Altered connectivity of dorsolateral prefrontal cortex (DLPFC) and hippocampus during working memory is considered an intermediate phenotype for schizophrenia (SCZ), but the relevance for other mental disorders with shared genetic background remains unknown. Here we investigated its presence in unaffected first-degree relatives of patients with bipolar disorder (BD) or major depressive disorder (MDD). Furthermore, we aimed to provide an independent replication of this phenotype in first-degree relatives of SCZ patients. We acquired functional magnetic resonance imaging (fMRI) data from 309 healthy controls and 218 healthy first-degree relatives of index patients with SCZ (n = 62), BD (n = 66) and MDD (n = 90), who completed the n-back working memory paradigm. We observed a significant group effect on DLPFC–hippocampus coupling (PFWE = .031, all P-values region of interest [ROI] corrected). Post hoc comparisons revealed that this effect was driven by the SCZ relatives, who showed a significant increase in the negative functional connectivity of the DLPFC and right hippocampus compared to controls (PFWE = .001), BD relatives (PFWE = .015) and trend-wise also MDD relatives (PFWE = .082). Comparison of BD and MDD relatives to the controls revealed no difference (PFWE-values > .451). Supplementary analyses suggested that the SCZ relatives finding is robust to a range of potential confounds, including structural differences. Our data further support altered DLPFC–hippocampus connectivity during working memory as an intermediate phenotype for SCZ. This suggests that this phenotype is relatively specific to SCZ and does not translate to other genetically related disorders in the mood-psychosis spectrum.
Cytogenetic analysis of a presumably tripronuclear zygote revealed that triploidy was caused by an endoreduplicated 46,XX complement. The remaining chromosomes yielded a hyperhaploid karyotype of 28,Y, +2, +3C, +D. The origin of this chromosomal composition is obscure. Besides endoreduplication in a normal 23,X oocyte pronucleus and fertilization by a normal 23,Y spermatozoon, an additional female pronucleus might have been formed due to an irregular chromosome distribution during second meiotic division. On the other hand, penetration by a hyperhaploid spermatozoon cannot be excluded with certainty.
Objective Hyperemesis gravidarum, severe nausea and vomiting in pregnancy, occurs in up to 2% of pregnancies and leads to significant weight loss, dehydration, electrolyte imbalance, and ketonuria. It is associated with both maternal and fetal morbidity. Familial aggregation studies and twin studies suggest a genetic component. In a recent GWAS, we showed that placentation, appetite, and cachexia genes GDF15 and IGFBP7 are linked to hyperemesis gravidarum (HG). The purpose of this study is to determine whether GDF15 and IGFBP7 are upregulated in HG patients. Methods We compared serum levels of GDF15 and IGFBP7 at 12 and 24 weeks' gestation in women hospitalized for HG, and two control groups, women with nausea and vomiting of pregnancy (NVP), and women with no NVP. Results We show GDF15 and IGFBP7 serum levels are significantly increased in women with HG at 12 weeks' gestation. Serum levels of hCG are not significantly different between cases and controls. At 24 weeks gestation, when symptoms have largely resolved, there is no difference in GDF15 and IGFBP7 serum levels between cases and controls. Conclusion This study supports GDF15 and IGFBP7 in the pathogenesis of HG and may be useful for prediction and diagnosis. The GDF15-GFRAL brainstem-activated pathway was recently identified and therapies to treat conditions of abnormal appetite are under intense investigation. Based on our findings, HG should be included.Hyperemesis gravidarum – Übelkeit und übermäßiges Erbrechen in der Schwangerschaft – tritt in bis zu 2% aller Schwangerschaften auf und führt zu erheblichem Gewichtsverlust, Austrocknung, Elektrolytentgleisungen und Ketonurie. Sie ist mit mütterlicher sowie fetaler Morbidität assoziiert. Familiäre Aggregationsstudien und Zwillingsstudien deuten auf eine genetische Komponente hin. In einer kürzlich publizierten, genomweiten Assoziationsstudie konnten wir zeigen, dass es einen Zusammenhang zwischen den Plazentations-, Appetit- und Kachexie-Genen GDF-15 und IGFBP-7 und Hyperemesis gravidarum (HG) gibt. Ziel dieser Studie war es, zu prüfen, ob GDF-15 und IGFBP-7 in HG-Patientinnen hochreguliert sind. Methoden Wir verglichen die GDF-15- und IGFBP-7-Spiegel in SSW 12 und 24 von Frauen, die wegen HG ins Krankenhaus eingewiesen wurden, mit den GDF-15- und IGFBP7-Spiegeln von 2 Kontrollgruppen (Frauen mit normaler Übelkeit und Erbrechen in der Schwangerschaft und Frauen ohne Übelkeit und Erbrechen in der Schwangerschaft). Ergebnisse Die GDF-15- und IGFBP-7-Spiegel von Frauen mit HG waren in SSW 12 signifikant erhöht. Dagegen unterschied sich der hCG-Serumspiegel nicht wesentlich zwischen Fällen und Kontrollen. In SSW 24 hatten sich die Symptome weitgehend gelegt, und es gab keine Unterschiede in den GDF-15- und IGFBP-7-Spiegeln zwischen Fällen und Kontrollen. Schlussfolgerung Diese Studie unterstützt die Hypothese, dass GDF-15 und IGFBP-7 eine Rolle bei der Pathogenese von HG spielen und dass sie bei der Vorhersage und Diagnose nützlich sein könnten. Der GDF-15-GFRAL-Hirnstamm-aktivierte Signalweg wurde vor Kurzem identifiziert, und es wird intensiv nach Therapien zur Behandlung von abnormen Essgelüsten geforscht. Vor dem Hintergrund unserer Ergebnisse sollte HG ebenfalls einbezogen werden.
Internationally, potential effects of national SARS-CoV-2-related lockdowns on stillbirth rates have been reported, but data for Germany, including risk factors for fetal pregnancy outcome, are lacking. The aim of this study is to compare the stillbirth rates during the two first lockdown periods in 2020 with previous years from 2010 to 2019 in a large Bavarian cohort.This study is a secondary analysis of the Bavarian perinatal data from 2010 to 2020, including 349,245 births. Univariate and multivariable regression analyses were performed to investigate the effect of two Bavarian lockdowns on the stillbirth rate in 2020 compared to the corresponding periods from 2010 to 2019.During the first lockdown, the stillbirth rate was significantly higher compared to the reference period (4.04 vs. 3.03 stillbirths per 1000 births; P = 0.03). After adjustment for seasonal and long-term trends, this effect can no longer be observed (P = 0.2). During the second lockdown, the stillbirth rate did not differ in univariate (3.46 vs. 2.93 stillbirths per 1000 births; P = 0.22) as well as in multivariable analyses (P = 0.68), compared to the years 2010 to 2019.After adjustment for known long-term effects, in this study we did not find evidence that the two Bavarian lockdowns had an effect on the rate of stillbirths.
Zusammenfassung Ziel Die Datenlage zu Geburtseinleitungen bei einem small-for-gestational-age Fetus (SGA-Fetus) oder einer intrauterinen Wachstumsrestriktion (IUGR) ist limitiert, sodass das Ziel dieser Untersuchung war, Geburtseinleitungen bei SGA-/IUGR-Feten mit Geburtseinleitungen bei Schwangerschaften mit einem fetalen Schätzgewicht oberhalb der 10. Perzentile zu vergleichen. Material und Methodik In diese multizentrische Kohortenstudie wurden Einlingsschwangerschaften am Termin eingeschlossen. Geburtseinleitungen bei SGA-/IUGR-Feten (IUGR-Gruppe) wurden mit Geburtseinleitungen bei Feten mit einem fetalen Schätzgewicht oberhalb der 10. Perzentile (Kontrollgruppe) verglichen. Der primäre Zielparameter war die Kaiserschnitt-Rate. Ergebnisse Es gab keinen Unterschied bezüglich der Kaiserschnitt-Rate zwischen den beiden Gruppen (27,0 vs. 26,2%, p=0,9154). In der IUGR-Gruppe lag jedoch häufiger ein pathologisches CTG (30,8 vs. 21,9%, p=0,0214) vor, und es wurden mehr Fetalblutanalysen (2,5 vs. 0,5%, p=0,0261) durchgeführt. Die Rate an kindlichen Verlegungen in die Kinderklinik war ebenfalls in der IUGR-Gruppe höher (40,0 vs. 12,8%, p<0,0001). Schlussfolgerung Geburtseinleitungen bei wachstumsrestringierten Feten sind nicht mit einer höheren Rate an Kaiserschnitten assoziiert.
Pregnancies and breastfeeding are two important protective factors concerning breast cancer risk. Breast volume and breast volume changes might be a breast phenotype that could be monitored during pregnancy and breastfeeding without ionizing radiation or expensive equipment. The aim of the present study was to document changes in breast volume during pregnancy prospectively. In the prospective Clinical Gravidity Association Trial and Evaluation programme, pregnant women were followed up prospectively from gestational week 12 to birth. Three-dimensional breast surface imaging and subsequent volume assessments were performed. Factors influencing breast volume at the end of the pregnancy were assessed using linear regression models. Breast volumes averaged 420 ml at the start of pregnancy and 516 ml at the end of pregnancy. The first, second and third quartiles of the volume increase were 41, 95 and 135 ml, respectively. Breast size increased on average by 96 ml, regardless of the initial breast volume. Breast volume increases during pregnancy, but not all womens' breasts respond to pregnancy in the same way. Breast volume changes during pregnancy are an interesting phenotype that can be easily assessed in further studies to examine breast cancer risk.
Low-frequency variants play an important role in breast cancer (BC) susceptibility. Gene-based methods can increase power by combining multiple variants in the same gene and help identify target genes.
Purpose Induction of labour for small-for-gestational-age (SGA) foetus or intrauterine growth restriction (IUGR) is common, but data are limited. The aim of this study was therefore to compare labour induction for SGA/IUGR with cases of normal foetal growth above the 10th percentile. Material and Methods This historical multicentre cohort study included singleton pregnancies at term. Labour induction for SGA/IUGR (IUGR group) was compared with cases of foetal growth above the 10th percentile (control group). Primary outcome measure was caesarean section rate. Results The caesarean section rate was not different between the 2 groups (27.0 vs. 26.2%, p = 0.9154). In the IUGR group, abnormal CTG was more common (30.8 vs. 21.9%, p = 0.0214), and foetal blood analysis was done more often (2.5 vs. 0.5%, p = 0.0261). There were more postpartum transfers to the NICU in the IUGR group (40.0 vs. 12.8%, p < 0.0001), too. Conclusion Induction of labour for foetal growth restriction was not associated with an increased rate of caesarean section.
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