Higher adaptive functioning and lower rate of psychotic comorbidity in married versus unmarried individuals with 22q11.2 deletion syndrome.

22q11.2 deletion syndrome (22q11.2DS) is a relatively common genetic disorder. Due to improvement in pediatric care, affected individuals live into adulthood, some of whom marry or have committed relationships, and reproduce. The current study aimed to identify the factors that discriminate between married and unmarried adults with 22q11.2DS. In the presents study, 90 adults with 22q11.2DS (48 men/42 women), aged 29.8 ± 10.3 years, were included in the analysis. Psychiatric comorbidities, IQ score, and adaptive functioning were assessed using gold-standard diagnostic tools. Demographic factors, marital status, and reproductive status were evaluated by self-reports. Of the sample 25 adults (27.7%) were married and 14 (56%) of those had children. Married, as compared to unmarried individuals, were older, had less psychotic comorbidities, showed higher adaptive functioning in all domains of the Vineland Adaptive Behavior Scale, and had higher rates of independent living and sustained employment. Unexpectedly, married individuals showed higher rates of mood disorders and full scale IQ scores did not discriminate between the groups. We propose that multiple factors are associated with marital status among individuals with 22q11.2DS. Identification of key personal, functional, and social characteristics of those who married and reproduced may help counseling health professionals and clinicians in advising affected individuals and their families.

Psychiatric and cognitive characteristics of individuals with Danon disease (LAMP2 gene mutation).

Danon disease (DD) is a rare X-linked disorder caused by loss-of-function mutations in the LAMP2 gene, which encodes lysosome-associated membrane protein. It is characterized by the triad of hypertrophic cardiomyopathy, myopathy, and intellectual disability. Whereas the molecular and pathophysiological mechanisms underlying this disorder have been previously reported and continue to be explored, the cognitive deficits and psychiatric comorbidities manifested in DD remain an understudied topic. We systematically assessed cognitive abilities and psychiatric comorbidities in 13 males and females. Most of the participants in our cohort (n = 9; 75%) had an IQ score within the normal range, while only one participant had intellectual disability. Participants' performance on the Cognitive Neuropsychiatric Battery (CNB) showed only mildly impaired cognitive abilities in most modules, except in the executive functioning test, which was low compared to healthy controls. Of note, 69% of the participants met criteria for at least one psychiatric disorder, mainly mood and anxiety disorders, occurring alone or in combination in the same patient. The results of the present study challenge earlier reports suggesting that mental retardation is a core constituent in DD. Of importance, it underscores the need to refer Danon patients to psychiatric assessment.

Oxytocin selectively modulates brain response to stimuli probing social synchrony.

The capacity to act collectively within groups has led to the survival and thriving of Homo sapiens. A central group collaboration mechanism is "social synchrony," the coordination of behavior during joint action among affiliative members, which intensifies under threat. Here, we tested brain response to vignettes depicting social synchrony among combat veterans trained for coordinated action and following life-threatening group experience, versus controls, as modulated by oxytocin (OT), a neuropeptide supporting social synchrony. Using a randomized, double-blind, within-subject design, 40 combat-trained and control male veterans underwent magnetoencephalography (MEG) twice following OT/placebo administration while viewing two social vignettes rated as highly synchronous: pleasant male social gathering and coordinated unit during combat. Both vignettes activated a wide response across the social brain in the alpha band; the combat scene triggered stronger activations. Importantly, OT effects were modulated by prior experience. Among combat veterans, OT attenuated the increased response to combat stimuli in the posterior superior temporal sulcus (pSTS) - a hub of social perception, action observation, and mentalizing - and enhanced activation in the inferior parietal lobule (IPL) to the pleasant social scene. Among controls, OT enhanced inferior frontal gyrus (IFG) response to combat cues, demonstrating selective OT effects on mirror-neuron and mentalizing networks. OT-enhanced mirror network activity was dampened in veterans reporting higher posttraumatic symptoms. Results demonstrate that the social brain responds online, via modulation of alpha rhythms, to stimuli probing social synchrony, particularly those involving threat to survival, and OT's enhancing versus anxiolytic effects are sensitive to salient experiences within social groups.

Prior exposure to extreme pain alters neural response to pain in others.

In the extant literature examining the brain mechanisms implicated in pain perception, researchers have theorized that the overlapping responses to pain in the self and in others mark the human capacity for empathy. Here we investigated how prior exposure to extreme pain affects pain perception, by assessing the dynamics of pain processing in veterans who were previously exposed to severe injury. Forty-three participants (28 pain-exposed and 15 controls) underwent whole-head magnetoencephalography (MEG) while viewing photographs of limbs in painful and nonpainful (neutral) conditions. Among controls, an early (0-220 ms) "pain effect" in the posterior cingulate and sensorimotor cortices, and a later (760-900 ms) "pain effect" in the posterior cingulate cortex, superior temporal gyrus/insula, and fusiform gyrus were found, indicated by enhanced alpha suppression to the pain versus nonpain conditions. Importantly, pain-exposed participants exhibited an atypical pain response in the posterior cingulate cortex, indicated by a normative response to pain, but no pain-to-no-pain differentiation. This may suggest that individuals exposed to extreme pain may perceive neutral stimuli as potentially threatening. Our findings demonstrate alterations in pain perception following extreme pain exposure, chart the sequence from automatic to evaluative pain processing, and emphasize the importance of considering past experiences in studying the neural response to others' states.

Oxytocin shapes parental motion during father-infant interaction.

An infant-oriented parental repertoire contributes to an infant's development and well-being. The role of oxytocin (OT) in promoting affiliative bonds and parenting has been established in numerous animal and human studies. Recently, acute administration of OT to a parent was found to enhance the carer's, but at the same time also the infant's, physiological and behavioural readiness for dyadic social engagement. Yet, the exact cues that are involved in this affiliative transmission process remain unclear. The existing literature suggests that motion and vocalization are key social signals for the offspring that facilitates social participation, and that distance and motion perception are modulated by OT in humans. Here, we employed a computational method on video vignettes of human parent-infant interaction including 32 fathers that were administered OT or a placebo in a crossover experimental design. Results indicate that OT modulates parental proximity to the infant, as well as the father's head speed and head acceleration but not the father's vocalization during dyadic interaction. Similarly, the infant's OT reactivity is positively correlated with father's head acceleration. The current findings are the first to report a relationship between the OT system and parental motion characteristics, further suggesting that the cross-generation transmission of parenting in humans might be underlaid by nuanced, infant-oriented, gestures relating to the carer's proximity, speed and acceleration within the dyadic context.

The experience of labor, maternal perception of the infant, and the mother's postpartum mood in a low-risk community cohort.

Postpartum negative mood interferes with maternal-infant bonding and carries long-term negative consequences for infant growth. We examined the effects of birth-related risks on mother's postpartum anxiety and depression. A community cohort of 1,844 low-risk women who delivered a singleton term baby completed measures assessing delivery, emotions during labor, attitudes toward pregnancy and infant, mood regulation, and postpartum anxiety and depression. Under conditions of low risk, 20.5% of parturient women reported high levels of depressive symptoms. Following Cesarean Section Delivery (CSD), 23% reported high depressive symptoms, compared to 19% following Vaginal Delivery (VGD), and 21% after Assisted Vaginal Delivery (AVGD). State anxiety was highest in CSD and lowest in VGD. Mothers undergoing CSD experienced labor as most negative, reported highest somatic symptoms during the last trimester, and were least efficient in regulating negative mood. Postpartum depression was independently associated with higher maternal age, CSD, labor pain, lower negative and higher positive emotions during labor, inefficient mood regulation, somatic symptoms, and more negative and less positive perception of fetus during last trimester. Results demonstrate that elevated depressive symptoms are prevalent in the postpartum even under optimal socioeconomic and health conditions and increase following CSD. Interventions to increase positive infant-related perceptions and emotions may be especially important for promoting bond formation following CSD.

Genetic and peripheral markers of the oxytocin system and parental care jointly support the cross-generational transmission of bonding across three generations.

BACKGROUND: Human and animal research indicates that oxytocin (OT) plays a key role in the cross-generational transmission of parental bonding, and human studies suggest that allelic variations on the oxytocin receptor gene (OXTR) and circulating OT levels interact with patterns of parental care to shape children's social-affiliative competencies. Yet, no study to date has tested the joint contribution of OT and parental care across three generations. METHODS: The study included 345 participants comprising 115 family lines of grandmothers, mothers, and their infants. Salivary OT and allelic variations on the OXTR (rs53576 and rs2254298) and CD38 (rs3796863) single nucleotide polymorphisms (SNPs), which have been previously associated with parental bonding, were assessed in all participants. Parental care was measured from grandmothers to mothers and from mothers to their infants. RESULTS: Mothers receiving parenting characterized by high overprotection from grandmothers showed more rejection toward their infants only when carrying the G allele on the OXTRrs53576 (AG/GG). These mothers of highly overprotective grandmothers also had lower oxytocin levels. Infants who were OXTRrs2254298 A carriers (AA/AG) and whose mothers reported more rejection toward their infants had higher oxytocin levels. Grandmothers receiving higher overprotection from great-grandmothers showed poorer parenting style compared to grandmothers experiencing lower parental overprotection only when carrying the OXTRrs2254298 GG genotype. CONCLUSIONS: Our findings are the first to demonstrate how genetic and peripheral markers on the oxytocin system interact with experienced parenting to shape bonding across three generations. Results have important implications for specifying the biological and behavioral determinants associated with the continuity of adaptive versus maladaptive patterns of attachment across generations.

Testing the Efficacy of a Smartphone Application in Improving Medication Adherence, Among Children with ADHD.

BACKGROUND: Adherence to medication is a key factor for successful treatment of children with ADHD. However, most children do not adhere to their pharmacotherapy regimen, and have no contact with their physician during the first month of pharmacotherapy. A mobile health (mHealth) approach may bridge the gap between physicians and patients, allowing for more frequent communications as well as better monitoring of adherence to the prescribed treatment. METHOD: The study sample included 39 children with ADHD (27 boys), aged 9.56±2.41 years. Participants were randomly assigned to one of the following two groups: (1) a study group in which participants and their parents were prompted to use a mobile application (i.e., mobile app or app); or to (2) a control group in which participants were treated as usual, without the app. Pill counts, which is a common strategy for confirming medication adherence, was recorded at week 4 and week 8. Clinical assessment conducted at baseline, week 4, and week 8. RESULTS: Participants who were prescribed with the app demonstrated higher overall pill counts over 8-weeks period, F=4.33, p<.05. In addition, a significant improvement in total CRS score was found among the study group compared to controls in week 4 and week 8, F=4.74, p<.05. CONCLUSIONS: The current study provides initial support for the feasibility of a new mobile app in promoting adherence to stimulants among youth with ADHD.

Elevated Proinflammatory Markers in 22q11.2 Deletion Syndrome Are Associated With Psychosis and Cognitive Deficits.

OBJECTIVE: 22q11.2 deletion syndrome (22q11.2DS) is a neurogenetic disorder whose phenotype includes high rates of a schizophrenia-like psychotic disorder and immune system abnormalities. Thus, 22q11.2DS is an ideal model for studying the relationship between psychosis and inflammation. The aim of the present study was to identify inflammatory markers that may play a role in the pathophysiologic pathways associated with psychosis and cognitive deficits in 22q11.2DS. METHODS: Forty-nine individuals with 22q11.2DS (13 with psychotic disorders according to DSM-IV criteria and 36 without psychotic disorders) and 30 age- and sex-matched healthy controls underwent psychiatric and cognitive assessments at an outpatient clinic. Blood samples from all participants were analyzed for C-reactive protein (CRP), interleukin (IL)-6, IL-10, tumor necrosis factor alpha (TNFα), and IL-1 receptor antagonist levels. The study was conducted between August 2014 and September 2015. RESULTS: The 22q11.2DS participants had elevated levels of CRP (P = .004), IL-6 (P = .001), TNFα (P < .001), and IL-10 (P = .028) compared with controls. Furthermore, the psychotic 22q11.2DS participants had higher levels of IL-6 (P < .001) and IL-6/IL-10 ratio (used as an indicator for proinflammatory activation, P < .001) compared with the nonpsychotic 22q11.2DS individuals and controls. IL-6 levels and the IL-6/IL-10 ratio correlated with the severity of the cognitive deficits in the 22q11.2DS participants. CONCLUSIONS: Our preliminary findings indicate an involvement of inflammatory processes in the pathophysiology of psychosis and cognitive deficits in 22q11.2DS and are in line with the accumulating evidence for the role of neuroinflammation in nonsyndromic schizophrenia.

Negative subthreshold psychotic symptoms distinguish 22q11.2 deletion syndrome from other neurodevelopmental disorders: A two-site study.

About one third of individuals with 22q11.2 deletion syndrome (22q11.2DS) develop schizophrenia. Notably, a full-blown psychotic disorder is usually preceded by subthreshold symptoms. Therefore, it is important to identify early signs of psychosis in this population, a task that is complicated by the intellectual disabilities typically seen in 22q11.2DS. We aimed to identify subthreshold psychotic symptoms that distinguish 22q11.2DS from other neurodevelopmental disorders. The study included two independent cohorts from Tel Aviv and Philadelphia. 22q11.2DS (N=171) and typically developing (TD; N=832) individuals were enrolled at both sites and further compared to two groups with intellectual disabilities: Williams syndrome (WS; N=21) in the Tel Aviv cohort and idiopathic developmental disabilities (IDD; N=129) in the Philadelphia cohort. Participants and their primary caregivers were interviewed with the Structured Interview for Prodromal Symptoms (SIPS) and psychopathologies were assessed using standardized tools; general cognitive abilities were assessed with the Computerized Neurocognitive Battery. Negative/disorganized subthreshold syndrome was significantly more common in the 22q11.2DS group than in the WS (OR=3.90, 95% CI=1.34-11.34) or IDD (OR=5.05, 95% CI=3.01-10.08) groups. The 22q11.2DS group had higher scores than the two intellectual disabilities groups on several SIPS negative items, including avolition and decreased expression of emotion. Overall, there were few significant correlations between level of cognitive deficits and severity of negative symptoms in 22q11.2DS and only in the Tel Aviv cohort. Our findings suggest that 22q11.2DS individuals at the age of risk for developing psychosis should be closely monitored for negative symptoms.

Subthreshold Psychosis in 22q11.2 Deletion Syndrome: Multisite Naturalistic Study.

Nearly one-third of individuals with 22q11.2 deletion syndrome (22q11.2DS) develop a psychotic disorder during life, most of them by early adulthood. Importantly, a full-blown psychotic episode is usually preceded by subthreshold symptoms. In the current study, 760 participants (aged 6-55 years) with a confirmed hemizygous 22q11.2 microdeletion have been recruited through 10 medical sites worldwide, as part of an international research consortium. Of them, 692 were nonpsychotic and with complete measurement data. Subthreshold psychotic symptoms were assessed using the Structured Interview for Prodromal Syndromes (SIPS). Nearly one-third of participants met criteria for positive subthreshold psychotic symptoms (32.8%), less than 1% qualified for acute positive subthreshold symptoms, and almost a quarter met criteria for negative/disorganized subthreshold symptoms (21.7%). Adolescents and young adults (13-25 years) showed the highest rates of subthreshold psychotic symptoms. Additionally, higher rates of anxiety disorders and attention deficit/hyperactivity disorder (ADHD) were found among the study participants with subthreshold psychotic symptoms compared to those without. Full-scale IQ, verbal IQ, and global functioning (GAF) scores were negatively associated with participants' subthreshold psychotic symptoms. This study represents the most comprehensive analysis reported to date on subthreshold psychosis in 22q11.2DS. Novel findings include age-related changes in subthreshold psychotic symptoms and evidence that cognitive deficits are associated with subthreshold psychosis in this population. Future studies should longitudinally follow these symptoms to detect whether and how early identification and treatment of these manifestations can improve long-term outcomes in those that eventually develop a psychotic disorder.

Mother-Child Interaction as a Window to a Unique Social Phenotype in 22q11.2 Deletion Syndrome and in Williams Syndrome.

Mother-child interactions in 22q11.2 Deletion syndrome (22q11.2DS) and Williams syndrome (WS) were coded for maternal sensitivity/intrusiveness, child's expression of affect, levels of engagement, and dyadic reciprocity. WS children were found to express more positive emotions towards their mothers compared to 22q11.2DS children and those with developmental delay in a conflict interaction. During the same interaction, dyads of 22q11.2DS children were characterized by higher levels of maternal intrusiveness, lower levels of child's engagement and reduced reciprocity compared to dyads of typically developing children. Finally, 22q11.2DS children with the COMT Met allele showed less adaptive behaviors than children with the Val allele. Dyadic behaviors partially coincided with the distinct social phenotypes in these syndromes and are potential behavioral markers of psychopathological trajectory.

Oxytocin affects spontaneous neural oscillations in trauma-exposed war veterans.

Exposure to combat-related trauma often leads to lifetime functional impairments. Previous research demonstrated the effects of oxytocin (OT) administration on brain regions implicated in post-traumatic stress disorder (PTSD); yet OT's effects on brain patterns in trauma-exposed veterans have not been studied. In the current study the effects of OT on spontaneous brain oscillatory activity were measured in 43 veterans using magnetoencephalography (MEG): 28 veterans who were exposed to a combat-related trauma and 15 trauma-unexposed controls. Participants participated in two experimental sessions and were administered OT or placebo (PBO) in a double-blind, placebo-control, within-subject design. Following OT/PBO administration, participants underwent a whole-head MEG scan. Plasma and salivary OT levels were assessed each session. Spontaneous brain activity measured during a 2-min resting period was subjected to source-localization analysis. Trauma-exposed veterans showed higher resting-state alpha (8-13 Hz) activity compared to controls in the left dorsolateral prefrontal cortex (dlPFC), specifically in the superior frontal gyrus (SFG) and the middle frontal gyrus (MFG), indicating decreased neural activity in these regions. The higher alpha activity was "normalized" following OT administration and under OT, group differences were no longer found. Increased resting-state alpha was associated with lower baseline plasma OT, reduced salivary OT reactivity, and more re-experiencing symptoms. These findings demonstrate effects of OT on resting-state brain functioning in prefrontal regions subserving working memory and cognitive control, which are disrupted in PTSD. Results raise the possibility that OT, traditionally studied in social contexts, may also enhance performance in cognitive tasks associated with working memory and cognitive control following trauma exposure.

The association between 2D:4D ratio and cognitive empathy is contingent on a common polymorphism in the oxytocin receptor gene (OXTR rs53576).

Both testosterone and oxytocin influence an individual's accuracy in inferring another's feelings and emotions. Fetal testosterone, and the second-to-forth digit ratio (2D:4D) as its proxy, plays a role in social cognitive development, often by attenuating socio-affective skill. Conversely, oxytocin generally facilitates socio-affiliative and empathic cognition and behavior. A common polymorphism in the oxytocin receptor gene, OXTR rs53576, has been repeatedly linked with psychosocial competence, including empathy, with individuals homozygous for the G allele typically characterized by enhanced socio-cognitive skills compared to A allele carriers. We examined the role of oxytocin and testosterone in collectively contributing to individual differences in cognitive empathy as measured by Baron-Cohen's "Reading the Mind in the Eyes" task (RMET). Findings are based on a large cohort of male and female students (N=1463) of Han Chinese ethnicity. In line with existing literature, women outperformed men in the RMET. Men showed significantly lower 2D:4D ratio compared to women, indicating higher exposure to testosterone during the prenatal period. Interestingly, variation in the OXTR gene was found to interact with 2D:4D to predict men's (but not women's) RMET performance. Among men with GG allelic variation, those with low fetal testosterone performed better on the RMET, compared to men with GG and high fetal testosterone, suggesting greater identification of another's emotional state. Taken together, our data lend unique support to the mutual influence of the oxytocin and testosterone systems in shaping core aspect of human social cognition early in development, further suggesting that this effect is gender-specific.

Oxytocin-augmented labor and risk for autism in males.

The use of synthetic oxytocin (OT) to induce and/or augment labor and delivery is on the rise. Maternal exposure to OT during birth may have adverse effects on the infant's development, including increased risk for autism. Yet, studies that test this biologically plausible association and whether it is modified by sex are limited and show inconsistent findings. To this end, we conducted an epidemiological analysis, including all singleton live births in Denmark between 2000 and 2009 (N = 557,040), with a follow-up through 2012. A total of 2110 children in this cohort were subsequently diagnosed with autistic disorder according to the ICD-10-DCR. Augmentation of labor with OT was modestly associated with an increased risk for autism in males (HR 1.13; 95% CI, 1.00-1.26; P = 0.04), but not in females (0.99; 0.77-1.27; P=0.95). Among males exposed to OT augmentation, 560 were subsequently diagnosed with autistic disorder, and among those not exposed, 1177 met criteria for autism (incidence rate 103.2 and 81.4 per 100,000 person-years, respectively). Our findings suggest a modest association between OT-augmented labor and risk for autism in males. However, given the known benefits of using synthetic OT during labor and delivery caution is warranted when interpreting the findings. Future studies should also investigate dose-dependent effect of OT on infant's development.

Oxytocin administration, salivary testosterone, and father-infant social behavior.

The growing involvement of fathers in childcare is followed by an increased interest in the neurobiology of fatherhood; yet, experimental work on the neuroendocrine basis of paternal care in humans is limited. The steroid Testosterone (T) and the neuropeptide Oxytocin (OT) have each been implicated in complex social behavior including parenting. However, no study to date explored the interaction between these two hormones in the context of fathering. In the current study we first test the relationship between father's basal salivary T and father and infant's social behaviors during parent-child interaction. Second, we examine the effects of intranasal OT administration on father's T production, and, finally, address the relations between OT-induced change in father's T with father-infant social behavior. Thirty-five fathers and their infants participated in a double-blind, placebo-controlled, within-subject study. Father-infant interaction was micro-coded for paternal and infant social behavior and synchrony was measured as the coordination between their gaze, affect, and vocalizations. Father's salivary T levels were measured at baseline and three times after administration. Results indicate that lower baseline T correlated with more optimal father and infant's behaviors. OT administration altered T production in fathers, relative to the pattern of T in the placebo condition. Finally, OT-induced change in T levels correlated with parent-child social behaviors, including positive affect, social gaze, touch, and vocal synchrony. Findings support the view that neuroendocrine systems in human males evolved to support committed parenting and are the first to describe the dynamic interactions between OT and T within a bio-behavioral synchrony model.

Oxytocin administration alters HPA reactivity in the context of parent-infant interaction.

The neuropeptide oxytocin (OT) and the steroid cortisol (CT) have each been implicated in complex social behavior, including parenting, and one mechanism by which OT is thought to exert its pro-social effects is by attenuating hypothalamic-pituitary-adrenal (HPA) response to stress. Yet, no study to date has tested whether OT functions to reduce CT production in the context of the parent-infant attachment. In the current study, we examined the effects of intranasal OT administered to the parent on parent's and infant's CT levels following parent-child interaction that included a social stressor. Utilizing a double-blind, placebo-controlled, within-subject design, 35 fathers and their 5-month-old infants were observed in a face-to-face-still-face paradigm twice, one week apart. Interactions were micro-coded for social synchrony, and salivary CT were repeatedly assessed from parent and child. Results showed that OT increased fathers' overall CT response to the stress paradigm. Furthermore, OT altered infants' physiological and behavioral response as a function of parent-infant synchrony. Among infants experiencing high parent-infant synchrony, OT elevated infant HPA reactivity and increased infant social gaze to the father while father maintained a still-face. On the other hand, among infants experiencing low social synchrony, parental OT reduced the infant's stress response and diminished social gaze toward the unavailable father. Results are consistent with the "social salience" hypothesis and highlight that OT effects on human social functioning are not uniform and depend on the individual's attachment history and social skills. Our findings call to further investigate the effects of OT administration within developmental contexts, particularly the parent-infant relationship.

Salivary vasopressin increases following intranasal oxytocin administration.

Extant research has documented the effects of intranasal administration of oxytocin (OT), and to a lesser degree Arginine Vasopressin (AVP) - two structurally-related neuropeptides - on brain and behaviour, yet the effects of exogenous manipulation of one on circulating levels of the other remain unknown. Studies have shown that OT administration impacts the peripheral levels of numerous hormones; however, whether OT administration also increases AVP concentrations has not been explored. Utilizing a double-blind placebo-controlled within-subject design, ten male and female subjects provided ten saliva samples over four consecutive hours: at baseline and nine times following OT administration. Results indicate that salivary AVP increased in the first hour following OT manipulation (OT condition: mean AVP=2.17 pg/ml, SE=28, placebo condition: mean AVP=1.42 pg/ml, SE=.18) but returned to baseline levels at the next assessment (80 min) and remained low for the remaining period. Similar to OT, AVP showed high degree of individual stability and baseline levels of AVP correlated with AVP concentrations at the first and second post-administration hours regardless of drug condition (Pearson r=.85-.93). Validity of salivary AVP ELISA measurement was verified by demonstrating individual stability of salivary AVP over a six-month period (r=.70, p<.000) as well correlation with plasma levels over the same period (r=.32, p=.037) in a sample of 45 young adults who did not participate in the current study. Overall, findings suggest a potential crosstalk between OT and AVP and indicate that baseline levels of the two neuropeptides may shape the degree to which these systems respond to exogenous manipulation.

Plasma oxytocin distributions in a large cohort of women and men and their gender-specific associations with anxiety.

Research has consistently addressed the relations between plasma oxytocin (OT) - a nonapeptide implicated in mammalian social bonding - and psychological distress, but the direction of the association remains unclear. Utilizing the largest sample of plasma OT to date (N=473), the current study had two goals. First, we described the distributions of plasma OT in women and men, and second, we examined whether the relations between OT and two types of anxiety - trait and attachment anxiety - are moderated by gender. Results indicated that OT values (M=375.78 pg/ml, SD=264.03, range=51.40-2752.30) clustered around the mean with a long right tail, indicating trend toward high values. In most participants (N=323), OT was measured again six months after initial assessment and OT levels were highly stable within individuals. After removing outliers 2.5 SD above the mean (≥1098 pg/ml for men and ≥988 pg/ml for women), men showed significantly higher mean OT than women (women: 327.13 pg/ml, SD=164.43; men: 399.91, SD=183.65; t=2.57, p=.01). Gender was found to moderate the relations between OT and anxiety. Trait anxiety was lower among men with higher OT but no such links emerged for women, supporting the hypothesized anxiolytic effects of OT in males only. Furthermore, women with extreme values (≥988 pg/ml) had three times the probability of being classified as highly anxious (STAI-T≥45). Higher OT in women correlated with greater attachment anxiety, but no such relationships were found for men. Results are consistent with models on the differential associations between the neurobiology of attachment and the experience of anxiety in women and men.