Guido Bondolfi

Decreased serum brain-derived neurotrophic factor levels in major depressed patients.

Recent findings with animal models have suggested a possible role for brain-derived neurotrophic factor (BDNF) in depression. We have therefore hypothesized that depression could be characterized by low levels of serum BDNF. Major depressed patients (15F + 15M) diagnosed according to DSM-IV criteria and healthy controls (15F + 15M) participated in the study. Serum BDNF was assayed with the ELISA method and the severity of depression was evaluated with Montgomery-Asberg-Depression Rating Scale (MADRS). BDNF levels were significantly lower in patients than in controls: 22.6 +/- 3 and 26.5 +/- 7 ng/ml (t-test = 2.7; d.f. = 58; P < 0.01). They were negatively correlated to the MADRS scores (r = -0.55; P < 0.02). Female patients were more depressed and released less BDNF than men. Analysis of covariance (MADRS and gender as independent variable vs. BDNF as dependent variable) indicated that depression severity mainly accounted for the negative correlation. These results suggest that major depression is characterized by low serum BDNF levels and support the hypothesis of neurotrophic factor involvement in affective disorders.

Low brain-derived neurotrophic factor (BDNF) levels in serum of depressed patients probably results from lowered platelet BDNF release unrelated to platelet reactivity.

BACKGROUND Recent reports have suggested a role for brain-derived neurotrophic factor (BDNF) in psychiatric disorders. Decreased serum BDNF levels have been reported in major depression, but the cause of this decrease has not yet been investigated. The goal of this study was to assess blood BDNF and a platelet activation index, PF4. METHODS Forty-three drug-free patients (27 female, 16 male) diagnosed with major depression and 35 healthy control subjects (18 female, 17 male) were assessed for plasma, serum, and blood BDNF content. Brain-derived neurotrophic factor and PF4 were assayed with enzyme-linked immunosorbent assay methods, and severity of depression was evaluated with the Montgomery-Asberg Depression Rating Scale. RESULTS Serum and plasma BDNF levels were decreased in depressed patients compared with control subjects. In whole blood, BDNF levels were unaltered in the depressed subjects compared with control subjects. The serum/blood BDNF ratio was lower in patients with major depression. Increased plasma but not serum PF4 levels were observed in depressed subjects compared with control subjects. CONCLUSIONS Our results suggest that an alteration of serum or plasma BDNF is not due to the change in blood BDNF but rather is probably related to mechanisms of BDNF release. Secretion of BDNF seems to be independent of platelet reactivity; other mechanisms are therefore probably involved and need to be elucidated.

Partial normalization of serum brain-derived neurotrophic factor in remitted patients after a major depressive episode.

We had previously reported decreased serum brain-derived neurotrophic factor (BDNF) levels in depressed patients. In the present study, we tested the hypothesis that antidepressant treatment would normalize serum BDNF levels, at least in a subgroup of patients. Major depressed patients (15 females and 11 males) diagnosed according to DSM-IV criteria and healthy controls (13 females and 13 males) participated in this study. Serum BDNF was assayed with the ELISA method for depressed and remitted patients and the severity of depression was evaluated with the Montgomery-Asberg Depression Rating Scale. An analysis of variance showed that treatment had an effect [F(1, 24) = 4.46, p = 0.045] on the normalization of serum BDNF levels. We also found a correlation between the severity of depression (r = 0.51, p = 0.008), the pretreatment BDNF levels (r = 0.62, p = 0.001) and the difference in serum BDNF levels after antidepressant treatment. These results suggest that antidepressant treatment has a positive effect on serum BDNF levels and support the hypothesis of neurotrophic factor involvement in affective disorders.

Depression relapse prophylaxis with Mindfulness-Based Cognitive Therapy: replication and extension in the Swiss health care system.

Background Mindfulness-Based Cognitive Therapy (MBCT) is a group intervention that integrates elements of Cognitive Behavioural Therapy (CBT) with components of mindfulness training to prevent depressive relapse. The efficacy of MBCT compared to Treatment As Usual (TAU), shown in two randomized controlled trials indicates a significant decrease in 1-year relapse rates for patients with at least three past depressive episodes. The present study is the first independent replication trial comparing MBCT + TAU to TAU alone across both language and culture (Swiss health care system). Methods Sixty unmedicated patients in remission from recurrent depression (≥ 3 episodes) were randomly assigned to MBCT + TAU or TAU. Relapse rate and time to relapse were measured over a 60 week observation period. The frequency of mindfulness practices during the study was also evaluated. Results Over a 14-month prospective follow-up period, time to relapse was significantly longer with MBCT + TAU than TAU alone (median 204 and 69 days, respectively), although both groups relapsed at similar rates. Analyses of homework adherence revealed that following treatment termination, the frequency of brief and informal mindfulness practice remained unchanged over 14 months, whereas the use of longer formal meditation decreased over time. Limitations Relapse monitoring was 14 months in duration and prospective reporting of mindfulness practice would have yielded more precise frequency estimates compared to the retrospective methods we utilized. Conclusions Further studies are required to determine which patient characteristics, beyond the number of past depressive episodes, may predict differential benefits from this therapeutic approach.

Prevalence estimates of pathological gambling in Switzerland

Objective: The purpose of this study was to evaluate the prevalence of pathological gambling in the Swiss adult population before the introduction of new forms of gambling, and the link between pathological gambling and alcohol abuse.

CYP2D6 and ABCB1 Genetic Variability : Influence on Paroxetine Plasma Level and Therapeutic Response

Paroxetine is characterized by large interindividual pharmacokinetic variability and heterogeneous response patterns. The present study investigates plasma concentration and therapeutic response to paroxetine for the influence of age, sex, and CYP2D6 and ABCB1 polymorphisms, the latter gene encoding for the permeability glycoprotein. Genotyping for CYP2D6 (alleles *3, *4, *5, *6, and *xN) and ABCB1 polymorphisms (61A>G, 2677G>T, and 3435C>T) was performed in 71 depressed patients who started 20 mg paroxetine per day and had plasma concentration measured after 2 weeks at a fixed dose. A dose increase to 30 mg per day was possible starting at week 2. For 63 patients, severity of depression (Montgomery-Åsberg Depression Rating Scale) was assessed at weeks 0, 2, and 4 and every 2 weeks thereafter until discontinuation. Persistent response was defined as 50% improvement from baseline score sustained from the first occurrence to study end point. Paroxetine concentration significantly differed between female and male patients (median, 28 versus 16 ng/mL; P = 0.001). Differences were not significant between CYP2D6 heterozygous and homozygous extensive metabolizers (median, 27 versus 22 ng/mL; P = 0.074) and between ABCB1 genotypes (P > 0.10). When considered in a multivariate model, CYP2D6 heterozygous extensive metabolizer phenotype (P = 0.062) and female gender (P = 0.001) predicted 1.3-fold and 1.6-fold higher paroxetine concentration, respectively, but fraction of explained variability was modest (21%). Frequency of persistent response at study end point did not significantly differ according to CYP2D6 heterozygous extensive metabolizer versus homozygous extensive metabolizer phenotype and ABCB1 polymorphisms in univariate analyses. After adjusting for age, sex, paroxetine concentration at week 2, and daily dose at study end point, ABCB1 genotype contributed to improving the model significantly for 61A>G (P = 0.043), but not 2677G>T (P = 0.068) and 3435C>T (P = 0.11). None of two poor metabolizers and four ultrarapid metabolizers showed persistent response to paroxetine. The hypothesis that permeability glycoprotein activity might be a relevant predictor of therapeutic response deserves to be further investigated while controlling for pharmacokinetic variability.

Efficacy of Mindfulness-Based Cognitive Therapy in Prevention of Depressive Relapse: An Individual Patient Data Meta-analysis From Randomized Trials

IMPORTANCE Relapse prevention in recurrent depression is a significant public health problem, and antidepressants are the current first-line treatment approach. Identifying an equally efficacious nonpharmacological intervention would be an important development. OBJECTIVE To conduct a meta-analysis on individual patient data to examine the efficacy of mindfulness-based cognitive therapy (MBCT) compared with usual care and other active treatments, including antidepressants, in treating those with recurrent depression. DATA SOURCES English-language studies published or accepted for publication in peer-reviewed journals identified from EMBASE, PubMed/Medline, PsycINFO, Web of Science, Scopus, and the Cochrane Controlled Trials Register from the first available year to November 22, 2014. Searches were conducted from November 2010 to November 2014. STUDY SELECTION Randomized trials of manualized MBCT for relapse prevention in recurrent depression in full or partial remission that compared MBCT with at least 1 non-MBCT treatment, including usual care. DATA EXTRACTION AND SYNTHESIS This was an update to a previous meta-analysis. We screened 2555 new records after removing duplicates. Abstracts were screened for full-text extraction (S.S.) and checked by another researcher (T.D.). There were no disagreements. Of the original 2555 studies, 766 were evaluated against full study inclusion criteria, and we acquired full text for 8. Of these, 4 studies were excluded, and the remaining 4 were combined with the 6 studies identified from the previous meta-analysis, yielding 10 studies for qualitative synthesis. Full patient data were not available for 1 of these studies, resulting in 9 studies with individual patient data, which were included in the quantitative synthesis. RESULTS Of the 1258 patients included, the mean (SD) age was 47.1 (11.9) years, and 944 (75.0%) were female. A 2-stage random effects approach showed that patients receiving MBCT had a reduced risk of depressive relapse within a 60-week follow-up period compared with those who did not receive MBCT (hazard ratio, 0.69; 95% CI, 0.58-0.82). Furthermore, comparisons with active treatments suggest a reduced risk of depressive relapse within a 60-week follow-up period (hazard ratio, 0.79; 95% CI, 0.64-0.97). Using a 1-stage approach, sociodemographic (ie, age, sex, education, and relationship status) and psychiatric (ie, age at onset and number of previous episodes of depression) variables showed no statistically significant interaction with MBCT treatment. However, there was some evidence to suggest that a greater severity of depressive symptoms prior to treatment was associated with a larger effect of MBCT compared with other treatments. CONCLUSIONS AND RELEVANCE Mindfulness-based cognitive therapy appears efficacious as a treatment for relapse prevention for those with recurrent depression, particularly those with more pronounced residual symptoms. Recommendations are made concerning how future trials can address remaining uncertainties and improve the rigor of the field.

Mindful Attention Awareness Scale (MAAS) : psychometric properties of the French translation and exploration of its relations with emotion regulation strategies

Over the past few years, several questionnaires have been developed to measure mindfulness. The Mindful Attention Awareness Scale (MAAS) was created to specifically capture attention and awareness in daily life (Brown & Ryan, 2003). In this article, we present a French adaptation of the MAAS. In the 1st study, we explored the psychometric properties of this adaptation. In the 2nd study, we investigated its relation to cognitive emotion regulation and depressive symptomatology using path analysis. As in the original version of the MAAS, the French adaptation has a strong 1-factor structure. Moreover, there was a negative relationship between the MAAS and the severity of depressive symptoms, both directly and indirectly. The indirect pathway was mediated by the nonadaptive cognitive emotion regulation strategy of self-blame and the adaptive cognitive emotion regulation strategy of positive reappraisal. In conclusion, this questionnaire represents a valid mindfulness measure for French-speaking clinicians and researchers.

Genetic predictors of response to serotonergic and noradrenergic antidepressants in major depressive disorder: a genome-wide analysis of individual-level data and a meta-analysis

Testing whether genetic information could inform the selection of the best drug for patients with depression, Rudolf Uher and colleagues searched for genetic variants that could predict clinically meaningful responses to two major groups of antidepressants.

Prevalence of pathological gambling in Switzerland after the opening of casinos and the introduction of new preventive legislation

Objective: This survey aimed to evaluate the prevalence of pathological gambling (PG) in the Swiss population in 2005 and the link between PG and alcohol abuse. This replication study made it possible to compare the prevalence rates of PG measured before and after the introduction of casinos and new preventive legislation.