Genetic Association of Recovery from Eating Disorders: The Role of GABA Receptor SNPs.

Follow-up studies of eating disorders (EDs) suggest outcomes ranging from recovery to chronic illness or death, but predictors of outcome have not been consistently identified. We tested 5151 single-nucleotide polymorphisms (SNPs) in approximately 350 candidate genes for association with recovery from ED in 1878 women. Initial analyses focused on a strictly defined discovery cohort of women who were over age 25 years, carried a lifetime diagnosis of an ED, and for whom data were available regarding the presence (n=361 ongoing symptoms in the past year, ie, 'ill') or absence (n=115 no symptoms in the past year, ie, 'recovered') of ED symptoms. An intronic SNP (rs17536211) in GABRG1 showed the strongest statistical evidence of association (p=4.63 × 10(-6), false discovery rate (FDR)=0.021, odds ratio (OR)=0.46). We replicated these findings in a more liberally defined cohort of women age 25 years or younger (n=464 ill, n=107 recovered; p=0.0336, OR=0.68; combined sample p=4.57 × 10(-6), FDR=0.0049, OR=0.55). Enrichment analyses revealed that GABA (γ-aminobutyric acid) SNPs were over-represented among SNPs associated at p<0.05 in both the discovery (Z=3.64, p=0.0003) and combined cohorts (Z=2.07, p=0.0388). In follow-up phenomic association analyses with a third independent cohort (n=154 ED cases, n=677 controls), rs17536211 was associated with trait anxiety (p=0.049), suggesting a possible mechanism through which this variant may influence ED outcome. These findings could provide new insights into the development of more effective interventions for the most treatment-resistant patients.

Atopic dermatitis-like disease and associated lethal myeloproliferative disorder arise from loss of Notch signaling in the murine skin.

BACKGROUND: The Notch pathway is essential for proper epidermal differentiation during embryonic skin development. Moreover, skin specific loss of Notch signaling in the embryo results in skin barrier defects accompanied by a B-lymphoproliferative disease. However, much less is known about the consequences of loss of Notch signaling after birth. METHODOLOGY AND PRINCIPAL FINDINGS: To study the function of Notch signaling in the skin of adult mice, we made use of a series of conditional gene targeted mice that allow inactivation of several components of the Notch signaling pathway specifically in the skin. We demonstrate that skin-specific inactivation of Notch1 and Notch2 simultaneously, or RBP-J, induces the development of a severe form of atopic dermatitis (AD), characterized by acanthosis, spongiosis and hyperkeratosis, as well as a massive dermal infiltration of eosinophils and mast cells. Likewise, patients suffering from AD, but not psoriasis or lichen planus, have a marked reduction of Notch receptor expression in the skin. Loss of Notch in keratinocytes induces the production of thymic stromal lymphopoietin (TSLP), a cytokine deeply implicated in the pathogenesis of AD. The AD-like associated inflammation is accompanied by a myeloproliferative disorder (MPD) characterized by an increase in immature myeloid populations in the bone marrow and spleen. Transplantation studies revealed that the MPD is cell non-autonomous and caused by dramatic microenvironmental alterations. Genetic studies demontrated that G-CSF mediates the MPD as well as changes in the bone marrow microenvironment leading to osteopenia. SIGNIFICANCE: Our data demonstrate a critical role for Notch in repressing TSLP production in keratinocytes, thereby maintaining integrity of the skin and the hematopoietic system.

Disordered eating behaviors: what about boys?

PURPOSE: To determine the characteristics specific to boys with disordered eating behaviors (DEB) and the general context in which these DEB occur. METHOD: Data were drawn from the SMASH02 database, a survey carried out among post-mandatory school students in Switzerland aged 16-20 years in 2002. Only males (N=3890) were included, and were classified into into one of four groups based on their level of concern about weight/food and on their eating behaviors, as follows: group 1: one concern without behavior (N=862); group 2: more than one concern without behavior (N=361); group 3: at least one behavior (N=798); and a control group (N=1869), according to previously validated items. Groups were compared for personal, family, school, experience of violence, and health-compromising behaviors variables on the bivariate level. All significant variables were included in a multinomial logistic regression using Stata 9 software. RESULTS: About one-half of the boys reported either a concern or unhealthy eating behavior. Compared with the control group, boys from the three groups were more likely to be students and to report a history of sexual abuse, delinquency, depression, and feeling fat. In addition, boys from group 3 were more likely to report a history of dieting, early puberty, peer teasing, having experienced violence, frequent inebriation, and being overweight. CONCLUSION: DEB concern adolescent males more frequently than thought and seem to be integrated in a general dysfunctional context, in which violence is predominant. Adolescent males also need to be screened for DEB. Moreover, prevention programs should target the increasing social and media pressure regarding boys ideal body shape and raise public consciousness about this phenomenon.

Congenital disorder of glycosylation type Id (CDG Id): phenotypic, biochemical and molecular characterization of a new patient.

Congenital disorders of glycosylation (CDG) are a family of multisystem inherited disorders caused by defects in the biosynthesis of N- or O-glycans. Among the many different subtypes of CDG, the defect of a mannosyltransferase encoded by the human ALG3 gene (chromosome 3q27) is known to cause CDG Id. Six patients with CDG Id have been described in the literature so far. We further delineate the clinical, biochemical, neuroradiological and molecular features of CDG Id by reporting an additional patient bearing a novel missense mutation in the ALG3 gene. All patients with CDG Id display a slowly progressive encephalopathy with microcephaly, severe psychomotor retardation and epileptic seizures. They also share some typical dysmorphic features but they do not present the multisystem involvement observed in other CDG syndromes or any biological marker abnormalities. Unusually marked osteopenia is a feature in some patients and may remain undiagnosed until revealed by pathological fractures. Serum transferrin screening for CDG should be extended to all patients with encephalopathy of unknown origin, even in the absence of multisystem involvement.

Cono-spondylar dysplasia: Clinical, radiographic, and molecular findings of a previously unreported disorder.

We report on a consanguineous Arab family in which three sibs had an unusual skeletal dysplasia characterized by anterior defects of the spine leading to severe lumbar kyphosis and marked brachydactyly with cone epiphyses. The clinical phenotype also included dysmorphic facial features, epilepsy, and developmental delay. This constellation likely represents a previously undescribed skeletal dysplasia, most probably inherited in an autosomal recessive pattern. A homozygosity mapping approach has thus far failed to unearth the responsible gene as the region shared by these three sibs is 27.7 Mb in size and contains over 200 genes with no obvious candidate.

Rationale and first results of developing at-risk (prodromal) criteria for bipolar disorder.

Bipolar affective disorder (BD) is a severe, recurrent and disabling disorder with devastating consequences for individuals, families and society. Although these hazards and costs provide a compelling rationale for development of early detection and early intervention strategies in BD, the development of at-risk criteria for first episode mania is still in an early stage of development. In this paper we review the literature with respect to the clinical, neuroantomical and neuropsychological data, which support this goal. We also describe our recently developed bipolar at-risk criteria (BAR). This criteria comprises the peak age range of the first onset of bipolar disorder, genetic risk, presenting with sub-threshold mania, cyclothymic features or depressive symptoms. An initial pilot evaluation of the BAR criteria in 22 subjects indicated conversion rates to proxies of first-episode mania of 23% within 265 days on average, and high specificity and sensitivity of the criteria. If prospective studies confirm the validity of the BAR criteria, then the criteria would have the potential to open up new avenues of research for indicated prevention in BD and might therefore offer opportunities to ameliorate the severity of, or even prevent BD.

Screening for post-traumatic stress disorder (PTSD) in a psychiatric emergency setting

Background and Objectives: (i) to assess the prevalence of PTSD in a psychiatric emergency setting by means of a diagnostic instrument and to compare it with PTSD-prevalence of a clinically evaluated, historical sample; and (ii) to assess psychiatric residents' perception of the systematic use of this diagnostic instrument. Methods: A consecutive sample of patients (N = 403) evaluated for a psychiatric emergency was assessed with the module J (PTSD) of the MINI, the historical sample (N = 350), assessed by chart review, consisted of consecutive patients of the same setting evaluated one year prior to the study period. Residents' perceptions were assessed by means of a focus group. Results: While in only 0.57% of the historical sample (N = 350) a diagnosis of PTSD was recorded, 20.3% (N = 64) of the patients assessed with the diagnostic instrument (N = 316) qualified for a diagnosis of PTSD. Higher prevalence rates were observed in refugees and those without legal residency status (50%); patients from countries with a recent history of war (47.1%); those with four (44.4%) or three psychiatric co-morbidities (35.3%); migrants (29.8%) and patients without professional income (25%). Residents felt that the systematic use of the tool was not adequate in the psychiatric emergency setting for various reasons (e.g.: not suitable for a first or single consultation, negative impact on the clinical evaluation). Conclusions: The study confirms that PTSD is underdiagnosed in the psychiatric emergency setting. To improve the situation, targeted screening or educational and institutional strategies are needed.

Training referential communicative skills to individuals with autism spectrum disorder: a pilot study

Summary. The present study reports the effects of referential communication training in individuals formally diagnosed with autism spectrum disorder (ASD). Participants were 20 children with ASD (M age = 14.3 yr., SD = 4.2; 6 girls, 14 boys) in the role of speakers and 20 control children, who acted as listeners. They were all enrolled in mainstream compulsory education. Inclusion/exclusion criteria were defined according to the clinical diagnosis of ASD, the presence or absence of additional or associated disability, previous training in referential communication, and any drug treatment. Speakers were randomly assigned to one of two groups (trained vs untrained). Linguistic age, cognitive level, and autistic symptoms were analyzed, respectively, with the Peabody Picture Vocabulary Test (PPVT), the Wechsler Intelligence Scale (WISCR or WAISIII), and the Autistic Behavior Checklist (ABC). Communicative abilities were analyzed through two indexes related to message complexity and self-regulation. The trained group was trained in referential communication tasks (task analysis, role taking, and task evaluation), while the untrained group took part in a communicative game but without any specific communicative training. The results showed that the complexity of emitted messages had improved statistically significantly in the trained group as an effect of training. Ecological referential communication is shown to be an appropriate paradigm for studying the communicative process and its products and could be used to develop and implement a training program focused on those skills in which individuals with ASD are most deficient.

Assessment of emotional reactivity produced by exposure to virtual environments in patients with eating disorders

The aim of this study was to assess the usefulness of virtual environments representing situations that are emotionally significant to subjects with eating disorders (ED). These environments may be applied with both evaluative and therapeutic aims and in simulation procedures to carry out a range of experimental studies. This paper is part of a wider research project analyzing the influence of the situation to which subjects are exposed on their performance on body image estimation tasks. Thirty female patients with eating disorders were exposed to six virtual environments: a living-room (neutral situation), a kitchen with highcalorie food, a kitchen with low-calorie food, a restaurant with high-calorie food, a restaurant with low-calorie food, and a swimming-pool. After exposure to each environment the STAI-S (a measurement of state anxiety) and the CDB (a measurement of depression) were administered to all subjects. The results show that virtual reality instruments are particularly useful for simulating everyday situations that may provoke emotional reactions such as anxiety and depression, in patients with ED. Virtual environments in which subjects are obliged to ingest high-calorie food provoke the highest levels of state anxiety and depression.

Family burden related to clinical and functional variables of people with intellectual disability with and without a mental disorder

Few studies have been found that to assess the factors that explain higher levels of familyburden in adults with intellectualdisability (ID) and intellectualdisability and mental disorders (ID-MD). The aims of this study were to assess familyburden in people with ID and ID-MD and to determine which sociodemographic, clinical and functionaldisabilityvariables account for familyburden. The sample is composed of pairs of 203 participants with disability and their caregivers, of which 33.5% are caregivers of people with ID and 66.5% of ID-MD. Assessments were performed using scales of clinical and functionaldisability as the following instruments: Weschler Adult Intelligence Scale-III (WAIS-III), Inventory for Client and Agency Planning (ICAP), Psychiatric Assessment Schedule for Adults with Development Disability (PAS-ADD checklist), Disability Assessment Schedule of the World Health Organization (WHO-DAS-II) and familyburden (Subjective and Objective FamilyBurden Inventory - SOFBI/ECFOS-II). People with ID-MD presented higher levels of functionaldisability than those with ID only. Higher levels of familyburden were related to higher functionaldisability in all the areas (p < 0.006-0.001), lower intelligence quotient (p < 0.001), diagnosis of ID-MD (p < 0.001) and presence of organic, affective, psychotic and behavioral disorders (p < 0.001). Stepwise multiple regression showed that behavioral problems, affective and psychotic disorder, disability in participation in society, disability in personal care and presence of ID-MD explained more than 61% of the variance in familyburden. An integrated approach using effective multidimensional interventions is essential for both people with ID and ID-MD and their caregivers in order to reduce familyburden.

Using plan analysis in psychotherapeutic case formulation of borderline personality disorder.

A comprehensive understanding of the patient's problems is essential for a constructive therapeutic behaviour, especially in borderline personality disorder (BPD) where difficult interpersonal patterns are persistent. In these circumstances, the use of an integrative case formulation approach such as Plan Analysis, developed by K. Grawe and F. Caspar, can be of help for therapy planning. The focus here is on instrumental relations between behaviours and the hypothetical Plans and motives 'behind' those behaviours. The present qualitative study aimed at setting a prototypical Plan structure for n = 15 patients presenting a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, diagnosis of BPD using Plan Analysis. The first psychotherapeutic session of every outpatient was video-taped and evaluated according to the Plan Analysis procedure. Inter-rater reliability was established between two independent raters and was considered sufficient. The detailed prototypical Plan structure of BPD showed two main tendencies: first, the important presence of support-seeking among these patients and second, the will to be in control and to protect oneself. This study confirms the existence of several core similarities in the functioning of patients with BPD. These findings are in line with earlier studies and expand the latter with the aim of contributing to the understanding of BPD psychopathology. Clinical implications are discussed. Copyright © 2011 John Wiley & Sons, Ltd. KEY PRACTITIONER MESSAGE: Plan Analysis can especially be of help with patients who have difficult interpersonal patterns, as those presenting with BPD. Two tendencies were found within BPD patients: (1) support-seeking and (2) control and self-protecting Plans. Further research using Plan Analysis should focus on the identification and detail of emotions within BPD.

Exploring the proposed DSM-5 diagnostic threshold and severity scale for the alcohol use disorder

Aims :¦Several studies have questioned the validity of separating the diagnosis of alcohol abuse from that of alcohol dependence, and the DSM-5 task force has proposed combining the criteria from these two diagnoses to assess a single category of alcohol use disorders (AUD). Furthermore, the DSM-5 task force has proposed including a new 2-symptom threshold and a severity scale based on symptom counts for the AUD diagnosis. The current study aimed to examine these modifications in a large population-based sample.¦Method :¦Data stemmed from an adult sample (N=2588 ; mean age 51.3 years (s.d.: 0.2), 44.9% female) of current and lifetime drinkers from the PsyCoLaus study, conducted in the Lausanne area in Switzerland. AUDs and validating variables were assessed using a semi-structured diagnostic interview for the assessment of alcohol¦and other major psychiatric disorders. First, the adequacy of the proposed 2- symptom threshold was tested by comparing threshold models at each possible cutoff and a linear model, in relation to different validating variables. The model with the smallest Akaike Criterion Information (AIC) value was established as the best¦model for each validating variable. Second, models with varying subsets of individual AUD symptoms were created to assess the associations between each symptom and the validating variables. The subset of symptoms with the smallest AIC value was established as the best subset for each validator.¦Results :¦1) For the majority of validating variables, the linear model was found to be the best fitting model. 2) Among the various subsets of symptoms, the symptoms most frequently associated with the validating variables were : a) drinking despite having knowledge of a physical or psychological problem, b) having had a persistent desire or unsuccessful efforts to cut down or control drinking and c) craving. The¦least frequent symptoms were : d) drinking in larger amounts or over a longer period than was intended, e) spending a great deal of time in obtaining, using or recovering from alcohol use and f) failing to fulfill major role obligations.¦Conclusions :¦The proposed DSM-5 2-symptom threshold did not receive support in our data. Instead, a linear AUD diagnosis was supported with individuals receiving an increasingly severe AUD diagnosis. Moreover, certain symptoms were more frequently associated with the validating variables, which suggests that these¦symptoms should be considered as more severe.

What's so special about conversion disorder? A problem and a proposal for diagnostic classification.

Conversion disorder presents a problem for the revisions of DSM-IV and ICD-10, for reasons that are informative about the difficulties of psychiatric classification more generally. Giving up criteria based on psychological aetiology may be a painful sacrifice but it is still the right thing to do.