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Background: Several studies have shown associations between maternal interpersonal violence-related posttraumatic stress disorder (PTSD), child mental health problems, and impaired socioemotional development. However, the existing literature lacks evidence linking constellations of risk factors such as maternal interpersonal-violence-related PTSD, psychopathology, and interactive behavior with toddlers and outcome measures at school-age., Methods: This study involved a prospective, longitudinal investigation of 62 mothers and examined the relationship between maternal variables measured when children were in early childhood (mean age 27 months), and child outcomes when children were school-age (age mean = 83.2 months) while retaining a focus on the context of maternal PTSD. To identify and weigh associated dimensions comparatively, we employed sparse canonical correlation analysis (sCCA) aimed at associating dimensions of a dataset of 20 maternal variables in early childhood with that of more than 20 child outcome variables (i.e., child psychopathology, life-events, and socioemotional skills) at school-age., Results: Phase 1 variables with the highest weights were those of maternal psychopathology: PTSD, depressive and dissociative symptoms, and self-report of parental stress. The highest weighted Phase 2 child outcome measures were those of child psychopathology: PTSD, anxiety, and depressive symptoms as well as peer bullying and victimization., Conclusions: sCCA revealed that trauma-related concepts in mothers were significantly and reliably associated with child psychopathology and other indicators of risk for intergenerational transmission of violence and victimization. The results highlight the dimensional and multifaceted nature-both for mothers as well as children-of the intergenerational transmission of violence and associated psychopathology.

Background: Birth-related post-traumatic stress disorder occurs in 4.7% of mothers. No previous study focusing precisely on the stress factors related to the COVID-19 pandemic regarding this important public mental health issue has been conducted. However, the stress load brought about by the COVID-19 pandemic could have influenced this risk., Methods: We aimed to estimate the prevalence of traumatic childbirth and birth-related PTSD and to analyze the risk and protective factors involved, including the risk factors related to the COVID-19 pandemic. We conducted a prospective cohort study of women who delivered at the University Hospitals of Geneva between 25 January 2021 and 10 March 2022 with an assessment within 3 days of delivery and a clinical interview at one month post-partum., Results: Among the 254 participants included, 35 (21.1%, 95% CI: 15.1-28.1%) experienced a traumatic childbirth and 15 (9.1%, 95% CI: 5.2-14.6%) developed a birth-related PTSD at one month post-partum according to DSM-5. Known risk factors of birth-related PTSD such as antenatal depression, previous traumatic events, neonatal complications, peritraumatic distress and peritraumatic dissociation were confirmed. Among the factors related to COVID-19, only limited access to prenatal care increased the risk of birth-related PTSD., Conclusions: This study highlights the challenges of early mental health screening during the maternity stay when seeking to provide an early intervention and reduce the risk of developing birth-related PTSD. We found a modest influence of stress factors directly related to the COVID-19 pandemic on this risk.

The aim of this study was to examine associations between maternal mentalization, interactive behavior, and child symptoms in families in which mothers suffer from interpersonal violence-related posttraumatic stress disorder (IPV-PTSD). Fifty-six mothers and children (aged 12-42 months) including mothers with a diagnosis of IPV-PTSD were studied. Mentalization was measured by the Parental Reflective Functioning (PRF) Scale. Interactive behavior during free-play was measured via the CARE-Index. Child symptoms were measured by the Infant-Toddler Social and Emotional Assessment (ITSEA). Data analyses included non-parametric correlations and multiple linear regression. Results showed that lower IPV-PTSD and higher Maternal Reflective Functioning (MRF) were related to greater maternal sensitivity. Lower MRF and greater controlling behavior were related to child dysregulation. MRF was found to be lower in the subgroup of IPV-PTSD when the child's father was the perpetrator of IPV. Both MRF and interactive behavior are thus likely to be important targets for intervention during sensitive periods of early social-emotional development.

Parental Reflective Functioning is a parent's capacity to infer mental states in herself and her child. Parental Reflective Functioning is linked to the quality of parent-child attachment and promotes parent-child mutual emotion regulation. We examined neural correlates of parental reflective functioning and their relationship to physical abuse. Participants were mothers with (n = 26) and without (n = 22) history of childhood physical abuse. Parental reflective functioning was assessed by coding transcripts of maternal narrative responses on interviews. All mothers also underwent magnetic resonance imaging while watching video clips of children during mother-child separation and play. Parental reflective functioning was significantly lower among mothers with histories of childhood physical abuse. When mothers without history of childhood physical abuse watched scenes of separation versus play, brain activation was positively correlated with parental reflective functioning in the ventromedial prefrontal cortex, and negatively associated with the dorsolateral prefrontal cortex and insula. These associations were not present when limiting analyses to mothers reporting abuse histories. Regions subserving emotion regulation and empathy were associated with parental reflective functioning; yet these regions were not featured in maltreated mothers. These data suggest that childhood physical abuse exposure may alter the psychobiology that is linked to emotional comprehension and regulation., (Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.)

The aim of this study was to examine the relationship of maternal interpersonal violence-related posttraumatic stress disorder (IPV-PTSD), associated neural activity in response to mother-child relational stimuli, and child psychopathology indicators at child ages 12-42 months and one year later. The study tested the hypothesis that decreased maternal neural activity in regions that subserve emotion regulation would be associated with child symptoms associated with emotional dysregulation at both time points. Functional magnetic resonance imaging of 42 mothers with or without violence-exposure and associated IPV-PTSD were assessed. Their child's life-events and symptoms/behaviors indicative of high-risk subsequent PTSD diagnosis on a maternal-report questionnaire were measured one year later. Maternal IPV-PTSD severity was significantly associated with decreased ventromedial prefrontal cortex (vmPFC) activation in response to mother-child relational stimuli. Maternal IPV-PTSD severity and decreased vmPFC activation were then significantly associated with a child attachment disturbance at 12-42 months and symptoms/behaviors one year later, that were correlated with emotional dysregulation and risk for child PTSD. Maternal IPV-PTSD and child exposure to IPV were both predictive of child PTSD symptoms with maternal IPV-PTSD likely mediating the effects of child IPV exposure on child PTSD symptoms. These findings suggest that maternal IPV-PTSD severity and associated decreased vmPFC activity in response to mother-child relational stimuli are predictors of child psychopathology by age 12-42 months and one-year later. Significant findings in this paper may well be useful in understanding how maternal top-down cortico-limbic dysregulation promotes intergenerational transmission of IPV and related psychopathology and, thus should be targeted in treatment.

Background: Methylation of the serotonin 3A receptor gene (HTR3A) has been linked to child maltreatment and adult psychopathology. The present study examined whether HTR3A methylation might be associated with mothers' lifetime exposure to interpersonal violence (IPV), IPV-related psychopathology, child disturbance of attachment, and maternal neural activity., Methods: Number of maternal lifetime IPV exposures and measures of maternal psychopathology including posttraumatic stress disorder (PTSD), major depression and aggressive behavior (AgB), and a measure of child attachment disturbance known as "secure base distortion" (SBD) were assessed in a sample of 35 mothers and children aged 12-42 months. Brain fMRI activation was assessed in mothers using 30-s silent film excerpts depicting menacing adult male-female interactions versus prosocial and neutral interactions. Group and continuous analyses were performed to test for associations between clinical and fMRI variables with DNA methylation., Results: Maternal IPV exposure-frequency was associated with maternal PTSD; and maternal IPV-PTSD was in turn associated with child SBD. Methylation status of several CpG sites in the HTR3A gene was associated with maternal IPV and IPV-PTSD severity, AgB and child SBD, in particular, self-endangering behavior. Methylation status at a specific CpG site (CpG2_III) was associated with decreased medial prefrontal cortical (mPFC) activity in response to film-stimuli of adult male-female interactions evocative of violence as compared to prosocial and neutral interactions., Conclusions: Methylation status of the HTR3A gene in mothers is linked to maternal IPV-related psychopathology, trauma-induced brain activation patterns, and child attachment disturbance in the form of SBD during a sensitive period in the development of self-regulation., (Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.)

Women who have experienced interpersonal violence (IPV) are at a higher risk to develop posttraumatic stress disorder (PTSD), with dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis and impaired social behavior. Previously, we had reported impaired maternal sensitivity and increased difficulty in identifying emotions (i.e. alexithymia) among IPV-PTSD mothers. One of the aims of the present study was to examine maternal IPV-PTSD salivary cortisol levels diurnally and reactive to their child's distress in relation to maternal alexithymia. Given that mother-child interaction during infancy and early childhood has important long-term consequences on the stress response system, toddlers' cortisol levels were assessed during the day and in response to a laboratory stressor. Mothers collected their own and their 12-48month-old toddlers' salivary samples at home three times: 30min after waking up, between 2-3pm and at bedtime. Moreover, mother-child dyads participated in a 120-min laboratory session, consisting of 3 phases: baseline, stress situation (involving mother-child separation and exposure to novelty) and a 60-min regulation phase. Compared to non-PTSD controls, IPV-PTSD mothers - but not their toddlers, had lower morning cortisol and higher bedtime cortisol levels. As expected, IPV-PTSD mothers and their children showed blunted cortisol reactivity to the laboratory stressor. Maternal cortisol levels were negatively correlated to difficulty in identifying emotions. Our data highlights PTSD-IPV-related alterations in the HPA system and its relevance to maternal behavior. Toddlers of IPV-PTSD mothers also showed an altered pattern of cortisol reactivity to stress that potentially may predispose them to later psychological disorders., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Older nursing home residents often have a large number of diseases and frequently require multiple medications; the high consumption of psychotropic drugs is of particular concern. The majority of residents in nursing homes suffer from dementia, and the use of psychotropic drugs in these patients is very high. Prescription for short periods of time only are usually recommended to avoid the risk of adverse drug reactions and potentially severe drug-drug interactions (DDIs)., Objectives: The aim of this multicenter, prospective study was to optimize the prescription of psychotropic drugs, according to the Beers recommendations, in a sample of older patients living in nursing homes in Italy, through a multicomponent intervention, education of general practitioners, and the use of INTERcheck., Methods: The study was run in ten nursing homes in Northern Italy from September 2013 to May 2014 (9 months), with the voluntary participation of 14 general practitioners. Each physician was asked to enroll at least 20 consecutive unselected patients. Three educational interventions ('ex cathedra' presentations) were organized by the researchers involved in the project, and a fourth training session was also held on the use of INTERCheck, a Computerized Prescription Support System (CPSS) developed to optimize drug prescription for older people with multimorbidity. Drug prescription information and sociodemographic characteristics of each patient were collected at three different time points-before the educational and training sessions (T0), after 5 months (T1), and after 9 months (T2)., Results: Among the 272 patients included in the analysis, a significant reduction was observed in the mean number of drugs, and in the percentage receiving psychotropic drugs and potentially inappropriate psychotropic drugs (11.5 and 30.6 %, respectively; p < 0.0001). Patients exposed to at least one potentially severe DDI also decreased from 145 (53.3 %) at the first time point to 87 (32.0 %) at the last time point (p < 0.0001). Results were confirmed in the 181 patients for whom information regarding drug treatment was available at all time points., Conclusions: The combination of an educational intervention and the CPSS can achieve a significant reduction in potentially inappropriate psychotropic drug use, psychotropic duplicates, and potentially severe DDIs in nursing homes.

It is known that increased circulating glucocorticoids in the wake of excessive, chronic, repetitive stress increases anxiety and impairs Brain-Derived Neurotrophic Factor (BDNF) signaling. Recent studies of BDNF gene methylation in relation to maternal care have linked high BDNF methylation levels in the blood of adults to lower quality of received maternal care measured via self-report. Yet the specific mechanisms by which these phenomena occur remain to be established. The present study examines the link between methylation of the BDNF gene promoter region and patterns of neural activity that are associated with maternal response to stressful versus non-stressful child stimuli within a sample that includes mothers with interpersonal violence-related PTSD (IPV-PTSD). 46 mothers underwent fMRI. The contrast of neural activity when watching children-including their own-was then correlated to BDNF methylation. Consistent with the existing literature, the present study found that maternal BDNF methylation was associated with higher levels of maternal anxiety and greater childhood exposure to domestic violence. fMRI results showed a positive correlation of BDNF methylation with maternal brain activity in the anterior cingulate (ACC), and ventromedial prefrontal cortex (vmPFC), regions generally credited with a regulatory function toward brain areas that are generating emotions. Furthermore we found a negative correlation of BDNF methylation with the activity of the right hippocampus. Since our stimuli focus on stressful parenting conditions, these data suggest that the correlation between vmPFC/ACC activity and BDNF methylation may be linked to mothers who are at a disadvantage with respect to emotion regulation when facing stressful parenting situations. Overall, this study provides evidence that epigenetic signatures of stress-related genes can be linked to functional brain regions regulating parenting stress, thus advancing our understanding of mothers at risk for stress-related psychopathology.

Socio-emotional information processing during everyday human interactions has been assumed to translate to social-emotional information processing when parenting a child. Yet, few studies have examined whether this is indeed the case. This study aimed to improve on this by connecting the functional neuroimaging data when seeing socio-emotional interactions that are not parenting specific to observed maternal sensitivity. The current study considered 45 mothers of small children (12-42 months of age). It included healthy controls (HC) and mothers with interpersonal violence-related posttraumatic stress disorder (IPV-PTSD), as well as mothers without PTSD, both with and without IPV exposure. We found that anterior cingulate cortex (ACC) and ventromedial prefrontal cortex (vmPFC) activity correlated negatively with observed maternal sensitivity when mothers watched videos of menacing vs. prosocial adult male-female interactions. This relationship was independent of whether mothers were HC or had IPV-PTSD. We also found dorsolateral prefrontal cortex (dlPFC) activity to be correlated negatively with maternal sensitivity when mothers watched any kind of arousing adult interactions. With regards to ACC and vmPFC activity, we interpret our results to mean that the ease of general emotional information integration translates to parenting-specific behavior. Our dlPFC activity findings support the idea that the efficiency of top-down control of socio-emotional processing in non-parenting specific contexts may be predictive of parenting behavior.

Rituximab induces nephrotic syndrome (NS) remission in two-thirds of patients with primary membranous nephropathy (MN), even after other treatments have failed. To assess the relationships among treatment effect, circulating nephritogenic anti-phospholipase A2 receptor (anti-PLA2R) autoantibodies and genetic polymorphisms predisposing to antibody production we serially monitored 24-hour proteinuria and antibody titer in patients with primary MN and long-lasting NS consenting to rituximab (375 mg/m(2)) therapy and genetic analyses. Over a median (range) follow-up of 30.8 (6.0-145.4) months, 84 of 132 rituximab-treated patients achieved complete or partial NS remission (primary end point), and 25 relapsed after remission. Outcomes of patients with or without detectable anti-PLA2R antibodies at baseline were similar. Among the 81 patients with antibodies, lower anti-PLA2R antibody titer at baseline (P=0.001) and full antibody depletion 6 months post-rituximab (hazard ratio [HR], 7.90; 95% confidence interval [95% CI], 2.54 to 24.60; P<0.001) strongly predicted remission. All 25 complete remissions were preceded by complete anti-PLA2R antibody depletion. On average, 50% anti-PLA2R titer reduction preceded equivalent proteinuria reduction by 10 months. Re-emergence of circulating antibodies predicted disease relapse (HR, 6.54; 95% CI, 1.57 to 27.40; P=0.01), whereas initial complete remission protected from the event (HR, 6.63; 95% CI, 2.37 to 18.53; P<0.001). Eighteen patients achieved persistent antibody depletion and complete remission and never relapsed. Outcome was independent of PLA2R1 and HLA-DQA1 polymorphisms and of previous immunosuppressive treatment. Therefore, assessing circulating anti-PLA2R autoantibodies and proteinuria may help in monitoring disease activity and guiding personalized rituximab therapy in nephrotic patients with primary MN., (Copyright © 2015 by the American Society of Nephrology.)

Objective: immigrant women are at increased risk for health problems during pregnancy, and for antenatal and postnatal depression. This study aimed to identify sociodemographic and specific psychosocial risk factors of antenatal depression and obstetric complications in an economically and culturally heterogeneous sample., Design: prospective cross-sectional design., Setting: the study was conducted in a midwifery office., Participants: the community sample included 228 immigrant pregnant women with low French proficiency referred to birth preparation classes between 2006 and 2014 in Geneva, Switzerland., Measurement: depressive symptoms were measured during the third trimester of pregnancy using the Edinburgh Postnatal Depression Scale. A cut-off score ≥12 was considered to be indicative of antenatal depression., Findings: more than half of the participants had been living in Switzerland for less than five years and had a short-term residence permit. Thirty-seven per cent of women scored above the clinical cut-off score. Women with several risk factors, such as a precarious legal status, lack of marital support, difficult living conditions and being a newcomer to Switzerland, were at higher risk of depression. Women who encountered difficult living conditions were at higher risk of obstetric complications., Implications for Practice: these results confirm the findings of previous research, and highlight the need for early detection. Public health prevention policies should consist of multidimensional programmes to address simultaneously psychosocial, cultural and obstetric issues in pregnant immigrant women., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Maternal interpersonal violence-related post-traumatic stress disorder (IPV-PTSD) is known to be associated with impairment of a mother's capacity to participate in mutual emotion regulation during her child's first years of life. This study tested the hypothesis that maternal difficulty in identifying feelings in self and other, as an important dimension of the construct of alexithymia, together with maternal IPV-PTSD, would be negatively associated with maternal sensitivity. Maternal sensitivity to child emotional communication is a marker of maternal capacity to engage in mutual regulation of emotion and arousal. Following diagnostic interviews and administration of the Toronto Alexithymia Scale, 56 mothers and their toddlers (ages 12-42 months) were filmed during free-play and separation/novelty-exposure. Observed maternal sensitivity was coded via the CARE-Index. Maternal IPV-PTSD severity, difficulty in identifying emotions, and lower socio-economic status were all associated with less maternal sensitivity, and also with more maternal controlling and unresponsive behavior on the CARE-Index.

Prior research has shown that mothers with Interpersonal violence-related posttraumatic stress disorder (IPV-PTSD) report greater difficulty in parenting their toddlers. Relative to their frequent early exposure to violence and maltreatment, these mothers display dysregulation of their hypothalamic pituitary adrenal axis (HPA-axis), characterized by hypocortisolism. Considering methylation of the promoter region of the glucocorticoid receptor gene NR3C1 as a marker for HPA-axis functioning, with less methylation likely being associated with less circulating cortisol, the present study tested the hypothesis that the degree of methylation of this gene would be negatively correlated with maternal IPV-PTSD severity and parenting stress, and positively correlated with medial prefrontal cortical (mPFC) activity in response to video-stimuli of stressful versus non-stressful mother-child interactions. Following a mental health assessment, 45 mothers and their children (ages 12-42 months) participated in a behavioral protocol involving free-play and laboratory stressors such as mother-child separation. Maternal DNA was extracted from saliva. Interactive behavior was rated on the CARE-Index. During subsequent fMRI scanning, mothers were shown films of free-play and separation drawn from this protocol. Maternal PTSD severity and parenting stress were negatively correlated with the mean percentage of methylation of NR3C1. Maternal mPFC activity in response to video-stimuli of mother-child separation versus play correlated positively to NR3C1 methylation, and negatively to maternal IPV-PTSD and parenting stress. Among interactive behavior variables, child cooperativeness in play was positively correlated with NR3C1 methylation. Thus, the present study is the first published report to our knowledge, suggesting convergence of behavioral, epigenetic, and neuroimaging data that form a psychobiological signature of parenting-risk in the context of early life stress and PTSD.

Post-traumatic stress disorder (PTSD) is a disorder that involves impaired regulation of the fear response to traumatic reminders. This study tested how women with male-perpetrated interpersonal violence-related PTSD (IPV-PTSD) differed in their brain activation from healthy controls (HC) when exposed to scenes of male-female interaction of differing emotional content. Sixteen women with symptoms of IPV-PTSD and 19 HC participated in this study. During magnetic resonance imaging, participants watched a stimulus protocol of 23 different 20 s silent epochs of male-female interactions taken from feature films, which were neutral, menacing or prosocial. IPV-PTSD participants compared with HC showed (i) greater dorsomedial prefrontal cortex (dmPFC) and dorsolateral prefrontal cortex (dlPFC) activation in response to menacing vs prosocial scenes and (ii) greater anterior cingulate cortex (ACC), right hippocampus activation and lower ventromedial prefrontal cortex (vmPFC) activty in response to emotional vs neutral scenes. The fact that IPV-PTSD participants compared with HC showed lower activity of the ventral ACC during emotionally charged scenes regardless of the valence of the scenes suggests that impaired social perception among IPV-PTSD patients transcends menacing contexts and generalizes to a wider variety of emotionally charged male-female interactions., (© The Author (2014). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.)

Background/objective: "By-the-way" syndrome, a new problem raised by the patient at an encounter's closure, is common, but little is known about how physicians respond when it occurs. We analyzed the content of the syndrome, predictors of its appearance, and the physician response., Design/participants: Cross-sectional study of 92 videotaped encounters in an academic primary care clinic., Results: The syndrome occurred in 39.1% of observed encounters. Its major content was bio-psychosocial (39%), psychosocial (36%), or biomedical (25%), whereas physician responses were mostly biomedical (44%). The physician response was concordant with the patient's question in 61% of encounters if the content of the question was psychosocial, 21% if bio-psychosocial, and 78% if biomedical; 32% of physicians solicited the patient's agenda two times or more in the group without, versus 11% in the group with, the syndrome (P = 0.02). In 22% of the encounters, physicians did not give any answer to the patient's question, particularly (38.5%) if it was of psychosocial content., Conclusions: "By-the-way" syndrome is mainly bio-psychosocial or psychosocial in content, whereas the physician response is usually biomedical. Asking about the patient's agenda twice or more during the office visit might decrease the appearance of this syndrome.