Bipolar patients referred to specialized services of care: Not resistant but impaired by sub-syndromal symptoms. Results from the FACE-BD cohort.

OBJECTIVE: A national network of expert centers for bipolar disorders was set up in France to provide support, mainly for psychiatrists, who need help for managing bipolar disorder patients. The aims of this article are to present the main characteristics of the patients referred to an expert center in order to highlight the major disturbances affecting these patients and to understand the most significant difficulties encountered by practitioners dealing with bipolar disorder patients. METHODS: Patients were evaluated by trained psychiatrists and psychologists, with standardized and systematic assessment using interviews and self-report questionnaires. RESULTS: All patients (n = 839) met Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition criteria for bipolar disorder I (48.4%), bipolar disorder II (38.1%) or bipolar disorder-not otherwise specified (13.5%). Mean illness duration was 17 years (±11.3), with 41.9% of patients having a history of suicide attempts. Lifetime comorbidities were 43.8% for anxiety disorders and 32.8% for substance abuse. At the point of inclusion, most patients (76.2%) were not in an acute phase, being considered to have a syndromal remission, but which still required referral to a tertiary system of care. Among these patients, 37.5% had mild to moderate residual depressive symptoms (Montgomery and Asberg Depression Rating Scale ranging from 7 to 19) despite 39% receiving an antidepressant. However, 47.8% were considered to be poorly adherent to medication; 55% showed evidence of sleep disturbances, with half being overweight; 68.1% of patients showed poor functioning (Functioning Assessment Short Test ⩾ 12) with this being linked to residual depressive symptoms, sleep disturbances and increased body mass index. CONCLUSIONS: It appears that bipolar disorder patients referred to an expert center in most cases do not suffer from a severe or resistant illness but they rather have residual symptoms, including subtle but chronic perturbations that have a major impact on levels of functioning. The longitudinal follow-up of these patients will enable a better understanding of the evolution of such residual symptoms.

Staging and neuroprogression in bipolar disorder.

The apparently progressive nature of a considerable proportion of cases of bipolar disorder (BD) has been acknowledged in recently proposed clinical staging models. This has been part of an attempt to facilitate and refine diagnosis, treatment selection, and establish a prognosis. The study of the progressive nature of some cases of BD has given raise to the hypothesis of neuroprogression, which postulates that different stages of BD are associated with distinct neurobiological underpinnings. Given that BD may be intimately associated with chronic stress response and coping mechanisms over the course of illness, we propose that cellular resilience mechanisms may play a key role in the neuroprogression in BD. In the present study, we review neuroanatomical evidence of the progression that occurs in many cases of BD, as well as cellular resilience mechanisms and peripheral biomarkers associated with distinct stages of this disorder. In summary, cellular resilience mechanisms seem to be less efficient at later stages of BD, especially mitochondrial and endoplasmic reticulum-related responses to stress. These insights may help in developing staging models of BD, with a special emphasis on the search for biomarkers associated with illness progression.

Polymorphism of Toll-like receptor 4 gene in bipolar disorder.

BACKGROUND: Bipolar disorder (BD) is considered as a multifactorial disorder involving complex interactions between genetic and environmental factors, where immune dysfunction is thought to play a key etiopathogenic role. In particular, excess of winter births associated with early-life infections raise the possibility of the implication of innate immunity. Given the pivotal role of Toll-like receptor 4 (TLR-4), a major innate immune sensor molecule, we hypothesized that genetic variations of TLR-4 may be associated to BD. METHODS: Genomic DNAs from 572 BD patients and 202 healthy controls (HC) were analyzed for the distribution of six single nucleotides polymorphisms (SNPs) scattered along the TLR-4 locus (rs1927914, rs10759932, rs4986790, rs4986791, rs11536889 and rs11536891). Associations between BD and these polymorphisms were examined using the Chi-square test. RESULTS: We found that rs1927914 AA and rs11536891 TT genotype are more frequent in BD patients than in controls (corrected p; pc=.02 and .02 respectively) particularly in early-onset BD patients (pc=.004 and .006) born during the summer season (pc=.02 and .002 respectively). We also found that rs4986790 AG and rs4986791 CT genotypes were significantly associated with presence of autoimmune thyroiditis (pc=.002). LIMITATIONS: Our results are to be confirmed by replication in independent BD cohorts. CONCLUSIONS: We report for the first time a genetic association between BD and TLR-4 a major player of innate immunity. Possible mechanisms underlying bipolar disorders linking altered TLR-4 expression and increased susceptibility to infections and/or autoimmunity are discussed.

High prevalence and prescription of benzodiazepines for elderly: data from psychiatric consultation to patients from an emergency room of a general hospital.

OBJECTIVES: The aim of this study is to compare the use and prescription of psychotropic drugs, with emphasis on benzodiazepines, in elderly and non-elderly patients who are assisted at the emergency room by a psychiatric consultation of a university teaching hospital. METHOD: This is a cross-sectional study. We analyzed all records of psychiatric consultation in an emergency room of a general hospital from March 2009 until March 2010. Sociodemographic and clinical variables were compared between the group of elderly and non-elderly in two cutoff points (≥60 and ≥65 years), with emphasis on the use and prescription of benzodiazepines. RESULTS: Five hundred seventy-five records were found with 71 elderly and 504 nonelderly for the first cutoff point and 51 elderly and 524 nonelderly in the second. Differences between groups were found in all sociodemographic variables (gender, marital status, education, current occupational status). Elderly patients treated at emergency rooms used more psychotropic drugs, particularly antidepressants and benzodiazepines, than non-elderly. About 25% of the patients received benzodiazepine treatment in the emergency setting, and there was no statistical difference between age groups. CONCLUSION: There is a wide prevalence of benzodiazepine use among elderly patients in a psychiatric emergency service. Despite the recommendations for its judicious use, benzodiazepines were the most commonly used drug by psychiatrists on duty, regardless of patient's age. These results call for caution in prescribing these drugs and require alternatives to the treatment of psychiatric disorders in the elderly.