Cerebellar volume in schizophrenia and bipolar I disorder with and without psychotic features.

OBJECTIVE: There is growing evidence that cerebellum plays a crucial role in cognition and emotional regulation. Cerebellum is likely to be involved in the physiopathology of both bipolar disorder and schizophrenia. The objective of our study was to compare cerebellar size between patients with bipolar disorder, patients with schizophrenia, and healthy controls in a multicenter sample. In addition, we studied the influence of psychotic features on cerebellar size in patients with bipolar disorder. METHOD: One hundred and fifteen patients with bipolar I disorder, 32 patients with schizophrenia, and 52 healthy controls underwent 3 Tesla MRI. Automated segmentation of cerebellum was performed using FreeSurfer software. Volumes of cerebellar cortex and white matter were extracted. Analyses of covariance were conducted, and age, sex, and intracranial volume were considered as covariates. RESULTS: Bilateral cerebellar cortical volumes were smaller in patients with schizophrenia compared with patients with bipolar I disorder and healthy controls. We found no significant difference of cerebellar volume between bipolar patients with and without psychotic features. No change was evidenced in white matter. CONCLUSION: Our results suggest that reduction in cerebellar cortical volume is specific to schizophrenia. Cerebellar dysfunction in bipolar disorder, if present, appears to be more subtle than a reduction in cerebellar volume.

The serotonin-N-acetylserotonin-melatonin pathway as a biomarker for autism spectrum disorders.

Elevated whole-blood serotonin and decreased plasma melatonin (a circadian synchronizer hormone that derives from serotonin) have been reported independently in patients with autism spectrum disorders (ASDs). Here, we explored, in parallel, serotonin, melatonin and the intermediate N-acetylserotonin (NAS) in a large cohort of patients with ASD and their relatives. We then investigated the clinical correlates of these biochemical parameters. Whole-blood serotonin, platelet NAS and plasma melatonin were assessed in 278 patients with ASD, their 506 first-degree relatives (129 unaffected siblings, 199 mothers and 178 fathers) and 416 sex- and age-matched controls. We confirmed the previously reported hyperserotonemia in ASD (40% (35-46%) of patients), as well as the deficit in melatonin (51% (45-57%)), taking as a threshold the 95th or 5th percentile of the control group, respectively. In addition, this study reveals an increase of NAS (47% (41-54%) of patients) in platelets, pointing to a disruption of the serotonin-NAS-melatonin pathway in ASD. Biochemical impairments were also observed in the first-degree relatives of patients. A score combining impairments of serotonin, NAS and melatonin distinguished between patients and controls with a sensitivity of 80% and a specificity of 85%. In patients the melatonin deficit was only significantly associated with insomnia. Impairments of melatonin synthesis in ASD may be linked with decreased 14-3-3 proteins. Although ASDs are highly heterogeneous, disruption of the serotonin-NAS-melatonin pathway is a very frequent trait in patients and may represent a useful biomarker for a large subgroup of individuals with ASD.

Molecular characteristics of Human Endogenous Retrovirus type-W in schizophrenia and bipolar disorder.

Epidemiological and genome-wide association studies of severe psychiatric disorders such as schizophrenia (SZ) and bipolar disorder (BD), suggest complex interactions between multiple genetic elements and environmental factors. The involvement of genetic elements such as Human Endogenous Retroviruses type 'W' family (HERV-W) has consistently been associated with SZ. HERV-W envelope gene (env) is activated by environmental factors and encodes a protein displaying inflammation and neurotoxicity. The present study addressed the molecular characteristics of HERV-W env in SZ and BD. Hundred and thirty-six patients, 91 with BD, 45 with SZ and 73 healthy controls (HC) were included. HERV-W env transcription was found to be elevated in BD (P<10-4) and in SZ (P=0.012) as compared with HC, but with higher values in BD than in SZ group (P<0.01). The corresponding DNA copy number was paradoxically lower in the genome of patients with BD (P=0.0016) or SZ (P<0.0003) than in HC. Differences in nucleotide sequence of HERV-W env were found between patients with SZ and BD as compared with HC, as well as between SZ and BD. The molecular characteristics of HERV-W env also differ from what was observed in Multiple Sclerosis (MS) and may represent distinct features of the genome of patients with BD and SZ. The seroprevalence for Toxoplasma gondii yielded low but significant association with HERV-W transcriptional level in a subgroup of BD and SZ, suggesting a potential role in particular patients. A global hypothesis of mechanisms inducing such major psychoses is discussed, placing HERV-W at the crossroads between environmental, genetic and immunological factors. Thus, particular infections would act as activators of HERV-W elements in earliest life, resulting in the production of an HERV-W envelope protein, which then stimulates pro-inflammatory and neurotoxic cascades. This hypothesis needs to be further explored as it may yield major changes in our understanding and treatment of severe psychotic disorders.

Cardiometabolic determinants of mortality in a geriatric population: is there a "reverse metabolic syndrome"?

AIMS: Diabetes or insulin resistance, overweight, arterial hypertension, and dyslipidaemia are recognized risk factors for cardiovascular (CV) disease. However, their predictive value and hierarchy in elderly subjects remain uncertain. METHODS: We investigated the impact of cardiometabolic risk factors on mortality in a prospective cohort study of 331 elderly high-risk subjects (mean age+/-SD: 85+/-7 years). RESULTS: Two-year total mortality was predicted by age, diabetes, low BMI, low diastolic blood pressure (DBP), low total and HDL cholesterol, and previous CV events. The effect of diabetes was explained by previous CV events. In non-diabetic subjects, mortality was predicted by high insulin sensitivity, determined by HOMA-IR and QUICKI indices. In multivariate analyses, the strongest mortality predictors were low BMI, low HDL cholesterol and previous myocardial infarction. Albumin, a marker of malnutrition, was associated with blood pressure, total and HDL cholesterol, and HOMA-IR. The inflammation marker CRP was associated with low total and HDL cholesterol, and high HOMA-IR. CONCLUSION: In very old patients, low BMI, low DBP, low total and HDL cholesterol, and high insulin sensitivity predict total mortality, indicating a "reverse metabolic syndrome" that is probably attributable to malnutrition and/or chronic disorders. These inverse associations limit the relevance of conventional risk factors. Previous CV events and HDL cholesterol remain strong predictors of mortality. Future studies should determine if and when the prevention and treatment of malnutrition in the elderly should be incorporated into conventional CV prevention.

[Body composition and left ventricular geometry]. / Composition corporelle et géométrie ventriculaire.

Left ventricular mass and cardiac output are, particularly in obesity, correlated with fat free body mass. We assessed the relationship between ventricular geometry and fat body mass in treated hypertensives with or without normalization of blood pressure We investigated 175 patients (age: 57 +/- 15 years, M/F: 111/64, Mean blood pressure (MBP): 111 +/- 18 mmHg, BMI: 27.02 +/- 3.70 kg/m2: 20.3-39.6 kg/m2) with measure of body composition (impedancemetry Analycor2) and echographic left ventricular mass (adjusted to height2.7: mass2.7). Multiple correlation with adjustment to age and MBP were performed in men (M) and in women (W). Mass2.7 is correlated with fat mass percentage in men (R partial R: 5.6, p=0.02). LV diastolic diameter is correlated with fat free body mass while interventricular septum is correlated with fat body mass but only in men. In summary, in hypertensives not selected on BMI or BP, fat body mass is weakly correlated to ventricular wall thickness in men, probably mediated by sympathetic tone, while fat free body mass is related to ventricular volume in both gender probably through the water volume particularly in vascular bed. In conclusion, both components of body composition are differently, and weakly, linked to ventricular geometry in hypertensive patients.

[Structure and function of the arteries of very elderly people. The PROTEGER Study (Cardiovascular Prognosis and Therapeutic Optimization in Geriatrics)]. / Structure et fonction des artères des sujets très âgés-l'étude PROTEGER. (PRonostic cardio-vasculaire et Optimisation Thérapeutique En GERiatrie).

The purpose of PROTEGER, a multicenter prospective observational study, was to determine the contribution of hemodynamic, arterial, echocardiographic and biological parameters to the evaluation of individual cardiovascular risk in the elderly. The study included patients aged over 70 years hospitalized in geriatric units with overt cardiovascular disease. Cross sectional analysis of the first 194 subjects included in the study demonstrated a high rate of arterial alterations involving both structure and function. The principal alterations observed were: high pulse pressure despite normal mean systolic and diastolic pressures, frequent and diffuse arterial calcifications, reduced compliance and distensibility, increased thickness, diameter and incremental elastic modulus of the carotid and increased pulse wave velocity. Analysis of monitoring results in the PROTEGER study will demonstrate the role of hemodynamic measurements and arterial alterations in the prediction of cardiovascular risk in hospitalized elderly.

[Measurement of the carotid intima-media thickness. An innovative technique for assessing cardiovascular risk]. / La mesure de l'épaisseur intima-média carotidienne. Une technique innovante d'appréciation du risque cardio-vasculaire.

ASSESSMENT OF CARDIOVASCULAR RISK: Measurement of the intima-media thickness in the carotid artery is optimized by coupling high-resolution ultrasonography with automatic data processing systems, allowing improved precision. Although the optimal site of measurement remains controversial (common carotid, bifurcation, internal carotid), there appears to be a consensus on need for bilateral automatic measurement. The intima-media thickness is considered a marker of atheromatous disease and its diffusion. This parameter probably integrates the deleterious effect of different cardiovascular risk factors accumulated over decades. In addition, several prospective observation studies have reported a positive relationship between measurement of the intima-media thickness of the carotid artery and risk of cardiovascular events (myocardial infarction and stroke). DETECTION AID: Although the results issuing from epidemiology observation studies are still too preliminary, to evaluate the positive and negative predictive value for occurrence of clinical events in relation to different levels of thickness, this simple rapid and noninvasive measurement could be a useful tool for subjects with high cardiovascular risk. PERSPECTIVES: Measurement of arterial parameters, determined by high-resolution ultrasonography, will probably shortly become an integral part of the evaluation strategies for cardiovascular risk. Future comparative studies will provide an assessment of the comparative predictive value of these different parameters (quantitative structural analysis versus quantitative and qualitative analysis of the structure versus structural and functional analysis of the arteries).