Meta-analysis of CYP2C19 and CYP2D6 metabolic activity on antidepressant response from 13 clinical studies using genotype imputation.

Cytochrome P450 enzymes including CYP2C19 and CYP2D6 are important for antidepressant metabolism and polymorphisms of these genes have been determined to predict metabolite levels. Nonetheless, more evidence is needed to understand the impact of genetic variations on antidepressant response. In this study, individual clinical and genetic data from 13 studies of European and East Asian ancestry populations were collected.

Identifying the Common Genetic Basis of Antidepressant Response.

Background: Antidepressants are a first-line treatment for depression. However, only a third of individuals experience remission after the first treatment. Common genetic variation, in part, likely regulates antidepressant response, yet the success of previous genome-wide association studies has been limited by sample size.

Methodology for clinical genotyping of CYP2D6 and CYP2C19.

Many antidepressants, atomoxetine, and several antipsychotics are metabolized by the cytochrome P450 enzymes CYP2D6 and CYP2C19, and guidelines for prescribers based on genetic variants exist. Although some laboratories offer such testing, there is no consensus regarding validated methodology for clinical genotyping of CYP2D6 and CYP2C19. The aim of this paper was to cross-validate multiple technologies for genotyping CYP2D6 and CYP2C19 against each other, and to contribute to feasibility for clinical implementation by providing an enhanced range of assay options, customizable automated translation of data into haplotypes, and a workflow algorithm.

Genes associated with anhedonia: a new analysis in a large clinical trial (GENDEP).

A key feature of major depressive disorder (MDD) is anhedonia, which is a predictor of response to antidepressant treatment. In order to shed light on its genetic underpinnings, we conducted a genome-wide association study (GWAS) followed by investigation of biological pathway enrichment using an anhedonia dimension for 759 patients with MDD in the GENDEP study. The GWAS identified 18 SNPs associated at genome-wide significance with the top one being an intronic SNP (rs9392549) in PRPF4B (pre-mRNA processing factor 4B) located on chromosome 6 (P = 2.

Mental health service users' experiences of psychiatric re-hospitalisation - an explorative focus group study in six European countries.

Background: Psychiatric re-hospitalisation is considered costly and disruptive to individuals. The perspective of the mental health service user is largely unexplored in literature. The purpose of our study was to explore service users' experiences of psychiatric re-hospitalisation across six countries in Europe.

Antidepressant drug-specific prediction of depression treatment outcomes from genetic and clinical variables.

Individuals with depression differ substantially in their response to treatment with antidepressants. Specific predictors explain only a small proportion of these differences. To meaningfully predict who will respond to which antidepressant, it may be necessary to combine multiple biomarkers and clinical variables.

Association between C-reactive protein (CRP) with depression symptom severity and specific depressive symptoms in major depression.

Introduction: Population-based studies have associated inflammation, particularly higher C-reactive protein (CRP), with depressive severity, but clinical trials in major depressive disorder were rather non-specific without examining the role of gender. We aimed to investigate the association between CRP and overall depression severity including specific depressive symptoms and to examine potential gender differences.

Methods: We included 231 individuals with major depressive disorder from the Genome-Based Therapeutics Drugs for Depression (GENDEP) study.

Psychiatric readmissions and their association with physical comorbidity: a systematic literature review.

Background: Comorbidity between mental and physical disorder conditions is the rule rather than the exception. It is estimated that 25% of adult population have mental health condition and 68% of them suffer from comorbid medical condition. Readmission rates in psychiatric patients are high and we still lack understanding potential predictors of recidivism.

Combining clinical variables to optimize prediction of antidepressant treatment outcomes.

The outcome of treatment with antidepressants varies markedly across people with the same diagnosis. A clinically significant prediction of outcomes could spare the frustration of trial and error approach and improve the outcomes of major depressive disorder through individualized treatment selection. It is likely that a combination of multiple predictors is needed to achieve such prediction.

Exploring the role of drug-metabolising enzymes in antidepressant side effects.

Rationale: Cytochrome P450 enzymes are important in the metabolism of antidepressants. The highly polymorphic nature of these enzymes has been linked to variability in antidepressant metabolism rates, leading to hope regarding the use of P450 genotyping to guide treatment. However, evidence that P450 genotypic differences underlie the variation in treatment outcomes is inconclusive.

Relationship between affective temperaments and aggression in euthymic patients with bipolar mood disorder and major depressive disorder.

Background: So far there is a scarce of studies dealing with the relationship between different aspects of aggressive behaviour and affective temperaments among various mood disorders. The aim of the present study was to explore in a group of patients with affective mood disorders the relationship between affective temperaments and aggression.

Methods: 100 consecutive outpatients in euthymic phase of mood disorders (46 with bipolar disorder-type I, 18 with bipolar disorder-type II and 36 with major depressive disorder) were self-assessed with the Aggression Questionnaire and the short version of Slovenian Temperament Evaluation of Memphis, Pisa, Paris and San Diego - Autoquestionnaire (TEMPS-A).

An inflammatory biomarker as a differential predictor of outcome of depression treatment with escitalopram and nortriptyline.

Objective: Major depressive disorder has been linked with inflammatory processes, but it is unclear whether individual differences in levels of inflammatory biomarkers could help match patients to treatments that are most likely to be beneficial. The authors tested the hypothesis that C-reactive protein (CRP), a commonly available marker of systemic inflammation, predicts differential response to escitalopram (a serotonin reuptake inhibitor) and nortriptyline (a norepinephrine reuptake inhibitor).

Method: The hypothesis was tested in the Genome-Based Therapeutic Drugs for Depression (GENDEP) study, a multicenter open-label randomized clinical trial.

Genetic predictors of antidepressant side effects: a grouped candidate gene approach in the Genome-Based Therapeutic Drugs for Depression (GENDEP) study.

Background: The unwanted side effects associated with antidepressants are key determinants of treatment adherence in depression; propensity to experience these adverse drug reactions (ADRs) may be influenced by genetic variation. However, previous work attempting to ascertain the genetic variants involved has had limited success, in part due to the range of ADRs reported with antidepressants.

Method: ADRs reported with antidepressant treatment were categorised using their likely pharmacological basis; adrenergic, cholinergic, serotonergic and histaminergic.

Genetic differences in cytochrome P450 enzymes and antidepressant treatment response.

Aims: Antidepressant response varies between patients, possibly due to differences in the rate cytochrome P450 enzymes metabolise antidepressants into inactive compounds. Drug metabolism rates are influenced by common variants in the genes encoding these enzymes. However, it remains unclear whether treatment outcomes can be predicted by either CYP450 genotype or antidepressant serum concentration.

Self-report and clinician-rated measures of depression severity: can one replace the other?

Background: It has been suggested that clinician-rated scales and self-report questionnaires may be interchangeable in the measurement of depression severity, but it has not been tested whether clinically significant information is lost when assessment is restricted to either clinician-rated or self-report instruments. The aim of this study is to test whether self-report provides information relevant to short-term treatment outcomes that is not captured by clinician-rating and vice versa.

Methods: In genome-based drugs for depression (GENDEP), 811 patients with major depressive disorder treated with escitalopram or nortriptyline were assessed with the clinician-rated Montgomery-Åsberg Depression Rating Scale (MADRS), Hamilton Rating Scale for Depression (HRSD), and the self-report Beck Depression Inventory (BDI).

Psychometric properties of the Slovenian version of temperament evaluation of Memphis, Pisa, Paris, and San Diego-Autoquestionnaire (TEMPS-A): temperament profiles in Slovenian university students.

Background: TEMPS-A (Temperament Evaluation of Memphis, Pisa, Paris and San Diego-Autoquestionnaire) is a self-rated instrument that measures five affective temperaments: depressive, cyclothymic, hyperthymic, irritable, and anxious. The aim of our study was to examine the psychometric characteristics of the Slovenian TEMPS-A and to ascertain if temperament profile is related to the professions chosen by Slovenian students.

Methods: 892 Slovenian university students in six different professional fields (economics, geography, engineering, law, sports pedagogy and nursing) were included in our study.

Non-steroidal anti-inflammatory drugs and efficacy of antidepressants in major depressive disorder.

Background: It has been proposed that non-steroidal anti-inflammatory drugs (NSAIDs) may interfere with the efficacy of antidepressants and contribute to treatment resistance in major depressive disorder (MDD). This effect requires replication and a test of whether it is specific to serotonin-reuptake inhibiting (SRI) antidepressants.

Method: We tested the effect of concomitant medication with NSAIDs on the efficacy of escitalopram, a SRI antidepressant, and nortriptyline, a tricyclic antidepressant, among 811 subjects with MDD treated for up to 12 weeks in the GENDEP study.

Specific cognitive abilities are associated with diabetes self-management behavior among patients with type 2 diabetes.

Aim: Patients with diabetes differ in compliance to diabetes self-management which influences their long-term health. Psychological factors, namely depression and cognitive abilities, are associated with diabetes self-management behavior. The aim of the study was to identify independent association of particular cognitive functions with diabetes self-management.

Depression symptom dimensions as predictors of antidepressant treatment outcome: replicable evidence for interest-activity symptoms.

Background: Symptom dimensions have not yet been comprehensively tested as predictors of the substantial heterogeneity in outcomes of antidepressant treatment in major depressive disorder.

Method: We tested nine symptom dimensions derived from a previously published factor analysis of depression rating scales as predictors of outcome in 811 adults with moderate to severe depression treated with flexibly dosed escitalopram or nortriptyline in Genome-based Therapeutic Drugs for Depression (GENDEP). The effects of symptom dimensions were tested in mixed-effect regression models that controlled for overall initial depression severity, age, sex and recruitment centre.

Quality of life and clinical outcome comparison of semitendinosus and gracilis tendon versus patellar tendon autografts for anterior cruciate ligament reconstruction: an 11-year follow-up of a randomized controlled trial.

Background: There are still controversies about graft selection for primary anterior cruciate ligament reconstruction. Prospective, randomized long-term studies are needed to determine the differences between the graft materials.

Hypothesis: Eleven years after anterior cruciate ligament reconstruction there is no difference in functional outcome and quality of life between patients with patellar tendon or hamstring tendon autografts; however, the patients with patellar tendon autograft would have a higher prevalence of osteoarthritis.

Melancholic, atypical and anxious depression subtypes and outcome of treatment with escitalopram and nortriptyline.

Objective: To investigate whether subtypes of depression predict differential outcomes of treatment with selective serotonin-reuptake inhibitor (SSRI) and a tricyclic antidepressant in major depression.

Method: Among 811 adults with moderate-to-severe depression, melancholic, atypical, anxious and anxious-somatizing depression subtypes established at baseline were evaluated as predictors of outcome of treatment with flexible dosage of the SSRI escitalopram or the tricyclic antidepressant nortriptyline. The primary outcome measure was the Montgomery-Åsberg Depression Rating Scale (MADRS).