Hossein Pournajafi-Nazarloo

Oxytocin in pregnancy and the postpartum: relations to labor and its management

The purpose of this study was to examine variations in endogenous oxytocin levels in pregnancy and postpartum state. We also explored the associations between delivery variables and oxytocin levels. A final sample of 272 mothers in their first trimester of pregnancy was included for the study. Blood samples were drawn during the first trimester and third trimester of pregnancy and at 8u2009weeks postpartum. Socio-demographic data were collected at each time point and medical files were consulted for delivery details. In most women, levels of circulating oxytocin increased from the first to third trimester of pregnancy followed by a decrease in the postpartum period. Oxytocin levels varied considerably between individuals, ranging from 50u2009pg/mL to over 2000u2009pg/mL. Parity was the main predictor of oxytocin levels in the third trimester of pregnancy and of oxytocin level changes from the first to the third trimester of pregnancy. Oxytocin levels in the third trimester of pregnancy predicted a self-reported negative labor experience and increased the chances of having an epidural. Intrapartum exogenous oxytocin was positively associated with levels of oxytocin during the postpartum period. Our exploratory results suggest that circulating oxytocin levels during the third trimester of pregnancy may predict the type of labor a woman will experience. More importantly, the quantity of intrapartum exogenous oxytocin administered during labor predicted plasma oxytocin levels 2u2009months postpartum, suggesting a possible long-term effect of this routine intervention, the consequences of which are largely unknown.

Detection of salivary oxytocin levels in lactating women.

Oxytocin is a neuropeptide with widespread influence on many physiological and social functions including: labor and birth, lactation, sexual behavior, nurturing maternal behaviors, and stress reduction. However, our understanding of oxytocins roles has been hampered by lack of noninvasive methods for assessing oxytocin levels. The goal of the present study was to assess whether oxytocin could be detected in saliva and whether changes occurred in the pattern of oxytocin release among lactating women from before, at initiation and after breast feeding. Using a prospective repeated measures design, 11 research participants each provided 18 saliva samples during three feeding cycles (before, at initiation and after breast feeding) for two 24-hr data collection periods (Days 1 and 2). Within each day, saliva was collected at late evening, early morning, and late morning. Salivary samples were concentrated fourfold by dehydration prior to analysis and oxytocin was measured in saliva using an enzyme immunoassay (EIA). Salivary oxytocin values, when reconverted to their original levels, ranged from 6.44 to 61.05 pg/ml. Oxytocin values in saliva varied significantly as a function of the breast feeding cycle, but did not show reliable differences as a function of the time of feeding. Oxytocin was highest before feeding, followed by a decrease at initiation of feeding, and an increase at 30 min after feeding. The findings suggest that oxytocin release into saliva increases in anticipation of feedings. This study also supports the potential usefulness of salivary measures of oxytocin as a noninvasive index of changes in this peptide.

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.

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.

Plasma oxytocin explains individual differences in neural substrates of social perception.

The neuropeptide oxytocin plays a critical role in social cognition and behavior. A number of studies using intranasal administration have demonstrated that oxytocin improves social perception. However, little is known about the relationship between individual differences in endogenous levels of oxytocin and social cognition. In the current study, we assessed the relationship between endogenous oxytocin and brain activity during an animacy perception paradigm. Thirty-seven male participants underwent scanning and provided a blood sample for oxytocin analysis. In line with previous research, perception of animacy was associated with activations in superior temporal sulcus, inferior frontal gyrus, and medial prefrontal cortex (mPFC). Notably, participants’ levels of plasma oxytocin robustly predicted activation in areas critical for social cognitive processes, such that higher oxytocin levels were related to increased activity in dorsal mPFC, ventral mPFC, dorsolateral PFC, superior temporal gyrus, and temporoparietal junction (TPJ), suggesting differential processing of social stimuli. Together these results show that stable variations in endogenous oxytocin levels explain individual differences in social perception.

Autonomic Substrates of the Response to Pups in Male Prairie Voles

Caregiving by nonparents (alloparenting) and fathers is a defining aspect of human social behavior, yet this phenomenon is rare among mammals. Male prairie voles (Microtus ochrogaster) spontaneously exhibit high levels of alloparental care, even in the absence of reproductive experience. In previous studies, exposure to a pup was selectively associated with increased activity in oxytocin and vasopressin neurons along with decreased plasma corticosterone. In the present study, physiological, pharmacological and neuroanatomical methods were used to explore the autonomic and behavioral consequences of exposing male prairie voles to a pup. Reproductively naïve, adult male prairie voles were implanted with radiotransmitters used for recording ECG, temperature and activity. Males responded with a sustained increase in heart-rate during pup exposure. This prolonged increase in heart rate was not explained by novelty, locomotion or thermoregulation. Although heart rate was elevated during pup exposure, respiratory sinus arrhythmia (RSA) did not differ between these males and males exposed to control stimuli indicating that vagal inhibition of the heart was maintained. Blockade of beta-adrenergic receptors with atenolol abolished the pup-induced heart rate increase, implicating sympathetic activity in the pup-induced increase in heart rate. Blockade of vagal input to the heart delayed the males’ approach to the pup. Increased activity in brainstem autonomic regulatory nuclei was also observed in males exposed to pups. Together, these findings suggest that exposure to a pup activates both vagal and sympathetic systems. This unique physiological state (i.e. increased sympathetic excitation of the heart, while maintaining some vagal cardiac tone) associated with male caregiving behavior may allow males to both nurture and protect infants.

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

BACKGROUNDnIn 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 worse on female-dominant tasks (verbal memory/fluency) and better 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.nnnMETHODSnFifty-four women (23 with schizophrenia) completed cognitive assessments and provided blood for sex steroid assays and oxytocin at early follicular (days 2-4) and midluteal (days 20-22) phases. Men were included to verify the expected pattern of sex differences on cognitive tests.nnnRESULTSnExpected sex differences were observed on female-dominant and male-dominant tasks (p<0.001), but the magnitude of those differences did not differ between patients and controls (p=0.44). Cognitive performance did not change across the menstrual cycle on female-dominant or male-dominant tasks in either group. Estradiol and progesterone levels were unrelated to cognitive performance. Oxytocin levels did not change across the menstrual cycle but were positively related to performance on female-dominant tasks in female patients only (p<0.05).nnnCONCLUSIONSnSex differences in cognitive function are preserved in schizophrenia. Oxytocin levels do not change across the cycle, but relate to enhanced performance on female dominant tests in women. Physiological levels of oxytocin may thus have a more powerful benefit in some cognitive domains than estrogens in schizophrenia.

In search of an adult attachment stress provocation to measure effect on the oxytocin system: a pilot validation study.

BACKGROUND: Oxytocin is a promising biomarker for psychiatric conditions arising from early relational trauma, childhood maltreatment, and attachment dysregulation, including posttraumatic stress and dissociative disorders. OBJECTIVE: This exploratory pilot study examined plasma oxytocin as a biomarker for alterations in the attachment system. DESIGN: We used a single group, repeated-measures design with 15 women. The protocol used a film clip previously validated as a provocation to the hypothalamic–pituitary–adrenal axis. RESULTS: The repeated-measures ANOVA showed differences in oxytocin across the three time points. Correlations with oxytocin indicated that measures of dissociation and somatization correlated most strongly with higher levels of oxytocin measured during exposure to the film’s bonding scene and posttraumatic stress disorder correlated most strongly with lower levels at the film’s abandonment scene. Post hoc analyses revealed differences in oxytocin response related to psychopathology. CONCLUSION: Replication studies should characterize participants on a range of psychiatric conditions associated with attachment dysregulation.

Changes in social functioning and circulating oxytocin and vasopressin following the migration to a new country

Prior studies have reported associations between plasma oxytocin and vasopressin and markers of social functioning. However, because most human studies have used cross-sectional designs, it is unclear whether plasma oxytocin and vasopressin influences social functioning or whether social functioning modulates the production and peripheral release of these peptides. In order to address this question, we followed individuals who experienced major changes in social functioning subsequent to the migration to a new country. In this study, 59 new international students were recruited shortly after arrival in the host country and reassessed 2 and 5 months later. At each assessment participants provided information on their current social functioning and blood samples for oxytocin and vasopressin analysis. Results indicated that changes in social functioning were not related to changes in plasma oxytocin. Instead, baseline oxytocin predicted changes in social relationship satisfaction, social support, and loneliness over time. In contrast, plasma vasopressin changed as a function of social integration. Baseline vasopressin was not related to changes in social functioning over time. These results emphasize the different roles of plasma oxytocin and vasopressin in responses to changes in social functioning in humans.

The Role of Endogenous Oxytocin in Anxiolysis: Structural and Functional Correlates

BACKGROUNDnOxytocin is anxiolytic, and administration of synthetic oxytocin in humans reduces amygdala reactivity to negative stimuli. However, it is unknown whether endogenous oxytocin levels-which are heritable and stable across time-attenuate anxiety via similar mechanisms.nnnMETHODSnIn this study, we used plasma assays and structural and functional neuroimaging to examine potential anxiolytic effects of endogenous oxytocin in 73 participants.nnnRESULTSnWe found that higher endogenous oxytocin levels are associated with reduced central amygdala volume and blood oxygen level-dependent activity in response to aversive stimuli. In contrast to previous reports, we found that oxytocin was not related to patterns of functional connectivity between the amygdala and other brain regions.nnnCONCLUSIONSnTogether, our results underscore the importance of considering individual differences in participants endogenous oxytocin with respect to anxiety-related neural activity and neuromorphology.