Willem Van der Does

Predictors of mood response to acute tryptophan depletion: A reanalysis

Acute tryptophan depletion (ATD) induces depressive symptoms in 50-60% of selective serotonin reuptake inhibitor (SSRI) treated, recovered depressed patients. However, no reliable predictors of mood response to ATD have been established. In the present study, individual subject data of six ATD studies were pooled (‘mega-analysis’) in order to investigate the mediating role of clinical, demographic and biochemical characteristics in the mood response to ATD. A procedure was developed to make different versions of the Hamilton scale comparable. Recurrent depressive episodes, female gender, prior exposure to SSRI antidepressant treatment and previous serious suicidal thoughts/attempts all appear to be independent predictors of mood response to ATD. Chronicity of illness is the most powerful predictor. Residual symptoms of depression were not found to predict response to ATD. ATD may be useful to study the mechanism of action of SSRI antidepressants and individual biological vulnerability of the serotonin system. Whether the effects of ATD represent a reversal of the action of SSRI antidepressants or individual vulnerability probably depends upon the timing of the procedure in the course of remission of a depressive episode.

Cognitive reactivity to sad mood : structure and validity of a new measure

Abstract Cognitive reactivity to the experimental induction of sad mood has been found to predict relapse in recovered depressed patients. The present report describes the development and test of a questionnaire that aims to measure cognitive reactivity independently from a mood induction procedure. The Leiden Index of Depression Sensitivity (LEIDS) was filled out by 198 participants. After Principal Components Analysis, 26 items were retained, which comprised four factors with good psychometric properties: Negative Self-Evaluation; Acceptance/Coping; Indifference; and Harm Avoidance. In a sample of 48 college students, LEIDS scores — particularly Negative Self-Evaluation and Harm Avoidance — were rather strong predictors of cognitive reactivity in a mood induction procedure. In contrast, baseline depression and baseline cognitive dysfunction did not predict cognitive reactivity. It is concluded that the LEIDS is a promising measure of cognitive reactivity, and that clinical studies need to be carried out to test its ability to predict relapse of depression.

Attentional Bias Modification in Posttraumatic Stress Disorder: A Randomized Controlled Trial

Background: Attentional bias modification (ABM) is a new treatment for anxiety disorders. Three randomized controlled clinical trials have shown positive effects of ABM in social anxiety disorder and generalized anxiety disorder. This study investigated the efficacy of ABM in outpatients with chronic posttraumatic stress disorder (PTSD). Methods: Randomized controlled double-blind trial (n = 102). ABM and control treatment consisted of eight 20-min sessions over the course of 3 weeks. Symptoms and attentional bias were assessed before and after treatment and at 3-week follow-up. Results: ABM and the control treatment were equally effective in reducing the symptoms of PTSD. The effect sizes of the improvement (from before to after treatment) were 0.66 for ABM and 0.46 for the control treatment, which is comparable to the effect sizes of pill-placebos in pharmacotherapy trials of chronic PTSD. Both treatments did not affect attentional bias. The acceptability and tolerability of ABM was moderate. Conclusions: This version of ABM is not an effective treatment of PTSD.

Coeliac disease, diet adherence and depressive symptoms.

OBJECTIVES We aimed to investigate whether long-term adherence to a gluten-free diet is related to depressive symptoms in coeliac disease (CD) patients. METHODS A cross-sectional survey was performed in 2265 adult CD patients recruited through the Dutch Coeliac Association. Self-reported diet adherence was compared among groups based on self-reported depressive symptoms (categorized into current [1-month], remitted, and never). RESULTS The life-time prevalence rate of self-reported depressive symptoms was 39.0% (n=883), of whom 270 (11.9%) suffered from current depressive symptoms. Adherence to gluten-free diet was strict in 50.2% of patients, sufficient in 46.3%, and insufficient in 3.6%. Insufficient adherence was not associated with current depressive symptoms (odds ratio [OR] 0.95; 95% confidence interval [CI]: 0.48-1.92). Keeping a gluten-free diet for longer than five years was associated with lower OR of current depressive symptoms compared to being on a diet for less than two years (OR 0.69; 95% CI: 0.50-0.95). CONCLUSIONS Lifetime depressive symptoms may be present in one third of the CD patients who adhere to gluten-free diet. Long-term adherence to the gluten-free diet may reduce the risk of current depressive symptoms.

Different types of experimentally induced sad mood

Mood-induction procedures have been useful to investigate the role of dysfunctional cognitions in depression. In general, studies have shown that individuals with a history of depression endorse more dysfunctional attitudes following the induction of sad mood than never-depressed individuals. However, a recent study failed to find the expected differences between previously depressed and never-depressed participants. In the present study, two widely used mood-induction procedures were compared to investigate the possibility that different mood inductions lead to different outcomes. Forty-eight participants underwent two types of sad mood induction: focusing on a sad memory while listening to music and watching a movie fragment. Consistent with modern cognitive theory, mood-state dependency of dysfunctional cognitions (cognitive reactivity) was much higher in vulnerable individuals. This effect occurred during both mood inductions. However, the effects of the music induction were somewhat larger, and the correlation between change of mood and cognitive reactivity was significant in this condition only. Some other subtle differences between both procedures were found. In conclusion, although the effects of both inductions were largely similar, the musical induction is more sensitive, and is preferable for research into cognitive dysfunction in depression.

Repetitive negative thinking as a transdiagnostic factor in depression and anxiety: A conceptual replication

Comorbidity among affective disorders is high. Rumination has been found to mediate cross-sectional and prospective relations between anxiety and depressive symptoms in adolescents and adults. We examined whether rumination and worry, both forms of repetitive negative thinking, also explain the associations between affective disorders. This was studied using a prospective cohort study. In a mixed sample of 2981 adults (persons with a prior history of or a current affective disorder and healthy individuals) we assessed DSM-IV affective disorders (CIDI), rumination (LEIDS-R) and worry (PSWQ). All measures were repeated 2 years and 4 years later. Using structural equation models, we found that baseline rumination and worry partly mediated the association of baseline fear disorders (social anxiety disorder, panic disorder, agoraphobia) with distress disorders (dysthymia, major depressive disorder, generalized anxiety disorder). Moreover, baseline fear disorders predicted changes in distress disorders and changes in worry and rumination mediated these associations. The association between baseline distress disorders and changes in fear disorders was mediated by changes in rumination but not by changes in worry. From these results it can be concluded that repetitive negative thinking is an important transdiagnostic factor. Rumination and worry are partly responsible for the cross-sectional and prospective co-occurrence of affective disorders and may be suitable targets for treatment.

Association Between Smoking, Nicotine Dependence, and BDNF Val(66)Met Polymorphism with BDNF Concentrations in Serum

INTRODUCTION Nicotine use is associated with the upregulation of brain-derived neurotrophic factor (BDNF) in serum. An association between smoking and the BDNF Val(66)Met polymorphism has also been found. The aim of this study is to examine the levels of serum BDNF in never-smokers, former smokers, and current smokers-with and without nicotine dependence-and to examine the interaction of the polymorphism and smoking status with serum BDNF. METHODS We used baseline serum and gene data of BDNF on 2,088 participants from the Netherlands Study of Depression and Anxiety (NESDA) to investigate smoking-BDNF association while controlling for potential confounding variables. Nicotine dependence was assessed with the Fagerstrom Test for Nicotine Dependence (FTND). RESULTS Smokers with and without nicotine dependence had higher levels of serum BDNF than former and never-smokers. Nicotine dependence and number of cigarettes smoked per day did not add to the prediction of serum BDNF; however, total number of smoking years was a significant predictor of serum BDNF. There was no association of BDNF Val(66)Met, nor an interaction of this polymorphism and smoking status, with serum BDNF. CONCLUSIONS Current smoking and higher number of smoking years are associated with higher levels of serum BDNF, and this is independent of the BDNF genotype. Nicotine dependence itself is not associated with a further increase or decrease of serum BDNF. Longitudinal investigations that address changes in serum BDNF in incident smokers and/or in quitters may be useful to understand the association of smoking with BDNF.

Cognitive Reactivity, Implicit Associations, and the Incidence of Depression: A Two-Year Prospective Study

Background Cognitive reactivity to sad mood is a vulnerability marker of depression. Implicit self-depressed associations are related to depression status and reduced remission probability. It is unknown whether these cognitive vulnerabilities precede the first onset of depression. Aim To test the predictive value of cognitive reactivity and implicit self-depressed associations for the incidence of depressive disorders. Methods Prospective cohort study of 834 never-depressed individuals, followed over a two-year period. The predictive value of cognitive reactivity and implicit self-depressed associations for the onset of depressive disorders was assessed using binomial logistic regression. The multivariate model corrected for baseline levels of subclinical depressive symptoms, neuroticism, for the presence of a history of anxiety disorders, for family history of depressive or anxiety disorders, and for the incidence of negative life events. Results As single predictors, both cognitive reactivity and implicit self-depressed associations were significantly associated with depression incidence. In the multivariate model, cognitive reactivity was significantly associated with depression incidence, together with baseline depressive symptoms and the number of negative life events, whereas implicit self-depressed associations were not. Conclusion Cognitive reactivity to sad mood is associated with the incidence of depressive disorders, also when various other depression-related variables are controlled for. Implicit self-depressed associations predicted depression incidence in a bivariate test, but not when controlling for other predictors.

The effects of transcutaneous vagus nerve stimulation on conditioned fear extinction in humans.

A critical component of the treatment for anxiety disorders is the extinction of fear via repeated exposure to the feared stimulus. This process is strongly dependent on successful memory formation and consolidation. Stimulation of the vagus nerve enhances memory formation in both animals and humans. The objective of this study was to assess whether transcutaneous stimulation of the vagus nerve (tVNS) can accelerate extinction memory formation and retention in fear conditioned humans. To assess fear conditioning and subsequent fear extinction, we assessed US expectancy ratings, fear potentiated startle responses and phasic heart rate responses. We conducted a randomized controlled trial in thirty-one healthy participants. After fear conditioning participants were randomly assigned to receive tVNS or sham stimulation during the extinction phase. Retention of extinction memory was tested 24h later. tVNS accelerated explicit fear extinction learning (US expectancy ratings), but did not lead to better retention of extinction memory 24h later. We did not find a differential physiological conditioning response during the acquisition of fear and thus were unable to assess potential effects of tVNS on the extinction of physiological indices of fear. These findings complement recent studies that suggest vagus nerve stimulation could be a promising tool to improve memory consolidation and fear extinction.

Shorter communicationRepetitive negative thinking as a transdiagnostic factor in depression and anxiety: A conceptual replication

Comorbidity among affective disorders is high. Rumination has been found to mediate cross-sectional and prospective relations between anxiety and depressive symptoms in adolescents and adults. We examined whether rumination and worry, both forms of repetitive negative thinking, also explain the associations between affective disorders. This was studied using a prospective cohort study. In a mixed sample of 2981 adults (persons with a prior history of or a current affective disorder and healthy individuals) we assessed DSM-IV affective disorders (CIDI), rumination (LEIDS-R) and worry (PSWQ). All measures were repeated 2 years and 4 years later. Using structural equation models, we found that baseline rumination and worry partly mediated the association of baseline fear disorders (social anxiety disorder, panic disorder, agoraphobia) with distress disorders (dysthymia, major depressive disorder, generalized anxiety disorder). Moreover, baseline fear disorders predicted changes in distress disorders and changes in worry and rumination mediated these associations. The association between baseline distress disorders and changes in fear disorders was mediated by changes in rumination but not by changes in worry. From these results it can be concluded that repetitive negative thinking is an important transdiagnostic factor. Rumination and worry are partly responsible for the cross-sectional and prospective co-occurrence of affective disorders and may be suitable targets for treatment.