Trajectory of ghrelin and PYY around a test meal in males and females with avoidant/restrictive food intake disorder versus healthy controls.

Disruptions in appetite-regulating hormones may contribute to the development and/or maintenance of avoidant/restrictive food intake disorder (ARFID). No study has previously assessed fasting levels of orexigenic ghrelin or anorexigenic peptide YY (PYY), nor their trajectory in response to food intake among youth with ARFID across the weight spectrum. We measured fasting and postprandial (30, 60, 120 minutes post-meal) levels of ghrelin and PYY among 127 males and females with full and subthreshold ARFID (n = 95) and healthy controls (HC; n = 32). We used latent growth curve analyses to examine differences in the trajectories of ghrelin and PYY between ARFID and HC. Fasting levels of ghrelin did not differ in ARFID compared to HC. Among ARFID, ghrelin levels declined more gradually than among HC in the first hour post meal (p =.005), but continued to decline between 60 and 120 minutes post meal, whereas HC plateaued (p =.005). Fasting and PYY trajectory did not differ by group. Findings did not change after adjusting for BMI percentile (M(SD)ARFID = 37(35); M(SD)HC = 53(26); p =.006) or calories consumed during the test meal (M(SD)ARFID = 294(118); M(SD)HC = 384 (48); p <.001). These data highlight a distinct trajectory of ghrelin following a test meal in youth with ARFID. Future research should examine ghrelin dysfunction as an etiological or maintenance factor of ARFID.

Intranasal Oxytocin for Obesity.

BACKGROUND: Accumulating preclinical and preliminary translational evidence shows that the hypothalamic peptide oxytocin reduces food intake, increases energy expenditure, and promotes weight loss. It is currently unknown whether oxytocin administration is effective in treating human obesity. METHODS: In this randomized, double-blind, placebo-controlled trial, we randomly assigned adults with obesity 1:1 (stratified by sex and obesity class) to receive intranasal oxytocin (24 IU) or placebo four times daily for 8 weeks. The primary end point was change in body weight (kg) from baseline to week 8. Key secondary end points included change in body composition (total fat mass [g], abdominal visceral adipose tissue [cm2], and liver fat fraction [proportion; range, 0 to 1; higher values indicate a higher proportion of fat]), and resting energy expenditure (kcal/day; adjusted for lean mass) from baseline to week 8 and caloric intake (kcal) at an experimental test meal from baseline to week 6. RESULTS: Sixty-one participants (54% women; mean age ± standard deviation, 33.6 ± 6.2 years; body-mass index [the weight in kilograms divided by the square of the height in meters], 36.9 ± 4.9) were randomly assigned. There was no difference in body weight change from baseline to week 8 between oxytocin and placebo groups (0.20 vs. 0.26 kg; P=0.934). Oxytocin (vs. placebo) was not associated with beneficial effects on body composition or resting energy expenditure from baseline to week 8 (total fat: difference [95% confidence interval], 196.0 g [-1036 to 1428]; visceral fat: 3.1 cm2 [-11.0 to 17.2]; liver fat: -0.01 [-0.03 to 0.01]; resting energy expenditure: -64.0 kcal/day [-129.3 to 1.4]). Oxytocin compared with placebo was associated with reduced caloric intake at the test meal (-31.4 vs. 120.6 kcal; difference [95% confidence interval], -152.0 kcal [-302.3 to -1.7]). There were no serious adverse events. Incidence and severity of adverse events did not differ between groups. CONCLUSIONS: In this randomized, placebo-controlled trial in adults with obesity, intranasal oxytocin administered four times daily for 8 weeks did not reduce body weight. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others; ClinicalTrials.gov number, NCT03043053.).

Prospective 2-Year Course and Predictors of Outcome in Avoidant/Restrictive Food Intake Disorder.

OBJECTIVE: To evaluate the 2-year course and outcomes of full and subthreshold avoidant/restrictive food intake disorder (ARFID) in youth aged 9 to 23 at baseline using a prospective longitudinal design to characterize the remission and persistence of ARFID, evaluate diagnostic crossover, and identify predictors of outcome. Greater severity in each ARFID profile-sensory sensitivity, fear of aversive consequences, and lack of interest-was hypothesized to predict greater likelihood of illness persistence, controlling for age, sex, body mass index percentile, ARFID treatment status, and baseline diagnosis. METHOD: Participants (N = 100; age range, 9-23 years; 49% female; 91% White) were followed over 2 years. The Pica, ARFID, and Rumination Disorder Interview was used across 3 time points (baseline, year 1, year 2) to measure the severity of each ARFID profile and evaluate illness persistence or remission, and the Eating Disorder Assessment for DSM-5 was used to evaluate diagnostic crossover. RESULTS: Across the 2-year follow-up period, half the participants persisted with their original diagnosis, and 3% of participants experienced a diagnostic shift to anorexia nervosa. Greater severity in the sensory sensitivity and lack of interest profiles was associated with higher likelihood of ARFID persistence at year 1 only; greater severity in the fear of aversive consequences profile was associated with higher likelihood of ARFID remission at year 2 only. CONCLUSION: Findings underscore the distinctiveness of ARFID from other eating disorders and emphasize its persistence over 2 years. Results also highlight the predictive validity and prognostic value of ARFID profiles (ie, sensory sensitivity, fear of aversive consequences, lack of interest).

Oxytocin response to food intake in avoidant/restrictive food intake disorder.

OBJECTIVE: To investigate the response of anorexigenic oxytocin to food intake among adolescents and young adults with avoidant/restrictive food intake disorder (ARFID), a restrictive eating disorder characterized by lack of interest in food or eating, sensory sensitivity to food, and/or fear of aversive consequences of eating, compared with healthy controls (HC). DESIGN: Cross-sectional. METHODS: A total of 109 participants (54 with ARFID spectrum and 55 HC) were instructed to eat a ∼400-kcal standardized mixed meal. We sampled serum oxytocin at fasting and at 30-, 60-, and 120-min postmeal. We tested the hypothesis that ARFID would show higher mean oxytocin levels across time points compared with HC using a mixed model ANOVA. We then used multivariate regression analysis to identify the impact of clinical characteristics (sex, age, and body mass index [BMI] percentile) on oxytocin levels in individuals with ARFID. RESULTS: Participants with ARFID exhibited greater mean oxytocin levels at all time points compared with HC, and these differences remained significant even after controlling for sex and BMI percentile (P = .004). Clinical variables (sex, age, and BMI percentile) did not show any impact on fasting and postprandial oxytocin levels among individuals with ARFID. CONCLUSIONS: Consistently high oxytocin levels might be involved in low appetite and sensory aversions to food, contributing to food avoidance in individuals with ARFID.

Low bone mineral density is found in low weight female youth with avoidant/restrictive food intake disorder and associated with higher PYY levels.

BACKGROUND: Avoidant/restrictive food intake disorder (ARFID) is a restrictive eating disorder commonly associated with medical complications of undernutrition and low weight. In adolescence, a critical time for bone accrual, the impact of ARFID on bone health is uncertain. We aimed to study bone health in low-weight females with ARFID, as well as the association between peptide YY (PYY), an anorexigenic hormone with a role in regulation of bone metabolism, and bone mineral density (BMD) in these individuals. We hypothesized that BMD would be lower in low-weight females with ARFID than healthy controls (HC), and that PYY levels would be negatively associated with BMD. METHODS: We performed a cross-sectional study in 14 adolescent low-weight females with ARFID and 20 HC 10-23 years old. We assessed BMD (total body, total body less head and lumbar spine) using dual x-ray absorptiometry (DXA) and assessed fasting total PYY concentration in blood. RESULTS: Total body BMD Z-scores were significantly lower in ARFID than in HC (- 1.41 ± 0.28 vs. - 0.50 ± 0.25, p = 0.021). Mean PYY levels trended higher in ARFID vs. HC (98.18 ± 13.55 pg/ml vs. 71.40 ± 5.61 pg/ml, p = 0.055). In multivariate analysis within the ARFID group, PYY was negatively associated with lumbar BMD adjusted for age (ß = -0.481, p = 0.032). CONCLUSION: Our findings suggest that female adolescents with low-weight ARFID may have lower BMD than healthy controls and that higher PYY levels may be associated with lower BMD at some, but not all, sites in ARFID. Further research with larger samples will be important to investigate whether high PYY drives bone loss in ARFID.

Avoidant/restrictive food Intake disorder (ARFID) is a condition characterized by lack of interest in eating/food, sensory sensitivity and/or fear of aversive consequences of eating. It is associated with low weight and undernutrition, which can lead to medical complications. Specifically, low weight in patients with ARFID raises concerns of impaired bone health. In this study, we compared bone mineral density (BMD), a measure of bone health, in 14 low-weight females with ARFID and 20 healthy females 10­23 years old. We also examined the association between BMD and peptide YY (PYY), a hormone that induces satiety and inhibits bone formation. A strong negative association between bone health and PYY was previously reported in females with anorexia nervosa. Thus, we hypothesized a similar association in low weight females with ARFID. We found that BMD may be lower in low-weight females with ARFID than in healthy females and that higher PYY levels are associated with lower BMD at some but not all sites. We concluded that bone health may be a concern in low-weight females with ARFID. This finding is important as low BMD raises concerns for increased fracture risk, which in turn could have a detrimental effect on quality of life.

A randomized, double-blind, placebo-controlled clinical trial of 8-week intranasal oxytocin administration in adults with obesity: Rationale, study design, and methods.

BACKGROUND: Obesity affects more than one-third of adults in the U.S., and effective treatment options are urgently needed. Oxytocin administration induces weight loss in animal models of obesity via effects on caloric intake, energy expenditure, and fat metabolism. We study intranasal oxytocin, an investigational drug shown to reduce caloric intake in humans, as a potential novel treatment for obesity. METHODS: We report the rationale, design, methods, and biostatistical analysis plan of a randomized, double-blind, placebo-controlled clinical trial of intranasal oxytocin for weight loss (primary endpoint) in adults with obesity. Participants (aged 18-45 years) were randomly allocated (1:1) to oxytocin (four times daily over eight weeks) versus placebo. Randomization was stratified by biological sex and BMI (30 to <35, 35 to <40, ≥40 kg/m2). We investigate the efficacy, safety, and mechanisms of oxytocin administration in reducing body weight. Secondary endpoints include changes in resting energy expenditure, body composition, caloric intake, metabolic profile, and brain activation via functional magnetic resonance imaging in response to food images and during an impulse control task. Safety and tolerability (e.g., review of adverse events, vital signs, electrocardiogram, comprehensive metabolic panel) are assessed throughout the study and six weeks after treatment completion. RESULTS: Sixty-one male and female participants aged 18-45 years were randomized (mean age 34 years, mean BMI 37 kg/m2). The study sample is diverse with 38% identifying as non-White and 20% Hispanic. CONCLUSION: Investigating intranasal oxytocin's efficacy, safety, and mechanisms as an anti-obesity medication will advance the search for optimal treatment strategies for obesity and its associated severe sequelae.

Ghrelin and PYY in low-weight females with avoidant/restrictive food intake disorder compared to anorexia nervosa and healthy controls.

BACKGROUND: Avoidant/restrictive food intake disorder (ARFID) is characterized by restrictive eating and failure to meet nutritional needs but is distinct from anorexia nervosa (AN) because restriction is not motivated by weight/shape concerns. We examined levels of orexigenic ghrelin and anorexigenic peptide YY (PYY) in young females with ARFID, AN and healthy controls (HC). METHODS: 94 females (22 low-weight ARFID, 40 typical/atypical AN, and 32 HC ages 10-22 years) underwent fasting blood draws for total ghrelin and total PYY. A subset also provided blood 30, 60 and 120 min after a standardized meal. RESULTS: Females with ARFID ate less than those with AN or HC (ps<0.012); were younger (14.4 ± 3.2 years) than those with AN (18.9 ± 3.1 years) and HC (17.4 ± 3.1 years) (ps<0.003) and at a lower Tanner stage (3.1 ± 1.5) than AN (4.5 ± 1.1;) and HC (4.4 ± 1.1; ps<0.005), but did not differ in BMI percentiles or BMI Z-scores from AN (ps>0.44). Fasting and postprandial ghrelin were lower in ARFID versus AN (ps≤.015), but not HC (ps≥0.62). Fasting and postprandial PYY did not differ between ARFID versus AN or HC (ps≥0.13); ARFID did not demonstrate the sustained high PYY levels post-meal observed in those with AN and HC. Secondary analyses controlling age or Tanner stage and calories consumed showed similar results. Exploratory analyses suggest that the timing of the PYY peak in ARFID is earlier than HC, showing a peak PYY level 30 min post-meal (p = .037). CONCLUSIONS: ARFID and AN appear to have distinct patterns of secretion of gut-derived appetite-regulating hormones that may aid in differential diagnosis and provide new treatment targets.

Lower Oxytocin Levels Are Associated with Lower Bone Mineral Density and Less Favorable Hip Geometry in Hypopituitary Men.

INTRODUCTION: Hypopituitary patients are at risk for bone loss. Hypothalamic-posterior pituitary hormones oxytocin and vasopressin are anabolic and catabolic, respectively, to the skeleton. Patients with hypopituitarism may be at risk for oxytocin deficiency. Whether oxytocin and/or vasopressin contribute to impaired bone homeostasis in hypopituitarism is unknown. OBJECTIVES: To determine the relationship between plasma oxytocin and vasopressin levels and bone characteristics (bone mineral density [BMD] and hip structural analysis [HSA]) in patients who have anterior pituitary deficiencies only (APD group) or with central diabetes insipidus (CDI group). METHODS: This is a cross-sectional study. Subjects included 37 men (17 CDI and 20 APD), aged 20-60 years. Main outcome measures were fasting plasma oxytocin and vasopressin levels, and BMD and HSA using dual X-ray absorptiometry. RESULTS: Mean BMD and HSA variables did not differ between the CDI and APD groups. Mean BMD Z-scores at most sites were lower in those participants who had fasting oxytocin levels below, rather than above, the median. There were positive associations between fasting oxytocin levels and (1) BMD Z-scores at the spine, femoral neck, total hip, and subtotal body and (2) favorable hip geometry and strength variables at the intertrochanteric region in CDI, but not APD, participants. No associations between vasopressin levels and bone variables were observed in the CDI or ADP groups. CONCLUSIONS: This study provides evidence for a relationship between oxytocin levels and BMD and estimated hip geometry and strength in hypopituitarism with CDI. Future studies will be important to determine whether oxytocin could be used therapeutically to optimize bone health in patients with hypopituitarism.

Medical comorbidities and endocrine dysfunction in low-weight females with avoidant/restrictive food intake disorder compared to anorexia nervosa and healthy controls.

OBJECTIVE: To improve our understanding of medical complications and endocrine alterations in patients with low-weight avoidant/restrictive food intake disorder (ARFID) and how they may differ from those in anorexia nervosa (AN) and healthy controls (HC). METHOD: We performed an exploratory cross-sectional study comparing low-weight females with ARFID (n = 20) with females with AN (n = 42) and HC (n = 49) with no history of an eating disorder. RESULTS: We found substantial overlap in medical comorbidities and endocrine features in ARFID and AN, but with earlier onset of aberrant eating behaviors in ARFID. We also observed distinct medical and endocrine alterations in ARFID compared to AN, such as a greater prevalence of asthma, a lower number of menses missed in the preceding 9 months, higher total T3 levels, and lower total T4 : total T3 ratio; these differences persisted after adjusting for age and might reflect differences in pathophysiology, acuity of weight fluctuations, and/or nutritional composition of food consumed. CONCLUSION: These results highlight the need for prompt diagnosis and intensive therapeutic intervention from disease onset in ARFID.

A Diet High in Processed Foods, Total Carbohydrates and Added Sugars, and Low in Vegetables and Protein Is Characteristic of Youth with Avoidant/Restrictive Food Intake Disorder.

Avoidant/restrictive food intake disorder (ARFID) is characterized in part by limited dietary variety, but dietary characteristics of this disorder have not yet been systematically studied. Our objective was to examine dietary intake defined by diet variety, macronutrient intake, and micronutrient intake in children and adolescents with full or subthreshold ARFID in comparison to healthy controls. We collected and analyzed four-day food record data for 52 participants with full or subthreshold ARFID, and 52 healthy controls, aged 9-22 years. We examined frequency of commonly reported foods by logistic regression and intake by food groups, macronutrients, and micronutrients between groups with repeated-measures ANOVA. Participants with full or subthreshold ARFID did not report any fruit or vegetable category in their top five most commonly reported food categories, whereas these food groups occupied three of the top five groups for healthy controls. Vegetable and protein intake were significantly lower in full or subthreshold ARFID compared to healthy controls. Intakes of added sugars and total carbohydrates were significantly higher in full or subthreshold ARFID compared to healthy controls. Individuals with full or subthreshold ARFID had lower intake of vitamins K and B12, consistent with limited vegetable and protein intake compared to healthy controls. Our results support the need for diet diversification as part of therapeutic interventions for ARFID to reduce risk for nutrient insufficiencies and related complications.

Disrupted Oxytocin-Appetite Signaling in Females With Anorexia Nervosa.

CONTEXT: In healthy females, oxytocin levels decrease postmeal, corresponding to increased satiety. The postprandial response of oxytocin in females with anorexia nervosa (AN)/atypical AN is unknown. OBJECTIVES: To determine the pattern of postprandial serum oxytocin levels in females with AN/atypical AN, relationship with appetite, and effect of weight, eating behavior, and endogenous estrogen status. DESIGN: Cross-sectional. SETTING: Clinical research center. PARTICIPANTS: 67 women (36 with AN [<85% expected body weight (EBW)]; 31 with atypical AN [≥ 85% EBW)]), age 22.4 ± 0.9 (mean ± SEM) years, categorized by weight, restricting vs binge/purge behavior, and estrogen status. INTERVENTIONS: Standardized mixed meal. MAIN OUTCOME MEASUREMENTS: Blood sampling for oxytocin occurred fasting and 30, 60, and 120 minutes postmeal. Subjective appetite was assessed using visual analog scales. RESULTS: In females with AN/atypical AN, oxytocin levels decreased from fasting to 60 (P = 0.002) and 120 (P = 0.005) minutes postmeal. The decrease in oxytocin from fasting to 120 minutes was greater in females with atypical AN than AN (P = 0.027) and did not differ by restricting vs binge/purge behavior or estrogen status. Controlling for caloric intake, the decrease in oxytocin was inversely related to the decrease in hunger postmeal in females with atypical AN (P = 0.04). CONCLUSIONS: In females with AN/atypical AN, oxytocin levels decrease postmeal, as established in healthy females. Weight, but not restricting vs binge/purging nor endogenous estrogen status, affects postprandial oxytocin levels. The postprandial change in serum oxytocin levels is related to appetite in females with atypical AN only, suggesting a disconnect between oxytocin secretion and appetite in the undernourished state.

Low Plasma Oxytocin Levels and Increased Psychopathology in Hypopituitary Men With Diabetes Insipidus.

CONTEXT: Oxytocin (OT) and vasopressin share anatomical pathways of synthesis and secretion, and patients with central diabetes insipidus (CDI) presumably are at risk for OT deficiency. However, an OT-deficient state in hypopituitary patients has not been established. OBJECTIVES: We hypothesized that men with CDI compared to patients with similar anterior pituitary deficiencies (APD) but no CDI and healthy controls (HC) of similar age and body mass index, would have lower plasma OT levels, associated with increased psychopathology. DESIGN: Cross-sectional. SETTING: Clinical research center. PARTICIPANTS: Sixty-two men (20 CDI, 20 APD, 22 HC), age 18 to 60 years. INTERVENTIONS: Frequent sampling of blood every 5 minutes for OT over 1 hour and validated questionnaires to assess psychopathology. MAIN OUTCOMES: Pooled plasma OT levels; depressive, anxiety, and alexithymia symptoms; and quality of life. RESULTS: The mean 1-hour pool of fasting OT levels was lower in CDI compared with APD and HC (P = 0.02 and P = 0.009, respectively), with no differences between APD and HC (P = 0.78). Symptoms of depression, anxiety, and alexithymia were more pronounced in CDI than in HC (P = 0.001, P = 0.004, and P = 0.02, respectively). Although CDI and APD reported worse physical health compared with HC (P = 0.001 and P = 0.005) with no differences between APD and CDI, only CDI reported worse mental health compared with HC (P = 0.009). CONCLUSIONS: We have demonstrated low plasma OT levels and increased psychopathology in hypopituitary men with CDI, suggestive of a possible OT-deficient state. Larger studies of both sexes are required to confirm these findings and clinically characterize hypopituitary patients with OT deficiency.

Endogenous Oxytocin Levels in Relation to Food Intake, Menstrual Phase, and Age in Females.

CONTEXT: Oxytocin regulates a range of physiological processes including eating behavior and oxytocin administration reduces caloric intake in males. There are few data on oxytocin and eating behavior in healthy females or on the response of endogenous oxytocin to food intake and its relationship to appetite in humans. OBJECTIVES: To determine the postprandial pattern of oxytocin levels, the relationship between oxytocin and appetite, and the impact of menstrual cycle phase and age on oxytocin levels in females. DESIGN: Cross-sectional. SETTING: Clinical research center. PARTICIPANTS: Fifty-five healthy females (age 10 to 45 years). INTERVENTIONS: A standardized mixed meal was administered. MAIN OUTCOME MEASUREMENTS: Blood sampling for oxytocin occurred at fasting and at 30, 60, and 120 minutes postmeal. Appetite was assessed using Visual Analogue Scales pre- and postmeal. RESULTS: Mean fasting oxytocin levels were 1011.2 ± 52.3 pg/mL (SEM) and decreased at 30 and 60 minutes postmeal (P = 0.001 and P = 0.003, respectively). Mean oxytocin levels decreased19.6% ± 3.0% from baseline to nadir. Oxytocin area under the curve was lower in the early to midfollicular menstrual cycle phase (P = 0.0003) and higher in younger females (P = 0.002). The percent change in oxytocin (baseline to nadir) was associated with postprandial hunger (rs = -0.291, P = 0.03) and fullness (rs = 0.345, P = 0.009). These relations remained significant after controlling for calories consumed, menstrual cycle status, and age (P = 0.023 and P = 0.0001, respectively). CONCLUSIONS: Peripheral oxytocin levels in females decrease after a mixed meal and are associated with appetite independent of menstrual phase, age, and caloric intake, suggesting that endogenous oxytocin levels may play a role in perceived hunger and satiety.

Oxytocin secretion is pulsatile in men and is related to social-emotional functioning.

The hypothalamic hormone oxytocin (OXT) plays an important role in a range of physiological processes and social-emotional functioning in both sexes. In women, physiological stimuli, such as suckling and parturition, result in pulsatile release of OXT into the peripheral circulation via the posterior pituitary gland. However, data regarding OXT secretory patterns in men during a state of rest are limited. Further, the relationship between secretory dynamics of OXT and emotional measures has never been evaluated. We hypothesized a pulsatile pattern of OXT secretion in men, and explored the relationship between OXT secretory patterns and social-emotional functioning. METHODS: Deconvolution analysis was performed on serum OXT levels obtained every 5min over a period of 10h in 5 healthy normal weight men. Area under the curve (AUC), average OXT values, and pulse characteristics [pulse number, inter-pulse interval, pulse height and mass (area under each pulse)] were calculated. State Adult Attachment Measure (SAAM) assessed types of human attachment. Interpersonal Support Evaluation List (ISEL) assessed perception of social support. Toronto Alexithymia Scale (TAS-20) measured the ability to express and identify one's own emotions. RESULTS: Mean age was 22.8±1.2years, and BMI was 21.7±0.4kg/m2 (mean±SEM). Assuming a basal secretion of zero and a half life of five to seven minutes, we demonstrated the following: OXT AUC: 5421±1331pg/ml, mean OXT level: 9.1pg/ml, mean pulse number: 22±3/10hr, mean pulse height: 1.81±0.48pg/ml, mean pulse mass: 30.34±10.29pg/ml and mean inter-pulse interval: 27±4min. The SAAM Avoidant scale correlated negatively with mean OXT pulse height (r=-0.90, p=0.04) and pulse mass (r=-0.95, p=0.01). The ISEL Belonging score correlated positively with OXT AUC (r=0.89, p=0.04) and average OXT (r=0.93, p=0.02). ISEL Appraisal score also had a positive association with mean OXT pulse height (r=0.99, p=0.0006) and pulse mass (r=0.98, p=0.003). Finally, ISEL total score had a significant correlation with average OXT values (r=0.90, p=0.04). While none of the subjects had a score in the alexithymia range, TAS-20 Difficulty describing feelings score had an inverse correlation with OXT pulse height (r=-0.96, p=0.01) and pulse mass (r=-0.99, p=0.001). TAS-20 total score also had an inverse correlation with OXT pulse height (r=-0.94, p=0.02) and pulse mass (r=-0.96, p=0.009). CONCLUSION: We demonstrate a pulsatile pattern of peripheral OXT secretion in healthy men at rest. Subjects with lower OXT pulse height and pulse mass had a more avoidant style of attachment, felt less supported, and expressed greater difficulty in describing their feelings. Our findings support the concept that OXT is a key mediator of social-emotional functioning. Future studies to determine causality are warranted.