[Respiratory physiotherapy in private practice: Interest and prescription modalities]. / Kinésithérapie respiratoire libérale : intérêts et modalités de prescription.

INTRODUCTION: Respiratory diseases represent a major public health issue and impact both quality of life and life expectancy of the patients. STATE OF ART: Several interventions used in respiratory physiotherapy have been shown to reduce dyspnoea, improve quality of life and reduce hospitalisation in many respiratory diseases. However, respiratory physiotherapy remains poorly known to the medical community and may be under-prescribed. PERSPECTIVES: In order to improve the interdisciplinarity around the patient with respiratory impairment, we describe the interests and prescription modalities of liberal respiratory physiotherapy. In the context of respiratory physiotherapy acts, the precision of drafting prescription directly conditions the means implemented by the physiotherapist regarding care provided to the patient. CONCLUSION: The increased knowledge of prescribers, both concerning the prescription methods and the precise content of the rehabilitation sessions is one of the keys to their success.

Mental illness and cardiovascular health: observational and polygenic score analyses in a population-based cohort study.

BACKGROUND: Individuals with serious mental illness have a markedly shorter life expectancy. A major contributor to premature death is cardiovascular disease (CVD). We investigated associations of (genetic liability for) depressive disorder, bipolar disorder and schizophrenia with a range of CVD traits and examined to what degree these were driven by important confounders. METHODS: We included participants of the Dutch Lifelines cohort (N = 147 337) with information on self-reported lifetime diagnosis of depressive disorder, bipolar disorder, or schizophrenia and CVD traits. Employing linear mixed-effects models, we examined associations between mental illness diagnoses and CVD, correcting for psychotropic medication, demographic and lifestyle factors. In a subsample (N = 73 965), we repeated these analyses using polygenic scores (PGSs) for the three mental illnesses. RESULTS: There was strong evidence that depressive disorder diagnosis is associated with increased arrhythmia and atherosclerosis risk and lower heart rate variability, even after confounder adjustment. Positive associations were also found for the depression PGSs with arrhythmia and atherosclerosis. Bipolar disorder was associated with a higher risk of nearly all CVD traits, though most diminished after adjustment. The bipolar disorder PGSs did not show any associations. While the schizophrenia PGSs was associated with increased arrhythmia risk and lower heart rate variability, schizophrenia diagnosis was not. All mental illness diagnoses were associated with lower blood pressure and a lower risk of hypertension. CONCLUSIONS: Our study shows widespread associations of (genetic liability to) mental illness (primarily depressive disorder) with CVD, even after confounder adjustment. Future research should focus on clarifying potential causal pathways between mental illness and CVD.

Feasibility of a nasal breathing training during pulmonary rehabilitation. A pilot randomized controlled study.

Hyperventilation syndrome (HVS) is a common source of dyspnea and disability. While pulmonary rehabilitation (PR) including breathing exercises is indicated, randomized controlled trial are warranted to recommend one type of breathing exercise than another. We aimed to compare during PR, the effect of 5 sessions of nasal ventilation exercise (NV+PR) versus voluntary hypoventilation (vHV+PR) on exercise dyspnea (primary outcome) and capacity and health-related quality of life in patients. In this open label randomized controlled trial, 19 HVS patients (age=48.3 ± 15.2 y.o, female/male=18/1, Nijmegen score=33 ± 7.7) were randomized in a NV+PR (n = 9) or vHV+PR (n = 10) group. Modified Medical Research Council (mMRC) dyspnea, 6-minute walking distance (6MWD) with nasal/oral ventilation were assessed before and after 3 months of PR, and questionnaires (Nijmegen, VQ-11). There was a significant effect of PR of but no significant difference between groups in the improvements of dyspnea@max exercise (time effect (T): p < 0.01; group (G): p = 0.63; group*time interaction (G*T): p = 0.49), mMRC dyspnea (T: p < 0.01; G: p = 0.45; G*T: p = 0.62), 6MWD (T: p < 0.05; G: p = 0.36; G*T: p = 0.31), VQ-11 (T: p < 0.001; G: p = 0.16; G*T: p = 0.09) and plasma HCO3- (T: p < 0.05; G: p = 0.93; G*T; p = 0.36), Yet, Nijmegen score (T: p < 0.01; G: p = 0.32; G*T: p < 0.05) improvement was larger in NV+PR group. The exercise oronasal breathing shift during the 6MWT was significantly delayed in all patients (T: p < 0.05; G: p = 0.30; G*T: p = 0.32) and positively correlated with plasma HCO3-(r = 0.42; p < 0.05). Nasal exercise was not superior versus voluntary hypoventilation during PR in HVS patients. Yet, nasal exercise appeared feasible, leading to acquisition of a nasal breathing pattern during walking, improvement of PR outcomes and ventilatory alkalosis. The link between nasal breathing and hyperventilation is discussed in the light of the nasal ventilation rhythm in the limbic system and its role on the limbic emotional and ventilatory functions.

[Genetics and psychiatry]. / Genetica en psychiatrie.

BACKGROUND: For centuries, it has been suspected that the vulnerability to psychiatric problems might be heritable. In the 20th century, this was confirmed through twin and family studies, with heritability estimates ranging from ~30-40% for posttraumatic stress disorder and major depression to ~80 for schizophrenia and autism. In the 21st century, genome-wide association studies (GWASs) were introduced, a hypothesis-free design capable of locating DNA associations.

AIM: To describe the development of genetic research in psychiatry.

METHOD: Overview of selected literature.

RESULTS: Increasingly larger GWASs show that the risk for psychiatric disorders is influenced by a combination of environmental factors and the sum of many genetic variants with small effects that combine to explain much variation. A substantial proportion of these genetic effects overlap between psychiatric disorders, but also with positive outcomes, such as IQ and educational attainment.

CONCLUSION: We are experiencing a revolution in genetics, in which the sample size, and thus the predictive value of DNA, is growing faster than our understanding of the complexity of the inherited risk for psychiatric problems.
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Correction to: A Genetic Investigation of the Well-Being Spectrum.

In the original version of this article, unfortunately, in the acknowledgement section "National Institutes of Health (NIH, R37 AG033590-08) to J Cacioppo" was omitted. This has been corrected by publishing this erratum.

A Genetic Investigation of the Well-Being Spectrum.

The interrelations among well-being, neuroticism, and depression can be captured in a so-called well-being spectrum (3-phenotype well-being spectrum, 3-WBS). Several other human traits are likely linked to the 3-WBS. In the present study, we investigate how the 3-WBS can be expanded. First, we constructed polygenic risk scores for the 3-WBS and used this score to predict a series of traits that have been associated with well-being in the literature. We included information on loneliness, big five personality traits, self-rated health, and flourishing. The 3-WBS polygenic score predicted all the original 3-WBS traits and additionally loneliness, self-rated health, and extraversion (R2 between 0.62% and 1.58%). Next, using LD score regression, we calculated genetic correlations between the 3-WBS and the traits of interest. From all candidate traits, loneliness and self-rated health were found to have the strongest genetic correlations (rg = - 0.79, and rg= 0.64, respectively) with the 3-WBS. Lastly, we use Genomic SEM to investigate the factor structure of the proposed spectrum. The best model fit was obtained for a two-factor model including the 5-WBS traits, with two highly correlated factors representing the negative- and positive end of the spectrum. Based on these analyses we propose to include loneliness and self-rated health in the WBS and use a 5-phenotype well-being spectrum in future studies to gain more insight into the determinants of human well-being.

Predicting loneliness with polygenic scores of social, psychological and psychiatric traits.

Loneliness is a heritable trait that accompanies multiple disorders. The association between loneliness and mental health indices may partly be due to inherited biological factors. We constructed polygenic scores for 27 traits related to behavior, cognition and mental health and tested their prediction for self-reported loneliness in a population-based sample of 8798 Dutch individuals. Polygenic scores for major depressive disorder (MDD), schizophrenia and bipolar disorder were significantly associated with loneliness. Of the Big Five personality dimensions, polygenic scores for neuroticism and conscientiousness also significantly predicted loneliness, as did the polygenic scores for subjective well-being, tiredness and self-rated health. When including all polygenic scores simultaneously into one model, only 2 major depression polygenic scores remained as significant predictors of loneliness. When controlling only for these 2 MDD polygenic scores, only neuroticism and schizophrenia remain significant. The total variation explained by all polygenic scores collectively was 1.7%. The association between the propensity to feel lonely and the susceptibility to psychiatric disorders thus pointed to a shared genetic etiology. The predictive power of polygenic scores will increase as the power of the genome-wide association studies on which they are based increases and may lead to clinically useful polygenic scores that can inform on the genetic predisposition to loneliness and mental health.

Genome-wide association study of borderline personality disorder reveals genetic overlap with bipolar disorder, major depression and schizophrenia.

Borderline personality disorder (BOR) is determined by environmental and genetic factors, and characterized by affective instability and impulsivity, diagnostic symptoms also observed in manic phases of bipolar disorder (BIP). Up to 20% of BIP patients show comorbidity with BOR. This report describes the first case-control genome-wide association study (GWAS) of BOR, performed in one of the largest BOR patient samples worldwide. The focus of our analysis was (i) to detect genes and gene sets involved in BOR and (ii) to investigate the genetic overlap with BIP. As there is considerable genetic overlap between BIP, major depression (MDD) and schizophrenia (SCZ) and a high comorbidity of BOR and MDD, we also analyzed the genetic overlap of BOR with SCZ and MDD. GWAS, gene-based tests and gene-set analyses were performed in 998 BOR patients and 1545 controls. Linkage disequilibrium score regression was used to detect the genetic overlap between BOR and these disorders. Single marker analysis revealed no significant association after correction for multiple testing. Gene-based analysis yielded two significant genes: DPYD (P=4.42 × 10-7) and PKP4 (P=8.67 × 10-7); and gene-set analysis yielded a significant finding for exocytosis (GO:0006887, PFDR=0.019; FDR, false discovery rate). Prior studies have implicated DPYD, PKP4 and exocytosis in BIP and SCZ. The most notable finding of the present study was the genetic overlap of BOR with BIP (rg=0.28 [P=2.99 × 10-3]), SCZ (rg=0.34 [P=4.37 × 10-5]) and MDD (rg=0.57 [P=1.04 × 10-3]). We believe our study is the first to demonstrate that BOR overlaps with BIP, MDD and SCZ on the genetic level. Whether this is confined to transdiagnostic clinical symptoms should be examined in future studies.

Genetic effects influencing risk for major depressive disorder in China and Europe.

Major depressive disorder (MDD) is a common, complex psychiatric disorder and a leading cause of disability worldwide. Despite twin studies indicating its modest heritability (~30-40%), extensive heterogeneity and a complex genetic architecture have complicated efforts to detect associated genetic risk variants. We combined single-nucleotide polymorphism (SNP) summary statistics from the CONVERGE and PGC studies of MDD, representing 10 502 Chinese (5282 cases and 5220 controls) and 18 663 European (9447 cases and 9215 controls) subjects. We determined the fraction of SNPs displaying consistent directions of effect, assessed the significance of polygenic risk scores and estimated the genetic correlation of MDD across ancestries. Subsequent trans-ancestry meta-analyses combined SNP-level evidence of association. Sign tests and polygenic score profiling weakly support an overlap of SNP effects between East Asian and European populations. We estimated the trans-ancestry genetic correlation of lifetime MDD as 0.33; female-only and recurrent MDD yielded estimates of 0.40 and 0.41, respectively. Common variants downstream of GPHN achieved genome-wide significance by Bayesian trans-ancestry meta-analysis (rs9323497; log10 Bayes Factor=8.08) but failed to replicate in an independent European sample (P=0.911). Gene-set enrichment analyses indicate enrichment of genes involved in neuronal development and axonal trafficking. We successfully demonstrate a partially shared polygenic basis of MDD in East Asian and European populations. Taken together, these findings support a complex etiology for MDD and possible population differences in predisposing genetic factors, with important implications for future genetic studies.

Genome-wide association study of lifetime cannabis use based on a large meta-analytic sample of 32 330 subjects from the International Cannabis Consortium.

Cannabis is the most widely produced and consumed illicit psychoactive substance worldwide. Occasional cannabis use can progress to frequent use, abuse and dependence with all known adverse physical, psychological and social consequences. Individual differences in cannabis initiation are heritable (40-48%). The International Cannabis Consortium was established with the aim to identify genetic risk variants of cannabis use. We conducted a meta-analysis of genome-wide association data of 13 cohorts (N=32 330) and four replication samples (N=5627). In addition, we performed a gene-based test of association, estimated single-nucleotide polymorphism (SNP)-based heritability and explored the genetic correlation between lifetime cannabis use and cigarette use using LD score regression. No individual SNPs reached genome-wide significance. Nonetheless, gene-based tests identified four genes significantly associated with lifetime cannabis use: NCAM1, CADM2, SCOC and KCNT2. Previous studies reported associations of NCAM1 with cigarette smoking and other substance use, and those of CADM2 with body mass index, processing speed and autism disorders, which are phenotypes previously reported to be associated with cannabis use. Furthermore, we showed that, combined across the genome, all common SNPs explained 13-20% (P<0.001) of the liability of lifetime cannabis use. Finally, there was a strong genetic correlation (rg=0.83; P=1.85 × 10(-8)) between lifetime cannabis use and lifetime cigarette smoking implying that the SNP effect sizes of the two traits are highly correlated. This is the largest meta-analysis of cannabis GWA studies to date, revealing important new insights into the genetic pathways of lifetime cannabis use. Future functional studies should explore the impact of the identified genes on the biological mechanisms of cannabis use.

Genome-wide autozygosity is associated with lower general cognitive ability.

Inbreeding depression refers to lower fitness among offspring of genetic relatives. This reduced fitness is caused by the inheritance of two identical chromosomal segments (autozygosity) across the genome, which may expose the effects of (partially) recessive deleterious mutations. Even among outbred populations, autozygosity can occur to varying degrees due to cryptic relatedness between parents. Using dense genome-wide single-nucleotide polymorphism (SNP) data, we examined the degree to which autozygosity associated with measured cognitive ability in an unselected sample of 4854 participants of European ancestry. We used runs of homozygosity-multiple homozygous SNPs in a row-to estimate autozygous tracts across the genome. We found that increased levels of autozygosity predicted lower general cognitive ability, and estimate a drop of 0.6 s.d. among the offspring of first cousins (P=0.003-0.02 depending on the model). This effect came predominantly from long and rare autozygous tracts, which theory predicts as more likely to be deleterious than short and common tracts. Association mapping of autozygous tracts did not reveal any specific regions that were predictive beyond chance after correcting for multiple testing genome wide. The observed effect size is consistent with studies of cognitive decline among offspring of known consanguineous relationships. These findings suggest a role for multiple recessive or partially recessive alleles in general cognitive ability, and that alleles decreasing general cognitive ability have been selected against over evolutionary time.

Polygenic dissection of major depression clinical heterogeneity.

The molecular mechanisms underlying major depressive disorder (MDD) are largely unknown. Limited success of previous genetics studies may be attributable to heterogeneity of MDD, aggregating biologically different subtypes. We examined the polygenic features of MDD and two common clinical subtypes (typical and atypical) defined by symptom profiles in a large sample of adults with established diagnoses. Data were from 1530 patients of the Netherlands Study of Depression and Anxiety (NESDA) and 1700 controls mainly from the Netherlands Twin Register (NTR). Diagnoses of MDD and its subtypes were based on DSM-IV symptoms. Genetic overlap of MDD and subtypes with psychiatric (MDD, bipolar disorder, schizophrenia) and metabolic (body mass index (BMI), C-reactive protein, triglycerides) traits was evaluated via genomic profile risk scores (GPRS) generated from meta-analysis results of large international consortia. Single nucleotide polymorphism (SNP)-heritability of MDD and subtypes was also estimated. MDD was associated with psychiatric GPRS, while no association was found for GPRS of metabolic traits. MDD subtypes had differential polygenic signatures: typical was strongly associated with schizophrenia GPRS (odds ratio (OR)=1.54, P=7.8e-9), while atypical was additionally associated with BMI (OR=1.29, P=2.7e-4) and triglycerides (OR=1.21, P=0.006) GPRS. Similar results were found when only the highly discriminatory symptoms of appetite/weight were used to define subtypes. SNP-heritability was 32% for MDD, 38% and 43% for subtypes with, respectively, decreased (typical) and increased (atypical) appetite/weight. In conclusion, MDD subtypes are characterized by partially distinct polygenic liabilities and may represent more homogeneous phenotypes. Disentangling MDD heterogeneity may help the psychiatric field moving forward in the search for molecular roots of depression.

The association between lower educational attainment and depression owing to shared genetic effects? Results in ~25,000 subjects.

An association between lower educational attainment (EA) and an increased risk for depression has been confirmed in various western countries. This study examines whether pleiotropic genetic effects contribute to this association. Therefore, data were analyzed from a total of 9662 major depressive disorder (MDD) cases and 14,949 controls (with no lifetime MDD diagnosis) from the Psychiatric Genomics Consortium with additional Dutch and Estonian data. The association of EA and MDD was assessed with logistic regression in 15,138 individuals indicating a significantly negative association in our sample with an odds ratio for MDD 0.78 (0.75-0.82) per standard deviation increase in EA. With data of 884,105 autosomal common single-nucleotide polymorphisms (SNPs), three methods were applied to test for pleiotropy between MDD and EA: (i) genetic profile risk scores (GPRS) derived from training data for EA (independent meta-analysis on ~120,000 subjects) and MDD (using a 10-fold leave-one-out procedure in the current sample), (ii) bivariate genomic-relationship-matrix restricted maximum likelihood (GREML) and (iii) SNP effect concordance analysis (SECA). With these methods, we found (i) that the EA-GPRS did not predict MDD status, and MDD-GPRS did not predict EA, (ii) a weak negative genetic correlation with bivariate GREML analyses, but this correlation was not consistently significant, (iii) no evidence for concordance of MDD and EA SNP effects with SECA analysis. To conclude, our study confirms an association of lower EA and MDD risk, but this association was not because of measurable pleiotropic genetic effects, which suggests that environmental factors could be involved, for example, socioeconomic status.

[Innovations in interventional radiology applied to the field of otolaryngology: A pictorial essay].

The management of hypervascular ENT tumors is usually complex and requires a multidisciplinary approach because of the risk of serious intra-operative bleeding and of potential injuries to cranial nerves and/or large cervical vessels. Over the last four decades, advances in neuro-interventional radio­logical procedures have produced a range of adjunctive endo­vascular techniques in addition to conventional surgery. A pictorial essay in ENT specialty is presented in this article highlighting the most relevant innovations in interventional radiology.

Genome-wide analyses of borderline personality features.

The heritability of borderline personality (BP) features has been established in multiple twin and family studies. Using data from the borderline subscale of the Personality Assessment Inventory Borderline Features Scale (PAI-BOR) collected in two Dutch cohorts (N=7125), the Netherlands Twin Register and The Netherlands Study of Depression and Anxiety, we show that heritability of the PAI-BOR total score using genome-wide single-nucleotide polymorphism (SNPs) is estimated at 23%, and that the genetic variance is substantially higher in affect instability items compared with the other three subscales of the PAI-BOR (42.7% vs non-significant estimates for self-harm, negative relations and identity problems). We present results from a first genome-wide association study of BP features, which shows a promising signal on chromosome 5 corresponding to SERINC5, a protein involved in myelination. Reduced myelination has been suggested as possibly having a role in the development of psychiatric disorders characterized by lack of social interaction. The signal was confirmed in a third independent Dutch cohort drawn from the Erasmus Rucphen Family study (N=1301). Our analyses were complemented by investigating the heterogeneity that was implied by the differences in genetic variance components in the four subscales of the PAI-BOR. These analyses show that the association of SNPs tagging SERINC5 differs substantially across the 24 items of the PAI-BOR. Further, using reverse regression we showed that the effects were present only in subjects with higher scores on the PAI-BOR. Taken together, these results suggest that future genome-wide analyses can benefit substantially by taking into account the phenotypic and genetic heterogeneity of BP features.

Success and failure factors for hearing-aid prescription: results of a French national survey.

OBJECTIVES: To identify epidemiological, socioeconomic, audiometric and environmental factors of success and failure of hearing-aid prescription, and to assess hearing-aid efficacy at 6-9 months after prescription. PATIENTS AND METHODS: A prospective nationwide survey was conducted in France on 184 patients with age-related hearing loss. Inclusion data were collected by a questionnaire filled out by the ENT specialist and patient, and with a second questionnaire filled out by telephone contact with the patient 6-9 months later. RESULTS: One-third of patients failed to fulfill the prescription, either for financial reasons or for lack of interest in correcting their disability. For the other two-thirds, the factors favoring consultation with a hearing-aid fitting specialist seemed to be: leisure activity requiring good hearing, living in a couple or family, spontaneous initial ENT consultation, strong motivation, monthly income greater than €1200, longstanding hearing impairment, and difficulty in listening to television and following a conversation in noise. Eighty percent of hearing-aid trials were successful; 60% of prescriptions were thus followed by hearing-aid purchase. The main three criteria determining purchase were the advice of the hearing-aid fitting specialist, and the price and the effectiveness of the apparatus on trial. In the four daily life situations presented in the questionnaire, the hearing-aid was worn for 8 hours or more in 90% of cases, found useful in 70% and proved satisfactory in 70%. Age-related hearing loss, whether metabolic or sensorineural, benefited from hearing-aid correction in 86% of cases. CONCLUSIONS: Indications for hearing-aid prescription should take account of the patient's degree of motivation, awareness of disability, and income. The advice of the ENT and hearing-aid fitting specialists plays a key role in the patient's acceptance of the hearing-aid. Hearing-aids seem to enhance quality of life significantly in age-related hearing loss subjects.

Skeletal muscle effects of electrostimulation after COPD exacerbation: a pilot study.

Muscle dysfunction is a major problem in chronic obstructive pulmonary disease (COPD), particularly after exacerbations. We thus asked whether neuromuscular electrostimulation (NMES) might be directly useful following an acute exacerbation and if such a therapy decreases muscular oxidative stress and/or alters muscle fibre distribution. A pilot randomised controlled study of NMES lasting 6 weeks was carried out in 15 in-patients (n=9 NMES; n=6 sham) following a COPD exacerbation. Stimulation was delivered to the quadriceps and hamstring muscles (35 Hz). Primary outcomes were quadriceps force and muscle oxidative stress. At the end of the study, quadriceps force improvement was statistically different between groups (p=0.02), with a significant increase only in the NMES group (median (interquartile range) 10 (4.7-11.5) kg; p=0.01). Changes in the 6-min walking distance were statistically different between groups (p=0.008), with a significant increase in the NMES group (165 (125-203) m; p=0.003). NMES did not lead to higher muscle oxidative stress, as indicated by the decrease in total protein carbonylation (p=0.02) and myosin heavy chain carbonylation (p=0.01) levels. Finally, we observed a significant increase in type I fibre proportion in the NMES group. Our study shows that following COPD exacerbation, NMES is effective in counteracting muscle dysfunction and decreases muscle oxidative stress.

Lateral ankle sprain alters postural control in bipedal stance--part 1: restoration over the 30 days following the injury.

The time evolution of the postural behavior of 23 lateral ankle sprain patients (degrees I and II) were evaluated 14 h and 10 and 30 days on average after their injury and compared with those of 30 age-matched healthy individuals. The patients were tested with separate measurements of the reaction forces under each limb to highlight the possible compensatory mechanisms between the sound and the injured legs. Their postural behavior in bipedal stance was characterised by a weight-bearing asymmetry with more weight on the sound leg and an asymmetry of the postural stabilisation mechanisms, which are limited and perturbed under the injured leg. Pain appears to be the main factor for explaining these postural asymmetries. Despite these asymmetries, the patients were nonetheless more unstable than the individuals constituting the group control. Ten days later, only the weight-bearing asymmetry was still observed whereas 30 days later, the postural behavior was totally normal once again. Lateral ankle sprain perturbs the contribution of the injured leg in postural stabilisation, inducing a larger involvement of the sound leg in the postural stability process. These characteristics are largely reduced 10 days after the injury.