Benoit Trojak

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.

The Efficacy and Safety of Low Frequency Repetitive Transcranial Magnetic Stimulation for Treatment-resistant Depression: The Results From a Large Multicenter French RCT

CONTEXT The aim of this study was to assess whether the combination of low frequency repetitive transcranial magnetic stimulation (rTMS) and venlafaxine (150-225 mg/day) is effective and safe for treatment-resistant unipolar depression (TRD). METHOD In a multicenter (18 centers) randomized double blind controlled trial with three arms, 170 patients were allocated to receive active rTMS combined with active venlafaxine (n = 55), active rTMS combined with placebo venlafaxine (n = 60) or sham rTMS combined with active venlafaxine (n = 55). The patients received once daily sessions of active or sham 1 Hz rTMS applied over the right dorsolateral prefrontal cortex (360 pulses/day delivered at 120% of the resting motor threshold) for two to six weeks; rTMS was combined with active or sham venlafaxine (mean dose: 179.0 ± 36.6 mg/day). The primary outcome was the number of patients who achieved remission, which was defined as an HDRS17 score <8. RESULTS We reported a similar significant antidepressant effect in the 3 groups (P < 10(-6)), with a comparable delay of action and a comparable number of remitters at the endpoint (28% in the combination group, 41% in the rTMS group and 43% in the venlafaxine group; P = 0.59). CONCLUSION Low frequency rTMS appears to be as effective as venlafaxine and as effective as the combination of both treatments for TRD. Because of its short session duration (the duration of one session was 8.5 min) and its safety, slow rTMS might be a useful alternative treatment for patients with TRD.

Expression of oxidative stress-response genes is not activated in the prefrontal cortex of patients with depressive disorder

To test the hypothesis that the oxidative stress consistently detected in the peripheral blood of patients with depressive disorder impacts on the functionally relevant brain region, the expression level of nine major genes of the stress response and repair systems has been quantified in the prefrontal cortex of 24 depressive and 12 control subjects. These genes were: superoxide dismutase (SOD1), SOD2, catalase (CAT), gluthatione peroxidase 1 (GPx1), 8-oxoguanine DNA glycosylase (OGG1), nei-like 1 (NEIL1), methionine sulphoxide reductase A (MSRA), telomere repeat-binding factor 2 (TERF2) and C-FOS. Telomere length (a maker of chronic exposure to oxidative stress) has been measured in the DNA of the occipital cortex. No significant difference has been found between the compared groups. It must be concluded that the pathogenic role of the oxidative stress in the cerebral mechanism of depression cannot be inferred from the alteration of peripheral parameters.

Hypokalemia is associated with lengthening of QT interval in psychiatric patients on admission

Several studies have revealed a relatively high frequency of hypokalemia in the general psychiatric population. This may be explained by adrenergic stimulation observed in the acute phase of psychiatric disorders. Little is known about the effects of hypokalemia on cardiac repolarisation in these circumstances. The current study was designed to determine if the hypokalemia observed among patients with acute psychiatric disorders can cause significant QT interval prolongation, and thus increase the risk of ventricular arrhythmia. Electrocardiograms were obtained in 282 non-selected patients admitted to a psychiatric unit. Heart-rate adjusted QT intervals (QTc) were compared to serum potassium levels and to other risk factors for QT prolongation (bradycardia, age, gender, and administration of antipsychotics). Hypokalemia, diagnosed in more than 11% of the patients, was associated with a significantly longer QTc interval (means 423.5+/-40 ms vs 408.5+/-31 ms), as was female sex. Multiple linear regression analysis on the studied risk factors revealed that only hypokalemia and female sex were independently associated with lengthening of the QT interval. According to our results, hypokalemia seems to be one of the most important risk factors for QT prolongation. We therefore strongly recommend that psychiatric patients should be screened for hypokalemia on admission.

Transcranial direct current stimulation (tDCS) in behavioral and food addiction: a systematic review of efficacy, technical, and methodological issues.

Objectives: Behavioral addictions (BA) are complex disorders for which pharmacological and psychotherapeutic treatments have shown their limits. Non-invasive brain stimulation, among which transcranial direct current stimulation (tDCS), has opened up new perspectives in addiction treatment. The purpose of this work is to conduct a critical and systematic review of tDCS efficacy, and of technical and methodological considerations in the field of BA. Methods: A bibliographic search has been conducted on the Medline and ScienceDirect databases until December 2014, based on the following selection criteria: clinical studies on tDCS and BA (namely eating disorders, compulsive buying, Internet addiction, pathological gambling, sexual addiction, sports addiction, video games addiction). Study selection, data analysis, and reporting were conducted according to the PRISMA guidelines. Results: Out of 402 potential articles, seven studies were selected. So far focusing essentially on abnormal eating, these studies suggest that tDCS (right prefrontal anode/left prefrontal cathode) reduces food craving induced by visual stimuli. Conclusions: Despite methodological and technical differences between studies, the results are promising. So far, only few studies of tDCS in BA have been conducted. New research is recommended on the use of tDCS in BA, other than eating disorders.

Leukocyte telomere length in mastocytosis: Correlations with depression and perceived stress

BACKGROUND Mastocytosisis a rare disease associated with chronic symptoms related to mast cell mediator release. Patients with mastocytosis display high level of negative emotionality such as depression and stress sensibility. Brain mast cells are mainly localized in the diencephalon, which is linked to emotion regulatory systems. Negative emotionality has been shown to be associated with telomere shortening. Taken together these observations led us to hypothesize that mast cells activity could be involved in both negative emotionality and telomere shortening in mastocytosis. OBJECTIVE To demonstrate a possible relationship between negative emotionality in mastocytosis and leukocytes telomere length. METHODS Leukocyte telomere length and telomerase activity were measured among mastocytosis patients and were correlated with perceived stress and depression assessed by the Beck Depression Inventory revised and the Perceived Stress Scale. RESULTS Mild-severe depression scores were frequent (78.9%) as well as high perceived stress (42.11%). Telomere length was correlated to perceived stress (r=0.77; p=0.0001) but not to depression in our population. Patients displaying Wild-type KIT significantly presented higher perceived stress levels. Patients with the D816VC KIT mutation who had high perceived stress scores displayed significantly shorter telomere but not if they had high depression scores. CONCLUSION These findings suggest that high perceived stress in mastocytosis could accelerate the rate of leukocytes telomere shortening. Since mastocytosis is, by definition, a mast cell mediated disease; these cells could be involved in this phenomenon. Mechanistic causal relationships between these parameters need to be investigated.

Activation of a ΔFOSB dependent gene expression pattern in the dorsolateral prefrontal cortex of patients with major depressive disorder

BACKGROUND A ΔFOSB mediated transcriptional response in the nucleus accumbens (NAc) is induced by chronic social stress in rodent and a 50% down-regulation of ΔFOSB has been also reported in the NAc of eight depressed subjects. To evaluate the role of ΔFOSB in the prefrontal cortex which is critically involved in negative cognitive bias associated with major depressive disorder (MDD) we have quantified the mRNA levels of ΔFOSB and of five of its major target genes in the Brodmann area 46 from 24 patients with MDD (11 with psychotic symptoms) and 12 controls. METHOD Expression of the six genes has been quantified by a real-time quantitative PCR method: ΔFOSB, GRIA2 (encoding the GluR2 subunit of the AMPA receptor), SPARCL1 (encoding hevin), SG3 (encoding the secretogranin III), PCP4 (encoding the Purkinje cell protein 4), ATP6V0C (encoding a subunit of the lysosomal ATPase). RESULTS Expression of ΔFOSB and GRIA2 was significantly up-regulated (≈ 1.60) in the BA 46 of MDD patients. Overexpression of SCG3 and PCP4 was restricted to psychotic subjects. The mRNA levels of GRIA2, SCG3 and PCP4 were strongly correlated in the depressed group. LIMITATIONS All the patients were treated by antidepressants and the number of subjects in each subgroup was rather small. CONCLUSIONS Induction of a ΔFOSB mediated transcriptional pattern in the prefrontal cortex is opposite to the down-regulation observed in the NAc. The major consequence might be a shift in the excitability of the glutamatergic synapses which depends on GluR2 (high in the NAc and low in the BA 46).

Stroke with neuropsychiatric sequelae after cannabis use in a man: a case report

IntroductionThe outcome of cerebral ischemic stroke associated with cannabis use is usually favorable. Here we report the first case of cannabis-related stroke followed by neuropsychiatric sequelae.Case presentationA 24-year-old Caucasian man was discovered in a deeply comatose non-reactive state after cannabis use. A magnetic resonance imaging scan of his brain showed bilateral multiple ischemic infarcts. The patient remained deeply comatose for four days, after which time he developed other behavioral impairments and recurrent seizures.ConclusionStroke related to cannabis use can be followed by severe neuropsychiatric sequelae. Concomitant alcohol intoxication is essential neither to the occurrence of this neurologic event nor to its severity.

Intragenic FMR1 disease-causing variants: a significant mutational mechanism leading to Fragile-X syndrome

Fragile-X syndrome (FXS) is a frequent genetic form of intellectual disability (ID). The main recurrent mutagenic mechanism causing FXS is the expansion of a CGG repeat sequence in the 5′-UTR of the FMR1 gene, therefore, routinely tested in ID patients. We report here three FMR1 intragenic pathogenic variants not affecting this sequence, identified using high-throughput sequencing (HTS): a previously reported hemizygous deletion encompassing the last exon of FMR1, too small to be detected by array-CGH and inducing decreased expression of a truncated form of FMRP protein, in three brothers with ID (family 1) and two splice variants in boys with sporadic ID: a de novo variant c.990+1G>A (family 2) and a maternally inherited c.420-8A>G variant (family 3). After clinical reevaluation, the five patients presented features consistent with FXS (mean Hagerman’s scores=15). We conducted a systematic review of all rare non-synonymous variants previously reported in FMR1 in ID patients and showed that six of them are convincing pathogenic variants. This study suggests that intragenic FMR1 variants, although much less frequent than CGG expansions, are a significant mutational mechanism leading to FXS and demonstrates the interest of HTS approaches to detect them in ID patients with a negative standard work-up.

Interest of targeting either cortical area Brodmann 9 or 46 in rTMS treatment for depression: A preliminary randomized study

OBJECTIVE To assess the interest of specifically targeting Brodmann Areas (BA) 9 or 46 for rTMS treatment of depression. METHODS Patients with Treatment-Resistant Depression were randomly assigned to two treatment groups to receive either rTMS on BA 9 or on BA 46. Each patient underwent 10 sessions of 1Hz-rTMS for 2weeks. The Hamilton and Montgomery-Asberg Depression Rating Scales (HDRS, MADRS) were used under blind conditions to assess the therapeutic response (50% improvement). A Wilcoxon signed-rank test was used to compare the depression rating scales scores obtained before and after the 10 rTMS sessions for each of the two groups. The therapeutic results in the two groups were compared using the Mann-Whitney-Wilcoxon test. We also reported the effect sizes using Hedgess g. RESULTS Fifteen patients were included. Stimulation of both BA 9 (n=7) and BA 46 (n=8) led to similar therapeutic responses in the two groups (with moderate effect size), such as the mean decrease in HDRS (BA 9: p=0.015; BA 46: p=0.010) and MADRS (BA 9: p=0.042; BA 46: p=0.038) scores. CONCLUSION Our results do not come out in favor of one or the other BA. SIGNIFICANCE Stimulation of BA 9 and BA 46 appears to be equally effective in the treatment of depression.