[Addictive behaviors: Clinical facts]. / Conduites addictives : faits cliniques.

Despite the frequency of psychiatric comorbidities, substance use disorder must be understood as an autonomous pathology due to its own determinants, semiology and possibilities of evolution, either spontaneous or under treatment. The ease of access to multiple synthetic products via the Internet combined with the creativity of chemists are contributing to the emergence of novel practices ranging from chemsex to purple drank. Addictive behaviours result from a combination of individual factors (biological and psychological vulnerability) and contextual factors (availability and triviality of the toxicant in the environment). Other mental disorders are factors of vulnerability to addictive pathology as well as the addictive behaviours can reveal an emotional or psychotic pathology. The physician needs to hear the patient powerlessness hidden behind the craving and propose a therapy that may be chemical (including substitution treatment) and psychological. Most of the time, social support is necessary to correct the desocializing effects of substance use disorder or addictive behaviours.

[Early detection of mental health disorders at school: The Fil Harmonie pilot program]. / Détection précoce des troubles psychiques en milieu scolaire : le dispositif Fil Harmonie.

OBJECTIVE: Most psychiatric disorders arise during adolescence, a period of life during which school takes an important place. School in France has an official mission of health education and prevention, and early detection of mental disorders is part of these goals. The aim of this study is to describe an innovative service operating in Paris that helps educational staff to deal with students having psychological or psychiatric symptoms. The Fil Harmonie program was launched in 2011. It consists of a telephone line available to all educational staff working for high schools in Paris. METHODS: When in need of assistance, a member of the educational staff can call the dedicated hotline and expose the situation of their student to a trained psychologist. Over the course of the study, data concerning these phone calls were collected such as: socio-demographic characteristics of the student, the reason behind the call, the caller's professional role within the school, and care pathway information. All data collected during the phone calls were anonymized and computerized. We performed an observational descriptive study based on this data by using mixed methods: we integrated quantitative analysis and qualitative research in order to provide a better understanding of the Fil Harmonie program. RESULTS: Between 18 September 2013 and 12 May 2014, the Fil Harmonie program handled 68 calls from educational staff. Students concerned by the calls were aged between 11 and 22 and the average age was 17.3 years. Over half (52.5%) of the pupils concerned had never seen a mental health professional before the call. In more than 70% of cases, the caller was a school nurse while other professionals such as teachers or headmasters represented only a minority of the callers. Approximately two thirds (67.2%) of students were described by the caller as socially isolated and 48.2% were described as sad or anhedonic. One out of four (26.7%) had repeated a school year at least once, and 55.9% of young people for whom a member of staff contacted Fil Harmonie had been missing class. In 56.7% of cases, there had been no contact with the student's family about the psychological situation. The qualitative analysis particularly highlighted the complexity of the collaboration between the family and the educational staff. CONCLUSION: Schooling is an important opportunity to seize in mental health regarding early detection and access to care. By fostering collaboration between educational professionals and mental health services, Fil Harmonie meets a public health objective of prevention and should contribute to the reduction of care delays thus leading to better treatment outcome. Our study shows that such programs are feasible and answer a real need in our current health care system.

[Association between the violence in the community and the aggressive behaviors of psychotics during their hospitalizations]. / Relation entre la violence intra-hospitalière des patients avec psychoses et la violence dans la communauté.

BACKGROUND: Violence is a common issue in psychiatry and has multiple determiners. The aim of this study is to assess the psychotic inpatients' violence in association with the violence of the neighborhood from which the patients are drawn and to estimate the impact of this environmental factor with regard to other factors. METHOD: A prospective multicenter study was led in nine French cities. Eligible patients were psychotic involuntary patients hospitalized in the cities' psychiatric wards. During their treatments, any kind of aggressive behavior by the patients has been reported by the Overt Aggression Scale (OAS). RESULTS: From June 2010 to May 2011, 95 patients have been included. Seventy-nine per cent of the patients were violent during their hospitalizations. In a bivariate analysis, inpatient violence was significantly associated with different factors: male gender, patient violence history, substance abuse, manic or mixed disorder, the symptoms severity measured by the BPRS, the insight degree and the city crime rate. In a multivariate analysis, the only significant factors associated with the patients' violence were substance abuse, the symptoms severity and the crime rates from the different patients' cities. CONCLUSION: These results suggest that violence within the psychotic patients' neighborhood could represent a risk of violence during their treatments.

Modeling the effect of succimer (DMSA; dimercaptosuccinic acid) chelation therapy in patients poisoned by lead.

CONTEXT: Kinetic models could assist clinicians potentially in managing cases of lead poisoning. Several models exist that can simulate lead kinetics but none of them can predict the effect of chelation in lead poisoning. Our aim was to devise a model to predict the effect of succimer (dimercaptosuccinic acid; DMSA) chelation therapy on blood lead concentrations. MATERIALS AND METHODS: We integrated a two-compartment kinetic succimer model into an existing PBPK lead model and produced a Chelation Lead Therapy (CLT) model. The accuracy of the model's predictions was assessed by simulating clinical observations in patients poisoned by lead and treated with succimer. The CLT model calculates blood lead concentrations as the sum of the background exposure and the acute or chronic lead poisoning. The latter was due either to ingestion of traditional remedies or occupational exposure to lead-polluted ambient air. The exposure duration was known. The blood lead concentrations predicted by the CLT model were compared to the measured blood lead concentrations. RESULTS: Pre-chelation blood lead concentrations ranged between 99 and 150 µg/dL. The model was able to simulate accurately the blood lead concentrations during and after succimer treatment. The pattern of urine lead excretion was successfully predicted in some patients, while poorly predicted in others. CONCLUSIONS: Our model is able to predict blood lead concentrations after succimer therapy, at least, in situations where the duration of lead exposure is known.

Balneotherapy Together with a Psychoeducation Program for Benzodiazepine Withdrawal: A Feasibility Study.

Benzodiazepines should be prescribed on a short-term basis, but a significant proportion of patients (%) use them for more than 6 months, constituting a serious public health issue. Indeed, few strategies are effective in helping patients to discontinue long-term benzodiazepine treatments. The aim of this study was to assess the feasibility and the impact of a program including cognitive behavioural therapy, psychoeducation, and balneotherapy in a spa resort to facilitate long-term discontinuation of benzodiazepines. We conducted a prospective multicentre cohort study. Patients with long-term benzodiazepine use were recruited with the aim of anxiolytic withdrawal by means of a psychoeducational program and daily balneotherapy during 3 weeks. The primary efficacy outcome measure was benzodiazepine use 6 months after the program, compared to use at baseline. A total of 70 subjects were enrolled. At 6 months, overall benzodiazepine intake had decreased by 75.3%, with 41.4% of patients completely stopping benzodiazepine use. The results also suggest a significantly greater improvement in anxiety and depression symptoms among patients who discontinued benzodiazepines compared to patients who only reduced their use. Our findings suggest that balneotherapy in association with a psychoeducative program is efficient in subjects with benzodiazepine addiction.

Modelling dimercaptosuccinic acid (DMSA) plasma kinetics in humans.

CONTEXT: No kinetic models presently exist which simulate the effect of chelation therapy on lead blood concentrations in lead poisoning. OBJECTIVE: Our aim was to develop a kinetic model that describes the kinetics of dimercaptosuccinic acid (DMSA; succimer), a commonly used chelating agent, that could be used in developing a lead chelating model. MATERIAL AND METHODS: This was a kinetic modelling study. We used a two-compartment model, with a non-systemic gastrointestinal compartment (gut lumen) and the whole body as one systemic compartment. The only data available from the literature were used to calibrate the unknown model parameters. The calibrated model was then validated by comparing its predictions with measured data from three different experimental human studies. RESULTS: The model predicted total DMSA plasma and urine concentrations measured in three healthy volunteers after ingestion of DMSA 10 mg/kg. The model was then validated by using data from three other published studies; it predicted concentrations within a factor of two, representing inter-human variability. CONCLUSIONS: A simple kinetic model simulating the kinetics of DMSA in humans has been developed and validated. The interest of this model lies in the future potential to use it to predict blood lead concentrations in lead-poisoned patients treated with DMSA.

[Court-ordered treatment: Analysing a complex practise through a literature review]. / Les soins pénalement ordonnés : analyse d'une pratique complexe à travers une revue de la littérature.

INTRODUCTION: In France, there are two main types of court-ordered treatment (COT) as far as mental health is concerned: obligations of treatment and injunctions of treatment. Obligations of treatment date back from 1958 whereas the law implementing injunctions of treatment is fairly recent as it was passed in 1998. Obligations and injunctions of treatment are two different types of COT that differ in terms of proceedings (obligations of treatment require no preliminary forensic psychiatric assessment; as for injunctions of treatment, they require the appointment of a coordinating medical doctor) and that are applied for different offences. However, both are psychiatric commitment procedures connecting the judicial, medical and social fields and their overall numbers have been on the rise. These common psychiatric practices have seldom been assessed and no review of the literature on the subject has ever been published. Better knowledge of such forensic practices is essential to their improvement and even to adjust the legal framework of these measures that are enjoying a boom. The purpose of this literature review is to define the prevalence of COT as well as the sociodemographic, criminal and psychiatric characteristics of those concerned by such measures. MATERIAL AND METHODS: A review of the French medical literature on COT was carried out using Science Direct up to December 2013. The results of seven studies were included and analysed. This was completed with a review of the articles listed in social sciences and law databases (Cairn and Dalloz). RESULTS: It has become increasingly frequent to rely on psychiatric teams to implement COT while at the same time public mental health services have to face a surge in activity with restricted financial means. Obligations of treatment are far more common (about 20,000 court orders a year) than injunctions of treatment (about 4000 measures are currently being enforced). However the latter have showed an increase of 506% over the 2000 decade. Both measures mainly concern men (83-99%) who are rather low on the social scale. In about half of these men, no mental disorder was found, however the prevalence of personality disorders ranged from 22 to 65% while that of psychotic disorders was low. Injunctions of treatment concerned sex offenders (90% of cases) whereas obligations of treatment concern non-sexual abusers (40-70%) rather than sex offenders (20-30%). DISCUSSION: Psychiatric research on COT is still thin on the ground and its methodology does not allow rigorous evaluation though the use of such measures is growing. When confronted with people who have not sought any care or treatment, healthcare professionals are at a loss. In France, training in forensic psychiatry is inadequate and specialised healthcare (particularly for sex offenders) need improving to reach the level of those found in many other European countries. The purpose of psychiatric treatment differs from that of lawmakers whose aim is to prevent recidivism. However, better treatment consistency requires setting up partnerships between justice, health and social services. To improve connections, there are various avenues of work such as, for instance, the creation of coordinating medical doctors for injunctions of treatment in France or European experiments using a multidisciplinary approach to prevent recidivism in sex offenders. The framework of such a partnership remains to be created as it is part and parcel of COT but has not been provided for in the law. Healthcare jurisdictions as defined in the 2009 French National Health Law might provide an appropriate framework for mental health and law professionals to collaborate.

Evaluation of semi-generic PBTK modeling for emergency risk assessment after acute inhalation exposure to volatile hazardous chemicals.

BACKGROUND: Physiologically Based Toxicokinetic Models (PBTK) may facilitate emergency risk assessment after chemical incidents with inhalation exposure, but they are rarely used due to their relative complexity and skill requirements. We aimed to tackle this problem by evaluating a semi-generic PBTK model built in MS Excel for nine chemicals that are widely-used and often released in a chemical incident. MATERIAL & METHODS: The semi-generic PBTK model was used to predict blood concentration-time curves using inhalation exposure scenarios from human volunteer studies, case reports and hypothetical exposures at Emergency Response Planning Guideline, Level 3 (ERPG-3) levels.(2) Predictions using this model were compared with measured blood concentrations from volunteer studies or case reports, as well as blood concentrations predicted by chemical-specific models. The performances of the semi-generic model were evaluated on biological rationale, accuracy, and ease of use and range of application. RESULTS: Our results indicate that the semi-generic model can be easily used to predict blood levels for eight out of nine parent chemicals (dichloromethane, benzene, xylene, styrene, toluene, isopropanol trichloroethylene and tetrachloroethylene). However, for methanol, 2-propanol and dichloromethane the semi-generic model could not cope with the endogenous production of methanol and of acetone (being a metabolite of 2-propanol) nor could it simulate the formation of HbCO, which is one of the toxic end-points of dichloromethane. The model is easy and intuitive to use by people who are not so familiar with toxicokinetic models. CONCLUSION: A semi-generic PBTK modeling approach can be used as a 'quick-and-dirty' method to get a crude estimate of the exposure dose.

Evaluation of three physiologically based pharmacokinetic (PBPK) modeling tools for emergency risk assessment after acute dichloromethane exposure.

INTRODUCTION: Physiologically based pharmacokinetic (PBPK) models may be useful in emergency risk assessment, after acute exposure to chemicals, such as dichloromethane (DCM). We evaluated the applicability of three PBPK models for human risk assessment following a single exposure to DCM: one model is specifically developed for DCM (Bos) and the two others are semi-generic ones (Mumtaz and Jongeneelen). MATERIALS AND METHODS: We assessed the accuracy of the models' predictions by simulating exposure data from a previous healthy volunteer study, in which six subjects had been exposed to DCM for 1h. The time-course of both the blood DCM concentration and percentage of carboxyhemoglobin (HbCO) were simulated. RESULTS: With all models, the shape of the simulated time course resembled the shape of the experimental data. For the end of the exposure, the predicted DCM blood concentration ranged between 1.52-4.19mg/L with the Bos model, 1.42-4.04mg/L with the Mumtaz model, and 1.81-4.31mg/L with the Jongeneelen model compared to 0.27-5.44mg/L in the experimental data. % HbCO could be predicted only with the Bos model. The maximum predicted % HbCO ranged between 3.1 and 4.2% compared to 0.4-2.3% in the experimental data. The % HbCO predictions were more in line with the experimental data after adjustment of the Bos model for the endogenous HbCO levels. CONCLUSIONS: The Bos Mumtaz and Jongeneelen PBPK models were able to simulate experimental DCM blood concentrations reasonably well. The Bos model appears to be useful for calculating HbCO concentrations in emergency risk assessment.

[The interest of maintenance electroconvulsive therapy in mood disorders]. / Intérêt de l'électroconvulsivothérapie de maintenance dans les troubles de l'humeur.

Maintenance electroconvulsive therapy (M-ECT) is a treatment indicated for the treatment and prevention of recurrent depression in patients who either do not respond or do not tolerate psychotropic medication. We evaluated, retrospectively, clinical response to a 6-month minimum course of M-ECT in 25 patients with a diagnosis of bipolar disorder or schizoaffective disorder according to DSM IV-TR criterion. Our study demonstrated a significant improvement of Global Assessment of functioning (GAF) scores after a six month minimum course of M-ECT (34.8 ± 12.6 vs 65.6 ± 10.8; P<0.05) as well as Brief Psychiatric Rating Scale scores (BPRS): 79.3 ± 12.4 vs 43.4 ± 10.2; P<0.05). We observed a slight increase of Mini Mental State Examination (MMSE) scores after M-ECT; nonetheless, it was not statistically significant (24.2 ± 2.4 vs 26.2 ± 2.4; P=0.2). Regarding the mean duration of hospitalizations, we showed a statistically significant decrease in the median number of days of hospitalization (72 [59-93.50] days before M-ECT vs 43 [25-76] days since the first M-ECT; P=0.017). Maintenance ECT allowed a significant improvement in psychiatric symptoms and global functioning of the patients included in this study, as well as a decrease in the number of days of hospitalization. However, our pattern is limited because of its small size; so, further prospective studies in this field, including larger population is highly recommended.

Forgetting what you have checked: a link between working memory impairment and checking behaviors in obsessive-compulsive disorder.

BACKGROUND: Compulsive checking behaviors are common in obsessive-compulsive disorder (OCD). Several authors have suggested that these checking rituals could be related to memory deficits. Our aim was to test whether patients with OCD show working memory impairment in relation to their checking behavior. METHODS: We evaluated the verbal and visuospatial components of patients' and controls' working memory using the reading span and backward location span tests. Checking behaviors were measured by recording participants' eye movements during an image comparison task using a non-invasive, infra-red TOBII 1750 eyetracker. Participants were seated, head-free, in a natural position in front of the eyetracker screen where the images were displayed. RESULTS: Patients with OCD made more gaze moves to compare images than controls. Both patients' working memory spans were reduced, and the patients' deficit in the comparison task was negatively related to their working memory spans. CONCLUSIONS: This work demonstrates that checking behavior in OCD is linked to a general reduction of the patients' verbal and visuospatial working memory span.

Deficit of cognitive inhibition in depressed elderly: a neurocognitive marker of suicidal risk.

BACKGROUND: Cognitive deficits, in relation to ventral and dorsal prefrontal cortex dysfunctions, have been associated with a higher risk of suicidal acts in young adult patients. Although a public health concern, much less is known about the neurocognitive basis of suicidal behavior in elderly. Here, we aimed at assessing alterations in cognitive inhibition, a suspected major mechanism of the suicidal vulnerability, in suicidal depressed elderly. METHODS: We compared 20 currently depressed patients, aged 65 and older who recently attempted suicide to 20 elderly subjects with a current depression but no personal history of suicide attempt and 20 elderly controls. Using an extensive neuropsychological battery, we particularly examined different aspects of cognitive inhibition: access to relevant information (using the Reading with distraction task), suppression of no longer relevant information (Trail Making Test, Rule Shift Cards), and restraint of cognitive resources to relevant information (Stroop test, Hayling Sentence Completion test, Go/No-Go). RESULTS: After adjustment for age, intensity of depression, Mini-Mental State Examination score and speed of information processing, suicidal depressed elderly showed significant impairments in all 3 domains of cognitive inhibition in comparison to both control groups. LIMITATIONS: Our results need replication in a larger sample size. CONCLUSIONS: Our study suggests that the inability to inhibit neutral information access to working memory, restrain and delete irrelevant information may impair the patient's capacity to respond adequately to stressful situations subsequently leading to an increased risk of suicidal behavior during late-life depression. Interventions may be developed to specifically target cognitive impairment in the prevention of suicide in depressed elderly.

Alertness can be improved by an interaction between orienting attention and alerting attention in schizophrenia.

BACKGROUND: Attention is impaired in schizophrenia. Early attention components include orienting and alerting, as well as executive control networks. Previous studies have shown mainly executive control deficits, while few of them found orienting and alerting abnormalities. Here we explore the different attentive networks, their modulation and interactions in patients with schizophrenia. METHODS: Twenty-one schizophrenic patients (DSMIV), compared to 21 controls, performed a modified version of the Attention Network Task, in which an orienting paradigm (with valid, invalid and no cues) was combined with a flanker task (congruent/incongruent) and an alerting signal (tone/no tone), to assess orienting, executive control and alerting networks independently. RESULTS: Patients showed an abnormal alerting effect and slower overall reaction time compared to controls. Moreover, there was an interaction between orienting and alerting: patients are helped more than controls by the alerting signal in a valid orientation to solve the incongruent condition. CONCLUSION: These results suggest that patients with schizophrenia have altered alerting abilities. However, the orienting and alerting cues interact to improve their attention performance in the resolution of conflict, creating possibilities for cognitive remediation strategies.

A critical review of the contribution of eye movement recordings to the neuropsychology of obsessive compulsive disorder.

OBJECTIVE: Dysfunctions of saccadic and/or smooth pursuit eye movements have been proposed as markers of obsessive compulsive disorder (OCD), but experimental results are inconsistent. The aim of this paper was to review the literature on eye movement dysfunctions in OCD to assess whether or not saccades or smooth pursuit may be used to diagnose and characterize OCD. METHOD: Literature was searched using PubMed, ISI Web of Knowledge, and PsycINFO databases for all studies reporting eye movements in adult patients suffering from OCD. RESULTS: Thirty-three articles were found. As expected, eye movements of the patients with OCD were mostly assessed with simple oculomotor paradigms involving saccadic and/or smooth pursuit control. In contrast to patients with schizophrenia, however, patients with OCD only displayed rather unspecific deficits, namely slight smooth pursuit impairments and longer response latencies on antisaccade tasks. There was no relationship between these deficits and the severity of patients' symptoms. Interestingly, eye movements of the patients with OCD were almost never recorded during more complex cognitive tasks. CONCLUSION: As in schizophrenia and autism, eye movement recordings during more complex tasks might help to better characterize the cognitive deficits associated with OCD. Such recordings may reveal specific OCD-related deficits that could be used as reliable diagnostic and/or classification tools.

Correlations of cerebello-thalamo-prefrontal structure and neurological soft signs in patients with first-episode psychosis.

OBJECTIVE: This study aimed at determining brain structural imaging correlates of neurological soft signs (NSS) in patients suffering from a first-episode psychosis. METHOD: Fifty-two patients with a DSMIV diagnosis of first-episode psychosis (schizophrenia or schizophrenia spectrum disorder) were consecutively included. Subjects were assessed using a standardized neurological examination for motor coordination, motor integration and sensory integration. Anatomical magnetic resonance images (MRI) were analysed in the whole brain using optimized voxel-based morphometry. RESULTS: Neurological soft signs (NSS) total score (P-corrected = 0.013) and motor integration subscore (P-corrected = 0.035) were found to negatively correlate with grey matter structure of the dorsolateral prefrontal cortices. Motor coordination subscore was positively correlated with grey matter structure of the thalami (P-corrected = 0.002) and negatively with white matter structure of the cerebellum (P-corrected = 0.034). The addition of age and gender as covariate yielded similar results. We did not find any correlation between neither sensory integration subscore and grey matter structure nor NSS total score, motor integration subscore and voxel-based morphometry (VBM) white matter structure. CONCLUSION: Structural alteration in the cerebello-thalamo-prefrontal network is associated with neurological soft signs in schizophrenia, a candidate network for 'cognitive dysmetria'.

Association of Disrupted in Schizophrenia 1 (DISC1) missense variants with ultra-resistant schizophrenia.

Three common missense variants of the Disrupted in Schizophrenia 1 (DISC1) gene, rs3738401 (Q264R), rs6675281 (L607F) and rs821616 (S704C), have been variably associated with the risk of schizophrenia. In a case-control study, we examine whether these gene variants are associated with schizophrenia and ultra-resistant schizophrenia (URS) in a population of French Caucasian patients. The URS phenotype is characterized according to stringent criteria as patients who experience no clinical, social and/or occupational remission in spite of treatment with clozapine and at least two periods of treatment with distinct conventional or atypical antipsychotic drugs. We find a significant association between DISC1 missense variants and URS. The association with rs3738401 remains significant after appropriate correction for multiple testing. These results suggest that the DISC1 rs3738401 missense variant is statistically linked with ultra-resistance to antipsychotic treatment.