Raoul Belzeaux

Responder and nonresponder patients exhibit different peripheral transcriptional signatures during major depressive episode.

To date, it remains impossible to guarantee that short-term treatment given to a patient suffering from a major depressive episode (MDE) will improve long-term efficacy. Objective biological measurements and biomarkers that could help in predicting the clinical evolution of MDE are still warranted. To better understand the reason nearly half of MDE patients respond poorly to current antidepressive treatments, we examined the gene expression profile of peripheral blood samples collected from 16 severe MDE patients and 13 matched controls. Using a naturalistic and longitudinal design, we ascertained mRNA and microRNA (miRNA) expression at baseline, 2 and 8 weeks later. On a genome-wide scale, we detected transcripts with roles in various biological processes as significantly dysregulated between MDE patients and controls, notably those involved in nucleotide binding and chromatin assembly. We also established putative interactions between dysregulated mRNAs and miRNAs that may contribute to MDE physiopathology. We selected a set of mRNA candidates for quantitative reverse transcriptase PCR (RT-qPCR) to validate that the transcriptional signatures observed in responders is different from nonresponders. Furthermore, we identified a combination of four mRNAs (PPT1, TNF, IL1B and HIST1H1E) that could be predictive of treatment response. Altogether, these results highlight the importance of studies investigating the tight relationship between peripheral transcriptional changes and the dynamic clinical progression of MDE patients to provide biomarkers of MDE evolution and prognosis.

Assessment of psychiatric inpatient satisfaction: A systematic review of self-reported instruments

BACKGROUNDnThere is a growing concern about satisfaction with inpatient psychiatric services. There are currently numerous satisfaction instruments available to psychiatric inpatients, but little guidance on which among them to select.nnnAIMSnTo provide an overview of the psychometric properties and the content of satisfaction instruments available to psychiatric inpatients.nnnMETHODSnSystematic searches of Medline database to identify inpatient satisfaction questionnaires. Assessment of the instruments according to relevant psychometric properties.nnnRESULTSnFifteen satisfaction instruments were identified. The target population differed according to the instrument. Methods used to generate items were heterogeneous. These instruments were based on a mixed approach including patients points of view, expert opinions, and literature reviews, causing the content of questionnaires to vary. Reliability and validity were not systematically tested.nnnCONCLUSIONnThe validation of a common inpatient satisfaction instrument is a major challenge. Recommendations for the future development of satisfaction instruments may include: item generation based exclusively on the patients point of view; a validation process on a large and representative population; and an instrument combining generic (core questionnaire) and specific (additional modules) approaches.

Dissociating Bottom-Up and Top-Down Mechanisms in the Cortico-Limbic System during Emotion Processing

The cortico-limbic system is critically involved in emotional responses and resulting adaptive behaviors. Within this circuit, complementary regions are believed to be involved in either the appraisal or the regulation of affective state. However, the respective contribution of these bottom-up and top-down mechanisms during emotion processing remains to be clarified. We used a new functional magnetic resonance imaging (fMRI) paradigm varying 3 parameters: emotional valence, emotional congruency, and allocation of attention, to distinguish the functional variation in activity and connectivity between amygdala, anterior cingulate cortex (ACC), and dorsolateral prefrontal cortex (DLPFC). Bottom-up appraisal of negative compared with positive stimuli led to a greater amygdala response and stronger functional interaction between amygdala and both dorsal ACC and DLPFC. Top-down resolution of emotional conflict was associated with increased activity within ACC and higher functional connectivity between this structure, and both the amygdala and DLPFC. Finally, increased top-down attentional control caused greater engagement of the DLPFC, accompanied by increased connectivity between DLPFC and dorsal ACC. This novel task provides an efficient tool for exploring bottom-up and top-down processes underlying emotion and may be particularly helpful for investigating the neurofunctional underpinnings of psychiatric disorders.

Characteristics and profiles of bipolar I patients according to age-at-onset: findings from an admixture analysis.

BACKGROUNDnMany studies have used admixture analysis to separate age-at-onset (AAO) subgroups in bipolar patients, but few have looked at the phenomenological characteristics of these subgroups, in order to find out phenotypic markers.nnnMETHODSnAdmixture analysis was applied to identify the model best fitting the observed AAO distribution of a sample of 1082 consecutive DSM-IV bipolar I manic inpatients who were assessed for demographic, clinical, course of illness, comorbidity, and temperamental characteristics.nnnRESULTSnThe model best fitting the observed distribution of AAO was a mixture of three Gaussian distributions. We could identify three AAO subgroups: early, intermediate, and late age-at-onset (EAO, IAO, and LAO, respectively). Patients in the EAO subgroup were more often single young males exhibiting severe mania with psychotic features, a subcontinuous course of illness with substance use and panic comorbidity, more suicide attempts, and temperamental components sharing hypomanic features. Patients with LAO showed a less severe picture with more depressive temperamental components, alcohol use and comorbid general medical conditions. A less typical phenotype was present in IAO patients.nnnLIMITATIONSnThe following are the limitations of this study: retrospective design, and bias toward preferential enrollment of patients with manic predominant polarity.nnnCONCLUSIONSnThis study confirms that bipolar I disorder can be subdivided into three subgroups based on AAO distribution and shows that patients from these subgroups differ in phenotypes.

Self-assessment and characteristics of mixed depression in the French national EPIDEP study.

BACKGROUNDnStudies on mixed depression have been conducted so far on the basis of DSM-IV manic symptoms, i.e., a list of 7 symptoms which may provide limited information on the subsyndromal features associated with a full depressive episode.nnnMETHODSnAs part of the EPIDEP National Multisite French Study of 493 consecutive DSM-IV major depressive patients evaluated in at least two semi-structured interviews 1 month apart, 102 (23.8%) were classified as mixed depressives (≥3 hypomanic symptoms), and 146 (34%) as pure depressives (0 hypomanic symptom), after exclusion of bipolar I patients; hypomanic symptoms were assessed with the Multiple Visual Analog Scales of Bipolarity (MVAS-BP, 26 items) of Ahearn-Carroll in a self assessment format. A narrower definition of mixed depression, resting on those MVAS-BP items referring to DSM-IV hypomanic symptoms was also tested, as a sensitivity analysis.nnnRESULTSnCompared to pure depressives, mixed depressive patients had more psychotic symptoms, atypical features and suicide attempts during their index episode; their illness course was characterized by early age at onset, frequent episodes, rapid cycling, and comorbidities. Mixed depressive patients were more frequently bipolar with a family history of bipolar disorder, alcohol abuse, and suicide. A dose-response relationship was found between intradepression hypomania and several clinical features, including temperament measures. The following independent variables were associated with mixed depression: hyperthymic temperament, cyclothymic temperament, irritable temperament, and alcohol abuse. Using the narrower definition of mixed depression missed risk factors such as suicidality and comorbidities.nnnLIMITATIONSnThe following are the limitations of this study: retrospective design, recall bias, lack of sample homogeneity, no cross-validation of findings by hetero-evaluation of hypomanic symptoms.nnnCONCLUSIONSnEPIDEP data showed the feasibility and face validity of self-assessment of intradepressive hypomania. They replicated previous findings on the severity and high suicidal risk of mixed depression profile. They confirmed, for mixed depression, that mixed states occur when mood episodes are superimposed upon temperaments of opposite polarity. They finally suggested that a definition of mixed depression only based on DSM-IV-TR hypomanic symptoms may not allow to identify the most unstable subforms of the entity.

Mental Disorders Among Homeless People Admitted to a French Psychiatric Emergency Service

OBJECTIVEnThe aim of this study was to identify factors associated with homelessness status among patients admitted to the psychiatric emergency ward of a French public teaching hospital over a six-year study period (2001-2006).nnnMETHODSnThe study was based on a retrospective review of the psychiatric emergency wards administrative and medical computer databases. Each emergency care episode had accompanying data that included demographic, financial, clinical, and management information.nnnRESULTSnDuring this six-year study, the psychiatric service recorded 16,754 care episodes for 8,860 different patients, of which 591 were homeless (6.7%) and 8,269 were nonhomeless (93.3%). The mean+/-SD number of visits to the psychiatric emergency service was higher for homeless patients (4.9+/-12.3) than for nonhomeless patients (1.7+/-2.4) (p<.001). A total of 331 homeless patients (56.0%) had more than one care episode, whereas 2,180 (26.4%) of nonhomeless patients had more than one care episode. Factors associated with homelessness included being male, being single, and receiving financial assistance through government social programs. Schizophrenia (43.7%) and substance use disorders (31.0%) were the most common disorders among homeless patients. Aggressive behavior and violence were reported equally among homeless patients (3.5%) and nonhomeless patients (3.2%). Homeless patients were less likely than nonhomeless patients to be hospitalized after receiving care in the emergency ward (47.8% versus 51.1%) (p=.002).nnnCONCLUSIONSnAlthough there is near-universal access to free mental health care in France, study findings suggest that the quality and adequacy of subsequent care are not guaranteed. Multidisciplinary and collaborative solutions are needed to improve the management of mental health care for homeless patients.

A social network analysis of healthcare professional relationships in a French hospital

PURPOSEnThis paper aims to describe relationships among healthcare professionals in a French public hospital using social network analysis (SNA) and to improve health service quality by strengthening health service management and leadership.nnnDESIGN/METHODOLOGY/APPROACHnThis study was based on a questionnaire sent to randomly selected French public hospital professionals and administrators. Network composition measures were obtained using a name generator. Analysis focused on three main indicators: centrality, prestige, and clique participants. The SNA was carried out using UCINET and statistical analyses were performed with SPSS version 15.0.nnnFINDINGSnA total of 104 questionnaires were returned and analysed. Centrality, prestige and clique indicators were highly correlated (all p-value were less than 0.01). Physicians had the highest scores for the three indicators. Older age (> or = 45 years) was associated with higher centrality and clique numbers scores. Transversal activity was associated with higher scores than other specific activities (hospitalisation, ambulatory care), except for emergency care.nnnORIGINALITY/VALUEnThe paper shows how networks and SNA techniques provide novel and useful means to understand communication and collaboration between hospital professionals.

Risks associated with gender differences in bipolar I disorder

BACKGROUNDnPrevious studies have demonstrated that bipolar patients may differ in several features according to gender, but a number of the differences found remain controversial.nnnMETHODSnThe demographic, illness course, clinical, comorbidity and temperament characteristics of a total of 1090 consecutive DSM-IV bipolar I manic inpatients were compared according to gender.nnnRESULTSnBipolar illness in women was characterised by the predominance of depression, as indicated by a depressive polarity at onset, higher rates of mixed mania, more suicidal behaviour, and a greater number of temperaments with depressive propensities. In contrast, the manic component was found to predominate in men. Men also had an earlier onset of their illness. Women displayed more comorbidities with eating, anxiety, and endocrine/metabolic disorders, whereas men were more comorbid with alcoholism and other forms of substance abuse, neurological, and cancer disorders. The following independent variables were associated with male gender: being single (+), depressive temperament (-), excessive alcohol use (+), cyclothymic temperament (-), excessive other substance use (+), mood congruent psychotic features (+), and manic polarity at onset (+).nnnLIMITATIONSnThe retrospective design and the sample being potentially not representative of the bipolar disorder population are limitations.nnnCONCLUSIONSnFindings from this study tend to confirm most of the differences previously observed among bipolar men and women. Furthermore, these results draw attention to the risks that may be specifically linked to gender differences in bipolar I patients.

Depressive residual symptoms are associated with lower adherence to medication in bipolar patients without substance use disorder: results from the FACE-BD cohort.

BACKGROUNDnPoor adherence to medication is frequent in Bipolar Disorder (BD). It is associated with illness severity and increases total medical cost. Several factors are associated with poor adherence but previous studies included heterogeneous cohorts of patients with and without current mood episode, with and without SUD.nnnMETHODSnWe conducted a cross-sectional study, based on the Fondamental Advanced Centers of Expertise in Bipolar Disorders. 382 patients diagnosed with BD (type I, II or NOS) according to DSM-IV, with partial or complete remission and without comorbid SUD, were included. All patients had a large standardized clinical evaluation with structured interview and self reports. Side effects were evaluated with Patient Rated Inventory of Side Effects (PRISE). Adherence behavior was measured by a self reported scale, Medication Adherence Rating Scale (MARS). Univariate analyses and linear regression models were undertaken to determine factors associated with adherence.nnnRESULTSnResidual depressive symptoms (β=-0.155, p=0.004), and side effects (β=-0.142, p=0.008) were the main factors associated with adherence behavior in linear regression model. We found no association with residual manic symptoms, age at assessment, marital status, number of past mood episodes as well as past psychotic symptoms.nnnLIMITATIONnWe used no other assessment than self-rating scale for adherence behavior evaluation. We had no information concerning treatment regimen and patient/family knowledge about BD.nnnCONCLUSIONSnAdherence behavior in bipolar patients appears to be mainly influenced by the presence of residual depressive symptoms in patients without SUD. Improvement in diagnosis and pharmacotherapy of residual depressive symptoms has to be kept in mind to face low adherence to medication.

Neurofibromatose de type 1: Troubles psychiatriques et altération de la qualité de vie

Points essentiels La neurofibromatose de type 1 (NF1) est souvent associee aux troubles psychiatriques. Ils sont plus frequents chez les patients atteints de NF1 que dans la population generale (33% des patients). La dysthymie est le diagnostic le plus frequent (21% des patients). Une frequence importante de trouble de l’humeur de type depressif (7% des patients), de troubles anxieux (1 a 6% des patients) et de troubles de la personnalite (3% des patients) est observee. Le risque suicidaire est egalement accru (4 fois plus que dans la population generale). Les troubles de l’humeur bipolaires et la schizophrenie sont rares. L’alteration de la qualite de vie observee dans la NF1 semble etre un facteur important dans l’apparition de ces troubles psychiatriques. L’evaluation de celle-ci permettrait de definir une population a risque.Neurofibromatosis type 1 (NF1) is often associated with psychiatric disorders, which are more frequent in NF1 than in general population (33% of patients). Dysthymia is the most frequent diagnosis (21% of patients). There is also a high prevalence of depressive mood (7%), anxiety (1-6%), and personality (3%) disorders. The risk of suicide is four times greater than in the general population. Bipolar mood disorders or schizophrenia appear to be rare. The impaired quality of life associated with NF1 may play an important role in the development of psychiatric disorders. Quality of life assessments may help to identify a population at high risk.