scholarly journals S7. INVESTIGATING THE LINK BETWEEN THE PERIPHERAL ENDOCANNABINOID SYSTEM AND CENTRAL GLUTAMATERGIC NEUROTRANSMISSION IN EARLY PSYCHOSIS: A 7T-MRS STUDY

2020 ◽  
Vol 46 (Supplement_1) ◽  
pp. S32-S32
Author(s):  
Amedeo Minichino ◽  
Beata Godlewska ◽  
Philip Cowen ◽  
Philip Burnet ◽  
Belinda Lennox

Abstract Background Meta-analytic evidence showed increased levels of peripheral endocannabinoid metabolites in psychotic illness. Alterations in the endocannabinoid system are believed to compromise glutamate and dopamine transmission, which play a central role in pathophysiological models of psychosis. I will present preliminary data from an ongoing high-field proton magnetic resonance spectroscopy (MRS) study aimed at investigating the association between peripheral levels of endocannabinoid system metabolites and central glutamate metabolism in individuals at their first non-affective psychotic episode (NA-FEP) and healthy controls. Methods We expect to recruit 17 NA-FEP and 20 healthy controls by January 2020. Currently, we recruited 12 NA-FEP and 18 healthy controls from two different research facilities (Imperial College London and University of Oxford) as part of a cross-sectional study. Participants underwent MRS scanning at 7-T with voxels placed in right dorsolateral prefrontal cortex (right-DLPFC), anterior cingulate cortex (ACC), and occipital cortex. Neuro-metabolites will be calculated using the unsuppressed water signal as reference. Endocannabinoid metabolites were quantified from serum samples, collected during the same imaging session. Results Analyses are ongoing. Based on previous evidence, expected findings are: (i) reduced glutamate levels in the ACC and right-DLPFC of NA-FEP compared to controls; (ii) increased peripheral endocannabinoid metabolites in NA-FEP compared to controls; and (iii) inverse association between peripheral endocannabinoid metabolites and glutamate levels in ACC and right-DLPFC in NA-FEP Discussion This study will help clarifying the contribution of peripheral endocannabinoid system to central brain mechanisms of key relevance for psychotic illness. It will also add further evidence on the limited literature on high-resolution characterisation of brain metabolites in early psychosis. Strengths of the study include: (i) use of high-field MRS, which allows the estimation of glutamate-related compounds at higher precision than at lower field strength; (ii) reduced heterogeneity of the clinical sample (only male and NA-FEP). Limitations: small sample size and cross-sectional design.

2006 ◽  
Vol 188 (6) ◽  
pp. 510-518 ◽  
Author(s):  
R. Grant Steen ◽  
Courtney Mull ◽  
Robert Mcclure ◽  
Robert M. Hamer ◽  
Jeffrey A. Lieberman

BackgroundStudies of people with schizophrenia assessed using magnetic resonance imaging (MRI) usually include patients with first-episode and chronic disease, yet brain abnormalities may be limited to those with chronic schizophrenia.AimsTo determine whether patients with a first episode of schizophrenia have characteristic brain abnormalities.MethodSystematic review and meta-analysis of 66 papers comparing brain volume in patients with a first psychotic episode with volume in healthy controls.ResultsAtotal of 52 cross-sectional studies included 1424 patients with a first psychotic episode; 16 longitudinal studies included 465 such patients. Meta-analysis suggests that whole brain and hippocampal volume are reduced (both P < 0.0001) and that ventricular volume is increased (P < 0.0001) in these patients relative to healthy controls.ConclusionsAverage volumetric changes are close to the limit of detection by MRI methods. It remains to be determined whether schizophrenia is a neurodegenerative process that begins at about the time of symptom onset, or whether it is better characterised as a neurodevelopmental process that produces abnormal brain volumes at an early age.


2017 ◽  
Vol 44 (11) ◽  
pp. 1603-1611 ◽  
Author(s):  
Daniel R. Machin ◽  
Phillip E. Gates ◽  
Hans Vink ◽  
Tracy M. Frech ◽  
Anthony J. Donato

Objective.The aim of our study was to determine whether an automated capture and analysis system could detect differences in structure and function of sublingual microvessels in patients with systemic sclerosis (SSc) compared to healthy controls.Methods.Intravital microscopy of the sublingual microcirculation was automatically captured and analyzed in 40 patients with SSc and 10 age-matched healthy controls.Results.Total and perfused microvascular density were lower in patients with SSc compared with controls (total microvascular density: 2471 ± 134 µm/mm2 vs 3067 ± 197 µm/mm2, p = 0.020; perfused microvascular density: 1708 ± 92 µm/mm2 vs 2192 ± 144 µm/mm2, p = 0.009). However, the relative percentage of perfused to total microvascular density was similar between SSc and controls (72 ± 2% vs 71 ± 2%, respectively, p = 0.429). Mean red blood cell (RBC) fraction, which indicates the longitudinal tube hematocrit of microvessel segments, was lower in patients with SSc compared with controls (69 ± 1% vs 77 ± 1%, respectively, p < 0.001). Perfused boundary region (PBR), a marker of endothelial glycocalyx barrier properties, was higher in patients with SSc compared with controls (2.1 ± 0.0 µm vs 1.9 ± 0.0 µm, respectively, p = 0.012), suggestive of a dysfunctional glycocalyx. There was an inverse association of PBR with perfused microvascular density (r = −0.40, p = 0.004) and RBC fraction (r = −0.80, p < 0.001).Conclusion.Our results indicate that automated capture and analysis of sublingual microvessel segments produces detailed, objective microvascular structural and functional data that have allowed us to distinguish patients with SSc from controls. These data suggest that microvascular structural and functional abnormalities present in patients with SSc could be at least partly due to a dysfunctional glycocalyx.


2022 ◽  
Vol 12 ◽  
Author(s):  
Tom Maudrich ◽  
Susanne Hähner ◽  
Rouven Kenville ◽  
Patrick Ragert

BackgroundSomatosensory-evoked potentials (SEP) represent a non-invasive tool to assess neural responses elicited by somatosensory stimuli acquired via electrophysiological recordings. To date, there is no comprehensive evaluation of SEPs for the diagnostic investigation of exercise-induced functional neuroplasticity. This systematic review aims at highlighting the potential of SEP measurements as a diagnostic tool to investigate exercise-induced functional neuroplasticity of the sensorimotor system by reviewing studies comparing SEP parameters between athletes and healthy controls who are not involved in organized sports as well as between athlete cohorts of different sport disciplines.MethodsA systematic literature search was conducted across three electronic databases (PubMed, Web of Science, and SPORTDiscus) by two independent researchers. Three hundred and ninety-seven records were identified, of which 10 cross-sectional studies were considered eligible.ResultsDifferences in SEP amplitudes and latencies between athletes and healthy controls or between athletes of different cohorts as well as associations between SEP parameters and demographic/behavioral variables (years of training, hours of training per week &amp; reaction time) were observed in seven out of 10 included studies. In particular, several studies highlight differences in short- and long-latency SEP parameters, as well as high-frequency oscillations (HFO) when comparing athletes and healthy controls. Neuroplastic differences in athletes appear to be modality-specific as well as dependent on training regimens and sport-specific requirements. This is exemplified by differences in SEP parameters of various athlete populations after stimulation of their primarily trained limb.ConclusionTaken together, the existing literature suggests that athletes show specific functional neuroplasticity in the somatosensory system. Therefore, this systematic review highlights the potential of SEP measurements as an easy-to-use and inexpensive diagnostic tool to investigate functional neuroplasticity in the sensorimotor system of athletes. However, there are limitations regarding the small sample sizes and inconsistent methodology of SEP measurements in the studies reviewed. Therefore, future intervention studies are needed to verify and extend the conclusions drawn here.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Beata R. Godlewska ◽  
Amedeo Minichino ◽  
Uzay Emir ◽  
Ilinca Angelescu ◽  
Belinda Lennox ◽  
...  

AbstractAbnormalities in glutamate neurotransmission are linked to psychotic symptoms and cognitive dysfunction in schizophrenia. magnetic resonance spectroscopy (MRS) provides an acceptable means of measuring glutamate in the human brain but findings from patient studies at conventional magnetic field strength show considerable heterogeneity. Ultra-high-field MRS offers greater precision in glutamate measurement, particularly in delineation of glutamate from its precursor and metabolite, glutamine. This study aimed to use high-field (7 T) MRS to measure concentrations of glutamate and glutamine in three brain regions, anterior cingulate cortex (ACC), dorsolateral prefrontal cortex (DLPFC) and putamen (PUT), in young men with early psychosis. MRS was performed in 17 male participants with early psychosis and 18 healthy age-matched controls. Neurometabolite levels were calculated with unsuppressed water signal as the reference and corrected for individual grey matter, white matter and cerebrospinal fluid concentration. Cognitive function was measured with the Brief Assessment of Cognition in Schizophrenia (BACS). Compared to controls, patients with early psychosis had lower concentrations of glutamate and glutamine in ACC. No differences were apparent in the DLPFC and PUT. In patients with early psychosis, there was a highly significant correlation between glutamate concentration in ACC and performance on the BACS, though the numbers available for this analysis were small. Our finding of lower glutamate levels in ACC in patients with schizophrenia is consistent with a recent meta-analysis of 7 T studies and suggests that this abnormality is present in both patients with early psychosis and those with longer-established illness. The possible link between ACC glutamate and cognitive performance requires replication in larger studies.


2021 ◽  
Author(s):  
Andreas Walther ◽  
Clemens Kirschbaum ◽  
Susanne Wehrli ◽  
Nicole Rothe ◽  
Magdalena Wekenborg ◽  
...  

Background: The endocannabinoid system (ECS) is increasingly being recognized as key regulatory system coupled with the glucocorticoid system implicated in the pathophysiology of stress-related mental disorders. However, prior studies examining the ECS in depression or burnout have been inconclusive, of small sample size or of cross-sectional nature limiting interpretations of causal inferences or time-dependent effects.Methods: In a prospective community based cohort study including 128 individuals (women: 108), depression (PHQ-9) and burnout symptoms (MBI-GS) as well as hair cortisol and endocannabinoids were measured annually over four years. Cortisol, arachidonylethanolamide (AEA) and 2-arachidonyl-sn-glycerol/1-arachidonyl-sn-glycerol (2-AG/1-AG) were extracted from 3 cm hair segments reflecting cumulative concentrations of the last 3 months prior hair sampling.Results: Cross sectional group comparisons at baseline revealed reduced cortisol and AEA levels in the group with a positive major depressive disorder screening compared to individuals with low depression symptomatology (both p &lt; .05). Cortisol was also reduced in the group with a positive burnout screening compared to individuals with a negative screening at baseline (p &lt; .05). Longitudinal multilevel analysis, showed for the total sample that a within-person increase in burnout symptoms was associated with a decrease in cortisol levels over time (p &lt; .05). In the male subsample, a between-person increase in AEA levels across time was associated with a decrease in depression symptoms and vice versa. However, a within-person increase of AEA levels across time was associated with an increase in depression symptoms and vice versa (both p &lt; .05). Further, a within-person increase in burnout symptoms lead to a significant increase in AEA levels in the male subsample (p &lt; .05).Conclusions: While cross-sectional analyses suggest higher depression or burnout symptomatology to be associated with reduced cortisol and AEA release, longitudinal analyses disaggregating between- and within-person effects reveal a complex pattern. A within-person increase in burnout symptoms precedes a decrease in cortisol secretion suggesting an exhaustion of the HPA axis. Between-person analysis show only for men a negative association between depression symptoms and AEA levels over time. However, within-person effects, indicate an increase in depression symptoms to preced and to follow an increase in AEA levels, suggesting a dynamic counterregulatory mechanism between the EC and depression in men differing on the between- and within-person levels. These longitudinal associations further elucidate the time and sex dependent relation between depression, burnout, glucocorticoid and endocannabinoid secretion.


Crisis ◽  
2020 ◽  
pp. 1-5
Author(s):  
Ruthmarie Hernández-Torres ◽  
Paola Carminelli-Corretjer ◽  
Nelmit Tollinchi-Natali ◽  
Ernesto Rosario-Hernández ◽  
Yovanska Duarté-Vélez ◽  
...  

Abstract. Background: Suicide is a leading cause of death among Spanish-speaking individuals. Suicide stigma can be a risk factor for suicide. A widely used measure is the Stigma of Suicide Scale-Short Form (SOSS-SF; Batterham, Calear, & Christensen, 2013 ). Although the SOSS-SF has established psychometric properties and factor structure in other languages and cultural contexts, no evidence is available from Spanish-speaking populations. Aim: This study aims to validate a Spanish translation of the SOSS-SF among a sample of Spanish-speaking healthcare students ( N = 277). Method: We implemented a cross-sectional design with quantitative techniques. Results: Following a structural equation modeling approach, a confirmatory factor analysis (CFA) supported the three-factor model proposed by Batterham and colleagues (2013) . Limitations: The study was limited by the small sample size and recruitment by availability. Conclusion: Findings suggest that the Spanish version of the SOSS-SF is a valid and reliable tool with which to examine suicide stigma among Spanish-speaking populations.


2020 ◽  
Vol 16 (3) ◽  
pp. 204-210 ◽  
Author(s):  
Asirvatham A. Robert ◽  
Mohamed A. Al Dawish

From last few years, the pervasiveness of diabetes mellitus (DM), in Saudi Arabia, is growing at a frightening rate. Overall, one-fourth of the adult population is affected by DM, which is further predicted to rise to more than double by the year 2030. The most alarming is possibly the escalation propensity of diabetes, in recent years, where a nearly ten-fold increase has been witnessed over the past thirty years in Saudi Arabia. However, the number of research arbitrations on the prevalence and incidence of DM is woefully inadequate, as compared to developed countries. Apart from this, most of the existing research data carried out in Saudi Arabia is cross-sectional, with small sample sizes, which most often involve only certain parts of the country. Consequently, the present scenario demands more multidimensional and multisectoral research to strengthen the evidence base and to accumulate greater knowledge as a basis for measures and programmes to confront diabetes and its complications. Thus, the present report makes an attempt to depict the current trend of diabetes as well as intends to put forward essential measures for controlling diabetes in Saudi Arabia.


2020 ◽  
Vol 09 ◽  
Author(s):  
Nataly S. Beck ◽  
Melanie L. Lean ◽  
Kate V. Hardy ◽  
Jacob S. Ballon

Background: The typical age of onset for psychotic disorders is concurrent with the typical age of enrollment in higher education. College and graduate students often experience new academic and social demands that may leave them vulnerable to substance use and mental health problems, including the initial onset of a psychotic episode. Objective: To provide a current overview of the guidelines and literature for the diagnosis and treatment of first-onset psychosis with special consideration for the college and graduate student population in the United States. To highlight areas of need and provide recommendations for clinicians who work at educational institutions and their health services, along with general psychiatrists and psychologists who work with post-secondary education populations, to help close the treatment gap. Method: A review of interventions and best practice for the treatment of early psychosis in college students was conducted, informed by the authors’ current experience as clinicians with this population at a United States university. Results: Thorough psychiatric interviews and screening tools can help in the early identification of individuals at clinical high risk for and at first onset of psychosis. Coordinated specialty care services are the gold standard for early psychosis services, including psychotherapy (such as cognitive behavioral therapy and individual resiliency training), as well as support for a student to return to school or work. Individuals experiencing a first episode of psychosis in general respond better to lower doses of antipsychotics and may also experience more adverse effects. Conclusion: Return to a high level of functioning is possible in many cases of first onset of psychosis, and early identification and treatment is essential.


2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Alexandra Gaál Kovalčíková ◽  
Ľubica Tichá ◽  
Katarína Šebeková ◽  
Peter Celec ◽  
Alžbeta Čagalová ◽  
...  

Abstract Background Anorexia nervosa (AN) is a serious psychosomatic disorder with unclear pathomechanisms. Metabolic dysregulation is associated with disruption of redox homeostasis that might play a pivotal role in the development of AN. The aim of our study was to assess oxidative status and carbonyl stress in plasma, urine and saliva of patients with AN and healthy controls. Methods Plasma, spot urine, and saliva were collected from 111 girls with AN (aged from 10 to 18 years) and from 29 age-matched controls. Markers of oxidative stress and antioxidant status were measured using spectrophotometric and fluorometric methods. Results Plasma advanced oxidation protein products (AOPP) and advanced glycation end products (AGEs) were significantly higher in patients with AN than in healthy controls (by 96, and 82%, respectively). Accordingly, urinary concentrations of AOPP and fructosamines and salivary concentrations of AGEs were higher in girls with AN compared with controls (by 250, and 41% in urine; by 92% in saliva, respectively). Concentrations of thiobarbituric acid reactive substances (TBARS) in saliva were 3-times higher in the patients with AN than in the controls. Overall antioxidants were lower in plasma of girls with AN compared to the controls, as shown by total antioxidant capacity and ratio of reduced and oxidized glutathione (by 43, and 31%, respectively). Conclusions This is the first study assessing wide range of markers of oxidative status in plasma, urine and saliva of the patients with AN. We showed that both, higher levels of markers of oxidative stress and lower antioxidants play a role in redox disruption. Restoration of redox homeostasis might be of the clinical relevance


2021 ◽  
Vol 8 (1) ◽  
Author(s):  
Pasquale Loiudice ◽  
Marco Pellegrini ◽  
Michele Marinò ◽  
Barbara Mazzi ◽  
Ilaria Ionni ◽  
...  

Abstract Background Hemodynamic changes have been observed in patients with Graves’ disease. The aim of our study was to evaluate choroidal vascular change using the choroidal vascularity index (CVI) in patients with thyroid-associated ophthalmopathy (TAO). Methods In this cross-sectional observational study, 40 patients affected by TAO were recruited. Forty healthy individuals, matched for age and sex, served as controls. Foveal enhanced-depth imaging optical coherence tomography scans were obtained from all participants. Images were binarized using the ImageJ software and luminal area (LA) and total choroidal area (TCA) were measured. CVI was calculated as the proportion of LA to TCA. The relation between CVI or subfoveal choroidal thickness (SFCT) and clinical activity score, exophthalmometric value, diplopia status, gender, and age was evaluated. Results CVI was significantly higher in patients with TAO (P = 0.004). No significant difference was observed in SFCT (P = 0.200) and TCA (P = 0.153) comparing TAO patients and healthy controls. LA was significantly higher in TAO group (P = 0.045). On multiple regression analysis, CVI was associated with TCA (P = 0.043). No association was found between SFCT or CVI and TCA, clinical activity score, exophthalmometric value, Inami value, diplopia status, gender or age (P > 0.05). Conclusions This is the first study that has demonstrated an increase in CVI in eyes with TAO compared with healthy controls and has assessed its association with clinical features.


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