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Subjects suffering from bipolar disorder taking lithium are less likely to report physical pain: a FACE-BD study.
Risch, N, Dubois, J, Etain, B, Aouizerate, B, Bellivier, F, Belzeaux, R, Dubertret, C, Haffen, E, Januel, D, Leboyer, M, et al
European psychiatry : the journal of the Association of European Psychiatrists. 2023;(1):e8
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Abstract
BACKGROUND Physical pain is a common issue in people with bipolar disorder (BD). It worsens mental health and quality of life, negatively impacts treatment response, and increases the risk of suicide. Lithium, which is prescribed in BD as a mood stabilizer, has shown promising effects on pain. METHODS This naturalistic study included 760 subjects with BD ( FACE-BD cohort) divided in two groups: with and without self-reported pain (evaluated with the EQ-5D-5L questionnaire). In this sample, 176 subjects were treated with lithium salts. The objectives of the study were to determine whether patients receiving lithium reported less pain, and whether this effect was associated with the recommended mood-stabilizing blood concentration of lithium. RESULTS Subjects with lithium intake were less likely to report pain (odds ratio [OR] = 0.59, 95% confidence interval [CI], 0.35-0.95; p = 0.036) after controlling for sociodemographic variables, BD type, lifetime history of psychiatric disorders, suicide attempt, personality traits, current depression and anxiety levels, sleep quality, and psychomotor activity. Subjects taking lithium were even less likely to report pain when lithium concentration in blood was ≥0.5 mmol/l (OR = 0.45, 95% CI, 0.24-0.79; p = 0.008). CONCLUSIONS This is the first naturalistic study to show lithium's promising effect on pain in subjects suffering from BD after controlling for many confounding variables. This analgesic effect seems independent of BD severity and comorbid conditions. Randomized controlled trials are needed to confirm the analgesic effect of lithium salts and to determine whether lithium decreases pain in other vulnerable populations.
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Comparative analysis of anticholinergic burden scales to explain iatrogenic cognitive impairment and self-reported side effects in the euthymic phase of bipolar disorders: Results from the FACE-BD cohort.
Vidal, N, Brunet-Gouet, E, Frileux, S, Aouizerate, B, Aubin, V, Belzeaux, R, Courtet, P, D'Amato, T, Dubertret, C, Etain, B, et al
European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology. 2023;:67-79
Abstract
Bipolar disorders (BD) are characterized by cognitive impairment during the euthymic phase, to which treatments can contribute. The anticholinergic properties of medications, i.e., the ability of a treatment to inhibit cholinergic receptors, are associated with cognitive impairment in elderly patients and people with schizophrenia but this association has not been well characterized in individuals with remitted BD. Moreover, the validity of only one anticholinergic burden scale designed to assess the anticholinergic load of medications has been tested in BD. In a literature review, we identified 31 existing scales. We first measured the associations between 27 out of the 31 scales and objective cognitive impairment in bivariable regressions. We then adjusted the bivariable models with covariates: the scales significantly associated with cognitive impairment in bivariable and multiple logistic regressions were defined as having good concurrent validity to assess cognitive impairment. In a sample of 2,031 individuals with euthymic BD evaluated with a neuropsychological battery, two scales had good concurrent validity to assess cognitive impairment, whereas chlorpromazine equivalents, lorazepam equivalents, the number of antipsychotics, or the number of treatments had not. Finally, similar analyses with subjective anticholinergic side-effects as outcome variables reported 14 scales with good concurrent validity to assess self-reported peripheral anticholinergic side-effects and 13 to assess self-reported central anticholinergic side-effects. Thus, we identified valid scales to monitor the anticholinergic burden in BD, which may be useful in estimating iatrogenic cognitive impairment in studies investigating cognition in BD.
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Diethylstilbestrol and autism.
Soyer-Gobillard, MO, Gaspari, L, Courtet, P, Sultan, C
Frontiers in endocrinology. 2022;:1034959
Abstract
It is acknowledged that diethylstilbestrol (DES), a synthetic diphenol with powerful estrogenic properties, causes structural anomalies of the reproductive tract and increases the risk of cancer and genital malformations in children and grandchildren of mothers treated during pregnancy. Conversely, data on DES effects on neurodevelopment and psychiatric disorders in in-utero exposed children and their descendants are rare, especially concerning Autism Spectrum Disorders (ASD). Recent studies presented in this review strengthen the hypothesis that in-utero exposure to DES and also other synthetic estrogens and progestogens, which all are endocrine disruptors, contributes to the pathogenesis of psychiatric disorders, especially ASD. A large epidemiological study in the USA in 2010 reported severe depression in in-utero exposed children (n=1,612), and a French cohort study (n=1,002 in-utero DES exposed children) in 2016 found mainly bipolar disorders, schizophrenia, major depression, suicide attempts, and suicide. Few publications described ASD in in-utero exposed children, mainly a Danish cohort study and a large Chinese epidemiological study. Molecular studies on endocrine disruptors demonstrated the transgenerational induction of diseases and DES epigenetic impact (DNA methylation changes) at two genes implicated in neurodevelopment (ZFP57 and ADAM TS9). We recently described in an informative family, somatic and psychiatric disorders in four generations, particularly ASD in boys of the third and fourth generation. These data show that the principle of precaution must be retained for the protection of future generations: women (pregnant or not) should be extremely vigilant about synthetic hormones.
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Shared genetic risk between eating disorder- and substance-use-related phenotypes: Evidence from genome-wide association studies.
Munn-Chernoff, MA, Johnson, EC, Chou, YL, Coleman, JRI, Thornton, LM, Walters, RK, Yilmaz, Z, Baker, JH, Hübel, C, Gordon, S, et al
Addiction biology. 2021;(1):e12880
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Abstract
Eating disorders and substance use disorders frequently co-occur. Twin studies reveal shared genetic variance between liabilities to eating disorders and substance use, with the strongest associations between symptoms of bulimia nervosa and problem alcohol use (genetic correlation [rg ], twin-based = 0.23-0.53). We estimated the genetic correlation between eating disorder and substance use and disorder phenotypes using data from genome-wide association studies (GWAS). Four eating disorder phenotypes (anorexia nervosa [AN], AN with binge eating, AN without binge eating, and a bulimia nervosa factor score), and eight substance-use-related phenotypes (drinks per week, alcohol use disorder [AUD], smoking initiation, current smoking, cigarettes per day, nicotine dependence, cannabis initiation, and cannabis use disorder) from eight studies were included. Significant genetic correlations were adjusted for variants associated with major depressive disorder and schizophrenia. Total study sample sizes per phenotype ranged from ~2400 to ~537 000 individuals. We used linkage disequilibrium score regression to calculate single nucleotide polymorphism-based genetic correlations between eating disorder- and substance-use-related phenotypes. Significant positive genetic associations emerged between AUD and AN (rg = 0.18; false discovery rate q = 0.0006), cannabis initiation and AN (rg = 0.23; q < 0.0001), and cannabis initiation and AN with binge eating (rg = 0.27; q = 0.0016). Conversely, significant negative genetic correlations were observed between three nondiagnostic smoking phenotypes (smoking initiation, current smoking, and cigarettes per day) and AN without binge eating (rgs = -0.19 to -0.23; qs < 0.04). The genetic correlation between AUD and AN was no longer significant after co-varying for major depressive disorder loci. The patterns of association between eating disorder- and substance-use-related phenotypes highlights the potentially complex and substance-specific relationships among these behaviors.
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The quantitative ultrasound method for assessing low bone mass in women with anorexia nervosa.
Maïmoun, L, Renard, E, Huguet, H, Lefebvre, P, Boudousq, V, Mahadea, K, Picot, MC, Doré, R, Philibert, P, Seneque, M, et al
Archives of osteoporosis. 2021;(1):13
Abstract
UNLABELLED This study investigated the potential role of quantitative ultrasound (QUS) to assess low bone mass in anorexia nervosa patients (AN). Bone parameters from QUS and DXA were positively correlated and significantly reduced in AN compared with controls, suggesting that QUS is a pertinent technique to assess low bone mass in these patients. PURPOSE The aim of this study was to investigate the potential role of an alternative technique, quantitative ultrasound (QUS), to assess low bone mass in patients with anorexia nervosa (AN). METHODS Two hundred seven young women (134 patients with AN and 73 healthy controls) with ages ranging from 14.4 to 38.4 years participated in this observational cross-sectional study. Bone mass was concomitantly evaluated by DXA to determine areal bone mineral density (aBMD; g/cm2) at hip, lumbar spine, and radius and by QUS to determine broadband ultrasound attenuation (BUA; dB/MHz) at the heel. RESULTS BUA (66.5 ± 4.6 dB/MHz vs 61.0 ± 5.0 dB/MHz) and aBMD at the hip (0.916 ± 0.013 g/cm2 vs 0.806 ± 0.010 g/cm2), lumbar spine (0.966 ± 0.012 g/cm2 vs 0.886 ± 0.010 g/cm2), and radius (0.545 ± 0.005 g/cm2 vs 0.526 ± 0.04 g/cm2) were significantly decreased (p < 0.01) in patients with AN compared with controls. When patient and control data were pooled, BUA was significantly correlated with aBMD at the hip (r = 0.60, p < 0.001), lumbar spine (r = 0.48, p < 0.001), and radius (r = 0.40, p<0.001). In patients with AN, BUA and aBMD were mainly and positively correlated with weight, lean tissue mass, body mass index (BMI), and minimal BMI life and negatively with the duration of both disease and amenorrhea. Better concordance between the two techniques was obtained when absolute BUA and aBMD values were used according to the WHO T score classification. CONCLUSION BUA measurement at the heel by QUS appears to be a pertinent nonionizing technique to assess low bone mass in patients with AN.
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Effects of Hormonal Contraception Use on Cognitive Functions in Patients With Bulimia Nervosa.
Nobile, B, Maimoun, L, Jaussent, ID, Seneque, M, Dupuis-Maurin, K, Lefebvre, P, Courtet, P, Renard, E, Guillaume, S
Frontiers in psychiatry. 2021;:658182
Abstract
Background: Growing evidences indicate that sex hormones have an effect on cognitive functions, and that Bulimia Nervosa (BN) is associated with cognitive impairment. The aim of this study was to determine the effect of hormonal contraception (HC) use on four cognitive functions that are impaired in patients with BN. Methods: This retrospective exploratory study included 103 women with a diagnosis of BN based on the DSM-5 criteria. Their age ranged from 15 to 45 years, and 46.6% were taking HC (oral, transdermal, or intrauterine). Cognition was assessed with the d2 test (attention), Iowa gambling task (IGT; decision making), Brixton spatial anticipation test (set shifting), and Rey-Osterrieth complex figure test (central coherence). Data were analyzed with logistic regression models to estimate the adjusted odds ratios (OR) and 95% confidence intervals (CI) of HC effect on the neuropsychological test scores. Results: In the multivariate model, HC use was significantly associated with better scores for two d2 test indices: F-score [OR = 0.98, 95% CI = (0.95; 0.99)] and final total score ratio [OR = 0.87, 95% CI = (0.77; 0.99)]. HC was also associated with a better understanding of the IGT explicit rules. No difference between the two groups (HC and non-HC use) was detected for set shifting and central coherence. Conclusions: This exploratory study suggests that HC could have effects on the sustained attention and concentration in women with BN. More studies are needed to confirm these results.
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Combining mobile-health (mHealth) and artificial intelligence (AI) methods to avoid suicide attempts: the Smartcrises study protocol.
Berrouiguet, S, Barrigón, ML, Castroman, JL, Courtet, P, Artés-Rodríguez, A, Baca-García, E
BMC psychiatry. 2019;(1):277
Abstract
BACKGROUND The screening of digital footprint for clinical purposes relies on the capacity of wearable technologies to collect data and extract relevant information's for patient management. Artificial intelligence (AI) techniques allow processing of real-time observational information and continuously learning from data to build understanding. We designed a system able to get clinical sense from digital footprints based on the smartphone's native sensors and advanced machine learning and signal processing techniques in order to identify suicide risk. METHOD/DESIGN The Smartcrisis study is a cross-national comparative study. The study goal is to determine the relationship between suicide risk and changes in sleep quality and disturbed appetite. Outpatients from the Hospital Fundación Jiménez Díaz Psychiatry Department (Madrid, Spain) and the University Hospital of Nimes (France) will be proposed to participate to the study. Two smartphone applications and a wearable armband will be used to capture the data. In the intervention group, a smartphone application (MEmind) will allow for the ecological momentary assessment (EMA) data capture related with sleep, appetite and suicide ideations. DISCUSSION Some concerns regarding data security might be raised. Our system complies with the highest level of security regarding patients' data. Several important ethical considerations related to EMA method must also be considered. EMA methods entails a non-negligible time commitment on behalf of the participants. EMA rely on daily, or sometimes more frequent, Smartphone notifications. Furthermore, recording participants' daily experiences in a continuous manner is an integral part of EMA. This approach may be significantly more than asking a participant to complete a retrospective questionnaire but also more accurate in terms of symptoms monitoring. Overall, we believe that Smartcrises could participate to a paradigm shift from the traditional identification of risks factors to personalized prevention strategies tailored to characteristics for each patient. TRIAL REGISTRATION NUMBER NCT03720730. Retrospectively registered.
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Clinical guidelines for the management of treatment-resistant depression: French recommendations from experts, the French Association for Biological Psychiatry and Neuropsychopharmacology and the fondation FondaMental.
Bennabi, D, Charpeaud, T, Yrondi, A, Genty, JB, Destouches, S, Lancrenon, S, Alaïli, N, Bellivier, F, Bougerol, T, Camus, V, et al
BMC psychiatry. 2019;(1):262
Abstract
BACKGROUND Clear guidance for successive antidepressant pharmacological treatments for non-responders in major depression is not well established. METHOD Based on the RAND/UCLA Appropriateness Method, the French Association for Biological Psychiatry and Neuropsychopharmacology and the fondation FondaMental developed expert consensus guidelines for the management of treatment-resistant depression. The expert guidelines combine scientific evidence and expert clinicians' opinions to produce recommendations for treatment-resistant depression. A written survey comprising 118 questions related to highly-detailed clinical presentations was completed on a risk-benefit scale ranging from 0 to 9 by 36 psychiatrist experts in the field of major depression and its treatments. Key-recommendations are provided by the scientific committee after data analysis and interpretation of the results of the survey. RESULTS The scope of these guidelines encompasses the assessment of pharmacological resistance and situations at risk of resistance, as well as the pharmacological and psychological strategies in major depression. CONCLUSION The expert consensus guidelines will contribute to facilitate treatment decisions for clinicians involved in the daily assessment and management of treatment-resistant depression across a number of common and complex clinical situations.
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Clinical guidelines for the management of depression with specific comorbid psychiatric conditions French recommendations from experts (the French Association for Biological Psychiatry and Neuropsychopharmacology and the fondation FondaMental).
Bennabi, D, Yrondi, A, Charpeaud, T, Genty, JB, Destouches, S, Lancrenon, S, Allaili, N, Bellivier, F, Bougerol, T, Camus, V, et al
BMC psychiatry. 2019;(1):50
Abstract
BACKGROUND Recommendations for pharmacological treatments of major depression with specific comorbid psychiatric conditions are lacking. METHOD The French Association for Biological Psychiatry and Neuropsychopharmacology and the fondation FondaMental developed expert consensus guidelines for the management of depression based on the RAND/UCLA Appropriatneness Method. Recommendations for lines of treatment are provided by the scientific committee after data analysis and interpretation of the results of a survey of 36 psychiatrist experts in the field of major depression and its treatments. RESULTS The expert guidelines combine scientific evidence and expert clinician's opinion to produce recommendations for major depression with comorbid anxiety disorders, personality disorders or substance use disorders and in geriatric depression. CONCLUSION These guidelines provide direction addressing common clinical dilemmas that arise in the pharmacologic treatment of major depression with comorbid psychiatric conditions.
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Binge eating behaviours in bipolar disorders.
Boulanger, H, Tebeka, S, Girod, C, Lloret-Linares, C, Meheust, J, Scott, J, Guillaume, S, Courtet, P, Bellivier, F, Delavest, M
Journal of affective disorders. 2018;225:482-488
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Plain language summary
Bipolar disorder (BD) is a mental health condition that is often found alongside other health conditions including eating disorders such as anorexia nervosa and bulimia nervosa. More recently, it has been also associated with binge eating disorder (BED) which is characterised by frequent episodes of binge eating (BE), often involving a lot of food in a short space of time and a loss of control. It is estimated that 15-17% of people with BD binge eat, compared to 2-5% of the general population. The added burden of binge eating for those with BD includes increased mood instability, anxiety, additions, episodes of psychosis, obesity, suicide, and cardiovascular disease. This study aimed to explore the prevalence and characteristics of binge eating behaviour in those with BD attending BD clinics in France. Individuals with BD with and without binge eating behaviour were compared on factors including demographics and behavioural elements like eating habits. 145 outpatients with BD were included and assessed for binge eating using the Binge Eating Scale. 19% of BD patients were found to binge eat and was more likely in those with a shorter duration of BD, being emotional reactive and having higher levels of anxiety. However, the small sample meant it was hard to assess any differences in personality characteristics like impulsivity.
Abstract
BACKGROUND Recent research, especially from the USA, suggests that comorbid binge eating (BE) behaviour and BE disorder are frequent in individuals with Bipolar Disorder (BD). Although basic clinical associations between BD and BE have been investigated, less is known about psychological or temperamental dimensions and qualitative aspects of eating habits. In a French cohort of patients with BD, we investigated the prevalence of BE behaviour and any associations with illness characteristics, anxiety, impulsivity, emotional regulation and eating habits. METHODS 145 outpatients with BD (I and II) were assessed for the presence of BE behaviour using the Binge Eating Scale (BES). Characteristics identified in univariate analyses as differentiating BD cases with and without BE behaviour were then included in a backward stepwise logistic regression (BSLR) model. RESULTS In this sample, 18.6% of BD patients met criteria for BE behaviour. Multivariate analysis (BSLR) indicated that shorter duration of BD, and higher levels of anxiety and emotional reactivity were observed in BD with compared to BD without BE behaviour. LIMITATIONS Relatively small sample referred to specialist BD clinics and cross-sectional evaluation meant that it was not possible to differentiate between state and trait levels of impulsivity, emotional instability and disinhibition. These dimensions may also overlap with mood symptoms. CONCLUSION BE behaviour is common in females and males with BD. Emotional dysregulation and anxiety may represent important shared vulnerability factors for worse outcome of BD and increased likelihood of BE behaviour.