IL-33/sST2 signaling pathway in pulmonary thromboembolism: A clinical observational study.

BACKGROUND: Pulmonary thromboembolism (PTE) is a cardiovascular emergency that can result in mortality. In the interleukin-33 (IL-33) /soluble suppression of tumorigenicity 2 (sST2) signaling pathway, increased sST2 is a cardiovascular risk factor. This study aimed to investigate the effectiveness of biomarkers in the IL-33/sST2 signaling pathway in determining PTE diagnosis, clinical severity, and mortality. METHOD: This study was conducted as a single-center, prospective, observational study. Patients admitted to the emergency department and diagnosed with PTE constituted the patient group (n = 112), and healthy volunteers with similar sociodemographic characteristics constituted the control group (n = 62). Biomarkers in the IL-33/sST2 signaling pathway were evaluated for diagnosis, clinical severity, and prognosis. RESULTS: IL-33 was lower in the patient group than in the control group (275.89 versus 403.35 pg/mL), while sST2 levels were higher in the patient group than in the control group (53.16 versus 11.78 ng/mL) (p < 0.001 and p = 0.001; respectively). The AUC of IL-33 to diagnose PTE was 0.656 (95 % CI: 0.580-0.726). The optimal IL-33 cut-off point to diagnose PTE was ≤304.11 pg/mL (56.2 % sensitivity, 79 % specificity). The AUC of sST2 to diagnose PTE was 0.818 (95 % CI: 0.752-0.872). The optimal sST2 cut-off point to diagnose PTE was >14.48 ng/mL (83 % sensitivity, 71 % specificity). IL-33 levels were lower in patients with mortality (169.85 versus 332.04 pg/mL) compared to patients without mortality, whereas sST2 levels were higher in patients with mortality (118.32 versus 28.07 ng/mL) compared to patients without mortality (p > 0.001 for both). The AUC of IL-33 to predict the mortality of PTE was 0.801 (95 % CI: 0.715-0.870). The optimal IL-33 cut-off point to predict the mortality of PTE was ≤212.05 pg/mL (75 % sensitivity, 79.5 % specificity). The AUC of sST2 to predict the mortality of PTE was 0.824 (95 % CI: 0.740-0.889). The optimal sST2 cut-off point to predict the mortality of PTE was >81 ng/mL (95.8 % sensitivity, 78.4 % specificity). CONCLUSION: In the IL-33/ST2 signaling pathway, decreased IL-33 and increased sST2 are valuable biomarkers for diagnosis and prediction of mortality in patients with PTE.

Cannabis Dependence is Associated with Reduced Hippocampal Subregion Volumes Independently of Sex: Findings from an ENIGMA Addiction Working Group Multi-Country Study.

Background: Males and females who consume cannabis can experience different mental health and cognitive problems. Neuroscientific theories of addiction postulate that dependence is underscored by neuroadaptations, but do not account for the contribution of distinct sexes. Further, there is little evidence for sex differences in the neurobiology of cannabis dependence as most neuroimaging studies have been conducted in largely male samples in which cannabis dependence, as opposed to use, is often not ascertained. Methods: We examined subregional hippocampus and amygdala volumetry in a sample of 206 people recruited from the ENIGMA Addiction Working Group. They included 59 people with cannabis dependence (17 females), 49 cannabis users without cannabis dependence (20 females), and 98 controls (33 females). Results: We found no group-by-sex effect on subregional volumetry. The left hippocampal cornu ammonis subfield 1 (CA1) volumes were lower in dependent cannabis users compared with non-dependent cannabis users (p<0.001, d=0.32) and with controls (p=0.022, d=0.18). Further, the left cornu ammonis subfield 3 (CA3) and left dentate gyrus volumes were lower in dependent versus non-dependent cannabis users but not versus controls (p=0.002, d=0.37, and p=0.002, d=0.31, respectively). All models controlled for age, intelligence quotient (IQ), alcohol and tobacco use, and intracranial volume. Amygdala volumetry was not affected by group or group-by-sex, but was smaller in females than males. Conclusions: Our findings suggest that the relationship between cannabis dependence and subregional volumetry was not moderated by sex. Specifically, dependent (rather than non-dependent) cannabis use may be associated with alterations in selected hippocampus subfields high in cannabinoid type 1 (CB1) receptors and implicated in addictive behavior. As these data are cross-sectional, it is plausible that differences predate cannabis dependence onset and contribute to the initiation of cannabis dependence. Longitudinal neuroimaging work is required to examine the time-course of the onset of subregional hippocampal alterations in cannabis dependence, and their progression as cannabis dependence exacerbates or recovers over time.

Retrospective Examination of Infants With Congenital Neural Tube Defect.

INTRODUCTION: In the present study, neonates presenting with neural tube defects (NTDs) and undergoing observation within the confines of the neonatal intensive care unit (NICU) were subjected to a comprehensive assessment encompassing concurrent morbidities, clinical manifestations, laboratory parameters, and instituted interventions. MATERIALS AND METHODS: A retrospective examination was conducted on the medical records of 135 neonates diagnosed with congenital NTD within the temporal span from 2008 to 2018. The study cohort was drawn from the NICU of the Health Sciences University Erzurum Regional and Research Hospital Health Practice and Research Center. DISCUSSION: The current investigation encompasses a retrospective analysis of 135 patients diagnosed with NTD who received treatment at the NICU between the years 2008 and 2018. Among these, 74 individuals (54.2%) were male, while 61 (45.8%) were female. Maternal ages ranged from 17 to 46 years, with variations in the number of pregnancies, ranging from 1 to 10. Notably, 71 cases (52.6%) were delivered through normal spontaneous delivery, whereas 64 cases (47.4%) underwent cesarean section. The familial context revealed that five patients (3.6%) had siblings with a history of NTD, while no instances were noted where mothers had received antenatal folic acid support. Birth weights of the neonates ranged from 1425 to 4500 grams. Consanguinity was identified in the parental relationships of 17 cases (12.6%). The average diameter of the neural tube sac was determined to be 4.83 ± 1.94 cm (1-12 cm). Predominantly, the lumbosacral region emerged as the most common site of NTD, with meningomyelocele being the prevailing NTD type. Hydrocephalus coexisted in 67 cases, and notably, 44 instances exhibited the development of hydrocephalus post-sac operation. Eight patients were deemed inoperable, and the initial surgery transpired at an average age of 4.3 ± 2.6 (0-17) days. Flap closure constituted 32 of the surgical interventions, while primary closure was implemented in 95 cases. Neurogenic bladder antedated the operation in 14 patients, and 12 individuals developed neurogenic bladder postoperatively. Ventriculoperitoneal shunt placement was warranted in 47 patients. The average duration of hospitalization was 22.5 ± 14.4 days. Regrettably, three patients died due to complications and infections during their hospital stay. RESULT: NTD represents a significant cohort of pathologies necessitating a comprehensive and interdisciplinary management strategy. These anomalies are characterized by elevated morbidity and mortality rates, not only exerting substantial financial strains on societal, familial, and state healthcare resources but also inflicting profound emotional distress upon affected families. Crucially, periconceptional strategies emphasizing balanced nutrition coupled with targeted multivitamin and mineral supplementation, particularly the inclusion of folic acid, assume paramount importance in the prophylaxis of this debilitating condition.

Comparative Effectiveness of Epidural Steroid Injections in Patients With Disc Bulging and Disc Protrusion.

Purpose Discogenic low back pain is a widespread disorder in the world. Many methods have been developed and continue to be developed in the treatment of discogenic low back pain. We aimed to examine the effect of epidural steroid administration on disc bulging and disc protrusion in patients with discogenic low back pain. Design The clinical effects of interlaminar epidural steroids administered to 71 patients who were admitted to our clinic and whose treatment did not require surgery were radiologically divided into two groups disc bulging and disc protrusion. Patients were followed up for six months and clinical results were recorded. Methods The scores of the Visual Analog Scale (VAS) and Oswestry Disability Index (ODI) were measured before the procedure, one week after the procedure, one month after the procedure, and six months after the procedure. The normal distribution of continuous variables was evaluated using the Kolmogorov-Smirnov test. Continuous variables were compared with the Mann-Whitney U test and categorical variables were compared using the Chi-square test or Fisher's exact test. Results There was no significant difference in demographic data in patients with disc bulging and disc protrusion. In the disc protrusion group, the VAS scores in the first week after, the first month after and the sixth month after the procedure showed a significant decrease compared to the pre-procedure. There was no significant difference between the disc bulging and protrusion groups in the first week of post-procedure VAS score reduction. In the Disc Bulging group, the ODI score one week after, one month after, and six months after the procedure showed a significant decrease compared to the pre-procedure. In the Disc Protrusion group, the ODI score one week after, one month after, and six months after the procedure showed a significant decrease compared to the pre-procedure. Conclusion There was strong evidence that lumbar interlaminar steroid injection is an effective treatment for disc bulging and discogenic pain due to protrusion. When the ODI and VAS scores of patients with both disc bulging and disc protrusion were evaluated, it was seen that they benefited from epidural steroid injection. In the disc protrusion group, except for the first week of injection, relief due to the use of epidural steroids was observed to be greater compared to disc bulging.

Brain Anatomical Alterations in Young Cannabis Users: Is it All Hype? A Meta-Analysis of Structural Neuroimaging Studies.

Introduction: Cannabis use has a high prevalence in young youth and is associated with poor psychosocial outcomes. Such outcomes have been ascribed to the impact of cannabis exposure on the developing brain. However, findings from individual studies of volumetry in youth cannabis users are equivocal. Objectives: Our primary objective was to systematically review the evidence on brain volume differences between young cannabis users and nonusers aged 12-26 where profound neuromaturation occurs, accounting for the role of global brain volumes (GBVs). Our secondary objective was to systematically integrate the findings on the association between youth age and volumetry in youth cannabis users. Finally, we aimed to evaluate the quality of the evidence. Materials and Methods: A systematic search was run in three databases (PubMed, Scopus, and PsycINFO) and was reported using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We run meta-analyses (with and without controlling for GBV) of brain volume differences between young cannabis users and nonusers. We conducted metaregressions to explore the role of age on volumetric differences. Results: Sixteen studies were included. The reviewed samples included 830 people with mean age 22.5 years (range 14-26 years). Of these, 386 were cannabis users (with cannabis use onset at 15-19 years) and 444 were controls. We found no detectable group differences in any of the GBVs (intracranium, total brain, total white matter, and total gray matter) and regional brain volumes (i.e., hippocampus, amygdala, orbitofrontal cortex, and total cerebellum). Age and cannabis use level did not predict (standardized mean) volume group differences in metaregression. We found little evidence of publication bias (Egger's test p>0.1). Conclusions: Contrary to evidence in adult samples (or in samples mixing adults and youth), previous single studies in young cannabis users, and meta-analyses of brain function in young cannabis users, this early evidence suggests nonsignificant volume differences between young cannabis users and nonusers. While prolonged and long-term exposure to heavy cannabis use may be required to detect gross volume alterations, more studies in young cannabis users are needed to map in detail cannabis-related neuroanatomical changes.

The Value of Serum I-FABP Level in the Diagnosis of Acute Appendicitis.

BACKGROUND: Acute appendicitis is one of the most common abdominal emergencies worldwide. Biomarkers and imaging are valuable adjuncts to history and examination. Differentiating complicated and uncomplicated appendicitis is essential. Our aim is to investigate whether serum I-FABP could be a suitable diagnostic biomarker in diagnosing acute appendicitis in which inflammation and ischemia play a role in the pathophysiology. METHODS: Sixty-six patients with histopathologically confirmed acute appendicitis were included in the study. Blood samples were taken from the patient and control groups to examine serum I-FABP, white blood cell (WBC) counts, C-reactive protein (CRP), and procalcitonin (PCT) levels. RESULTS: Twenty-six patients (39.3%) had complicated appendicitis. When the patient and control groups were compared in terms of I-FABP, WBC, neutrophil-lymphocyte ratio, (NLR) CRP, and PCT values, a significant difference was found in all biochemical parameters (p < 0.001). We compared the levels of patients with uncomplicated and complicated appendicitis in terms of serum I-FABP, WBC, NLR, CRP, and PCT levels and found that only the I-FABP level was significantly different (p < 0.001), and the diagnostic sensitivity was higher in patients with complicated appendicitis compared with uncomplicated patients (AUC; 0.89 for I-FABP, 0.55, 0.57, 0.61, and 0.59 for WBC, NLR, CRP, and PCT respectively). CONCLUSIONS: I-FABP has no diagnostic advantage over WBC, CRP, and PCT to diagnose acute appendicitis. However, it is more sensitive than other biomarkers in differentiating complicated from uncomplicated appendicitis.

The Effects of Combined Physical and Cognitive Training on Inhibitory Control: A Systematic Review and Meta-Analysis.

While strong inhibitory control is critical for health and wellbeing, there are no broadly applicable effective behavioural interventions that enhance it. This meta-analysis examined the neurocognitive rationale for combined physical and cognitive training and synthesised the rapidly growing body of evidence examining combined paradigms to enhance inhibitory control. Across the research to date, there was a small positive effect (n studies = 16, n participants = 832) of combined training on improving inhibitory control. Sub-group analyses showed small-moderate positive effects when the physical component of the combined training was moderately intense, as opposed to low or vigorous intensities; moderate positive effects were found in older adults, as compared to adolescents and adults; and healthy individuals and those with vascular cognitive impairment, as compared to ADHD, ASD, mild cognitive impairment and cancer survivors. This is the first meta-analysis to provide evidence that combined physical, specifically when moderately intense, and cognitive training has the capacity to improve inhibitory control, particularly when delivered to healthy individuals and those experiencing age-related decline.

Diagnostic and Prognostic Value of Serum Endocan Levels in Patients With COVID-19.

We aimed to evaluate whether there was a relationship between endocan (human endothelial cell-specific molecule-1) levels and disease prognosis in patients who presented to the emergency department with coronavirus disease 2019 (COVID-19). A total of 60 patients with COVID-19 who were hospitalized from the emergency department to clinical wards and a control group consisting of healthy adult individuals (n = 28), were included in the study. The majority (93.3%) of the patients were discharged after recovery; 6.7% died. The median endocan value was 243.5 ng/mL in the patient group versus 201.5 ng/mL in the control group (P = .002). The median endocan level was 240.5 ng/mL in those discharged with recovery and 558 ng/mL in those who died (P = .001). There was no significant relationship in hospitalization duration, sex, tomography findings, and clinical outcomes. A 202 ng/mL serum endocan level had 86.7% sensitivity and 50% specificity for COVID-19. Serum endocan levels may be a useful biomarker both for the diagnosis of COVID-19 and to predict mortality.

Neuropsychological and neurophysiological predictors and consequences of cannabis and illicit substance use during neurodevelopment: a systematic review of longitudinal studies.

Adolescence and early adulthood are crucial periods of neurodevelopment characterised by functional, structural, and cognitive maturation, which helps prepare young people for adulthood. This systematic review of longitudinal studies aims to delineate neural predictors from neural consequences of cannabis and illicit substance use, as well as investigate the potential for the developing brain (at ages 10-25 years) to recover after damage. Five databases were searched to yield a total of 38 eligible studies, with some assessing multiple outcome techniques, including 22 neuroimaging, two neurophysiological, and 22 neuropsychological findings. High-quality evidence suggested that delayed or irregular neurodevelopment in executive functioning, particularly emotional perception, might predispose young people to higher frequency substance use. There was evidence of functional, structural, and cognitive deficits proceeding substance use, with harm potentially dependent on the frequency of use and recovery potentially dependent on the duration of use. Identifying aberrant neurodevelopment in young people is crucial for preventing substance use-related harm.

Sex and dependence related neuroanatomical differences in regular cannabis users: findings from the ENIGMA Addiction Working Group.

Males and females show different patterns of cannabis use and related psychosocial outcomes. However, the neuroanatomical substrates underlying such differences are poorly understood. The aim of this study was to map sex differences in the neurobiology (as indexed by brain volumes) of dependent and recreational cannabis use. We compared the volume of a priori regions of interest (i.e., amygdala, hippocampus, nucleus accumbens, insula, orbitofrontal cortex (OFC), anterior cingulate cortex and cerebellum) between 129 regular cannabis users (of whom 70 were recreational users and 59 cannabis dependent) and 114 controls recruited from the ENIGMA Addiction Working Group, accounting for intracranial volume, age, IQ, and alcohol and tobacco use. Dependent cannabis users, particularly females, had (marginally significant) smaller volumes of the lateral OFC and cerebellar white matter than recreational users and controls. In dependent (but not recreational) cannabis users, there was a significant association between female sex and smaller volumes of the cerebellar white matter and OFC. Volume of the OFC was also predicted by monthly standard drinks. No significant effects emerged the other brain regions of interest. Our findings warrant future multimodal studies that examine if sex and cannabis dependence are specific key drivers of neurobiological alterations in cannabis users. This, in turn, could help to identify neural pathways specifically involved in vulnerable cannabis users (e.g., females with cannabis dependence) and inform individually tailored neurobiological targets for treatment.

Mapping cortical and subcortical asymmetries in substance dependence: Findings from the ENIGMA Addiction Working Group.

Brain asymmetry reflects left-right hemispheric differentiation, which is a quantitative brain phenotype that develops with age and can vary with psychiatric diagnoses. Previous studies have shown that substance dependence is associated with altered brain structure and function. However, it is unknown whether structural brain asymmetries are different in individuals with substance dependence compared with nondependent participants. Here, a mega-analysis was performed using a collection of 22 structural brain MRI datasets from the ENIGMA Addiction Working Group. Structural asymmetries of cortical and subcortical regions were compared between individuals who were dependent on alcohol, nicotine, cocaine, methamphetamine, or cannabis (n = 1,796) and nondependent participants (n = 996). Substance-general and substance-specific effects on structural asymmetry were examined using separate models. We found that substance dependence was significantly associated with differences in volume asymmetry of the nucleus accumbens (NAcc; less rightward; Cohen's d = 0.15). This effect was driven by differences from controls in individuals with alcohol dependence (less rightward; Cohen's d = 0.10) and nicotine dependence (less rightward; Cohen's d = 0.11). These findings suggest that disrupted structural asymmetry in the NAcc may be a characteristic of substance dependence.

Pineal Gland Volume in Major Depressive and Bipolar Disorders.

Abnormal melatonin secretion has been demonstrated in patients with affective disorders such as major depressive disorder (MDD) and bipolar disorder (BD). However, magnetic resonance imaging (MRI) studies that previously investigated the volume of the pineal gland, which regulates circadian rhythms by secreting melatonin, in these patients reported inconsistent findings. The present study employed MRI to examine pineal gland volumes and pineal cyst prevalence in 56 MDD patients (29 currently depressed and 27 remitted patients), 26 BD patients, and matched controls (33 for MDD and 24 for BD). Pineal volumes and cyst prevalence in the current MDD, remitted MDD, and BD groups did not significantly differ from those of the healthy controls. However, pineal gland volumes were significantly smaller in the current MDD subgroup of non-melancholic depression than in the melancholic MDD subgroup. Interestingly, pineal volumes correlated negatively with the severity of loss of interest in the current MDD group. Medication and the number of affective episodes were not associated with pineal volumes in the MDD or BD group. While these results do not suggest that pineal volumes reflect abnormal melatonin secretion in affective disorders, they do point to the possibility that pineal abnormalities are associated with clinical subtypes of MDD and its symptomatology.

Cannabis Use in Adolescence: A Review of Neuroimaging Findings.

Objective: Shifting policies and widespread acceptance of cannabis for medical and/or recreational purposes have fueled worries of increased cannabis initiation and use in adolescents. In particular, the adolescent period is thought to be associated with an increased susceptibility to the potential harms of repeated cannabis use, due to being a critical period for neuromaturational events in the brain. This review investigates the neuroimaging evidence of brain harms attributable to adolescent cannabis use. Methods: PubMed and Scopus searches were conducted for empirical articles that examined neuroimaging effects in both adolescent cannabis users and adult user studies that explored the effect of age at cannabis use onset on the brain. Results: We found 43 studies that examined brain effect (structural and functional magnetic resonance imaging) in adolescent cannabis users and 20 that examined the link between onset age of cannabis use and brain effects in adult users. Studies on adolescent cannabis users relative to nonusers mainly implicate frontal and parietal regions and associated brain activation in relation to inhibitory control, reward, and memory. However, studies in adults are more mixed, many of which did not observe an effect of onset age of cannabis use on brain imaging metrics. Conclusions: While there is some evidence of compromised frontoparietal structure and function in adolescent cannabis use, it remains unclear whether the observed effects are specifically attributable to adolescent onset of use or general cannabis use-related factors such as depressive symptoms. The relative contribution of adolescent onset of cannabis use and use chronicity will have to be more comprehensively examined in prospective, longitudinal studies with more rigorous measures of cannabis use (dosage, exposure, dependence, constituent compounds such as the relative cannabinoid levels).

Subcortical surface morphometry in substance dependence: An ENIGMA addiction working group study.

While imaging studies have demonstrated volumetric differences in subcortical structures associated with dependence on various abused substances, findings to date have not been wholly consistent. Moreover, most studies have not compared brain morphology across those dependent on different substances of abuse to identify substance-specific and substance-general dependence effects. By pooling large multinational datasets from 33 imaging sites, this study examined subcortical surface morphology in 1628 nondependent controls and 2277 individuals with dependence on alcohol, nicotine, cocaine, methamphetamine, and/or cannabis. Subcortical structures were defined by FreeSurfer segmentation and converted to a mesh surface to extract two vertex-level metrics-the radial distance (RD) of the structure surface from a medial curve and the log of the Jacobian determinant (JD)-that, respectively, describe local thickness and surface area dilation/contraction. Mega-analyses were performed on measures of RD and JD to test for the main effect of substance dependence, controlling for age, sex, intracranial volume, and imaging site. Widespread differences between dependent users and nondependent controls were found across subcortical structures, driven primarily by users dependent on alcohol. Alcohol dependence was associated with localized lower RD and JD across most structures, with the strongest effects in the hippocampus, thalamus, putamen, and amygdala. Meanwhile, nicotine use was associated with greater RD and JD relative to nonsmokers in multiple regions, with the strongest effects in the bilateral hippocampus and right nucleus accumbens. By demonstrating subcortical morphological differences unique to alcohol and nicotine use, rather than dependence across all substances, results suggest substance-specific relationships with subcortical brain structures.

Amygdala volume mediates the relationship between externalizing symptoms and daily smoking in adolescence: A prospective study.

The current study examined amygdala and orbitofrontal cortex (OFC) volumes as mediators of the relationship between externalizing symptoms and daily smoking in adolescence. Externalizing behaviors are among the most robust predictors of adolescent smoking, and there is emerging evidence that volume reductions in the amygdala and OFC are associated with risk for substance misuse as well as aggressive, impulsive, and disinhibited tendencies. Using a prospective longitudinal design, we recruited 109 adolescents who provided data on brain volume and externalizing behaviors at age 12, and on smoking at age 18. Daily smoking at age 18 (n = 27) was predicted by externalizing behaviors (measured by the self-report Child Behavior Checklist, CBCL) as well as smaller right amygdala volumes. Right amygdala volumes mediated the relationship between externalizing symptoms and later smoking. These findings provide important insight into the neurobiological risk factors associated with adolescent smoking, and, more generally, into factors that may be associated with vulnerability to substance use disorders and related psychopathology.

Therapeutic Effects of Prolonged Cannabidiol Treatment on Psychological Symptoms and Cognitive Function in Regular Cannabis Users: A Pragmatic Open-Label Clinical Trial.

Introduction: Chronic cannabis use has been associated with impaired cognition and elevated psychological symptoms, particularly psychotic-like experiences. While Δ9-tetrahydrocannabinol (THC) is thought to be primarily responsible for these deleterious effects, cannabidiol (CBD) is purported to have antipsychotic properties and to ameliorate cognitive, symptomatic, and brain harms in cannabis users. However, this has never been tested in a prolonged administration trial in otherwise healthy cannabis users. Here, we report the first study of prolonged CBD administration to a community sample of regular cannabis users in a pragmatic trial investigating potential restorative effects of CBD on psychological symptoms and cognition. Materials and Methods: Twenty frequent cannabis users (16 male, median age 25 years) underwent a 10-week open-label trial of 200 mg of daily oral CBD treatment, while continuing to use cannabis as usual. The majority of participants were daily cannabis users who had used cannabis for several years (median 5.5 years of regular use). Participants underwent psychological and cognitive assessments at baseline (BL) and post-treatment (PT) and were monitored weekly throughout the trial. Results: CBD was well tolerated with no reported side effects; however, participants retrospectively reported reduced euphoria when smoking cannabis. No impairments to cognition were found, nor were there deleterious effects on psychological function. Importantly, participants reported significantly fewer depressive and psychotic-like symptoms at PT relative to BL, and exhibited improvements in attentional switching, verbal learning, and memory. Increased plasma CBD concentrations were associated with improvements in attentional control and beneficial changes in psychological symptoms. Greater benefits were observed in dependent than in nondependent cannabis users. Conclusions: Prolonged CBD treatment appears to have promising therapeutic effects for improving psychological symptoms and cognition in regular cannabis users. Our findings require replication given the lack of a placebo control in this pragmatic trial, but suggest that CBD may be a useful adjunct treatment for cannabis dependence.

Is There A Role For Lifestyle Interventions In Obsessive-Compulsive And Related Disorders?

Many of the currently available treatments for obsessive-compulsive and related disorders (OCRDs) such as pharmacotherapy augmentation strategies, partial hospitalization programs, deep brain stimulation, and neurosurgery are efficacious for individuals suffering from more severe forms of these conditions. Unfortunately, the application of these treatments in milder forms of illness and subclinical samples, which affect a substantial portion of the population, is not justifiable by their costs (e.g. cognitivebehavioral therapy) and/or potential for side effects (serotonin-reuptake inhibitors associated sexual side effects). As such, there is an urgent need to develop simple yet effective treatments, such as modifiable lifestyle interventions, that can be employed on a broader scale. Here, we review the current state of evidence that supports or refutes the efficacy of lifestyle approaches for OCRDs. We focus on dimensions of lifestyle that are deemed important for cardiovascular diseases; namely, physical activity, stress, sleep, diet and eating behaviors, alcohol consumption, and smoking. Despite the relative scarcity of welldesigned randomized controlled trials targeting unhealthy life styles in OCRDs, we found meditation-based therapies and interventions focusing on eliminating sedentarism to be promising approaches. In the future, these strategies may represent valid alternative for subjects with subthreshold symptoms or at risk for OCRDs or other "compulsive" disorders.

GABA concentration in sensorimotor cortex following high-intensity exercise and relationship to lactate levels.

KEY POINTS: Magnetic resonance spectroscopy was conducted before and after high-intensity interval exercise. Sensorimotor cortex GABA concentration increased by 20%. The increase was positively correlated with the increase in blood lactate. There was no change in dorsolateral prefrontal cortex. There were no changes in the glutamate-glutamine-glutathione peak. ABSTRACT: High-intensity exercise increases the concentration of circulating lactate. Cortical uptake of blood borne lactate increases during and after exercise; however, the potential relationship with changes in the concentration of neurometabolites remains unclear. Although changes in neurometabolite concentration have previously been demonstrated in primary visual cortex after exercise, it remains unknown whether these changes extend to regions such as the sensorimotor cortex (SM) or executive regions such as the dorsolateral prefrontal cortex (DLPFC). In the present study, we explored the acute after-effects of high-intensity interval training (HIIT) on the concentration of gamma-Aminobutyric acid (GABA) and the combined glutamate-glutamine-glutathione (Glx) spectral peak in the SM and DLPFC, as well as the relationship with blood lactate levels. Following HIIT, there was a robust increase in GABA concentration in the SM, as evident across the majority of participants. This change was not observed in the DLPFC. Furthermore, the increase in SM GABA was positively correlated with an increase in blood lactate. There were no changes in Glx concentration in either region. The observed increase in SM GABA concentration implies functional relevance, whereas the correlation with lactate levels may relate to the metabolic fate of exercise-derived lactate that crosses the blood-brain barrier.

Evidence that anhedonia is a symptom of opioid dependence associated with recent use.

BACKGROUND: Anhedonia is prevalent among substance-dependent populations. The hedonic allostasis model suggests this is due to the effects of addictive substances on neural substrates of reward processing. However, previous research may have been confounded by other factors likely to influence anhedonia, including tobacco use, psychopathology, and history of trauma and other stressors. Thus it remains unclear whether elevated anhedonia in substance-dependent populations is caused by substance use itself, or is due to other correlates of substance dependence. METHODS: Multivariate analysis of covariance was conducted to test whether opioid-dependent participants' anhedonia scores were elevated, relative to a non-dependent control group, after controlling for psychosocial factors likely to influence anhedonia. Correlational analyses within opioid-dependent participants were also conducted to examine whether anhedonia was associated with recent illicit opioid use or duration of abstinence. RESULTS: There was a modest, but significant, elevation in anhedonia in opioid-dependent participants, relative to controls (Partial η2=0.034, p=0.041) after controlling for psychosocial variables that were associated with anhedonia. Depressive symptoms and history of post-traumatic stress disorder also remained significantly associated with anhedonia in the adjusted model. Among participants on opioid pharmacotherapy, there were significant associations between frequency of recent illicit opioid use and scores on anhedonia measures (all rs>0.25, p<0.013), but among abstinent opioid-dependent participants, relationships between duration of abstinence and anhedonia were not significant (all rs<0.24, p>0.22). CONCLUSION: These findings support the hypothesis that use of opioids can cause anhedonia, although other psychosocial factors may also contribute to the high prevalence of anhedonia among opioid-dependent populations.

Orbitofrontal and caudate volumes in cannabis users: a multi-site mega-analysis comparing dependent versus non-dependent users.

RATIONALE: Cannabis (CB) use and dependence are associated with regionally specific alterations to brain circuitry and substantial psychosocial impairment. OBJECTIVES: The objective of this study was to investigate the association between CB use and dependence, and the volumes of brain regions critically involved in goal-directed learning and behaviour-the orbitofrontal cortex (OFC) and caudate. METHODS: In the largest multi-site structural imaging study of CB users vs healthy controls (HC), 140 CB users and 121 HC were recruited from four research sites. Group differences in OFC and caudate volumes were investigated between HC and CB users and between 70 dependent (CB-dep) and 50 non-dependent (CB-nondep) users. The relationship between quantity of CB use and age of onset of use and caudate and OFC volumes was explored. RESULTS: CB users (consisting of CB-dep and CB-nondep) did not significantly differ from HC in OFC or caudate volume. CB-dep compared to CB-nondep users exhibited significantly smaller volume in the medial and the lateral OFC. Lateral OFC volume was particularly smaller in CB-dep females, and reduced volume in the CB-dep group was associated with higher monthly cannabis dosage. CONCLUSIONS: Smaller medial OFC volume may be driven by CB dependence-related mechanisms, while smaller lateral OFC volume may be due to ongoing exposure to cannabinoid compounds. The results highlight a distinction between cannabis use and dependence and warrant examination of gender-specific effects in studies of CB dependence.