Relationship between changes in metabolic syndrome constituent components over 12 months of treatment and cognitive performance in first-episode schizophrenia.

Few studies have investigated the longitudinal effects of treatment-emergent metabolic syndrome changes on cognitive performance in first-episode psychosis. The aim of the present study was to determine the associations between changes in metabolic syndrome constituent component over 12 months of treatment and end-point cognitive performance in schizophrenia spectrum disorders. This single site-cohort study included 72 minimally treated or antipsychotic-naïve first-episode patients. Cognitive performance was evaluated using the MATRICS Consensus Cognitive Battery (MCCB). Our primary objective of interest was the relationship between metabolic syndrome constituent component changes over 12 months of treatment and end-point cognitive performance. Secondary objectives included investigating whether this relationship was affected by age, sex, antipsychotic dose, treatment duration and substance use. Weight gain predicted better overall cognition (p = 0.02) at end-point, adjusting for age, sex, substance use, baseline cognitive score and BMI, modal antipsychotic dose and treatment duration. Weight loss (p = 0.04) and substance use (p = 0.01) were both associated with poorer working memory performance at end-point. Low baseline BMI showed differential effects on end-point working memory performance in substance users (unfavorable) compared to non-users (favorable) (p < 0.05). In conclusion, weight gain over the course of antipsychotic treatment is associated with better overall cognitive performance and the working memory domain in first-episode schizophrenia spectrum disorder patients. In contrast, low baseline BMI may represent an unfavorable marker in substance users, who demonstrated weight loss compared to non-users.

Cumene hydroperoxide induced changes in oxidation-reduction potential in fresh and frozen seminal ejaculates.

Oxidation-reduction potential (ORP) is a newer integrated measure of the balance between total oxidants (reactive oxygen species-ROS) and reductants (antioxidants) that reflects oxidative stress in a biological system. This study measures ORP and evaluates the effect of exogenous induction of oxidative stress by cumene hydroperoxide (CH) on ORP in fresh and frozen semen using the MiOXSYS Analyzer. Semen samples from healthy donors (n = 20) were collected and evaluated for sperm parameters. All samples were then flash-frozen at -80°C. Oxidative stress was induced by CH (5 and 50 µmoles/ml). Static ORP (sORP-(mV/106 sperm/ml) and capacity ORP (cORP-µC/106 sperm/ml) were measured in all samples before and after freezing. All values are reported as mean ± SEM. Both 5 and 50 µmoles/ml of CH resulted in a significant decline in per cent motility compared to control in pre-freeze semen samples. The increase in both pre-freeze and post-thaw semen samples for sORP was higher in the controls than with 50 µmoles/ml of CH. The change from pre-freeze to post-thaw cORP was comparable. The system is a simple, sensitive and portable tool to measure the seminal ORP and its dynamic impact on sperm parameters in both fresh and frozen semen specimens.

Review of functional MRI in HIV: effects of aging and medication.

HIV-associated neurocognitive disorder (HAND) is a frequently occurring comorbidity of HIV infection. Evidence suggests this condition starts subclinical before a progression to a symptomatic stage. Blood oxygenated level dependent (BOLD) fMRI has shown to be a sensitive tool to detect abnormal brain function in an early stage and might therefore be useful to evaluate the effect of HIV infection on brain function. An extensive literature search was performed in June 2015. Eligibility criteria for included studies were as follows: (1) conducting with HIV-positive patients, (2) using BOLD fMRI, and (3) including a HIV-negative control group. A total of 19 studies were included in the review including 931 participants. Differences in activation between HIV-positive and -negative participants were found when testing multiple domains, i.e., attention, (working) memory, and especially executive functioning. Overall, HIV-positive patients showed hyperactivation in task-related brain regions despite equal performances as controls. Task performance was degraded only for the most complex tasks. A few studies investigated the effect of aging on fMRI, and most of them found no interaction with HIV infection. Only three studies evaluated the effect of combination antiretroviral therapy (cART) on functional data suggesting an increase in activation with the use of cART. fMRI is a sensitive instrument to detect subtle cognitive changes in HIV patients. Open questions remain regarding the effects of cART on fMRI and the effects of aging on fMRI.

Brain volume changes over the first year of treatment in schizophrenia: relationships to antipsychotic treatment.

BACKGROUND: Progressive brain volume reductions have been described in schizophrenia, and an association with antipsychotic exposure has been reported. METHODS: We compared percentage changes in grey and white matter volume from baseline to month 12 in 23 previously antipsychotic-naïve patients with a first episode of schizophrenia or schizophreniform disorder who were treated with the lowest effective dose of flupenthixol decanoate depot formulation, with 53 matched healthy individuals. Total antipsychotic dose was precisely calculated and its relationship with brain volume changes investigated. Relationships between volumetric changes and treatment were further investigated in terms of treatment response (changes in psychopathology and functionality) and treatment-related adverse-events (extrapyramidal symptoms and weight gain). RESULTS: Excessive cortical volume reductions were observed in patients [-4.6 (6.6)%] v. controls [-1.12 (4.0)%] (p = 0.009), with no significant group differences for changes in subcortical grey matter and white matter volumes. In a multiple regression model, the only significant predictor of cortical volume change was total antipsychotic dose received (p = 0.04). Cortical volume change was not significantly associated with the changes in psychopathology, functionality, extrapyramidal symptoms and body mass index or age, gender and duration of untreated psychosis. CONCLUSIONS: Brain volume reductions associated with antipsychotic treatment are not restricted to poor outcome patients and occur even with the lowest effective dose of antipsychotic. The lack of an association with poor treatment response or treatment-related adverse effects counts against cortical volume reductions reflecting neurotoxicity, at least in the short term. On the other hand, the volume reductions were not linked to the therapeutic benefits of antipsychotics.

The dopamine-related polymorphisms BDNF, COMT, DRD2, DRD3, and DRD4 are not linked with changes in CSF dopamine levels and frequency of HIV infection.

We showed previously that higher levels in CSF dopamine in HIV patients are associated with the presence of the dopamine transporter (DAT) 10/10-repeat allele which was also detected more frequently in HIV-infected individuals compared to uninfected subjects. In the current study, we investigated further whether other genetic dopamine (DA)-related polymorphisms may be related with changes in CSF DA levels and frequency of HIV infection in HIV-infected subjects. Specifically, we studied genetic polymorphisms of brain-derived neurotrophic factor, catechol-O-methyltransferase, and dopamine receptors DRD2, DRD3, and DRD4 genetic polymorphisms in uninfected and HIV-infected people in two different ethnical groups, a German cohort (Caucasian, 72 individuals with HIV infection and 22 individuals without HIV infection) and a South African cohort (Xhosan, 54 individuals with HIV infection and 19 individuals without HIV infection). We correlated the polymorphisms with CSF DA levels, HIV dementia score, CD4+ T cell counts, and HIV viral load. None of the investigated DA-related polymorphisms was associated with altered CSF DA levels, CD4+ T cell count, viral load, and HIV dementia score. The respective allele frequencies were equally distributed between HIV-infected patients and controls. Our findings do not show any influence of the studied genetic polymorphisms on CSF DA levels and HIV infection. This is in contrast to what we found previously for the DAT 3'UTR VNTR and highlights the specific role of the DAT VNTR in HIV infection and disease.

Ultraviolet Light Induced Generation of Reactive Oxygen Species.

As ultraviolet (UV) radiation is naturally and ubiquitously emitted by the sun, almost everyone is exposed to it on a daily basis, and it is necessary for normal physiological function. Human exposure to solar UV radiation thus has important health implications. The generation of reactive oxygen species (ROS) by UV radiation is one of the mechanisms through which UV light can manifest its possible detrimental effects on health. When an imbalance develops due to ROS generation exceeding the body's antioxidant defence mechanisms, oxidative stress can develop. Oxidative stress can lead to cellular damage (e.g. lipid peroxidation and DNA fragmentation), apoptosis and cell death. Broadly UV can induce ROS by affecting the cellular components directly or by means of photosensitization mechanisms. More specifically UV light can induce ROS by affecting the enzyme catalase and up-regulating nitric oxide synthase (NOS) synthesis. It may also cause a decrease in protein kinase C (PKC) expression leading to increased ROS production. UVR is capable of modifying DNA and other chromophores resulting in elevated ROS levels. The effects of raised ROS levels can vary based on the intracellular oxidant status of the cell. It is therefore important to protect yourself against the potentially harmful effects of UV light as it can lead to pathological UV-induced ROS production.

Are oxidative stress markers associated with unexplained male infertility?

Male infertility can be responsible for up to 20% of the cases attending fertility consultation facilities; nonetheless, the underlying molecular mechanisms that could explain it are still elusive. Therefore, we aimed to evaluate conventional and functional parameters of semen samples from patients who presented with male infertility of unknown origin. Conventional semen parameters and functional parameters (i.e. intracellular reactive oxygen species production, mitochondrial membrane potential, sperm chromatin structure assay, sperm membrane lipid peroxidation and antioxidant capacity of seminal plasma) were evaluated on semen samples from 54 healthy donors, 23 patients with idiopathic infertility and 34 fertile controls. No significant differences were observed in the conventional seminal parameters between the fertile and infertile men. However, increased intracellular reactive oxygen species (ROS) production and DNA fragmentation were observed in the infertile patients compared to the fertile group. Alterations in intracellular ROS production and DNA fragmentation could be associated with male idiopathic infertility. These parameters could eventually distinguish both groups more accurately than the conventional parameters. Our current results are encouraging, and the efficacy of these parameters in the clinical settings needs to be further assessed to establish their predictive potential as a marker of unexplained male infertility.

Large volume cryoprotectant-free vitrification: an alternative to conventional cryopreservation for human spermatozoa.

Vitrification is a simple and cost-effective method for the storage of human spermatozoa without the use of conventional cryoprotectants, by plunging the sperm suspension directly into liquid nitrogen. As a result, solidification of living cells without the formation of ice crystals is achieved during cooling. This study aimed to compare cryoprotectant-free vitrification to conventional cryopreservation protocols. Semen samples (n = 35) were collected from patients seeking diagnostic assistance at the Reproductive and Endocrine Unit at Steve Biko Academic Hospital. Samples were processed using a discontinuous density-gradient centrifugation method. Washed samples were split into two aliquots and cryopreserved either by means of cryoprotectant-free vitrification (sucrose + 1% albumin) or conventional slow freezing (TEST-yolk buffer). Post-thawing, the sperm motion parameters, mitochondrial membrane potential (Δψm) and DNA fragmentation were compared between the two groups. No significant differences were observed in the sperm motility parameters (P > 0.05). Significantly higher percentages of Δψm (11.99% ± 4.326% versus 6.58% ± 1.026%; P < 0.001) and lower percentages of DNA fragmentation (2.79% ± 1.017% versus 3.86% ± 1.38%; P < 0.01) were observed when comparing cryoprotectant-free vitrification to conventional cryopreservation. Cryoprotectant-free vitrification is a rapid and promising alternative to conventional methods resulting in good-quality spermatozoa post-thaw.

Revisiting the assessment of semen viscosity and its relationship to leucocytospermia.

With infertility challenges posing an obstacle to many couples, the extension of variables to assess male fertility is an important line of research. At the Reproductive Biology Unit where the study was undertaken, a considerable proportion of male patient's seeking fertility assessment presented with hyperviscous semen samples and elevated concentrations of leucocytes. Despite viscosity being included as part of a routine spermiogram, it raises a considerable amount of concern as it is assessed semiquantitatively. The study was undertaken to evaluate the quantification of semen viscosity in centipoise (cP) and to investigate whether a correlation exists between hyperviscosity and leucocytospermia. A total of 200 semen samples were assessed from a sample cohort of two population groups: 162 male patients undergoing fertility assessment and 38 volunteer donors. Semen viscosity was determined by measuring the filling time of a capillary-loaded Leja chamber and quantifying the viscosity in cP. Leucocytes were identified histochemically with a leucocyte peroxidase test. The viscosity when quantified in cP was significantly higher in the peroxidase positive sample group (9.01 ± 0.49 vs. 7.39 ± 0.23 cP; P < 0.005). The introduction of a more accurate method of quantifying viscosity may possibly help to identify, diagnose and treat patients suffering from leucocytospermia to ultimately enhance their fertility potential.

In vitro effects of nicotine on human spermatozoa.

Washed human spermatozoa from 12 normozoospermic donors were treated with different concentrations of nicotine 0.1, 1.0, 5.0 and 10.0 mm and were compared to spermatozoa suspended in nutrient medium only (control). Computer-aided sperm analysis was used to assess sperm kinematic properties after 30, 60, 120 and 180 min of incubation. Viability was assessed by means of a dye exclusion staining technique (eosin/nigrosin), while acrosome-reacted cells were identified under a fluorescent microscope using fluorescein isothiocyanate-Pisum sativum agglutinin as a probe. Nicotine significantly reduced total motility, progressive motility, curvilinear velocity, amplitude of lateral head displacement, beat cross-frequency, viability and caused spontaneous acrosome reaction at concentrations of ≥5.0 mm after 2 and 3 h of exposure. Nicotine concentrations of 0.1 and 1.0 mm had no significant effect (P < 0.05) on spermatozoa except that 1.0 mm significantly decreased (P < 0.05) sperm progressive motility at 2 and 3 h of incubation as well as viability after 3 h of incubation. This study concludes that the occurrence of high levels of nicotine in the body and seminal fluid might adversely affect fertilisation capacity of human spermatozoa through a mechanism that involves decreased motility, viability and premature induction of the acrosome reaction.

Hippocampus, amygdala, and insula activation in response to romantic relationship dissolution stimuli: A case-case-control fMRI study on emerging adult students.

BACKGROUND: Romantic relationship dissolutions (RRDs) are associated with posttraumatic stress symptoms (PTSS). Functional magnetic resonance imaging in RRD studies indicate overlapping neural activation similar to posttraumatic stress disorder. These studies combine real and hypothetical rejection, and lack contextual information and control and/or comparison groups exposed to non-RRD or DSM-5 defined traumatic events. AIM: We investigated blood oxygen level dependent (BOLD) activation in the hippocampus, amygdala, and insula of participants with RRDs compared with other traumatic or non-trauma stressors. METHODS: Emerging adults (mean age = 21.54 years; female = 74.7 %) who experienced an RRD (n = 36), DSM-5 defined trauma (physical and/or sexual assault: n = 15), or a non-RRD or DSM-5 stressor (n = 28) completed PTSS, depression, childhood trauma, lifetime trauma exposure, and attachment measures. We used a general and customised version of the International Affective Picture System to investigate responses to index-trauma-related stimuli. We used mixed linear models to assess between-group differences, and ANOVAs and Spearman's correlations to analyse factors associated with BOLD activation. RESULTS: BOLD activity increased between index-trauma stimuli as compared to neutral stimuli in the hippocampus and amygdala, with no significant difference between the DSM-5 Trauma and RRD groups. Childhood adversity, sexual orientation, and attachment style were associated with BOLD activation changes. Breakup characteristics (e.g., initiator status) were associated with increased BOLD activation in the hippocampus and amygdala, in the RRD group. CONCLUSION: RRDs should be considered as potentially traumatic events. Breakup characteristics are risk factors for experiencing RRDs as traumatic. LIMITATION: Future studies should consider more diverse representation across sex, ethnicity, and sexual orientation.

Relapse in schizophrenia: The role of factors other than non-adherence to treatment.

AIM: Relapse rates are very high in schizophrenia. However, little is known about the predictors of the time to relapse other than treatment non-adherence. We investigated possible risk factors for the time to relapse in patients with first-episode schizophrenia (n = 107) who received assured treatment by way of long-acting injectable antipsychotic over 24 months and who underwent regular clinical, cognitive, and metabolic assessments. METHODS: Using Cox regression analyses we assessed selected premorbid and baseline potential predictors of time to relapse. Relapse was defined using operationally defined relapse criteria. RESULTS: In the primary analysis only neurological soft signs total score retained significance, with higher scores predicting shorter time to relapse (HR = 1.05, 95% CI = 1.01-1.10, p = .029). In a more detailed secondary analysis poorer social relationships predicted shorter time to relapse (HR = 0.85, 95% CI = 0.76-0.95, p = .003). CONCLUSION: Our predominantly negative findings suggest that many of the previously implicated risk factors for the time to relapse are mediated by non-adherence rather than having a direct effect on relapse-proneness. Neurological soft signs, and perhaps quality of life in social relationships appear to play a role and merit further investigation.

Preoperative three-dimensional model creation of magnetic resonance brain images as a tool to assist neurosurgical planning.

BACKGROUND: Neurosurgeons regularly plan their surgery using magnetic resonance imaging (MRI) images, which may show a clear distinction between the area to be resected and the surrounding healthy brain tissue depending on the nature of the pathology. However, this distinction is often unclear with the naked eye during the surgical intervention, and it may be difficult to infer depth and an accurate volumetric interpretation from a series of MRI image slices. OBJECTIVES: In this work, MRI data are used to create affordable patient-specific 3-dimensional (3D) scale models of the brain which clearly indicate the location and extent of a tumour relative to brain surface features and important adjacent structures. METHODS: This is achieved using custom software and rapid prototyping. In addition, functionally eloquent areas identified using functional MRI are integrated into the 3D models. RESULTS: Preliminary in vivo results are presented for 2 patients. The accuracy of the technique was estimated both theoretically and by printing a geometrical phantom, with mean dimensional errors of less than 0.5 mm observed. CONCLUSIONS: This may provide a practical and cost-effective tool which can be used for training, and during neurosurgical planning and intervention.

Test-retest variability underlying fMRI measurements.

INTRODUCTION: A high test-retest reliability is of pivotal importance for many disciplines in fMRI research. To assess the current limits of fMRI reliability, we estimated the variability in true underlying Blood Oxygen Level Dependent (BOLD) activation, with which we mean the variability that would be found in the theoretical case when we could obtain an unlimited number of scans in each measurement. METHODS: In this test-retest study, subjects were scanned twice with one week apart, while performing a visual and a motor inhibition task. We addressed the nature of the variability in the underlying BOLD signal, by separating for each brain area and each subject the between-session differences in the spatial pattern of BOLD activation, and the global (whole brain) changes in the amplitude of the spatial pattern of BOLD activation. RESULTS: We found evidence for changes in the true underlying spatial pattern of BOLD activation for both tasks across the two sessions. The sizes of these changes in pattern activation were approximately 16% of the total activation within the pattern, irrespective of brain area and task. After spatial smoothing, this variability was greatly reduced, which suggests it takes place at a small spatial scale. The mean between-session differences in the amplitude of activation across the whole brain were 13.8% for the visual task and 23.4% for the motor inhibition task. CONCLUSIONS: Between-session changes in the true underlying spatial pattern of BOLD activation are always present, but occur at a scale that is consistent with partial voluming effects or spatial distortions. We found no evidence that the reliability of the spatial pattern of activation differs systematically between brain areas. Consequently, between-session changes in the amplitude of activation are probably due to global effects. The observed variability in amplitude across sessions warrants caution when interpreting fMRI estimates of height of brain activation. A Matlab implementation of the used algorithm is available for download at www.ni-utrecht.nl/downloads/ura.

A red palm oil diet can reduce the effects of oxidative stress on rat spermatozoa.

Male Wistar rats (n = 54) received daily supplementation of red palm oil (RPO: 0, 2, 4 ml). Subgroups were subsequently injected with saline, cumene hydroperoxide (cHP, 10 µm) or t-butyl hydroperoxide (tbHP, 20 µm) over a 60-day period after which animals were sacrificed. Epididymal sperm motility, concentration, reactive oxygen species (ROS), lipid peroxidation and enzymes were measured. Sperm concentration, motility, superoxide dismutase (SOD) concentration, glutathione (GSH) and catalase (CAT) activities were significantly lower, while dichlorofluorescein (DCF) and malondialdehyde (MDA) were higher in sperm of hydroperoxide-treated animals compared to controls (P < 0.05). DCF and MDA levels were significantly lower, while SOD, CAT and GSH were significantly higher in the sperm of rats supplemented with RPO in combination with hydroperoxide treatment when compared to those receiving hydroperoxide and no RPO supplementation (P < 0.05). Moreover, the DCF, SOD, CAT and GSH levels in the RPO hydroperoxide groups did not differ from control values (P > 0.05). RPO supplementation can successfully attenuate the oxidative stress-induced sperm damage due to organic hydroperoxide exposure. We therefore propose that a daily intake of RPO supplement to the diet might be helpful in protecting males against the adverse effects of high ROS in sperm function and help preserve fertility.

Physicochemical and Biological Evaluation of Curdlan-Poly(Lactic-Co-Glycolic Acid) Nanoparticles as a Host-Directed Therapy Against Mycobacterium Tuberculosis.

Nanoparticles (NPs) that can activate macrophages infected with the tuberculosis causative pathogen Mycobacterium tuberculosis, could be an effective host directed therapy for the disease. In this study, curdlan was conjugated to poly(lactic-co-glycolic acid) (PLGA) to produce immunotherapeutic NPs. Various physicochemical characterizations were used to evaluate the curdlan-PLGA copolymer and the NPs. Molecular dynamics and simulation studies were used to characterize the interaction between curdlan, on the polymer and on NPs, with the Dectin-1 macrophage receptor. NPs with varying curdlan densities were evaluated for their effects on the production of pro- and anti-inflammatory cytokines in M. tuberculosis infected RAW264.7 macrophages. The killing efficacy of the NPs against intracellular M. tuberculosis was assessed. Physicochemical characterization of the curdlan-PLGA copolymer and NPs indicated successful formation of curdlan-PLGA copolymer and NPs of varying curdlan density (0-8% w/w) had sizes between 330 and 453 nm. Modelling studies showed curdlan to have a strong affinity for Dectin-1. Cytotoxicity assays showed the NPs to be non-toxic over 72 h. The proinflammatory cytokine TNF-α was found to be significantly upregulated by the NPs. The NPs reduced intracellular M. tuberculosis burden over 72 h. These NPs are a promising host directed therapy for intracellular eradication of M. tuberculosis.

Associations between BMI and brain structures involved in food intake regulation in first-episode schizophrenia spectrum disorders and healthy controls.

Structural brain differences have been described in first-episode schizophrenia spectrum disorders (FES), and often overlap with those evident in the metabolic syndrome (MetS). We examined the associations between body mass index (BMI) and brain structures involved in food intake regulation in minimally treated FES patients (n = 117) compared to healthy controls (n = 117). The effects of FES diagnosis, BMI and their interactions on our selected prefrontal cortical thickness and subcortical gray matter volume regions of interest (ROIs) were investigated with hierarchical multivariate regressions, followed by post-hoc regressions for the individual ROIs. In a secondary analysis, we examined the relationships of other MetS risk factors and psychopathology with the brain ROIs. Both illness and BMI significantly predicted the grouped prefrontal cortical thickness ROIs, whereas only BMI predicted the grouped subcortical volume ROIs. For the individual ROIs, schizophrenia diagnosis predicted thinner left and right frontal pole and right lateral OFC thickness, and increased BMI predicted thinner left and right caudal ACC thickness. There were no significant main or interaction effects for diagnosis and BMI on any of the individual subcortical volume ROIs. Secondary analyses suggest associations between several brain ROIs and individual MetS risk factors, but not with psychopathology. Our findings indicate differential, independent effects for FES diagnosis and BMI on brain structures. Limited evidence suggests that the BMI effects are more prominent in FES. Exploratory analyses suggest associations between other MetS risk factors and some brain ROIs.

Gender role endorsement in first-episode schizophrenia spectrum disorders.

Sex (a biological distinction) and gender (a social construct) are inter-related, but semi-independent measures. The aim of our research was to compare gender role endorsement between first-episode schizophrenia spectrum disorder patients (n=77) and matched controls (n=64). The Bem Sex Role Inventory (BSRI) was used to assess masculinity and femininity scores as separate linear measures. This well-known research instrument also allowed us to examine gender as a categorical measure based on sex-specific cut-off scores calculated for controls as our normative reference sample using a median-split technique. First, we found that both masculinity and femininity scores differed between patients and controls. The distribution of gender as a categorical measure also differed between the two groups. Post-hoc testing with correction for multiple comparisons identified masculinity scores in particular as being lower in both male and female patients compared to controls of the corresponding sex. In conclusion, lower masculinity scores reported for chronic schizophrenia also affects first-episode patients with minimal prior treatment exposure irrespective of their biological sex. Future studies would do well to examine the associations of sex and gender with clinical and treatment outcomes from the perspective of the neurodevelopmental model of schizophrenia as a proposed "disorder of the self".

Cannabis use and hippocampal subfield volumes in males with a first episode of a schizophrenia spectrum disorder and healthy controls.

BACKGROUND: Both schizophrenia and cannabis use are associated with structural brain changes. The hippocampus is a region of particular interest due to its role in memory and select cognitive functions, impairment of which is a core feature of schizophrenia and has also been observed in substance abuse. This study aimed to explore the effects of recent/current cannabis use on hippocampal subfield volumes in male patients with first-episode schizophrenia spectrum disorders and matched controls. METHODS: This cross-sectional, case-control study included 63 patients and 58 controls scanned on 3T MRI scanners, with hippocampal segmentation performed using recently validated Freesurfer v6.0 software. Cannabis use status was determined by self and carer report together with urine toxicology screening, and patients were categorised as recent/current users or non-users. We used multivariate analysis of covariance (MANCOVA) with age, scan sequence, scan quality, and total intracranial volume as covariates, with subsequent analysis of variance (ANOVA) to test the effects of diagnosis and cannabis use status on individual hippocampal subfields. RESULTS: We found a group (patient/control) by cannabis use interaction effect in the subiculum, with decreased volumes observed in the cannabis non-using patients compared to the cannabis using patients, and decreased volumes in the cannabis using controls compared to the cannabis non-using controls. CONCLUSION: The increased subiculum volume in cannabis using patients compared to cannabis non-using patients raises important questions regarding the pathophysiology of schizophrenia and the role of cannabis use therein.

Seminal plasma metabolomics profiles following long (4-7 days) and short (2 h) sexual abstinence periods.

OBJECTIVE: Metabolomic profiling of seminal plasma has been suggested as a possible approach for a fast and non-invasive male infertility evaluation diagnosis. However, metabolomics profiles in normozoospermic men have not been thoroughly investigated, and the influence of ejaculation-abstinence has not been described. To provide interim reference values and find associations between the metabolomics profiles of human seminal plasma and length of ejaculation-abstinence period in normozoospermic men. STUDY DESIGN: Semen samples collected after long (4-7 days) and short abstinence (2 h) from 31 normozoospermic males were assessed for routine quality parameters before the seminal plasma was separated by centrifugation. Metabolomics profiles of the seminal plasma were then determined using untargeted Nuclear Magnetic Resonance Spectroscopy. RESULTS: In total, 30 metabolites were identified. Pyruvate showed a higher concentration, while fructose, acetate, choline, methanol, N-acetylglucosamine, O-acetylcarnitine, uridine, and sn-glycero-3-phosphocoline showed lower concentrations in samples collected after short abstinence (vs. long). All metabolites showed lower absolute amounts (volume × concentration) following shorter abstinence. However, the lower sperm concentration in samples collected after short abstinence resulted in higher absolute amounts of pyruvate and taurine per spermatozoa: pyruvate 1.92 (1.12-3.87) vs. 1.29 (0.83-2.62) (P < 0.001) and taurine 0.58 (0.36-0.92) vs. 0.43 (0.28-0.95) (P < 0.05) ng/106 spermatozoa. Simultaneously, there was a higher percentage of progressively motile spermatozoa in samples collected after the short abstinence. CONCLUSION: The generally lower concentrations of seminal metabolites after short abstinence periods may be related to the shorter time available for secretion and collection of these metabolites by the accessory glands and the epididymides. The concomitant lower number of spermatozoa in the second ejaculate resulted in increased absolute amounts of pyruvate and taurine per spermatozoa, accompanied by increased spermatozoa motility in these samples. The simultaneous increase in percentages of motile spermatozoa and absolute amounts of pyruvate and taurine per spermatozoa after shorter abstinence might indicate that these two metabolites play a more critical role in sperm motility, which should be further investigated in future studies.