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Mental disorders and related behaviors such as suicidality and violence have been associated to dysregulation of e g carbohydrate metabolism. We hypothesized that patients after suicide attempt, compared to healthy controls, would have higher insulin and lower glucagon levels in plasma and cerebrospinal fluid and that these changes would be associated to violent behavior. Twenty-eight medication-free patients (10 women, 18 men), hospitalized after suicide attempt, and 19 healthy controls (7 women, 12 men) were recruited with the aim to study risk factors for suicidal behavior. Psychological/psychiatric assessment was performed with SCID I and II or the SCID interview for healthy volunteers respectively, the Karolinska Interpersonal Violence Scale (KIVS) for assessment of lifetime violence expression behavior, the Montgomery-Åsberg-Depression-Scale (MADRS) and the Comprehensive Psychological Rating Scale (CPRS) for symptomatic assessment of depression and appetite. Fasting levels of insulin and glucagon were measured in plasma (P) and cerebrospinal fluid (CSF). Suicide attempters had higher insulin- and lower glucagon-levels in plasma- and CSF compared to controls. Except for P-glucagon these associations remained significant after adjusting for age and/or BMI. Patients reported significantly more expressed interpersonal violence compared to healthy volunteers. Expressed violence was significantly positively correlated with P- and CSF-insulin and showed a significant negative correlation with P-glucagon in study participants. These findings confirm and extend prior reports that higher insulin and lower glucagon levels in plasma and cerebrospinal fluid are associated with suicidal behavior pointing towards a potential autonomic dysregulation in the control of insulin and glucagon secretion in suicidal patients., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

The oxytocin system is regarded as being of relevance for social interaction. In spite of this, very few studies have investigated the relationship between oxytocin and personality traits in clinical psychiatric populations. We assessed the relationship between personality traits and plasma oxytocin levels in a population of 101 medication-free psychiatric outpatients (men = 37, women = 64). We used the Karolinska Scale of Personality (KSP) and diagnostic and symptomatic testing. Plasma oxytocin levels were analysed with a specific radioimmunoassay at inclusion and after one month for testing of stability. Plasma oxytocin levels were stable over time and did not differ between patients with or without personality disorders, nor were they related to severity of depressive or anxiety symptoms. The KSP factors Impulsiveness and Negative Emotionality were significant independent predictors of plasma oxytocin. A subscale analysis of these personality factors showed significant positive correlations between baseline plasma oxytocin and the KSP subscales monotony avoidance and psychic anxiety. The significant association between the KSP factor Impulsiveness and oxytocin levels observed at baseline was observed also one month later in men. These findings suggest that personality traits such as Impulsiveness and Negative emotionality which are linked to social functioning in several psychiatric disorders seem to be associated with endogenous plasma oxytocin levels. These variations in oxytocin levels might have an impact on social sensitivity or social motivation with possible gender differences., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Data from animal studies suggest that oxytocin is an important modulating neuropeptide in regulation of social interaction. One human study has reported a negative correlation between CSF oxytocin levels, life history of aggression and suicidal behaviour. We hypothesized that CSF oxytocin levels would be related to suicidal behaviour, suicide intent, lifetime interpersonal violence and suicide risk. 28 medication free suicide attempters and 19 healthy volunteers participated in this cross sectional and longitudinal study. CSF and plasma morning basal levels of oxytocin were assessed with specific radio-immunoassays. The Beck Suicide Intent Scale (SIS), the Freeman scale and the Karolinska Interpersonal Violence Scale (KIVS) were used to assess suicide intent and lifetime violent behaviour. All patients were followed up for cause of death. The mean follow-up was 21 years. Suicide attempters had lower CSF oxytocin levels compared to healthy volunteers p=0.077. In suicide attempters CSF oxytocin showed a significant negative correlation with the planning subscale of SIS. CSF oxytocin showed a significant negative correlation with suicide intent, the planning subscale of SIS and Freeman interruption probability in male suicide attempters. Correlations between plasma oxytocin levels and the planning subscale of SIS and Freeman interruption probability were significant in male suicide attempters. Lifetime violent behaviour showed a trend to negative correlation with CSF oxytocin. In the regression analysis suicide intent remained a significant predictor of CSF oxytocin corrected for age and gender whereas lifetime violent behaviour showed a trend to be a predictor of CSF oxytocin. Oxytocin levels did not differ significantly in suicide victims compared to survivors. CSF oxytocin may be an important modulator of suicide intent and interpersonal violence in suicide attempters., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Oxytocin induces a long-lasting reduction of blood pressure in rats. The aim of the present study was to investigate the effects of an acute stressor on blood pressure and heart rate in rats previously exposed to repeated administration of intracerebroventricular (ICV) oxytocin. For this purpose oxytocin (0.3 microg, ICV) was administered to male rats once a day during 5 days. Blood pressure and heart rate were measured before and after treatment. In addition, blood pressure and heart rate were measured during 30 min after exposure to 10s of noise from an alarm clock. The oxytocin treatment reduced blood pressure significantly (systolic: 108+/-4.6 vs. 121+/-1.8, p<0.01, diastolic: 96+/-5.1 vs. 108+/-3.0, p<0.01), whereas heart rate remained unchanged. In contrast, systolic and diastolic blood pressure increased significantly after the exposure to the ringing alarm clock in the oxytocin-treated rats (p<0.05), and became equal to the blood pressure in controls. In addition, heart rate increased and stayed significantly higher in the oxytocin-treated rats compared to the controls during the 30 min observation period (ANOVA p<0.01). Twenty-four hours later, blood pressure was again significantly lower in the oxytocin-treated rats compared to controls (p<0.01). In conclusion, oxytocin decreased blood pressure without changing pulse rate. However, when the oxytocin-treated rats were subjected to the unexpected noise from a ringing alarm clock blood pressure and heart rate increased significantly. No such effect was observed in the control group. Thus repeated oxytocin treatment can, in spite of decreasing blood pressure during basal conditions, increase cardiovascular reactivity to some types of stressors.

During breastfeeding or suckling, maternal oxytocin levels are raised by somatosensory stimulation. Oxytocin may, however, also be released by nonnoxious stimuli such as touch, warm temperature etc. in plasma and in cerebrospinal fluid. Consequently, oxytocin may be involved in physiological and behavioral effects induced by social interaction in a more general context. In both male and female rats oxytocin exerts potent physiological antistress effects. If daily oxytocin injections are repeated over a 5-day period, blood pressure is decreased by 10-20 mmHg, the withdrawal latency to heat stimuli is prolonged, cortisol levels are decreased and insulin and cholecystokinin levels are increased. These effects last from 1 to several weeks after the last injection. After repeated oxytocin treatment weight gain may be promoted and the healing rate of wounds increased. Most behavioral and physiological effects induced by oxytocin can be blocked by oxytocin antagonists. In contrast, the antistress effects can not, suggesting that unidentified oxytocin receptors may exist. The prolonged latency in the tail-flick test can be temporarily reversed by administration of naloxone, suggesting that endogenous opioid activity has been increased by the oxytocin injections. In contrast, the long-term lowering of blood pressure and of cortisol levels as well as the sedative effects of oxytocin have been found to be related to an increased activity of central alpha 2-adrenoceptors. Positive social interactions have been related to health-promoting effects. Oxytocin released in response to social stimuli may be part of a neuroendocrine substrate which underlies the benefits of positive social experiences. Such processes may in addition explain the health-promoting effects of certain alternative therapies. Because of the special properties of oxytocin, including the fact that it can become conditioned to psychological state or imagery, oxytocin may also mediate the benefits attributed to therapies such as hypnosis or meditation.

This paper outlines two pathways through which social support can influence the prevention or progression of cardiovascular disease: health behaviors and neuroendocrine mechanisms. Its primary focus is on neuroendocrine pathways, reviewing data which suggest that lack of social support is etiologically related to coronary artery lesion development through two mechanisms: sympathetic-adrenomedullary influences on platelet function, heart rate and blood pressure in the initial endothelial injury; and pituitary-adrenal cortical factors involved in smooth muscle cell proliferation during progression of the lesion after injury has taken place. It hypothesizes that the buffering effect of social support on the cardiovascular system is mediated primarily through mechanisms associated with the release of oxytocin.

A group of 17 consecutive regularly menstruating women who gained at least 5 kg the previous year (Group 1) was compared with a control group of similar age, parity and social class (Group 2). Galactorrhea was observed in 6/17 women from group 1 and in 1/16 women from group 2 (chi 2 4.571; p < .05). Average morning prolactin levels were higher in group 1 (8.15 +/- 4.92 micrograms/l) than in group 2 (5.29 +/- 2.48 micrograms/l; p < .05). The two groups were similar in their morning thyroxin, triiodothyronine, TSH, estradiol, cortisol, gastrin, cholecystokinin, somatostatin, oxytocin, insulin and IGF-1 levels. Leptin levels were significantly higher in group 1 than in group 2 (18.85 +/- 10.63 micrograms/l vs. 10.15 +/- 6.38 micrograms/l; p < .02) but this difference could be attributed exclusively to the higher body mass index (BMI) of group 1 (MANCOVA). Analysis of the distribution of basal prolactin levels in group 1 revealed a skewed distribution due to the presence of six outliers (Barnett and Lewis test associated with Mahalanobis distance) whose values were higher than the highest value found in group 2. These outliers were henceforth considered as subgroup 1a, and the remnant patients in group 1 as subgroup 1b. Besides the expected difference in basal prolactin levels between subgroups 1a and 1b (13.72 +/- 3.69 and 5.12 +/- 1.81 micrograms/l, respectively) and the higher frequency of galactorrhea in group 1a (4/6 vs. 2/11; p < .05) no other differences were observed in clinical or basal biochemical parameters. Following domperidone (10 mg, i.v.) the percentual increase in prolactin (delta Prl 20'/Prl 0') was significantly lower in group 1 than in group 2 (23.9 + 15.2 vs. 37.0 +/- 21.2; p < .05). In absolute values, the prolactin rise in subgroup 1a (100.7 +/- 45.5 micrograms/l) was significantly lower (p < .02) than that of subgroup 1b (157.3 +/- 50.3 micrograms/l) and group 2 (152.7 +/- 34.5 micrograms/l). Group 1 (and each one of its two sub-groups) also differed from group 2 in a higher incidence of meaningful life-events the year preceding the study. This study confirms previous observations that recent weight gain in women is preceded by important life-events and is associated with galactorrhea and increased prolactin levels in a number of them. Besides, it provides evidence that the increased prolactin levels are due to reduced hypothalamic dopaminergic tone.

Adult male Sprague-Dawley rats were administered the 5-HT subtype selective receptor agonists 8-OH-DPAT (0.5-2.0 mg/kg), buspirone (2-8 mg/kg) (5-HT1A), TFMPP (0.125-2.0 mg/kg) (5-HT1B), DOI (0.125-2.0 mg/kg) (5-HT2A) and m-CPBG (1.25-20.0 mg/kg) (5-HT3), subcutaneously. Oxytocin, cholecystokinin (CCK), somatostatin and gastrin plasma levels were determined by standard RIA techniques 30 and 120 min after injection of the respective 5-HT receptor agonist. It was found that the 5-HT1A and the 5-HT2A/C, but not the 5-HT2B or the 5-HT3 receptor agonists produced an increase in plasma oxytocin levels and these effects were, at least partially, antagonized by the corresponding subtype selective antagonists (-)pindolol (2 mg/kg) and ritanserin (2 mg/kg), respectively, administered 10 min before 8-OH-DPAT (0.5 mg/kg) or DOI (0.5 mg/kg). The maximal response to the 5-HT1A receptor agonists (approx. 120 nmol/l) was from 8 to 5 times the maximal response to the 5-HT2A C receptor agonist. In addition, 8-OH-DPAT and DOI caused a decrease in plasma CCK levels, whereas the 5-HT1B receptor agonist TFMPP gave rise to an increase in plasma CCK levels. There were no statistically significant effects by any of the 5-HT receptor agonists on plasma somatostatin or gastrin levels under the present conditions. It is suggested that the clinical effects of new anxiolytic 5-HT1A receptor agonists, such as buspirone, to an extent may be mediated via an increased release of oxytocin.

The vagal nerves convey information between the brain and the gastrointestinal tract in both afferent and efferent direction. The efferent vagal nerves regulate gastrointestinal secretory and motor function and also the activity in the endocrine system of the gut. Gastrointestinal function and anabolic metabolism is optimized during gestation and lactation as a means of saving energy for this calorie-demanding process. This enhanced activity seems to involve central oxytocinergic transmission which increases efferent vagal nerve activity as reflected by altered levels of gastrointestinal hormones in plasma. In parallel a behaviour pattern characterized by sedation is induced. In addition, vagal afferents transfer information from the gut to the brain, e.g. as to the presence or absence of calories in the gastrointestinal tract. It is well known that satiety and sedation following a meal is in part caused by an activation of vagal afferents in response to food intake. Cholecystokinin released from the intestine is one of the factors that triggers the afferent vagal nerve activity. Also reproductive "interactive behaviours" such as milk ejection and maternal behaviour can be induced by CCK via afferent activation of vagal nerves. In contrast, when no food reaches the gut, milk production and ejection is blocked. Parts of these effects are vagally mediated, since they can be observed in vagotomized rats receiving full amounts of calories.

In earlier studies performed on a group of women with gastrointestinal symptoms, significant positive correlations between the gastrointestinal hormone gastrin and anxiety, and a negative correlation with socialization were obtained. These and other relationships were tested on 33 healthy women. A comprehensive and concise statistical model was used for the analysis of correlations between, on one hand, the levels of oxytocin and the gastrointestinal hormones gastrin, cholecystokinin, somatostatin and insulin, and, on the other hand, personality traits. Almost all explained variance of the hormone levels could be referred to three personality trait factors, Anxiety, Aggressive non-conformity, and Detachment. The statistical explanation of the gastrin level variance was most successful, the three personality trait factors explaining 48% of this variance. Gastrin "increased" Anxiety while reducing Aggressive non-conformity and Detachment. A similar pattern for insulin was also reliable. Considering general trends, the negative correlations between all hormones and Detachment are interesting. Present data suggest that there is a psychoendocrinological antithesis to the fight-flight individual, characterized by high activity in the sympathoadrenal system: these contrasting persons, with high levels of the gastrointestinal hormones gastrin and insulin, tend to be warm and caring and non-aggressive--but often not free from anxiety. We do not think that the demonstrated associations between hormone levels and personality traits implicate a direct causal relationship. They rather may mirror the activity of centrally acting or hypothalamic control systems which influence both behavioural and endocrine profiles.

The Karolinska Scales of Personality (KSP) and some dimensions of the Bergman scale reflecting social dependency and self-confidence were used in 24 individuals with functional disorders of the gastrointestinal tract. Patients showed higher scores of somatic anxiety, indirect aggression and irritability and lower scores in socialization when compared with a reference group. The levels of gastrointestinal symptoms as well as the levels of some hormones related to vagal nerve activity in this patient group have been reported in a previous publication. When the scores obtained in personality inventories were related to symptom levels, we found significant correlations with intestinal but not abdominal symptoms. Gastrin levels correlated inversely with socialization. Somatostatin levels on the other hand, correlated negatively with social dependency and positively with self-confidence in the Bergman scale. Interestingly, oxytocin levels correlated positively with social dependency and in addition with indirect aggression and verbal aggression. The correlation between hormone levels and scores of personality dimensions will be interpreted and discussed within a physiological context.

Twenty-four individuals with functional disorders of the gastrointestinal tract participated in the study. Symptoms from the upper and lower gastrointestinal tract were recorded by means of a self-administered questionnaire before, 3 months and 3 yr after participation in group therapy. Blood was sampled from the patients while they were subjected to three different provocations (a friendly greeting, a food stimulus and a stress stimulus). Ten subjects without gastrointestinal symptoms participated in an identical experiment. Gastrin, somatostatin and oxytocin levels were measured with radioimmunoassay. Both gastrin and somatostatin levels were influenced by the provocations and by the greeting and the stress stimulus in particular. In principle, the controls tended to react with a parasympathetic response pattern following the interactive stimuli, whereas the individuals with functional disorders of the gastrointestinal tract reacted with an activation of the sympathetic nervous system. Somatostatin levels were significantly higher and oxytocin levels lower in patients than in controls and gastrin levels tended to be higher in patients than in controls. Most individuals reported both gastric as well as intestinal symptoms. Gastrin levels correlated positively with total symptom level and somatostatin levels with intestinal symptoms scores reported by the patients.