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.

Is the relationship between major depressive disorder and self-reported alcohol use disorder an artificial one ?

AIMS: Many studies have suggested a close relationship between alcohol use disorder (AUD) and major depressive disorder (MDD). This study aimed to test whether the relationship between self-reported AUD and MDD was artificially strengthened by the diagnosis of MDD. This association was tested comparing relationships between alcohol use and AUD for depressive people and non-depressive people. METHODS: As part of the Cohort Study on Substance Use Risk Factors, 4352 male Swiss alcohol users in their early twenties answered questions concerning their alcohol use, AUD and MDD at two time points. Generalized linear models for cross-sectional and longitudinal associations were calculated. RESULTS: For cross-sectional associations, depressive participants reported a higher number of AUD symptoms (β = 0.743, P < 0.001) than non-depressive participants. Moreover, there was an interaction (β = -0.204, P = 0.001): the relationship between alcohol use and AUD was weaker for depressive participants rather than non-depressive participants. For longitudinal associations, there were almost no significant relationships between MDD at baseline and AUD at follow-up, but the interaction was still significant (β = -0.249, P < 0.001). CONCLUSION: MDD thus appeared to be a confounding variable in the relationship between alcohol use and AUD, and self-reported measures of AUD seemed to be overestimated by depressive people. This result brings into question the accuracy of self-reported measures of substance use disorders. Furthermore, it adds to the emerging debate about the usefulness of substance use disorder as a concept, when heavy substance use itself appears to be a sensitive and reliable indicator.

Interobserver agreement and validity of bedside 'positive signs' for functional weakness, sensory and gait disorders in conversion disorder: a pilot study.

BACKGROUND: Conversion disorder (CD) is no longer a diagnosis of exclusion. The new DSM-V criteria highlight the importance of 'positive signs' on neurological examination. Only few signs have been validated, and little is known about their reliability. OBJECTIVE: The aim was to examine the clinical value of bedside positive signs in the diagnosis of CD presenting with weakness, gait or sensory symptoms by assessing their specificity, sensitivity and their inter-rater reliability. PATIENTS AND METHODS: Standardised video recorded neurological examinations were performed in 20 consecutive patients with CD and 20 'organic' controls. Ten previously validated sensory and motor signs were grouped in a scale. Thirteen additional motor/sensory 'positive signs', 14 gait patterns and 1 general sign were assessed in a pilot validation study. In addition, two blinded independent neurologists rated the video recordings to assess the inter-rater reliability (Cohen's κ) of each sign. RESULTS: A score of ≥4/14 on the sensory motor scale showed a 100% specificity (CI 85 to 100) and a 95% sensitivity (CI 85 to 100). Among the additional tested signs, 10 were significantly more frequent in CD than controls. The interobserver agreement was acceptable for 23/38 signs (2 excellent, 10 good, 11 moderate). CONCLUSIONS: Our study confirms that six bedside 'positive signs' are highly specific for CD with good-excellent inter-rater reliability; we propose to consider them as 'highly reliable signs'. In addition 13 signs could be considered as 'reliable signs' and six further signs as 'suggestive signs' while all others should be used with caution until further validation is available.

Characterization and occurence of eairly softening disorder in 'golden' papaya fruits

The occurrence of green skin and soft pulp in 'Golden' papaya fruit during certain seasons has been reported by farmers in the northern of the state of Espirito Santo, Brazil. The objective of this study was to characterize and determine the occurrence of this disorder, which was referred as "early softening disorder". Fruits were harvested weekly for 11 months (from September to July). The fruits were stored at 10°C, and then fruit flesh firmness and skin color were analyzed. The results of the firmness test were submitted to regression analysis assuming a linear trendline. The slope of the curve was called the 'softening index' (SI). Fruits with early softening are characterized by a loss of firmness in less than 10 days, even when stored under refrigeration. Although softened, the skin of the fruit remains partially green. Fruits with the disorder occurred more frequently from mid-summer to mid-autumn (February to May). It is not possible to distinguish early softening disorder fruits from those without the disorder by skin color and flesh firmness analysis at the time of the harvest.

Clinical management and burden of bipolar disorder: a multinational longitudinal study (WAVE-bd Study)

BACKGROUND: Studies in bipolar disorder (BD) to date are limited in their ability to provide a whole-disease perspective--their scope has generally been confined to a single disease phase and/or a specific treatment. Moreover, most clinical trials have focused on the manic phase of disease, and not on depression, which is associated with the greatest disease burden. There are few longitudinal studies covering both types of patients with BD (I and II) and the whole course of the disease, regardless of patients' symptomatology. Therefore, the Wide AmbispectiVE study of the clinical management and burden of Bipolar Disorder (WAVE-bd) (NCT01062607) aims to provide reliable information on the management of patients with BD in daily clinical practice. It also seeks to determine factors influencing clinical outcomes and resource use in relation to the management of BD. METHODS: WAVE-bd is a multinational, multicentre, non-interventional, longitudinal study. Approximately 3000 patients diagnosed with BD type I or II with at least one mood event in the preceding 12 months were recruited at centres in Austria, Belgium, Brazil, France, Germany, Portugal, Romania, Turkey, Ukraine and Venezuela. Site selection methodology aimed to provide a balanced cross-section of patients cared for by different types of providers of medical aid (e.g. academic hospitals, private practices) in each country. Target recruitment percentages were derived either from scientific publications or from expert panels in each participating country. The minimum follow-up period will be 12 months, with a maximum of 27 months, taking into account the retrospective and the prospective parts of the study. Data on demographics, diagnosis, medical history, clinical management, clinical and functional outcomes (CGI-BP and FAST scales), adherence to treatment (DAI-10 scale and Medication Possession Ratio), quality of life (EQ-5D scale), healthcare resources, and caregiver burden (BAS scale) will be collected. Descriptive analysis with common statistics will be performed. DISCUSSION: This study will provide detailed descriptions of the management of BD in different countries, particularly in terms of clinical outcomes and resources used. Thus, it should provide psychiatrists with reliable and up-to-date information about those factors associated with different management patterns of BD. TRIAL REGISTRATION NO: ClinicalTrials.gov: NCT01062607.

Brain functional abnormality in schizo-affective disorder: an fMRI study.

Background.Schizo-affective disorder has not been studied to any significant extent using functional imaging. The aim of this study was to examine patterns of brain activation and deactivation in patients meeting strict diagnostic criteria for the disorder. METHOD: Thirty-two patients meeting research diagnostic criteria (RDC) for schizo-affective disorder (16 schizomanic and 16 schizodepressive) and 32 matched healthy controls underwent functional magnetic resonance imaging (fMRI) during performance of the n-back task. Linear models were used to obtain maps of activations and deactivations in the groups. RESULTS: Controls showed activation in a network of frontal and other areas and also deactivation in the medial frontal cortex, the precuneus and the parietal cortex. Schizo-affective patients activated significantly less in prefrontal, parietal and temporal regions than the controls, and also showed failure of deactivation in the medial frontal cortex. When task performance was controlled for, the reduced activation in the dorsolateral prefrontal cortex (DLPFC) and the failure of deactivation of the medial frontal cortex remained significant. CONCLUSIONS: Schizo-affective disorder shows a similar pattern of reduced frontal activation to schizophrenia. The disorder is also characterized by failure of deactivation suggestive of default mode network dysfunction.

Mood disorders in eating disorder patients: Prevalence and chronology of ONSET.

OBJECTIVES: In a clinical population, we estimated the frequency of mood disorders among 271 patients suffering from Anorexia Nervosa (AN) and Bulimia Nervosa (BN) in comparison to a control group matched for age and gender. METHOD: The frequency of mood disorders was measured using the Mini International Neuropsychiatric Interview (MINI), DSM-IV version. RESULTS: Mood disorders were more frequent among eating disorder (ED) patients than among controls, with a global prevalence of the order of 80% for each ED group. The majority of the mood disorders comorbid with ED were depressive disorders (MDD and dysthymia). The relative chronology of onset of these disorders was equivocal, because mood disorders in some cases preceded and in others followed the onset of the eating disorders. LIMITATIONS: Our sample was characterized by patients with severe ED and high comorbidities, and thus do not represent the entire population of AN or BN. This also may have resulted in an overestimation of prevalence. CONCLUSION: Mood disorders appear significantly more frequently in patients seeking care for ED than in controls. These results have implications for the assessment and treatment of ED patients, and for the aetio-pathogenesis of these disorders.

Efficacy of brief interdisciplinary psychotherapeutic intervention for motor conversion disorder and nonepileptic attacks.

OBJECTIVE: The objective was to compare a brief interdisciplinary psychotherapeutic intervention to standard care as treatments for patients recently diagnosed with severe motor conversion disorder or nonepileptic attacks. METHODS: This randomized controlled trial of 23 consecutive patients compared (a) an interdisciplinary psychotherapeutic intervention group receiving four to six sessions by a consultation liaison psychiatrist, the first and last sessions adding a neurological consultation and a joint psychiatric and neurological consultation, and (b) a standard care group. After intervention, patients were assessed at 2, 6 and 12 months with the Somatoform Dissociation Questionnaire (SDQ-20), Clinical Global Impression scale, Rankin scale, use of medical care, global mental health [Montgomery and Asberg Depression Rating Scale, Beck Depression Inventory, mental health component of Short Form (SF)-36] and quality of life (SF-36). We calculated linear mixed models. RESULTS: Our intervention brought a statistically significant improvement of physical symptoms [as measured by the SDQ-20 (P<.02) and the Clinical Global Impression scale (P=.02)] and psychological symptoms [better scores on the mental health component of the SF-36 (P<.05) and on the Beck Depression Inventory (P<.05)] and a reduction in new hospital stays after intervention (P<.05). CONCLUSION: A brief psychotherapeutic intervention taking advantage of a close collaboration with neurology consultants in the setting of consultation liaison psychiatry appears effective.

Executive dysfunction and memory impairment in schizoaffective disorder: a comparison with bipolar disorder, schizophrenia and healthy controls.

BACKGROUND: Deficits in memory and executive performance are well-established features of bipolar disorder and schizophrenia. By contrast, data on cognitive impairment in schizoaffective disorder are scarce and the findings are conflicting. METHOD: We used the Wechsler Memory Scale (WMS-III) and the Behavioural Assessment of the Dysexecutive Syndrome (BADS) to test memory and executive function in 45 schizophrenic patients, 26 schizomanic patients and 51 manic bipolar patients in comparison to 65 healthy controls. The patients were tested when acutely ill. RESULTS: All three patient groups performed significantly more poorly than the controls on global measures of memory and executive functioning, but there were no differences among the patient groups. There were few differences in memory and executive function subtest scores within the patient groups. There were no differences in any test scores between manic patients with and without psychotic symptoms. CONCLUSIONS: Schizophrenic, schizomanic and manic patients show a broadly similar degree of executive and memory deficits in the acute phase of illness. Our results do not support a categorical differentiation across different psychotic categories with regard to neuropsychological deficits.

"Efficacy of brief interdisciplinary psychotherapeutic intervention for moto conversion disorder and non-epileptic attacks"

Comparer une intervention psychothérapeutique interdisciplinaire brève à une prise en charge standard comme traitements pour des patients ayant récemment été diagnostiqués comme souffrant d'un trouble de conversion moteur sévère ou d'attaques non-épileptiques. Méthodes Cette étude randomisée contrôlée de 23 patients consécutifs a comparé a) un groupe d'intervention psychothérapeutique interdisciplinaire recevant 4-6 séances par un psychiatre de liaison, la première et dernière séance étant couplée à une consultation neurologique et à une consultation conjointe par le neurologue et le psychiatre; b) un groupe de prise en charge standard. Après l'intervention, les patients ont été évalués à 2, 6 et 12 mois par le questionnaire de dissociation somatoforme SDQ-20, l'échelle d'impression clinique globale, l'échelle de Rankin, l'utilisation des services de santé, la santé mentale en général (MADRS, échelle de dépression de Beck, composante de santé mentale du SF-36), la qualité de vie (SF-36). Nous avons calculé des modèles linéaires mixtes. Résultats Notre intervention a mené à une amélioration statistiquement significative ? des symptômes physiques (par une mesure du SDQ-20 (p<0.02), et par l'échelle de l'impression clinique globale (p=0.02)) ? des symptômes psychologiques (meilleurs scores à la composante de santé mentale du SF-36 (p<0.05) et à l'inventaire de dépression de Beck (p<0.05)) ? et à une réduction des nouvelles hospitalisations après l'intervention (p<0.05). Conclusion Une intervention psychothérapeutique interdisciplinaire brève en étroite collaboration avec des spécialistes en neurologie dans un cadre de psychiatrie de consultation et liaison a un effet statistiquement significatif sur l'amélioration de patients souffrant de trouble de conversion moteur et d'attaques non-épileptiques.

The specificity of the familial aggregation of early-onset bipolar disorder: A controlled 10-year follow-up study of offspring of parents with mood disorders.

BACKGROUND: Two major sources of heterogeneity of mood disorders that have been demonstrated in clinical, family and genetic studies are the mood disorder subtype (i.e. bipolar (BPD) and major depressive disorder (MDD)) and age of onset of mood episodes. Using a prospective high-risk study design, our aims were to test the specificity of the parent-child transmission of BPD and MDD and to establish the risk of psychopathology in offspring in function of the age of onset of the parental disorder. METHODS: Clinical information was collected on 208 probands (n=81 with BPD, n=64 with MDD, n=63 medical controls) as well as their 202 spouses and 372 children aged 6-17 years at study entry. Parents and children were directly interviewed every 3 years (mean duration of follow-up=10.6 years). Parental age of onset was dichotomized at age 21. RESULTS: Offspring of parents with early onset BPD entailed a higher risk of BPD HR=7.9(1.8-34.6) and substance use disorders HR=5.0(1.1-21.9) than those with later onset and controls. Depressive disorders were not significantly increased in offspring regardless of parental mood disorder subtype or age of onset. LIMITATIONS: Limited sample size, age of onset in probands was obtained retrospectively, age of onset in co-parents was not adequately documented, and a quarter of the children had no direct interview. CONCLUSIONS: Our results provide support for the independence of familial aggregation of BPD from MDD and the heterogeneity of BPD based on patterns of onset. Future studies should further investigate correlates of early versus later onset BPD.