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 .

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.

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.

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.

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.

Childhood trauma dependent anxious depression sensitizes HPA axis function.

Anxious depression is a common subtype of major depressive disorder (MDD) and is associated with greater severity and poorer outcome. Alterations of the hypothalamic-pituitary-adrenal (HPA) axis, especially of the glucocorticoid receptor (GR) function, are often observed in MDD, but evidence lacks for anxious depression. Childhood adversity is known to influence both the HPA axis and risk of MDD.