Naturally occurring low sociality in female rhesus monkeys: A tractable model for autism or not?

BACKGROUND: Autism spectrum disorder (ASD) is characterized by persistent social interaction impairments and is male-biased in prevalence. We have established naturally occurring low sociality in male rhesus monkeys as a model for the social features of ASD. Low-social male monkeys exhibit reduced social interactions and increased autistic-like trait burden, with both measures highly correlated and strongly linked to low cerebrospinal fluid (CSF) arginine vasopressin (AVP) concentration. Little is known, however, about the behavioral and neurochemical profiles of female rhesus monkeys, and whether low sociality in females is a tractable model for ASD. METHODS: Social behavior assessments (ethological observations; a reverse-translated autistic trait measurement scale, the macaque Social Responsiveness Scale-Revised [mSRS-R]) were completed on N = 88 outdoor-housed female rhesus monkeys during the non-breeding season. CSF and blood samples were collected from a subset of N = 16 monkeys across the frequency distribution of non-social behavior, and AVP and oxytocin (OXT) concentrations were quantified. Data were analyzed using general linear models. RESULTS: Non-social behavior frequency and mSRS-R scores were continuously distributed across the general female monkey population, as previously found for male monkeys. However, dominance rank significantly predicted mSRS-R scores in females, with higher-ranking individuals showing fewer autistic-like traits, a relationship not previously observed in males from this colony. Females differed from males in several other respects: Social behavior frequencies were unrelated to mSRS-R scores, and AVP concentration was unrelated to any social behavior measure. Blood and CSF concentrations of AVP were positively correlated in females; no significant relationship involving any OXT measure was found. LIMITATIONS: This study sample was small, and did not consider genetic, environmental, or other neurochemical measures that may be related to female mSRS-R scores. CONCLUSIONS: Dominance rank is the most significant predictor of autistic-like traits in female rhesus monkeys, and CSF neuropeptide concentrations are unrelated to measures of female social functioning (in contrast to prior CSF AVP findings in male rhesus monkeys and male and female autistic children). Although preliminary, this evidence suggests that the strong matrilineal organization of this species may limit the usefulness of low sociality in female rhesus monkeys as a tractable model for ASD.

Sex-specific issues of central and peripheral arginine-vasopressin concentrations in neurocritical care patients.

BACKGROUND: Arginine-Vasopressin (AVP) is a nonapeptide that exerts multiple functions within the central nervous system and in the blood circulation that might contribute to outcome in critically ill patients. Sex differences have been found for mental and physical effects of AVP. For example, stress response and response due to hemorrhage differ between males and females, at least in animal studies. Data on humans -especially on AVP within the central nervous system (CNS)-are scarce, as cerebrospinal fluid (CSF) which is said to represent central AVP activity, has to be collected by means of invasive procedures. Here we present data on 30 neurocritical care patients where we simultaneously collected blood, CSF and saliva to analyze concentrations in the central and peripheral compartments. PATIENTS AND METHODS: 30 neurocritical care patients were included (13 male, 13 postmenopausal female, 4 premenopausal female) with a median age of 60 years. CSF, plasma and saliva were obtained simultaneously once in each patient and analyzed for AVP concentrations. Correlations between the central compartment represented by CSF, and the peripheral compartment represented by plasma and saliva, were identified. Relations between AVP concentrations and serum sodium and hematocrit were also determined. RESULTS: In the whole patient collective, only very weak to weak correlations could be detected between AVP plasma/CSF, plasma/saliva and CSF/saliva as well as between AVP concentrations in each of the compartments and serum sodium/hematocrit. Regarding the subgroup of postmenopausal females, a significant moderate correlation could be detected for AVP in plasma and CSF and AVP CSF and serum sodium. CONCLUSION: Absolute concentrations of AVP in central and peripheral compartments did not show sex differences. However, correlations between AVP plasma and CSF and AVP CSF and serum sodium in postmenopausal females indicate differences in AVP secretion and AVP response to triggers that deserve further examination.

Neonatal CSF vasopressin concentration predicts later medical record diagnoses of autism spectrum disorder.

Autism spectrum disorder (ASD) is a brain disorder characterized by social impairments. ASD is currently diagnosed on the basis of behavioral criteria because no robust biomarkers have been identified. However, we recently found that cerebrospinal fluid (CSF) concentration of the "social" neuropeptide arginine vasopressin (AVP) is significantly lower in pediatric ASD cases vs. controls. As an initial step in establishing the direction of causation for this association, we capitalized upon a rare biomaterials collection of newborn CSF samples to conduct a quasi-prospective test of whether this association held before the developmental period when ASD first manifests. CSF samples had been collected in the course of medical care of 0- to 3-mo-old febrile infants (n = 913) and subsequently archived at -70 °C. We identified a subset of CSF samples from individuals later diagnosed with ASD, matched them 1:2 with appropriate controls (n = 33 total), and quantified their AVP and oxytocin (OXT) concentrations. Neonatal CSF AVP concentrations were significantly lower among ASD cases than controls and individually predicted case status, with highest precision when cases with comorbid attention-deficit/hyperactivity disorder were removed from the analysis. The associations were specific to AVP, as ASD cases and controls did not differ in neonatal CSF concentrations of the structurally related neuropeptide, OXT. These preliminary findings suggest that a neurochemical marker of ASD may be present very early in life, and if replicated in a larger, prospective study, this approach could transform how ASD is detected, both in behaviorally symptomatic children, and in infants at risk for developing it.

Absence of a diurnal rhythm of oxytocin and arginine-vasopressin in human cerebrospinal fluid, blood and saliva.

PURPOSE: The aims of our study were to determine first circadian influences on central concentrations of the neuropeptides oxytocin and arginine-vasopressin and second to investigate if these central concentrations are associated with those in the peripheral compartments blood and saliva in neurocritical care patients. We therefore included patients with external ventricular drain who attended a neurosurgical intensive care unit and were not exposed to painful or stressful stimuli during the sampling period. For this purpose, blood, cerebrospinal fluid and saliva were collected in a 24-hour-interval at the timepoints 06:00, 12:00, 18:00 and 24:00. RESULTS: In none of the three body fluids examined, significant time-dependent fluctuations of oxytocin and arginine-vasopressin concentrations could be detected during the 24-hour sampling period. The only exception was the subgroup of postmenopausal women whose oxytocin concentrations in cerebrospinal fluid at 12:00 were significantly higher than at 18:00. Correlations of blood and cerebrospinal fluid and blood and saliva neuropeptide levels were very weak to weak at each timepoint. Cerebrospinal fluid and saliva oxytocin levels showed a moderate correlation at 06:00 but did correlate very weak at the other timepoints. CONCLUSIONS: Central as well as peripheral oxytocin and arginine-vasopressin concentrations in neurocritical care patients did not show significant diurnal fluctuations. No strong correlations between central and peripheral neuropeptide concentrations could be detected under basal conditions. If investigators even though decide to use saliva concentrations as surrogate parameter for central neuropeptide activity, they have to consider that correlations of cerebrospinal fluid and saliva oxytocin seem to be highest in the early morning.

Influence of perioperative stress on central and peripheral oxytocin and arginine-vasopressin concentrations.

Perioperative stress provides not only physical, but also psychic and emotional aspects, which may influence the hypothalamic neuropeptide system. Studies investigating the perioperative course of central neuropeptide activity are missing. Therefore, the present study aimed to determine perioperative fluctuations in central and concomitant peripheral concentrations of the hypothalamic neuropeptides oxytocin (OXT) and arginine-vasopressin (AVP), as well as their impact on perioperative anxiety and depression. Cerebrospinal fluid (CSF), blood and saliva were collected from 12 patients who underwent elective endovascular aortic repair with a routinely inserted spinal catheter. AVP and OXT concentrations were analysed at four timepoints: (i) the evening before the operation; (ii) the operation day immediately before anaesthesia induction; (iii) intraoperatively after the stent was placed; and (iv) on day 1 after the operation. Patients completed the Hospital Anxiety and Depression Scale (HADS) at timepoints 1 and 4. For CSF OXT, the present study showed a significant intraoperative decline, accompanied by a decrease in saliva. OXT blood concentrations before anaesthesia induction were higher than at the evening before the operation. OXT concentrations in CSF and saliva correlated well at timepoints 2-4. AVP concentrations in CSF, blood and saliva did not show any significant changes perioperatively. However, postoperative AVP blood concentrations showed a significant negative correlation with anxiety and depression scores according to the HADS. This pilot study demonstrates perioperative fluctuations in central OXT concentrations, which are better reflected by saliva than by blood. Further studies are required to determine whether OXT and AVP can predict postoperative post-traumatic stress disorder.

Arginine vasopressin in cerebrospinal fluid is a marker of sociality in nonhuman primates.

Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by core social impairments. ASD remains poorly understood because of the difficulty in studying disease biology directly in patients and the reliance on mouse models that lack clinically relevant, complex social cognition abilities. We use ethological observations in rhesus macaques to identify male monkeys with naturally occurring low sociality. These monkeys showed differences in specific neuropeptide and kinase signaling pathways compared to socially competent male monkeys. Using a discovery and replication design, we identified arginine vasopressin (AVP) in cerebrospinal fluid (CSF) as a key marker of group differences in monkey sociality; we replicated these findings in an independent monkey cohort. We also confirmed in an additional monkey cohort that AVP concentration in CSF is a stable trait-like measure. Next, we showed in a small pediatric cohort that CSF AVP concentrations were lower in male children with ASD compared to age-matched male children without ASD (but with other medical conditions). We demonstrated that CSF AVP concentration was sufficient to accurately distinguish ASD cases from medical controls. These data suggest that AVP and its signaling pathway warrant consideration in future research studies investigating new targets for diagnostics and drug development in ASD.

The role of arginine vasopressin in electroacupuncture treatment of primary sciatica in human.

It has been implicated that electroacupuncture can relieve the symptoms of sciatica with the increase of pain threshold in human, and arginine vasopressin (AVP) in the brain rather than the spinal cord and blood circulation participates in antinociception. Our previous study has proven that AVP in the brain played a role in the process of electroacupuncture analgesia in rat. The goal of the present study was to investigate the role of AVP in electroacupuncture in treating primary sciatica in human. The results showed that (1) AVP concentration of cerebrospinal fluid (CSF) (7.5 ± 2.5 pg/ml), not plasma (13.2 ± 4.2 pg/ml) in primary sciatica patients was lower than that in health volunteers (16.1 ± 3.8 pg/ml and 12.3 ± 3.4 pg/ml), although the osmotic pressure in CSF and plasma did not change; (2) electroacupuncture of the bilateral "Zusanli" points (St. 36) for 60 min relieved the pain sensation in primary sciatica patients; (3) electroacupuncture increased the AVP level of CSF, not plasma in primary sciatica patients; and (4) there was the positive correlation between the effect of electroacupuncture relieving the pain and the AVP level of CSF in the primary sciatica patients. The data suggested that central AVP, not peripheral AVP might improve the effect of electroacupuncture treatment of primary sciatica in human, i.e., central AVP might take part in the electroacupuncture relieving the pain sensation in primary sciatica patients.

The influence of psychological stress on arginine vasopressin concentration in the human plasma and cerebrospinal fluid.

Psychological stress is strain affecting the intangible self, caused by problems in adaptation, perception, and emotions. Previous studies have demonstrated that arginine vasopressin (AVP) plays an important role in psychological stress. The goal of present study was to investigate the interaction between AVP release and cardiovascular functions by measuring AVP concentration and recording blood pressure or heart rate during psychological stress in human. The results showed that (1) psychological stress not only increased the systolic blood pressure, diastolic blood pressure and heart rate, but also elevated the cortisol and AVP concentration in both plasma and CSF in a stress level-dependent manner; (2) there was a positive relationship between plasma AVP concentration and systolic blood pressure, diastolic blood pressure, heart rate or plasma cortisol concentration; (3) there was also a positive relationship between AVP concentrations in plasma and CSF AVP. The data suggested that plasma AVP, which might come from the central nervous system, might influence the cardiovascular functions during psychological stress in human.

Effect of intranasal arginine vasopressin on human headache.

Arginine vasopressin (AVP), a nonapeptide hormone of posterior pituitary, reaches the central nervous system from systemic blood circulation with a difficulty because of the blood-brain barrier (BBB). The interest has been expressed in the use of the nasal route for delivery of AVP to the brain directly, exploiting the olfactory pathway. Our previous study has demonstrated that AVP in the brain rather than the spinal cord and blood circulation plays an important role in rat pain modulation. For understanding the role of AVP on pain modulation in human, the communication tried to investigate the effect of intranasal AVP on human headache. The results showed that (1) AVP concentration in both plasma and cerebrospinal fluid (CSF) increased significantly in headache patients, who related with the headache level; (2) there was a positive relationship between plasma and CSF AVP concentration in headache patients; and (3) intranasal AVP could relieve the human headache in a dose-dependent manner. The data suggested that intranasal AVP, which was delivered to the brain through olfactory region, could treat human headache and AVP might be a potential drug of pain relief by intranasal administration.

The effect of treatment with ketoconazole on central CRH systems of depressed patients.

OBJECTIVES: Steroid-synthesis inhibitors are reported to reduce psychopathology in treatment-resistant depressed patients. METHODS: We studied the effect of a 3-week treatment with ketoconazole on the evening plasma concentrations of cortisol, corticosteroid-binding globulin (CBG), dehydroepiandrosterone-sulfate (DHEA-S) and adrenocorticotrope hormone (ACTH) as well as morning cerebrospinal fluid (CSF) concentrations of cortisol, corticotropin-releasing hormone (CRH) and arginine-vasopressin (AVP) in six elderly treatment-resistant depressed patients. RESULTS: While we found plasma cortisol concentrations to be unchanged, a decline in plasma DHEA-S concentrations indicated effective steroid-synthesis inhibition. In morning CSF we found CRH concentrations that did not change. CONCLUSIONS: Our preliminary observations indicate that the treatment of depressed patients with the steroid-synthesis inhibitor ketoconazole does not lead to a major increase in CSF CRH secretion.

[Effects of moxibustion at head-points on levels of somatostatin and arginine vasopressin from cerebrospinal fluid in patients with vascular dementia: a randomized controlled trial].

BACKGROUND: There are obvious changes in neuropeptides from plasma and cerebrospinal fluid in patients with vascular dementia (VaD), and regulating the levels of neuropeptides is a key for prevention and treatment of VaD. OBJECTIVE: To observe the clinical efficacy of moxibustion at head-points in treatment of vascular dementia (VaD), and assess its effects on memory-related neuropeptides. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS: A total of 65 VaD patients from Acupuncture Hospital, Anhui University of Traditional Chinese Medicine, were randomly divided into moxibustion group (33 cases) and Western medicine group (32 cases). Patients in the moxibustion group were treated with indirect moxibustion with common monkshood cake for 20 min. Patients in the Western medicine group were orally administered piracetam tablets, 0.8 g for three times a day. One treatment course was 4 weeks, and they were treated for 4 treatment courses. MAIN OUTCOME MEASURES: The scores of Hasegawa's Dementia Scale (HDS), Mini-Mental State Examination (MMSE), and Activity of Daily Living Scale (ADL), as well as the levels of learning and memory-related neuropeptides from cerebrospinal fluid such as somatostatin (SS) and arginine vasopressin (AVP) were measured before and after treatment in the two groups. RESULTS: Total response rate was significantly higher in the moxibustion group than in the Western medicine group (P<0.01). There were significant differences in scores of HDS, MMSE and ADL between before and after treatment in the two groups(P<0.05 or P<0.01). After treatment, the scores of HDS, MMSE and ADL in the moxibustion group were more improved as compared with those in the Western medicine group (P<0.05 or P<0.01). The levels of SS and AVP after treatment were higher than those before treatment in the two groups(P<0.01). After treatment, the increased levels of SS and AVP were higher in the moxibustion group than in the Western medicine group (P<0.01). CONCLUSION: Moxibustion is effective in improving the clinical symptom scores and regulating the levels of neuropeptides associated with learning and memory in VaD patients.

Early change of plasma and cerebrospinal fluid arginine vasopressin in traumatic subarachnoid hemorrhage.

OBJECTIVE: To investigate the changes and effects of arginine vasopressin (AVP) in patients with acute traumatic subarachnoid hemorrhage (tSAH). METHODS: The plasma and cerebrospinal fluid (CSF) level of AVP, and intracranial pressure (ICP) were measured in a total of 21 patients within 24 hours after tSAH. The neurological status of the patients was evaluated by Glasgow Coma Scale (GCS). Correlation between AVP and ICP, GCS was analyzed respectively. Meanwhile, 18 healthy volunteers were recruited as control group. RESULTS: Compared with control group, the levels (pg/ml) of AVP in plasma and CSF (x+/-s) in tSAH group were significantly increased within 24 hours (38.72+/-24.71 vs 4.54+/-1.38 and 34.61+/-21.43 vs 4.13+/-.26, P less than 0.01), and was remarkably higher in GCS less than or equal to 8 group than GCS larger than 8 group (50.96+/-36.81 vs 25.26+/-12.87 and 44.68+/-31.72 vs 23.53+/-10.94, P less than 0.05). The CSF AVP level was correlated with ICP (r eqaul to 0.46, P less than 0.05), but no statistically significant correlation was found between plasma AVP, CSF AVP and initial GCS (r equal to -0.29, P larger than 0.05 and r equal to -0.32, P larger than 0.05, respectively). The ICP (mm Hg) in tSAH patients was elevated and higher in GCS less than or equal to 8 group than in GCS larger than 8 group (25.9+/-9.7 vs 17.6+/-5.2, P less than 0.05). CONCLUSION: Our research suggests that AVP is correlated with the severity of tSAH, and may be involved in the pathophysiological process of brain damage in the early stage after tSAH. It seems that compared with the plasma AVP concentration, CSF AVP is more related to the severity of tSAH.

Effect of tooth pulp stimulation on oxytocin and vasopressin release into the cerebrospinal fluid and fluid perfusing the cerebral ventricles in rats.

OBJECTIVE: Stress- and pain-related stimuli cause a release of vasopressin (AVP) and oxytocin (OT) into the cerebrospinal fluid (CSF) and extracellular fluid of the brain in various animal species. The aim of the study was to investigate the effect of stimulation of the nociceptive afferent terminals in the tooth pulp on the release of AVP and OT into CSF in rats under chloralose anesthesia. METHODS: Cerebrospinal fluid was collected from the cerebellomedullary cistern and then 30-minute perfusions of the lateral cerebral ventricles with artificial cerebrospinal fluid (aCSF) were carried out. The perfusate was collected from the cerebellomedullary cistern at rest (control), during electric stimulation of the tooth pulp which induced nociceptive trigemino-hypoglossal reflex, and after stimulation. In the collected CSF and aCSF perfusates, AVP-like immunoreactivity (AVPLI) and OT-like immunoreactivity (OT-LI) were determined by radioimmunoassay (RIA). RESULTS: The concentrations of AVP-LI and OT-LI in CSF were found to reach 21 pg/ml and 67 pg/ml, respectively. Electric tooth pulp stimulation exerted no effect on AVP and OT release into the fluid perfusing the cerebral ventricles during stimulation. CONCLUSION: It was found that noxious stimulus from the tooth pulp is not a factor affecting significantly AVP and OT release into CSF.

Effects of centrally administered vasopressin on orofacial pain perception in rats.

Vasopressin (AVP) appears in the cerebrospinal fluid and plays an important role in nociceptive modulation in the central nervous system. The effect of increased concentration of AVP in the cerebrospinal fluid on the excitability of the hypoglossal nerve nucleus was investigated. The experiments were carried out on rats under chloralose anesthesia. Amplitudes of the retractory evoked tongue jerks (ETJ) of the outstretched tongue during the perfusion of cerebral ventricles with solutions containing AVP or its antagonists and also opioid and serotonin antagonists were recorded. Perfusion of the ventricles with AVP in 100 microM concentration suppressed the ETJ amplitude to 66 +/- 3.83%, and in 200 microM concentration, to 53 +/- 3.18% of the control. V1 vasopressin receptor antagonist, d(CH2)5,Tyr(Me)AVP, blocked the suppressive effect caused by cerebral ventricle perfusion with AVP from 64 +/- 4.11% to 83 +/- 1.58%, whereas V2 vasopressin receptor antagonist, d(CH2)5[Ile2, Ile4]AVP, did not block the antinociceptive effect of AVP. Analgesic effect of AVP was also inhibited by opioid and serotonin receptor antagonists, naloxone and methysergide, respectively. Naloxone blocked the suppressive effect of 100 microM AVP from 64 +/- 5.63% to 92 +/- 3.70% and methysergide from 65 +/- 3.62% to 80 +/- 2.72% of the control. The results indicate that exogenous AVP plays an antinociceptive role in the brain of rats penetrating the lining of the cerebral ventricles into the cerebrospinal fluid and exerting a modulating effect on the tongue motor center situated near III and IV cerebral ventricle. V1 vasopressin receptor, but not V2 vasopressin receptor, is involved in this activity in the CNS. The antinociception of AVP seems to be mediated by opioid and serotonergic pathways.

Vasopressin in CSF and plasma in depressed suicide attempters: preliminary results.

Increased plasma arginine vasopressin (AVP) concentrations have been reported in depressed suicide attempters. Plasma AVP is primarily produced by the magnocellular system in response to increased plasma osmolality, and central AVP may be independently regulated. In the present study we investigated cerebrospinal fluid (CSF) and plasma AVP concentrations in depressed patients and controls. Nineteen drug-free depressed psychiatric inpatients (nine suicide attempters) and nine neurological control subjects underwent lumbar puncture and psychiatric evaluation. CSF and plasma concentrations of AVP, serotonin (5-HT), 5-hydroxyindoleacetic acid (5-HIAA), homovanillic acid (HVA), and cortisol were assayed. In 15 depressed patients (eight suicide attempters), the combined dexamethasone/corticotropin-releasing hormone (Dex/CRH) test was performed to examine the hypothalamic-pituitary-adrenocortical (HPA) system. There were no differences between depressed subjects and controls in all parameters measured. Suicide attempters did not differ from nonattempters. In depressed patients, plasma AVP correlated positively with cortisol. There was no relationship between CSF AVP and monoamine metabolites in CSF.

Oral administration of a corticotropin-releasing hormone receptor antagonist significantly attenuates behavioral, neuroendocrine, and autonomic responses to stress in primates.

We evaluated the effects of the lipophilic nonpeptide corticotropin-releasing hormone (CRH) type 1 receptor antagonist antalarmin on the behavioral, neuroendocrine, and autonomic components of the stress response in adult male rhesus macaques. After oral administration, significant antalarmin concentrations were detected in the systemic circulation and the cerebrospinal fluid by a mass spectrometry-gas chromatography assay developed specifically for this purpose. Pharmacokinetic and dose-response studies suggested that an oral dose of 20 mg/kg was optimal for behavioral and endocrine effects. We then administered this dose in a double-blind, placebo-controlled fashion to monkeys exposed to an intense social stressor: namely, placement of two unfamiliar males in adjacent cages separated only by a transparent Plexiglas screen. Antalarmin significantly inhibited a repertoire of behaviors associated with anxiety and fear such as body tremors, grimacing, teeth gnashing, urination, and defecation. In contrast, antalarmin increased exploratory and sexual behaviors that are normally suppressed during stress. Moreover, antalarmin significantly diminished the increases in cerebrospinal fluid CRH as well as the pituitary-adrenal, sympathetic, and adrenal medullary responses to stress. We conclude that CRH plays a broad role in the physiological responses to psychological stress in primates and that a CRH type 1 receptor antagonist may be of therapeutic value in human psychiatric, reproductive, and cardiovascular disorders associated with CRH system hyperactivity.

Cerebrospinal fluid levels of oxytocin in Prader-Willi syndrome: a preliminary report.

BACKGROUND: Prader-Willi syndrome (PWS) is a genetic disorder characterized by mental retardation, appetite dysregulation, and a high risk for obsessive-compulsive disorder (OCD). Microscopic abnormalities of the hypothalamus have been described in PWS, and oxytocin has been implicated in both appetite regulation and OCD. METHODS: Oxytocin and arginine vasopressin (AVP) were measured in the cerebrospinal fluid of 5 subjects with PWS (2 male, 3 female) and in 6 normal control subjects (all female). RESULTS: CSF oxytocin was elevated in PWS (9.2 +/- 3.9 pmol/L) as compared to normal control subjects (5.1 +/- 0.9 pmol/L, p = 0.045), a finding that was more significant when excluding male subjects from analysis (p = 0.02). AVP was not significantly different between the groups as a whole. CONCLUSIONS: These data provide further evidence for hypothalamic and oxytocinergic dysfunction in PWS. The associations between oxytocin, appetite regulation, and obsessive compulsive symptomatology in PWS warrant further investigation.

Cerebrospinal fluid vasopressin levels: correlates with aggression and serotonin function in personality-disordered subjects.

BACKGROUND: Animal studies suggest that central vasopressin plays a facilitatory role in aggressive behavior. To examine this possibility in humans, the relationship between cerebrospinal fluid (CSF) arginine vasopressin (AVP) and indices of aggression and central serotonin system function was examined in personality-disordered subjects. METHODS: We used CSF (AVP), CSF 5-hydroxyindoleacetic acid, and the prolactin response to d-fenfluramine challenge (PRL[d-FEN]) as central indices of vasopressin and serotonergic system function, respectively, in 26 subjects who met the DSM-IV criteria for personality disorder. Measures of aggression and impulsivity included the Life History of Aggression assessment and the Barratt Impulsiveness Scales. RESULTS: The CSF AVP level was correlated directly with life history of general aggression and aggression against persons and inversely with PRL[d-FEN] responses (but not with CSF 5-hydroxyindoleacetic acid), which in turn was correlated inversely with these 2 measures of life history of aggression. The positive relationship between CSF AVP and life history of aggression remained even when the variance associated with PRL[d-FEN] responses in these subjects was accounted for. CONCLUSION: Central AVP may play a role in enhancing, while serotonin plays a role in inhibiting, aggressive behavior in personality-disordered individuals. In addition to the possibility of central AVP and serotonin interacting to influence human aggression, central AVP may also influence human aggressive behavior through a mechanism independent of central serotonin in personality-disordered subjects.

Endocrine changes in cerebrospinal fluid, pituitary effluent, and peripheral plasma of anesthetized ponies.

OBJECTIVE: To investigate the effects of inhalation and total IV anesthesia on pituitary-adrenal activity in ponies. ANIMALS: 9 healthy ponies: 5 geldings and 4 mares. PROCEDURE: Catheters were placed in the cavernous sinus below the pituitary gland and in the subarachnoid space via the lumbosacral space. After 72 hours, administration of acepromazine was followed by induction of anesthesia with thiopentone and maintenance with halothane (halothane protocol), or for the IV protocol, anesthesia induction with detomidine and ketamine was followed by maintenance with IV infusion of a detomidine-ketamine-guaifenesin combination. Arterial blood pressure and gas tensions were measured throughout anesthesia. Peptide and catecholamine concentrations were measured in pituitary effluent, peripheral plasma, and CSF. Peripheral plasma cortisol, glucose, and lactate concentrations also were measured. RESULTS: Intravenous anesthesia caused less cardiorespiratory depression than did halothane. ACTH, metenkephalin, arginine vasopressin, and norepinephrine pituitary effluent and peripheral plasma concentrations were higher during halothane anesthesia, with little change during intravenous anesthesia. Pituitary effluent plasma beta-endorphin and peripheral plasma cortisol concentrations increased during halothane anesthesia only. Dynorphin concentrations did not change in either group. Hyperglycemia developed during intravenous anesthesia only. Minimal changes occurred in CSF hormonal concentrations during anesthesia. CONCLUSION: The pituitary gland has a major role in maintaining circulating peptides during anesthesia. Compared with halothane, IV anesthesia appeared to suppress pituitary secretion.