Preventing mood and anxiety disorders in youth: a multi-centre RCT in the high risk offspring of depressed and anxious patients

<p>Abstract</p> <p>Background</p> <p>Anxiety and mood disorders are highly prevalent and pose a huge burden on patients. Their offspring is at increased risk of developing these disorders as well, indicating a clear need for prevention of psychopathology in this group. Given high comorbidity and non-specificity of intergenerational transmission of disorders, prevention programs should target both anxiety and depression. Further, while the indication for preventive interventions is often elevated symptoms, offspring with other high risk profiles may also benefit from resilience-based prevention programs.</p> <p>Method/design</p> <p>The current STERK-study (Screening and Training: Enhancing Resilience in Kids) is a randomized controlled clinical trial combining selected and indicated prevention: it is targeted at both high risk individuals without symptoms and at those with subsyndromal symptoms. Individuals without symptoms meet two of three criteria of the High Risk Index (HRI; female gender, both parents affected, history of a parental suicide (attempt). This index was developed in an earlier study and corresponds with elevated risk in offspring of depressed patients. Children aged 8–17 years (n = 204) with subthreshold symptoms or meeting the criteria on the HRI are randomised to one of two treatment conditions, namely (a) 10 weekly individual child CBT sessions and 2 parent sessions or (b) minimal information. Assessments are held at pre-test, post-test and at 12 and 24 months follow-up. Primary outcome is the time to onset of a mood or anxiety disorder in the offspring. Secondary outcome measures include number of days with depression or anxiety, child and parent symptom levels, quality of life, and cost-effectiveness. Based on models of aetiology of mood and anxiety disorders as well as mechanisms of change during interventions, we selected potential mediators and moderators of treatment outcome, namely coping, parent–child interaction, self-associations, optimism/pessimism, temperament, and emotion processing.</p> <p>Discussion</p> <p>The current intervention trial aims to significantly reduce the risk of intergenerational transmission of mood and anxiety disorders with a short and well targeted intervention that is directed at strengthening the resilience in potentially vulnerable children. We plan to evaluate the effectiveness and cost-effectiveness of such an intervention and to identify mechanisms of change.</p> <p>Trial registration</p> <p>NTR2888</p

Extraversion is linked to volume of the orbitofrontal cortex and amygdala

Contains fulltext : 103145.pdf (publisher's version ) (Open Access)Neuroticism and extraversion are personality factors associated with the vulnerability for developing depression and anxiety disorders, and are possibly differentially related to brain structures implicated in the processing of emotional information and the generation of mood states. To date, studies on brain morphology mainly focused on neuroticism, a dimension primarily related to negative affect, yielding conflicting findings concerning the association with personality, partially due to methodological issues and variable population samples under study. Recently, extraversion, a dimension primarily related to positive affect, has been repeatedly inversely related to with symptoms of depression and anxiety disorders. In the present study, high resolution structural T1-weighted MR images of 65 healthy adults were processed using an optimized Voxel Based Morphometry (VBM) approach. Multiple regression analyses were performed to test for associations of neuroticism and extraversion with prefrontal and subcortical volumes. Orbitofrontal and right amygdala volume were both positively related to extraversion. Extraversion was differentially related to volume of the anterior cingulate cortex in males (positive) and females (negative). Neuroticism scores did not significantly correlate with these brain regions. As extraversion is regarded a protective factor for developing anxiety disorders and depression and has been related to the generation of positive affect, the present results indicate that the reduced likelihood of developing affective disorders in individuals high on extraversion is related to modulation of emotion processing through the orbitofrontal cortex and the amygdala.6 p

The generalizability of psychotherapy efficacy trials in major depressive disorder: an analysis of the influence of patient selection in efficacy trials on symptom outcome in daily practice

Abstract Background Treatment guidelines for major depressive disorder (MDD) are based on results from randomized clinical trials, among others in psychotherapy efficacy trials. However, patients in these trials differ from routine practice patients since trials use stringent criteria for patient selection. It is unknown whether the exclusion criteria used in psychotherapy efficacy trials (PETs) influence symptom outcome in clinical practice. We first explored which exclusion criteria are used in PETs. Second, we investigated the influence of commonly used exclusion criteria on symptom outcome in routine clinical practice. Methods We performed an extensive literature search in PubMed, PsycInfo and additional databases for PETs for MDD. From these, we identified commonly used exclusion criteria. We investigated the influence of exclusion criteria on symptom outcome by multivariate regression models in a sample of patients suffering from MDD according to the MINIplus from a routine clinical practice setting (n=598). Data on routine clinical practice patients were gathered through Routine Outcome Monitoring. Results We selected 20 PETs and identified the following commonly used exclusion criteria: ‘a baseline severity threshold of HAM-D≤14’, ‘current or past abuse or dependence of alcohol and/or drugs’ and ‘previous use of medication or ECT’. In our routine clinical practice sample of patients suffering from MDD (n=598), presence of ‘current or past abuse of or dependence on alcohol and/or drugs’ had no significant influence on outcome.‘Meeting a baseline severity threshold of HAM-D≤14’ and ‘previous use of medication or ECT’ were associated with better outcome, but the explained variance of the models was very small (R2=2-11%). Conclusions The most consistently used exclusion criteria are not a major threat to the generalizability of results found in PETs. However, PETs do somewhat improve their results by exclusion of patients with minor depression and patients who used antidepressants prior to psychotherapy.</p

Placebo effects in the neuroendocrine system: Conditioning of the oxytocin responses

OBJECTIVE: There is evidence that placebo effects may influence hormone secretion. However, few studies have examined placebo effects in the endocrine system, including oxytocin placebo effects. We studied whether it is possible to trigger oxytocin placebo effects using a classical conditioning paradigm. METHODS: Ninety-nine women were assigned to a conditioned, control, or drug control group. In the two-phase conditioning paradigm, participants in the conditioned and drug control groups received an oxytocin nasal spray combined with a distinctive smell (conditioned stimulus [CS]) for three acquisition days, whereas the control group received placebo spray. Subsequently, the conditioned and control groups received placebo spray with the CS and the drug control group received oxytocin spray for three evocation days. Salivary oxytocin was measured several times during each day. Pain sensitivity and facial evaluation tests previously used in oxytocin research were also administered. RESULTS: On evocation day 1, in the conditioned group, oxytocin significantly increased from baseline to 5 minutes after CS (B[slope] = 19.55, SE = 5.88, p < .001) and remained increased from 5 to 20 (B = -10.42, SE = 5.81, p = .071) and 50 minutes (B = -0.70, SE = 3.37, p = .84). On evocation day 2, a trend for increase in oxytocin was found at 5 minutes (B = 15.22, SE = 8.14, p = .062). No placebo effect was found on evocation day 3 (B = 3.57, SE = 3.26, p = .28). Neither exogenous nor conditioned oxytocin affected pain or facial tasks. CONCLUSIONS: Results indicate that oxytocin release can be conditioned and that this response extinguishes over time. Triggering hormonal release by placebo manipulation offers various clinical possibilities, such as enhancing effects of pharmacological treatments or reducing dosages of medications. TRIAL REGISTRATION: The study was registered as a clinical trial on www.trialregister.nl (number NTR5596).status: publishe

Resting-State Functional Connectivity in Patients with Long-Term Remission of Cushing’s Disease

Glucocorticoid disturbance can be a cause of psychiatric symptoms. Cushing's disease represents a unique model for examining the effects of prolonged exposure to high levels of endogenous cortisol on the human brain as well as for examining the relation between these effects and psychiatric symptomatology. This study aimed to investigate resting-state functional connectivity (RSFC) of the limbic network, the default mode network (DMN), and the executive control network in patients with long-term remission of Cushing's disease. RSFC of these three networks of interest was compared between patients in remission of Cushing's disease (n=24; 4 male, mean age=44.96 years) and matched healthy controls (n=24; 4 male, mean age=46.5 years), using probabilistic independent component analysis to extract the networks and a dual regression method to compare both groups. Psychological and cognitive functioning was assessed with validated questionnaires and interviews. In comparison with controls, patients with remission of Cushing's disease showed an increased RSFC between the limbic network and the subgenual subregion of the anterior cingulate cortex (ACC) as well as an increased RSFC of the DMN in the left lateral occipital cortex. However, these findings were not associated with psychiatric symptoms in the patient group. Our data indicate that previous exposure to hypercortisolism is related to persisting changes in brain function