[Accelerated telomere erosion in schizophrenia: A literature review]. / Érosion prématurée des télomères et schizophrénies : synthèse et hypothèses.

Schizophrenia is associated with a weighted average of 14.5 years of potential life lost according to a recent meta-analysis. This is partly explained by high rates of suicide and a high prevalence of non-psychiatric comorbidity (cardiovascular diseases, diabetes, cancers…). However, all these causes could not fully explain the loss of life expectancy in people suffering from schizophrenia. Life expectancy has been strongly correlated with telomere length (TL). Telomeres are noncoding structures consisting of DNA TTAGGG tandem repeats and associated proteins located at the end of the chromosomes. Their role is to help preserve genome stability by protecting chromosomal ends from the loss of genetic material. The progressive loss of telomeric material during cell divisions has led researchers to consider telomeres as molecular clocks that measure the number of divisions left until cellular death. The fact that both shorter telomeres and schizophrenia have been associated with a decrease in life expectancy has fueled the interest in the study of TL in schizophrenia. In this article, after a detailed review of the literature on the relationships between telomere length and schizophrenia, we discuss the different pathophysiological mechanisms which might explain this association. Based on this analysis, in the last part of the article we discuss potential research, therapeutic and prevention prospects. To date, the majority of the studies and meta-analyses found a decrease in TL in subjects with schizophrenia compared to control subjects. Conversely, all the studies exploring the TL in subjects suffering from first episode psychosis (FEP) have shown no significant difference from TL in control subjects. This suggests that excessive shortening of telomeres occurs during the course of the disease, thus it seems more probable that schizophrenia (or processes associated with it) affects TL rather than telomere erosion being a cause of the disorder. Several pathophysiological, non-mutually exclusive mechanisms have been proposed to explain the observed data. A first hypothesis to explain the acceleration of the physiological process of telomere erosion in schizophrenia is the activation of inflammation processes and oxidative stress as a consequence of schizophrenia per se. However, it seems more probable that reduced TL may be a result of cumulative exposure to chronic stress related to schizophrenia. Indeed, in healthy individuals a growing body of evidence has linked chronic stress to accelerated shortening of TL. This might explain why telomere erosion is too small to be detected in FEP patients who are younger and have a shorter duration of illness than subjects with schizophrenia. Based on these both explanations, telomere alterations may be considered as a biomarker of illness progression and might be useful for illness staging. Identifying processes associated with TL reduction might improve our understanding of the increased mortality and morbidity in schizophrenia, improve reliability of diagnosis, and hopefully suggest means for prevention and/or treatment. Treatments that prevent exposure and/or vulnerability to stressful life events that ameliorate schizophrenia may also prevent or decelerate telomere erosion. In this perspective, engaging subjects suffering from schizophrenia in a healthy diet and regular activity could be both promising strategies to protect telomere maintenance and improve health span at old age. In addition, the inflammatory process and oxidative stress involved in the physiopathology in at least a subgroup of subjects with schizophrenia could also be responsible for telomere erosion. Thus, an efficient anti-inflammatory therapeutic approach that targets these specific pathways could be of interest in this subgroup to limit telomere erosion. Mindfulness-based stress reduction (MBSR) therapies have been shown to reduce telomere erosion by increasing telomerase activity, although these psychological therapies should be used carefully in psychosis. Finally, advancing our understanding of the relationship between stress, inflammation and TL is of great interest for psychiatric research and for understanding stress effects in this population.

Trends in Partial Disability-Free Life Expectancy between the Ages of 45 and 70 in Canada, 2000-2014.

To better evaluate the benefits of a possible increase in the normal retirement age, this article proposes to examine recent trends in the health status of Canadians between 45 and 70 years of age. Using the Sullivan method, trends from 2000 to 2014 in partial disability-free life expectancy (PDFLE) between the ages of 45 and 70 years are computed. Disability is estimated using attributes of the Health Utility Index correlated with the capacity to work, and is looked at by level of severity. Data from the Canadian Community Health Survey were used to estimate the prevalence of disability. Results reveal a slight increase in partial life expectancy between the ages of 45 and 70, and a larger number of those years spent in poor health since the beginning of the 2000s. Hence, this study brings no evidence in support of the postponement of the normal retirement age if this policy were solely based on gains in life expectancy.

Evolution of life expectancy of patients with Duchenne muscular dystrophy at AFM Yolaine de Kepper centre between 1981 and 2011.

OBJECTIVES: Retrospective study over the last 30 years of life expectancy in patients suffering from Duchenne muscular dystrophy (DMD). Analysis of the role of ventilatory assistance and causes of death. PATIENTS AND METHODS: One hundred and nineteen adult DMD patients were hosted during 1981 to 2011 at AFM Yolaine de Kepper centre, Saint-Georges-sur-Loire, France. Patients' life expectancy was calculated using Kaplan-Meier model. RESULTS: Life expectancy without or with ventilatory assistance was 22.16 and 36.23 years, respectively. Similarly, life expectancy of patients born from 1970 (mostly with ventilatory assistance) was 40.95 years old from 1970 and 25.77 years old before 1970. Causes of death changed. Cardiac origins of death have increased from 8% to 44%. CONCLUSION: Ventilator assistance, in this study mostly through tracheotomy prolongs by more than 15 years life expectancy of DMD patients. It allows conservation of a satisfactory quality of life, and should be systematically proposed to patients.

[Genetic diagnostics of cancer diseases]. / Genetische Diagnostik bei Krebserkrankungen.

Cancer is caused by genetic alterations, but only 10% of the cancer diseases are inherited. The probability for an individual or a family of having inherited cancer, individual consequences of the respective results of genetic testing, as well as its costs and reimbursement by the health insurance must be addressed by expert genetic counseling which at-risk requires special expertise. Identification of a germline mutation which may predispose to a variety of different cancer types allows determination of an individual's specific life time risk in symptomatic as well as in a-symptomatic family members. Identification of the underlying defective gene in heritable cancer disorders also enables optimized preventive and novel therapeutic approaches specifically targeting the underlying molecular pathomechanisms.

Les cancers sont d'origine génétique, mais seulement 10% sont héréditaires, et l'anomalie génétique n'est pas toujours connue. Ces prédispositions peuvent être détectées par des analyses génétiques, à condition que l'assurance maladie prenne en charge les coûts, et que les conséquences individuelles soient discutées en conseil génétique. Le diagnostic prédictif met le patient dans une situation particulière. En effet, la découverte d'une prédisposition héréditaire à un cancer permet d'évaluer l'espérance de vie, aussi bien pour les malades que pour les porteurs sains de la mutation. Par ailleurs, la détection du défaut génétique permet d'optimiser la prise en charge du patient et ainsi prolonger son espérance de vie. Enfin, la connaissance des mécanismes pathogènes sous-jacents ouvre de nouvelles approches thérapeutiques adaptées à chacun.