Salivary immune markers are not associated with self-reported childhood maltreatment or psychopathology in adults.

BACKGROUND: Psychological stress has repeatedly been found to be associated with pro-inflammatory markers in blood, and neuro-inflammation may play a role in the development of psychopathology after early life stress. Salivary immune testing is a novel method to non-invasively assess immune functioning. We examined a large range of salivary immune markers in relation to self-reported childhood maltreatment and psychopathology in an adult sample. METHODS: Participants (N = 118, 51% female, mean age = 46.6 yrs, range 22-64) were drawn from a cross-sectional three-generation study, and supplied 2 ml of saliva via passive drool. They reported on childhood maltreatment experiences and on psychopathological symptoms in the last 6 months. Hair cortisol was additionally assessed in a subsample (n = 68). Levels of IL1ß, IL6, IL8, IFNγ, TNFα, tIgE, sIgA, FLCƛ, and FLCƙ were assessed. RESULTS: Linear mixed model analyses showed that several salivary immune markers were associated with age (sIgA and IgE), BMI (sIgA, IL1ß, and IL6), sex (FLCs and IgE), and bad health (IL6, IL8, TNFα). No associations with (anti-inflammatory) medication use or oral health problems were found. Notably, no associations between the immune markers and self-reported childhood maltreatment, psychopathology, or hair cortisol were found. CONCLUSIONS: Salivary immune measures were found to be sensitive to individual differences in age, sex, health and BMI. However. in the current sample there was no indication of inflammation in relation to chronic psychological stress. Larger studies, including participants with higher stress levels, are needed to further examine associations between salivary immune markers and psychological stress.

Exploring the role of endocrine factors in sensitive parenting in men.

Parental sensitivity has been studied extensively in parenting research. Recently, there has been increasing attention to endocrine factors that may be related to parental sensitivity, such as oxytocin, vasopressin, testosterone, and cortisol. Although hormones do not act in isolation, few studies integrated multiple hormones and examined their combined associations with parental sensitivity. The current study aimed to explore the hormonal correlates of paternal sensitivity by examining in 79 first-time fathers of young infants (2-4 months old) (1) the separate and combined associations of basal oxytocin, vasopressin, testosterone, and cortisol levels with sensitivity, and (2) the associations between paternal sensitivity and oxytocin, vasopressin, testosterone, and cortisol reactivity following father-infant interactions. We additionally explored whether interactions between the various basal hormone levels could predict paternal sensitivity. Saliva for the quantification of fathers' hormone levels was sampled before and after an interaction with their infant to determine basal levels and reactivity. Results revealed no significant associations between sensitivity and basal hormone levels or reactivity. However, results indicated that cortisol and testosterone interacted in their effects on paternal sensitive parenting. Namely, fathers with low basal cortisol levels showed more sensitivity with increasing T levels, but fathers with high cortisol levels were less sensitive with increasing T levels. However, it should be noted that the latter slope was not significantly different from zero. These findings suggest that variations in parental sensitivity might be better explained by interactions between hormones than by single hormone levels.

Towards a neural model of infant cry perception.

Previous work suggests that infant cry perception is supported by an evolutionary old neural network consisting of the auditory system, the thalamocingulate circuit, the frontoinsular system, the reward pathway and the medial prefrontal cortex. Furthermore, gender and parenthood have been proposed to modulate processing of infant cries. The present meta-analysis (N = 350) confirmed involvement of the auditory system, the thalamocingulate circuit, the dorsal anterior insula, the pre-supplementary motor area and dorsomedial prefrontal cortex and the inferior frontal gyrus in infant cry perception, but not of the reward pathway. Structures related to motoric processing, possibly supporting the preparation of a parenting response, were also involved. Finally, females (more than males) and parents (more than non-parents) recruited a cortico-limbic sensorimotor integration network, offering a neural explanation for previously observed enhanced processing of infant cries in these sub-groups. Based on the results, an updated neural model of infant cry perception is presented.

Testosterone reactivity to infant crying and caregiving in women: The role of oral contraceptives and basal cortisol.

Several studies have shown that mothers and fathers have significant lower levels of testosterone (T) than non-mothers and non-fathers, and that in men caregiving is related to a decrease in T. To date, only a few studies have examined T in women. We examined T reactivity to a crying infant simulator in 160 women. Use of oral contraceptives (OC), basal cortisol (CORT) levels and childhood experiences of maternal love withdrawal were taken into account. T levels were consistently significantly higher in women not using OC. In women not using OC, high basal CORT was related to higher initial T levels and larger decreases of T during caregiving. No effect of basal CORT was found in women with OC use. Childhood experiences of maternal love withdrawal did not affect T levels. This is the first study to show support for a decrease of T in women while taking care of a crying infant, supporting the Challenge hypothesis and the Steroid/Peptide Theory of Social Bonds.

As tears go by: Baby tears trigger more brain activity than adult tears in nulliparous women.

The current functional magnetic resonance imaging study examines brain activity during the perception of infant and adult tears. Infant tears evoke stronger responses in the visual cortex than adult tears, indicating that infant tears are highly salient. In addition, our study shows that infant tears uniquely activate somatosensory pain regions, which could stimulate actions directed at the elimination of the source of pain. Shedding tears may be a strong means to elicit the parent's sharing of the infant's feelings, thereby strengthening caregiver-infant bonding and securing infant survival.

Adult attachment representation moderates psychotherapy treatment efficacy in clinically depressed inpatients.

BACKGROUND: We explored in a sample of clinically depressed patients the influence of attachment security and unresolved trauma on psychotherapeutic outcome as well as changes in attachment representation through psychotherapeutic intervention. METHODS: The sample consisted of 85 women (aged 19-52), 43 clinically depressed patients from a psychosomatic inpatient unit, and 42 healthy control subjects matched for age and education. Average length of hospitalization in the patient group was eight weeks. Attachment representations were assessed with the Adult Attachment Interview at the time of admission (baseline) and at discharge. Depressive symptoms were measured using the PHQ-9 at T1 and T2. RESULTS: Insecure attachment representations were overrepresented in depressed patients. Treatment effects were moderated by baseline attachment representation: patients with higher attachment security scores at admission benefited more from the inpatient treatment and were less depressed at time of discharge than less secure patients (η(2)=.07). Generally, attachment security increased (η(2)=.19) and depressive symptoms decreased (η(2)=.23) after inpatient psychotherapy treatment in the patient group. No significant effects for unresolved symptoms were found. LIMITATIONS: The study is not a randomized controlled study, but used a quasi-experimental matched control group design with female subjects only. CONCLUSIONS: Our results suggest that attachment representations play a major role in both the development and treatment of clinical depression. Baseline attachment security may influence psychotherapeutic outcome, perhaps through relational factors such as therapeutic working alliance. Inpatient psychotherapy may also need to address psychological issues associated with depression such as attachment insecurity.

The Role of Oxytocin in Parenting and as Augmentative Pharmacotherapy: Critical Issues and Bold Conjectures.

Despite the sometimes heated debate about the validity of human oxytocin studies, experimental oxytocin research with intranasal administration is a growing field with promising preliminary findings. The effects of intranasally administered oxytocin compared to placebo on brain neural activity have been supported in animal studies and in human studies of neural resting state. In several studies, oxytocin sniffs have been shown to lead to down-regulation of amygdala activation in response to infant attachment vocalisations. Meta-analytic evidence shows that oxytocin enhances the salience of (emotional) stimuli, lowers stress and arousal, and elevates empathic concern and tender care, in particular for offspring and in-group members. Less firm evidence points at the amnestic effects of oxytocin. We also note that the average effect sizes of oxytocin experiments are small to modest, and that most studies include a small number of subjects and thus are seriously underpowered, which implies a high risk for publication bias and nonreplicability. Nevertheless, we argue that the power of within-subjects experiments with oxytocin has been underestimated. Much more work is needed, however, to create a firm knowledge base of the neural and behavioural effects of oxytocin. Human oxytocin research is still taking place in the context of discovery, in which bold conjectures are being generated. In the context of justification, these conjectures should subsequently be subjected to stringent attempts at refutations before we jump to theoretical or clinical conclusions. For this context of justification, we propose a multisite multiple replications project on the social stimuli salience enhancing effect of oxytocin. Clinical application of oxytocin is premature. Meta-analytically, the use of oxytocin in clinical groups tends to show only effectiveness in changing symptomatology in individuals with autism spectrum disorders but, even then, it is not yet a validated therapy and its use is premature because safety and long-term side-effects have not been sufficiently studied, in particular in children.

Methylation of the oxytocin receptor gene in clinically depressed patients compared to controls: The role of OXTR rs53576 genotype.

The emerging field of epigenetics provides a biological basis for gene-environment interactions relevant to depression. We focus on DNA methylation of exon 1 and 2 of the oxytocin receptor gene (OXTR) promoter. The research aims of the current study were to compare OXTR DNA methylation of depressed patients with healthy control subjects and to investigate possible influences of the OXTR rs53576 genotype. The sample of the present study consisted of 43 clinically depressed women recruited from a psychosomatic inpatient unit and 42 healthy, female control subjects - mean age 30 years (SD = 9). DNA methylation profiles of the OXTR gene were assessed from leukocyte DNA by means of bisulfite sequencing. Depressed female patients had decreased OXTR exon 1 DNA methylation compared to non-depressed women. The association between depression and methylation level was moderated by OXTR rs53576 genotype. Exon 2 methylation was associated with OXTR rs53576 genotype but not with depression. Our findings suggest exon-specific methylation mechanisms. Exon 1 methylation appears to be associated with depressive phenotypes whereas exon 2 methylation is influenced by genotype. Previously reported divergent associations between OXTR genotype and depression might be explained by varying exon 1 methylation. In order to further understand the etiology of depression, research on the interplay between genotype, environmental influences and exon-specific methylation patterns is needed.

Sniffing around oxytocin: review and meta-analyses of trials in healthy and clinical groups with implications for pharmacotherapy.

The popularity of oxytocin (OT) has grown exponentially during the past decade, and so has the number of OT trials in healthy and clinical groups. We take stock of the evidence from these studies to explore potentials and limitations of pharmacotherapeutic applications. In healthy participants, intranasally administered OT leads to better emotion recognition and more trust in conspecifics, but the effects appear to be moderated by context (perceived threat of the 'out-group'), personality and childhood experiences. In individuals with untoward childhood experiences, positive behavioral or neurobiological effects seem lowered or absent. In 19 clinical trials, covering autism, social anxiety, postnatal depression, obsessive-compulsive problems, schizophrenia, borderline personality disorder and post-traumatic stress, the effects of OT administration were tested, with doses ranging from 15 IU to more than 7000 IU. The combined effect size was d=0.32 (N=304; 95% confidence interval (CI): 0.18-0.47; P<0.01). However, of all disorders, only studies on autism spectrum disorder showed a significant combined effect size (d=0.57; N=68; 95% CI: 0.15-0.99; P<0.01). We hypothesize that for some of the other disorders, etiological factors rooted in negative childhood experiences may also have a role in the diminished effectiveness of treatment with OT.

Attachment insecurity predicts child active resistance to parental requests in a compliance task.

AIM: We studied the effects of early mother-child relationship quality and child temperament on the development of child compliance and active resistance in a large population-based cohort study (n = 534). BACKGROUND: Parenting and the quality of the parent-child relationship can either hamper or support the development of child compliance directly or in interplay with child temperament. METHODS: Mother-infant dyads were observed at 14 and 36 months and maternal and child behaviours were independently coded. The quality of compliance was assessed at 36 months in a clean-up task. Child behaviour was coded using a system differentiating between two dimensions: Compliance and Active Resistance. RESULTS: Controlling for concurrent maternal sensitivity, child temperament, and gender children with a more insecure attachment relationship showed higher levels of active resistance during Clean-Up than more securely attached children. The effect was stronger for boys than for girls and mainly driven by attachment avoidance. CONCLUSIONS: Early attachment is an important contributor to child socialization of moral behaviour.

Serotonin transporter genotype 5HTTLPR as a marker of differential susceptibility? A meta-analysis of child and adolescent gene-by-environment studies.

We present results of a meta-analysis of gene-by-environment (G × E) studies involving the serotonin transporter genotype 5HTTLPR to evaluate empirical support for two competing conceptual frameworks in developmental psychopathology: diathesis-stress and differential susceptibility. From a diathesis-stress perspective, the cumulative negative effects of the short allele (ss and sl genotypes) and adverse environments on development have been stressed. From a differential-susceptibility perspective, carriers of the s allele are predicted to be more open to adverse as well as positive environments, for better and for worse. Studies with children and adolescents up to 18 years of age (N=9361) were included. We found 41 effect sizes (N=5863) for the association between negative environments and developmental outcomes with or without significant moderation by 5HTTLPR genotype and 36 effect sizes (N=3498) for the potentially 5HTTLPR-moderated association between positive environments and developmental outcomes. Five moderators were examined: age, ethnicity, genotyping (biallelic or triallelic) and methods used to assess environment and outcome. In the total set of studies, including studies with mixed ethnicities, we found that ss/sl carriers were significantly more vulnerable to negative environments than ll carriers, thus supporting the diathesis-stress model. In the Caucasian samples, however, ss/sl carriers also profited significantly more from positive environmental input than ll carriers. Associations between (positive or negative) environment and (positive or negative) developmental outcome were absent for ll carriers. The meta-analytic findings support the hypothesis that in Caucasian samples 5HTTLPR is a genetic marker of differential susceptibility. G × E interactions might be critically dependent on ethnicity.

Physiological reactivity to infant crying: a behavioral genetic study.

In this study, we examined adults' cardiac reactivity to repeated infant cry sounds in a genetically informative design. Three episodes of cry stimuli were presented to a sample of 184 adult twin pairs. Cardiac reactivity increased with each cry episode, indicating that subjects were increasingly sensitized to repeated infant distress signals. Non-parents showed more cardiac reactivity than parents, and males displayed a larger increase in heart rate (HR) in response to repeated cry sounds than females. Multivariate genetic modeling showed that the genetic component of adults' HR while listening to infant crying was substantial. Genetic factors explained 37-51% of the variance in HR and similar genes influenced HR at baseline and HR reactivity to infant crying. The remaining variance in HR across the cry paradigm was accounted for by unique environmental influences (including measurement error). These results point to genetic and experiential effects on HR reactivity to infant crying that may contribute to the explanation of variance in sensitive and harsh parenting.

Supporting insensitive mothers: the Vilnius randomized control trial of video-feedback intervention to promote maternal sensitivity and infant attachment security.

OBJECTIVE: This randomized control trial examined the effects of a short-term, interaction-focused and attachment-based video-feedback intervention (VIPP: video-feedback intervention to promote positive parenting). Design VIPP effect on mothers' sensitive responsiveness and infant-mother attachment security was evaluated in a sample (n = 54) of low sensitive, non-clinical, middle class Lithuanian mothers. METHODS: Maternal sensitivity was assessed in a free play session with the Ainsworth's sensitivity scale, and attachment security was observed using the Attachment Q sort for home observations. RESULTS: We found that the intervention mothers indeed significantly improved their sensitive responsiveness through participation in our VIPP. The effect size was large according to Cohen's criteria, d = 0.78. VIPP enhanced maternal sensitive responsiveness even when maternal age, educational level, depression, daily hassles, efficacy, infant gender, and infant negative and positive affect were controlled for. However, attachment security in the VIPP infants was not enhanced after the intervention, compared with the control infants, and the infants did not seem to be differentially susceptible to the increase in maternal sensitivity dependent on their temperamental reactivity. CONCLUSION: We suggest that a relatively brief and low-cost programme can provide effective support for mothers who lack sensitivity in the interactions with their infants.

Attachment representations in Dutch veterans with and without deployment-related PTSD.

In this study we tested for a protective effect of secure attachment representations in the development of posttraumatic stress disorder (PTSD). In a design with a control group, we replicated and extended a recent study that found no underrepresentation of secure attachment representations in veterans with PTSD (Nye, Katzman, Bell, Kilpatrick, Brainard, & Haaland, 2008). Furthermore, we examined the association of the Adult Attachment Interview (AAI) classification of unresolved loss or trauma and PTSD symptomatology. The Adult Attachment Interview and the Clinician Administered PTSD Scale (CAPS) were administered with 31 veterans with PTSD and 29 trauma-exposed veterans without PTSD of similar age and country of deployment. Patient and control groups did not differ in the prevalence of secure attachment representations, neither did unresolved and not unresolved subjects differ in prevalence of secure attachment representations. Unresolved state of mind with respect to deployment related trauma was found to correlate strongly with total CAPS score. This study shows no protective effect of secure attachment representations in the development of PTSD. AAI unresolved state of mind with respect to deployment related trauma and PTSD correlate strongly, due to the common core phenomenon of lack of integration.

Dopamine system genes associated with parenting in the context of daily hassles.

The current study examined the molecular genetic foundations of sensitive parenting in humans and is the first to test the interaction between genes and environment in modulating parental sensitive responses to children. In a community sample of 176 Caucasian, middle class mothers with their 23-month-old toddlers at risk for externalizing behavior problems, the association between daily hassles and sensitive parenting was investigated. We tested whether two dopamine-related genes, dopamine D4 receptor (DRD4) and catechol-O-methyltransferase (COMT) gene polymorphisms, modulate parents' vulnerability to the negative influence of daily hassles on sensitive parenting behavior to their offspring. Sensitive parenting was observed in structured settings, and parents reported on their daily hassles through a standard questionnaire. In parents with the combination of genes leading to the least efficient dopaminergic system functioning (COMT val/val or val/met, DRD4-7Repeat), more daily hassles were associated with less sensitive parenting, and lower levels of daily hassles were associated with more sensitive parenting d = 1.12. The other combinations of COMT and DRD4 polymorphisms did not show significant associations between daily hassles and maternal sensitivity, suggesting differential susceptibility to hassles depending on parents' dopaminergic system genes. It is concluded that the study of (multiple) gene-environment interactions (in the current case: gene by gene by environment interaction, G x G x E) may explain why some parents are more and others less impacted by daily stresses in responding sensitively to their offspring's signals.

No association of the dopamine D4 receptor (DRD4) and -521 C/T promoter polymorphisms with infant attachment disorganization.

In a first molecular genetic study Lakatos and colleagues found an association between attachment disorganization and the dopamine D4 receptor (DRD4) gene polymorphism, in particular in the presence of the -521 T allele in the promoter region of the DRD4 gene. Replication of their study in a sample of 132 infants did not confirm the role of the DRD4 7+ -allele and the -521C/T promoter gene in disorganized attachment. Although our sample was larger, and contained more children with CT or TT alleles, which enhanced the probability of finding the DRD4 and C/T interaction, the association was not found. Even when we combined our sample with the Lakatos sample, the interaction effect of the DRD4 and -521 C/T polymorphisms on disorganized attachment was absent.

The importance of shared environment in infant-father attachment: a behavioral genetic study of the attachment q-sort.

In this first behavior genetic study on infant-father attachment, we estimated genetic and environmental influences on infant-father attachment behaviors and on temperamental dependency, both assessed with the Attachment Q-Sort (AQS; B. E. Vaughn & E. Waters, 1990; E. Waters, 1995). Mothers of mono- and dizygotic twins (N = 56 pairs) sorted the AQS with a focus on the infant's behaviors in the presence of the father. Genetic modeling showed that attachment was largely explained by shared environmental (59%) and unique environmental (41%) factors. For dependency, genetic factors explained 66% of the variance, and unique environmental factors including measurement error explained 34%. Attachment to father appears to be, to a significant degree, a function of the environment that twins share.

The similarity of siblings' attachments to their mother.

Do siblings develop similar attachment relationships with their mother? Attachment theory suggests that brothers and sisters growing up in the same family are likely to relate in similar ways to their parents, at least when parental attachment representations and interactive styles remain stable across time. In the current study, sibling attachment data from three research groups (from Pennsylvania State University, Leiden University, and the University of Western Ontario) have been pooled to assemble a sufficiently large sample of observations (N = 138 sibling pairs) for a detailed comparison of sibling attachment relationships. Spacing between the births, differences in maternal sensitivity, and gender of siblings were examined as possible sources of concordance of nonconcordance. Attachment security (including disorganized attachment) of each sibling was assessed with the Strange Situation procedure between 12 and 14 months after birth. Maternal sensitivity was observed with the same rating scale in a laboratory play session in one of the studies and in home observations in the others. Sibling relationships were found to be significantly concordant when classified as secure/nonsecure (62% concordance, p < .01, 1-tailed, intraclass correlation = .23) but not when further subcategorized. Maternal insensitivity to both siblings (shared environment) was associated with concordance of sibling nonsecurity. Siblings of the same gender were more likely to form concordant relationships with their mother (68%; p < .01, 1-tailed, intraclass correlation = .37) than those of opposite gender. Same-sex sibling concordance was comparable to the concordance found for monozygotic twins in earlier studies. Genetic factors may, therefore, play a relatively small role in the development of attachment.

Insecure and disorganised attachment in children with a pervasive developmental disorder: relationship with social interaction and heart rate.

This study on children with a Pervasive Developmental Disorder (PDD; N = 32), children with developmental language disorder (N = 22), and normally developing children (N = 28) sought to answer questions concerning attachment and autistic behaviour. We could replicate the finding that children with a PDD are able to develop secure attachment relationships to their primary caregiver. Children with PDD who had an insecure attachment showed fewer social initiatives and responses than children with PDD who had a secure attachment, even when the insecurely and securely attached PDD children were matched on chronological and mental age. Children with both a PDD and mental retardation were more often classified as disorganised. Three findings suggested that a disorganised attachment does not merely reflect the presence of "autistic" behaviour: (1) children with PDD did not reveal higher rates of a disorganised attachment than matched comparison children; (2) having a PDD diagnosis and having a disorganised attachment were found to be associated with opposite effects on an ethological measure of level of behavioural organisation; and (3) a disorganised attachment but not a PDD diagnosis was associated with an increase in heart rate during parting with the caregiver and a decrease in heart rate during reunion.

Frightening maternal behavior linking unresolved loss and disorganized infant attachment.

Main and Hesse's (1990) model in which frightening (threatening, frightened, or dissociated) parental behavior explains why infants of parents with unresolved loss develop disorganized attachment relationships was tested. Unresolved loss using the Adult Attachment Interview in a nonclinical middle-class sample of 85 mothers who had experienced the loss of someone important was assessed. Disorganized attachment was examined in the Strange Situation. Parental behavior was recorded during 22-hr home visits. The model applied to mothers with currently insecure attachment representations. Secure mothers with unresolved loss displayed less frightening behavior than other mothers, and unresolved loss in secure mothers did not predict disorganized attachment of their infants. Frightening behavior predicted infant disorganized attachment irrespective of maternal security.