Transforming Growth Factor-ß Receptor-Mediated, p38 Mitogen-Activated Protein Kinase-Dependent Signaling Drives Enhanced Myofibroblast Differentiation during Skin Wound Healing in Mice Lacking Hyaluronan Synthases 1 and 3.

Normal myofibroblast differentiation is critical for proper skin wound healing. Neoexpression of α-smooth muscle actin (α-SMA), a marker for myofibroblast differentiation, is driven by transforming growth factor (TGF)-ß receptor-mediated signaling. Hyaluronan and its three synthesizing enzymes, hyaluronan synthases (Has 1, 2, and 3), also participate in this process. Closure of skin wounds is significantly accelerated in Has1/3 double-knockout (Has1/3-null) mice. Herein, TGF-ß activity and dermal collagen maturation were increased in Has1/3-null healing skin. Cultures of primary skin fibroblasts isolated from Has1/3-null mice had higher levels of TGF-ß activity, α-SMA expression, and phosphorylation of p38 mitogen-activated protein kinase at Thr180/Tyr182, compared with wild-type fibroblasts. p38α mitogen-activated protein kinase was a necessary element in a noncanonical TGF-ß receptor signaling pathway driving α-SMA expression in Has1/3-null fibroblasts. Myocardin-related transcription factor (MRTF), a cofactor that binds to the transcription factor serum response factor (SRF), was also critical. Nuclear localization of MRTF was increased, and MRTF binding to SRF was enhanced in Has1/3-null fibroblasts. Inhibition of MRTF or SRF expression by RNA interference suppresses α-SMA expression at baseline and diminished its overexpression in Has1/3-null fibroblasts. Interestingly, total matrix metalloproteinase activity was increased in healing skin and fibroblasts from Has1/3-null mice, possibly explaining the increased TGF-ß activation.

Impact of the COVID-19 Pandemic On Violence Against Children: A Narrative Review.

PURPOSE OF REVIEW: The goal of this paper was to explore the different ways the COVID-19 pandemic has affected violence against children (VAC). RECENT FINDINGS: Recent research of peer-reviewed articles using operational or survey data revealed the pandemic's impact in terms of institutional responses, risk and mediating factors, changes in VAC dynamics, and a likely increase in child marriage. Findings include a decrease in institutional responses, activities, and prevention case openings; an increased incidence of interparental intimate partner violence (IPV) witnessing cases, hospital admissions for suspected Abusive Head Trauma (AHT), other pediatric injuries, and sexual violence; a change in family conflict dynamics; and an estimated increase in child marriages. It also revealed mediating factors between the relationship of the pandemic and VAC (such as parental stress and mental health symptoms), as well as risk factors observed by service providers, which include the risk of mental health symptoms of both parents and children. Post-pandemic VAC research can be improved by utilizing operational or survey data in a meaningful way to be able to derive sound intervention approaches to diminish the pandemic's impact on VAC and child marriage. We also propose for researchers to integrate child marriage into the definition of VAC.

Psychosocial work stress and parent-child bonding during the COVID-19 pandemic: clarifying the role of parental symptoms of depression and aggressiveness.

BACKGROUND: Parental work stress and impaired mental health seem to have intensified during the current COVID-19 pandemic. Both can have a negative impact on parent-child bonding: psychosocial work stress in the course of a spillover effect from work to family and symptoms of impaired mental health as part of a crossover effect from parent to child. This potentially affects the child's development in the long term. METHOD: This cross-sectional study examined the relationship between psychosocial work stress and parent-child bonding during the early COVID-19 pandemic (May-June 2020). Symptoms of depression and aggressiveness were considered as mediators of this relationship. The sample consisted of employees in Eastern Germany (n = 380; 42.9% mothers, 57.1% fathers), aged 24-55 years, with children aged 0-36 months. RESULTS: In the total sample, an association was only found after adjusting for potential confounders, indicating that higher psychosocial work stress is associated with weaker bonding between the parent and child (ß = 0.148, p = .017, 95% CI [0.566, 5.614]). The separate analyses for mothers and fathers did not reveal a statistically significant relationship between psychosocial work stress and parent-child bonding. In the total sample, the higher the psychosocial work stress was, the higher were the parental symptoms of depression (ß = 0.372, p < .001, 95% CI [3.417, 5.696]) and aggressiveness ß = 0.254, p < .001, 95% CI [1.008, 3.208]). The mental health symptoms in turn were related to weaker parent-child bonding (symptoms of depression ß = 0.320, p < .001, 95% CI [0.345, 0.749]; symptoms of aggressiveness ß = 0.394, p < .001, 95% CI [0.697, 1.287]). The results furthermore suggested that parental mental health symptoms mediate the association between psychosocial work stress and parent-child bonding (symptoms of depression, ab = 2.491, 95% CI [1.472, 3.577] and of aggressiveness, ab = 2.091, 95% CI [1.147, 3.279]). The mediation effect was also found in the separate analyses for the mothers and fathers. DISCUSSION: The results of this study during the early COVID-19 pandemic in Germany highlight the importance of prevention as well as intervention measures in relation to psychosocial work stress that may play a debilitating role in the context of family relationships. In addition, the results suggest that both employers and employees should be made aware of the importance of psychosocial work stress, as it can have a negative impact on mental health, which in turn may have a major influence on family relationships.

Social and Nonsocial Autism Symptom Domains in Children and Adolescents with Autism Spectrum Disorder and Attention-Deficit/Hyperactivity Disorder: Insights into Their Symptomatological Interplay.

INTRODUCTION: Autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) share overlapping symptomatology, particularly with regard to social impairments (including peer relationship difficulties), and they frequently co-occur. However, the nature of their co-occurrence remains unclear. Therefore, the current study aimed to examine the nature of the transdiagnostic link between ASD and ADHD from a symptomatological point of view measured with the Autism Diagnostic Observation Schedule (ADOS Module 3) and the Autism Diagnostic Interview-Revised (ADI-R). METHODS: We analyzed the social and nonsocial ASD symptom domain scores from both diagnostic instruments in 4 clinically referred groups (i.e., ASD, ADHD, ASD + ADHD, and no psychiatric diagnosis) without other co-occurring mental disorders using a two-by-two full-factorial MANOVA design with the factors ASD (yes/no) and ADHD (yes/no). RESULTS: We found no ASD by ADHD interaction effects across all symptom domain scores of ADOS and ADI-R, except for ADOS imagination/creativity. There were only main effects of the factor ASD but no main effects of ADHD. Follow-up contrasts showed that exclusively, ASD had an impact on the measured symptomatology in case of co-occurring ASD + ADHD. CONCLUSION: Overall, the results support an additive model of the symptomatology across areas of communication, social interaction, and stereotyped behaviors and restricted interests in case of the co-occurrence of ASD and ADHD when assessed with ADOS/ADI-R. Thus, one can assume that the phenotypic overlap of ASD + ADHD may be less complicated than suspected - at least with regard to ASD symptomatology - and that in the presence of ADHD, ASD symptomatology is generally well measurable with best-practice diagnostic instruments.

[Domestic violence and its psychological consequences during the COVID-19 pandemic-key findings from German-speaking countries]. / Häusliche Gewalt und ihre psychischen Folgen während der COVID-19-Pandemie ­ Zentrale Befunde aus dem deutschsprachigen Raum.

The impact of traumatic experiences on mental health during the COVID-19 pandemic has been insufficiently discussed in the German-speaking countries. Against this background, a working group of scientifically and clinically active colleagues was formed on behalf of the German-Speaking Society for Psychotraumatology (DeGPT). The aim of the working group was to summarize central research findings on the incidence of domestic violence and associated psychological distress during the COVID-19 pandemic in German-speaking countries and to discuss their implications. In addition, associations between pre-existing childhood trauma and psychological distress during the pandemic should be illuminated. The present narrative review was prepared for this purpose.The results of the studies conducted indicate high prevalences of domestic violence during the COVID-19 pandemic, which, however, predominantly correspond to pre-pandemic prevalences. Adults with current or pre-existing interpersonal traumatic experiences during childhood or adolescence reported increased psychological distress during the pandemic compared with adults without such experiences. A number of risk factors (e.g., female gender, lower frequency of social contacts) increased the risk of psychological distress and posttraumatic stress disorder symptoms during the pandemic. According to these findings, people with current or past interpersonal trauma exposure represent a vulnerable group with special support needs during pandemic contexts.

Mental health of working parents during the COVID-19 pandemic: can resilience buffer the impact of psychosocial work stress on depressive symptoms?

BACKGROUND: The COVID-19 pandemic has confronted working parents with an accumulation of stressors regarding changes in work, family, and social life, putting their mental health at risk. Stressors include altered working conditions such as working from home or changes in working hours as well as the difficulty to reconcile work and childcare due to the closure of childcare facilities. The present study examined the relationship of psychosocial work stress (i.e., work-privacy conflict and effort-reward imbalance at work) and depressive symptoms in working parents and whether this association was moderated by individual resilience. METHODS: Data of the present study (n = 452) were collected in Germany between May and June 2020 as part of the DREAMCORONA study. A subsample of working mothers (n = 191) and fathers (n = 261) completed the subscale for work-privacy conflict (WPC) of the Copenhagen Psychosocial Questionnaire, the Effort-Reward Imbalance (ERI) Questionnaire, the Connor-Davidson Resilience Scale (CD-RISC), and the Edinburgh Postnatal Depression Scale (EPDS). Multiple linear regression analyses including moderation were performed, controlling for gender, working hours per week, and a lifetime history of depression as potential confounders. RESULTS: Both WPC (ß = 0.336, p < .001) and ERI (ß = 0.254, p < .001) were significantly associated with depressive symptoms. Resilience moderated the relationship between ERI and depressive symptoms (ß = - 0.101, p = .018), indicating that higher resilience weakened the relationship. However, this effect was not found regarding the relationship between WPC and depressive symptoms (ß = 0.055, p = .167). CONCLUSIONS: The results highlight the need for measures to reduce psychosocial work stressors such as WPC and ERI during the COVID-19 pandemic on the one hand and to promote resilience on the other hand. The findings partially support the potential protective role of resilience buffering the association between psychosocial stress and mental health in working parents. Longitudinal studies are needed to confirm this effect.

CD44 inhibits α-SMA gene expression via a novel G-actin/MRTF-mediated pathway that intersects with TGFßR/p38MAPK signaling in murine skin fibroblasts.

Well-regulated differentiation of fibroblasts into myofibroblasts (MF) is critical for skin wound healing. Neoexpression of α-smooth muscle actin (α-SMA), an established marker for MF differentiation, is driven by TGFß receptor (TGFßR)-mediated signaling. Hyaluronan (HA) and its receptor CD44 may also participate in this process. To further understand this process, primary mouse skin fibroblasts were isolated and treated in vitro with recombinant TGF-ß1 (rTGF-ß1) to induce α-SMA expression. CD44 expression was also increased. Paradoxically, CD44 knockdown by RNA interference (RNAi) led to increased α-SMA expression and α-SMA-containing stress fibers. Removal of extracellular HA or inhibition of HA synthesis had no effect on α-SMA levels, suggesting a dispensable role for HA. Exploration of mechanisms linking CD44 knockdown to α-SMA induction, using RNAi and chemical inhibitors, revealed a requirement for noncanonical TGFßR signaling through p38MAPK. Decreased monomeric G-actin but increased filamentous F-actin following CD44 RNAi suggested a possible role for myocardin-related transcription factor (MRTF), a known regulator of α-SMA transcription and itself regulated by G-actin binding. CD44 RNAi promoted nuclear accumulation of MRTF and the binding to its transcriptional cofactor SRF. MRTF knockdown abrogated the increased α-SMA expression caused by CD44 RNAi, suggesting that MRTF is required for CD44-mediated regulation of α-SMA. Finally, chemical inhibition of p38MAPK reversed nuclear MRTF accumulation after rTGF-ß1 addition or CD44 RNAi, revealing a central involvement of p38MAPK in both cases. We concluded that CD44 regulates α-SMA gene expression through cooperation between two intersecting signaling pathways, one mediated by G-actin/MRTF and the other via TGFßR/p38MAPK.

Hyaluronan synthase 2 protects skin fibroblasts against apoptosis induced by environmental stress.

A balanced turnover of dermal fibroblasts is crucial for structural integrity and normal function of the skin. During recovery from environmental injury (such as UV exposure and physical wounding), apoptosis is an important mechanism regulating fibroblast turnover. We are interested in the role that hyaluronan (HA), an extracellular matrix molecule synthesized by HA synthase enzymes (Has), plays in regulating apoptosis in fibroblasts. We previously reported that Has1 and Has3 double knock-out (Has1/3 null) mice show accelerated wound closure and increased numbers of fibroblasts in the dermis. In the present study, we report that HA levels and Has2 mRNA expression are higher in cultured Has1/3 null primary skin fibroblasts than in wild type (WT) cells. Apoptosis induced by two different environmental stressors, UV exposure and serum starvation (SS), was reduced in the Has1/3 null cells. Hyaluronidase, added to cultures to remove extracellular HA, surprisingly had no effect upon apoptotic susceptibility to UVB or SS. However, cells treated with 4-methylumbelliferone to inhibit HA synthesis were sensitized to apoptosis induced by SS or UVB. When fibroblasts were transfected with Has2-specific siRNA that lowered Has2 mRNA and HA levels by 90%, both Has1/3 null and WT cells became significantly more sensitive to apoptosis. The exogenous addition of high molecular weight HA failed to reverse this effect. We conclude that Has1/3 null skin fibroblasts (which have higher levels of Has2 gene expression) are resistant to stress-induced apoptosis.

Relationship satisfaction and family routines of young parents before and during the first year of the COVID-19 pandemic: A latent growth curve analysis.

With the onset of the COVID-19 pandemic, parents had to reorganize their family routines under many external stressors (e.g., limited external childcare), which could have negatively affected their relationship satisfaction. This study aimed to examine the changes in relationship satisfaction of young parents from pre-pandemic times up to the second wave of the COVID-19 pandemic in Germany in December 2020 and whether these changes were different for mothers and fathers. Additionally, the role of perceived pandemic-related stress and changes in family routines was investigated. Data from 564 participants from DREAMCORONA, a sub-study of the prospective longitudinal cohort study "Dresden Study on Parenting, Work, and Mental Health" (DREAM), were analyzed. Relationship satisfaction was assessed at three measurement points (T0: pre-pandemic, i.e., August 2018-March 2020; T1: May-June 2020; T2: October-December 2020). To estimate changes in relationship satisfaction over time, Latent Growth Curve Models were calculated. Changes in family routines (i.e., changes in the division of housework and childcare from T0 to T1 as well as the availability of external childcare facilities at T1) and perceived pandemic-related stress at T1 were used as predictors. The models were adjusted for education and number of children per household. There was no significant change in relationship satisfaction over time, with no differences between mothers and fathers. The multi-group model revealed that changes in the division of housework and childcare predicted changes in relationship satisfaction in mothers, but not in fathers. For mothers, doing more housework than before the pandemic was negatively associated with changes in their relationship satisfaction over time. Additionally, reporting that their partner did more childcare than before the pandemic was positively associated with the relationship satisfaction of mothers. Our results indicate no general negative prospective association between the COVID-19 pandemic and parental relationship satisfaction over time. Nevertheless, our findings highlight the importance of the division of housework and childcare for mothers' relationship satisfaction and how pandemic-related changes in family routines alter this association.

Does parental mental health mediate the association between parents' perceived stress and parent-infant bonding during the early COVID-19 pandemic?

BACKGROUND: The spread of the COVID-19 virus was declared a pandemic in March 2020. New restrictions such as 'lockdowns' and 'social distancing' created challenges for individuals' work-life balance, financial situation, family life, and physical and mental health. The global population's stress levels rose in response to these changes, leading to a widespread deterioration of mental health. One group particularly affected was parents of infants and very young children. Poor parental mental health may disrupt parent-infant bonding, with negative consequences for infant well-being and development. AIMS: To consider parent-infant bonding in relation to parents' perceived stress and psychological distress during the first lockdown, and to examine whether associations of stress with parent-infant bonding were mediated by parental mental health. METHODS: DREAMCORONA (n = 738: 471 mothers and 267 partners) is a sub-study of the prospective German cohort study 'DREAM'. The SPSS modelling tool PROCESS was used to assess whether parental mental health mediated the relationship between parents' perceived stress response to the COVID-19 pandemic and parent-infant bonding, while controlling for covariates. RESULTS: Higher levels of parental stress were strongly associated with higher levels of depression, anxiety, and aggression symptoms for both parents. In addition, there was a significant relationship between parents' self-reported stress levels and parent-infant bonding. This relationship was mediated by symptoms of depression and anxiety for fathers and by symptoms of anger-hostility for both parents. CONCLUSION: Increased parental stress during the early pandemic was associated with poorer parent-infant bonding. This has important implications for the management of any future public health crises.

Prevalence and risk factors of intimate partner violence during the COVID-19 pandemic: Results from the population-based study DREAMCORONA.

OBJECTIVES: This study examines the 12-month prevalence rates of intimate partner violence (IPV) victimization, including psychological, physical, and sexual forms, in women and men. It also aims to identify changes in IPV victimization during the COVID-19 pandemic and to explore factors associated with the occurrence of any IPV victimization during this period. METHODS: Data from the DREAMCORONA study in Germany collected from May 2020 to February 2021 included 737 participants, i.e., (expectant) mothers (64%) and fathers (36%). The Revised Conflict Tactics Scale (CTS2S) short form was used to assess the 12-month IPV victimization. Prevalence of IPV victimization as well as changes in IPV victimization during the pandemic were analyzed descriptively, with results stratified by sex. Multiple logistic regression was employed to identify risk factors for IPV. RESULTS: Psychological IPV was found to be the most prevalent form of violence, with the occurrence of any psychological IPV affecting 48.5% of women and 39.4% of men, while 2.6% of women and 3.3% of men reported the occurrence of any physical IPV victimization, and 2.8% of women and 1.5% of men reported the occurrence of any sexual IPV victimization. Of those who experienced the occurrence of any IPV in the last 12 months, 89.7% of women and 89.8% of men were victimized by one single act of violence. The majority of affected participants reported no change in psychological and physical IPV victimization during the pandemic. Nevertheless, for certain IPV behaviors on the psychological and physical IPV victimization subscales, both affected women and men also reported higher frequencies during the COVID-19 pandemic. Multiple logistic regression revealed that higher levels of relationship satisfaction were negatively associated with the occurrence of any IPV victimization for women and men, whereas greater levels of own anger-hostility symptoms were positively associated with the occurrence of any IPV victimization. CONCLUSIONS: Psychological IPV was present in almost every second (expectant) couple. The majority of affected women and men reported no change in their psychological and physical IPV victimization, suggesting that they continued to experience IPV during the pandemic. This underlines the importance of promoting healthier relationship dynamics, coping strategies, and emotional well-being to reduce the risk of IPV, even in times of crisis. Our study sheds light on the early stages of the pandemic and highlights the ongoing need for research into the temporal dynamics of IPV.

Validation of the Employment Precariousness Scale and its associations with mental health outcomes: results from a prospective community-based study of pregnant women and their partners in Dresden, Germany.

OBJECTIVE: To translate the Employment Precariousness Scale (EPRES) from Spanish into German (EPRES-Ge), adapt it to the German context, assess the psychometric properties and show prospective associations with mental health outcomes within the peripartum period. DESIGN: Analyses encompassed descriptive statistics, exploratory factor analysis, confirmatory factor analysis (CFA) to validate the structure of the EPRES, and multivariate regression analyses with mental health outcomes 8 weeks after birth. PARTICIPANTS: Self-report data from 3,455 pregnant women and their partners within the Dresden Study on Parenting, Work, and Mental Health prospective longitudinal cohort study were used. RESULTS: The EPRES-Ge with five dimensions and 20 items showed good internal consistency (Cronbach's α=0.77). All scales showed good reliability coefficients of α=0.73-0.85 and good item-subscale correlations of r=0.63-0.98, with the exception of subscale rights, which showed poor reliability of α=0.30 and item-subscale correlations of r=0.45-0.68. Exploratory analysis and CFA confirmed the proposed five-dimensional structure, explaining 45.08% of the cumulative variance. Regression analyses with mental health outcomes after birth revealed statistically significant associations (ß=0.12-0.20). CONCLUSIONS: The EPRES-Ge is a valuable tool for assessing employment precariousness as a multidimensional construct. The scales could be adapted to the German working context. Precarious employment, as measured by the EPRES-Ge, is a determinant of mental health problems in young families.

Changes in relationship satisfaction in the transition to parenthood among fathers.

To date, research on the transition to parenthood and associated changes in relationship satisfaction (RS) has focused predominantly on mothers with their firstborn. This study targeted fathers to investigate their trajectories of RS with a particular focus on emerging differences between first- and second-time fathers. It furthermore considered various predictors such as the role of age, education, income, duration of relationship, marital status, child's biological sex, and child temperament. Data from a total of 606 fathers from the prospective longitudinal cohort study DREAM were analyzed. The analyses included assessments of four measurement time points (T1: prepartum; T2-T4: postpartum) over a period of more than 2 years. Latent growth curve modeling was applied with RS as the dependent variable and number of children as one of eight predictors of growth over time. First-time fathers showed higher initial RS, however experienced a steeper decline in the transition to parenthood than second-time fathers. At 8 weeks postpartum, first-time fathers still reported higher RS than second-time fathers. While RS continued to decline for first-time fathers up until 14 months postpartum, second-time fathers experienced an increase in RS. At 14 months and 2 years postpartum, second-time fathers showed higher RS scores than first-time fathers. Similar to first-time mothers, first-time fathers seem to experience a stronger RS decline during the transition to parenthood than second-time fathers, suggesting that especially couples becoming parents for the first time should be prepared for expected changes in their relationship.

Maternal postpartum depressive symptoms: The predictive role of objective and subjective birth experience and hair glucocorticoids.

BACKGROUND: Having a negative childbirth experience is a known risk-factor for developing postpartum depression (PPD). Alterations of the hypothalamus-pituitary-adrenal (HPA)-axis have been discussed as a potential underlying mechanism. However, research on the association between negative birth experiences and long-term integrated glucocorticoids (GCs) is lacking. This study aimed to examine whether objective and subjective birth experience predicted long-term GCs and PPD symptoms. METHODS: Measures of objective and subjective birth experience, PPD symptoms, and hair strands for the assessment of hair cortisol concentrations (HairF), hair cortisone concentrations (HairE), and HairF/HairE ratio, were provided eight weeks after childbirth by 235 mothers participating in the study DREAMHAIR. RESULTS: A negative objective birth experience predicted a higher HairF/HairE ratio but was not associated with HairF or HairE. The subjective birth experience did not explain additional variance in hair GCs but was a significant predictor for PPD symptoms. A higher HairF/HairE ratio predicted PPD symptoms when controlling for prepartum depressive symptoms and number of lifetime traumatic events. LIMITATIONS: Analyses were based on a relatively homogeneous sample and women reported in general positive birth experiences and low levels of depressive symptoms. Therefore, results should be applied to the broader population with caution. CONCLUSIONS: Our results suggest that negative objective birth experience is associated with an altered HairF/HairE ratio, which in turn, seems to be a promising biomarker to identify women at risk for developing PPD. A negative subjective birth experience may be less critical for alterations of the HPA-axis but remains an essential risk factor for PPD.

Childbirth-related posttraumatic stress symptoms - examining associations with hair endocannabinoid concentrations during pregnancy and lifetime trauma.

Evidence has linked alterations of the endocannabinoid system with trauma exposure and posttraumatic stress disorder (PTSD). Childbirth-related PTSD symptoms (CB-PTSS) affect about every eighth woman and can negatively influence the entire family. While aetiological models of CB-PTSD include psychological risk factors such as maternal trauma history and negative subjective birth experience (SBE), they lack biological risk indicators. We investigated whether lifetime trauma and CB-PTSS were associated with long-term endocannabinoid concentrations during pregnancy. Further, we tested endocannabinoids as mediators between lifetime trauma and CB-PTSS and whether SBE moderated such mediational paths. Within the prospective cohort study DREAMHAIR, 263 expectant mothers completed trauma assessments and provided hair samples for quantification of long-term endocannabinoid levels (anandamide [AEA], 2-arachidonoylglycerol [1-AG/2-AG], and N-acyl-ethanolamides [NAE]) prior to their anticipated birth date. Two months postpartum, CB-PTSS and SBE were measured. Regression models controlling for relevant confounders showed no association between lifetime trauma and hair endocannabinoids during pregnancy, yet higher number of lifetime trauma events and lower hair AEA were significantly associated with CB-PTSS, with the latter finding not remaining significant when Bonferroni corrections due to multiple testing were applied. While hair AEA did not mediate the association between lifetime trauma and CB-PTSS, the effect of lower hair AEA on CB-PTSS was stronger upon negative SBE. Results suggest greater lifetime trauma and reduced maternal hair AEA during pregnancy may be associated with increased risk for CB-PTSS, particularly upon negative SBE. Findings confirm lifetime trauma as a CB-PTSS risk factor and add important preliminary insights on the role of endocannabinoid ligand alterations and SBE in CB-PTSS pathology.

The association between maternal symptoms of depression and hair glucocorticoids in infants across the perinatal period.

BACKGROUND: Maternal symptoms of depression constitute an early adversity for infants that is considered to exert its effects via the maternal-placental-fetal neuroendocrine axis. Previous research implicates associations between maternal prenatal symptoms of depression and infants' glucocorticoid (GC) levels shortly after birth. To date, associations have not been investigated in the early postnatal period. The current study aimed to investigate the influence of maternal perinatal symptoms of depression on infants' neonatal and postnatal hair GCs providing a retrospective reflection of integrated cortisol secretion in the intrauterine and early postnatal period, respectively. METHODS: As part of a prospective cohort study, hair samples of infants were taken up to two weeks after delivery (N = 152) and again eight weeks after delivery (N = 165). Liquid chromatography-tandem mass spectrometry was used to determine hair cortisol and cortisone in scalp-near 2-cm hair segments. Maternal symptoms of depression were assessed during pregnancy and eight weeks postnatally based on the Edinburgh Postnatal Depression Scale. RESULTS: Higher maternal prenatal symptoms of depression showed a significant association with higher infants' neonatal hair cortisol, when controlling for confounding variables (i.e., gestational age, mode of delivery, parity, storage time, pregnancy complications). A non-significant trend for this effect was found for the hair cortisol-to-cortisone ratio while no effect occurred for hair cortisone. No association of maternal postnatal symptoms of depression with infants' postnatal hair GCs was observed. Further exploratory analyses revealed no relationship between a change of maternal prenatal to postnatal symptoms of depression with the change from infants' neonatal to postnatal hair GC levels or postnatal hair GCs. CONCLUSION: Our results suggest that maternal prenatal symptoms of depression are associated with dysregulated infants' hair cortisol levels mainly incorporated in the intrauterine period which, in turn, might contribute to increased susceptibility for later diseases. However, no relationship was observed in infants' hair samples additionally reflecting hair GCs of the early postnatal period. Future studies should consider research on associations between maternal symptoms of depression and infants' hair GCs also later in life and take into account additional risk factors with potential impacts on GC secretion during early infancy.

Significant Association of Poly-A and Fok1 Polymorphic Alleles of the Vitamin D Receptor with Vitamin D Serum Levels and Incidence of Squamous Cutaneous Neoplasia.

Vitamin D3, a prohormone, is converted to circulating calcidiol and then to calcitriol, the hormone that binds to the vitamin D receptor (VDR) (a nuclear transcription factor). Polymorphic genetic sequence variants of the VDR are associated with an increased risk of breast cancer and melanoma. However, the relationship between VDR allelic variants and the risk of squamous cell carcinoma and actinic keratosis remains unclear. We examined the associations between two VDR polymorphic sites, Fok1 and Poly-A, and serum calcidiol levels, actinic keratosis lesion incidence, and the history of cutaneous squamous cell carcinoma in 137 serially enrolled patients. By evaluating the Fok1 (F) and (f) alleles and the Poly-A long (L) and short (S) alleles together, a strong association between genotypes FFSS or FfSS and high calcidiol serum levels (50.0 ng/ml) was found; conversely, ffLL patients showed very low calcidiol levels (29.1 ng/ml). Interestingly, the FFSS and FfSS genotypes were also associated with reduced actinic keratosis incidence. For Poly-A, additive modeling showed that Poly-A (L) is a risk allele for squamous cell carcinoma, with an OR of 1.55 per copy of the L allele. We conclude that actinic keratosis and squamous cell carcinoma should be added to the list of squamous neoplasias that are differentially regulated by the VDR Poly-A allele.

The impact of postpartum obsessive-compulsive symptoms on child development and the mediating role of the parent-child relationship: A prospective longitudinal study.

Background: The first 2 years of life are a particularly sensitive period for the parent-child relationship as well as a healthy, age-appropriate child development. Both have been shown to be linked to postpartum depressive and anxiety symptoms, while the role of obsessive-compulsive symptoms, which are also common, is still largely understudied. In addition, fathers have been neglected in this area of research. This study, which includes both mothers and fathers, aims to investigate the longitudinal associations between postpartum obsessive-compulsive symptoms and different domains of child development, as well as the mediating role of the parent-child relationship. Methods: Data were drawn from the prospective longitudinal study DREAM, with 674 mothers and 442 fathers from the general population completing self-report questionnaires at four measurement points. Longitudinal associations between parental postpartum obsessive-compulsive symptoms 8 weeks postpartum, the parent-child relationship 14 months postpartum, and child development 24 months postpartum were investigated using regression and mediation analyses. A number of potential confounding variables were considered, i.e., age, academic degree, postpartum depressive and anxiety symptoms of the parents, preterm birth and temperament of the child, as well as COVID-19 pandemic-driven adversities. Results: When adjusting for confounders, neither maternal nor paternal postpartum obsessive-compulsive symptoms had adverse effects on the respective parent-child relationship and child development. Further, no mediating role of the parent-child relationship between parental postpartum obsessive-compulsive symptoms and child development could be confirmed. Instead, we found that the mother- and father-child relationship were differentially related to specific child developmental domains. For mothers, a poorer mother-child relationship was prospectively related to poorer fine motor development. For fathers, a poorer father-child relationship prospectively predicted a poorer overall development as well as poorer gross motor, fine motor, problem-solving, and personal-social development. Conclusion: Our results suggest that negative effects on the parent-child relationship and child development may only become apparent in full-blown postpartum obsessive-compulsive disorder. Given the differential impact on specific developmental domains, our findings also suggest that it is crucial to consider both parents in clinical practice as well as in future research, rather than focusing only on the mother-child dyad.

A data driven machine learning approach to differentiate between autism spectrum disorder and attention-deficit/hyperactivity disorder based on the best-practice diagnostic instruments for autism.

Autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) are two frequently co-occurring neurodevelopmental conditions that share certain symptomatology, including social difficulties. This presents practitioners with challenging (differential) diagnostic considerations, particularly in clinically more complex cases with co-occurring ASD and ADHD. Therefore, the primary aim of the current study was to apply a data-driven machine learning approach (support vector machine) to determine whether and which items from the best-practice clinical instruments for diagnosing ASD (ADOS, ADI-R) would best differentiate between four groups of individuals referred to specialized ASD clinics (i.e., ASD, ADHD, ASD + ADHD, ND = no diagnosis). We found that a subset of five features from both ADOS (clinical observation) and ADI-R (parental interview) reliably differentiated between ASD groups (ASD & ASD + ADHD) and non-ASD groups (ADHD & ND), and these features corresponded to the social-communication but also restrictive and repetitive behavior domains. In conclusion, the results of the current study support the idea that detecting ASD in individuals with suspected signs of the diagnosis, including those with co-occurring ADHD, is possible with considerably fewer items relative to the original ADOS/2 and ADI-R algorithms (i.e., 92% item reduction) while preserving relatively high diagnostic accuracy. Clinical implications and study limitations are discussed.

Paternal Leave and Father-Infant Bonding: Findings From the Population-Based Cohort Study DREAM.

Background: Father-infant bonding is important for child development. Yet, in contrast to mother-infant bonding, little is known about factors that might facilitate father-infant bonding. With new generations of fathers being more involved in childcare, this study aims to examine the impact of paternal leave duration on father-infant bonding, and whether this relation is mediated by the amount of time fathers actively spend on childcare. Methods: Data of n = 637 fathers were derived from the German population-based cohort study "Dresden Study on Parenting, Work, and Mental Health" (DREAM). Mediation analyses were conducted. Duration of paternal leave (predictor), weekly hours spent on childcare (mediator), and father-infant bonding (outcome) were measured at 14 months postpartum. The potential confounders current status of paternal leave, part-time work during paternal leave, duration of solo paternal leave, age, education, and partnership satisfaction were included in a second mediation analysis. Results: Without considering confounders, duration of paternal leave positively predicted father-infant bonding through weekly hours spent on childcare. When adding confounders to the model, this indirect path did not stay significant. Moreover, in the adjusted model and on the direct path duration of paternal leave negatively predicted father-infant bonding. Additionally, partnership satisfaction positively predicted father-infant bonding. Some study variables were significantly associated with the mediator. Longer duration of paternal leave, currently being on paternal leave, younger age, and lower educational level predicted more weekly hours spent on childcare. Conclusions: Duration of paternal leave not being a stable predictor for father-infant bonding suggests that fathers, who do not have the opportunity to take long periods of paternal leave, can still form strong bonds with their infants. Other factors, for example partnership satisfaction, which might represent fathers' underlying capacity to bond, might be more crucial for father-infant bonding. At the same time, results should not be interpreted in a way that father involvement (e.g., paternal leave/time spent) does not matter for children's development. The finding that longer duration of paternal leave increases weekly hours spent on childcare supports the idea that facilitating father involvement can be achieved by paternal leave incentives such as non-transferable father months.