Children with maltreatment exposure exhibit rumination-like spontaneous thought patterns: association with symptoms of depression, subcallosal cingulate cortex thickness, and cortisol levels.

BACKGROUND: Childhood maltreatment is associated with pervasive risk for depression. However, the immediate cognitive and neural mechanisms that mediate this risk during development are unknown. We here studied the impact of maltreatment on self-generated thought (SGT) patterns and their association with depressive symptoms, subcallosal cingulate cortex (SCC) thickness, and cortisol levels in children. METHODS: We recruited 183 children aged 6-12 years, 96 of which were exposed to maltreatment. Children performed a mind wandering task to elicit SGTs. A subgroup of children underwent structural magnetic resonance imaging (N = 155) for SCC thickness analyses and saliva collection for quantification of free cortisol concentrations (N = 126) was collected. Using network analysis, we assessed thought networks and compared these networks between children with and without maltreatment exposure. Using multilevel analyses, we then tested the association between thought networks of children with maltreatment exposure with depressive symptoms, SCC thickness, and cortisol levels. RESULTS: Children exposed to maltreatment generated fewer positively valenced thoughts. Network analysis revealed rumination-like thought patterns in children with maltreatment exposure, which were associated with depressive symptoms, SCC thickness, and cortisol levels. Children with maltreatment exposure further exhibited decreased future-self thought coupling, which was associated with depressive symptoms, while other-related and past-oriented thoughts had the greatest importance within the network. CONCLUSIONS: Using a novel network analytic approach, we provide evidence that children exposed to maltreatment exhibit ruminative clustering of thoughts, which is associated with depressive symptoms and neurobiological correlates of depression. Our results provide a specific target for clinical translation to design early interventions for middle childhood. Targeting thought patterns in children with maltreatment exposure may be an effective strategy to effectively mitigate depression risk early in life.

The ReCoDe addiction research consortium: Losing and regaining control over drug intake-Findings and future perspectives.

Substance use disorders (SUDs) are seen as a continuum ranging from goal-directed and hedonic drug use to loss of control over drug intake with aversive consequences for mental and physical health and social functioning. The main goals of our interdisciplinary German collaborative research centre on Losing and Regaining Control over Drug Intake (ReCoDe) are (i) to study triggers (drug cues, stressors, drug priming) and modifying factors (age, gender, physical activity, cognitive functions, childhood adversity, social factors, such as loneliness and social contact/interaction) that longitudinally modulate the trajectories of losing and regaining control over drug consumption under real-life conditions. (ii) To study underlying behavioural, cognitive and neurobiological mechanisms of disease trajectories and drug-related behaviours and (iii) to provide non-invasive mechanism-based interventions. These goals are achieved by: (A) using innovative mHealth (mobile health) tools to longitudinally monitor the effects of triggers and modifying factors on drug consumption patterns in real life in a cohort of 900 patients with alcohol use disorder. This approach will be complemented by animal models of addiction with 24/7 automated behavioural monitoring across an entire disease trajectory; i.e. from a naïve state to a drug-taking state to an addiction or resilience-like state. (B) The identification and, if applicable, computational modelling of key molecular, neurobiological and psychological mechanisms (e.g., reduced cognitive flexibility) mediating the effects of such triggers and modifying factors on disease trajectories. (C) Developing and testing non-invasive interventions (e.g., Just-In-Time-Adaptive-Interventions (JITAIs), various non-invasive brain stimulations (NIBS), individualized physical activity) that specifically target the underlying mechanisms for regaining control over drug intake. Here, we will report on the most important results of the first funding period and outline our future research strategy.

[Emotional Abuse in Childhood and Adolescence: Biological Embedding and Clinical Implications]. / Emotionaler Missbrauch in Kindheit und Jugend ­ Biologische Einbettung und klinische Implikationen.

Emotional abuse, defined as degrading, manipulative, or neglectful behaviors by caregivers, represents a common adverse experience for children and adolescents, often co-occurring with other maltreatment types. Exposure to emotional abuse significantly affects mental health across the lifespan and is particularly associated with elevated depression risk.This review examinesmechanisms, by which emotional abuse influences brain development and the neuroendocrine stress response system and discusses the roles of genetic vulnerability and epigenetic processes in contributing to an elevated mental health risk. Emotional abuse has similar effects on brain networks responsible for emotion processing and regulation as other maltreatment types.Moreover, it uniquely affects networks related to self-relevant information and socio-cognitive processes. Furthermore, emotional abuse is associated with an impaired recovery of the neuroendocrine response to acute stress. Similar to other maltreatment types, emotional abuse is associated with epigenetic changes in genes regulating the neuroendocrine stress response system that are implicated in increased mental health risk.These findings suggest that emotional abuse has equally detrimental effects on children'smental health as physical or sexual abuse, warranting broader societal awareness and enhanced early detection efforts. Early interventions should prioritize emotion regulation, social cognition, self-esteemenhancement, and relationship- oriented approaches for victims of emotional abuse.

Sensory-Tactile Functional Mapping and Use-Associated Structural Variation of the Human Female Genital Representation Field.

The precise location of the human female genital representation field in the primary somatosensory cortex (S1) is controversial and its capacity for use-associated structural variation as a function of sexual behavior remains unknown. We used a functional magnetic resonance imaging (fMRI)-compatible sensory-tactile stimulation paradigm to functionally map the location of the female genital representation field in 20 adult women. Neural response to tactile stimulation of the clitoral region (vs right hand) identified individually-diverse focal bilateral activations in dorsolateral areas of S1 (BA1-BA3) in alignment with anatomic location. We next used cortical surface analyses to assess structural thickness across the 10 individually most activated vertices per hemisphere for each woman. We show that frequency of sexual intercourse within 12 months is correlated with structural thickness of the individually-mapped left genital field. Our results provide a precise functional localization of the female genital field and provide support for use-associated structural variation of the human genital cortex.SIGNIFICANCE STATEMENT We provide a precise location of the human female genital field in the somatosensory cortex and, for the first time, provide evidence in support of structural variation of the human genital field in association with frequency of genital contact. Our study represents a significant methodological advance by individually mapping genital fields for structural analyses. On a secondary level, our results suggest that any study investigating changes in the human genital field must map the field individually to achieve sufficient precision. Our results pave the way for future research into the plasticity of the human genital cortex as a function of normal or adverse experience as well as changes in pathologic conditions, i.e., sexual dysfunction, sexual deviation, or sexual risk-taking behavior.

The association between history of prenatal loss and maternal psychological state in a subsequent pregnancy: an ecological momentary assessment (EMA) study.

BACKGROUND: Prenatal loss which occurs in approximately 20% of pregnancies represents a well-established risk factor for anxiety and affective disorders. In the current study, we examined whether a history of prenatal loss is associated with a subsequent pregnancy with maternal psychological state using ecological momentary assessment (EMA)-based measures of pregnancy-specific distress and mood in everyday life. METHOD: This study was conducted in a cohort of N = 155 healthy pregnant women, of which N = 40 had a history of prenatal loss. An EMA protocol was used in early and late pregnancy to collect repeated measures of maternal stress and mood, on average eight times per day over a consecutive 4-day period. The association between a history of prenatal loss and psychological state was estimated using linear mixed models. RESULTS: Compared to women who had not experienced a prior prenatal loss, women with a history of prenatal loss reported higher levels of pregnancy-specific distress in early as well as late pregnancy and also were more nervous and tired. Furthermore, in the comparison group pregnancy-specific distress decreased and mood improved from early to late pregnancy, whereas these changes across pregnancy were not evident in women in the prenatal loss group. CONCLUSION: Our findings suggest that prenatal loss in a prior pregnancy is associated with a subsequent pregnancy with significantly higher stress and impaired mood levels in everyday life across gestation. These findings have important implications for designing EMA-based ambulatory, personalized interventions to reduce stress during pregnancy in this high-risk group.

Relationship between Borderline Personality Disorder, Emotional Availability, and Cortisol Output in Mother-Child Dyads.

BACKGROUND: Mothers with borderline personality disorder (BPD) often show altered emotional availability toward their own child and heightened stress vulnerability. The aims of the present study were (1) to examine total cortisol output in saliva during mother-child interaction in mothers with BPD and their children and (2) to test whether maternal nonhostility as a subscale of emotional availability mediates the relationship between maternal BPD and child total cortisol output. METHODS: We investigated 16 mothers with BPD and 30 healthy control mothers (HC) and 29 children of mothers with BPD and 33 children of HC mothers. Children were between 5 and 12 years old. Salivary cortisol was collected prior to and twice after an episode of a 21-min standardized play situation between mother and child. Nonhostility was rated using the emotional availability scales. Analyses of covariance were computed to test for group differences in total cortisol output (measured with area under the curve with respect to ground). Pearson's correlation was calculated to test the association between maternal and child total cortisol output. To test the second question, a mediation analysis according to Preacher and Hayes was conducted. RESULTS: Mothers with BPD and their children had lower total cortisol output. Maternal and child total cortisol output was significantly correlated. Contrary to our hypothesis, maternal nonhostility did not mediate the relationship between BPD and child total cortisol output. CONCLUSION: Results imply that the hormonal stress activity of mothers with BPD and their children is altered, which may reflect modified stress regulation and stress vulnerability in mother and child and may impact on mother-child interaction. The finding of a positive association between mother's and child total cortisol output could indicate an intergenerational transmission of these alterations.

Exposure to childhood maltreatment and systemic inflammation across pregnancy: The moderating role of depressive symptomatology.

BACKGROUND: Childhood maltreatment (CM) has long-term consequences for dysregulation of the immune system which is particularly pronounced when mental and physical health sequelae have manifested. Higher proinflammatory state has been shown in non-pregnant state in association with CM as well as with depression, one of the most frequent and pernicious psychiatric sequelae of CM. During pregnancy, however, this association is less clear. Given the important role of maternal inflammatory state during pregnancy for fetal, pregnancy, and birth outcomes, we sought to examine the association between CM and proinflammatory state during pregnancy considering the moderating role of maternal depressive symptoms characterized serially across pregnancy. METHODS: A prospective, longitudinal study of 180 healthy pregnant women was conducted with serial assessments in early (12.98 ± 1.71 weeks gestation), mid (20.53 ± 1.38 weeks gestation) and late (30.42 ± 1.4 weeks gestation) pregnancy. Maternal history of CM was assessed with the Childhood Trauma Questionnaire (CTQ) and the total score was used as an indicator of CM experience. Maternal depressive symptoms were assessed at each pregnancy visit with the Center for Epidemiologic Studies Depression Scale (CES-D). Serum concentrations of tumor necrosis factor (TNF)-α and interleukin (IL)-6 were obtained at each pregnancy visit and combined to a composite maternal proinflammatory score. Linear mixed effects models were employed to assess the association between CTQ score, CES-D score, and proinflammatory score during pregnancy, adjusting for potential confounders. RESULTS: Gestational age was associated with the proinflammatory score (B = 0.02; SE = 0.00; p < .001), indicating an increase in inflammation across gestation. Neither CTQ score nor depressive symptoms were independently associated with the proinflammatory score (ps > 0.28). However, the interaction between CTQ score and depressive symptoms was associated with the proinflammatory score (B = 0.03, SE = 0.01, p < .05), indicating higher inflammation across pregnancy with increasing levels of depressive symptoms during pregnancy in women with higher CTQ scores. Exploratory analyses suggested that this interaction was mainly driven by CTQ subscale scores assessing experiences of abuse rather than neglect. CONCLUSIONS: These findings suggest a moderating role of maternal depressive symptoms during pregnancy on the association of early life stress with inflammation and thus highlight the importance of the timely assessment of both CM exposure and depressive symptoms which might allow for the development of targeted and individualized interventions to impact inflammation during pregnancy and to ameliorate the detrimental long-term effects of CM. The current findings add to a better understanding of the prenatal biological pathways that may underlie intergenerational transmission of maternal CM.

Immediate impact of child maltreatment on mental, developmental, and physical health trajectories.

OBJECTIVE: The immediate impact of child maltreatment on health and developmental trajectories over time is unknown. Longitudinal studies starting in the direct aftermath of exposure with repeated follow-up are needed. METHOD: We assessed health and developmental outcomes in 6-month intervals over 2 years in 173 children, aged 3-5 years at study entry, including 86 children with exposure to emotional and physical abuse or neglect within 6 months and 87 nonmaltreated children. Assessments included clinician-administered, self- and parent-report measures of psychiatric and behavioral symptoms, development, and physical health. Linear mixed models and latent growth curve analyses were used to contrast trajectories between groups and to investigate the impact of maltreatment features on trajectories. RESULTS: Maltreated children exhibited greater numbers of psychiatric diagnoses (b = 1.998, p < .001), externalizing (b = 13.29, p < .001) and internalizing (b = 11.70, p < .001) symptoms, impairments in cognitive (b = -11.586, p < .001), verbal (b = -10.687, p < .001), and motor development (b = -7.904, p = .006), and greater numbers of medical symptoms (b = 1.021, p < .001) compared to nonmaltreated children across all time-points. Lifetime maltreatment severity and/or age at earliest maltreatment exposure predicted adverse outcomes over time. CONCLUSION: The profound, immediate, and stable impact of maltreatment on health and developmental trajectories supports a biological embedding model and provides foundation to scrutinize the precise underlying mechanisms. Such knowledge will enable the development of early risk markers and mechanism-driven interventions that mitigate adverse trajectories in maltreated children.

Elevated inflammatory markers in women with remitted major depressive disorder and the role of early life maltreatment.

Major depressive disorder (MDD) has been linked to elevated inflammation markers. It remains unclear whether the elevation of C-reactive protein (CRP) and interleukin-6 (IL-6) levels are not only observable in acute MDD but also in patients after remission. MDD is a common sequela of early life maltreatment (ELM), which has also been associated with elevated inflammation markers. While the majority of studies investigated (acute) MDD and ELM as isolated predictors of inflammation, a few studies found inflammation levels to be more pronounced in patients with MDD that were exposed to ELM. This investigation included both ELM and MDD in one study and aimed at distinguishing between the effects of MDD in remission (rMDD) and ELM and investigating potential accumulative effects on the inflammatory markers CRP and IL-6 in a population of N = 126 women (n = 122 for CRP and n = 66 for IL-6). We further investigated how disorder characteristics (course and severity) and specific types of ELM affect levels of CRP and IL-6. We found that rMDD predicted levels of CRP and IL-6 and physical abuse predicted levels of CRP when considering both predictors simultaneously, while other types of ELM did not. A later onset of MDD and a shorter time interval since the last episode were associated with higher levels of IL-6. Our findings contribute to the existing literature on the association between MDD and inflammation, suggesting that elevated levels of inflammation markers may persist even after remission of MDD. Our findings on physical abuse as a specific predictor of CRP in the presence of rMDD suggest that different types of ELM could result in distinct inflammation profiles.

Assembling a cohort for in-depth, longitudinal assessments of the biological embedding of child maltreatment: Methods, complexities, and lessons learned.

As championed by the work of Ed Zigler, investing in nurturing environments for all children is a chief tenet of primary prevention that will have far-reaching benefits to the health and welfare of all members of society. Children who endure child maltreatment (CM) are among society's most vulnerable. Prospective longitudinal research aimed at a comprehensive understanding of the mechanisms linking CM to subsequent adverse health consequences is needed to improve outcomes and to strengthen causal inference. This paper outlines the methods of the Child Health Study (CHS), a large, state-wide longitudinal cohort of recently maltreated and nonmaltreated youth aged 8-13 who will be assessed every 2 years. The CHS is designed to include in-depth assessments of multiple environmental, behavioral, neural, physiological, and molecular mechanisms through which CM may impact a broad spectrum of youth development, including behavioral and physical health outcomes. In addition to describing the conceptual framework and methods underlying the CHS, we provide information on valuable "lessons learned" in the hopes of supporting future research efforts facing similar challenges. The ultimate goal of this research is demonstrating how policies regarding CM impact the well-being, resilience and recovery of survivors and that they are worthy of large public investment.

Alterations of empathy in mothers with a history of early life maltreatment, depression, and borderline personality disorder and their effects on child psychopathology.

BACKGROUND: Early life maltreatment (ELM), borderline personality disorder (BPD), and major depressive disorder (MDD) have been associated with empathy deficits in different domains. Lack of maternal empathy has also been related to child behavioral problems. As ELM, BPD, and MDD often co-occur, we aimed to identify dissociable effects on empathy due to these three factors. In addition, we aimed to investigate their indirect effects via empathy on child psychopathology. METHODS: We included 251 mothers with and without MDD (in remission), BPD and ELM and their children, aged 5-12. We used the Interpersonal Reactivity Index as a measure of empathy on four different dimensions (personal distress, empathic concern, perspective taking, and fantasy) and the Child Behavior Checklist as a measure of child psychopathology. RESULTS: Having included all three factors (ELM, MDD, BPD) in one analysis, we found elevated personal distress in MDD and BPD, and lower levels of perspective-taking in BPD, but no effects from ELM on any empathy subscales. Furthermore, we found indirect effects from maternal BPD and MDD on child psychopathology, via maternal personal distress. CONCLUSION: The present study demonstrated the dissociable effects of maternal ELM, MDD, and BPD on empathy. Elevated personal distress in mothers with BPD and MDD may lead to higher levels of child psychopathology.

Immediate and longitudinal effects of maltreatment on systemic inflammation in young children.

Exposure to child maltreatment increases the risk for psychiatric and physical diseases. Inflammation has been proposed as a mechanism through which early adverse experiences become biologically embedded. However, most studies providing evidence for the link between early adverse exposures and inflammation have been retrospective or cross-sectional in design, or did not assess inflammation immediately after maltreatment in young children. In the present study we investigated the association between childhood maltreatment and salivary C-reactive protein (CRP) concentrations in a population of N = 173 children, 3-5 years of age, who were recruited in the immediate aftermath of maltreatment and followed-up longitudinally every 6 months over a period of 2 years. We found that the association between maltreatment and CRP concentrations was significantly moderated by child sex, such that in girls, CRP concentrations were higher in the maltreated compared to the control group, and this difference was stable across the 2-year follow-up-period, while in boys, there was no association between maltreatment and CRP. Our findings suggest that the effect of maltreatment on inflammation may already emerge right after exposure at a very young age in girls and manifest over time. Our study provides important evidence for the development of personalized, early interventions strategies targeting the early-life period.

Addiction Research Consortium: Losing and regaining control over drug intake (ReCoDe)-From trajectories to mechanisms and interventions.

One of the major risk factors for global death and disability is alcohol, tobacco, and illicit drug use. While there is increasing knowledge with respect to individual factors promoting the initiation and maintenance of substance use disorders (SUDs), disease trajectories involved in losing and regaining control over drug intake (ReCoDe) are still not well described. Our newly formed German Collaborative Research Centre (CRC) on ReCoDe has an interdisciplinary approach funded by the German Research Foundation (DFG) with a 12-year perspective. The main goals of our research consortium are (i) to identify triggers and modifying factors that longitudinally modulate the trajectories of losing and regaining control over drug consumption in real life, (ii) to study underlying behavioral, cognitive, and neurobiological mechanisms, and (iii) to implicate mechanism-based interventions. These goals will be achieved by: (i) using mobile health (m-health) tools to longitudinally monitor the effects of triggers (drug cues, stressors, and priming doses) and modify factors (eg, age, gender, physical activity, and cognitive control) on drug consumption patterns in real-life conditions and in animal models of addiction; (ii) the identification and computational modeling of key mechanisms mediating the effects of such triggers and modifying factors on goal-directed, habitual, and compulsive aspects of behavior from human studies and animal models; and (iii) developing and testing interventions that specifically target the underlying mechanisms for regaining control over drug intake.

Effects of stress on 6- and 7-year-old children's emotional memory differs by gender.

Understanding effects of emotional valence and stress on children's memory is important for educational and legal contexts. This study disentangled the effects of emotional content of to-be-remembered information (i.e., items differing in emotional valence and arousal), stress exposure, and associated cortisol secretion on children's memory. We also examined whether girls' memory is more affected by stress induction. A total of 143 6- and 7-year-old children were randomly allocated to the Trier Social Stress Test for Children (n = 103) or a control condition (n = 40). At 25 min after stressor onset, children incidentally encoded 75 objects varying in emotional valence (crossed with arousal) together with neutral scene backgrounds. We found that response bias corrected memory was worse for low-arousing negative items than for neutral and positive items, with the latter two categories not being different from each other. Whereas boys' memory was largely unaffected by stress, girls in the stress condition showed worse memory for negative items, especially the low-arousing ones, than girls in the control condition. Girls, compared with boys, reported higher subjective stress increases following stress exposure and had higher cortisol stress responses. Whereas a higher cortisol stress response was associated with better emotional memory in girls in the stress condition, boys' memory was not associated with their cortisol secretion. Taken together, our study suggests that 6- and 7-year-old children, more so girls, show memory suppression for negative information. Girls' memory for negative information, compared with that of boys, is also more strongly modulated by stress experience and the associated cortisol response.

[Oxytocin and maltreatment potential : Influence of maternal depression, borderline personality disorder and experience of early childhood maltreatment]. / Oxytocin und Misshandlungspotenzial : Einfluss von mütterlicher Depression, Borderline-Persönlichkeitsstörung und frühkindlicher Misshandlungserfahrung.

BACKGROUND: The "empathy hormone" oxytocin (OXT) is associated with social interaction and parent-child interaction. Mothers with mental stress factors, e.g., history of depression, borderline personality disorder or early life maltreatment in their own childhood often show distinct maternal behavior. The objectives of the study were (1) to examine the association between these three stress factors and maternal OXT within one analysis. (2) Moreover, OXT was tested as a potential mediator for the association between maternal experience of early childhood maltreatment and abuse potential against their own child. METHODS: Plasma OXT concentrations of 52 mothers during the follicular phase were collated (healthy control mothers n = 22, history of depression n = 23, borderline personality disorder n = 7). The maternal history of psychiatric disorders and experiences of early childhood maltreatment were examined via interviews. Regression and mediation analyses were applied to answer the research questions. RESULTS: Early childhood maltreatment was associated with reduced plasma OXT; however, maternal history of depression and borderline personality disorder were not related to OXT concentrations. In particular, having experienced parental antipathy in one's own childhood was associated with reduced OXT levels but OXT did not mediate the association between maternal early childhood experiences of maltreatment and abuse potential of their own child. CONCLUSION: In the present study alterations in plasma OXT concentrations were not associated with psychiatric disorders, such as a history of depression or borderline personality disorder but more with a potential etiological factor of these disorders, i.e. experience of maltreatment in their own childhood.

Child abuse potential in mothers with early life maltreatment, borderline personality disorder and depression.

BACKGROUND: Early life maltreatment (ELM), borderline personality disorder (BPD) and major depressive disorder (MDD) have been shown to increase the potential of abuse. Emotion regulation is an identified mediator for the association of ELM and BPD with abuse potential. Until now, there has been no study to account for the co-occurrence of these risk factors in one analysis, although BPD and MDD are known as common sequelae of ELM. This is paired with a lack of studies investigating the effects of abuse potential on child well-being.AimsOur study aims at (a) disentangling the effects of maternal ELM, MDD and BPD on abuse potential; (b) exploring the role of emotion regulation as a mediator; and (c) testing for intergenerational effects of abuse potential on child psychopathology. METHOD: The research design included 114 mothers with/without ELM, BPD and MDD in remission and their children, all of which were between 5 and 12 years of age. A path analysis was conducted to investigate the multiple associations between our variables. RESULTS: ELM, MDD and BPD were all associated with abuse potential, with emotion regulation acting as a mediator for BPD and MDD. Furthermore, an elevated abuse potential was related to higher psychopathology in the child. CONCLUSIONS: History of ELM as well as the common sequelae, BPD and MDD, pose risks for child abuse. Our findings suggest improvement of emotion regulation as a potential target for intervention programs. These programs should also aim at non-substantiated cases because even an elevated abuse potential affected child mental health.Declaration of interestNone.

Effects of Antenatal Maternal Depressive Symptoms and Socio-Economic Status on Neonatal Brain Development are Modulated by Genetic Risk.

This study included 168 and 85 mother-infant dyads from Asian and United States of America cohorts to examine whether a genomic profile risk score for major depressive disorder (GPRSMDD) moderates the association between antenatal maternal depressive symptoms (or socio-economic status, SES) and fetal neurodevelopment, and to identify candidate biological processes underlying such association. Both cohorts showed a significant interaction between antenatal maternal depressive symptoms and infant GPRSMDD on the right amygdala volume. The Asian cohort also showed such interaction on the right hippocampal volume and shape, thickness of the orbitofrontal and ventromedial prefrontal cortex. Likewise, a significant interaction between SES and infant GPRSMDD was on the right amygdala and hippocampal volumes and shapes. After controlling for each other, the interaction effect of antenatal maternal depressive symptoms and GPRSMDD was mainly shown on the right amygdala, while the interaction effect of SES and GPRSMDD was mainly shown on the right hippocampus. Bioinformatic analyses suggested neurotransmitter/neurotrophic signaling, SNAp REceptor complex, and glutamate receptor activity as common biological processes underlying the influence of antenatal maternal depressive symptoms on fetal cortico-limbic development. These findings suggest gene-environment interdependence in the fetal development of brain regions implicated in cognitive-emotional function. Candidate biological mechanisms involve a range of brain region-specific signaling pathways that converge on common processes of synaptic development.

[Early-life stress and vulnerability for disease in later life]. / Frühe Stresserfahrungen und Krankheitsvulnerabilität.

BACKGROUND: The rapidly growing research field of developmental programming of health and disease risk investigates the early life origins of individual vulnerability for common, complex disorders that confer a major burden of disease. OBJECTIVES: The present article introduces the concept of developmental programming of disease vulnerability and summarizes studies on the mental and physical health consequences of exposure to childhood trauma and prenatal stress. Biological mechanisms that mediate disease risk after early life stress are discussed. The possibility of transgenerational transmission of effects of childhood trauma in exposed women to their children and potential mechanisms of this transmission are also presented. CONCLUSION: A substantial number of studies show associations between early life stress and risk for mental and somatic diseases in later life. The underlying mechanisms are currently being studied at the molecular and epigenetic level. Potentially, these findings will allow unprecedented opportunities to improve the precision of current clinical diagnostic tools and the success of interventions. However, there is currently a lack of translation of research findings related to developmental programming to clinical applications.

Cardiovascular risk factor distribution and subjective risk estimation in urban women--the BEFRI study: a randomized cross-sectional study.

BACKGROUND: Awareness represents a major modulator for the uptake of preventive measures and healthy life-style choices. Women underestimate the role of cardiovascular diseases as causes of mortality, yet little information is available about their subjective risk awareness. METHODS: The Berlin Female Risk Evaluation (BEFRI) study included a randomized urban female sample aged 25-74 years, in which 1,066 women completed standardized questionnaires and attended an extensive clinical examination. Subjective estimation was measured by a 3-point Likert scale question asking about subjective perception of absolute cardiovascular risk with a 10 year outlook to be matched to the cardiovascular risk estimate according to the Framingham score for women. RESULTS: An expected linear increase with age was observed for hypertension, hyperlipidemia, obesity, and vascular compliance measured by pulse pressure. Knowledge about optimal values of selected cardiovascular risk factor indicators increased with age, but not the perception of the importance of age itself. Only 41.35% of all the participants correctly classified their own cardiovascular risk, while 48.65% underestimated it, and age resulted as the most significant predictor for this subjective underestimation (OR = 3.5 for age >50 years compared to <50, 95% CI = 2.6-4.8, P <0.0001). Therefore, although socioeconomic factors such as joblessness (OR = 1.9, 95% CI = 1.4-2.6, P <0.0001) and combinations of other social risk factors (low income, limited education, simple job, living alone, having children, statutory health coverage only; OR = 1.5, 95% CI = 1.1-2.1, P = 0.009) also significantly influenced self-awareness, age appeared as the strongest predictor of risk underestimation and at the same time the least perceived cardiovascular risk factor. CONCLUSIONS: Less than half of the women in our study population correctly estimated their cardiovascular risk. The study identifies age as the strongest predictor of risk underestimation in urban women and at the same time as the least subjectively perceived cardiovascular risk factor. Although age itself cannot be modified, our data highlights the need for more explicit risk counseling and information campaigns about the cardiovascular relevance of aging while focusing on measures to control coexisting modifiable risk factors.

Effects of stress throughout the lifespan on the brain, behaviour and cognition.

Chronic exposure to stress hormones, whether it occurs during the prenatal period, infancy, childhood, adolescence, adulthood or aging, has an impact on brain structures involved in cognition and mental health. However, the specific effects on the brain, behaviour and cognition emerge as a function of the timing and the duration of the exposure, and some also depend on the interaction between gene effects and previous exposure to environmental adversity. Advances in animal and human studies have made it possible to synthesize these findings, and in this Review a model is developed to explain why different disorders emerge in individuals exposed to stress at different times in their lives.