Lore Brunel

Chronic Peripheral Inflammation is Associated With Cognitive Impairment in Schizophrenia: Results From the Multicentric FACE-SZ Dataset

OBJECTIVES Inflammation, measured by abnormal blood C-reactive protein (CRP) level, has been described in schizophrenia (SZ), being inconsistently related to impaired cognitive functions. The aim of the present study is to investigate cognitive impairment associated with abnormal CRP levels in a large multi-centric sample of community-dwelling SZ patients, using a comprehensive neuropsychological battery. METHOD Three hundred sixty-nine community-dwelling stable SZ subjects (76.2% men, mean age 32.7 y) were included and tested with a comprehensive battery of neuropsychological tests. Abnormal CRP level was defined as >3mg/L. RESULTS Multiple factor analysis revealed that abnormal CRP levels, found in 104 patients (28.2%), were associated with impaired General Intellectual Ability and Abstract Reasoning (aOR = 0.56, 95% CI 0.35-0.90, P = .014), independently of age, sex, education level, psychotic symptomatology, treatments, and addiction comorbidities. Abnormal CRP levels were also associated with the decline of all components of working memory (respectively effect size [ES] = 0.25, P = .033; ES = 0.27, P = .04; ES = 0.33, P = .006; and ES = 0.38, P = .004) and a wide range of other impaired cognitive functions, including memory (ES = 0.26, P = .026), learning abilities (ES = 0.28, P = .035), semantic memory (ES = 0.26, P = .026), mental flexibility (ES = 0.26, P = .044), visual attention (ES = 0.23, P = .004) and speed of processing (ES = 0.23, P = .043). CONCLUSION Our results suggest that abnormal CRP level is associated with cognitive impairment in SZ. Evaluating the effectiveness of neuroprotective anti-inflammatory strategies is needed in order to prevent cognitive impairment in SZ.

Metabolic syndrome, abdominal obesity and hyperuricemia in schizophrenia: Results from the FACE-SZ cohort

OBJECTIVE Abdominal obesity was suggested to be a better predictor than Metabolic Syndrome (MetS) for cardiovascular mortality, however this is has not been extensively studied in schizophrenia. Hyperuricemia (HU) was also suggested to be both an independent risk factor for greater somatic comorbidity and a global metabolic stress marker in patients with schizophrenia. The aim of this study was to estimate the prevalence of MetS, abdominal obesity and HU, to examine the association between metabolic parameters with HU in a cohort of French patients with schizophrenia or schizo-affective disorder (SZ), and to estimate the prevalence rates of treatment of cardio-vascular risk factors. METHOD 240 SZ patients (age=31.4years, male gender 74.3%) were systematically included. Metabolic syndrome was defined according to the International Diabetes Federation and HU if serum uric acid level was above 360μmol/L. RESULTS MetS, abdominal obesity and HU were found respectively in 24.2%, 21.3% and 19.6% of patients. In terms of risk factors, multiple logistic regression showed that after taking into account the potential confounders, the risk for HU was higher in males (OR=5.9, IC95 [1.7-21.4]) and in subjects with high waist circumference (OR=3.1, IC95 [1.1-8.3]) or hypertriglyceridemia (OR=4.9, IC95 [1.9-13]). No association with hypertension, low HDL cholesterol or high fasting glucose was observed. Only 10% of patients with hypertension received a specific treatment, 18% for high fasting glucose and 8% for dyslipidemia. CONCLUSIONS The prevalence of MetS, abdominal obesity and hyperuricemia is elevated in French patients with schizophrenia, all of which are considerably under-diagnosed and undertreated. HU is strongly associated with abdominal obesity but not with psychiatric symptomatology.

(Mis)use of Prescribed Stimulants in the Medical Student Community: Motives and Behaviors: A Population-Based Cross-Sectional Study

AbstractThe aim of this study was to estimate the prevalence of psychostimulant use in the French medical community and their motives.A population-based cross-sectional study using a self-administered online survey was done.A total of 1718 French students and physicians (mean age, 26.84±7.19 years, 37.1% men) were included. Self-reported lifetime use, motives, socio-demographic and academic features for over the counter (OTC), medically prescribed (MPP), and illicit (IP) psychostimulant users were reported. Lifetime prevalence of psychostimulant use was 33% (29.7% for OTC, 6.7% for MPP, and 5.2% for IP). OTC consumption mainly aimed at increasing academic performance and wakefulness during competitive exams preparation. OTC consumption started early and was predictive of later MPP use. Corticoids were the most frequently consumed MPP (4.5%) before methylphenidate and modafinil. Motives for MPP consumption were increased academic performance, concentration, memory, and wakefulness.Psychostimulant use is common among French medical community. Our results suggest that restrictions on methylphenidate and modafinil prescriptions are effective at limiting their use. However, these restrictions may explain the observed rates of corticoids consumption, which raise a new public health problem, given that corticoids may have severe side effects.

Akathisia: prevalence and risk factors in a community-dwelling sample of patients with schizophrenia. Results from the FACE-SZ dataset.

The main objective of this study was to determine the prevalence of akathisia in a community-dwelling sample of patients with schizophrenia, and to determine the effects of treatments and the clinical variables associated with akathisia. 372 patients with schizophrenia or schizoaffective disorder were systematically included in the network of FondaMental Expert Center for Schizophrenia and assessed with validated scales. Akathisia was measured with the Barnes Akathisia Scale (BAS). Ongoing psychotropic treatment was recorded. The global prevalence of akathisia (as defined by a score of 2 or more on the global akathisia subscale of the BAS) in our sample was 18.5%. Patients who received antipsychotic polytherapy were at higher risk of akathisia and this result remained significant (adjusted odd ratio=2.04, p=.025) after controlling the influence of age, gender, level of education, level of psychotic symptoms, substance use comorbidities, current administration of antidepressant, anticholinergic drugs, benzodiazepines, and daily-administered antipsychotic dose. The combination of second-generation antipsychotics was associated with a 3-fold risk of akathisia compared to second-generation antipsychotics used in monotherapy. Our results indicate that antipsychotic polytherapy should be at best avoided and suggest that monotherapy should be recommended in cases of akathisia. Long-term administration of benzodiazepines or anticholinergic drugs does not seem to be advisable in cases of akathisia, given the potential side effects of these medications.

Childhood trauma, depression and negative symptoms are independently associated with impaired quality of life in schizophrenia. Results from the national FACE-SZ cohort

OBJECTIVES Depression and negative symptoms have been associated with impaired Quality of life (QoL) in schizophrenia (SZ). However, childhood trauma may influence both QoL and depression in SZ patients, with consequences for the management of impaired QoL in SZ patients. The aim of the present study was to determine if childhood trauma was associated with impaired QoL in schizophrenia. METHOD A sample of 544 community-dwelling stabilized SZ patients enrolled in FACE-SZ cohort were utilized in this study (74.1% males, mean aged 32.3years, mean illness duration 10.6years). QoL was self-reported with the S-QoL18 questionnaire. Childhood trauma was self-reported with the Childhood Trauma Questionnaire. Depression was measured by the Calgary Depression Rating Scale for Schizophrenia. Psychotic severity was measured by the Positive and Negative Syndrome Scale for Schizophrenia (PANSS). Other clinical factors, treatments, comorbidities, functioning and sociodemographical variables were also recorded, with validated scales. RESULTS Overall, 151 participants (27.8%) had a current major depressive episode and 406 (82.5%) reported at least one episode of historical childhood trauma. In multivariate analyses, lower QoL total score was associated with a history of childhood trauma (β=-0.21, p<0.0001), psychotic negative symptoms (β=-0.11, p=0.04), current depression (β=-0.0.38, p<0.0001) and male gender (β=-0.16, p<0.0001). CONCLUSION Impaired QoL is independently associated with negative symptoms, depression and childhood trauma in schizophrenia.

Disparities in suicide mortality trends between United States of America and 25 European countries: retrospective analysis of WHO mortality database

The objective was to examine changes in temporal trends in suicide mortality in 26 Western countries by retrospective trend analysis of the WHO mortality database on causes of deaths. From 1990 to 2010, there was a median reduction in suicide mortality of 22.7%, ranging from a 46% reduction in Estonia to a 26.2% increase in Romania. Suicide mortality decreased by ≥20% in 15 countries, and the reduction tended to be greater in countries with higher mortality in 1990. In most of the central European countries mortality strongly declined. The median changes in the age groups were −25.3% (range −62.9% to 72.6%) in people aged 15–24 years, −36.9% (−60.5% to 32.4%) in 25–34 years, −3.6% (−57.1% to 92%) in 35–54 years, −12.2% (−37% to 65,7%) in 55–74 years and −16.1% (−54.5% to 166.7%) in ≥75 years. Suicide prevention programs in youths and in the elderly seem to be effective (at least in females for the elderly) and efforts should be pursued in this way. However, suicide mortality of the people aged 35–54 years has increased in half of the studied countries between 1990 and 2010. Public policies should further orientate their efforts toward this population.

A Bayesian framework systematic review and meta-analysis of anesthetic agents effectiveness/tolerability profile in electroconvulsive therapy for major depression

The aim of this study was to assess the efficacy and tolerability/acceptability of 6 anesthetic agents in ECT for depressive disorders. We systematically reviewed 14 double-blind randomized controlled trials (610 participants). Efficacy was measured by the mean scores on validated depression scales at 6 ECT (or the nearest score if not available), number of responders at the end of treatment and seizure duration. The acceptability was measured by the proportion of patients who dropped out of the allocated treatment, and the tolerability by the number of serious adverse events and post-treatment cognition assessment. After excluding the trials responsible for heterogeneity, depression scores of patients who were administered methohexital were found to be significantly more improved than those who received propofol (p = 0.001). On the contrary, those who were administered propofol had lower depression scores than those with thiopental at the end of treatment (p = 0.002). Compared to propofol, methohexital was found to be significantly associated with higher seizure duration (p = 0.018). No difference was found for the acceptability profile (all p > 0.05). In summary, ketamine and methohexital may be preferred to propofol or thiopental in regard of effectiveness in depression scores and increased seizure duration. Further studies are warranted to compare ketamine and methohexital.

Do the treasures of 'big data' combined with behavioural intervention therapies contain the key to the mystery of large psychiatric issues?

‘The August issue of Acta Psychiatrica Scandinavica brings an overview of psychiatric register research through more than half a century (1). The authors end the article by recommending revitalizing the small clinical register. They also recommend a further investigation and development of ‘big data’ research, a possibility becoming realistic due to progress in electronic technology. The article is accompanied by an editorial comment by Robert Stewart discussing further the concept of big data’ (2). ‘Big data’ is a collection of a large and complex data sets complicated to process using on-hand database management tools or traditional data processing applications. Many articles described the challenges big data has raised using the ‘three V’s’: volume, velocity, and variety. The world’s technological per capita capacity to store information has roughly doubled every 40 months since the 1980s to 2012, 2.5 data exabytes (2.5 9 10) were created each day. Miscellaneous applications of big data extractions have been suggested, in areas as diverse as marketing, finance, insurance, transport and security. Big data could save billions of dollars for healthcare system, by automated procedures for refund, detecting fraud as well as by improving prevention, dynamic epidemiology, diagnosis and treatment monitoring. Therefore, big data is a tremendous opportunity for health care in psychiatry. Big data alone may be used from a substantially observational point of view, but it could be combined with behavioural intervention therapies (BITs) such as Web-based and mobile interventions, which permit the aggregation of big amount of data across large numbers of users (e.g., usage data, patient workflow, sensor readings). The following are examples in which big data (alone or combined to BITs) could be used in research, help patients and psychiatrists in their practice, as well as reduce costs in mental health.

Nicotine dependence is associated with depression and childhood trauma in smokers with schizophrenia: results from the FACE-SZ dataset

In a perspective of personalized care for smoking cessation, a better clinical characterization of smokers with schizophrenia (SZ) is needed. The objective of this study was to determine the clinical characteristics of SZ smokers with severe nicotine (NIC) dependence. 240 stabilized community-dwelling SZ smokers (mean age = 31.9 years, 80.4% male gender) were consecutively included in the network of the FondaMental Expert Centers for Schizophrenia and assessed with validated scales. Severe NIC dependence was defined by a Fagerstrom questionnaire score ≥ 7. Depression was defined by a Calgary score ≥ 6. Childhood trauma was self-reported by the Childhood Trauma Questionnaire score (CTQ). Ongoing psychotropic treatment was recorded. Severe NIC dependence was identified in 83 subjects (34.6%), depression in 60 (26.3%). 44 (22.3%) subjects were treated by antidepressants. In a multivariate model, severe NIC dependence remained associated with depression (OR = 3.2, p = 0.006), male gender (OR = 4.5, p = 0.009) and more slightly with childhood trauma (OR = 1.03, p = 0.044), independently of socio-demographic characteristics, psychotic symptoms severity, psychotropic treatments and alcohol disorder. NIC dependence was independently and strongly associated with, respectively, depression and male gender in schizophrenia, and only slightly with history of childhood trauma. Based on these results, the care of both nicotine dependence and depression should be evaluated for an effective smoking cessation intervention in schizophrenia.

Differential effects of childhood trauma and cannabis use disorders in patients suffering from schizophrenia

BACKGROUND Childhood trauma (CT) and cannabis use are both environmental and modifier risk factors for schizophrenia. However, little is known about how they interact in schizophrenia. We examined the main effect of each of these two environmental factors on the clinical expression of the disease using a large set of variables, and we tested whether and how cannabis and CT interact to influence the course and the presentation of the illness. METHODS A sample of 366 patients who met the DSM-IV-TR criteria for schizophrenia was recruited through the FACE-SCZ (Fondamental Advanced Centre of Expertise - Schizophrenia) network. Patients completed a large standardized clinical evaluation including Structured Clinical Interview for DSM Disorders-I (SCID-I), Positive and Negative Symptoms Scale (PANSS), Columbia-Suicide Severity Rating Scale (C-SSRS), Global Assessment of Functioning (GAF), Short-Quality of Life-18 (S-QoL-18), and Medication Adherence Rating Scale (MARS). We assessed CT with the Childhood Trauma Questionnaire and cannabis status with SCID-I. RESULTS CT significantly predicted the number of hospitalizations, GAF, and S-QoL-18 scores, as well as the PANSS total, positive, excitement, and emotional distress scores. Cannabis use disorders significantly predicted age of onset, and MARS. There was no significant interaction between CT and cannabis use disorders. However, we found evidence of a correlation between these two risk factors. CONCLUSIONS CT and cannabis both have differential deleterious effects on clinical and functional outcomes in patients with schizophrenia. Our results highlight the need to systematically assess the presence of these risk factors and adopt suitable therapeutic interventions.