum disorder

BACKGROUND We investigated if alterations in higher-order association areas related to schizophrenia, namely the heteromodal association cortex (HASC), are also observable in subjects with autism spectrum disorder (ASD). METHODS A group of 18 children with ASD and 18 healthy controls (HC) underwent magnetic resonance imaging (MRI). The examination comprised an analysis of group differences in gray matter (GM) volume, surface area (SA) and hemispheric lateralization. RESULTS Differences in GM volumes in children with ASD and HC were detected in frontal and parietal areas related to the HASC. No HASC structure that showed changes in GM volume exhibited differences in SA. Alterations in hemispheric lateralization between ASD and HC are seen in a frontal area of the HASC. CONCLUSIONS Our results indicate that changes in HASC areas are not restricted to schizophrenia, but extend to other psychiatric disorders, namely ASD. The lacking group differences in SA indicate that changes in GM volume are possibly evoked by other variables than SA in children with ASD.

Higher prevalence of colonization with Gardnerella vaginalis and gram-negative anaerobes in patients with recurrent miscarriage and elevated peripheral natural killer cells

The role of vaginal infections in recurrent miscarriage (RM) is discussed controversially and screening is not recommended in international guidelines. Peripheral and uterine NK cells (pNK, uNK) play an important role in the establishment of a healthy pregnancy and are targets of immune diagnostics in RM patients. The aim of this study was to analyze the composition of the vaginal microbiota in RM patients and to correlate the findings to clinical characteristics as well as NK cell parameters. In total, n=243 RM patients with ≥3 consecutive miscarriages were recruited between 11/2011 and 03/2016. Vaginal swabs were analyzed by microbiological culture. Further, a cervical swab was taken in n=187 patients and the presence of Chlamydia trachomatis was evaluated by a molecular assay. Peripheral blood levels of CD45+CD3-CD56+CD16+ pNK (determined by four-color fluorescence flow cytometry) and CD56+ uNK (uterine biopsy, determined by immunohistochemistry) were analyzed. The prevalence of Gardnerella vaginalis colonization in RM patients was 19.0%, gram-negative anaerobes 20.5%, Candida species 7.9%, group B Streptococcus 11.0% and Enterobacteriaceae 14.8%. Commensal lactobacilli were absent in 14.5% of the women. Chlamydia trachomatis was detected in n=1 case (0.53%). The prevalence of Gardnerella vaginalis and gram-negative anaerobes in RM patients with elevated pNK (>280/μl, n=69) was significantly higher (p=0.012, p=0.04) compared to patients with normal pNK (n=174). In conclusion, RM patients with elevated pNK suffer more often from colonization by Gardnerella vaginalis and gram-negative anaerobes. This might indicate an association between the vaginal microbiota, local inflammation, changes in immune parameters and miscarriage.

Störung der Frühschwangerschaft und Aborte

Klinische, laborchemische und sonografische Methoden erlauben die fruhe und zuverlassige Diagnose und Beurteilung einer Fruhschwangerschaft. Die serielle Bestimmung des humanen Choriongonadotropins (hCG) gestattet eine Unterscheidung zwischen intakter und gestorter Implantation. Mit der transvaginalen Sonografie konnen Informationen uber den Implantationsort, die Vitalitat des Embryos und das Vorliegen einer Mehrlingsschwangerschaft gewonnen werden. Zudem ermoglicht die sonografische Beurteilung eine weitgehend zuverlassige Bestimmung des Gestationsalters. Unter dem Begriff „Abort“ wird im deutschsprachigen Raum ein (nichtartifizieller) Verlust der Schwangerschaft vor Eintritt der Lebensfahigkeit des Kindes verstanden. Von Bedeutung ist hierbei die Unterscheidung zwischen sporadischen und habituellen Aborten, wobei ein habituelles Abortgeschehen bei 3 oder mehr aufeinanderfolgenden Fehlgeburten vorliegt. Im ersten Kapitelteil wird auf die klinischen Stadien und die vielfaltigen Ursachen von sporadischen Aborten eingegangen, wahrendem der zweite Kapitelteil die habituellen Aborte und ihre Risikofaktoren behandelt.

Strukturelle Konnektivität und Diffusionstensor-Bildgebung bei Autismus-Spektrum-Störungen

Over the past years, diffusion tensor imaging (DTI) has become an important brain-imaging technique in neuropsychiatric research. DTI allows noninvasive visualization of white matter tracts. In addition, with DTI it is possible to quantify the structural integrity of the investigated fiber tracts. In child and adolescent psychiatry, DTI has become an increasingly important research tool, especially for conditions like autism spectrum disorders (ASD). Yet, correct interpretation of DTI findings can be challenging, especially for clinicians. Thus, the present review article explains the basic principles of this frequently used imaging technique as well as essential indices, like fractional anisotropy, radial, mean, and axial diffusivity and its two main applications, fibertracking and whole brain analysis. The strengths and weaknesses as well as future perspectives are discussed in light of DTI studies in children and adolescents with ASD.