Hair cortisol and childhood trauma predict psychological therapy response in depression and anxiety disorders

Objective Around 30–50% of patients with depression and anxiety disorders fail to respond to standard psychological therapy. Given that cortisol affects cognition, patients with altered hypothalamic–pituitary–adrenal (HPA) axis functioning may benefit less from such treatments. To investigate this, reliable pretreatment cortisol measures are needed. Method N = 89 outpatients with depression and anxiety disorders were recruited before undergoing therapy within an Improving Access to Psychological Therapies (IAPT) service. Three-month hair cortisol was determined, and the Childhood Trauma Questionnaire was administered. Patients were classified as responders if they showed significant decreases in depression (>= 6 points on the Patient Health Questionnaire) or anxiety (>= 5 points on the Generalised Anxiety Disorder Scale). Results Non-responders in terms of depression (57%) had lower pretreatment hair cortisol concentrations (P = 0.041) and reported more physical abuse (P = 0.024), sexual abuse (P = 0.010) and total trauma (P = 0.039) when compared to responders. Non-responders in terms of anxiety (48%) had lower pretreatment hair cortisol (P = 0.027), as well as higher levels of emotional abuse (P = 0.034), physical abuse (P = 0.042) and total trauma (P = 0.048). Conclusion If future research confirms hair cortisol to be a predictor of psychological therapy response, this may prove a useful clinical biomarker which identifies a subgroup requiring more intensive treatment

Effects of voriconazole on Cryptococcus neoformans

Voriconazole is a broad-spectrum triazole that offers extended activity against molds and yeasts that are not susceptible to earlier azole-type drugs. Recent studies indicate that melanization can severely reduce the susceptibility of certain antifungal drugs, but there is no information as to whether voriconazole is vulnerable to this effect. The activity of voriconazole on C. neoformans was assessed by MIC analysis and time-kill assays for melanized and nonmelanized cells. Cell morphology, capsule release, and phagocytosis of C. neoformans were studied in the presence or absence of subinhibitory concentrations of voriconazole. Voriconazole was fungicidal at concentrations of ≥8 μg/ml in vitro against the strains of C. neoformans examined, and its efficacy was not diminished by melanization. Cells grown in subinhibitory concentrations of voriconazole had smaller cellular and capsular volumes than cells grown in the absence of drug. The induction of the capsule by serum was not affected by voriconazole. Cells grown in subinhibitory concentrations of voriconazole released their capsule and were phagocytosed at rates comparable with yeast grown without the antifungal. The high activity of voriconazole against both melanized and nonmelanized cells results suggest that voriconazole may be a particularly valuable drug for cryptococcosis

Development of Parkinsonism following exposure to aripiprazole: two case reports

which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Introduction: Aripiprazole is a novel atypical neuroleptic used in the treatment of psychosis. A few recent studies have demonstrated an association between the use of aripiprazole and an exacerbation of Parkinsonism, although this relationship is poorly defined. To our knowledge, this is the first case series describing an onset of Parkinsonism in patients without prior history of Parkinson’s diseas

High cocoa polyphenol rich chocolate may reduce the burden of the symptoms in chronic fatigue syndrome

<p>Abstract</p> <p>Background</p> <p>Chocolate is rich in flavonoids that have been shown to be of benefit in disparate conditions including cardiovascular disease and cancer. The effect of polyphenol rich chocolate in subjects with chronic fatigue syndrome (CFS) has not been studied previously.</p> <p>Methods</p> <p>We conducted a double blinded, randomised, clinical pilot crossover study comparing high cocoa liquor/polyphenol rich chocolate (HCL/PR) in comparison to simulated iso-calorific chocolate (cocoa liquor free/low polyphenols(CLF/LP)) on fatigue and residual function in subjects with chronic fatigue syndrome. Subjects with CFS having severe fatigue of at least 10 out of 11 on the Chalder Fatigue Scale were enrolled. Subjects had either 8 weeks of intervention in the form of HCL/PR or CLF/LP, with a 2 week wash out period followed by 8 weeks of intervention with the other chocolate.</p> <p>Results</p> <p>Ten subjects were enrolled in the study. The Chalder Fatigue Scale score improved significantly after 8 weeks of the HCL/PR chocolate arm [median (range) Exact Sig. (2-tailed)] [33 (25 - 38) vs. 21.5 (6 - 35) 0.01], but that deteriorated significantly when subjects were given simulated iso-calorific chocolate (CLF/CP) [ 28.5 (17 - 20) vs. 34.5 (13-26) 0.03]. The residual function, as assessed by the London Handicap scale, also improved significantly after the HCL/PR arm [0.49 (0.33 - 0.62) vs. 0.64 (0.44 - 0.83) 0.01] and deteriorated after iso-calorific chocolate [00.44 (0.43 - 0.68) vs. 0.36 (0.33 - 0.62)0.03]. Likewise the Hospital Anxiety and Depression score also improved after the HCL/PR arm, but deteriorated after CLF/CP. Mean weight remained unchanged throughout the trial.</p> <p>Conclusion</p> <p>This study suggests that HCL/PR chocolate may improve symptoms in subjects with chronic fatigue syndrome.</p

Can evidence change belief ? Reported mobile phone sensitivity following individual feedback of an inability to discriminate active from sham signals

Abstract Objective: In this study, we tested whether providing individuals, who described being sensitive to mobile phone signals, with accurate feedback about their ability to discriminate an active mobile phone signal from a sham signal had any impact on their subsequent symptom levels or their perceived sensitivity to mobile phones. Methods: Sixty-nine participants who reported sensitivity to mobile phones took part in a doubleblind, placebo-controlled provocation study. Perceived sensitivity to mobile phones was assessed using a version of the Sensitive Soma Assessment Scale (SSAS) and the severity of any symptoms attributed to mobile phones was recorded. Both the overall (&quot;negative&quot;) findings of the provocation study and the participant&apos;s own individual results (&quot;correct&quot; or &quot;incorrect&quot; at detecting a mobile phone signal) were then described to them. Six months later, perceived sensitivity and symptom severity were measured again. Results: Fifty-eight participants (84%) received feedback and participated in the 6-month follow-up. No significant differences in SSAS scores or in symptom severity scores were found between individuals told that they were correct (n=31) or incorrect (n=27) in their ability to detect mobile phone signals in the provocation study. Conclusion: The provision of accurate feedback was insufficient to change attributions or reduce symptoms in this study. However, an overtly negative reaction to feedback was not observed among most participants, and some participants were willing to consider that factors other than electromagnetic field may be relevant in causing or exacerbating their symptoms. Discussing possible psychological factors with electromagnetic hypersensitivity patients may be beneficial for some

Persistent fatigue induced by interferon-alpha: a novel, inflammation-based, proxy model of chronic fatigue syndrome.

The role of immune or infective triggers in the pathogenesis of Chronic Fatigue Syndrome (CFS) is not yet fully understood. Barriers to obtaining immune measures at baseline (i.e., before the trigger) in CFS and post-infective fatigue model cohorts have prevented the study of pre-existing immune dysfunction and subsequent immune changes in response to the trigger. This study presents interferon-alpha (IFN-α)-induced persistent fatigue as a model of CFS. IFN-α, which is used in the treatment of chronic Hepatitis C Virus (HCV) infection, induces a persistent fatigue in some individuals, which does not abate post-treatment, that is, once there is no longer immune activation. This model allows for the assessment of patients before and during exposure to the immune trigger, and afterwards when the original trigger is no longer present. Fifty-five patients undergoing IFN-α treatment for chronic HCV were assessed at baseline, during the 6-12 months of IFN-α treatment, and at six-months post-treatment. Measures of fatigue, cytokines and kynurenine pathway metabolites were obtained. Fifty-four CFS patients and 57 healthy volunteers completed the same measures at a one-off assessment, which were compared with post-treatment follow-up measures from the HCV patients. Eighteen patients undergoing IFN-α treatment (33%) were subsequently defined as having 'persistent fatigue' (the proposed model for CFS), if their levels of fatigue were higher six-months post-treatment than at baseline; the other 67% were considered 'resolved fatigue'. Patients who went on to develop persistent fatigue experienced a greater increase in fatigue symptoms over the first four weeks of IFN-α, compared with patients who did not (Δ Treatment Week (TW)-0 vs. TW4; PF: 7.1 ± 1.5 vs. RF: 4.0 ± 0.8, p = 0.046). Moreover, there was a trend towards increased baseline interleukin (IL)-6, and significantly higher baseline IL-10 levels, as well as higher levels of these cytokines in response to IFN-α treatment, alongside concurrent increases in fatigue. Levels increased to more than double those of the other patients by Treatment Week (TW)4 (p =  0.011 for IL-6 and p = 0.001 for IL-10). There was no evidence of an association between persistent fatigue and peripheral inflammation six-months post-treatment, nor did we observe peripheral inflammation in the CFS cohort. While there were changes in kynurenine metabolites in response to IFN-α, there was no association with persistent fatigue. CFS patients had lower levels of the ratio of kynurenine to tryptophan and 3-hydroxykynurenine than controls. Future studies are needed to elucidate the mechanisms behind the initial exaggerated response of the immune system in those who go on to experience persistent fatigue even if the immune trigger is no longer present, and the change from acute to chronic fatigue in the absence of continued peripheral immune activation

Perturbations in gut microbiota composition in psychiatric disorders: a review and meta-analysis

Importance: evidence of gut microbiota perturbations has accumulated for multiple psychiatric disorders, with microbiota signatures proposed as potential biomarkers. However, no attempts have been made to evaluate the specificity of these across the range of psychiatric conditions. Objective: to conduct an umbrella and updated meta-analysis of gut microbiota alterations in general adult psychiatric populations and perform a within- and between-diagnostic comparison. Data Sources: Cochrane Library, PubMed, PsycINFO, and Embase were searched up to February 2, 2021, for systematic reviews, meta-analyses, and original evidence. Study Selection: a total of 59 case-control studies evaluating diversity or abundance of gut microbes in adult populations with major depressive disorder, bipolar disorder, psychosis and schizophrenia, anorexia nervosa, anxiety, obsessive compulsive disorder, posttraumatic stress disorder, or attention-deficit/hyperactivity disorder were included. Data Extraction and Synthesis: between-group comparisons of relative abundance of gut microbes and beta diversity indices were extracted and summarized qualitatively. Random-effects meta-analyses on standardized mean difference (SMD) were performed for alpha diversity indices. Main Outcomes and Measures: Alpha and beta diversity and relative abundance of gut microbes. Results: A total of 34 studies provided data and were included in alpha diversity meta-analyses (n = 1519 patients, n = 1429 control participants). Significant decrease in microbial richness in patients compared with control participants were found (observed species SMD = -0.26; 95% CI, -0.47 to -0.06; Chao1 SMD = -0.5; 95% CI, -0.79 to -0.21); however, this was consistently decreased only in bipolar disorder when individual diagnoses were examined. There was a small decrease in phylogenetic diversity (SMD = -0.24; 95% CI, -0.47 to -0.001) and no significant differences in Shannon and Simpson indices. Differences in beta diversity were consistently observed only for major depressive disorder and psychosis and schizophrenia. Regarding relative abundance, little evidence of disorder specificity was found. Instead, a transdiagnostic pattern of microbiota signatures was found. Depleted levels of Faecalibacterium and Coprococcus and enriched levels of Eggerthella were consistently shared between major depressive disorder, bipolar disorder, psychosis and schizophrenia, and anxiety, suggesting these disorders are characterized by a reduction of anti-inflammatory butyrate-producing bacteria, while pro-inflammatory genera are enriched. The confounding associations of region and medication were also evaluated. Conclusions and Relevance: This systematic review and meta-analysis found that gut microbiota perturbations were associated with a transdiagnostic pattern with a depletion of certain anti-inflammatory butyrate-producing bacteria and an enrichment of pro-inflammatory bacteria in patients with depression, bipolar disorder, schizophrenia, and anxiety.