Cortisol output in adolescents with chronic fatigue syndrome:Pilot study on the comparison with healthy adolescents and change after cognitive behavioural guided self-help treatment

ObjectiveThis study examined cortisol in adolescents with chronic fatigue syndrome (CFS) compared to healthy adolescents and changes in cortisol after cognitive behavioural guided self-help treatment. Exploratory analyses investigated the association between cortisol output and psychological variables.MethodsSalivary cortisol was measured upon awakening, at 15, 30, 45 and 60 min afterwards and at 12 noon, 4:00 p.m. and 8:00 p.m., in adolescents with CFS and healthy controls (HC). Groups were matched for age, gender, menarche status, menstrual cycle and awakening time. Twenty-four adolescents with CFS provided saliva samples six months after treatment. The main outcome measure was total salivary output over the day, calculated by area under the curve (AUC). The salivary awakening response was also assessed.ResultsCortisol output over the day was significantly lower in the CFS group (n = 46) than in healthy controls (n = 33). Within the CFS group, lower daily cortisol output was associated with higher self-reported perfectionist striving and prosocial behaviour. There were no significant group differences in the awakening response (n = 47 CFS versus n = 34 HC). After treatment, adolescents with CFS (n = 21) showed a significant increase in daily cortisol output, up to normal levels.ConclusionThe reduced daily cortisol output in adolescents with CFS is in line with adult findings. Associations between reduced cortisol output and two psychological variables—perfectionism and prosocial behaviour—are consistent with cognitive behavioural models of chronic fatigue syndrome. The mild hypocortisolism is reversible; cortisol output had returned to healthy adolescent levels by six months after cognitive behavioural guided self-help treatment

Antitumor Pentamethylcyclopentadienyl Rhodium Complexes of Maltol and Allomaltol: Synthesis, Solution Speciation and Bioactivity

The reaction of the dimer [RhIII(pentamethylcyclopentadienyl)(m-Cl)Cl]2 ([RhIII(Cp*)(m- Cl)Cl]2) with the hydroxypyrone ligands maltol and allomaltol affords complexes of the general formula [RhIII(Cp*)(L)Cl] under standard and microwave conditions. The organometallic compounds were characterized by standard analytical methods and in the case of the allomaltol derivative in the solid state by single-crystal X-ray diffraction analysis. The complexes showed similar cytotoxicity profiles and were proved to be moderately active against various human cancer cell lines. The stoichiometry and stability of these complexes were determined in aqueous solution by pH-potentiometry, 1H NMR spectroscopy and UVvisible spectrophotometry. Speciation was studied in the presence and in the absence of chloride ions. Hydrolysis of [RhIII(Cp*)(H2O)3]2+ gave dimeric mixed hydroxido species [(RhIII(Cp*))2(m-OH)3]+ and [(RhIII(Cp*))2(m-OH)2Z2] (Z = H2O/Cl‒). Formation of the mononuclear complexes [RhIII(Cp*)(L)Z] of maltol and allomaltol with similar and moderate stability was found. These species predominate at physiological pH and decompose only partially at micromolar concentrations. In addition, hydrolysis of the aqua complex or the chlorido/hydroxido co-ligand exchange resulted in the formation of the mixed-hydroxido species [RhIII(Cp*)(L)(OH)] in the basic pH range. Replacement of the chlorido by an aqua ligand in the complex [RhIII(Cp*)(L)Cl] was monitored and with the help of the equilibrium constants the extent of aquation at various chloride concentrations of the extra- and intracellular milieu can be predicted. Complexation of these RhIII complexes was compared to analogous [RuII(h6-p-cymene)] species and higher conditional stabilities were found in the case of the RhIII compounds at pH 7.4

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

A narrative review on the similarities and dissimilarities between myalgic encephalomyelitis/chronic fatigue syndrome (me/cfs) and sickness behavior

It is of importance whether myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a variant of sickness behavior. The latter is induced by acute infections/injury being principally mediated through proinflammatory cytokines. Sickness is a beneficial behavioral response that serves to enhance recovery, conserves energy and plays a role in the resolution of inflammation. There are behavioral/symptomatic similarities (for example, fatigue, malaise, hyperalgesia) and dissimilarities (gastrointestinal symptoms, anorexia and weight loss) between sickness and ME/CFS. While sickness is an adaptive response induced by proinflammatory cytokines, ME/CFS is a chronic, disabling disorder, where the pathophysiology is related to activation of immunoinflammatory and oxidative pathways and autoimmune responses. While sickness behavior is a state of energy conservation, which plays a role in combating pathogens, ME/CFS is a chronic disease underpinned by a state of energy depletion. While sickness is an acute response to infection/injury, the trigger factors in ME/CFS are less well defined and encompass acute and chronic infections, as well as inflammatory or autoimmune diseases. It is concluded that sickness behavior and ME/CFS are two different conditions

A morphometric signature of depressive symptoms in unmedicated patients with mood disorders

OBJECTIVE: A growing literature indicates that unipolar depression and bipolar depression are associated with alterations in grey matter volume. However, it is unclear to what degree these patterns of morphometric change reflect symptom dimensions. Here, we aimed to predict depressive symptoms and hypomanic symptoms based on patterns of grey matter volume using machine learning. METHOD: We used machine learning methods combined with voxel-based morphometry to predict depressive and self-reported hypomanic symptoms from grey matter volume in a sample of 47 individuals with unmedicated unipolar and bipolar depression. RESULTS: We were able to predict depressive severity from grey matter volume in the anteroventral bilateral insula in both unipolar depression and bipolar depression. Self-reported hypomanic symptoms did not predict grey matter loss with a significant degree of accuracy. DISCUSSION: The results of this study suggest that patterns of grey matter volume alteration in the insula are associated with depressive symptom severity across unipolar and bipolar depression. Studies using other modalities and exploring other brain regions with a larger sample are warranted to identify other systems that may be associated with depressive and hypomanic symptoms across affective disorders

Inflammation, Glutamate, and Cognition in Bipolar Disorder Type II:A Proof of Concept Study

Background: Two current theories regarding the neuroscientific bases of mood disorders involve alterations in glutamatergic neurotransmission and excessive activation of inflammatory pathways. We hypothesized that glutamate (Glu) levels and peripheral inflammatory markers would be associated with cognitive function, in patients with Bipolar Disorder Type II (BP-II), and that such factors would be associated with psychological treatment outcomes. Aims: The primary aim of this study was to explore the relationship between the neurotransmitter Glu, cytokines (CRP, IL_6, and TNFa) and neuropsychological and related functioning. The secondary aim was to assess cognitive functioning as a predictor of poor response to psychological therapy. Methods: Proton magnetic resonance spectroscopy data were acquired from the anterior cingulate cortex (ACC) of 15 participants with BP-II, and 13 healthy controls in a 3T magnetic resonance imaging scanner. The Digit Symbol Task (DST) for processing speed, TMT-B for executive function and Rey Auditory Verbal Learning Test (RAVLT) were administered to assess cognitive domains. Results: There was no significant difference in anterior cingulate Glu, or inflammatory markers between groups. Furthermore, we found no significant difference between groups in any cognitive tests. Scores on the DST were found to be significantly associated with poor response to psychological therapy. Conclusions: This study may highlight an association between neuropsychological dysfunction and treatment outcome in euthymic patients with BP-II. We did not find any association between peripheral inflammatory markers and brain Glu levels. This may have been in part due to the small sample size.</p

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

Study protocol for a randomised pragmatic trial comparing the clinical and cost effectiveness of Lithium and Quetiapine augmentation in treatment resistant Depression (the LQD study)

Background: Approximately 30–50% of patients with major depressive disorder can be classed as treatment resistant, widely defined as a failure to respond to two or more adequate trials of antidepressants in the current episode. Treatment resistant depression is associated with a poorer prognosis and higher mortality rates. One treatment option is to augment an existing antidepressant with a second agent. Lithium and the atypical antipsychotic quetiapine are two such add-on therapies and are currently recommended as first line options for treatment resistant depression. However, whilst neither treatment has been established as superior to the other in short-term studies, they have yet to be compared head-to-head in longer term studies, or with a superiority design in this patient group.Methods: The Lithium versus Quetiapine in Depression (LQD) study is a parallel group, multi-centre, pragmatic, open label, patient randomised clinical trial designed to address this gap in knowledge. The study will compare the clinical andcost effectiveness of the decision to prescribe lithium or quetiapine add-on therapy to antidepressant medication for patients with treatment resistant depression. Patients will be randomised 1:1 and followed up over 12 months, with the hypothesis being that quetiapine will be superior to lithium. The primary outcomes will be: (1) time to all-cause treatment discontinuation over one year, and (2) self-rated depression symptoms rated weekly for one year via the Quick Inventory of Depressive Symptomatology. Other outcomes will include between group differences in response and remission rates, quality of life, social functioning, cost-effectiveness and the frequency of serious adverse events and side effects.Discussion: The trial aims to help shape the treatment pathway for patients with treatment resistant depression, by determining whether the decision to prescribe quetiapine is superior to lithium. Strengths of the study include its pragmatic superiority design, broad inclusion criteria (external validity) and longer follow up than previous studies.Trial registration: ISRCTN registry: ISRCTN16387615, registered 28 February 2016. ClinicalTrials.gov: NCT03004521, registered 17 November 2016.<br/