Meta-analysis of genome-wide association data identifies a risk locus for major mood disorders on 3p21.1.

The major mood disorders, which include bipolar disorder and major depressive disorder (MDD), are considered heritable traits, although previous genetic association studies have had limited success in robustly identifying risk loci. We performed a meta-analysis of five case-control cohorts for major mood disorder, including over 13,600 individuals genotyped on high-density SNP arrays. We identified SNPs at 3p21.1 associated with major mood disorders (rs2251219, P = 3.63 x 10(-8); odds ratio = 0.87; 95% confidence interval, 0.83-0.92), with supportive evidence for association observed in two out of three independent replication cohorts. These results provide an example of a shared genetic susceptibility locus for bipolar disorder and MDD.

Strategies of emotion regulation in adolescents and young adults with substance dependence or eating disorders

Some authors argue that both substance dependence and eating disorders should be considered as dependent behaviours. Similarities and differences between these disorders, however, remain unclear. This study compares processes of emotion regulation in adolescents and young adults (15 to 25 years old) with substance dependence (SD) or eating disorders (ED). One hundred and thirteen SD, 50 ED and 86 non-clinical subjects (NC), recruited in four French and Swiss locations, completed a self-report questionnaire of emotion regulation strategies. This questionnaire addresses the subjects' relationships, concerning past and present family, and refers to Main's (1990) concept of primary strategy (balanced activation and deactivation of attachment behaviours), and of secondary strategies (hyperactivation or excessive deactivation of the attachment system). Participants were also questioned in structured interviews, about life events and DSM-IV classification criteria. SD reported more adverse events than ED and NC. SD and ED reported using fewer primary strategies than NC, and SD had secondary strategies that were different from those of ED. Patients with eating disorders reported more hyperactivation, and SD reported more deactivation of the attachment system. It is hypothesized that while subjects with SD and ED have in common poorly regulated strategies, they differ in the way they process emotion or relationship-related information.

The tangible common denominator of substance use disorders: a reply to commentaries to Rehm et al. (2013a).

In response to our suggestion to define substance use disorders via 'heavy use over time', theoretical and conceptual issues, measurement problems and implications for stigma and clinical practice were raised. With respect to theoretical and conceptual issues, no other criterion has been shown, which would improve the definition. Moreover, heavy use over time is shown to be highly correlated with number of criteria in current DSM-5. Measurement of heavy use over time is simple and while there will be some underestimation or misrepresentation of actual levels in clinical practice, this is not different from the status quo and measurement of current criteria. As regards to stigma, research has shown that a truly dimensional concept can help reduce stigma. In conclusion, 'heavy use over time' as a tangible common denominator should be seriously considered as definition for substance use disorder.

Reliability and validity of the Alcohol Use Disorders Identification Test (AUDIT) imbedded within a general health risk screening questionnaire: results of a survey in 332 primary care patients.

BACKGROUND: Self-administered, general health risk screening questionnaires that are administered while patients wait in the doctor's office may be a reasonable and timesaving approach to address the requirements of preventive medicine in a typical 10-min medical visit. The psychometric characteristics of the Alcohol Use Disorders Identification Test (AUDIT) incorporated within a health questionnaire (H-AUDIT) have not been examined. METHODS: The reliability and validity of the self-administered AUDIT were compared between the H-AUDIT and the AUDIT used as a single scale (S-AUDIT) in 332 primary care patients. RESULTS: No major demographic or alcohol use characteristics were found between the 166 subjects who completed the H-AUDIT and the 166 individuals who completed the S-AUDIT. The test-retest reliability of the 166 subjects who completed the H-AUDIT [estimated by Spearman correlation coefficient at a 6-week interval (0.88), internal consistency (total correlation coefficients for all items ranged from 0.38 to 0.69; Cronbach alpha index 0.85), and the sensitivity and specificity of the H-AUDIT were used to identify at-risk drinkers' areas under receiver operating characteristic (0.77) and alcohol-dependent subjects' areas under receiver operating characteristic (0.89)] was similar to the same measurements obtained with the 166 individuals who completed the S-AUDIT. CONCLUSIONS: The AUDIT incorporated in a health risk screening questionnaire is a reliable and valid self-administered instrument to identify at-risk drinkers and alcohol-dependent individuals in primary care settings.

Disorders of pupillary structure and function.

Neurologists are frequently consulted because of a pupillary abnormality. An unequal size of the pupils, an unusual shape, white colored pupils, or a poorly reactive pupil are common reasons for referral. A directed history and careful observation of the iris and pupil movements can bear out ocular pathology such as congenital or structural anomalies as the cause of abnormal pupils. Thereafter, it is important to evaluate the neurologic causes of anisocoria and poor pupil function. The first part of this article emphasizes pupillary abnormalities frequently encountered in infants and children and discusses some of the more common acquired iris structural defects. The second part focuses on evaluation of lesions in the neural pathways that result in pupillary dysfunction, with particular attention to those conditions having neurologic, systemic, or visual implications.

Trouble dissociatif: une clinique à l'interface de la neurologie et de la psychiatrie [Dissociative disorders: neurologists and psychiatrists working together]

Les troubles dissociatifs se présentent souvent par une clinique neurologique atypique impliquant une démarche diagnostique complexe à l'interface de la neurologie et de la psychiatrie. La restitution du diagnostic aux patients et leur prise en charge nécessitent une étroite collaboration interdisciplinaire. Les connaissances actuelles sont encore limitées, mais ce domaine est enrichi par des études récentes en neurosciences cliniques. Cet article présente les principaux aspects des troubles dissociatifs et formule un concept de prise en charge. Dissociative disorders often have an atypical neurological presentation requiring a complex diagnostic process at the interface between neurology and psychiatry. A strong interdisciplinary collaboration is needed for diagnosis restitution and patient treatment. Current knowledge is still scarce but recent studies in clinical neuroscience enrich this field. This article presents the main aspects of dissociative disorders and suggests a treatment framework

Does lamotrigine use in pregnancy increase orofacial cleft risk relative to other malformations?

OBJECTIVE: To investigate whether first trimester exposure to lamotrigine (LTG) monotherapy is specifically associated with an increased risk of orofacial clefts (OCs) relative to other malformations, in response to a signal regarding increased OC risk. METHODS: Population-based case-control study with malformed controls based on EUROCAT congenital anomaly registers. The study population covered 3.9 million births from 19 registries 1995-2005. Registrations included congenital anomaly among livebirths, stillbirths, and terminations of pregnancy following prenatal diagnosis. Cases were 5,511 nonsyndromic OC registrations, of whom 4,571 were isolated, 1,969 were cleft palate (CP), and 1,532 were isolated CP. Controls were 80,052 nonchromosomal, non-OC registrations. We compared first trimester LTG and antiepileptic drug (AED) use vs nonepileptic non-AED use, for mono and polytherapy, adjusting for maternal age. An additional exploratory analysis compared the observed and expected distribution of malformation types associated with LTG use. RESULTS: There were 72 LTG exposed (40 mono- and 32 polytherapy) registrations. The ORs for LTG monotherapy vs no AED use were 0.67 (95% CI 0.10-2.34) for OC relative to other malformations, 0.80 (95% CI 0.11-2.85) for isolated OC, 0.79 (95% CI 0.03-4.35) for CP, and 1.01 (95% CI 0.03-5.57) for isolated CP. ORs for any AED use vs no AED use were 1.43 (95% CI 1.03-1.93) for OC, 1.21 (95% CI 0.82-1.72) for isolated OC, 2.37 (95% CI 1.54-3.43) for CP, and 1.86 (95% CI 1.07-2.94) for isolated CP. The distribution of other nonchromosomal malformation types with LTG exposure was similar to non-AED exposed. CONCLUSION: We find no evidence of a specific increased risk of isolated orofacial clefts relative to other malformations due to lamotrigine (LTG) monotherapy. Our study is not designed to assess whether there is a generalized increased risk of malformations with LTG exposure.

Pluralized life courses? An exploration of the life trajectories of individuals with psychiatric disorders.

BACKGROUND: : Most of the existing research relating to the life courses of people with psychiatric symptoms focuses on the occurrence and the impact of non-normative events on the onsets of crises; it usually disregards the more regular dimensions of life, such as work, family and intimate partnerships that may be related to the timing and seriousness of psychiatric problems. An additional reason for empirically addressing life trajectories of individuals with psychiatric problems relates to recent changes of family and occupational trajectories in relation to societal trends such as individualization and pluralization of life courses.¦AIM: : This paper explores the life trajectories of 86 individuals under clinical supervision and proposes a typology of their occupational, co-residence and intimacy trajectories. The results are discussed in light of the life-course paradigm.¦METHOD: : A multidimensional optimal matching analysis was performed on a sample of 86 individuals under clinical supervision to create a typology of trajectories. The influence of these trajectories on psychiatric disorders, evaluated using a SCL-90-R questionnaire, was then assessed using linear regression modelling.¦RESULTS: : The typologies of trajectories showed that the patients developed a diversity of life trajectories. Individuals who have developed a standard life course with few institutionalization periods reported more symptoms and distress than individuals with an institutionalized life trajectory.¦CONCLUSION: : The results of this study stress that psychiatric patients are social actors who are influenced by society at large and its ongoing process of change. Therefore, it is essential to take into account the diversity of occupational and family trajectories when dealing with individuals in therapeutic settings.

Assessing attachment cognitions and their associations with depression in youth with eating or drug misuse disorders.

The study investigates associations between attachment cognitions and depression symptoms in 71 15-25-year-olds, 26 of whom have eating disorders, and 20 of whom are drug misusers. Attachment cognitions were measured with the CaMir Q-sort, which provides indexes for secure, avoidant, and preoccupied attachment, as well as scores on 13 dimensions. The BDI-13 was used to measure depressive symptomatology. Consistent with the literature, BDI scores were associated with cognitions of preoccupied attachment. They were also related to cognitions of avoidant attachment, confirming Bowlby's theory on defensive exclusion. For participants with eating disorders, depressive symptomatology was related to preoccupation and parental interference, whereas for drug misusers, it was negatively related to security, preoccupation, parental support, and lack of parental concern. These findings help understand how attachment cognitions may participate in depressive symptomatology, namely in youth whose behavior problems may be associated with specific attachment experiences.

Multifaceted roles of peroxisome proliferator-activated receptors (PPARs) at the cellular and whole organism levels.

Chronic disorders, such as obesity, diabetes, inflammation, non-alcoholic fatty liver disease and atherosclerosis, are related to alterations in lipid and glucose metabolism, in which peroxisome proliferator-activated receptors (PPAR)α, PPARβ/δ and PPARγ are involved. These receptors form a subgroup of ligand-activated transcription factors that belong to the nuclear hormone receptor family. This review discusses a selection of novel PPAR functions identified during the last few years. The PPARs regulate processes that are essential for the maintenance of pregnancy and embryonic development. Newly found hepatic functions of PPARα are the mediation of female-specific gene repression and the protection of the liver from oestrogen induced toxicity. PPARα also controls lipid catabolism and is the target of hypolipidaemic drugs, whereas PPARγ controls adipocyte differentiation and regulates lipid storage; it is the target for the insulin sensitising thiazolidinediones used to treat type 2 diabetes. Activation of PPARβ/δ increases lipid catabolism in skeletal muscle, the heart and adipose tissue. In addition, PPARβ/δ ligands prevent weight gain and suppress macrophage derived inflammation. In fact, therapeutic benefits of PPAR ligands have been confirmed in inflammatory and autoimmune diseases, such as encephalomyelitis and inflammatory bowel disease. Furthermore, PPARs promote skin wound repair. PPARα favours skin healing during the inflammatory phase that follows injury, whilst PPARβ/δ enhances keratinocyte survival and migration. Due to their collective functions in skin, PPARs represent a major research target for our understanding of many skin diseases. Taken altogether, these functions suggest that PPARs serve as physiological sensors in different stress situations and remain valuable targets for innovative therapies.

Nosology and classification of genetic skeletal disorders: 2010 revision.

Genetic disorders involving the skeletal system arise through disturbances in the complex processes of skeletal development, growth and homeostasis and remain a diagnostic challenge because of their variety. The Nosology and Classification of Genetic Skeletal Disorders provides an overview of recognized diagnostic entities and groups them by clinical and radiographic features and molecular pathogenesis. The aim is to provide the Genetics, Pediatrics and Radiology community with a list of recognized genetic skeletal disorders that can be of help in the diagnosis of individual cases, in the delineation of novel disorders, and in building bridges between clinicians and scientists interested in skeletal biology. In the 2010 revision, 456 conditions were included and placed in 40 groups defined by molecular, biochemical, and/or radiographic criteria. Of these conditions, 316 were associated with mutations in one or more of 226 different genes, ranging from common, recurrent mutations to "private" found in single families or individuals. Thus, the Nosology is a hybrid between a list of clinically defined disorders, waiting for molecular clarification, and an annotated database documenting the phenotypic spectrum produced by mutations in a given gene. The Nosology should be useful for the diagnosis of patients with genetic skeletal diseases, particularly in view of the information flood expected with the novel sequencing technologies; in the delineation of clinical entities and novel disorders, by providing an overview of established nosologic entities; and for scientists looking for the clinical correlates of genes, proteins and pathways involved in skeletal biology. © 2011 Wiley-Liss, Inc.

Prévention des troubles lymphatiques et de leurs complications [Lymphatic disorders and prevention of their complications].

The prevalence of lymphedema is clearly underestimated. Too few patients receive treatment. It requires several specifically trained participants and must be conceived in the long term given the chronic nature and the incurability of this pathology. Prevention is therefore of major importance. Successfully applied to operated women for breast cancer, other models of coverage deserve to be developed to reduce the incidence of lymphedema and its complications, particularly after oncologic, orthopedic and vascular surgery and for patients affected by venous insufficiency.

Physical activity and pregnancy

SUMMARY : The traditional medical advice for pregnant women has been to reduce their physical activity (PA) levels. The advice was based on concerns that exercise could affect pregnancy outcomes by increasing core body temperature, by increasing the risk of maternal musculoskeletal injury and by altering the transplacental transport of oxygen and nutrients to maternal skeletal muscle rather than to the developing foetus. In the meantime, several studies have provided new information on adaptation of the pregnant woman and her foetus to moderate PA. New investigations have shown no adverse maternal or neonatal outcomes, abnormal foetal growth, increase in early pregnancy loss, or late pregnancy complications. Moreover, enrolment in moderate PA has proven to result in marked health benefits including improved maternal cardiovascular function, reduction of excessive weight gain and fat retention, less complicated labour, improved foetal stress tolerance and neurobehavioral maturation. In view of the beneficial effects, current recommendations encourage healthy pregnant women to engage in 30 minutes of moderate PA on most, if not all, days of the week. This thesis work addressed several questions. Firstly, it examined whether compliance with the recommended levels of PA during pregnancy results in better preparedness for the sudden physical exertion of labour and delivery. Secondly, it measured PA during pregnancy as compared to postpartum. Lastly, it assessed the influence of pre-pregnancy body mass index on gestational resting metabolic rate. Data collection was conducted on healthy women living in Switzerland during the third trimester of pregnancy and postpartum. Total and activity energy expenditure was assessed through 24-hour heart rate and accelerations recordings, and cardiovascular fitness through an individual step-test. Information related to pregnancy, labour and delivery was collected from medical records. The results indicate that a minimum 30 min of moderate PA per day during pregnancy are associated with better cardiovascular fitness and lower risk of operative delivery with no negative effects on maternal and foetal conditions (study 1). Despite these benefits, a substantial proportion of pregnant women (39%) living in Switzerland do not meet the PA recommendations. The decrease in activity related energy expenditure during pregnancy compared to postpartum was measured to be around 100 kcal/day (~13%), whereas the total energy expenditure was found to increase by 300 kcal/day (study 2). Thus, the energy cost of late pregnancy in Switzerland corresponds to 200 kca/day. These findings are based on average values of the study group. It should be noted, however, that large variations in individual energy expenditure may occur depending on the pre-pregnancy body mass index (study 3). When adjusted to body weight, gestational resting metabolic rate is significantly lower among women of high pre-pregnancy body mass index compared to women of normal or low pre-pregnancy body mass index. This can be explained by the fact that resting metabolic rate is primarily a function of fat-free mass, and when expressed per kg body weight, it decreases as the percentage of body fat increases. If energy intake is not modified appropriately in order to match lower energy cost per kg body weight in overweight and obese women it will result in positive energy balance, thus contributing to the current trend towards increasing adiposity in affluent society. The results of these studies go beyond the current state of knowledge on PA and pregnancy (study 4) and provide valid evidence to guide clinical practice. In view of the current epidemic of sedentary behaviour and obesity related pathology, the findings contribute new and reliable information to public health policies regarding the effects of PA in pregnancy, an important period of life for both mother and infant.

Insufficient coping behavior under chronic stress and vulnerability to psychiatric disorders

Epidemiological data indicate that 75% of subjects with major psychiatric disorders have their onset in the age range of 17-24 years. An estimated 35-50% of college and university students drop out prematurely due to insufficient coping skills under chronic stress, while 85% of students receiving a psychiatric diagnosis withdraw from college/university prior to the completion of their education. In this study we aimed at developing standardized means for identifying students with insufficient coping skills under chronic stress and at risk for mental health problems. A sample of 1,217 college students from 3 different sites in the U.S. and Switzerland completed 2 self-report questionnaires: the Coping Strategies Inventory "COPE" and the Zurich Health Questionnaire "ZHQ" which assesses "regular exercises", "consumption behavior", "impaired physical health", "psychosomatic disturbances", and "impaired mental health". The data were subjected to structure analyses by means of a Neural Network approach. We found 2 highly stable and reproducible COPE scales that explained the observed inter-individual variation in coping behavior sufficiently well and in a socio-culturally independent way. The scales reflected basic coping behavior in terms of "activity-passivity" and "defeatism-resilience", and in the sense of stable, socio-culturally independent personality traits. Correlation analyses carried out for external validation revealed a close relationship between high scores on the defeatism scale and impaired physical and mental health. This underlined the role of insufficient coping behavior as a risk factor for physical and mental health problems. The combined COPE and ZHQ instruments appear to constitute powerful screening tools for insufficient coping skills under chronic stress and for risks of mental health problems.