Background. Response and remission defined by cut-off values on the last observed depression severity score are commonly used as outcome criteria in clinical trials, but ignore the time course of symptomatic change and may lead to inefficient analyses. We explore alternative categorization of outcome by naturally occurring trajectories of symptom change.Method. Growth mixture models were applied to repeated measurements of depression severity in 807 participants with major depression treated for 12 weeks with escitalopram or nortriptyline in the part-randomized Genome-based Therapeutic Drugs for Depression study. Latent trajectory classes were validated as outcomes in drug efficacy comparison and pharmacogenetic analyses.Results. The final two-piece growth mixture model categorized participants into a majority (75 %) following a gradual improvement trajectory and the remainder following a trajectory with rapid initial improvement. The rapid improvement trajectory was over-represented among nortriptyline-treated participants and showed an antidepressant-specific pattern of pharmacogenetic associations. In contrast, conventional response and remission favoured escitalopram and produced chance results in pharmacogenetic analyses. Controlling for drop-out reduced drug differences on response and remission but did not affect latent trajectory results.Conclusions. Latent trajectory mixture models capture heterogeneity in the development of clinical response after the initiation of antidepressants and provide an outcome that is distinct from traditional endpoint measures. It differentiates between antidepressants with different modes of action and is robust against bias due to differential discontinuation.

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Patients with major depression often report pain. In this article, we review the current literature regarding the prevalence and consequences, as well as the pathophysiology, of unexplained painful physical symptoms (UPPS) in patients with major depressive disorder (MDD). UPPS are experienced by approximately two-thirds of depressed patients. The presence of UPPS makes a correct diagnosis of depression more difficult. Moreover, UPPS are a predictor of a poor response to treatment and a more chronic course of depression. Pain, in the course of depression, also has a negative impact on functioning and quality of life. Frequent comorbidity of depression and UPPS has inspired the formulation of an hypothesis regarding a shared neurobiological mechanism of both conditions. Evidence from neuroimaging studies has shown that frontal-limbic dysfunction in depression may explain abnormal pain processing, leading to the presence of UPPS. Increased levels of proinflamatory cytokines and substance P in patients with MDD may also clarify the pathophysiology of UPPS. Finally, dysfunction of the descending serotonergic and noradrenergic pathways that normally suppress ascending sensations has been proposed as a core mechanism of UPPS. Psychological factors such as catastrophizing also play a role in both depression and chronic pain. Therefore, pharmacological treatment and/or cognitive therapy are recommended in the treatment of depression with UPPS. Some data suggest that serotonin and noradrenaline reuptake inhibitors (SNRIs) are more effective than selective serotonin reuptake inhibitors (SSRIs) in the alleviation of depression and UPPS. However, the pooled analysis of eight randomised clinical trials showed similar efficacy of duloxetine (an SNRI) and paroxetine (an SSRI) in reducing UPPS in depression. Further integrative studies examining genetic factors (e.g. polymorphisms of genes for interleukins, serotonin transporter and receptors), molecular factors (e.g. cytokines, substance P) and neuroimaging findings (e.g. functional studies during painful stimulation) might provide further explanation of the pathophysiology of UPPS in MDD and therefore facilitate the development of more effective methods of treatment.

Depression and physical disability were the most important predictors of QOL after stroke since their impact on QOL was more robust in comparison to the remaining variables. For improving QOL, a comprehensive care for patients aimed at reducing physical dependence and ameliorating depressive symptoms could be recommended.

The aim of this study was to investigate selected measures of creativity in schizophrenic patients and their relationship with neurocognitive executive functions Forty-three inpatients with paranoid schizophrenia who were in symptomatic remission (a total of 60) and 45 healthy control participants were included. Creativity was assessed using the Barron-Welsh Art Scale (BWAS) and the inventiveness part of the Berlin Intelligence Structure Test (BIS). Executive functions were measured by means of the Wisconsin Card Sorting Test (WCST). Schizophrenic patients gave responses on the BWAS, had lower total score on the BIS and in the figural test, and performed worse on all domains of the WCST compared with control subjects. Their lower scores on the BIS correlated with lower scores on the WCST. Our results indicate that remitted schizophrenic patients perform worse on selected measures of creativity than healthy subjects and that executive dysfunctions may partially explain these deficits.