P. Gorwood

Massively multiplayer online role-playing games: comparing characteristics of addict vs non-addict online recruited gamers in a French adult population

BackgroundMassively Multiplayer Online Role-Playing Games (MMORPGs) are a very popular and enjoyable leisure activity, and there is a lack of international validated instruments to assess excessive gaming. With the growing number of gamers worldwide, adverse effects (isolation, hospitalizations, excessive use, etc.) are observed in a minority of gamers, which is a concern for society and for the scientific community. In the present study, we focused on screening gamers at potential risk of MMORPG addiction.MethodsIn this exploratory study, we focused on characteristics, online habits and problematic overuse in adult MMORPG gamers. In addition to socio-demographical data and gamer behavioral patterns, 3 different instruments for screening addiction were used in French MMORPG gamers recruited online over 10 consecutive months: the substance dependence criteria for the Diagnostic and Statistical Manual of Mental Disorder, fourth revised edition (DSM-IV-TR) that has been adapted for MMORPG (DAS), the qualitative Goldberg Internet Addiction Disorder scale (GIAD) and the quantitative Orman Internet Stress Scale (ISS). For all scales, a score above a specific threshold defined positivity.ResultsThe 448 participating adult gamers were mainly young adult university graduates living alone in urban areas. Participants showed high rates of both Internet addiction (44.2% for GIAD, 32.6% for ISS) and DAS positivity (27.5%). Compared to the DAS negative group, DAS positive gamers reported significantly higher rates of tolerance phenomenon (increased amount of time in online gaming to obtain the desired effect) and declared significantly more social, financial (OR: 4.85), marital (OR: 4.61), family (OR: 4.69) and/or professional difficulties (OR: 4.42) since they started online gaming. Furthermore, these gamers self-reported significantly higher rates (3 times more) of irritability, daytime sleepiness, sleep deprivation due to play, low mood and emotional changes since online gaming onset.ConclusionsThe DAS appeared to be a good first-line instrument to screen MMORPG addiction in online gamers. This study found high MMORPG addiction rates, and self-reported adverse symptoms in important aspects of life, including mood and sleep. This confirms the need to set up relevant prevention programs against online game overuse.

EPA guidance on tobacco dependence and strategies for smoking cessation in people with mental illness.

Tobacco dependence is the most common substance use disorder in adults with mental illness. The prevalence rates for tobacco dependence are two to four times higher in these patients than in the general population. Smoking has a strong, negative influence on the life expectancy and quality of life of mental health patients, and remains the leading preventable cause of death in this group. Despite these statistics, in some countries smokers with mental illness are disadvantaged in receiving intervention and support for their tobacco dependence, which is often overlooked or even tolerated. This statement from the European Psychiatric Association (EPA) systematically reviews the current evidence on tobacco dependence and withdrawal in patients with mental illness and their treatment. It provides seven recommendations for the core components of diagnostics and treatment in this patient group. These recommendations concern: (1) the recording process, (2) the timing of the intervention, (3) counselling specificities, (4) proposed treatments, (5) frequency of contact after stopping, (6) follow-up visits and (7) relapse prevention. They aim to help clinicians improve the care, health and well-being of patients suffering from mental illness.

SMARCA2 and other genome-wide supported schizophrenia-associated genes: regulation by REST/NRSF, network organization and primate-specific evolution

The SMARCA2 gene, which encodes BRM in the SWI/SNF chromatin-remodeling complex, was recently identified as being associated with schizophrenia (SZ) in a genome-wide approach. Polymorphisms in SMARCA2, associated with the disease, produce changes in the expression of the gene and/or in the encoded amino acid sequence. We show here that an SWI/SNF-centered network including the Smarca2 gene is modified by the down-regulation of REST/NRSF in a mouse neuronal cell line. REST/NRSF down-regulation also modifies the levels of Smarce1, Smarcd3 and SWI/SNF interactors (Hdac1, RcoR1 and Mecp2). Smarca2 down-regulation generates an abnormal dendritic spine morphology that is an intermediate phenotype of SZ. We further found that 8 (CSF2RA, HIST1H2BJ, NOTCH4, NRGN, SHOX, SMARCA2, TCF4 and ZNF804A) out of 10 genome-wide supported SZ-associated genes are part of an interacting network (including SMARCA2), 5 members of which encode transcription regulators. The expression of 3 (TCF4, SMARCA2 and CSF2RA) of the 10 genome-wide supported SZ-associated genes is modified when the REST/NRSF-SWI/SNF chromatin-remodeling complex is experimentally manipulated in mouse cell lines and in transgenic mouse models. The REST/NRSF-SWI/SNF deregulation also results in the differential expression of genes that are clustered in chromosomes suggesting the induction of genome-wide epigenetic changes. Finally, we found that SMARCA2 interactors and the genome-wide supported SZ-associated genes are considerably enriched in genes displaying positive selection in primates and in the human lineage which suggests the occurrence of novel protein interactions in primates. Altogether, these data identify the SWI/SNF chromatin-remodeling complex as a key component of the genetic architecture of SZ.

Treatment response in major depression: Effects of personality dysfunction and prior depression

BACKGROUNDnThe impact of personality dysfunction on the outcome of treatment for depression remains debated.nnnAIMSnTo examine the relationship between the number of prior depressive episodes, personality dysfunction and treatment response for depression.nnnMETHODnIn a large sample (n = 8229) of adult out-patients with a major depressive episode (DSM-IV), personality dysfunction was assessed using the Standardised Assessment of Personality - Abbreviated Scale (SAPAS). Potential predictors of treatment response at 6 weeks were examined via structural equation modelling.nnnRESULTSnThe amount of personality dysfunction and number of prior episodes of depression were both associated with poor response to treatment. Once personality dysfunction was controlled for, the number of prior episodes of depression was not associated with treatment response.nnnCONCLUSIONSnPersonality dysfunction is associated with impaired short-term response to antidepressant treatment in major depression. The apparent detrimental effect of prior depression on treatment response may be accounted for by pre-existing personality dysfunction.

Paliperidone palmitate versus oral antipsychotics in recently diagnosed schizophrenia.

OBJECTIVEnRelapse and acute exacerbation are common in schizophrenia and may impact treatment response and outcome. Evidence is conflicting in respect to superiority of long-acting injectable antipsychotic therapies versus oral antipsychotics in relapse prevention. This randomized controlled study assessed the efficacy of paliperidone palmitate versus oral antipsychotics for relapse prevention.nnnMETHODnEligible patients with a recent diagnosis of schizophrenia (within 1-5 years) were randomized 1:1 to paliperidone palmitate (n=376) or oral antipsychotic monotherapy (n=388) and entered a 2-week initial acute oral treatment phase. Patients who met predefined response criteria were eligible to enter the 24-month rater-blinded core treatment phase. Patients were evaluated for relapse, symptoms, functioning, quality of life, treatment satisfaction, and tolerability.nnnRESULTSnIn the core treatment phase, time to relapse was significantly longer in the paliperidone palmitate (n=352) compared with the oral antipsychotics arm (n=363): 85% of patients were relapse-free at 469 versus 249 days (P=0.019). Significantly fewer patients receiving paliperidone palmitate met the relapse criteria (52 [14.8%] versus 76 [20.9%, oral antipsychotics]; P=0.032), representing a 29.4% relative risk reduction. For paliperidone palmitate, a significantly greater improvement in Positive and Negative Syndrome Scale total score on Day 8 (P=0.021) and a trend at endpoint (P=0.075) were observed. Functioning improvements were comparable between treatment arms. No new safety signals were identified.nnnCONCLUSIONnThe observed time to relapse superiority of paliperidone palmitate over oral antipsychotics provides further evidence for the value of long-acting injectable antipsychotic therapies in the treatment of schizophrenia, including during the early stages of illness.

Improving treatment adherence in your patients with schizophrenia: the STAY initiative.

Partial and non-adherence to medication is a common problem in schizophrenia, leading to an increased risk of relapse, increased likelihood of hospitalization and poorer long-term outcomes. In contrast, continuous medication in the treatment of schizophrenia is associated with positive outcomes, including improved clinical status, improved quality of life and functioning, and reduced risk of relapse and rehospitalization. Strategies aimed at improving medication adherence are therefore key for patients to achieve their treatment goals. In an attempt to address the issues of partial/non-adherence to antipsychotic medication in schizophrenia, a group of psychiatrists convened to discuss and develop a set of principles aimed at helping patients adhere to their medication. These principles were then refined and developed into the STAY (the Six principles to improve Treatment Adherence in Your patients) initiative following presentation to a wider group of psychiatrists from across Europe. This manuscript summarizes these principles and explains the rationale for their selection. These principles are: (1) recognizing that most patients with schizophrenia are at risk of partial/non-adherence at some time during the course of their illness; (2) the benefits of a good therapeutic alliance for identifying potential adherence issues; (3) tailored treatment plans to meet an individual’s needs, including the most suitable route of delivery of antipsychotic medication; (4) involving family/key persons in care and psychoeducation of the patient, assuming the patient agrees to this; (5) ensuring optimal effectiveness of care; and (6) ensuring continuity in the care of patients with schizophrenia. The application of these six principles should help to raise awareness of and address poor patient adherence, as well as generally improving care of patients with schizophrenia. In turn, this should lead to improved overall clinical outcomes for patients receiving long-term treatment for schizophrenia.

Morningness–eveningness and treatment response in major depressive disorder

In a large, prospective, 8-week open study of 721 outpatients receiving agomelatine treatment for a current major depressive episode (MDE), morningness–eveningness (Composite Scale of Morningness) was assessed before and after treatment to investigate possible changes in morningness–eveningness after treatment and evaluate whether morningness–eveningness at baseline predicted treatment response. A change towards morningness was observed after treatment. This change was greater in responders than non-responders. Moreover, being a morning type at baseline was an independent predictor of response to treatment. Once thought to be a trait variable, morningness–eveningness is a potential treatment target that should be systematically assessed in MDE patients.

Novel routes to bipolar disorder drug discovery

Introduction: Bipolar disorder (BD) is a severe and chronic medical condition typified by episodic recurrent mania (or hypomania) in addition to major depression. BD is associated with a number of negative outcomes including premature death, reduced quality of life and can also lead to other complications including impaired cognitive function. Unfortunately, the currently available pharmacological treatments for BD are insufficient for many with the condition. Areas covered: This review focuses on known therapeutic targets of mood stabilizing drugs including: the glycogen synthase kinase-3 (GSK-3), the phosphoinositide pathway and protein kinase C (PKC), the brain-derived neurotrophic factor (BDNF), and histone deacetylases (HDACs). This article also presents new promising therapeutic targets including: the glutamatergic pathway, mitochondrial modulators, neuropeptide-converting endopeptidases, the insulin transduction pathway, the purinergic system and the melatoninergic system. Expert opinion: Challenges in improving methods and tools to generate, integrate and analyze high-dimensional data are required to allow opening novel routes to BD drug discovery. Through the application of systems biology approaches and the use of bioinformatical tools to integrate all omics data, it will be possible in the near future to gain deeper insights into pathophysiology of BD. This will in turn lead to the identification and exploitation of new potential therapeutic approaches.

Is it worth assessing progress as early as week 2 to adapt antidepressive treatment strategy? Results from a study on agomelatine and a global meta-analysis.

CONTEXTnA delay of 4-8weeks before modifying the prescribed antidepressant treatment is usually proposed when incomplete treatment response is observed. A number of studies nevertheless proposed that the lack of early improvement (usually 20% decrease of severity at week 2) is predictive of the absence of subsequent treatment response, potentially saving weeks of inadequate treatment, but with no information for non-interventional studies devoted to outpatients.nnnMETHODnTwo thousand nine hundred and thirty-eight outpatients with major depressive disorder were included in a multicentre, non-interventional study, assessing at inclusion, week 2 and week 6, mood (QIDS-C, CGI, PGI and VAS) sleep (LSEQ) and functionality (SDS). All metrics at week 2 were tested for their capacity to predict response (and then remission) at week 6, all patients being treated by agomelatine. A meta-analysis of all studies (n=12) assessing the predictive role of improvement at week 2 was also performed, assessing specific effect size of published studies and the weight of the different parameters they used.nnnRESULTSnThe QIDS-C and the CGI-I were the only instruments with an area under the curve over 0.7, with different cut-offs for treatment response and remission. A decrease of more than five points at the QIDS-C had the highest positive predictive value for treatment response, and a CGI-I over three had the highest negative predictive value, which would favour relying on the clinicians for warning (too high CGI-I), and on instruments for confidence (favourable decrease of the QIDS-C). The meta-analysis of all studies also detected a large effect size of early improvement, stressing how rating week 2 severity could be beneficial in clinical practice.nnnCONCLUSIONSnPrevious reports stressing the interest of an assessment at week 2 were reinforced by the present results, which also defined more accurately what could be the most appropriate cut-offs, and how combining these early results could be more effective.

Estimated cost of a factitious disorder with 6-year follow-up

Long-term follow up is rarely described for patients with Factitious Disorder, mainly because of the lack of access to patients confidential information. In addition, the financial burden of multiple uses of health care system has not been examined so far. We report a 6-year follow-up for a patient with Factitious Disorder who first reported neurological then psychiatric symptoms, and investigate the cost of his detected hospitalizations.