Can the DEX/CRH test or markers of oxidative stress distinguish work-related stress from major depressive disorder and normal controls?

Hypothalamic-pituitary-adrenal (HPA)-axis hyperactivity measured by the combined dexamethasone-CRH test (DEX-CRH test) has been found in patients with major depressive disorder (MDD), whereas hypoactivity has been found in patients with work-related stress. We aimed to investigate the DEX-CRH test as a biomarker to distinguish between MDD and work-related stress (exhaustion disorder - ED). We hypothesized that there would be lower cortisol and ACTH response in participants with ED compared to MDD and healthy controls (HC).

When a test is more than just a test: Findings from patient interviews and survey in the trial of a technology to measure antidepressant medication response (the PReDicT Trial).

Background: A RCT of a novel intervention to detect antidepressant medication response (the PReDicT Test) took place in five European countries, accompanied by a nested study of its acceptability and implementation presented here. The RCT results indicated no effect of the intervention on depression at 8 weeks (primary outcome), although effects on anxiety at 8 weeks and functioning at 24 weeks were found.

Methods: The nested study used mixed methods.

Heart rate variability, interoceptive accuracy and functional connectivity in middle-aged and older patients with depression.

Background And Objective: Major depressive disorder (MDD) is associated with increased cardiac morbidity. Reduced heart rate variability (HRV) as well as lower interoceptive accuracy (IAc) have been observed in MDD as possible sympathomimetic mechanisms related to insula activity. The salience network (SN) anchored by the insula has been posited as a crucial functional network for cardiac sensations and the default mode network (DMN) for MDD.

The HPA Axis as Target for Depression.

Major depressive disorder (MDD) is a stress-related mental disorder with a lifetime prevalence of 20% and, thus, is one of the most prevalent mental health disorders worldwide. Many studies with a large number of patients support the notion that abnormalities of the hypothalamus-pituitaryadrenal (HPA) axis are crucial for the development of MDD. Therefore, a number of strategies and drugs have been investigated to target different components of the HPA axis: 1) corticotrophinreleasing hormone (CRH) 1 receptor antagonists; 2) vasopressin V receptor antagonists, 3) glucocorticoid receptor antagonists, and 4) FKBP5 antagonists.

Deep phenotyping as a contribution to personalized depression therapy: the GEParD and DaCFail protocols.

Depressive patients suffer from a complex of symptoms of varying intensity compromising their mood, emotions, self-concept, neurocognition, and somatic function. Due to a mosaic of aetiologies involved in developing depression, such as somatic, neurobiological, (epi-)genetic factors, or adverse life events, patients often experience recurrent depressive episodes. About 20-30% of these patients develop difficult-to-treat depression.

Effects of Pharmacokinetic Gene Variation on Therapeutic Drug Levels and Antidepressant Treatment Response.

Introduction: Pharmacogenetic testing is proposed to minimize adverse effects when considered in combination with pharmacological knowledge of the drug. As yet, limited studies in clinical settings have investigated the predictive value of pharmacokinetic (pk) gene variation on therapeutic drug levels as a probable mechanism of adverse effects, nor considered the combined effect of pk gene variation and drug level on antidepressant treatment response.

Methods: Two depression cohorts were investigated for the relationship between pk gene variation and antidepressant serum concentrations of amitriptyline, venlafaxine, mirtazapine and quetiapine, as well as treatment response.

Inhibition of acid sphingomyelinase increases regulatory T cells in humans.

Genetic deficiency for acid sphingomyelinase or its pharmacological inhibition has been shown to increase Foxp3 regulatory T-cell frequencies among CD4 T cells in mice. We now investigated whether pharmacological targeting of the acid sphingomyelinase, which catalyzes the cleavage of sphingomyelin to ceramide and phosphorylcholine, also allows to manipulate relative CD4 Foxp3 regulatory T-cell frequencies in humans. Pharmacological acid sphingomyelinase inhibition with antidepressants like sertraline, but not those without an inhibitory effect on acid sphingomyelinase activity like citalopram, increased the frequency of Foxp3 regulatory T cell among human CD4 T cells .

The clinical effectiveness of using a predictive algorithm to guide antidepressant treatment in primary care (PReDicT): an open-label, randomised controlled trial.

Depressed patients often do not respond to the first antidepressant prescribed, resulting in sequential trials of different medications. Personalised medicine offers a means of reducing this delay; however, the clinical effectiveness of personalised approaches to antidepressant treatment has not previously been tested. We assessed the clinical effectiveness of using a predictive algorithm, based on behavioural tests of affective cognition and subjective symptoms, to guide antidepressant treatment.

Impaired fear learning and extinction, but not generalization, in anxious and non-anxious depression.

Fear conditioning and generalization are well-known mechanisms in the pathogenesis of anxiety disorders. Extinction of conditioned fear responses is crucial for the psychotherapeutic treatment of these diseases. Anxious depression as a subtype of major depression shares characteristics with anxiety disorders.

Stress impairs response to antidepressants via HPA axis and immune system activation.

Childhood trauma as well as severe events occurring later in life have been associated with the development of major depressive disorder (MDD). However, the interaction of early and later occurring adverse events in patients with MDD is understudied. This study aims to disentangle this interaction by investigating the effects on two of the main stress-response systems of the body, the hypothalamic-pituitaryadrenal (HPA-) axis and the immune system in depressed patients.

Long-term effects of stress early in life on microRNA-30a and its network: Preventive effects of lurasidone and potential implications for depression vulnerability.

Exposure to early life stress can interfere with neurodevelopmental trajectories to increase the vulnerability for psychiatric disorders later in life. With this respect, epigenetic mechanisms play a key role for the long-lasting changes in brain functions that may elicit and sustain psychopathologic outcomes. Here, we investigated DNA methylation changes as possible epigenetic mechanism mediating the effect of prenatal stress (PNS), an experimental paradigm associated with behavioral and molecular alterations relevant for psychiatric disorders.

Hypothalamic-pituitary-adrenal axis and stress.

Stress is associated with the onset of several stress-related mental disorders that occur more frequently in women than in men, such as major depression or posttraumatic stress disorder (PTSD). The hypothalamic-pituitary-adrenal (HPA) axis is the major component of the neuroendocrine network responding to internal and external challenges. The proper functioning of the HPA axis is critical for the maintenance of mental and physical health, as dysregulations of the HPA axis have been linked to several mental and physical disorders.

Higher venlafaxine serum concentrations necessary for clinical improvement? Time to re-evaluate the therapeutic reference range of venlafaxine.

Background: The therapeutic reference range for venlafaxine in antidepressant treatment has been defined as 100 to 400 ng/mL. However, in an everyday setting active moiety concentrations above the therapeutic reference range were often reported.

Aim: The aim of this study was to re-evaluate the therapeutic reference range of venlafaxine.

DNA hypomethylation of the Krüppel-like factor 11 (KLF11) gene promoter: a putative biomarker of depression comorbidity in panic disorder and of non-anxious depression?

Panic disorder (PD) is one of the most common anxiety disorders and often occurs comorbidly with major depressive disorder (MDD). Altered methylation of the monoamine oxidase A (MAOA) gene has been implicated in the etiology of both PD and MDD. The Krüppel-like factor 11 (KLF11; alias TIEG2), an activating transcription factor of the MAOA gene, has been found to be increased in MDD, but has not yet been investigated in PD.

Extent of cortisol suppression at baseline predicts improvement in HPA axis function during antidepressant treatment.

Background: A dysregulation in the hypothalamic-pituitary-adrenal (HPA)-axis function has been repeatedly observed in major depressive disorders (MDD). Normalization of this dysregulation, i.e.

Nortriptyline serum concentration as a predictor for cardiac risk in amitriptyline-treated patients.

Purpose: Tricyclic antidepressants have been shown to affect electrocardiogram (ECG) parameters, but there is limited evidence in relation to the serum concentrations. Therefore, we aimed to evaluate a prediction of cardiac risk in amitriptyline- and doxepin-treated patients by serum concentrations.

Patients And Methods: The association between serum concentrations of amitriptyline (n = 100) and doxepin (n = 71) and ECG parameters was retrospectively examined using linear regression analysis.

Covariation bias in depression - a predictor of treatment response?

Covariation bias, defined as an overestimation of the relationship between fear-relevant stimuli and aversive consequences, is a well-investigated cognitive bias in anxiety disorders. As patients with affective disorders also show biased information processing, the aim of the present study was to investigate whether depressed patients also display a covariation bias between negative stimuli and aversive consequences. Covariation estimates of 62 inpatients with a current severe depressive episode were assessed at admission (n = 31) or after 6 weeks of treatment (n = 31) and were compared in a between-group design with 31 age- and sex-matched healthy controls.

Smoking Is Associated With Lower Dose-Corrected Serum Concentrations of Escitalopram.

Background: Tobacco smoking rates in depressive patients are higher compared with the general population. Smoking was demonstrated to accelerate the metabolism of different drugs metabolized by CYP1A2, but possibly also by CYP2C19 and CYP3A4. The principle aim of the present investigation from 2015 to 2018 was to determine the differences in the pharmacokinetics of escitalopram between smokers and nonsmokers.

Roadmap for Routine Pharmacogenetic Testing in a Psychiatric University Hospital.

Major depressive disorder (MDD) implicates a huge burden for patients and society. Although currently available antidepressants are effective treatment options, more than 50% of the patients do not respond to the first administered antidepressant. In addition, in more than 25% with antidepressants-treated patients, adverse effects occur.

Determination of hydroxybupropion in human serum for routine therapeutic drug monitoring in psychiatry: A tool for dose-individualization in treatment with bupropion.

Therapeutic drug monitoring (TDM) has become a clinical routine in psychiatry. Nevertheless, for bupropion there is only one method available that is suitable for routine use. However, it involves a complex sample clean-up.

Identification of dynamic glucocorticoid-induced methylation changes at the FKBP5 locus.

Background: Epigenetic mechanisms may play a major role in the biological embedding of early-life stress (ELS). One proposed mechanism is that glucocorticoid (GC) release following ELS exposure induces long-lasting alterations in DNA methylation (DNAm) of important regulatory genes of the stress response. Here, we investigate the dynamics of GC-dependent methylation changes in key regulatory regions of the FKBP5 locus in which ELS-associated DNAm changes have been reported.

Pathological Concentration of C-reactive Protein is Correlated to Increased Concentrations of Quetiapine, But Not of Risperidone, Olanzapine and Aripiprazole in a Naturalistic Setting.

Introduction: Infections can alter drug clearance, but the impact of inflammation-induced changes is still not well known. The aim of the investigation was to examine the effect of pathological C-reactive protein (CRP) values (≥0.5 mg/dL) and leukocyte count on the metabolism of 4 different atypical antipsychotics.