Isabelle Jaussent

Plasma Osteoprotegerin Is Associated with Mortality in Hemodialysis Patients

Expression of bone proteins resulting from transdifferentiation of vascular smooth muscle cells into osteoblasts suggests that vascular calcifications are a bioactive process. Regulating molecules such as osteoprotegerin (OPG) and receptor activator of NF-kappaB ligand (RANKL) could play a key role in bone-vascular calcification imbalance. This study investigated the contribution of these proteins as well as mineral metabolism disorders in hemodialysis (HD) patient outcome. A total of 185 HD patients were followed up prospectively for 2 yr. In addition to clinical characteristics, mineral metabolism markers as well as OPG and soluble RANKL (sRANKL) were measured at baseline. After 2 yr, survival rates were described with Kaplan-Meier and compared with Cox regression analyses; 50 patients died (27 from cardiovascular diseases). Calcium, phosphate, and calcium x phosphate product were not associated with mortality. Both hyperparathyroidism (parathyroid hormone > or =300 pg/ml) and hypoparathyroidism (parathyroid hormone <150 pg/ml) were poorly associated with all-cause and cardiovascular mortality. By contrast, elevated OPG levels predicted all-cause (relative risk [RR] 2.67; 95% confidence interval [CI] 1.32 to 5.41; P = 0.006) and cardiovascular mortality (RR 3.15; 95% CI 1.14 to 8.69; P = 0.03). Low levels of sRANKL were associated with a protective effect for all-cause mortality (RR 0.45; 95% CI 0.21 to 0.94; P = 0.03). The association of OPG with all-cause mortality was stronger in patients with C-reactive protein > or =12.52 mg/L. In this condition, both highest (RR 5.68; 95% CI 1.48 to 22.73; P = 0.01) and lowest tertiles (RR 5.37; 95% CI 147 to 1968; P = 0.01) significantly predicted poor outcome. These results show that regulating-bone molecules, especially OPG, are strong predictors of mortality in HD patients, suggesting that OPG is a vascular risk factor, in particular in patients who have high C-reactive protein levels. OPG determination therefore should be added to the biologic follow-up of these patients.

Insomnia Symptoms in Older Adults: Associated Factors and Gender Differences

OBJECTIVES the aim of this study was to examine the factors associated with insomnia in community-dwelling elderly as a function of the nature and number of insomnia symptoms (IS), e.g., difficulty with initiating sleep (DIS), difficulty with maintaining sleep (DMS), and early morning awakening (EMA). METHODS is were assessed in a sample of 2,673 men and 3,213 women aged 65 years and older. The participants were administered standardized questionnaires regarding the frequency of IS and other sleep characteristics (snoring, nightmares, sleeping medication, and sleepiness) and various sociodemographic, behavioral and clinical variables, and measures of physical and mental health. RESULTS more than 70% of men and women reported at least one IS, DMS being the most prevalent symptom in both men and women. Women reported more frequently two or three IS, whereas men reported more often only one IS. Multivariate regression analyses stratified by gender showed that men and women shared numerous factors associated with IS, sleeping medication, nightmares, sleepiness, chronic diseases, and depression being independently associated with two or three IS. For both sexes, age was associated with only one IS in all age categories. Loud snoring was strongly associated with increased DMS in men only. High body mass index increased the risk for DIS in men but tended to decrease it in women. In women, hormonal replacement therapy, Mediterranean diet, and caffeine and alcohol intake had a protective effect. CONCLUSION our data suggest that women may have specific predisposition factors of multiple IS, which may involve both behavioral and hormonal factors. Identification and treatment of these risk factors may form the basis of an intervention program for reduction of IS in the elderly.

Excessive sleepiness is predictive of cognitive decline in the elderly.

STUDY OBJECTIVES To examine the association of sleep complaints reported at baseline (insomnia complaints and excessive daytime sleepiness (EDS)) and medication, with cognitive decline in community-dwelling elderly. DESIGN An 8-yr longitudinal study. SETTING The French Three-City Study. PARTICIPANTS There were 4,894 patients without dementia recruited from 3 French cities and having a Mini-Mental Status Examination (MMSE) score ≥ 24 points at baseline. MEASUREMENTS AND RESULTS Questionnaires were used to evaluate insomnia complaints (poor sleep quality (SQ), difficulty in initiating sleep (DIS), difficulty in maintaining sleep (DMS), early morning awakening (EMA)), EDS, and sleep medication at baseline. Cognitive decline was defined as a 4-point reduction in MMSE score during follow-up at 2, 4, and 8 yr. Logistic regression models were adjusted for sociodemographic, behavioral, physical, and mental health variables, and apolipoprotein E genotype. EDS independently increased the risk of cognitive decline (odds ratio (OR) = 1.26, 95% confidence interval (CI) = 1.02-1.56), especially for those patients who also developed dementia during the follow-up period (OR = 1.39, 95% CI = 1.00-1.97). The number of insomnia complaints and DMS were negatively associated with MMSE cognitive decline (OR = 0.77, 95% CI = 0.60-0.98 for 3-4 complaints, OR = 0.81, 95% CI = 0.68-0.96, respectively). The 3 other components of insomnia (SQ, DIS, EMA) were not significantly associated with MMSE cognitive decline. CONCLUSIONS Our results suggest that EDS may be associated independently with the risk of cognitive decline in the elderly population. Such results could have important public health implications because EDS may be an early marker and potentially reversible risk factor of cognitive decline and onset of dementia.

Is it valid to measure suicidal ideation by depression rating scales

OBJECTIVE To date, most researchers rely on suicidal items of scales primarily designed to measure depression severity to capture suicidal ideation (SI). This study aims at investigating how well the suicide item of the clinician rated Hamilton Scale for Depression (HAM-D) and principal factors derived from this scale correlate with SI scores derived from a well validated measure of SI: the Becks scale for SI (SSI). METHOD 281 suicide attempters consecutively hospitalized between 2007 and 2009 were assessed by using the SSI, the HAM-D and the self-report Beck Depression Inventory (BDI). Principal Component Analysis (PCA) was computed to extract main factors. Correlations between these factors, BDIs and HAM-Ds suicide items and the SSI scores were then computed. RESULTS Three components were derived from the PCA. Factor 2 showed a major loading for the HAM-D suicide item. Both the HAM-D suicide item and Factor 2 positively correlated with the SSI total score (both p<0.00001). Moreover, the BDI suicide item highly correlated with the Factor 2 (p<0.001) and the SSI total score (p<0.00001). Finally, the HAM-D suicide item correlated significantly with the number of suicide attempts (p=0.0001) and the age at the first attempt (p=0.002). LIMITATIONS Our sample was heterogeneous and future studies should refine the taxonomy of the suicidal behavior in specific sub-populations. The study design was cross-sectional and replication in a prospective study is needed. CONCLUSION These findings suggest that the use of a single suicide item or a dimensional factor derived from a depression scale might be a valid approach to assess the suicidal ideations. Moreover, the results suggest that clinician rated scales as well as self-report questionnaires are equally valid to do so.

Interaction between BDNF Val66Met and childhood trauma on adult's violent suicide attempt.

Genetic factors, specially those related to serotoninergic activities, and childhood maltreatment have both been implicated in suicidal behaviour (SB). However, little attention has been paid to the possible interaction between genes and childhood maltreatment in the comprehension of SB. Brain‐derived neurotrophic factor (BDNF) plays an important role in the growth of serotoninergic neurons during childhood and therefore is a good candidate for studies on SB. Moreover, decreased levels of BDNF have been found in the prefrontal cortex of suicide victims. In our study we wanted to see if Val66Met (a BDNF functional single‐nucleotide polymorphism) could moderate the effect of childhood maltreatment on the onset, number and violence of SB in a sample of 813 Caucasian suicide attempters. Childhood maltreatment was evaluated using the Childhood Trauma Questionnaire. We used a regression framework to test the interaction between Val66Met and childhood maltreatment. Childhood sexual abuse was associated with violent suicide attempts (SA) in adulthood only among Val/Val individuals and not among Val/Met or Met/Met individuals (P = 0.05). The severity of childhood maltreatment was significantly associated with a higher number of SA and with a younger age at onset of suicide attempt. This result suggests that Val66Met modulates the effect of childhood sexual abuse on the violence of SB. It is proposed that childhood sexual abuse elicits brain structural modifications through BDNF dysfunction and enhances the risk of violent SB in adulthood.

Association of adverse childhood environment and 5-HTTLPR Genotype with late-life depression.

OBJECTIVE Neurobiological and clinical studies suggest that childhood maltreatment may result in functional and structural nervous system changes that predispose the individual to depression. This vulnerability appears to be modulated by a polymorphism in the serotonin gene-linked promoter region (5-HTTLPR). Little is known, however, about the persistence of this vulnerability across the life span, although clinical studies of adult populations suggest that gene-environment interaction may diminish with aging. METHOD Depressive symptomatology and adverse and protective childhood events were examined in a population of 942 persons aged 65 years and older, taking into account sociodemographic characteristics and proximal competing causes of depression (widowhood, recent life events, vascular and neurologic disorder, and disability). Subjects were recruited between March 1999 and February 2001 and were diagnosed as depressed if they met 1 of 3 criteria: a diagnosis of major depression on the Mini-International Neuropsychiatric Interview, a score higher than 16 on the Center for Epidemiologic Studies-Depression Scale, or current treatment with an antidepressant. RESULTS Exposure to traumatic events in childhood doubled the risk of late-life depression and increased the risk of repeated episodes. Not all events were found to be pathogenic; significant risk was associated with excessive sharing of parental problems, poverty or financial difficulties, mental disorder in parents, excessive physical punishment, verbal abuse from parents, humiliation, and mistreatment by an adult outside the family. Interactions were observed between the 5-HTTLPR long (L) allele, poverty, and excessive sharing of parental problems. CONCLUSIONS Certain types of childhood trauma continue to constitute risk factors for depression in old age, outweighing more proximal causes. Gene environment vulnerability interaction is linked in older age to the L-carrying genotype, modulating the effects of general environmental conditions rather than aggressive acts on the individual, perhaps due to increased cardiac reactivity.

The Influence of Four Serotonin-Related Genes on Decision-Making in Suicide Attempters

Genetic factors have been associated with the vulnerability to suicidal behavior. We previously reported decision‐making impairment in suicide attempters and hypothesized that these cognitive alterations may represent an endophenotype of suicidal behavior. In this study, we aimed to investigate the influence of four serotonin‐related genes relevant to suicidal behavior on decision‐making, in a large population of suicide attempters. The Iowa Gambling Task was used to assess decision‐making in 168 patients with a personal history of attempted suicide. Patients were genotyped for four serotonergic polymorphisms: 5HTTLPR, TPH1 A218C, MAOA u‐VNTR, and TPH2 rs1118997. Patients carrying the 5HTTLPR‐ll and ‐sl, TPH1‐CC and ‐AC, MAOA‐HH (in women) and TPH2‐AA genotypes significantly improved their performance during the task, suggesting a genetic modulation of the learning process required for advantageous decision‐making. In contrast, genotypes previously associated with a higher risk of suicidal behavior, a greater sensitivity to the environment and a higher propensity to negative feelings are those conferring poorer learning abilities. We hypothesize that the influence of genetic factors on the vulnerability to suicidal behavior may partly be achieved through their modulation of decision‐making and particularly its learning component.

Recurrent hypersomnia: a review of 339 cases.

Based on 339 cases this review identifies, quantifies and compares 4 clinical forms of recurrent hypersomnia (1) Kleine-Levin syndrome (KLS) (239 cases), (2) Kleine-Levin syndrome without compulsive eating (KLS WOCE) (54 cases), (3) Menstrual related hypersomnia (MRH) (18 cases) and Recurrent hypersomnia with comorbidity (RHC) (28 cases). A second part of the review considers the main current issues on recurrent hypersomnia: the predisposing factors, including a window on family cases; the pathophysiology based on clinical patterns, neuroimaging data, neuropathological examinations and cerebrospinal fluid (CSF) hypocretin-1 measurements; the issues of recurrence and of a possible disruption of the circadian timing system; the relationships between recurrent hypersomnia and mood disorders; and a note on the atypical Kleine-Levin syndrome. The main outcomes of this study are a clear nosologic distinction of the different forms of recurrent hypersomnia, the finding that the prevalence of familial cases of KLS is in the same range as in narcolepsy, the suggestion of the possible involvement of a large set of cortical and subcortical structures in recurrent hypersomnia and some clues in favour of a relationship between recurrent hypersomnia and mood disorders.

Childhood trauma as a correlative factor of suicidal behavior via aggression traits. Similar results in an Italian and in a French sample

BACKGROUND AND OBJECTIVE Childhood trauma and aggressive traits are considered risk factors for suicidal behavior. The hypothesis we aimed to test in this study was the existence of an association between childhood trauma and aggression in two distinct samples of Italian and French suicide attempters. METHOD Study participants comprise 587 subjects with different psychiatric diagnoses according to DSM-IV-TR criteria. Three different samples were analyzed and compared: a group of French suicide attempters (N=396; mean age 40.47 SD=13.52; M/F: 110/286); a group of Italian suicide attempters (N=103; mean age 38.60 SD=12.04; M/F 27/76) and an Italian psychiatric comparison group (N=88; mean age: 41.49 SD=12.05; M/F; 37/51). Patients were interviewed with the Brown-Goodwin Assessment for Lifetime History of Aggression (BGLHA) and the Childhood Trauma Questionnaire (CTQ) 34-items for Italian data and 28-items for French data. RESULTS When compared with the comparison group, Italian suicide attempters had significantly higher scores on the BGLHA scale and reported higher scores on the CTQ scores for physical abuse, sexual abuse and emotional abuse. Significant correlations between childhood trauma and aggression were found in both groups, Italian and French, of suicide attempters. CONCLUSION The hypothesis tested was supported as psychiatric patients who had attempted suicide reported significantly more childhood trauma and aggression. Significant correlations were found between aggressive behavior, and childhood trauma in suicidal patients. This finding was replicated in two independently recruited samples in two countries with different prevalence of suicidal behavior.

Determinants of excessive daytime sleepiness in a French community-dwelling elderly population

Epidemiological studies have suggested that excessive daytime sleepiness (EDS) is associated with depression, but the association between EDS and other psychiatric disorders has not been investigated. The aim of this study was to investigate the association of EDS with a wide range of psychiatric disorders and health‐related conditions in the elderly population. Two thousand two hundred and fifty‐nine non‐institutionalised persons aged 65‐years and over randomly recruited from the Montpellier district, France, completed the Epworth Sleepiness Scale (ESS). Psychiatric status was assessed by the Mini International Neuropsychiatric Interview and demographic and other health information was obtained. This cross‐sectional study was conducted from March 1999 to February 2001. Men were significantly more likely to report EDS (ESS score>10) compared with women (12.0% versus 6.0% respectively). EDS was significantly associated in univariate analyses with chronic diseases, early awakening, snoring, severity of depression and lifetime prevalence of manic and hypomanic episodes. A multivariate analysis revealed that the lifetime prevalence of manic and hypomanic episodes, snoring and gender (male) were independently associated with EDS. No independent association with other psychiatric disorders was found.