No decrease in perseverance and performance on cognitive tasks in Danish cohort of hormonal contraceptive users.

Cognitive consequences of hormonal contraceptives (HCs) are largely underexplored, despite the popularity of use. This study investigates the association between perseverance during cognitively challenging tasks and the use of HCs among Danish women. We hypothesised that women using HCs show decreased perseverance across tasks compared to their naturally cycling counterparts. We further hypothesised that HC using women would show decreased performance as a measure of accuracy (i.e. more incorrect answers) compared to naturally cycling women. The study used a cross-sectional repeated measures design, consisting of a Danish version of the Anagram Persistence Task and the Hagen Matrices Test, followed by an extensive survey documenting menstrual and HC history for each participant. The study was conducted online. Data processing was conducted on data from 129 participants. The former hypothesis was analysed through multilevel regression with a nested random effects structure on log-transformed data. The latter hypothesis was analysed through a multilevel generalised linear model with a nested random effects structure using the binomial family. No support was found for either of the hypotheses.

Exploration of possible sex bias in acute social stress research: a semi-systematic review.

Stress can have a significant impact on the daily lives of individuals and can increase vulnerability to a number of medical conditions. This study aims to estimate the ratio of male to female participants in acute social stress research in healthy individuals. We examined original research articles published over the last 20 years. Each article was screened to determine the total number of female and male participants. We extracted data from 124 articles involving a total of 9539 participants. A total of 4221 (44.2%) participants were female, 5056 (53.0%) were male and 262 (2.7%) were unreported. Articles incorporating only females were significantly underrepresented compared to articles incorporating only males. Forty articles (63.5%) which presented data from both females and males, failed to analyse and interpret the results by sex, a significant methodological limitation. In conclusion, in the literature published over the last 20 years, female participants are significantly underrepresented. In the studies where females are represented, severe methodological limitations are apparent. Researchers should be conscious of sexual dimorphism, menstrual phase and use of hormonal contraception, which may impact the interpretation of their results.

Development and validation of the Male Post-coital Affect Scale for heterosexual men.

OBJECTIVE: The aim of this study was to examine the reliability and validity of the Male Post-coital Affect Scale (MPAS), which was developed to assess positive post-coital feelings in men. METHODS: After a pilot study, we validated our scale on a sample of American heterosexual men, who answered our questionnaire on the internet through Amazon Mechanical Turk. We tested the reliability using internal consistency. The validity was examined by assessing content, face and construct validity by testing the association between our scale, the Experience in Close Relationships Scale and other instruments. RESULTS: A total of 484 volunteers were included in the study. Cronbach's α for the scale was 0.83. Our scale was negatively correlated with attachment avoidance, r(482) = -0.36, p < 0.001) and Perceived Stress Scale, r(482) = -0.18, p < 0.001, and positively correlated with sexual satisfaction, r(482) = 0.18, p < 0.001. CONCLUSION: The MPAS is a reliable and valid tool to assess positive post-coital feelings in men.

Cerebral water content mapping in cirrhosis patients with and without manifest HE.

Hepatic encephalopathy (HE) is a frequent and debilitating complication of cirrhosis and its pathogenesis is not definitively clarified. Recent hypotheses focus on the possible existence of low-grade cerebral edema due to accumulation of osmolytes secondary to hyperammonemia. In the present study we investigated increases in cerebral water content by a novel magnetic resonance impedance (MRI) technique in cirrhosis patients with and without clinically manifest HE. We used a 3 T MRI technique for quantitative cerebral water content mapping in nine cirrhosis patients with an episode of overt HE, ten cirrhosis patients who never suffered from HE, and ten healthy aged-matched controls. We tested for differences between groups by statistical non-parametric mapping (SnPM) for a voxel-based spatial evaluation. The patients with HE had significantly higher water content in white matter than the cirrhosis patients (0.6%), who in turn, had significantly higher content than the controls (1.7%). Although the global gray matter water content did not differ between the groups, the patients with HE had markedly higher thalamic water content than patients who never experienced HE (6.0% higher). We found increased white matter water content in cirrhosis patients, predominantly in those with manifest HE. This confirms the presence of increasing degrees of low-grade edema with exacerbation of pathology. The thalamic edema in manifest HE may lead to compromised basal ganglia-thalamo-cortical circuits, in accordance with the major clinical symptoms of HE. The identification of the thalamus as particularly inflicted in manifest HE is potentially relevant to the pathophysiology of HE.

Neuropeptide Y and religious commitment in healthy young women.

OBJECTIVE: The present study explores the relationship between neuroactive hormones and religious commitment. We hypothesised that religious commitment is mediated by neuropeptide Y and oxytocin. These neurohormones have a well-established role in general well-being, anxiety regulation, stress-resilience, social affiliation and spirituality. METHODS: Sixty healthy women (median age 21) participated in the study and completed the Religious Commitment Inventory and other psychometric surveys. Blood was sampled from each participant and serum levels of neuropeptide Y were measured using radioimmunoassay. Oxytocin, stress and sex hormones were measured using enzyme-linked immunosorbent assay. Correlations were tested using non-parametric statistical methods. RESULTS: We found a positive correlation between serum neuropeptide Y levels and religious commitment, but not between oxytocin and religious commitment. CONCLUSIONS: The present study provides preliminary evidence that neuropeptide Y is a biological correlate of religious commitment.

Predicting psychogenic non-epileptic seizures from serum levels of neuropeptide Y and adrenocorticotropic hormone.

OBJECTIVE: Patients with psychogenic non-epileptic seizures (PNES) may present with convulsive events that are not accompanied by epileptiform brain activity. Video-electroencephalography (EEG) monitoring is the gold standard for diagnosis, yet not all patients experience convulsive episodes during video-EEG sessions. Hence, we aimed to construct a predictive model in order to detect PNES from serum hormone levels, detached from an evaluation of patients' convulsive episodes. METHODS: Fifteen female patients with PNES and 60 healthy female controls participated in the study, providing blood samples for hormone analysis. A binomial logistic regression model and the leave-one-out cross-validation were employed. RESULTS: We found that levels of neuropeptide Y and adrenocorticotropic hormone were the optimal combination of predictors, with over 90% accuracy (area under the curve=0.980). CONCLUSIONS: The ability to diagnose PNES irrespective of convulsive events would represent an important step considering its feasibility and affordability in daily clinical practice.

Vulnerability to psychogenic non-epileptic seizures is linked to low neuropeptide Y levels.

Psychogenic non-epileptic seizures (PNES) is a conversion disorder that reflects underlying psychological distress. Female patients with PNES often present with a history of prolonged stressors, especially sexual abuse. In the current study, we studied the relationship between neuropeptide Y (NPY) and PNES symptoms in women with a history of sexual abuse. NPY has been associated with resilience to stress and we hypothesized that low levels would increase the extent and severity of PNES symptoms in this patient population. Serum levels of NPY, and related hormones were measured in fifteen female PNES patients and sixty female controls. PNES patients reported more severe abuse histories, feeling of abandonment, and decreased perception of quality of life than controls. Importantly, they also had lower NPY levels. Our analysis indicates that low levels of NPY in PNES may confer greater vulnerability to exhibit seizure-like symptoms and lower quality of life.

Suppressed play behaviour and decreased oxytocin receptor binding in the amygdala after prenatal exposure to low-dose valproic acid.

To better understand the role of the neuropeptide oxytocin in autism spectrum disorder (ASD), we investigated potential deficits in social play behaviour and oxytocin receptor (OXTR) density alterations in the amygdala in a rodent model of ASD. Pregnant rats were injected daily with 20 or 100 mg/kg valproic acid (VPA) or saline from day 12 until the end of pregnancy. The number of pinning and pouncing events was assessed at postnatal days 29-34. Brains from male offspring (n=7/group) were removed at postnatal day 50. We performed quantitative autoradiography with an OXTR radioligand, the [I]-ornithine vasotocin analogue, in brain slices from the amygdala and other limbic brain regions involved in rat social behaviour. The results demonstrated a significant reduction in pinning behaviour and decreased OXTR density in the central nucleus of the amygdala in the 20 mg/kg VPA group. However, the 100 mg/kg VPA group had no significant changes in the number of play behaviour-related events or OXTR binding in the central nucleus of the amygdala. The reduction in OXTR density in the amygdala may be a critical disrupting mechanism affecting social behaviour in pervasive disorders such as ASD.

Treatment of gambling disorder patients with comorbid depression.

OBJECTIVE: This study was conducted to investigate and clinically assess comorbid depression and its relevance in individuals suffering from gambling disorders. The DSM-V defines the condition of gambling disorder as a persistent and recurrent problematic gambling behaviour leading to clinically significant impairment or distress. METHOD: A total of 61 subjects with gambling disorders were assessed using the Structured Clinical Interview for the DSM-IV (SCID-I), the South Oaks Gambling Screen (SOGS) and the Major Depression inventory (MDI). RESULTS: Two-way analysis of variance showed highly significant treatment outcomes associated with reductions in SOGS, F(1,60)=84.79, p<0.0001, MDI, F(1,60)=38.13, p<0.0001, craving, F(1,60)=29.59, p<0.0001, and gambling control, 47.65, p<0.0001. There was also a highly significant outcome associated with comorbidity in MDI, F(1,60)=9.17, p<0.0001. Finally, there was a significant interaction effect between treatment outcome and comorbidity, F(1,60)=3.90, p<0.005, suggesting that both treatment and comorbidity contributed to reductions in depressive symptoms. CONCLUSION: These results suggest and highlights the importance and benefits of integrated treatment of gambling disorders and its comorbidity, but also stresses the importance of adequate screening and detection of these two variables.

Excessive sucrose consumption reduces synaptic density and increases cannabinoid receptors in Göttingen minipigs.

Diets high in sucrose and fat are becoming more prevalent the world over, accompanied by a raised prevalence of cardiovascular diseases, cancers, diabetes, obesity, and metabolic syndrome. Clinical studies link unhealthy diets with the development of mental health disorders, particularly depression. Here, we investigate the effects of 12 days of sucrose consumption administered as 2 L of 25% sucrose solution daily for 12 days in Göttingen minipigs on the function of brain receptors involved in reward and motivation, regulating feeding, and pre- and post-synaptic mechanisms. Through quantitative autoradiography of cryostat sections containing limbic brain regions, we investigated the effects of sucrose restricted to a 1-h period each morning, on the specific binding of [3H]raclopride on dopamine D2/3 receptors, [3H]UCB-J at synaptic vesicle glycoprotein 2A (SV2A), [3H]MPEPγ at metabotropic glutamate receptor subtype 5 (mGluR5) and [3H]SR141716A at the cannabinoid receptor 1 (CB1). Compared to control diet animals, the sucrose group showed significantly lower [3H]UCB-J and [3H]MPEPγ binding in the prefrontal cortex. The sucrose-consuming minipigs showed higher hippocampal CB1 binding, but unaltered dopamine D2/3 binding compared to the control group. We found that the sucrose diet reduced the synaptic density marker while increasing CB1 binding in limbic brain structures, which may subserve maladaptive changes in appetite regulation and feeding. Further studies of the effects of diets and lifestyle habits on brain neuroreceptor and synaptic density markers are warranted.

Adrenocorticotropic hormone secretion in response to anticipatory stress and venepuncture: The role of menstrual phase and oral contraceptive use.

INTRODUCTION: Oral contraceptives (OCs) are primarily known for their effects on the reproductive system, but they can also impact the hypothalamic-pituitary-adrenal (HPA) axis. The present study aimed to compare plasma adrenocorticotropic hormone (ACTH) responses to the anticipatory stress of participating in a scientific experiment and venepuncture in OC users versus naturally cycling (NC) women, with a focus on variations throughout the menstrual cycle. METHODS: We recruited 131 young women (average age 20.5) and obtained blood samples to measure plasma ACTH concentrations immediately after venepuncture and again after 15 min of group activities designed to facilitate interpersonal attachment and stress-buffering. RESULTS: ACTH levels decreased in 70% of all participants throughout the group activities. A two-way repeated measures ANOVA highlighted a significant interaction between time and OC use, indicating differential changes in ACTH levels during social interaction between OC users and NC women. Further, the post-hoc analysis revealed that a period of stress-buffering group activities significantly decreased ACTH levels in NC women during menstrual and secretory phases, but not during the proliferative phase. In contrast, OC users did not display a decrease during group activities, regardless of the phase. CONCLUSION: This study underscores the influence of OC use on stress regulation, demonstrating that OCs not only modulate reproductive functions but also impact ACTH stress reactivity. Additionally, it emphasizes the importance of considering hormonal contraceptive use and menstrual cycle phases when assessing female stress responses.

Spontaneous partial recovery of striatal dopaminergic uptake despite nigral cell loss in asymptomatic MPTP-lesioned female minipigs.

The Göttingen minipig is a large animal with a gyrencephalic brain that expresses -complex behavior, making it an attractive model for Parkinson's disease research. Here, we investigate the temporal evolution of presynaptic dopaminergic function for 14 months after injections of 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) into the minipig using a multi-tracer longitudinal positron emission tomography (PET) design. We injected seven sedated minipigs with 1-2 mg/kg of MPTP, and two with saline, three times a week over four weeks. We monitored behavioral deficits using a validated motor scale and walking mat. Brains were imaged with (+)-⍺-[11C]-dihydrotetrabenazine ([11C]-DTBZ) and [18F]-dihydroxyphenylalanine ([18F]-FDOPA) PET at baseline and 1, 3, 10 and 14 months after MPTP injection, and immunohistochemistry was used to assess nigral cell loss. The minipigs showed mild bradykinesia and impaired coordination at early timepoints after MPTP. PET revealed decreases of striatal [11C]-DTBZ and [18F]-FDOPA uptake post-MPTP with partial spontaneous recovery of [18F]-FDOPA after 10 months. Postmortem analysis estimated an MPTP-induced nigral loss of 57% tyrosine hydroxylase+ and 43% Nissl-stained cells. Normal motor function despite substantial damage to the dopaminergic system is consistent with prodromal Parkinson's disease, and offers an opportunity for testing disease-modifying therapies. However, partial spontaneous recovery of dopamine terminal function must be taken into account in future studies.

Tracer input for kinetic modelling of liver physiology determined without sampling portal venous blood in pigs.

PURPOSE: Quantification of hepatic tracer kinetics by PET requires measurement of tracer input from the hepatic artery (HA) and portal vein (PV). We wished to develop a method for estimating dual tracer input without the necessity to sample PV blood. METHODS: Pigs weighing 40 kg were given bolus doses of C(15)O (CO), 2-[(18)F]fluoro-2-deoxy-D-glucose (FDG), [(11)C]-methylglucose (MG), 2-[(18)F]fluoro-2-deoxy-D-galactose (FDGal) or H(2)(15)O(H(2)O). Tracer concentration 3-min time courses were measured in the femoral artery and PV by blood sampling. Blood flow was measured in the HA and PV using flow-meters. A model for transfer of tracer through the splanchnic circulation was used to estimate values of a tracer-specific model parameter ß. Tracer-specific mean values of ß were used to estimate tracer concentration time courses in the PV from the measured arterial concentration. A model-derived dual-input was calculated using the mean HA flow fraction (0.25) and validated by comparison of the use of the measured dual-input and a kinetic model with a fixed "true" K(1)(true), i.e. clearance of tracer from blood to liver cells. RESULTS: The rank order of the means of ß was CO < FDG ≈ MG < FDGal < H(2)O, reflecting their different splanchnic mean transit times. Estimated K(1)(est) was not significantly different from "true" K(1)(true). CONCLUSION: The hepatic dual tracer input, which is of great importance for the assessment of processes such as transfer across the plasma-hepatocyte membrane or hepatic blood perfusion, can be well approximated in pigs without the necessity to sample PV blood and measure hepatic blood flow; only arterial blood sampling is needed.

Clinical evaluation of the accuracy and precision of the CDI 500 in-line blood gas monitor with and without gas calibration.

During cardiopulmonary bypass blood gases can be analyzed with laboratory equipment or with an in-line monitor giving instant results. The manufacturer of the CDI 500 in-line blood gas monitor recommends gas calibration before use. In acute cases there may not be time to perform a gas calibration. We hypothesized that after calibration against laboratory results, the CDI values of pH, pO2, and pCO2 will keep the same level of accuracy, whether the CDI has been gas calibrated or not. We performed a prospective randomized observational study using a study group without gas calibration (29 patients) and a control group with gas calibration (29 patients). Blood sampling was done at the beginning of bypass, and 30 minutes later. After each blood sample the CDI was in-vivo calibrated to the values simultaneously obtained from the ABL. Before in-vivo calibration values from the CDI without gas calibration were significantly different from the ABL-values in accuracy as well as precision, whereas the results from the gas calibrated CDI were largely consistent with the ABL. Before in-vivo calibration, the CDI without gas calibration was completely unreliable. After in-vivo calibration there was no statistical difference between the values of the CDI with and without calibration. We recommend gas calibration of the CDI before use in the period before in-vivo calibration.

A robust method for the detection of small changes in relaxation parameters and free water content in the vicinity of the substantia nigra in Parkinson's disease patients.

Alterations in the substantia nigra are strongly associated with Parkinson's disease. However, due to low contrast and partial volume effects present in typical MRI images, the substantia nigra is not of sufficient size to obtain a reliable segmentation for region-of-interest based analysis. To combat this problem, the approach proposed here offers a method to investigate and reveal changes in quantitative MRI parameters in the vicinity of substantia nigra without any a priori delineation. This approach uses an alternative method of statistical, voxel-based analysis of quantitative maps and was tested on 18 patients and 15 healthy controls using a well-established, quantitative free water mapping protocol. It was possible to reveal the topology and the location of pathological changes in the substantia nigra and its vicinity. Moreover, a decrease in free water content, T1 and T2* in the vicinity of substantia nigra was indicated in the Parkinson's disease patients compared to the healthy controls. These findings reflect a disruption of grey matter and iron accumulation, which is known to lead to neurodegeneration. Consequently, the proposed method demonstrates an increased sensitivity for the detection of pathological changes-even in small regions-and can facilitate disease monitoring via quantitative MR parameters.

Elevated plasma oxytocin levels and higher satisfaction with life in young oral contraceptive users.

Oral contraception (OC) is used by approximately fifty-five million women in the USA alone and is listed as an essential medicine by the World Health Organisation. Altered mood is a common reason for OC cessation. Here we investigate the effects of OC on hormones that are linked to mood. We obtained blood samples from 185 young women (average age 21.2) in two cohorts and tested the effects of OC on plasma levels of oxytocin, adrenocorticotropic hormone (ACTH), estradiol, progesterone and testosterone. We related plasma hormone levels with self-reported measures of mood, well-being and depression. OC-users in both cohorts showed elevated basal oxytocin, lower ACTH, estradiol, progesterone and testosterone compared with non-OC users. Satisfaction With Life Score (SWLS) was higher in OC -users compared to non-OC users, with no differences in the Beck Depression Score (BDI) and Positive And Negative Affect Schedule (PANES). In conclusion, our data show alterations in hormone levels and SWLS in response to OC.

Type of Anaesthetic Influences [11C]MDL100,907 Binding to 5HT2A Receptors in Porcine Brain.

PURPOSE: Anaesthesia routinely is used in animal neuroimaging in order to reduce head motion artefacts and minimize the influence of stress. However, anaesthetics can modify radioligand binding profiles at receptor targets studied by positron emission tomography (PET). Here, we determined the effects of two routine anaesthetics on the binding of a tracer of the serotonin 5HT2A receptors. PROCEDURES: Isoflurane- and propofol-anesthetised Göttingen minipigs were imaged with [11C]MDL100,907 PET and analysed using regions of interest and statistical non-parametric mapping. RESULTS: The binding potentials of the tracer in striatum under isoflurane anaesthesia significantly exceeded those obtained under propofol anaesthesia, an effect we attribute to the higher blood flow in brain induced by the former. CONCLUSIONS: Interactions between radioligands and anaesthesia must be carefully evaluated in the design of in vivo neuroimaging and interpretation of data.

Neonatal male circumcision is associated with altered adult socio-affective processing.

BACKGROUND: Neonatal male circumcision is a painful skin-breaking procedure that may affect infant physiological and behavioral stress responses as well as mother-infant interaction. Due to the plasticity of the developing nociceptive system, neonatal pain might carry long-term consequences on adult behavior. In this study, we examined whether infant male circumcision is associated with long-term psychological effects on adult socio-affective processing. METHODS: We recruited 408 men circumcised within the first month of life and 211 non-circumcised men and measured socio-affective behaviors and stress via a battery of validated psychometric scales. RESULTS: Early-circumcised men reported lower attachment security and lower emotional stability while no differences in empathy or trust were found. Early circumcision was also associated with stronger sexual drive and less restricted socio-sexuality along with higher perceived stress and sensation seeking. LIMITATIONS: This is a cross-sectional study relying on self-reported measures from a US population. CONCLUSIONS: Our findings resonate with the existing literature suggesting links between altered emotional processing in circumcised men and neonatal stress. Consistent with longitudinal studies on infant attachment, early circumcision might have an impact on adult socio-affective traits or behavior.

Sucrose intake lowers µ-opioid and dopamine D2/3 receptor availability in porcine brain.

Excessive sucrose consumption elicits addiction-like craving that may underpin the obesity epidemic. Opioids and dopamine mediate the rewarding effects of drugs of abuse, and of natural rewards from stimuli such as palatable food. We investigated the effects of sucrose using PET imaging with [11C]carfentanil (µ-opioid receptor agonist) and [11C]raclopride (dopamine D2/3 receptor antagonist) in seven female anesthetized Göttingen minipigs. We then gave minipigs access to sucrose solution for one hour on 12 consecutive days and performed imaging again 24 hours after the final sucrose access. In a smaller sample of five minipigs, we performed an additional [11C]carfentanil PET session after the first sucrose exposure. We calculated voxel-wise binding potentials (BPND) using the cerebellum as a region of non-displaceable binding, analyzed differences with statistical non-parametric mapping, and performed a regional analysis. After 12 days of sucrose access, BPND of both tracers had declined significantly in striatum, nucleus accumbens, thalamus, amygdala, cingulate cortex and prefrontal cortex, consistent with down-regulation of receptor densities. After a single exposure to sucrose, we found decreased binding of [11C]carfentanil in nucleus accumbens and cingulate cortex, consistent with opioid release. The lower availability of opioid and dopamine receptors may explain the addictive potential associated with intake of sucrose.

18Fluorodeoxyglucose Accumulation in Arterial Tissues Determined by PET Signal Analysis.

BACKGROUND: Arterial 18fluorodeoxyglucose (FDG) positron emission tomography (PET) is considered a measure of atherosclerotic plaque macrophages and is used for quantification of disease activity in clinical trials, but the distribution profile of FDG across macrophages and other arterial cells has not been fully clarified. OBJECTIVES: The purpose of this study was to analyze FDG uptake in different arterial tissues and their contribution to PET signal in normal and atherosclerotic arteries. METHODS: Wild-type and D374Y-PCSK9 transgenic Yucatan minipigs were fed a high-fat, high-cholesterol diet to induce atherosclerosis and subjected to a clinical FDG-PET and computed tomography scan protocol. Volumes of arterial media, intima/lesion, macrophage-rich, and hypoxic tissues were measured in serial histological sections. Distributions of FDG in macrophages and other arterial tissues were quantified using modeling of the in vivo PET signal. In separate transgenic minipigs, the intra-arterial localization of FDG was determined directly by autoradiography. RESULTS: Arterial FDG-PET signal appearance and intensity were similar to human imaging. The modeling approach showed high accuracy in describing the FDG-PET signal and revealed comparable FDG accumulation in macrophages and other arterial tissues, including medial smooth muscle cells. These findings were verified directly by autoradiography of normal and atherosclerotic arteries. CONCLUSIONS: FDG is taken up comparably in macrophage-rich and -poor arterial tissues in minipigs. This offers a mechanistic explanation to a growing number of observations in clinical imaging studies that have been difficult to reconcile with macrophage-selective FDG uptake.