Is adult separation anxiety associated with offspring risk for internalizing psychiatric problems?

BACKGROUND: Awareness of adult separation anxiety (ASA) is growing, but there is a dearth of knowledge about how separation anxiety aggregates in families. We examined the intergenerational associations of separation anxiety and other forms of internalizing problems in an American community sample of 515 predominantly white children and their parents. METHODS: Children's separation anxiety (CSA), depression, and other anxiety disorders were modeled as latent factors using diagnoses from interviews and symptom scores from questionnaires completed by mothers, fathers, and children when children were 9 years old and again 3 years later. Parents' separation anxiety was assessed via a questionnaire and parents' other anxiety, depressive, and substance use disorders were assessed with a diagnostic interview when children were nine. Relationships between parents' and children's psychopathology were modeled using s.e.m. RESULTS: Mothers' and fathers' ASA were related to all three psychopathology factors in offspring, over and above other parental disorders, in concurrent and prospective analyses. CSA was also related to maternal depression concurrently and prospectively and to maternal anxiety prospectively. Of all paternal psychopathology variables, only ASA was significantly related to children's psychopathology in either model. CONCLUSIONS: Results indicate that parental separation anxiety is an important, but non-specific, risk factor for children's psychopathology. The pathway by which this risk is transmitted may be genetic or environmental, and the observed statistical associations likely also encompass child-to-parent effects.

Mental Health Challenges Among First Nations Adolescents Living Off-Reserve in Ontario, Canada.

Limited data exist on the mental health challenges facing First Nations adolescents and the factors that modify these difficulties. The current study compared levels of common mental health challenges among 112 off-reserve First Nations and 3334 non-First Nations adolescents (12-17 years old) and examined the impact of maternal psychological distress on these mental health challenges. First Nations adolescents self-reported higher symptoms of conduct, oppositional-defiant, attention-deficit hyperactivity, major depressive, social phobia, generalized anxiety, and separation anxiety disorders and all associations remained statistically significant after adjusting for covariates. Moderation analyses found that increasing levels of maternal distress were associated more strongly with symptoms of oppositional defiant, attention-deficit hyperactivity, major depressive, and generalized anxiety disorders in First Nations adolescents. Future work aimed at improving the mental health of First Nations youth that focus on supporting these adolescents, and their mothers in particular, could result in substantial benefits.

To Leave is to Die a Little: Assessing the Symptom Structure of Separation Anxiety Disorder in Left-Behind Emerging Adults.

The literature on separation anxiety disorder (SAD) presented two contentious issues relating to its assessment. First, studies are scarce in assessing the symptom structure of DSM-5 SAD among the adult population. Second, the accuracy in assessing the severity of SAD through measuring the intensity of disturbance and the frequency of occurrence of symptoms is yet to be studied. To address these limitations, the present study aimed to: (1) examine the latent factor structure of the newly developed separation anxiety disorder symptom severity inventory (SADSSI); (2) evaluate the necessity of using frequency or intensity formats through comparison of differences in the latent level; and (3) investigate SAD latent class analysis. Utilizing 425 left-behind emerging adults (LBA), the findings showed that a general factor with two dimensions (i.e., response formats) measuring frequency and intensity symptom severity separately has excellent fit and good reliability. Finally, the latent class analysis yielded a three-class solution best fitting to the data. Overall, the data provided evidence for the psychometric soundness of SADSSI as an assessment tool for separation anxiety symptoms among LBA.

A LONGITUDINAL STUDY OF CHILDHOOD SEPARATION ANXIETY DISORDER AND ITS IMPLICATIONS FOR ADOLESCENT PSYCHOPATHOLOGY.

A prevalent psychiatric disorder called Child Separation Anxiety Disorder (SAD) is characterized by extreme discomfort when a child gets separated from their primary carers. While SAD's quick consequences on kids are well-researched, its long-term implications for teenage psychopathology have received less attention. This longitudinal study aims to ascertain the connection between child SAD and future psychopathological consequences in adolescents. 500 adolescents were chosen as part of the adolescent depression project, and at the age of 17, we retrospectively evaluated past and present mental disorders. At ages 25 and 32, they conducted diagnostic evaluations of these people during adolescence while they continued to monitor them. Based on childhood/adolescent assessments, the participants were split into different groups: SAD (n=34), other forms of Anxiety (n=76), a control group with combined psychiatric conditions (n=205), and mentally sound control group (n=185). Statistics were evaluated by hierarchical multiple logistic regression after various illnesses and pertinent demographic variables were considered. It implies that SAD has a high risk (80.2%) of being a significant risk indicator for the emergence of mental illnesses in young adults. This study highlights the importance of early SAD management and therapy and the possible advantages of treating SAD in lowering the likelihood of developing other mental health problems in adolescence. It also emphasizes the value of continuous studies to comprehend these connections and enhance the effects on SAD sufferers' psychological well-being.

Relationship of behavioral inhibition to separation anxiety in a sample (N = 377) of adult individuals with mood and anxiety disorders.

BACKGROUND: Behavioral Inhibition (BI) is an early temperamental trait characterized by shyness, withdrawal, avoidance, uneasiness, and fear of unfamiliar situations, people, objects, and events. The DSM-5 refers to behavioral inhibition as a temperamental factor related to neurodevelopmental conditions in childhood, including attention deficit hyperactivity disorder, selective mutism, and specific phobias; and to its influence on adult anxiety disorders including social anxiety disorder, agoraphobia, and generalized anxiety disorder, but, interestingly, not separation anxiety disorder (SAD). However, there are phenomenological overlaps between BI and SAD. We aimed to explore whether there is a correlation between BI as an early temperamental trait and childhood or adult separation anxiety disorder. METHODS: The study was conducted in 377 consecutive adults (mean age 40.2±12.4 years) outpatients with anxiety and mood disorders as the principal diagnosis, grouped on the presence/absence of a DSM-5 diagnosis of childhood or adult separation anxiety disorder. Separation anxiety was assessed by the Structured Clinical Interview for Separation Anxiety (SCI-SAS) and the Adult Separation Anxiety Checklist (ASA27). Behavioral inhibition was assessed by the Retrospective Self-Report of Inhibition (RSRI). RESULTS: The four comparison groups included: 1) 168 patients without childhood or adult SAD, 2) 81 with adult SAD, 3) 97 with both adult SAD and childhood SAD, and 4) 31 with childhood SAD only. The group with both adult and childhood SAD had the highest scores on RSRI total and sub-scale scores. Both groups with adult SAD had significantly higher RSRI scores than the group with only childhood SAD or without SAD. Significant bivariate correlations were found between ASA-27 scores and RSRI scores. Correlations between RSRI scores and measures of anxiety and depressive symptoms were significantly weaker than those on the ASA-27. Regression analyses showed a significant predictive value of RSRI scores on ASA-27 total score, but not of age of onset of SAD. CONCLUSIONS: BI has an onset in the very first years of life and may represent a potential developmental endophenotype for later anxiety disorders. Our findings indicate that BI and separation anxiety are connected in individuals with affective and anxiety disorders. This may have important clinical and therapeutic implications for preventive interventions.

Multi-level Hierarchical Complex Behavior Monitoring System for Dog Psychological Separation Anxiety Symptoms.

An increasing number of people own dogs due to the emotional benefits they bring to their owners. However, many owners are forced to leave their dogs at home alone, increasing the risk of developing psychological disorders such as separation anxiety, typically accompanied by complex behavioral symptoms including excessive vocalization and destructive behavior. Hence, this work proposes a multi-level hierarchical early detection system for psychological Separation Anxiety (SA) symptoms detection that automatically monitors home-alone dogs starting from the most fundamental postures, followed by atomic behaviors, and then detecting separation anxiety-related complex behaviors. Stacked Long Short-Term Memory (LSTM) is utilized at the lowest level to recognize postures using time-series data from wearable sensors. Then, the recognized postures are input into a Complex Event Processing (CEP) engine that relies on knowledge rules employing fuzzy logic (Fuzzy-CEP) for atomic behaviors level and higher complex behaviors level identification. The proposed method is evaluated utilizing data collected from eight dogs recruited based on clinical inclusion criteria. The experimental results show that our system achieves approximately an F1-score of 0.86, proving its efficiency in separation anxiety symptomatic complex behavior monitoring of a home-alone dog.

A Multi-level Longitudinal Model of Risk Factors for Generalized and Separation Anxiety Symptoms in a Community Sample of 6-year-olds.

The current longitudinal study examined the relations between variables in four domains-contextual (SES, family conflict, stress), parent (caretaker depression), parenting (support hostility, autonomy granting), and child (negative affect, effortful control, sensory regulation, attachment)-and both the presence of generalized and separation anxiety symptoms at age 6 in a community sample of 796 children and the change in these anxiety symptoms from ages 4 to 6. Anxiety was highly stable over time. Specific results revealed both direct and indirect pathways between age 4 and age 5 variables, and age 6 anxiety. Caretaker depression and the child variables of attachment, effortful control, negative affect, and sensory regulation were directly related to anxiety symptoms at age 6. Contextual variables (SES) at age 4 were indirectly related to age 6 anxiety through parent depression at age 5. Parent depression was indirectly related to age 6 anxiety through age 5 child negative affect. Child negative affect at age 4 was indirectly related to age 6 anxiety through age 5 effortful control and age 4 effortful control was indirectly related to age 6 anxiety through age 5 negative affect. With the exception of attachment, there was a reduction in the impact of other variables when initial levels of anxiety symptoms were included in the model. Implications of results for early intervention and further study are discussed.

Relationship Between Adult Separation Anxiety and Attachment Styles and Vaginismus.

BACKGROUND: Vaginismus has an unknown etiology, is comorbid with anxiety, and is the most common sexual dysfunction in sexual dysfunction outpatient clinics in Turkey. AIM: This study aimed to determine the frequency of adult separation anxiety disorder (ASAD) and styles of attachment in patients with vaginismus and to investigate its relationship with female sexual dysfunction. METHODS: Sixty women with vaginismus and 60 healthy controls were compared using the Relationship Scales Questionnaire, Female Sexual Function Index (FSFI), and Adult Separation Anxiety Questionnaire (ASA-27). OUTCOMES: We report the results of the questionnaires with their implication on the etiology of vaginismus. RESULTS: Separation anxiety and fearful and dismissive avoidance attachment style in the vaginismus group were significantly higher than in the control group. Both total FSFI scores and arousal, pain, and satisfaction subscale scores were higher in the control group. CLINICAL IMPLICATIONS: ASAD should be evaluated and addressed separately, when necessary, in the treatment of vaginismus. STRENGTHS & LIMITATIONS: The relationship between ASAD and vaginismus has been shown for the first time. Study limitations included the assessment of factors influencing the study results based on self-reporting and possible recall bias. CONCLUSION: Attachment and comorbidity research in vaginismus needs to shift from just reporting disturbances, to identify various clinical variables, such as the severity of the vaginismus, response to therapy, and differences in therapeutic modalities, in terms of outcome. Unlubilgin E, Tetik S, Aksoy I, et al. Relationship Between Adult Separation Anxiety and Attachment Styles and Vaginismus. J Sex Med 2021;18:1752-1758.

Separation anxiety disorder among outpatients with major depressive disorder: Prevalence and clinical correlates.

Prior studies have reported that separation anxiety disorder (SEPAD) can continue into or may begin in adulthood. Association of SEPAD with other psychiatric disorders has been frequently examined, and high rates of comorbidities have been found. The aim of this study was to investigate the prevalence and clinical correlation of SEPAD in adult patients undergoing treatment for major depressive disorder (MDD). The study sample was comprised of 100 outpatients. Participants underwent a DSM-5-based comprehensive assessment. Purposefully-designed semi-structured sociodemographic information and illness history forms were filled out by the researchers, and diagnoses of SEPAD were made using the Structured Clinical Interview for Separation Anxiety Symptoms, Separation Anxiety Symptom Inventory and Adult Separation Anxiety Survey. The frequency of SEPAD was 41% in patients with MDD, three-quarters of whom were adult onset. The use of new-generation antidepressants, adjunctive medications and comorbidity of other anxiety disorders were higher in patients with SEPAD (p < 0.05). SEPAD was highly prevalent, with a majority of cases starting in adulthood among patients with MDD, while SEPAD comorbidity was associated with high levels of anxiety and an increased likelihood of suboptimal response to usual depression treatment. Further studies are required to define the relevance and pathological basis for the comorbidity of SEPAD in people with MDD.

Parenting Stress Moderates the Relation between Parental Trauma Exposure and Child Anxiety Symptoms.

Trauma exposure can lead to poor psychological health not only for those directly affected, but also for their children. Additional research is needed to understand mechanisms in the intergenerational sequelae of traumatic stress. The current study examined parenting stress as a moderator of the association between parents' lifetime trauma exposure and school-aged children's internalizing symptoms (N = 139 dyads). Results of multiple regression analyses showed that the relationships between parental trauma exposure and child separation anxiety and harm avoidance were significant when parenting stress was moderate to high, but not when parenting stress was low. Parental trauma exposure was not significantly associated with child depressive symptoms. Clinical implications include the importance of screening and addressing parents' trauma exposure and parenting stress in the context of child and family mental health services. Further research is needed to explicate the mechanisms linking parents' trauma exposure with child anxiety symptoms.

Do Maternal Parenting Behaviors Indirectly Link Toddler Dysregulated Fear and Child Anxiety Symptoms?

Dysregulated fear (DF), display of high-fear in low-threat contexts, has been shown to predict child anxiety development. Maternal protective, comforting, and intrusive behaviors have also been linked to child anxiety development and may be candidate mechanisms linking DF to anxiety. First, the relation between DF (age 2) and child separation anxiety (age 4) as indirectly linked by maternal protective, comforting, and intrusive behaviors was investigated. Second, the relation between DF and social anxiety (age 4) through parenting behaviors was investigated. Results suggested DF significantly predicted child separation anxiety through maternal intrusive behaviors, above and beyond protective and comforting behaviors. Neither protective nor comforting parenting behavior served as indirect effects between DF and separation anxiety. No parenting behaviors were found to indirectly link the relation between DF and social anxiety. Results suggest that multiple parenting behaviors are involved as environmental mechanisms by which DF predicts separation anxiety.

Anxiety Symptoms Differ in Youth With and Without Tic Disorders.

We compared anxiety symptoms in youth with and without tic disorders by comparing scores on the Multidimensional Anxiety Scale for Children (MASC) in youth with tic disorders to those in a concurrent community control group and in a group of treatment-seeking anxious youth from the Child/Adolescent Anxiety Multimodal Study (CAMS). Data from 176 youth with tic disorders, 93 control subjects, and 488 CAMS participants were included. Compared to youth with tic disorders, controls had lower total MASC scores (p < 0.0001) and CAMS participants had similar total MASC scores (p = 0.13). Separation Anxiety (p = 0.0003) and Physical Symptom (p < 0.0001) subscale scores were higher in youth with tic disorders than in CAMS participants. We conclude that the anxiety symptom profile differs in youth with and without tic disorders, which may have important implications for targeting treatment of anxiety in youth with tic disorders.

Community-Based Prevalence of Externalizing and Internalizing Disorders among School-Aged Children and Adolescents in Four Geographically Dispersed School Districts in the United States.

The Project to Learn About Youth-Mental Health (PLAY-MH; 2014-2018) is a school-based, two-stage study designed to estimate the prevalence of selected mental disorders among K-12 students in four U.S.-based sites (Colorado, Florida, Ohio, and South Carolina). In Stage 1, teachers completed validated screeners to determine student risk status for externalizing or internalizing problems or tics; the percentage of students identified as being at high risk ranged from 17.8% to 34.4%. In Stage 2, parents completed a structured diagnostic interview to determine whether their child met criteria for fourteen externalizing or internalizing disorders; weighted prevalence estimates of meeting criteria for any disorder were similar in three sites (14.8%-17.8%) and higher in Ohio (33.3%). PLAY-MH produced point-in-time estimates of mental disorders in K-12 students, which may be used to supplement estimates from other modes of mental disorder surveillance and inform mental health screening and healthcare and educational services.

[Separation anxiety disorder]. / Trennungsangststörung.

In the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) separation anxiety disorder has been included in the chapter on anxiety disorders, thereby removing the age of onset restriction that previously required first onset during childhood or adolescence. Separation anxiety disorder has a lifetime prevalence of 4.8% and onset often occurs after the age of 18 years. Despite the high prevalence, separation anxiety disorder is often underdiagnosed and subsequently remains untreated. This narrative review summarizes the etiology, clinical features, diagnostic criteria as well as important differential diagnostic aspects, common comorbidity profiles and treatment implications of separation anxiety disorder. Furthermore, relevant implications for everyday practice and future perspectives for treatment and research are discussed.

[Preoperative video distraction alleviates separation anxiety and improves induction compliance of preschool children: a randomized controlled clinical trial].

Objective: To explore the effect of video distraction on preoperative separation anxiety and induction compliance of preschool children receiving strabismus surgery under general anesthesia. Methods: In this prospective trial, 80 children aged 3 to 6 years scheduled for strabismus surgery under inhalation anesthesia were randomly allocated to one of two groups, a control group and a video distraction group, with 40 cases in each group. Children in the video distraction group continuously watched videos from waiting in the holding area, separating with parents, entering the operating room and induction of anesthesia, while children in the control group didn't watch videos during the same process. The modified Yale Preoperative Anxiety Scale (mYPAS) of children were recorded upon arriving at the holding area(T1)and separating with parents(T2). Induction Compliance Checklist (ICC) score was recorded when the anesthesia induction was performed. The emergence time, the occurrence rate of adverse events in post-anesthesia care unit (PACU) including nausea and vomiting, laryngospasm, severe cough, hypoxemia and sinus bradycardia, incidence of postoperative adverse reactions such as pain, dizziness, nausea and vomiting and lethargy, the parents' satisfaction of anesthesia were also assessed. Results: There were no significant difference in mYPAS score and the proportion of mYPAS score>30 between 2 groups at T1 (all P>0.05). At T2, the mYPAS score and the proportion of mYPAS score>30 in video distraction group were (34.41±13.23) and 52.50%, which were lower than those in control group (50.64±20.96, 87.50%) with statistically significant difference (all P<0.05). The ICC score of video distraction group was lower than that of the control group, which was (1.83±2.26) vs (4.03±2.99), and the difference was statistically significant (P<0.05). The proportion of children with ICC score=0 in video distraction group was 37.50%, which was higher than that in the control group (12.50%), while the proportion of children with ICC score=4-10 was lower than that of the control group, which was 17.50% vs 45.00%, and the difference was statistically significant (P<0.05). No significant intergroup differences were observed in emergence time, incidence of adverse events in PACU, and incidence of postoperative adverse reactions (P>0.05). The parents' satisfaction of anesthesia in the video distraction group was (9.23±0.89), which was higher than that in the control group (8.63±1.23), with statistically significant (P<0.05). Conclusion: Preoperative video distraction alleviates separation anxiety, improves induction compliance of preschool children receiving strabismus surgery under general anesthesia, and increases the parents' satisfaction of anesthesia.

[Clara: from containment to the transformation of separation anxiety]. / De la contenance à la transformation de l'anxiété de séparation.

In the psychological care of separation disorders in child psychiatry, hospitalisation intervenes as a last resort, when care in an out-of-hospital structure but also in environments close to the child is no longer sufficient to contain his anxiety. A clinical example illustrates how nurses are led to position themselves and to think about care. It shows to what extent our containing functions can be an adapted response to the needs of the child in hospital.

Hypothalamus-pituitary-adrenal axis imbalance and inflammation contribute to sex differences in separation- and restraint-induced depression.

Whether social contact contributes to the underlying mechanisms of depression and the observed sex differences is unclear. In this study, we subjected young male and female mice to separation- and restraint-induced stress for 4 weeks and assessed behaviors, neurotransmitter levels, hormones, and inflammatory cytokines. Results showed that, compared with controls, male mice exposed to stress displayed significant decreases in body weight and sucrose preference after 1 week. In the fourth week, they exhibited a higher degree of anxiety (open field test) and depressive-like behavior (forced swim test). Moreover, the males showed significant decreases in monoamine neurotransmitters, including norepinephrine and dopamine in striatum, and an increase in pro-inflammatory cytokines, such as tumor necrosis factor α and interleukin 1ß in serum. In contrast, females showed persistent loss of weight during stress and displayed significant decreases in sucrose preference after stress. Importantly, the females but not males showed activation of the hypothalamus-pituitary-adrenal (HPA) axis, with significantly higher levels adrenocorticotropic hormone. Additionally, mRNA level of c-fos and AVP showed there was significant interaction between stress and sex. Finally, we conclude that an imbalance of the HPA axis and inflammation might be important contributors to sex differences in separation/restraint-induced depressive behavior and that changes might be mediated by c-fos and AVP.

Internet-delivered cognitive behavior therapy with minimal therapist support for anxious children and adolescents: predictors of response.

BACKGROUND: In general, Internet-delivered cognitive behavior therapy (iCBT) produces significant reductions in child and adolescent anxiety, but a proportion of participants continue to show clinical levels of anxiety after treatment. It is important to identify demographic, clinical, and family factors that predict who is most likely to benefit from iCBT in order to better tailor treatment to individual needs. METHODS: Participants were 175 young people (7-18 years) with an anxiety disorder, and at least one of their parents, who completed an iCBT intervention with minimal therapist support. Multilevel modeling (MLM) examined predictors of response to iCBT as measured by the slope for changes in the primary outcome measures of child- and parent-reported anxiety scores, from pretreatment, to 12-weeks, 6-month, and 12-month follow-ups, controlling for pretreatment total clinician severity ratings of all anxiety diagnoses. RESULTS: Child age, gender, father age, parental education, parental mental health, parenting style, and family adaptability and cohesion did not significantly predict changes in anxiety in the multivariate analyses. For child-reported anxiety, greater reductions were predicted by a separation anxiety disorder diagnosis (SEP) and elevated depression, with lower reductions predicted by poor couple relationship quality. For parent-reported child anxiety, greater reductions were predicted by higher pretreatment total CSRs, SEP, and lower family income, with lower reductions for children of older mothers. Irrespective of these predictors of change, children in general showed reductions in anxiety to within the normal range. CONCLUSIONS: Overall, children responded well to iCBT irrespective of the demographic, clinical, and family factors examined here. Poor couple relationship quality and older mother age were risk factors for less positive response to iCBT in terms of reductions in anxiety symptoms although still to within the normal range.

Separation anxiety in PTSD: A pilot study of mechanisms in patients undergoing IPT.

INTRODUCTION: Separation anxiety disorder (SAD) comprises one aspect of attachment dysregulation or insecurity. Although SAD aggravates posttraumatic stress disorder (PTSD) risk, no clinical research has tracked how many patients with PTSD have SAD, its clinical associations, or its response to PTSD treatment. Our open trial of interpersonal psychotherapy (IPT) for veterans with PTSD assessed these SAD domains. METHODS: Twenty-nine veterans diagnosed with chronic PTSD on the Clinician-Administered PTSD Scale were assessed for SAD using the Structured Clinical Interview for Separation Anxiety Symptoms (SCI-SAS), and for Symptom-Specific Reflective Function (SSRF), another dysregulated-attachment marker capturing patients' emotional understanding of their symptoms. Patients received 14 IPT sessions for PTSD with assessments at baseline, Week 4 (SCI-SAS and SSRF), and termination for SAD, PTSD, and depression. RESULTS: At baseline, 69% of patients met SAD criteria. Separation anxiety did not correlate with baseline PTSD severity, depressive severity, or age when traumatized; patients with and without SAD had comparable PTSD and depression severity. Patients with baseline comorbid SAD who completed IPT (N = 17) reported significantly improved adult separation anxiety (p = .009). Adult SAD improvements predicted depressive improvement (p = .049). Patients with SAD showed a stronger relationship between early SSRF gains and subsequent adult SAD improvement (p = .021) compared with patients without SAD. DISCUSSION: This first exploration of dysregulated/insecure attachment features among patients with PTSD found high SAD comorbidity and adult SAD improvement among patients with SAD following IPT. Highly impaired attachment patients normalized attachment posttreatment: 14-session IPT improved attachment dysregulation. This small study requires replication but begins to broaden clinical understanding of separation anxiety, attachment dysregulation, and PTSD.

Early rearing history influences oxytocin receptor epigenetic regulation in rhesus macaques.

Adaptations to stress can occur through epigenetic processes and may be a conduit for informing offspring of environmental challenge. We employed ChIP-sequencing for H3K4me3 to examine effects of early maternal deprivation (peer-rearing, PR) in archived rhesus macaque hippocampal samples (male, n = 13). Focusing on genes with roles in stress response and behavior, we assessed the effects of rearing on H3K4me3 binding by ANOVA. We found decreased H3K4me3 binding at genes critical to behavioral stress response, the most robust being the oxytocin receptor gene OXTR, for which we observed a corresponding decrease in RNA expression. Based on this finding, we performed behavioral analyses to determine whether a gain-of-function nonsynonymous OXTR SNP interacted with early stress to influence relevant behavioral stress reactivity phenotypes (n = 194), revealing that this SNP partially rescued the PR phenotype. PR infants exhibited higher levels of separation anxiety and arousal in response to social separation, but infants carrying the alternative OXTR allele did not exhibit as great a separation response. These data indicate that the oxytocin system is involved in social-separation response and suggest that epigenetic down-modulation of OXTR could contribute to behavioral differences observed in PR animals. Epigenetic changes at OXTR may represent predictive adaptive responses that could impart readiness to respond to environmental challenge or maintain proximity to a caregiver but also contribute to behavioral pathology. Our data also demonstrate that OXTR polymorphism can permit animals to partially overcome the detrimental effects of early maternal deprivation, which could have translational implications for human psychiatric disorders.