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Recent studies have demonstrated anxiolytic potential of pharmacological endocannabinoid (eCB) augmentation approaches in a variety of preclinical models. Pharmacological inhibition of endocannabinoid-degrading enzymes, such as fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL), elicit promising anxiolytic effects in rodent models with limited adverse behavioral effects, however, the efficacy of dual FAAH/MAGL inhibition has not been investigated. In the present study, we compared the effects of FAAH (PF-3845), MAGL (JZL184) and dual FAAH/MAGL (JZL195) inhibitors on (1) anxiety-like behaviors under non-stressed and stressed conditions, (2) locomotor activity and body temperature, (3) lipid levels in the brain and (4) cognitive functions. Behavioral analysis showed that PF-3845 or JZL184, but not JZL195, was able to prevent restraint stress-induced anxiety in the light-dark box assay when administered before stress exposure. Moreover, JZL195 treatment was not able to reverse foot shock-induced anxiety-like behavior in the elevated zero maze or light-dark box. JZL195, but not PF-3845 or JZL184, decreased body temperature and increased anxiety-like behavior in the open-field test. Overall, JZL195 did not show anxiolytic efficacy and the effects of JZL184 were more robust than that of PF-3845 in the models examined. These results showed that increasing either endogenous AEA or 2-AG separately produces anti-anxiety effects under stressful conditions but the same effects are not obtained from simultaneously increasing both AEA and 2-AG.
AIMS - Psychosocial factors amplify symptoms of Interstitial Cystitis (IC/BPS). While psychosocial self-management is efficacious in other pain conditions, its impact on an IC/BPS population has rarely been studied. The objective of this review is to learn the prevalence and impact of psychosocial factors on IC/BPS, assess baseline psychosocial characteristics, and offer recommendations for assessment and treatment.
METHOD - Following PRISMA guidelines, primary information sources were PubMed including MEDLINE, Embase, CINAHL, and GoogleScholar. Inclusion criteria included: (i) a clearly defined cohort with IC/BPS or with Chronic Pelvic Pain Syndrome provided the IC/BPS cohort was delineated with quantitative results from the main cohort; (ii) all genders and regions; (iii) studies written in English from 1995 to April 14, 2017; (iv) quantitative report of psychosocial factors as outcome measures or at minimum as baseline characteristics.
RESULTS - Thirty-four of an initial 642 articles were reviewed. Quantitative analyses demonstrate the magnitude of psychosocial difficulties in IC/BPS, which are worse than average on all measures, and fall into areas of clinical concern for 7 out of 10 measures. Meta-analyses shows mean Mental Component Score of the Short-Form 12 Health Survey (MCS) of 40.80 (SD 6.25, N = 2912), where <36 is consistent with severe psychological impairment. Averaged across studies, the population scored in the range seen in clinical depression (CES-D 19.89, SD 13.12, N = 564) and generalized anxiety disorder (HADS-A 8.15, SD 4.85, N = 465).
CONCLUSION - The psychological impact of IC/BPS is pervasive and severe. Existing evidence of treatment is lacking and suggests self-management intervention may be helpful.
© 2017 Wiley Periodicals, Inc.
Depression and anxiety are the most common psychiatric disorders, representing a major public health concern. Dysregulation of oxidative and inflammatory systems may be associated with psychiatric disorders, such as depression and anxiety. Due to the need to find appropriate animal models to the understanding of such disorders, we queried whether 2 BXD recombinant inbred (RI) mice strains (BXD21/TyJ RI and BXD84/RwwJ RI mice) and C57BL/6 wild-type mice show differential performance in depression and anxiety related behaviors and biomarkers. Specifically, we assessed social preference, elevated plus maze, forced swim, and Von Frey tests at 3-4 months-of-age, as well as activation of cytokines and antioxidant mRNA levels in the cortex at 7 months-of-age. We report that (1) the BXD84/RwwJ RI strain exhibits anxiety disorder and social avoidance-like behavior (2) BXD21/TyJ RI strain shows a resistance to depression illness, and (3) sex-dependent cytokine profiles and allodynia with elevated inflammatory activity were inherent to male BXD21/TyJ RI mice. In conclusion, we provide novel data in favor of the use of BXD recombinant inbred mice to further understand anxiety and depression disorders.
Copyright © 2017 Elsevier Ltd. All rights reserved.
Racial/ethnic differences in health are evident among men. Previous work suggests associations between mental and physical health but few studies have examined how mood/anxiety disorders and chronic physical health conditions covary by age, race, and ethnicity among men. Using data from 1,277 African American, 629 Caribbean Black, and 371 non-Hispanic White men from the National Survey of American Life, we examined associations between race/ethnicity and experiencing one or more chronic physical health conditions in logistic regression models stratified by age and 12-month mood/anxiety disorder status. Among men <45 years without mood/anxiety disorders, Caribbean Blacks had lower odds of chronic physical health conditions than Whites. Among men aged 45+ years with mood/anxiety disorders, African Americans had greater odds of chronic physical health conditions than Whites. Future studies should explore the underlying causes of such variation and how studying mental and chronic physical health problems together may help identify mechanisms that underlie racial disparities in life expectancy among men.
Although pediatric functional abdominal pain (FAP) has been linked to abdominal pain later in life, childhood predictors of long-term outcomes have not been identified. This study evaluated whether distinct FAP profiles based on patterns of pain and adaptation in childhood could be identified and whether these profiles predicted differences in clinical outcomes and central sensitization (wind-up) on average 9years later. In 843 pediatric FAP patients, cluster analysis was used to identify subgroups at initial FAP evaluation based on profiles of pain severity, gastrointestinal (GI) and non-GI symptoms, pain threat appraisal, pain coping efficacy, catastrophizing, negative affect, and activity impairment. Three profiles were identified: high pain dysfunctional, high pain adaptive, and low pain adaptive. Logistic regression analyses controlling for age and sex showed that, compared with pediatric patients with the low pain adaptive profile, those with the high pain dysfunctional profile were significantly more likely at long-term follow-up to meet criteria for pain-related functional gastrointestinal disorder (FGID) (odds ratio: 3.45, confidence interval: 1.95 to 6.11), FGID with comorbid nonabdominal chronic pain (odds ratio: 2.6, confidence interval: 1.45 to 4.66), and FGID with comorbid anxiety or depressive psychiatric disorder (odds ratio: 2.84, confidence interval: 1.35 to 6.00). Pediatric patients with the high pain adaptive profile had baseline pain severity comparable to that of the high pain dysfunctional profile, but had outcomes as favorable as the low pain adaptive profile. In laboratory pain testing at follow-up, high pain dysfunctional patients showed significantly greater thermal wind-up than low pain adaptive patients, suggesting that a subgroup of FAP patients has outcomes consistent with widespread effects of heightened central sensitization.
Copyright © 2012 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.
Genetic factors underlying trait neuroticism, reflecting a tendency towards negative affective states, may overlap genetic susceptibility for anxiety disorders and help explain the extensive comorbidity amongst internalizing disorders. Genome-wide linkage (GWL) data from several studies of neuroticism and anxiety disorders have been published, providing an opportunity to test such hypotheses and identify genomic regions that harbor genes common to these phenotypes. In all, 11 independent GWL studies of either neuroticism (n=8) or anxiety disorders (n=3) were collected, which comprised of 5341 families with 15 529 individuals. The rank-based genome scan meta-analysis (GSMA) approach was used to analyze each trait separately and combined, and global correlations between results were examined. False discovery rate (FDR) analysis was performed to test for enrichment of significant effects. Using 10 cM intervals, bins nominally significant for both GSMA statistics, P(SR) and P(OR), were found on chromosomes 9, 11, 12, and 14 for neuroticism and on chromosomes 1, 5, 15, and 16 for anxiety disorders. Genome-wide, the results for the two phenotypes were significantly correlated, and a combined analysis identified additional nominally significant bins. Although none reached genome-wide significance, an excess of significant P(SR)P-values were observed, with 12 bins falling under a FDR threshold of 0.50. As demonstrated by our identification of multiple, consistent signals across the genome, meta-analytically combining existing GWL data is a valuable approach to narrowing down regions relevant for anxiety-related phenotypes. This may prove useful for prioritizing emerging genome-wide association data for anxiety disorders.
The current study examined the relations of measures of cognitive reappraisal and secondary control coping with working memory abilities, positive and negative affect, and symptoms of anxiety and depression in young adults (N=124). Results indicate significant relations between working memory abilities and reports of secondary control coping and between reports of secondary control coping and cognitive reappraisal. Associations were also found between measures of secondary control coping and cognitive reappraisal and positive and negative affect and symptoms of depression and anxiety. Further, the findings suggest that reports of cognitive reappraisal may be more strongly predictive of positive affect whereas secondary control coping may be more strongly predictive of negative affect and symptoms of depression and anxiety. Overall, the results suggest that current measures of secondary control coping and cognitive reappraisal capture related but distinct constructs and suggest that the assessment of working memory may be more strongly related to secondary control coping in predicting individual differences in distress.
Obsessive-compulsive disorder (OCD) and generalized anxiety disorder (GAD) are both defined by excessive negatively-valenced cognitions. Although obsessional thoughts are considered essential to OCD and perseverative worry is considered essential to GAD, these excessive cognitions have been found to co-occur in both disorders. Accordingly, a common diathesis may influence the emergence of excessive thoughts in both disorders. The present study examined deficits in attentional control as a cognitive vulnerability that may contribute to both obsessional thought and perseverative worry. Patients with OCD (n=30), GAD (n=29), and non-clinical controls (NCC; n=29) completed measures of obsessional thoughts, perseverative worry, and attentional control. Deficits in self-reported attentional control were found in both OCD and GAD relative to the NCC. However, attentional control was only related to excessive cognition in the GAD patient group, where deficits were associated with increased perseverative worry. Mediational modeling suggested that trait anxiety mediated the relationship between attentional control and perseverative worry in GAD. Implications of these findings for conceptualizing the role of attentional control in the genesis of excessive cognitions in OCD and GAD are discussed.
Copyright © 2011 Elsevier Ltd. All rights reserved.