Multiples étiologies de l'angioedème [The multiple etiologies of angioedema]

L'angioedème est une affection fréquente, dont les étiologies sont multiples. Les angioedèmes habituellement associés à une urticaire sont en général dus à une libération d'histamine et répondent en principe aux antihistaminiques et à l'adrénaline. Il s'agit des angioedèmes d'origine allergique, des réactions anaphylactoïdes, souvent d'origine médicamenteuse (AINS), des angioedèmes physiques et de l'angioedème récurrent idiopathique. La bradykinine joue certainement un rôle dans la genèse des angioedèmes associés aux inhibiteurs de l'enzyme de conversion de l'angiotensine et rarement aux antagonistes du récepteur de l'angiotensine II, ainsi que dans celle des rares angioedèmes héréditaires ou liés à un déficit acquis en Ci-inhibiteur. L'urticaire est alors absente et les antihistaminiques ainsi que l'adrénaline sont inefficaces. Angioedema is a frequent disorder with multiple aetiologies. Angioedemas associated with urticaria are usually caused by histamine release and respond to anti-histamines and adrenalin. They include allergic angioedemas, anaphylactoid reactions (mostly drug-induced, e.g. NSAID), physical angioedemas and recurrent idiopathic angioedema. Bradykinin probably plays a causative role in the pathogenesis of ACE-inhibitor or angiotensin II receptor blocker related angioedemas, as well as in the pathogenesis of the rare hereditary or acquired C1-inhibitor deficiency angioedemas. Urticaria is then typically absent and anti-histamines, as well as adrenalin, are ineffective

Absence of association between specific common variants of the obesity-related FTO gene and psychological and behavioral eating disorder phenotypes.

Extensive population-based genome-wide association studies have identified an association between the FTO gene and BMI; however, the mechanism of action is still unknown. To determine whether FTO may influence weight regulation through psychological and behavioral factors, seven single-nucleotide polymorphisms (SNPs) of the FTO gene were genotyped in 1,085 individuals with anorexia nervosa (AN) and 677 healthy weight controls from the international Price Foundation Genetic Studies of Eating Disorders. Each SNP was tested in association with eating disorder phenotypes and measures that have previously been associated with eating behavior pathology: trait anxiety, harm-avoidance, novelty seeking, impulsivity, obsessionality, compulsivity, and concern over mistakes. After appropriate correction for multiple comparisons, no significant associations between individual FTO gene SNPs and eating disorder phenotypes or related eating behavior pathology were identified in cases or controls. Thus, this study found no evidence that FTO gene variants associated with weight regulation in the general population are associated with eating disorder phenotypes in AN participants or matched controls. © 2011 Wiley-Liss, Inc.

Determinants of the development of post-traumatic stress disorder, in the general population.

PURPOSE: To assess (1) the lifetime prevalence of exposure both to trauma and post-traumatic stress disorder (PTSD); (2) the risk of PTSD by type of trauma; and (3) the determinants of the development of PTSD in the community. METHODS: The Diagnostic Interview for Genetic Studies was administered to a random sample of an urban area (N = 3,691). RESULTS: (1) The lifetime prevalence estimates of exposure to trauma and PTSD were 21.0 and 5.0%; respectively, with a twice as high prevalence of PTSD in women compared to men despite a similar likelihood of exposure in the two sexes; (2) Sexual abuse was the trauma involving the highest risk of PTSD; (3) The risk of PTSD was most strongly associated with sexual abuse followed by preexisting bipolar disorder, alcohol dependence, antisocial personality, childhood separation anxiety disorder, being victim of crime, witnessing violence, Neuroticism and Problem-focused coping strategies. After adjustment for these characteristics, female sex was no longer found to be significantly associated with the risk of PTSD. CONCLUSIONS: The risk for the development of PTSD after exposure to traumatic events is associated with several factors including the type of exposure, preexisting psychopathology, personality features and coping strategies which independently contribute to the vulnerability to PTSD.

Reduced left hemisphere dominance for multiple versus single anagram solutions and its modulation by individuals' schizotypy

Problem solving (including insight, divergent thinking) seems to rely on the right hemisphere (RH). These functions are difficult to assess behaviorally. We propose anagram resolution as a suitable paradigm. University students (n=32) performed three tachistoscopic lateralized visual half-field experiments (stimulus presentation 150ms). In Experiment 1, participants recalled four-letter strings. Subsequently, participants provided solutions for four-letter anagrams (one solution in Experiment 2; two solutions in Experiment 3). Additionally, participants completed a schizotypy questionnaire (O-LIFE). Results showed a right visual field advantage in Experiment 1 and 2, but no visual field advantage in Experiment 3. In Experiment 1, increasing positive schizotypy associated with a RH performance shift. Problem solving seems to require increasingly the RH when facing several rather than one solution. This result supports previous studies on the RH's role in remote associative, metaphor and discourse processing. The more complex language requirements, the less personality traits seem to matter.

Multiple pulmonary artery aneurysms in tuberous sclerosis complex.

Tuberous sclerosis complex (TSC) is a rare genetic disorder characterised by multiple hamartomas, caused by inactivating mutations of the TSC1/TSC2 tumour suppressor genes. Classical pulmonary involvement in tuberous sclerosis complex (TSC) consists of lymphangioleiomyomatosis and/or multiple micronodular pneumocyte hyperplasia (MMPH). Association of TSC with pulmonary artery aneurysm (PAA) has been only exceptionally described. We report here the first case of TSC with multiple PAA in combination with MMPH, cardiac rhabdomyomas and bone, skin and brain involvement.

Associations between mood, anxiety or substance use disorders and inflammatory markers after adjustment for multiple covariates in a population-based study.

Inflammation is one possible mechanism underlying the associations between mental disorders and cardiovascular diseases (CVD). However, studies on mental disorders and inflammation have yielded inconsistent results and the majority did not adjust for potential confounding factors. We examined the associations of several pro-inflammatory cytokines (IL-1β, IL-6 and TNF-α) and high sensitive C-reactive protein (hsCRP) with lifetime and current mood, anxiety and substance use disorders (SUD), while adjusting for multiple covariates. The sample included 3719 subjects, randomly selected from the general population, who underwent thorough somatic and psychiatric evaluations. Psychiatric diagnoses were made with a semi-structured interview. Major depressive disorder was subtyped into "atypical", "melancholic", "combined atypical-melancholic" and "unspecified". Associations between inflammatory markers and psychiatric diagnoses were assessed using multiple linear and logistic regression models. Lifetime bipolar disorders and atypical depression were associated with increased levels of hsCRP, but not after multivariate adjustment. After multivariate adjustment, SUD remained associated with increased hsCRP levels in men (β = 0.13 (95% CI: 0.03,0.23)) but not in women. After multivariate adjustment, lifetime combined and unspecified depression were associated with decreased levels of IL-6 (β = -0.27 (-0.51,-0.02); β = -0.19 (-0.34,-0.05), respectively) and TNF-α (β = -0.16 (-0.30,-0.01); β = -0.10 (-0.19,-0.02), respectively), whereas current combined and unspecified depression were associated with decreased levels of hsCRP (β = -0.20 (-0.39,-0.02); β = -0.12 (-0.24,-0.01), respectively). Our data suggest that the significant associations between increased hsCRP levels and mood disorders are mainly attributable to the effects of comorbid disorders, medication as well as behavioral and physical CVRFs.

Neurocognitive deficits and personality traits among euthymic patients with mood disorders in late life.

BACKGROUND: Previous studies revealed that acute depressive episodes are associated with both cognitive deficits and modified personality patterns in late life. Whether or not these psychological changes are present after remission remains a matter of debate. To date, no study provided concomitant assessment of cognition and psychological functions in this particular clinical setting. METHOD: Using a cross-sectional design, 58 remitted outpatients (36 with unipolar early-onset depression (EOD) and 22 with bipolar disorder (BD)) were compared to 62 healthy controls. Assessment included detailed neurocognitive measures and evaluation of the five factor personality dimensions (NEO-Personality Inventory). RESULTS: Group comparisons revealed significant slower processing speed, working and episodic memory performances in BD patients. EOD patients showed cognitive abilities comparable to those of elderly controls. In NEO PI assessment, both BD and EOD patients displayed higher Depressiveness facet scores. In addition, the EOD but not BD group had lower Extraversion factor, and Warmth and Positive Emotion facet scores than controls. CONCLUSIONS: After remission from acute affective symptoms, older BD patients show significant impairment in several cognitive functions while neuropsychological performances remained intact in elderly patients with EOD. Supporting a long-lasting psychological vulnerability, EOD patients are more prone to develop emotion-related personality trait changes than BD patients.

Personality trait risk factors for attempted suicide among young women with eating disorders.

OBJECTIVE: - Clinical observations and a review of the literature led us to hypothesize that certain personality and character traits could provide improved understanding, and thus improved prevention, of suicidal behaviour among young women with eating disorders. METHOD: - The clinical group consisted of 152 women aged between 18 and 24 years, with DSM-IV anorexia nervosa/restrictive type (AN-R = 66), anorexia nervosa/purging type (AN-P = 37), bulimia nervosa/non-purging type (BN-NP = 9), or bulimia nervosa/purging type (BN-P = 40). The control group consisted of 140 subjects. The assessment measures were the Minnesota Multiphasic Personality Inventory-second version (MMPI-2) scales and subscales, the Beck Depression Inventory (BDI) used to control for current depressive symptoms, plus a specific questionnaire concerning suicide attempts. RESULTS: - Suicide attempts were most frequent in subjects with purging behaviour (30.0% for BN-P and 29.7% for AN-P). Those attempting suicide among subjects with eating disorders were mostly students (67.8%). For women with AN-R the scales for 'Depression' and 'Antisocial practices' represented significant suicidal risk, for women with AN-P the scales for 'Hysteria', 'Psychopathic deviate', 'Shyness/Self-consciousness', 'Antisocial Practices', 'Obsessiveness' and 'Low self-esteem' were risk indicators and for women with BN-P the 'Psychasthenia', 'Anger' and 'Fears' scales were risk indicators. CONCLUSION: - This study provides interesting results concerning the personality traits of young women with both eating disorders and suicidal behaviour. Students and those with purging behaviour are most at risk. Young women should be given more attention with regard to the risk of suicide attempts if they: (a). have AN-R with a tendency to self-punishment and antisocial conduct, (b). have AN-P with multiple physical complaints, are not at ease in social situations and have antisocial behaviour, or (c). if they have BN-P and tend to be easily angered with obsessive behaviour and phobic worries. The MMPI-2 is an interesting assessment method for the study of traits indicating a risk of suicidal behaviour in young subjects, after controlling for current depressive pathology.

Early intervention for conversion disorder: neurologists and psychiatrists working together

It has been shown that for the reaction catalyzed by "biodegradative" L-threonine dehydratase from E. coli strains K-12 and 980 in 0.5 M phosphate-carbonate buffer, pH 8.4 and pH 9.5, the plots of initial reaction rate (v) versus the initial substrate concentration ([S]0 are characterized by several inflection points, i. e. an intermediate plateau. The plot of v versus the allosteric activator (AMP) concentration have very complicated shapes: there are several inflection points, and also the maximum at L-threonine concentration equal to 3-10(2) and 5-10(-2) M. High AMP concentrations inhibit the enzyme at high substrate concentrations. The reduced glutathion dose not influence the enzyme and does not alter the activating effect of AMP. On the basis of the data obtained it is proposed that the substrate and AMP shift the equilibrium between multiple oligomeric enzyme forms differing in catalytic activity and kinetic manifestations of allosteric interactions between the active and allosteric AMP-binding sites towards polymerization. Thus, the functioning the enzyme under study is discussed in the frames of the model of dissociating regulatory enzymes with multiple intermediate oligomeric forms.

Personality traits, behavioral and psychological symptoms and cognitive decline in patients at an early stage of Alzheimer's disease

The aim of this doctoral thesis was to study personality characteristics of patients at an early stage of Alzheimer's disease (AD), and more specifically to describe personality and its changes over time, and to explore its possible links with psychological and symptoms (BPS) and cognitive level. The results were compared to those of a group of participants without cognitive disorder through three empirical studies. In the first study, the findings showed significant personality changes that follow a specific trend in the clinical group. The profil of personality changes showed an increase in Neuroticism and a decrease in Extraversion, Openess to experiences, and Conscientiousness over time. The second study highlighted that personality and BPS occur early in the cours of AD. Recognizing them as possible precoce signs of neurodegeneration may prove to be a key factor for early detection and intervention. In the third study, a significant association between personality changes and cognitive status was observed in the patients with incipient AD. Thus, changes in Neuroticism and Conscientiousness were linked with cognitive deterioration, whereas decreased Openness to experiences and Conscientiousness over time predicted loss of independence in daily functioning. Other well-known factors such as age, education level or civil status were taken into account to predict cognitive decline. The three studies suggested five important implications: (1) cost-effective screening should take into account premorbid and specific personality changes; (2) psycho-educative interventions should provide information on the possible personality changes and BPS that may occur at the beginning of the disease; (3) using personality traits alongside other variables in the future studies on prevention might help to better understand AD's etiology; (4) individual treatment plans (psychotherapeutic, social, and pharmacological) might be adapted to the specific changes in personality profiles; (5) more researches are needed to study the impact of social-cultural and lifestyle variables on the development of AD.

Specificities of defense mechanisms in bipolar affective disorder: relations with symptoms and therapeutic alliance.

Defense mechanisms as a central notion of psychoanalysis have inspired various levels of interest in research in psychotherapy and psychopathology. Defense specificities have only recently been investigated systematically with regard to several clinical diagnoses, such as affective and personality disorders. For the present study, 30 inpatients diagnosed with Bipolar Affective Disorder I (BD) were interviewed. An observer-rater method, the Defense Mechanisms Rating Scales (DMRS), applied to session-transcripts, of assessment of defenses was used. A matched, nonclinical control group was introduced. Defense specificities in BD encompass a set of 5 immature defenses, of which omnipotence is linked with symptom level. The level of the therapeutic alliance is predicted by mature defenses. These results are discussed with regard to the psychological vulnerability of BD, and treatment implications for psychodynamic psychotherapy with such challenging patients are evoked.

A genetic risk score combining 32 SNPs is associated with body mass index and improves obesity prediction in people with major depressive disorder.

BACKGROUND: Obesity is strongly associated with major depressive disorder (MDD) and various other diseases. Genome-wide association studies have identified multiple risk loci robustly associated with body mass index (BMI). In this study, we aimed to investigate whether a genetic risk score (GRS) combining multiple BMI risk loci might have utility in prediction of obesity in patients with MDD. METHODS: Linear and logistic regression models were conducted to predict BMI and obesity, respectively, in three independent large case-control studies of major depression (Radiant, GSK-Munich, PsyCoLaus). The analyses were first performed in the whole sample and then separately in depressed cases and controls. An unweighted GRS was calculated by summation of the number of risk alleles. A weighted GRS was calculated as the sum of risk alleles at each locus multiplied by their effect sizes. Receiver operating characteristic (ROC) analysis was used to compare the discriminatory ability of predictors of obesity. RESULTS: In the discovery phase, a total of 2,521 participants (1,895 depressed patients and 626 controls) were included from the Radiant study. Both unweighted and weighted GRS were highly associated with BMI (P <0.001) but explained only a modest amount of variance. Adding 'traditional' risk factors to GRS significantly improved the predictive ability with the area under the curve (AUC) in the ROC analysis, increasing from 0.58 to 0.66 (95% CI, 0.62-0.68; χ(2) = 27.68; P <0.0001). Although there was no formal evidence of interaction between depression status and GRS, there was further improvement in AUC in the ROC analysis when depression status was added to the model (AUC = 0.71; 95% CI, 0.68-0.73; χ(2) = 28.64; P <0.0001). We further found that the GRS accounted for more variance of BMI in depressed patients than in healthy controls. Again, GRS discriminated obesity better in depressed patients compared to healthy controls. We later replicated these analyses in two independent samples (GSK-Munich and PsyCoLaus) and found similar results. CONCLUSIONS: A GRS proved to be a highly significant predictor of obesity in people with MDD but accounted for only modest amount of variance. Nevertheless, as more risk loci are identified, combining a GRS approach with information on non-genetic risk factors could become a useful strategy in identifying MDD patients at higher risk of developing obesity.

Phenotypic Association Analyses With Copy Number Variation in Recurrent Depressive Disorder.

BACKGROUND: Defining the molecular genomic basis of the likelihood of developing depressive disorder is a considerable challenge. We previously associated rare, exonic deletion copy number variants (CNV) with recurrent depressive disorder (RDD). Sex chromosome abnormalities also have been observed to co-occur with RDD. METHODS: In this reanalysis of our RDD dataset (N = 3106 cases; 459 screened control samples and 2699 population control samples), we further investigated the role of larger CNVs and chromosomal abnormalities in RDD and performed association analyses with clinical data derived from this dataset. RESULTS: We found an enrichment of Turner's syndrome among cases of depression compared with the frequency observed in a large population sample (N = 34,910) of live-born infants collected in Denmark (two-sided p = .023, odds ratio = 7.76 [95% confidence interval = 1.79-33.6]), a case of diploid/triploid mosaicism, and several cases of uniparental isodisomy. In contrast to our previous analysis, large deletion CNVs were no more frequent in cases than control samples, although deletion CNVs in cases contained more genes than control samples (two-sided p = .0002). CONCLUSIONS: After statistical correction for multiple comparisons, our data do not support a substantial role for CNVs in RDD, although (as has been observed in similar samples) occasional cases may harbor large variants with etiological significance. Genetic pleiotropy and sample heterogeneity suggest that very large sample sizes are required to study conclusively the role of genetic variation in mood disorders.

NBAS mutations cause a multisystem disorder involving bone, connective tissue, liver, immune system, and retina.

We report two unrelated patients with a multisystem disease involving liver, eye, immune system, connective tissue, and bone, caused by biallelic mutations in the neuroblastoma amplified sequence (NBAS) gene. Both presented as infants with recurrent episodes triggered by fever with vomiting, dehydration, and elevated transaminases. They had frequent infections, hypogammaglobulinemia, reduced natural killer cells, and the Pelger-Huët anomaly of their granulocytes. Their facial features were similar with a pointed chin and proptosis; loose skin and reduced subcutaneous fat gave them a progeroid appearance. Skeletal features included short stature, slender bones, epiphyseal dysplasia with multiple phalangeal pseudo-epiphyses, and small C1-C2 vertebrae causing cervical instability and myelopathy. Retinal dystrophy and optic atrophy were present in one patient. NBAS is a component of the synthaxin-18 complex and is involved in nonsense-mediated mRNA decay control. Putative loss-of-function mutations in NBAS are already known to cause disease in humans. A specific founder mutation has been associated with short stature, optic nerve atrophy and Pelger-Huët anomaly of granulocytes (SOPH) in the Siberian Yakut population. A more recent report associates NBAS mutations with recurrent acute liver failure in infancy in a group of patients of European descent. Our observations indicate that the phenotypic spectrum of NBAS deficiency is wider than previously known and includes skeletal, hepatic, metabolic, and immunologic aspects. Early recognition of the skeletal phenotype is important for preventive management of cervical instability. © 2015 Wiley Periodicals, Inc.

Environmental factors in multiple sclerosis [Environmental factors in multiple sclerosis]

Although multiple sclerosis (MS) is recognized as a disorder involving the immune system, the interplay of environmental factors and individual genetic susceptibility seems to influence MS onset and clinical expression, as well as therapeutic responsiveness. Multiple human epidemiological and animal model studies have evaluated the effect of different environmental factors, such as viral infections, vitamin intake, sun exposure, or still dietary and life habits on MS prevalence. Previous Epstein-Barr virus infection, especially if this infection occurs in late childhood, and lack of vitamin D (VitD) currently appear to be the most robust environmental factors for the risk of MS, at least from an epidemiological standpoint. Ultraviolet radiation (UVR) activates VitD production but there are also some elements supporting the fact that insufficient UVR exposure during childhood may represent a VitD-independent risk factor of MS development, as well as negative effect on the clinical and radiological course of MS. Recently, there has been a growing interest in the gut-brain axis, a bidirectional neuro-hormonal communication system between the intestinal microbiota and the central nervous system (CNS). Indeed, components of the intestinal microbiota may be pro-inflammatory, promote the migration of immune cells into the CNS, and thus be a key parameter for the development of autoimmune disorders such as MS. Interestingly most environmental factors seem to play a role during childhood. Thus, if childhood is the most fragile period to develop MS later in life, preventive measures should be applied early in life. For example, adopting a diet enriched in VitD, playing outdoor and avoiding passive smoking would be extremely simple measures of primary prevention for public health strategies. However, these hypotheses need to be confirmed by prospective evaluations, which are obviously difficult to conduct. In addition, it remains to be determined whether and how VitD supplementation in adult life would be useful in alleviating the course of MS, once this disease has already started. A better knowledge of the influence of various environmental stimuli on MS risk and course would certainly allow the development of add-on therapies or measures in parallel to the immunotherapies currently used in MS.