Cocaine use disorder effects on blood oxytocin levels and OXTR DNA methylation.

Substance use disorders have been associated with alterations in the oxytocinergic system, but few studies have investigated both the peptide and epigenetic mechanisms potentially implicated in the regulation of oxytocin receptor. In this study, we compared plasma oxytocin and blood DNA methylation in the OXTR gene between people with and without cocaine use disorder (CUD). We measured the oxytocin levels of 51 people with CUD during acute abstinence and of 30 healthy controls using an enzyme immunoassay. The levels of DNA methylation in four CpG sites at exon III of the OXTR gene were evaluated in a subsample using pyrosequencing. The Addiction Severity Index was used to assess clinical characteristics. We found higher oxytocin levels in men with CUD (56.5 pg/mL; 95% CI: 48.2-64.7) than in control men (33.6 pg/mL; 95% CI: 20.7-46.5), while no differences between women with and without CUD were detected. With a moderate effect size, the interaction effect between group and sex remained significant when controlling for height, weight and age data. A positive correlation in the CUD sample was found between oxytocin levels and days of psychological suffering prior to treatment enrollment. No group differences were observed regarding DNA methylation data. This suggests that CUD is associated with higher peripheral oxytocin levels in men during acute abstinence. This finding may be considered in future studies that aim at using exogenous oxytocin as a potential treatment for cocaine addiction.

Association of Prolactin, Oxytocin, and Homocysteine With the Clinical and Cognitive Features of a First Episode of Psychosis Over a 1-Year Follow-Up.

BACKGROUND: The clinical debut of schizophrenia is frequently a first episode of psychosis (FEP). As such, there is considerable interest in identifying associations between biological markers and clinical or cognitive characteristics that help predict the progression and outcome of FEP patients. Previous studies showed that high prolactin, low oxytocin, and high homocysteine are factors associated with FEP 6 months after diagnosis, at which point plasma levels were correlated with some clinical and cognitive characteristics. METHODS: We reexamined 75 patients at 12 months after diagnosis to measure the evolution of these molecules and assess their association with clinical features. RESULTS: At follow-up, FEP patients had lower prolactin levels than at baseline, and patients treated with risperidone or paliperidone had higher prolactin levels than patients who received other antipsychotic agents. By contrast, no changes in oxytocin and homocysteine plasma levels were observed between the baseline and follow-up. In terms of clinical features, we found that plasma prolactin and homocysteine levels were correlated with the severity of the psychotic symptoms in male FEP patients, suggesting that they might be factors associated with psychotic symptomatology but only in men. Together with oxytocin, these molecules may also be related to sustained attention, verbal ability, and working memory cognitive domains in FEP patients. CONCLUSION: This study suggests that focusing on prolactin, oxytocin, and homocysteine at a FEP may help select adequate pharmacological treatments and develop new tools to improve the outcome of these patients, where sex should also be borne in mind.

Affectionate touch and diurnal oxytocin levels: An ecological momentary assessment study.

Background: Affectionate touch, which is vital for mental and physical health, was restricted during the Covid-19 pandemic. This study investigated the association between momentary affectionate touch and subjective well-being, as well as salivary oxytocin and cortisol in everyday life during the pandemic. Methods: In the first step, we measured anxiety and depression symptoms, loneliness and attitudes toward social touch in a large cross-sectional online survey (N = 1050). From this sample, N = 247 participants completed ecological momentary assessments over 2 days with six daily assessments by answering smartphone-based questions on affectionate touch and momentary mental state, and providing concomitant saliva samples for cortisol and oxytocin assessment. Results: Multilevel models showed that on a within-person level, affectionate touch was associated with decreased self-reported anxiety, general burden, stress, and increased oxytocin levels. On a between-person level, affectionate touch was associated with decreased cortisol levels and higher happiness. Moreover, individuals with a positive attitude toward social touch experiencing loneliness reported more mental health problems. Conclusions: Our results suggest that affectionate touch is linked to higher endogenous oxytocin in times of pandemic and lockdown and might buffer stress on a subjective and hormonal level. These findings might have implications for preventing mental burden during social contact restrictions. Funding: The study was funded by the German Research Foundation, the German Psychological Society, and German Academic Exchange Service.

Variable Levels of Oxytocin During Sepsis: The Role of Oxytocin in Sepsis Pathophysiology.

BACKGROUND: Although the role of oxytocin in the pathophysiology of sepsis is still unknown, rising preclinical evidence suggests that oxytocin is possibly involved. However, no direct clinical studies have measured the levels of oxytocin during sepsis. In this preliminary study, the serum oxytocin levels were evaluated throughout the duration of sepsis. METHOD: Twenty-two male patients over 18 years of age with a SOFA score of 2 points or more who were admitted to the ICU were included. Patients with a history of neuroendocrine, psychiatric, and neurologic disorders, cancer, an infection caused by COVID-19, shock due to reasons other than sepsis, a history of psychiatric or neurologic medication use, and those who died during the study were excluded. The main endpoint included the measurement of serum oxytocin levels using radioimmunoassay at 6, 24, and 48 h of the ICU admission. RESULTS: Mean serum oxytocin level was higher at 6 h of ICU admission (41.27 ± 13.14 ng/L) than after 24 and 48 h of ICU admission (22.63 ± 5.75 and 20.97 ± 7.61 ng/L respectively) (P-value < .001). CONCLUSION: Our study, while reporting increased serum oxytocin levels in the initial phase of sepsis and decline afterward, supports the possible contribution of oxytocin in the pathophysiology of sepsis. Given that oxytocin seems to modulate the innate immune system, future investigations are necessary to assess the potential role of oxytocin in the pathophysiology of sepsis.

Plasma Oxytocin Is Not Associated with Social Cognition or Behavior in Frontotemporal Dementia and Alzheimer's Disease Syndromes.

INTRODUCTION: Changes in social behavior and emotion processing are common in frontotemporal dementia (FTD) and semantic dementia (SD), and less so in Alzheimer's disease (AD). Recent research has investigated oxytocin as a potential treatment for these symptoms; however, whether plasma oxytocin is associated with social-emotional symptoms of dementia remains underexplored. METHODS: Thirty behavioral-variant FTD (bvFTD), 28 SD, 39 AD, and 24 controls underwent blood sampling to measure oxytocin. Participants completed an emotion processing battery. Carers completed the Cambridge Behavioral Inventory and the Neuropsychiatric Inventory. RESULTS: Patients with bvFTD were severely impaired in emotion processing and behavioral ratings, with milder impairment in SD and AD. No difference in plasma oxytocin was observed between groups (p = 0.632). No significant associations were found between oxytocin and social behavior or emotion processing (r values between -0.241 and 0.227, all p values >0.099). CONCLUSION: Our results indicate that plasma oxytocin is not reduced in dementia and is unrelated to social, emotional, and behavioral features. We noted high interindividual variability in our data; hence, future investigations should consider methodological influences such as serum versus saliva and diurnal variation on oxytocin function. These results demonstrate that current measurement measures of plasma oxytocin have limited utility in determining the role of oxytocin in FTD. Alternative oxytocin measures may prove more sensitive and should be considered when conducting clinical trials.

Depressive symptomatology, temperament and oxytocin serum levels in a sample of healthy female university students.

BACKGROUND: Depressive symptomatology is prevalent among female university students with adverse effects on their quality of life and academic performance. Previous research suggested associations between depressive symptomatology and oxytocin levels and between depressive symptomatology and Temperament Traits. Despite this evidence, to the best of our knowledge no research has studied the effects fboth oxytocin serum levels and temperament dimensions on depressivesymptoms in a healthy sample. The present study aimed to analyse the effect of oxytocin levels and temperament traits on depressive symptomatology in healthy female university students. METHODS: All participants completed the Beck Depression Inventory and the Adult Temperament Questionnaire. Blood samples were collected between 8 and 8H30 a.m. after 12 h of fasting and between 5 and 8 day of the menstrual cycle and serum oxytocin levels were quantified using a commercial enzyme-linked immunosorbent assay. A hierarchical multiple regression model using a stepwise method was conducted to identify predictors of depression. RESULTS: Forty-five women aged between 18 and 25 years old (19.37 ± 1.32 years) volunteered to participate in this study. Depressive symptomatology was negatively associated with oxytocin serum levels and "Negative affect" and positively associated with "Effortful control" and "Activation Control". In the final regression model, only oxytocin level was a predictor (B = - 0.090, p < 0.0001), the model explaining 65.2% of the depression variation. Oxytocin played a mediation role between "Negative affects" and Depressive symptomatology. CONCLUSIONS: Our results showed that oxytocin level, rather than personality dimensions, was associated with depressive symptomatology. These results highlight the relevance of the discussion on the use of oxytocin as a biological marker of emotional and social symptoms that characterize depression.

Cerebral and extracerebral distribution of radioactivity associated with oxytocin in rabbits after intranasal administration: Comparison of TTA-121, a newly developed oxytocin formulation, with Syntocinon.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder associated with deficits in social interactions/communication. Despite the large number of ASD patients, there is no drug approved to treat its core symptoms. Recently, Syntocinon (oxytocin nasal spray) has been reported to have a therapeutic effect on ASD. However, the disadvantage of Syntocinon for ASD treatment is that 6 puffs/administration are required to achieve the effective pharmacological dose. Furthermore, there are no published reports evaluating the cerebral distribution profile of oxytocin after intranasal administration. TTA-121 is a newly developed intranasal oxytocin formulation with high bioavailability produced by optimizing the physicochemical properties. In this study, we prepared the same formula as Syntocinon as the control formulation (CF), and the cerebral and extracerebral distribution of oxytocin in rabbits after single intranasal administration of 3H-labeled oxytocin formulations-[3H]TTA-121 and [3H]CF were examined and compared. The area under the concentration-time curve to the time of the last quantifiable concentration (AUCt) in the whole brain was 3.6-fold higher in the [3H]TTA-121 group than in the [3H]CF group, indicating increased delivery of radioactivity to the brain by TTA-121 than by CF. Since the distribution profiles showed no notable differences in radioactivity between the olfactory bulb and trigeminal nerve, intranasally-administered oxytocin was probably transferred to the brain via both pathways. The results also showed an increase in radioactivity in the prefrontal area and the precuneus, which are probable sites of pharmacological action as shown in clinical studies using functional magnetic resonance imaging (fMRI), confirming that intranasally-administered oxytocin could reach these tissues.

Oxytocin increases perceived competence and social-emotional engagement with brands.

Humans express loyalty to consumer brands much like they do in human relationships. The neuroactive chemical oxytocin is an important biological substrate of human attachment and this study tested whether consumer-brand relationships can be influenced by oxytocin administration. We present a mathematical model of brand attachment that generates empirically-testable hypotheses. The model is tested by administering synthetic oxytocin or placebo to male and female participants (N = 77) who received information about brands and had an opportunity to purchase branded products. We focused on two brand personality dimensions: warmth and competence. Oxytocin increased perceptions of brand competence but not brand warmth relative to placebo. We also found that participants were willing to pay more for branded products through its effect on brand competence. When writing about one's favorite brands, oxytocin enhanced the use of positive emotional language as well as words related to family and friends. These findings provide preliminary evidence that consumers build relationships with brands using the biological mechanisms that evolved to form human attachments.

Serum concentrations of oxytocin, DHEA and follistatin are associated with osteoporosis or sarcopenia in community-dwelling postmenopausal women.

BACKGROUND: Osteoporosis and sarcopenia are major health issues in postmenopausal women due to their high prevalence and association with several adverse outcomes. However, no biomarkers may be used for screening and diagnosis. The current study investigated potential biomarkers for osteoporosis and/or sarcopenia in postmenopausal women. METHODS: A cross-sectional study on 478 healthy community-dwelling postmenopausal women aged 50-90 years was performed. Osteoporosis and sarcopenia were defined according to the World Health Organization (WHO) and Asian Working Group for Sarcopenia (AWGS). RESULTS: Dehydroepiandrosterone (DHEA) was related to muscle strength (ß = 0.19, p = 0.041) and function (ß = 0.58, p = 0.004). Follistatin (ß = - 0.27, p = 0.01) was related to muscle mass. Oxytocin (ß = 0.59, p = 0.044) and DHEA (ß = 0.51, p = 0.017) were related to bone mass. After adjusting for age, oxytocin (odds ratio (OR) 0.75; 95% confidence intervals (CI) 0.63-0.98; p = 0.019) was associated with osteoporosis, and DHEA (OR 0.73; 95% CI 0.51-0.96; p = 0.032) and follistatin (OR 1.66; 95% CI 1.19-3.57; p = 0.022) were associated with sarcopenia. CONCLUSIONS: Postmenopausal women with sarcopenia were more likely to have lower DHEA levels and higher follistatin levels, and postmenopausal women with osteoporosis were more likely to have lower oxytocin levels.

Reproduction-Associated Hormones and Adult Hippocampal Neurogenesis.

The levels of reproduction-associated hormones in females, such as estrogen, progesterone, prolactin, and oxytocin, change dramatically during pregnancy and postpartum. Reproduction-associated hormones can affect adult hippocampal neurogenesis (AHN), thereby regulating mothers' behavior after delivery. In this review, we first briefly introduce the overall functional significance of AHN and the methods commonly used to explore this front. Then, we attempt to reconcile the changes of reproduction-associated hormones during pregnancy. We further update the findings on how reproduction-related hormones influence adult hippocampal neurogenesis. This review is aimed at emphasizing a potential role of AHN in reproduction-related brain plasticity and its neurobiological relevance to motherhood behavior.

An improved sample extraction method reveals that plasma receptor for advanced glycation end-products (RAGE) modulates circulating free oxytocin in mice.

The receptor for advanced glycation end-products (RAGE) binds oxytocin (OT) and transports it from the blood to the brain. As RAGE's OT-binding capacity was lost in RAGE knockout (KO) mice, we predicted that circulating concentrations of unbound (free) OT should be elevated compared to wild-type (WT) mice. However, this hypothesis has not yet been investigated. Unfortunately, the evaluation of the dynamics of circulating free and bound plasma OT is unclear in immunoassays, in part because of interference from plasma proteins. A radioimmunoassay (RIA) is considered the gold standard method for overcoming this issue, but is more challenging to implement; thus, commercially available enzyme-linked immunosorbent assays (ELISAs) are more commonly used. Here, we developed a pre-treatment method to remove the interference-causing components from plasma before performing ELISA. The acetonitrile protein precipitation (PPT) approach was reliable, with fewer steps needed to measure free OT concentrations than by solid-phase extraction of plasma samples. PPT-extracted plasma samples yielded higher concentrations of OT in RAGE KO mice than in WT mice using ELISA. After peripheral OT injection, free OT plasma levels spiked immediately then rapidly declined in WT mice, but remained high in KO mice. These results suggest that plasma samples with PPT pre-treatment appear to be superior and that circulating soluble RAGE can most likely serve as a buffer for plasma OT, which indicates a novel physiological function of RAGE.

Comparison of external calibration and isotope dilution LC-ICP-MS/MS for quantitation of oxytocin and its selenium analogue in human plasma.

In the present study, a method for quantitation of the pharmaceutical peptide oxytocin (OT) and its diselenide-containing analogue (SeOT) in human plasma was developed using gradient elution LC-ICP-MS/MS. Plasma samples were precipitated with acetonitrile containing 1.0% TFA in a volume ratio of 1+3 (sample+precipitation agent) before analysis. Post-column isotope dilution analysis (IDA) was applied for quantitation and was compared with external calibration. Both calibration methods appeared to be fit for purpose regarding figures of merit including linearity, precision, LOD, LOQ and recovery. Analysis of OT and SeOT showed that selenium-based analysis is considerably more sensitive and selective compared to the sulfur-based analysis. Despite the relatively simpler setup of external calibration, IDA can be advantageous because it compensates for instrument drift and changes in organic solvent concentration. The method was applied for a stability study showing the degradation of OT and SeOT in plasma. The degradation of SeOT was faster than the degradation of OT in plasma. Thus, possible stability effects should be considered before replacing a disulfide bridge with a diselenide bridge or introducing a diselenide label in a potential drug.

Targeting the Oxytocin System to Ameliorate Early Life Depressive-Like Behaviors in Maternally-Separated Rats.

Oxytocin (OXT) -"the love hormone"- has been involved in the anti-depressant activity of some selective serotonin reuptake inhibitors (SSRIs). The exact mechanism underlying the OXT pathway in depression is not fully clear. This study aimed to investigate the effect of OXT analogue, carbetocin (CBT) and the SSRI, escitalopram (ESCIT) on depressive-like behaviors following maternal separation (MS). It is worthy to mention that intranasal CBT has been approved by U.S. Food and Drug Administration (FDA) for Prader-Willi syndrome. Adolescent Wistar albino maternally-separated rats were given CBT, (100 µg/animal/d via inhalation route), and, ESCIT, (20 mg kg-1, per os ( p.o.)) either alone or in combination for 7 d. Repeated 3-h MS demonstrated increased immobility time in forced swim test (FST) and decreased locomotor activity in open field test. MS elevated plasma level of adrenocortico-trophic hormone (ACTH) but notably reduced plasma OXT, with no effect on hippocampal OXT-R expression. Following MS, hippocampal contents of 5-hydroxytryptamine receptors (5HT1A-R), serotonin transporter (SERT) were increased. CBT and ESCIT corrected the behavioral dysfunction in FST and suppressed the high levels of ACTH. Additionally, both treatments boosted OXT level, reduced 5HT1A-R and normalized SERT contents, which reflects increased availability of serotonin. Finally, CBT markedly ameliorated the histopathological damage induced by MS and suppressed the increased glial fibrillary acidic protein. CBT and ESCIT manage depressive-like behavior by positively affecting serotonergic and oxytocinergic systems. Targeting OXT system -using CBT- ameliorated depressive like behaviors induced by maternal separation most probably via enhancing OXT plasma levels, attenuating hormonal ACTH and restoring the expression of hippocampal oxytocin and serotonin mechanisms.

Specificity of plasma oxytocin immunoassays: A comparison of commercial assays and sample preparation techniques using oxytocin knockout and wildtype mice.

Oxytocin has garnered much interest due to its role in affective states, social behaviors, and diverse physiological functions. However, approaches for measuring endogenous oxytocin concentrations have generated considerable controversy and debate. Common procedures for measuring oxytocin often produce uncorrelated results, and the detected concentrations frequently vary across two orders of magnitude. These findings have led some researchers to argue that immunoassays of plasma oxytocin may be unreliable and nonspecific, particularly when samples are not first processed using an extraction procedure. Here, we assess the specificity of oxytocin immunoassays using plasma samples from wildtype (WT) and oxytocin knockout (KO) mice. Plasma samples from both genotypes were measured using immunoassay and were measured with or without a solid-phase extraction. Using a commercially available kit from Arbor Assays, we demonstrate that both techniques generate a clear contrast between genotypes, with wildtype samples containing high concentrations of oxytocin (unextracted mean = 468 pg/ml; extracted mean = 381 pg/ml), while knockout samples measured below the lower limit of detection. Analytical validations demonstrated good parallelism and spike recovery for both methods. Furthermore, the same wildtype samples measured with both procedures were highly correlated (r = 0.95), although unextracted samples measured at significantly higher concentrations (p = 2.0 ×10-7, Cohen's d = 2.65). To test the generalizability of these results across immunoassay kits, we performed additional assays with kits from Cayman Chemical and Enzo Life Sciences. The Cayman Chemical kit produced results similar to Arbor Assays with a clean signal differentiating WT and KO plasma, both with and without an extraction step. The Enzo kit also differentiated the genotypes, with correlation between extracted and unextracted samples, but was considerably more susceptible to interference without the extraction, as evidenced by false positive signal in KO plasma samples. The extent to which these results generalize to other species remains unknown and challenging to assess.

Oxytocin levels tend to be lower in autistic children: A meta-analysis of 31 studies.

LAY ABSTRACT: Oxytocin is a hormone that mediates interpersonal relationships through enhancing social recognition, social memory, and reducing stress. It is released centrally into the cerebrospinal fluid, as well as peripherally into the blood, where it can easily be measured. Some studies indicate that the oxytocin system with its social implications might be different in people with autism spectrum disorder. With summarizing evidence of 31 studies, this meta-analysis suggests that children with autism spectrum disorder have lower blood oxytocin levels compared to neurotypical individuals. This might not be the case for adults with autism spectrum disorder, where we could not find a difference. Our findings motivate further exploration of the oxytocin system in children with autism spectrum disorder. This could lead to therapeutic options in treating autism spectrum disorder in childhood.

Oxytocin and cortisol release during suckling, hand-milking and machine milking in camels.

This research paper addresses the hypothesis that oxytocin (OT) could be released during suckling and during milking with and without the presence of a calf and that this release could be regulated by maternal behaviour. Plasma concentration patterns of OT and cortisol (CORT) were measured in six Tunisian dromedary camels during 2 suckling episodes, 2 manual milking episodes with calves beside the mother and 2 machine milking episodes without calves present. Various patterns of OT release were observed between each camel including specific two peak release patterns. Higher plasma OT concentrations were found during the suckling and hand-milking episodes with simultaneous suckling of calves, than during the machine milking episodes without calves. Exclusive mechanical milking episodes also evoked significant mean OT release, although greatly reduced compared to suckling and hand milking. The low basal levels and classical CORT release patterns suggested non-stressful management practices were used and there were very limited differences in udder stimulation between managements. The OT release induced by exclusive suckling and suckling together with hand-milking gives a reference point for what a good milk ejection stimulation is in camels. The important and specific reduction of OT release during machine milking without the calf present could be a physiological consequence of the maternal behaviour (selectivity for the own young) and to a lesser extent explained by a lower stimulation by machine milking.

Brief communication: Plasma cortisol concentration is affected by lactation, but not intra-nasal oxytocin treatment, in beef cows.

In mammals, including sheep and mice, lactation attenuates the hypothalamo-pituitary-adrenal axis and plasma cortisol concentration. Oxytocin, one neuropeptide present in the blood during lactation, may contribute to such stress attenuation. Providing oxytocin intra-nasally increases plasma oxytocin concentration in cattle and can be used in non-lactating cows to mirror plasma oxytocin concentration of lactating cows. Therefore, our hypothesis was that there would be no difference in plasma cortisol between non-lactating beef cows intra-nasally administered oxytocin and lactating beef cows intra-nasally treated with saline. Twenty Bos taurus cows were randomly allocated by lactational status to one of four treatments, in a 2×2 factorial arrangement: 1) Non-lactating, saline (NL-S; n = 5); 2) Non-lactating, oxytocin (NL-OXT; n = 5); 3) Lactating, saline (L-S; n = 5); and 4) Lactating, oxytocin (L-OXT; n = 5). Two hours pre-treatment, cows were catheterized, moved to their appropriate chute and baseline blood samples were collected at -60, -45, -30, and 0 minutes before treatments were administered. Directly following the 0-minute sample, cows were administered their intra-nasal treatment via a mucosal atomization device. Subsequently, blood was collected at 2, 4, 6, 8, 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, and 120 minutes. Non-lactating cows had greater (P = 0.02) plasma cortisol concentration compared with lactating cows. There was no lactation by treatment interactions for either plasma cortisol (P = 0.55) or oxytocin (P = 0.89) concentration. Although a treatment by time interaction was identified for oxytocin (P < 0.0001), there was no main effect of lactation on plasma oxytocin concentration (P = 0.34). Similar oxytocin and dissimilar cortisol concentration in lactating and non-lactating cows indicate that oxytocin alone cannot be responsible for reduced plasma cortisol in lactating ruminants. Further investigations are needed to elucidate alternative mechanisms that may be involved in the stress hypo-responsive condition of lactating mammals.

Oxytocin levels in response to pituitary provocation tests in healthy volunteers.

OBJECTIVE: Oxytocin, secreted into circulation through the posterior pituitary, regulates lactation, weight, and socio-behavioral functioning. Oxytocin deficiency has been suggested in patients with hypopituitarism; however, diagnostic testing for oxytocin deficiency has not been developed. The aim of this study was to investigate known pituitary provocation tests to stimulate plasma oxytocin. DESIGN: Sixty-five healthy volunteers underwent either the hypertonic saline or arginine infusion test, known to stimulate copeptin, or the oral macimorelin test, known to stimulate growth hormone. Plasma oxytocin was measured before and once plasma sodium level ≥ 150 mmol/L for the hypertonic saline, after 60 min for the arginine infusion, and after 45 min for the oral macimorelin test (expected peak of copeptin and growth hormone levels, respectively). Primary outcome was a change from basal to stimulated oxytocin levels using paired t-tests. RESULTS: As expected, copeptin increased in response to hypertonic saline and arginine infusion (P < 0.001), and growth hormone increased to oral macimorelin (P < 0.001). Oxytocin increased in response to hypertonic saline infusion from 0.4 (0.2) to 0.6 pg/mL (0.3) (P = 0.003) but with a high variance. There was no change to arginine infusion (P = 0.4), and a trend to lower stimulated levels to oral macimorelin (P = 0.05). CONCLUSION: Neither the arginine infusion nor the oral macimorelin test stimulates plasma oxytocin levels, whereas there was an increase with high variance upon hypertonic saline infusion. As a predictable rise in most participants is required for a reliable pituitary provocation test, none of the investigated pituitary provocation tests can be recommended diagnostically to identify patients with an oxytocin deficiency.

Oxytocin blood concentrations in alcohol use disorder: A cross-sectional, longitudinal, and sex-separated study.

Alcohol use disorder (AUD) is a severe illness, for which we lack sufficient mechanistic understanding. Preliminary evidence associates AUD with the oxytocin (OXT) system. Here we investigated alterations in endogenous OXT blood concentrations in patients with AUD and their association with alcohol drinking and prospective course. In sex-separated analyses, OXT serum concentrations of 200 in-patients with AUD (56.5% male; baseline, 24-72 h of abstinence) were compared with those of 240 age-matched healthy controls (55.4% male), investigated longitudinally (follow-up, 5 days later), and tested for associations with alcohol drinking behavior and prospective 24-month alcohol-related hospital readmissions. At baseline, the patients showed increased OXT concentrations relative to controls (men, 156%, P < 0.001; women, 124%, P = 0.002). The elevations normalized at follow-up. In male patients, baseline OXT concentrations correlated positively with alcohol concentration at admission, the amount of alcohol consumption per drinking year, and the number of previous withdrawal treatments (Rho > 0.195, P < 0.044). In beverage type-specific analysis, baseline OXT concentrations correlated with liquor consumption positively in male and negatively in female patients (|Rho| > 0.277, P < 0.017). Higher baseline OXT concentrations predicted more readmissions and fewer days to the first readmission (|Rho| > 0.185, P < 0.050) in male patients. This study provides novel and sex-separated insights into the role of the OXT system in AUD. We identified a mechanism that might underlie the sex-separated choice of beverage type and established that increased OXT concentrations during early abstinence predict a worse outcome in male patients with AUD.

Oxytocin receptor gene polymorphism and low serum oxytocin level are associated with hyperphagia and obesity in adolescents.

BACKGROUND/OBJECTIVES: In recent years, oxytocin (OXT) and polymorphisms in the oxytocin receptor (OXTR) gene have been reported to play roles in obesity pathogenesis. However, there was no study evaluating OXTR gene variants in childhood obesity. The aim of the study was to investigate the relation of OXTR gene polymorphisms and serum OXT levels with metabolic and anthropometric parameters in obese and healthy adolescents. SUBJECTS/METHODS: The study was a multi-centered case-control study, which was conducted on obese and healthy adolescents aged between 12 and 17 years. Serum OXT and leptin levels were measured, and OXTR gene variants were studied by qPCR (rs53576) and RFLP (rs2254298) methods. RESULTS: A total of 250 obese and 250 healthy adolescents were included in this study. In the obese group, serum OXT level was lower and leptin level was higher than the control group. In the obese group, frequencies of homozygous mutant (G/G) and heterozygous (A/G) genotypes for rs53576 polymorphism were higher than the control group. Homozygous mutant(G/G) and heterozygous (A/G) genotypes for rs53576 polymorphism were found to increase the risk of obesity compared to the wild type (A/A) genotype [OR = 6.05 and OR = 3.06; p < 0.001, respectively]. In patients with homozygous mutant (G/G) and heterozygous (A/G) genotype for rs53576 polymorphism, serum OXT levels were lower than the wild type (A/A) genotype. In the obese group, hyperphagia score was higher than the control group and correlated negatively with serum OXT level. CONCLUSIONS: This study revealed that low serum OXT level, which is associated with hyperphagia may be an underlying cause for obesity in adolescents. For rs53576 polymorphism of the OXTR gene, obesity risk is higher in patients with homozygous mutant(G/G) and heterozygous(A/G)genotypes.