Long-term consequences of childhood emotional abuse in mothers on parental load and child mental health.

BACKGROUND: Childhood emotional maltreatment can be associated with long-term consequences on mental health. In addition, transgenerational transmission of adverse childhood experiences to the next generation can occur and thus have an impact on the mental health of one's own children. OBJECTIVE: The purpose of this study was to examine the role of stress on the association between childhood emotional maltreatment and parental load what is referred to in this study as limitations in parental functioning that affect the resources available to parents to cope with the demands of raising, caring for, and providing for their child. Furthermore the effect of parental load on the mental health of one's own children will be examined. PARTICIPANTS AND SETTING: N = 237 mother-child dyads (age mother M = 33.76, SD = 4.07 years; age child M = 11.91 months, SD = 0.89 months) from a longitudinal cohort study were examined at two different measuring points. METHODS: Emotional abuse, perceived stress, parental load and child mental health were assessed using self and external report questionnaires. RESULTS: The calculation of a mediation showed that the association of emotional abuse and parental load was completely mediated by perceived stress (indirect effect ab = 0.44, 95 %-CI[0.17, 0.78]). In addition, effects of parental load on the child's mental health (ß = 0.13, 95%CI [0.07;0.20]), mainly hyperactivity (ß = 0.06, 95%CI [0.03;0.11]) and prosocial behavior (ß = -0.04, 95%CI [-0.07; -0.01]), were evident. CONCLUSIONS: The results of this study provide evidence that the mental health of children can be influenced in the long term by increased parental load.

Maternal insecure attachment representation as a long-term risk factor for disrupted mother-child-interaction and child mental health.

Maternal childhood maltreatment (CM) represents an important factor in the transmission of trauma that may lead to impaired child mental health. Apart from childhood maltreatment insecure attachment has been identified as a risk factor for insensitive caregiving behavior, which may affect child's mental health. The aim of this study is to identify the working mechanisms in the relationship between maternal CM and child mental health, considering maternal attachment representation, mother-child-interaction und maternal helplessness and fear. N = 103 mother-child-dyads from a longitudinal cohort study were examined at four different measuring points. Data was assessed using self and external report questionnaires as well as the AMBIANCE scales during the Strange Situation Procedure and the Adult Attachment Projective Picture System (AAP). Maternal CM experience did not predict an insecure attachment representation (OR = 2.46 [0.98, 6.53], p = .060). Maternal insecure attachment was associated with higher AMBIANCE scores (F(8, 94) = 11.46, p < .001), which indicates more disrupted communication between mother and child. AMBIANCE scores in turn predicted higher self-perceived helplessness (F(9, 93) = 8.62, p < .001) and fear (F(9, 93) = 7.40, p < .001) in mothers. Helplessness and fear both were associated with higher SDQ-scores, indicating more mental health problems in children (F(10, 92) = 3.98, p < .001; F(10, 92) = 3.87, p < .001). The results of this study highlight how even insecure attachment in a low-risk sample has a long-term impact on parenting behavior and child mental health, therefore underlining the need of early intervention programs in affected and at-risk families.

Emotional problems in young children during the SARS-CoV-2-pandemic and child attachment.

Background: Restrictions imposed by national governments during SARS-CoV-2-pandemic have impacted the mental health of children around the world. Studies have already proven the importance of secure attachment acting as a protective factor in child development. Therefore, children with secure attachment have a higher chance of developing and using appropriate coping mechanisms. Objective: The goal of this study was to explore the possible connection between the pandemic, as well as child attachment, and young children's emotional health. The general hypothesis assumes a lower rate of emotional problems among children with secure attachment and a higher rate of emotional problems among children with insecure-disorganized attachment, as well as an increase of these problems during the pandemic. Method: The analysis included N = 129 mothers (M = 39.98 years) and their children (M = 5.19 years). Via an online survey, which was held at different time points during the pandemic, information on the children's emotional problems was retrieved. The survey used the Strengths and Difficulties Questionnaire (SDQ). Data regarding the quality of attachment was collected via the Strange Situations Test (SST). At this point the participating children were approximately 12 months old. Results: The calculation of a mixed ANCOVA showed, that attachment quality had a significant influence on children's emotional problems [F(2, 121) = 4.01, p = .021]. The interaction effect between time and child attachment reached significance [F(3.45, 208.42) = 3.58, p = .011]. The calculation of an additional mixed ANCOVA showed, that the reported emotional problems of girls were higher than those of boys F(1, 118) = 4.56, p = .035). Conclusions: Our study shows that there is an association between attachment security and emotional problems and the impact of the SARS-CoV-2 pandemic on the mental health of preschool children in Germany. The emotional problems of all children increased, especially the disorganized attached children had been reported as emotionally stressed in the first lockdown. The results indicate the need for preventive services (for children and parents) to promote and maintain stress coping skills in order to maintain children's mental health in times of crisis.

SARS-CoV-2 pandemic as a catalyst? Development of emotional problems of preschool children of mothers with childhood maltreatment experiences in the course of the pandemic-a longitudinal analysis.

Background: SARS-CoV-2 pandemic have posed great challenges for all families and children. Health risks and fears associated with SARS-CoV-2 negatively affect the parental mental health and perceived stress, which in turn influence parental coping and thereby impairs the mental health and well-being of their children. Additional risk factors within the parents, such as maternal childhood maltreatment (CM) experiences, may increase the risk of children to develop emotional problems during the pandemic. Objective: The purpose of this longitudinal study is to determine whether preschool children of mothers with CM are at higher risk of developing emotional problems during the pandemic than preschool children of mothers without CM. Method: 74 mothers from a birth cohort examining pathways to resilience or vulnerability in the transgenerational transmission of CM, provided information on emotional problems of their children (aged 3-7 years) at two measurement time points (t1: May 2020, t2: March 2021) as part of an online "SARS-CoV-2 pandemic" survey. In addition, parents were asked for a retrospective assessment of their children's emotional problems before the pandemic at time t1. Children's emotional problems were assessed using the "emotional problems" scale of the German version of the Strengths and Difficulties Questionnaire (SDQ) and linked to previously collected data on mothers' childhood maltreatment experiences, which were collected using the German short version of the Trauma in Childhood Questionnaire (CTQ). Results: Our analyses showed that children's emotional problems increased significantly over the SARS-CoV-2 pandemic [F(1.86, 116.88) = 3.72, p = 0.030 η 2 = 0.06] and were rated significantly higher in the group of children of mothers with CM, than in the group of mothers without CM [F(1, 63) = 126.06, p < 0.001 η 2 = 0.67]. Furthermore children's emotional problems of mothers with CM increased significantly more and reached a clinically significant value during the pandemic than for children of mothers without CM [F(1.86, 116.88) = 8.89, p < 0.001, η 2 = 0.12]. Conclusions: Children of mothers with CM appear to be at increased risk of developing emotional problems during the pandemic. CM therefore needs to be considered as an additional risk factor in the impact of the pandemic on children.

Atypical maternal interaction is associated with elevated levels of hair cortisol in children.

The quality of maternal caregiving is an important factor in the healthy development of a child. One consequence of prolonged insensitive and atypical maternal interaction behavior (e.g., withdrawing from interactions with the child and role-reversal, i.e., the takeover of the parental role or parts of it by the child) in mother-child-dyads can cause alteration of the child's stress response system. Higher salivary cortisol concentrations were reported in infants and toddlers directly after negative interactions with their parents. However, no study to date has examined the association between atypical maternal interaction behavior and hair cortisol concentrations (HCC) in infants. Here, we studied the association of maternal interaction behavior with HCC of the child. Mother-child dyads (N = 112) participated in the longitudinal study My Childhood-Your Childhood. The AMBIANCE scale and its subscales were used to assess atypical maternal interaction behavior during the Strange Situation Procedure. Chronic stress levels in the child were assessed by HCC of 3 cm hair strands at the age of 12 months. Maternal educational level (operationalized in highest education level) served as a control variable. Robust multiple linear regression analyses revealed that role/boundary confusion was associated with HCC, i.e., the higher atypical interaction behavior of the mother the higher the HCC in the children. By measuring hair cortisol in this study, it is possible to determine the average long-term activity of the child's stress response system.Thus, atypical maternal interaction behavior could be a risk factor for persistent stress in children, contributing to a higher risk for negative health outcomes in later life. The results of this study highlight the importance of early intervention programs that focus on the relationship between mother and child.

Truncation of titin's elastic PEVK region leads to cardiomyopathy with diastolic dysfunction.

RATIONALE: The giant protein titin plays key roles in myofilament assembly and determines the passive mechanical properties of the sarcomere. The cardiac titin molecule has 2 mayor elastic elements, the N2B and the PEVK region. Both have been suggested to determine the elastic properties of the heart with loss of function data only available for the N2B region. OBJECTIVE: The purpose of this study was to investigate the contribution of titin's proline-glutamate-valine-lysine (PEVK) region to biomechanics and growth of the heart. METHODS AND RESULTS: We removed a portion of the PEVK segment (exons 219 to 225; 282 aa) that corresponds to the PEVK element of N2B titin, the main cardiac titin isoform. Adult homozygous PEVK knockout (KO) mice developed diastolic dysfunction, as determined by pressure-volume loops, echocardiography, isolated heart experiments, and muscle mechanics. Immunoelectron microscopy revealed increased strain of the N2B element, a spring region retained in the PEVK-KO. Interestingly, the PEVK-KO mice had hypertrophied hearts with an induction of the hypertrophy and fetal gene response that includes upregulation of FHL proteins. This contrasts the cardiac atrophy phenotype with decreased FHL2 levels that result from the deletion of the N2B element. CONCLUSIONS: Titin's PEVK region contributes to the elastic properties of the cardiac ventricle. Our findings are consistent with a model in which strain of the N2B spring element and expression of FHL proteins trigger cardiac hypertrophy. These novel findings provide a molecular basis for the future differential therapy of isolated diastolic dysfunction versus more complex cardiomyopathies.

Detoxification of promutagenic aldehydes derived from methylpyrenes by human aldehyde dehydrogenases ALDH2 and ALDH3A1.

Methylated polycyclic aromatic hydrocarbons can be metabolically activated via benzylic hydroxylation and sulpho conjugation to reactive esters, which can induce mutations and tumours. Yet, further oxidation of the alcohol may compete with this toxification. We previously demonstrated that several human alcohol dehydrogenases (ADH1C, 2, 3 and 4) oxidise various benzylic alcohols (derived from alkylated pyrenes) to their aldehydes with high catalytic efficiency. However, all these ADHs also catalysed the reverse reaction, the reduction of the aldehydes to the alcohols, with comparable or higher efficiency. Thus, final detoxification requires elimination of the aldehydes by further biotransformation. We have expressed two human aldehyde dehydrogenases (ALDH2 and 3A1) in bacteria. All pyrene aldehydes studied (1-, 2- and 4-formylpyrene, 1-formyl-6-methylpyrene and 1-formyl-8-methylpyrene) were high-affinity substrates for ALDH2 (K(m)=0.027-0.9 microM) as well as ALDH3A1 (K(m)=0.78-11 microM). Catalytic efficiencies (k(cat)/K(m)) were higher for ALDH2 than ALDH3A1 by a moderate to a very large margin depending on the substrate. Most important, they were also substantially higher than the catalytic efficiencies of the various ADHs for the reduction the aldehydes to the alcohols. These kinetic properties ensure that ALDHs, and particularly ALDH2, can complete the ADH-mediated detoxification.

Effect of pentachlorophenol and 2,6-dichloro-4-nitrophenol on the activity of cDNA-expressed human alcohol and aldehyde dehydrogenases.

Pentachlorophenol (PCP) and 2,6-dichloro-4-nitrophenol (DCNP), potent inhibitors of phenol sulphotransferases, are frequently used in animal studies to elucidate the role of these enzymes in the biotransformation and toxicity of xenobiotics. An unexpected finding with 1-hydroxymethylpyrene--a strong decrease in the excretion of the corresponding carboxylic acid in rats concurrently treated with PCP-led us to suspect that this sulphotransferase inhibitor may also affect alcohol dehydrogenases (ADHs) and/or aldehyde dehydrogenases (ALDHs). Subsequently we investigated the influence of PCP and DCNP on the activity of cDNA-expressed human ADHs and ALDHs. PCP inhibited all four ADHs studied. The inhibition was strong for ADH3 (K(i) 1.4 microM, K(i)' 5.2 microM, mixed-type) and ADH2 (K(i) 3.7 microM, competitive), but moderate for ADH4 (K(i) 81 microM, competitive) and ADH1C (K(i)' 310 microM, uncompetitive). Activities of ALDH2 and ALDH3A1 were unaffected by PCP (used up to a concentration of 1 mM). In contrast, DCNP primarily inhibited ALDH2 (K(i)=K(i)' 7.4 microM, non-competitive), showed moderate competitive inhibition of ADH2 (K(i) 160 microM) and ADH4 (K(i) 710 microM), but did not affect the remaining enzymes (ADH1C, ADH3 and ALDH3A1). The study demonstrates that caution is required when using putative specific enzyme inhibitors in biotransformation studies.

Altered contractility of skeletal muscle in mice deficient in titin's M-band region.

We investigated the contractile phenotype of skeletal muscle deficient in exons MEx1 and MEx2 (KO) of the titin M-band by using the cre-lox recombination system and a multidisciplinary physiological approach to study skeletal muscle contractile performance. At a maximal tetanic stimulation frequency, intact KO extensor digitorum longus muscle was able to produce wild-type levels of force. However, at submaximal stimulation frequency, force was reduced in KO mice, giving rise to a rightward shift of the force-frequency curve. This rightward shift of the force-frequency curve could not be explained by altered sarcoplasmic reticulum Ca(2+) handling, as indicated by analysis of Ca(2+) transients in intact myofibers and expression of Ca(2)(+)-handling proteins, but can be explained by the reduced myofilament Ca(2+) sensitivity of force generation that we found. Western blotting experiments suggested that the excision of titin exons MEx1 and MEx2 did not result in major changes in expression of titin M-band binding proteins or phosphorylation level of the thin-filament regulatory proteins, but rather in a shift toward expression of slow isoforms of the thick-filament-associated protein, myosin binding protein-C. Extraction of myosin binding protein-C from skinned muscle normalized myofilament Ca(2+) sensitivity of the KO extensor digitorum longus muscle. Thus, our data suggest that the M-band region of titin affects the expression of genes involved in the regulation of skeletal muscle contraction.