Behavioral and epigenetic consequences of oxytocin treatment at birth.

Oxytocin is used in approximately half of all births in the United States during labor induction and/or augmentation. However, the effects of maternal oxytocin administration on offspring development have not been fully characterized. Here, we used the socially monogamous prairie vole to examine the hypothesis that oxytocin exposure at birth can have long-term developmental consequences. Maternally administered oxytocin increased methylation of the oxytocin receptor (Oxtr) in the fetal brain. As adults, oxytocin-exposed voles were more gregarious, with increased alloparental caregiving toward pups and increased close social contact with other adults. Cross-fostering indicated that these effects were the result of direct action on the offspring, rather than indirect effects via postnatal changes in maternal behavior. Male oxytocin-exposed offspring had increased oxytocin receptor density and expression in the brain as adults. These results show that long-term effects of perinatal oxytocin may be mediated by an epigenetic mechanism

Effects of sex, menstrual cycle phase, and endogenous hormones on cognition in schizophrenia

In women with schizophrenia, cognition has been shown to be enhanced following administration of hormone therapy or oxytocin. We examined how natural hormonal changes across the menstrual cycle influence cognition in women with schizophrenia. We hypothesized that female patients would perform better on “female-dominant” tasks (verbal memory/fluency) and worse on “male-dominant” tasks (visuospatial) during the early follicular phase (low estradiol and progesterone) compared to midluteal phase (high estradiol and progesterone) in relation to estradiol but not progesterone

Reduced Levels of Vasopressin and Reduced Behavioral Modulation of Oxytocin in Psychotic Disorders

Oxytocin (OT) and arginine vasopressin (AVP) exert robust influence on social affiliation and specific cognitive processes in healthy individuals. Abnormalities in these neuroendocrine systems have been observed in psychotic disorders, but their relation to impairments in behavioral domains that these endocrines modulate is not well understood. We compared abnormalities of OT and AVP serum concentrations in probands with schizophrenia (n = 57), schizoaffective disorder (n = 34), and psychotic bipolar disorder (n = 75); their first-degree relatives without a history of psychosis (n = 61, 43, 91, respectively); and healthy controls (n = 66) and examined their association with emotion processing and cognition. AVP levels were lower in schizophrenia (P = .002) and bipolar probands (P = .03) and in relatives of schizophrenia probands (P = .002) compared with controls. OT levels did not differ between groups. Familiality estimates were robust for OT (h 2 = 0.79, P = 3.97e−15) and AVP (h 2 = 0.78, P = 3.93e−11). Higher levels of OT were associated with better emotion recognition (β = 0.40, P < .001) and general neuropsychological function (β = 0.26, P = .04) in healthy controls as expected but not in any proband or relative group. In schizophrenia, higher OT levels were related to greater positive symptom severity. The dissociation of OT levels and behavioral function in all proband and relative groups suggests that risk and illness factors associated with psychotic disorders are not related to reduced OT levels but to a disruption in the ability of physiological levels of OT to modulate social cognition and neuropsychological function. Decreased AVP levels may be a marker of biological vulnerability in schizophrenia because alterations were seen in probands and relatives, and familiality was high

Oxytocin and Vasopressin Are Dysregulated in Williams Syndrome, a Genetic Disorder Affecting Social Behavior

The molecular and neural mechanisms regulating human social-emotional behaviors are fundamentally important but largely unknown; unraveling these requires a genetic systems neuroscience analysis of human models. Williams Syndrome (WS), a condition caused by deletion of ∼28 genes, is associated with a gregarious personality, strong drive to approach strangers, difficult peer interactions, and attraction to music. WS provides a unique opportunity to identify endogenous human gene-behavior mechanisms. Social neuropeptides including oxytocin (OT) and arginine vasopressin (AVP) regulate reproductive and social behaviors in mammals, and we reasoned that these might mediate the features of WS. Here we established blood levels of OT and AVP in WS and controls at baseline, and at multiple timepoints following a positive emotional intervention (music), and a negative physical stressor (cold). We also related these levels to standardized indices of social behavior. Results revealed significantly higher median levels of OT in WS versus controls at baseline, with a less marked increase in AVP. Further, in WS, OT and AVP increased in response to music and to cold, with greater variability and an amplified peak release compared to controls. In WS, baseline OT but not AVP, was correlated positively with approach, but negatively with adaptive social behaviors. These results indicate that WS deleted genes perturb hypothalamic-pituitary release not only of OT but also of AVP, implicating more complex neuropeptide circuitry for WS features and providing evidence for their roles in endogenous regulation of human social behavior. The data suggest a possible biological basis for amygdalar involvement, for increased anxiety, and for the paradox of increased approach but poor social relationships in WS. They also offer insight for translating genetic and neuroendocrine knowledge into treatments for disorders of social behavior

Neuroendocrine and behavioural responses to exposure to an infant in male prairie voles.

Paternal behaviour and pair-bond formation are defining characteristics of social monogamy. However, in comparison to pair-bonding, the endocrine factors associated with the male care of young are not well studied. In the present study, plasma concentrations of oxytocin, vasopressin and corticosterone (CORT) were measured in reproductively naïve male prairie voles as a function of exposure to an infant or control manipulations (i.e. handling or exposure to a wooden dowel). Plasma oxytocin concentrations were transiently elevated within 10 min of pup exposure. Although plasma CORT concentration typically increases after handling, after 10 min of pup exposure, the concentration of plasma CORT was not increased, suggesting an attenuation of CORT release by pup exposure. Group differences in the concentrations of plasma hormones were no longer detected at 20 or 60 min after treatment. These patterns of rapid change in the concentrations of plasma oxytocin and CORT were observed in both juvenile and adult males but not detected after control procedures. Plasma vasopressin, assessed only in adult males, did not vary as a function of pup exposure or other manipulations. In the paraventricular nucleus of the hypothalamus, pup exposure also increased activation (as assessed by the measurement of c-Fos) of neurones that stained for either oxytocin or vasopressin, whereas it decreased c-Fos expression in neurones stained for corticotrophin-releasing hormone. In addition, brief pup exposure (20 min) facilitated subsequent partner preference formation when alloparental males and pup attackers were considered as a group. In the context of other studies, these data support the hypothesis that neuroendocrine changes associated with male alloparental behaviour are related to those implicated in pair-bonding

Neuroendocrine and behavioural responses to exposure to an infant in male prairie voles.

Paternal behaviour and pair-bond formation are defining characteristics of social monogamy. However, in comparison to pair-bonding, the endocrine factors associated with the male care of young are not well studied. In the present study, plasma concentrations of oxytocin, vasopressin and corticosterone (CORT) were measured in reproductively naïve male prairie voles as a function of exposure to an infant or control manipulations (i.e. handling or exposure to a wooden dowel). Plasma oxytocin concentrations were transiently elevated within 10 min of pup exposure. Although plasma CORT concentration typically increases after handling, after 10 min of pup exposure, the concentration of plasma CORT was not increased, suggesting an attenuation of CORT release by pup exposure. Group differences in the concentrations of plasma hormones were no longer detected at 20 or 60 min after treatment. These patterns of rapid change in the concentrations of plasma oxytocin and CORT were observed in both juvenile and adult males but not detected after control procedures. Plasma vasopressin, assessed only in adult males, did not vary as a function of pup exposure or other manipulations. In the paraventricular nucleus of the hypothalamus, pup exposure also increased activation (as assessed by the measurement of c-Fos) of neurones that stained for either oxytocin or vasopressin, whereas it decreased c-Fos expression in neurones stained for corticotrophin-releasing hormone. In addition, brief pup exposure (20 min) facilitated subsequent partner preference formation when alloparental males and pup attackers were considered as a group. In the context of other studies, these data support the hypothesis that neuroendocrine changes associated with male alloparental behaviour are related to those implicated in pair-bonding

Behavioral and epigenetic consequences of oxytocin treatment at birth.

Oxytocin is used in approximately half of all births in the United States during labor induction and/or augmentation. However, the effects of maternal oxytocin administration on offspring development have not been fully characterized. Here, we used the socially monogamous prairie vole to examine the hypothesis that oxytocin exposure at birth can have long-term developmental consequences. Maternally administered oxytocin increased methylation of the oxytocin receptor (Oxtr) in the fetal brain. As adults, oxytocin-exposed voles were more gregarious, with increased alloparental caregiving toward pups and increased close social contact with other adults. Cross-fostering indicated that these effects were the result of direct action on the offspring, rather than indirect effects via postnatal changes in maternal behavior. Male oxytocin-exposed offspring had increased oxytocin receptor density and expression in the brain as adults. These results show that long-term effects of perinatal oxytocin may be mediated by an epigenetic mechanism