Fig 1 - uploaded by Toni E Ziegler
Content may be subject to copyright.
![Children’s baseline levels of AVP were sampled from urine collections pooled across 4 days before the experimental sessions. Children who had experienced early neglect had lower overall levels of AVP than family-reared children [ F (1,37) ϭ 7.61, P Ͻ 0.01].](profile/Toni-Ziegler/publication/7464675/figure/fig1/AS:280568043458560@1443904042200/Childrens-baseline-levels-of-AVP-were-sampled-from-urine-collections-pooled-across-4.png)
Children’s baseline levels of AVP were sampled from urine collections pooled across 4 days before the experimental sessions. Children who had experienced early neglect had lower overall levels of AVP than family-reared children [ F (1,37) ϭ 7.61, P Ͻ 0.01].
Source publication
The formation of social attachments is a critical component of human relationships. Infants begin to bond to their caregivers from the moment of birth, and these social bonds continue to provide regulatory emotional functions throughout adulthood. It is difficult to examine the interactions between social experience and the biological origins of th...
Context in source publication
Context 1
... manipulation. OT and AVP levels (given in mmg creatinine) were equivalent for boys and girls in both groups (OT: girls 17.03, boys 13.88; AVP: girls 31.66, boys 32.07). Basal levels of OT did not differ between the previously neglected and control children (previous neglect: M 12.12, SD 10.61; control: M 18.99, SD 20.96). However, as shown in Fig. 1, children who had experienced early neglect had lower overall levels of AVP than family-reared children. These results suggest that social deprivation may inhibit the development of the AVP system. Functionally, central AVP appears to be critical for recognizing familiar individuals, a key component of forming social bonds ...
Similar publications
Child maltreatment often has a negative impact on the development of social behavior and health. The biobehavioral mechanisms through which these adverse outcomes emerge, however, are not clear. To better understand the ways in which early life adversity affects subsequent social behavior, changes in the neuropeptide oxytocin (OT) in children (n =...
Citations
... There exists a hypothesis suggesting that behavior is influenced by genetics, and thus to some extent, it can be considered heritable (18,19). The extent to which individuals are exposed to hormones during prenatal development may be a determinant of propensities for various social behaviors (20,21). Likewise, distinct biological and genetic factors may influence individuals' predispositions towards particular social behaviors during particular stages of development. ...
Studies conducted on Caucasian subjects have shown a link between increased testosterone levels and an increase in interpersonal betrayal behaviors as well as a reduction in the 2D:4D ratio. It's unclear, however, whether this holds for tribes in Africa. Although 2D:4D may be used as a measure of exposure to prenatal testosterone, it is important to recognize that this association is limited to those who identify as Caucasian. The present study aims to determine the association of the 2D:4D ratio with trustworthiness in the African population. Four hundred and two (402) people were selected at random from two organizations in the Kano state. Both TOAKAN and the Tsaya da Kafarka Taxi Drivers Association are involved in this matter. Participating individuals' ages varied from eighteen to fifty (18-50). A direct method of measuring was used to approximate the lengths of the second and fourth digits. To further assess how trustworthy people perceive one another, a 45-question trustworthiness questionnaire (TQ) was also created. The mean value of 2D: 4DR was 0.98±0.04 which was higher than 2D: 4DL with a mean value of 0.96±0.05. Two components of the dependability scale, 2D: 4DRight(R), Total trustworthiness, and Consistency, were shown to have a positive and statistically significant relationship. On the other hand, no association was found between the 2D:4DLeft (L) and any of the dependability metrics.
... of negative child-caregiver relationships include differences in OXT that are centrally involved in social relationships. For example, lower-than-average levels of OXT are found in the cerebrospinal fluid (CSF) of adult women with a history of CM [170] and in the urine of socially deprived children interacting with their mothers [171]. Furthermore, there is an association between a history of CM and abnormal OXT levels in the saliva and blood, specifically in adults: increased salivary OXT levels are seen even with a history of less severe forms of CM [172] and lower OXT receptor (OXTR) protein expression is found in peripheral blood mononuclear cells [168]. ...
Childhood maltreatment is a risk factor for psychopathologies, and influences brain development at specific periods, particularly during early childhood and adolescence. This narrative review addresses phenotypic alterations in sensory systems associated with specific types of childhood maltreatment exposure, periods of vulnerability to the neurobiological effects of maltreatment, and the relationships between childhood maltreatment and brain structure, function, connectivity, and network architecture; psychopathology; and resilience. It also addresses neurobiological alterations associated with maternal communication and attachment disturbances, and uses laboratory-based measures during infancy and case–control studies to elucidate neurobiological alterations in reactive attachment disorders in children with maltreatment histories. Moreover, we review studies on the acute effects of oxytocin on reactive attachment disorder and maltreatment and methylation of oxytocin regulatory genes. Epigenetic changes may play a critical role in initiating or producing the atypical structural and functional brain alterations associated with childhood maltreatment. However, these changes could be reversed through psychological and pharmacological interventions, and by anticipating or preventing the emergence of brain alterations and subsequent psychopathological risks.
... In line with stress models (e. g., stress-diathesis model, allostatic model by McEwen, 1998a), and based on past evidence, the ongoing pandemic, is anticipated to potentially threaten mental health (Gotlib et al., 2021) or exacerbate pre-existing vulnerabilities. As postulated by McEwen (1998a), chronic stress exposure (e. g., "repeated hits") may lead to continuous activation of the hypothalamo-pituitary-adrenal axis (HPA-axis), resulting in an inadequate stress response (Fries et al., 2005;Heim et al., 2000). Such may manifest as either hyper-or hypocortisolism (Lupien et al., 2009;Miller et al., 2007). ...
... Such may manifest as either hyper-or hypocortisolism (Lupien et al., 2009;Miller et al., 2007). Thus, posing a susceptibility to the development of somatic and psychiatric conditions (Chrousos, 2009;Fries, et al., 2005;Gaab et al., 2005;Heim et al., 2000;Khoury et al., 2019;, especially in the presence of future adversities (Qin et al., 2016). The link between cortisol dysregulation and mental disorders has been observed in several studies (e.g., depression; Halligan et al., 2007, Kennis et al., 2020, Schuler et al., 2017. ...
... Similar studies did not examine whether pre-pandemic cortisol levels independently predicted psychological well-being during the pandemic (Ibar et al., 2021;Rajcani et al., 2021). In general, our results underpin the concept of current stress models postulating cortisol dysregulation as a biological susceptibility for the development of mental disorders (Chrousos, 2009;Fries, et al., 2005;Gaab et al., 2005;Heim et al., 2000;Lupien et al., 2009;McEwen, 1998a), especially in the presence of future adversities (Qin et al., 2016). ...
... In humans, some evidence links alterations in the oxytocin system to the quality of social relationships early in life. For example, preschoolaged children with previous experiences of social deprivation (i.e., who were raised in an orphanage and later adopted into families in the United States) showed lower levels of urinary oxytocin after interactions with their adoptive mothers (Fries et al., 2005). Similar results were found with 9-to 10-year-olds who had been in orphanages, who did not show a reduction in cortisol stress responses after social interactions with their adoptive parents (Hostinar et al., 2015a), even though they reported having supportive parents (Hostinar et al., 2015a). ...
Loneliness becomes more prevalent as youth transition from childhood into adolescence. A key underlying process may be the puberty‐related increase in biological stress reactivity, which can alter social behavior and elicit conflict or social withdrawal ( fight‐or‐flight behaviors) in some youth, but increase prosocial ( tend‐and‐befriend ) responses in others. In this article, we propose an integrative theoretical model that identifies the social, personality, and biological characteristics underlying individual differences in social–behavioral responses to stress. This model posits a vicious cycle whereby youth who respond to stress with fight‐or‐flight tendencies develop increasing and chronic levels of loneliness across adolescence, whereas youth who display tend‐and‐befriend behaviors may be buffered from these consequences. Based on research supporting this model, we propose multiple avenues for intervention to curtail the prevalence of loneliness in adolescence by targeting key factors involved in its development: social relationships, personality, and stress‐induced behavioral and biological changes.
... Recent studies on children with autism spectrum disorder (ASD) indicate that intranasal OT administration is generally well tolerated with few side effects (23-26). Increasing evidence supports the important role of neuropeptide OT in regulating mother-infant bonding and attachment in humans (27,28), and atypical OT levels in plasma, cerebrospinal fluid, and saliva have been found in children subjected to maltreatment and lacking attachment or bonding with a primary caregiver (29)(30)(31)(32)(33)(34). OT acts both as a neurotransmitter and neuromodulator, regulating neuroendocrine, psychophysiological, and socioemotional responses in animals and humans (22,28,35,36). ...
... Recent studies on children with autism spectrum disorder (ASD) indicate that intranasal OT administration is generally well tolerated with few side effects (23-26). Inreasing evidence supports the important role of neuropeptide OT in regulating mother-infant bonding and attachment in humans (27,28), and atypical OT levels in plasma, cerebrospinal fluid, and saliva have been found in children subjected to maltreatment and lacking attachment or bonding with a primary caregiver (29)(30)(31)(32)(33)(34). OT acts both as a neurotransmitter and neuromodulator, regulating neuroendocrine, psychophysiological, and socioemotional responses in animals and humans (22,28,35,36). ...
Reactive attachment disorder (RAD) is associated with socially and emotionally withdrawn/inhibited behaviors and reduced neural responses to rewards. Children and adolescents with RAD show aberrant attachment behaviors, and existing psychotherapies are difficult to maintain; therefore, pharmacological interventions to aid and boost treatment responses are needed. Oxytocin (OT) administration is known to promote reward functioning. We investigated whether single-use intranasal OT administration improved neural responses during reward processing in patients with RAD compared with healthy controls. Twenty-four male children and adolescents with RAD (10–18 years old) and 27 age- and sex-matched typically developing individuals (10–17 years old) were included in this randomized, double-blind, placebo-controlled, cross-over, functional magnetic resonance imaging study. Following a single intranasal OT (24 IU) or placebo administration, neural responses were investigated using a monetary reward task. In the RAD group, OT significantly increased subjective motivation scores, significantly enhanced activation in the right middle frontal gyrus, and reduced activation in the right precentral gyrus during the monetary reward task. Additional analyses revealed increased activation in the bilateral caudate at a more lenient threshold. Under placebo conditions, the severity of internalizing problems in patients with RAD was negatively correlated with ventral striatal activity. Moreover, the effect of OT on ventral striatum activity was positively associated with the severity of internalizing problems in patients with RAD. Intranasal OT administration enhanced activity in the reward pathway in male children and adolescents with RAD, suggesting that exogenous OT promotes reward processing and reward-related motivational behavior in these individuals. Further investigation is needed to fully understand the neural mechanisms of intranasal OT and identify novel targets for pediatric cases with RAD.
Clinical trial registration: UMIN-CTR; UMIN000013215. URL: https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000015419
... A meta-analysis showed that intranasal OXT administration can attenuate HPAA reactivity in response to a laboratory stressor that stimulates the HPAA (Cardoso et al., 2014). Early life stress has also been shown to impact OXT signaling in childhood and altered cerebral spinal fluid and plasma concentrations of OXT in adulthood (Fries et al., 2005;Heim et al., 2009;Opacka-Juffry & Mohiyeddini, 2012). This co-occurrence of abnormal OXT and HPAA signaling suggests that disruption to the bidirectional associations between these systems may shape trajectories of stress-related disorders later in life (Toepfer et al., 2017). ...
Maternal prenatal psychosocial stress is associated with adverse hypothalamic–pituitary–adrenal axis (HPAA) function among infants. Although the biological mechanisms influencing this process remain unknown, altered DNA methylation is considered to be one potential mechanism. We investigated associations between maternal prenatal psychological distress, infant salivary DNA methylation, and stress physiology at 12 months. Mother's distress was measured via depression and anxiety in early and late pregnancy in a cohort of 80 pregnant adolescents. Maternal hair cortisol was collected during pregnancy. Saliva samples were collected from infants at 12 months to quantify DNA methylation of three stress‐related genes (FKBP5, NR3C1, OXTR) (n = 62) and diurnal cortisol (n = 29). Multivariable linear regression was used to test for associations between prenatal psychological distress, and infant DNA methylation and cortisol. Hair cortisol concentrations in late pregnancy were negatively associated with two sites of FKBP5 (site 1: B = −22.33, p = .003; site 2: B = −15.60, p = .012). Infants of mothers with elevated anxiety symptoms in late pregnancy had lower levels of OXTR2 CpG2 methylation (B = −2.17, p = .03) and higher evening salivary cortisol (B = 0.41, p = .03). Furthermore, OXTR2 methylation was inversely associated with evening cortisol (B = −0.14, p‐value ≤ .001). Our results are, to our knowledge, the first evidence that the methylation of the oxytocin receptor may contribute to the regulation of HPAA during infancy.
... Indeed, early life adversities were found to be associated with decreased OXT cerebrospinal fluid concentrations in women and nonhuman primates (Heim et al., 2009;Strathearn, 2011) and with decreased OXT plasma levels in men (Opacka-Juffry & Mohiyeddini, 2012). Children who experienced severe emotional neglect early on showed no change in OXT levels after physical contact with their mother, whereas children who were raised in a caring environment showed an increase of OXT (Fries et al., 2005). Neural responses to OXT administration also seem to be dependent on early life adversities, which has repeatedly been shown in male participants in studies relating to stress reactivity (Fan et al., 2015;Grimm et al., 2014;Meinlschmidt & Heim, 2007). ...
Sensitivity for rewarding cues and distress signals from children is fundamental to human caregiving and modulated by the neuropeptide oxytocin. In a functional magnetic resonance imaging study, we investigated whether oxytocin regulates neural responses to reward or distress cues form children. In a placebo‐controlled, within‐subject design, we measured neural responses to positive, negative, and neutral cues from children in 22 healthy female subjects who received oxytocin (24 IU) versus placebo. Further, based on current literature, we hypothesized that oxytocin effects are modulated by experiences of childhood trauma. The task elicited valence‐specific effects—positive images activated the ventromedial prefrontal cortex, left anterior cingulate cortex, and right putamen, and images of children in distress activated the bilateral amygdala, hippocampus, and right medial superior frontal cortex. The effects of oxytocin depended on subjective reports of childhood emotional neglect. Self‐reported neglect interacted with oxytocin administration in the amygdala, hippocampus, and prefrontal areas. In individuals with higher scores of emotional neglect, oxytocin increased neural reactivity of limbic structures to positive and neutral images. Our findings need replication in larger samples and can therefore be considered preliminary but are in line with the recent literature on the modulating effect of childhood adversity on the sensitivity to oxytocin administration.
... Two cases that the study looked at were both children diagnosed with disinhibited RAD associated with other comorbidities; both children were started on a regimen of sertraline and both showed improvement in their moods and behavior at home and in school [13]. Wismer et al. noted that "children with an early history of severe maltreatment have shown reduced levels of vasopressin during an experimental social physical interaction study with their adoptive mothers when these levels are expected to rise" [23]. The reduction in vasopressin and even oxytocin can be implicated in the lack of development of social and emotional bonds in children exposed to maltreatment. ...
Reactive attachment disorder (RAD), classified under Trauma and Stressor Related Disorders in the DSM-5 manual, is a childhood psychiatric illness due to familial or social neglect or due to maltreatment. It is characterized by an inhibited and withdrawn social and emotional behavior toward an adult caregiver, typically before the age of 5. Neurobiological changes in patients with RAD have been shown to be substantially significant with features such as loss of grey matter volume and neurotransmitter deficiencies that not only impact the ability to form healthy attachments but also increase the risk of comorbidities such as depression and anxiety.
Different theories, including the current mediation hypothesis and learning theory of attachment, showed childhood maltreatment from caregivers and desensitization toward deficiencies in social development in children from special education teachers to be key components in the development of RAD. Patients with RAD had an increased risk of developing psychiatric comorbidities, including learning disabilities and mood disorders. Institutionalized care and childhood maltreatment have a significant impact on the development of RAD.
RAD is an underdiagnosed and underreported condition with significant repercussions that can severely impact the development of a child. By being able to raise awareness and promote further research into refining the diagnostic methodology, treatment protocols, and long-term follow-up, children afflicted with this condition may be able to develop better socio-emotional bonds and reduce the incidence of comorbidities such as depression and attention deficit hyperactivity disorder.
... A meta-analysis showed that intranasal OXT administration can attenuate HPAA reactivity in response to a laboratory stressor that stimulates the HPAA (Cardoso et al., 2014). Early life stress has also been shown to impact OXT signaling in childhood and altered cerebral spinal fluid and plasma concentrations of OXT in adulthood (Fries et al., 2005;Heim et al., 2009;Opacka-Juffry & Mohiyeddini, 2012). This co-occurrence of abnormal OXT and HPAA signaling suggests that disruption to the bidirectional associations between these systems may shape trajectories of stress-related disorders later in life (Toepfer et al., 2017). ...
Objectives:Maternal prenatal psychosocial stress is associated with adverse hypothalamic-pituitary-adrenal axis function among infants. While the biological mechanisms influencing this process remain unknown, altered DNA methylation is considered to be one potential mechanism. We investigated associations between maternal prenatal psychological distress, infant salivary DNA methylation and stress physiology at 12 months. Methods:Mother’s distress was measured via depression and anxiety in early and late pregnancy in a cohort of 80 pregnant adolescents. Maternal hair cortisol was collected during pregnancy. Saliva samples were collected from infants at 12 months to quantify DNA methylation of three stress-related genes (FKBP5, NR3C1, OXTR) (n=62) and diurnal cortisol (n=29). Multivariable linear regression was used to test for associations between prenatal psychological distress, and infant DNA methylation and cortisol. Results:Hair cortisol concentrations in late pregnancy were negatively associated with two sites of FKBP5 (Site 1: B=-22.33, p=0.003; Site 2: B=-15.60, p=0.012). Infants of mothers with elevated anxiety symptoms in late pregnancy had lower levels of OXTR2 CpG2 methylation (B=-2.17, p=0.03) and higher evening salivary cortisol (B=0.41, p=0.03). Furthermore, OXTR2 methylation was inversely associated with evening cortisol (B=-.14, p-value≤0.001). Discussion: Our results are, to our knowledge, the first evidence that methylation of the oxytocin receptor may contribute to the regulation of hypothalamic-pituitary-adrenal axis during infancy
