M Wichers

Unveiling patterns of affective responses in daily life may improve outcome prediction in depression: A momentary assessment study

OBJECTIVE Daily life affective responses are closely linked to vulnerability and resilience in depression. Prediction of future clinical course may be improved if information on daily life emotional response patterns is taken into account. METHOD Female subjects with a history of major depression (n=83), recruited from a population twin register, participated in a longitudinal study using momentary assessment technology with 4 follow-up measurements. The effect of baseline daily life emotional response patterns (affect variability, stress-sensitivity and reward experience) on follow-up depressive symptomatology was examined. RESULTS Both reward experience (B=-0.30, p=0.001) and negative affect variability (B=0.46, p=0.001) predicted future negative affective symptoms independent of all other dynamic emotional patterns and conventional predictors. CONCLUSION Daily life information on dynamic emotional patterns adds to the prediction of future clinical course, independent of severity of symptoms and neuroticism score. Better prediction of course may improve decision-making regarding quantitative and qualitative aspects of treatment.

Mechanisms of gene–environment interactions in depression: evidence that genes potentiate multiple sources of adversity

BACKGROUND Previous work suggests that daily life stress-sensitivity may be an intermediary phenotype associated with both genetic risk for depression and developmental stress exposures. In the current analysis we hypothesized that genetic risk for depression and three environmental exposures over the course of development [prenatal stress, childhood adversity and adult negative life events (NLEs)] combine synergistically to produce the phenotype of stress-sensitivity. METHOD Twin pairs (n=279) participated in a momentary assessment study using the Experience Sampling Method (ESM), collecting appraisals of stress and negative affect (NA) in the flow of daily life. Prospective data on birthweight and gestational age, questionnaire data on childhood adversity and recent NLEs, and interview data on depression were used in the analyses. Daily life stress-sensitivity was modelled as the effect of ESM daily life stress appraisals on ESM NA. RESULTS All three developmental stress exposures were moderated by genetic vulnerability, modelled as dizygotic (DZ) or monozygotic (MZ) co-twin depression status, in their effect on daily life stress-sensitivity. Effects were much stronger in participants with MZ co-twin depression and a little stronger in participants with DZ co-twin depression status, compared to those without co-twin depression. NLE main effects and NLE genetic moderation were reducible to birthweight and childhood adversity. CONCLUSIONS The findings are consistent with the hypothesis that adult daily life stress-sensitivity is the result of sensitization processes initiated by developmental stress exposures. Genes associated with depression may act by accelerating the process of stress-induced sensitization.

Early increase in vegetative symptoms predicts IFN-alpha-induced cognitive-depressive changes.

BACKGROUND The vegetative symptoms of depression resemble the symptoms of malaise associated with activation of the inflammatory response system (IRS), and can be regarded as an expression of a central motivational state that resets the organisms priorities to promote recovery from infection. Early vegetative symptoms, however, may also contribute to the high rates of depression seen later in the course of immune activation. We hypothesized that the onset of vegetative-depressive symptoms early in the treatment with the pro-inflammatory cytokine IFN-alpha in chronic hepatitis C patients would increase the risk for subsequent depressive cognitions. METHOD Sixteen patients eligible for IFN-alpha treatment and free of psychiatric disorders were recruited. The DSM-IV, the Multidimensional Fatigue Inventory, and the Montgomery-Asberg Depression Rating Scale (MADRS) were administered at baseline and 1, 2, 4, 8, 12 and 24 weeks after treatment was initiated. Cognitive-depressive and vegetative-depressive symptom clusters were constructed. RESULTS Fatigue and depression scores increased significantly during IFN-alpha treatment. Depression scores were highest at week 8 of treatment. First week increase in vegetative-depressive symptom score predicted cognitive-depressive symptom score at week 8 and at week 24. CONCLUSIONS During IFN-alpha treatment, vegetative symptoms of depression appear earlier than, and are predictive of, their cognitive counterparts. This finding suggests that low mood state may in part be driven by the increase in early vegetative-depressive symptoms in the course of IFN-alpha-induced immune activation.

Does reactivity to stress cosegregate with subclinical psychosis? A general population twin study

Objective:  This study assessed the relationship between stress reactivity (trait 1) and psychosis (trait 2) across genetically related persons (cross‐twin, cross‐trait design) to examine whether stress reactivity is an uncontaminated and unconfounded familial marker of psychosis risk.

Meeting risk with resilience: high daily life reward experience preserves mental health

Geschwind N, Peeters F, Jacobs N, Delespaul P, Derom C, Thiery E, van Os J, Wichers M. Meeting risk with resilience: high daily life reward experience preserves mental health.

Risk factors predicting onset and persistence of subthreshold expression of bipolar psychopathology among youth from the community

Tijssen MJA, Van Os J, Wittchen HU, Lieb R, Beesdo K, Wichers M. Risk factors predicting onset and persistence of subthreshold expression of bipolar psychopathology among youth from the community

Disentangling the causal inter-relationship between negative life events and depressive symptoms in women: a longitudinal twin study

BACKGROUND Negative life events are strongly associated with the development of depression. However, the etiologic relationship between life events and depression is complex. Evidence suggests that life events can cause depression, and depression increases the risk for life events. Additionally, third factors influencing both phenotypes may be involved. In this work we sought to disentangle these relationships using a genetically informative longitudinal design. METHOD Adult female twins (n=536, including 281 twin pairs) were followed up for measurements of negative life event exposure and depressive symptoms. Four follow-ups were completed, each approximately 3 months apart. Model fitting was carried out using the Mx program. RESULTS The best-fitting model included causal paths from life events to depressive symptoms for genetic and shared environmental risk factors, whereas paths from depressive symptoms to life events were apparent for shared environmental factors. Shared latent influence on both phenotypes was found for individual-specific effects. CONCLUSIONS Life events and depressive symptoms have complex inter-relationships that differ across sources of variance. The results of the model, if replicated, indicate that reducing life event exposure would reduce depressive symptoms and that lowering depressive symptoms would decrease the occurrence of negative life events.

Therapygenetics in mindfulness-based cognitive therapy: do genes have an impact on therapy-induced change in real-life positive affective experiences?

Positive affect (PA) has an important role in resilience against depression and has been shown to increase with mindfulness-based cognitive therapy (MBCT). To elucidate the underlying mechanisms of change in PA as well as develop insights that may benefit personalized medicine, the current study examined the contribution of genetic variation to individual differences in change in PA in response to MBCT. Individuals (n=126) with residual depressive symptoms were randomized to either an MBCT group or treatment as usual. PA was assessed using experience sampling methodology (ESM). Single-nucleotide polymorphisms (SNPs) in genes known to be involved in reward functioning were selected. SNPs in the genes for brain-derived neurotrophic factor (BDNF), the muscarinic acetylcholine receptor M2 (CHRM2), the dopamine receptor D4 (DRD4) and the μ1 opioid receptor (OPRM1) significantly moderated the impact of treatment condition over time on PA. Genetic variation in the genes for CHRM2 and OPRM1 specifically had an impact on the level of PA following MBCT. The current study shows that variation in response to MBCT may be contingent on genetic factors associated with the regulation of PA. These findings contribute to our understanding of the processes moderating response to treatment and prediction of treatment outcome.

Positive emotions from social company in women with persisting subclinical psychosis: lessons from daily life

Altered social reward functioning is associated with psychosis irrespective of stage and severity. Examining the role of social reward functioning prospectively in relation to psychotic experiences before these become persistent and potentially disabling can aid in elucidating social mechanisms that induce shifts toward more severe psychotic states, without the confounding effects of clinical disorder.

Does antidepressant medication in patients with hepatitis C undergoing interferon alpha treatment reduce therapeutic efficacy

Activation of the inflammatory immune system, as evidenced by the effects of interferon α (IFNα) treatment, induces depressive symptoms. Prescription of a selective serotonin reuptake inhibitor (SSRI) is now advocated in combination with antiviral therapy in patients exposed to IFNα when early symptoms of depression emerge. The recently published article written by Kraus et al ( Gut 2008; 57 :531–6) gives further evidence for the efficacy of SSRIs to treat depressive symptoms during IFNα treatment. The mechanisms by which SSRIs reduce depressive symptoms remain unclear. Several hypotheses, such as impact on serotonin activity or neurotrophic actions, have been proposed. Another, that has good face validity in this context, is that the anti-inflammatory properties of SSRIs mediate at least in part the decrease in depressive symptoms. Antidepressants have been shown in …