Response to serotonin reuptake inhibitors in OCD is not influenced by common CYP2D6 polymorphisms

The cornerstone of pharmacotherapy for OCD is serotonin reuptake inhibition, either with clomipramine or with selective serotonin reuptake inhibitors (SSRIs). In spite of the success of serotonin reuptake inhibiting drugs, nearly half of OCD patients do not respond to treatment. Treatment response may be affected by genetic polymorphisms of the P450 metabolic system. The four most common enzyme-activity reducing polymorphisms of the P450 CYP2D6 enzyme were determined in 91 outpatients with primary OCD according to DSM-IV criteria, receiving dosages titrated upward to 300 mg/day of venlafaxine or 60 mg/day of paroxetine, using a fixed dosing schedule. Our results show that the investigated CYP2D6 polymorphisms are not a decisive factor in the response to paroxetine and venlafaxine treatment in OCD in spite of their highly significant effect on the blood levels of these medicines

Self-reported suicidal ideation among individuals with first episode psychosis and healthy controls:Findings from the international multicentre EU-GEI study

Introduction: Suicidal ideation is common among individuals with first episode psychosis (FEP), with prevalence estimates up to 56.5 %. Despite its high prevalence, relatively little is known about how sociodemographic, clinical and/or developmental characteristics contribute to the experience of suicidal ideation in individuals with FEP. Methods: In this cross-sectional study (FEP n = 551 and controls n = 857), univariate logistic regression analyses were performed to study the associations of sociodemographic, clinical, and developmental factors with suicidal ideation in individuals with FEP as well as controls. Suicidal ideation was assessed using the Community Assessment of Psychic Experiences (CAPE). In addition, multivariate logistic regression analyses were conducted based on a stepwise approach. Results: In FEP, only depressive symptoms remained significantly associated with suicidal ideation when all correlates were integrated into one model. In the multivariate model in controls, depressive symptoms, positive symptoms, and traumatic childhood experiences were significantly associated with suicidal ideation. Conclusions: This study showed that depressive symptoms are an important factor relating to suicidal ideation in individuals with FEP, over and above other clinical, sociodemographic, and developmental factors. This underscores the relevance of screening for suicidal ideation in individuals with FEP, and highlights the need for a better understanding of the diagnostic uncertainty and course of mood symptoms in early psychosis. Limitations: Cross-sectional study design, self-reported questionnaires.</p

Elektroconvulsietherapie bij persisterende depressie in Nederland; zeer lage toepassingsgraad

BACKGROUND: Of all depressive disorders, 20% has a persistent course. For persistent depressive patients, electroconvulsive therapy (ect) is recommended for this patient population, since it is the most potent treatment for depression. The Dutch depression guideline advises the use of ect for persistent depressive disorder at approximately 12 months after inadequate efficacy of psychotherapy and/or pharmacological treatment. AIM: To quantify the use of electroconvulsive therapy in persistent depressive patients in the Netherlands. method Quantitative research using the Dutch registration system (diagnosis-treatment-combination; dbc) information system (dis) of the Dutch Healthcare Authority (Nza). RESULTS: Of the patients within the dbc system (in 2014) with the main diagnosis of unipolar depression, 23.597 (26%) were registered for more than two years and could be classified as having a persistent depressive episode. Of these latter patients, only 278 (1.2%) received ect. conclusion In the Netherlands, only 1.2% of patients with a persistent depression received ect, whereas this treatment could have been considered for 26% of this group.The low application rate might be caused by professionals' inadequate knowledge about ect and the premature use of the handicap model

The functional connectome in obsessive-compulsive disorder: resting-state mega-analysis and machine learning classification for the ENIGMA-OCD consortium

Current knowledge about functional connectivity in obsessive-compulsive disorder (OCD) is based on small-scale studies, limiting the generalizability of results. Moreover, the majority of studies have focused only on predefined regions or functional networks rather than connectivity throughout the entire brain. Here, we investigated differences in resting-state functional connectivity between OCD patients and healthy controls (HC) using mega-analysis of data from 1024 OCD patients and 1028 HC from 28 independent samples of the ENIGMA-OCD consortium. We assessed group differences in whole-brain functional connectivity at both the regional and network level, and investigated whether functional connectivity could serve as biomarker to identify patient status at the individual level using machine learning analysis. The mega-analyses revealed widespread abnormalities in functional connectivity in OCD, with global hypo-connectivity (Cohen’s d: -0.27 to -0.13) and few hyper-connections, mainly with the thalamus (Cohen’s d: 0.19 to 0.22). Most hypo-connections were located within the sensorimotor network and no fronto-striatal abnormalities were found. Overall, classification performances were poor, with area-under-the-receiver-operating-characteristic curve (AUC) scores ranging between 0.567 and 0.673, with better classification for medicated (AUC = 0.702) than unmedicated (AUC = 0.608) patients versus healthy controls. These findings provide partial support for existing pathophysiological models of OCD and highlight the important role of the sensorimotor network in OCD. However, resting-state connectivity does not so far provide an accurate biomarker for identifying patients at the individual level.ISSN:1359-4184ISSN:1476-557