Aart H. Schene

Mood is indirectly related to serotonin, norepinephrine and dopamine levels in humans: a meta-analysis of monoamine depletion studies

Dysfunction in the monoamine systems of serotonin (5-HT), norepinephrine (NE) and dopamine (DA) may causally be related to major depressive disorder (MDD). Monoamine depletion studies investigate the direct effects of monoamines on mood. Acute tryptophan depletion (ATD) or para-chlorophenylalanine (PCPA) deplete 5-HT, acute phenylalanine/tyrosine depletion (APTD) or alpha-methyl-para-tyrosine (AMPT) deplete NE/DA. Available depletion studies found conflicting results in heterogeneous populations: healthy controls, patients with previous MDD in remission and patients suffering from MDD. The decrease in mood after 5-HT and NE/DA depletion in humans is reviewed and quantified. Systematic search of MEDLINE and EMBASE (1966–October 2006) and cross-references was carried out. Randomized studies applying ATD, PCPA, APTD or AMPT vs control depletion were included. Pooling of results by meta-analyses was stratified for studied population and design of the study (within or between subjects). Seventy-three ATD, 2 PCPA, 10 APTD and 8 AMPT studies were identified of which 45 ATD and 8 APTD studies could be meta-analyzed. 5-HT or NE/DA depletion did not decrease mood in healthy controls. 5-HT or NE/DA depletion slightly lowered mood in healthy controls with a family history of MDD. In drug-free patients with MDD in remission, a moderate mood decrease was found for ATD, without an effect of APTD. ATD induced relapse in patients with MDD in remission who used serotonergic antidepressants. In conclusion, monoamine depletion studies demonstrate decreased mood in subjects with a family history of MDD and in drug-free patients with MDD in remission, but do not decrease mood in healthy humans. Although depletion studies usefully investigate the etiological link of 5-HT and NE with MDD, they fail to demonstrate a causal relation. They presumably clarify a vulnerability trait to become depressed. Directions for further investigation of this vulnerability trait are proposed.

Reducing long term sickness absence by an activating intervention in adjustment disorders: a cluster randomised controlled design

Aims: To compare an innovative activating intervention with “care as usual” (control group) for the guidance of employees on sickness leave because of an adjustment disorder. It was hypothesised that the intervention would be more effective than care as usual in lowering the intensity of symptoms, increasing psychological resources, and decreasing sickness leave duration. Methods: A prospective, cluster randomised controlled trial was carried out with 192 patients on first sickness leave for an adjustment disorder. Symptom intensity, sickness duration, and return to work rates were measured at 3 months and 12 months. Analyses were performed on an intention to treat basis. Results: At 3 months, significantly more patients in the intervention group had returned to work compared with the control group. At 12 months all patients had returned to work, but sickness leave was shorter in the intervention group than in the control group. The recurrence rate was lower in the intervention group. There were no differences between the two study groups with regard to the decrease of symptoms. At baseline, symptom intensity was higher in the patients than in a normal reference population, but decreased over time in a similar manner in both groups to approximately normal levels. Conclusion: The experimental intervention for adjustment disorders was successful in shortening sick leave duration, mainly by decreasing long term absenteeism.

Preventing relapse/recurrence in recurrent depression with cognitive therapy: a randomized controlled trial

This article reports on the outcome of a randomized controlled trial of cognitive group therapy (CT) to prevent relapse/recurrence in a group of high-risk patients diagnosed with recurrent depression. Recurrently depressed patients (N = 187) currently in remission following various types of treatment were randomized to treatment as usual, including continuation of pharmacotherapy, or to treatment as usual augmented with brief CT. Relapse/recurrence to major depression was assessed over 2 years. Augmenting treatment as usual with CT resulted in a significant protective effect, which intensified with the number of previous depressive episodes experienced. For patients with 5 or more previous episodes (41% of the sample), CT reduced relapse/recurrence from 72% to 46%. Our findings extend the accumulating evidence that cognitive interventions following remission can be useful in preventing relapse/recurrence in patients with recurrent depression.

Neural correlates of dysfunctional emotion regulation in major depressive disorder. A systematic review of neuroimaging studies

Abnormal emotion processing is a core feature of major depressive disorder (MDD). Since the emergence of functional neuroimaging techniques, many studies have been conducted in MDD subjects to elucidate the underlying abnormalities in the neural systems involved in emotion regulation. In this systematic review, we discuss this research in the context of the neural model of emotion regulation previously described by Phillips et al. (2008). This model differentiates between automatic and voluntary emotion regulation subprocesses. Automatic regulation subprocesses were shown to involve predominantly medial prefrontal cortical structures, in addition to the hippocampus and parahippocampus, while voluntary regulation processes additionally recruited lateral prefrontal cortical regions. In conclusion, although the available data is limited, findings suggest that MDD subjects demonstrate abnormally reduced activity in lateral prefrontal cortices during explicit voluntary control of emotional experience. During early, automatic stages of emotion regulation, on the other hand, MDD subjects appear to achieve successful emotion regulation by recruiting additional lateral prefrontal neural regions, that may be mediated by medial prefrontal, especially rostral/dorsal anterior cingulate gyrus (ACG) functioning. Dysfunctional automatic regulation may impair successful voluntary emotion regulation, and may present a target for novel therapeutic approaches in MDD.

The personal impact of schizophrenia in Europe.

The personal impact of schizophrenia is poorly described in the scientific literature. The European Psychiatric Services: Inputs Linked to Outcome Domains and Needs (EPSILON) study compared representative treated prevalence cohorts of patients with schizophrenia in five European countries, to assess unmet needs, impact on caregivers, quality of life, satisfaction with services, symptoms and disability. Of the 404 patients, 79% undertook no work of any kind, and 65% were single. Low quality of life was associated with: anxiety, depression, psychotic symptoms, more previous psychiatric admissions, alcohol abuse, having no reliable friends nor daily contact with family, being unemployed, and having few leisure activities. The most frequently occurring unmet needs among the patients were: daytime activities, company and intimate relationships, psychotic symptoms, psychological distress, and information. The most common worries of relatives were about the patients health, and their own future, safety and financial position. Psychiatric services were therefore largely ineffective in managing the personal impact of schizophrenia, especially upon work, home and family life. Research, clinical practice and disability policy developments need to address a wider range of consequences of the disorder than symptoms alone.

Family caregiving in depression: impact on caregivers' daily life, distress, and help seeking

BACKGROUND Attention to caregiving consequences has been mainly restricted to schizophrenia, although studies suggest that relatives of depressed patients also experience considerable distress. These studies, however, were conducted on small samples or with nonvalidated instruments. In our study, the caregiving consequences of 260 spouses and relatives of depressed patients were assessed with a well-validated 31-item questionnaire, the Involvement Evaluation Questionnaire (IEQ). METHODS The IEQ was mailed to spouses and relatives of patients with major depression, dysthymic disorder, or other depressive disorders. Other instruments used were the Ways of Coping Checklist (WCC), a Dutch Social Support Questionnaire, and the Zung Self-rating Depression Scale (SDS). RESULTS About 25-50% of caregivers worried about the patients general health, treatment, safety, and future. They had to urge the patient to undertake activities, or took over tasks. There were relational strains, and they felt burdened, especially when the patient was in an acute phase. Caregivers often felt distressed and had to visit a (mental) health practitioner. Also, children were affected; caregivers reported high levels of difficult behavior, loss of appetite, sleeplessness, less playing, and less attention at school. Caregiving consequences occur less often than in schizophrenia, but the patterns are quite comparable. CONCLUSIONS Caregiving consequences in depression occur frequently and cause distress in caregivers and patients children. Attention should be paid to support relatives and spouses of depressed patients. Special attention should be paid to patients children.

Comparing patterns and costs of schizophrenia care in five European countries: the EPSILON study

Objective: To compare service utilization and cost profiles of people with schizophrenia living in Europe in order to understand differences in treatment and care costs.

Adjuvant occupational therapy for work-related major depression works : randomized trial including economic evaluation

BACKGROUND Major depression has far-reaching consequences for work functioning and absenteeism. In most cases depression is treated by medication and clinical management. The addition of occupational therapy (OT) might improve outcome. We determined the cost-effectiveness of the addition of OT to treatment as usual (TAU). METHOD Sixty-two adults with major depression and a mean absenteeism of 242 days were randomized to TAU (out-patient psychiatric treatment) or TAU+OT [6 months, including (i) diagnostic phase with occupational history and work reintegration plan, and (ii) therapeutic phase with individual sessions and group sessions]. Main outcome domains were depression, work resumption, work stress and costs. Assessments were at baseline and at 3, 6, 12 and 42 months. RESULTS The addition of OT to TAU: (i) did not improve depression outcome, (ii) resulted in a reduction in work-loss days during the first 18 months, (iii) did not increase work stress, and (iv) had a 75.5% probability of being more cost-effective than TAU alone. CONCLUSION Addition of OT to good clinical practice does not improve depression outcome, improves productivity without increasing work stress and is superior to TAU in terms of cost-effectiveness.

Quality of life in patients with schizophrenia in five European countries: the EPSILON study

Objective: To compare subjective quality of life (QOL) and objective QOL indicators in patients with schizophrenia from five European sites: Amsterdam, Copenhagen, London, Santander and Verona.

Resting-state functional connectivity in major depressive disorder: A review

Major depressive disorder (MDD) affects multiple large-scale functional networks in the brain, which has initiated a large number of studies on resting-state functional connectivity in depression. We review these recent studies using either seed-based correlation or independent component analysis and propose a model that incorporates changes in functional connectivity within current hypotheses of network-dysfunction in MDD. Although findings differ between studies, consistent findings include: (1) increased connectivity within the anterior default mode network, (2) increased connectivity between the salience network and the anterior default mode network, (3) changed connectivity between the anterior and posterior default mode network and (4) decreased connectivity between the posterior default mode network and the central executive network. These findings correspond to the current understanding of depression as a network-based disorder.