Comparison between continued inpatient treatment versus day patient treatment after short inpatient care in early onset anorexia nervosa (COTIDEA trial): a study protocol for a non-inferiority randomised controlled trial.

BACKGROUND: In children with early-onset anorexia nervosa (first symptoms before 13 years old, EO-AN), experts recommend initial outpatient treatment but in-patient treatment (IP) is frequently indicated due to acute medical instability or for those who have not improved with outpatient treatment. This IP can target either a partial weight restauration or a total weight normalization (return to the previous BMI growth trajectory). There are no evidence in the literature on which is the better therapeutic option in EOAN. But as long length of stay induce social isolation, with elevated costs, we wonder if a stepped-care model of daypatient treatment (DP) after short IP stabilisation may be a treatment option as effective as full-time IP to target weight normalization. We designed a two-arm randomised controlled trial testing the non-inferiority of a stepped-care model of DP after short IP stabilisation versus full-time IP. METHODS: Eighty-eight children aged 8 to 13 years suffering from EOAN with initial severe undernutrition will be randomly allocated to either IP treatment as usual or a stepped care DP model both targeting weight normalization. Assessments will be conducted at inclusion, somatic stabilization, weight normalization, 6 months and 12 months post randomisation. The primary outcome will be BMI at 12 months post-randomisation. Secondaries outcomes will included clinical (tanner stage), biological (prealbumin, leptin, total ghrelin and IGF1) and radiological (bone mineralization and maturation) outcomes, eating symptomatology and psychiatric assessments, motivation to change, treatment acceptability and quality of life assessments, cost-utility and cost-effectiveness analyses. DISCUSSION: COTIDEA will provide rigorous evaluation of treatment alternative to full-time inpatient treatment to allow a reduction of social iatrogenic link to hospital length of stay and associated costs. TRIAL REGISTRATION: Trial is registered on ClinicalTrials.gov (NCT04479683).

Inpatient target discharge weight for early-onset anorexia nervosa: Restoring premorbid BMI percentile to improve height prognosis.

OBJECTIVE: Early-onset anorexia nervosa (EO-AN) is characterized by restricted food intake leading to low body weight, emerging before 14 years old. Most patients reaching a target body mass index (BMI) around the 25th percentile at hospitalization discharge display an incomplete prospective height catch-up. A better understanding of height prognosis determinants is required. METHODS: In 74 children with an EO-AN, we collected height and weight premorbidly, at hospitalization, and at discharge, 6 months, 12 months, and at longer-term follow-up of 36 months. We defined a height prognosis parameter (HPP) as the difference between the height percentile at follow-up times and the premorbid height percentile. We explored the relationship between weight parameters and height catch-up at follow-up with linear regression analyses. RESULTS: A higher weight suppression (WS) - i.e., difference between premorbid and current BMI - at admission and discharge was associated with lower HPP - i.e., a greater loss of height - at 12 months and 36 months follow-up. Similarly, a higher premorbid BMI percentile was associated with a lower HPP at 12 and 36 months. CONCLUSION: Target discharge weight for EO-AN patients should be tailored and based on premorbid BMI trajectory to improve height prognosis.

[Suicide attempts with a violent method: Experience of a transdisciplinary psychiatric ward combining psychiatric and somatic care]. / Prise en charge des tentatives de suicide graves : expérience d'un service transdisciplinaire de psychiatrie.

INTRODUCTION: Suicide is the second leading cause of death in young adults. Suicide attempts by violent methods predict later completed suicide and premature mortality. Suicide prevention is a major public health issue in this specific population. The French Student Health Foundation (FSEF) developed a psychiatric ward that includes psychiatric and somatic approaches. This transdisciplinary unit provides mixed psychiatric and rehabilitation treatments for those persons who have attempted suicide and have severe somatic injuries. METHODS: We conducted a retrospective study including all subjects admitted into the transdisciplinary unit from 1st January 2011 to 31 December 2017, after a suicide attempt by jumping from a height, in front of a moving object, or by crashing of a motor vehicle. Data was obtained from the medical and administrative records of the clinic. RESULTS: In total, 215 persons were admitted into the transdisciplinary unit after a suicide attempt by a violent mean. Among them, 91.6% had jumped from a height, 7.4% had jumped in front of a train or a metro and 0.9% had crashed a motor vehicle. They were on average 25.5years old and 50.2% were men. 45.1% had a diagnosis of schizophrenic disorders and 34.4% of mood disorders. A total of 35.6% presented at least one previous suicide attempt, and among them 40.3% had previously attempted suicide with a violent mean. Substance abuse, mostly alcohol and/or cannabis, featured in 40.8% of subject history. The subjects hospitalised in the transdisciplinary unit had multiple, severe injuries: 78.1% had spine fractures, 69.8% had lower limb fractures, 47.9% had pelvic fractures and 43.3% had upper limb fractures. Moreover, 25.5% of them had sacral root damages. The length of stay averaged 184days and varied in a large range (less than a month to more than two years). The Activities of Daily Living scores were higher than 3 (out of a maximum score of 4) reflecting an important need of assistance. These scores decreased significantly during the hospitalisation for dressing, feeding, continence and locomotion but remained high for comportment and communication. At discharge, the physical sequelae were still important: 61% of people hospitalised had pain that required step 2 or 3 analgesics, 44% had analgesics for neuropathic pain, 80% had lower limb impairments, most often with walking limitation, and 26% had continence disorders. The psychotropic treatments at discharge were related to the psychiatric disorders observed and included 42% antidepressants, 63% neuroleptics and 16% mood stabilizers. CONCLUSION: This study highlights the severity of the somatic and psychiatric disorders affecting people who are admitted into this transdisciplinary unit. These subjects who have attempted suicide require particular care with multidisciplinary management in order to promote their rehabilitation, reintegration and prevent a suicide reattempt.

Bipolar disorders in severe anorexia nervosa: prevalence and relationships.

BACKGROUND: The comorbidity between anorexia nervosa (AN) and bipolar disorders (BD) among subjects with AN is a matter of some debate, regarding its existence, its impact on the clinical manifestations of AN and the nature of the relationship between these disorders. Our aims were: (1) to evaluate the prevalence of BD among patients with severe AN; and (2) to determine whether people with a history of BD present particular clinical AN characteristics in comparison to people with a comorbid major depressive disorder or with any mood disorder comorbidity. METHODS: 177 AN subjects were surveyed to assess their nutritional state, dietary symptomatology, psychiatric comorbidities, treatments received and associated response. The diagnosis of BD relied on DSM-5 criteria, using the short-CIDI. The discriminant features of patients with AN and suspected BD were identified, comparing them to the characteristics of AN patients without any mood disorder and AN patients suffering from major depressive disorder. RESULTS: Among AN subjects, 11.3% were suspected to have BD. In comparison with the two other groups, these patients had more severe clinical profiles in terms of duration of AN (6.7 years, p = 0.020), nutritional state (p max  =  0.031), levels of anxious, depressive and dietary symptoms, lifetime comorbidity with anxious disorders, quality-of-life (p =  0.001) and treatment (antidepressant and mood stabilizers, (p  =  0.029)). LIMITATIONS: The participants were hospitalized in a tertiary center with severe AN. The diagnosis of BD requires evaluation using a more precise diagnostic instrument CONCLUSION: These results underline the importance of systematic early detection of BD and mood disorders among individuals with severe AN, to provide optimum treatment. LEVEL OF EVIDENCE: III: Evidence obtained from a cross-sectional study.

[Diversity of hospital care for anorexia nervosa in psychiatry in France]. / Diversité des prises en charge hospitalières de l'anorexie mentale en psychiatrie en France.

BACKGROUND: Hospitalization is rare in anorexia nervosa (AN) and local application of indications is heterogeneous. However, no study has evaluated the effect of these different treatment modalities on the mean length of stay. Our objective was to describe the context and modalities of a wide range of hospital care programs offered to patients with anorexia nervosa in eleven specialized French psychiatric centers for patients from childhood to adulthood. This work was carried out within the framework of the EVHAN (Evaluation of Hospitalization for AN, Eudract number: 2007-A01110-53, registered in Clinical trials) research program. The EVHAN program comprises five main lines: weight objectives at discharge, the practice or not of a separation period, the use of clear nutritional dietary objectives (cognitive/behavioral), the intensity of family involvement in treatment, and the existence or absence of a stabilization phase before ending inpatient treatment. These main lines will make it possible to study the impact of treatment modalities on the future of patients in the short and medium term (at discharge and at 1-year follow-up). METHODS: The eleven centers are located in France (Bordeaux, Nantes, Paris and Ile-de-France, Rouen and Saint-Étienne). Various staff members (psychiatrists, somatic doctors, nurses, dieticians, psychologists) from each center were interviewed using a semi-structured questionnaire. Data on operating modalities and context of care were collected and analyzed. RESULTS: Four of the eleven centers were exclusively child/adolescent centers, and seven of 11 were adolescent (from 11, 13 or 16 years) and young adult centers. All centers offered a graduated approach from outpatient to full hospitalization. The majority had a number of beds allocated for patients with eating disorders. The criteria for hospitalization were homogeneous with respect to somatic and/or psychic severity prefiguring the consensus criteria defined by the French Health Authority (HAS) in 2010. Child/adolescent units used the weight curve to set weight objectives at discharge (between the 10th and 50th percentiles). Most adult units used weight objectives at discharge corresponding to a body mass index between 17 and 20kg/m2. Nine centers used a written or oral care contract. One unit did not separate the patient from her/his usual environment, the others had a practice gradient of partial separation and total separation times. These were either short, lasting a maximum of 3 weeks, or long, lasting more than 3 weeks. Conversely, patients were not isolated within the unit, and benefited from a rich social life, depending on her/his physical condition. The patient's family was in contact with the team and fully supported. The longest periods of separation involved adolescents and adults. Nutritional support varied from a group approach (meals in the dining room, standardized meals of the care center) to very individualized approaches within a specific framework. All the units reported meeting with families at least once during the hospitalization; with the patient's parents for child/adolescent patients and/or unmarried patients and with the husband/wife for married patients. The majority of the centers requested a phase of weight stabilization, whatever the age before hospital discharge. CONCLUSION: There is international and national consensus regarding the indications for hospitalization, and the main lines of multidisciplinary care to be developed within this framework. However, local application of these indications was heterogeneous resulting in diverse modalities of hospital care for anorexia nervosa in France. Specialized teams have developed management strategies arising from their "team culture". The complexity of the anorexic pathology, due to the psyche-soma intrication and the diversity of age groups, highlights the complexity of care available. The impact of this diversity of hospital care on patient outcomes will be studied as a result of this work.

[What factors explain the length of hospitalization for anorexia nervosa: A systematic review]. / Quels facteurs expliquent la durée d'hospitalisation pour anorexie mentale: revue systématique de la littérature.

OBJECTIVES: The cost of hospital treatment for anorexia nervosa (AN) is very high given its duration. Identifying factors related to length of hospital stay (LOS) would make it possible to consider targeted therapeutic strategies that, by optimizing care, would reduce their duration and costs. The objective of this work is to identify the factors related (predictive and associated) to LOS for AN. METHODS: Systematic review of existing literature up to October 2020, based on Pubmed, according to PRISMA recommendations (Preferred Reported Items for Systematic reviews and Meta-Analysis). Factors related to LOS have been described in two categories: factors related to clinical aspects ; and factors related to therapeutic aspects and management modalities. We distinguished predictive factors (identified as pre-hospitalization or contemporaneous with hospital admission) and associated factors (observed during hospitalization) for each category. RESULTS: Thirteen articles were selected. Samples from the selected studies ranged from 35 to 381 subjects, mostly women with restrictive type AN (R-AN), but some samples included all types of AN, or focused on purging-type forms. The mean age at admission ranged from 13.6 years (Standard Deviation-SD:±1.6) to 30.3 years (SD :±13.9), corresponding to adolescent, adult or mixed samples. Mean body mass indices at admission ranged from 12.3 (SD±1.4) to 16.6 (SD:±2.1). The duration of disease progression ranged from 11.7 months±2.2 to 9.7 years. Mean LOS are short for studies conducted in pediatrics or in medical services (ranging from 13.0 days [SD±7.3] to 22.1 days [SD±9.4]); they are more variable for studies conducted in psychiatry: from 15.6 days (SD±1.0) to 150.2 days (SD±80.8). Among the factors related to an increase in LOS, clinical predictors included: older age at onset or admission; longer duration of the disorder; low minimum body weight during AN; low BMI at admission; purgative form of anorexia nervosa; and high levels of dietary symptoms (asceticism and ineffectiveness dimensions on Eating Disorder Inventory-2). Therapeutic and management modality predictive factors were: a higher number of hospitalizations for AN; the use of enteral nutrition (nasogastric or percutaneous gastric tube) on admission or during hospitalization; the use of intravenous renutrition coupled with oral renutrition; hospitalization far from the patient's home; absence of hospital care in psychiatry after medical stabilization in a somatic unit; compulsory hospitalization. Associated factors were: the presence of psychiatric comorbidities; greater weight gain during hospitalization. Among the factors related to a decrease in LOS, the clinical predictive factor were: greater self-confidence at admission (measured by the Eating Disorder Recovery Self-Efficacy Questionnaire). Therapeutic and management modality predictors included: increased caloric intake of oral renutrition on admission; intake of oral nutritional supplements on admission; and hospitalization in urban areas. The associated factor was: compliance with the weight contract in the adolescent population. DISCUSSION: Factors related to an increase in LOS are explained by: higher resistance to treatment, higher severity of the disease, the time required for weight gain in services using cognitive-behavioural therapy, complications associated with renutrition modalities such as parenteral renutrition, difficulties in organising outpatient follow-up which require better consolidation of inpatient treatment and the lack of multidisciplinary care in medical services. Factors related to a decrease in LOS are due to: faster weight gain, the presence of a greater number of outpatient follow-up structures close to the hospital and better adherence to treatment to complete the weight contract. CONCLUSIONS: Taking these factors into account during hospitalization for AN would help optimize care, duration and costs. This situation therefore requires the development of therapeutic trials targeting the identified factors in order to reduce LOS in the treatment of AN.

Nutritional status and anxious and depressive symptoms in anorexia nervosa: a prospective study.

The interweaving of malnutrition and symptoms of anxiety and depression in anorexia Nervosa (AN) is mentioned without any consensus regarding the course of anxious-depressive symptoms in relation to nutritional status in the course of treatment of patients with AN. The objectives of the current study in a large sample of AN inpatients were to assess the relationships between anxiety and depression symptoms and nutritional status both over the course of inpatient treatment and at discharge. 222 consecutive inpatients with AN (DSM-IV TR) were assessed (entrance and discharge) for duration of illness, psychiatric treatments, sociodemographic data and with psychometric scales for different psychopathological symptoms [depressive (BDI), anxiety and depressive (HAD scale), obsessive-compulsive (MOCI) and social phobia (LSAS fear score)]. Nutritional status was assessed with Body Mass Index (BMI) and body composition by bioelectrical impedance. The Fat free mass index [FFMI = FFM (kg)/height (m2)] was considered for the analysis. Two models were developed where the dependent variables were each psychopathological score at discharge (BDI, HAD anxiety, MOCI, and LSAS fear) in the cross-sectional model, and their variation in the longitudinal model (where a positive score reflected symptom decrease at discharge). A fixed set of predictors, defined on presumed clinical and statistical relevance (FFMI in the cross-sectional model and Variation of FFMI in the longitudinal model), were considered in each model, without any model selection procedure. This is the first study to confirm a positive relationship between the course of eating disorder symptoms and that of anxious-depressive symptoms during inpatient treatment of AN even after adjustment on a vast array of possibly confounding factors.

Absence of relationships between depression and anxiety and bone mineral density in patients hospitalized for severe anorexia nervosa.

INTRODUCTION: Low BMD is frequent in anorexia nervosa (AN), depression, and during SSRI treatment but relation between these elements in AN is not established. The aims of this study were to assess the relationships between depression and anxiety, SSRI prescription, and (1) low BMD during inpatient treatment and (2) BMD change 1 year after hospital discharge. METHODS: From 2009 to 2011, 212 women with severe AN have been included in the EVHAN study (EValuation of Hospitalisation for AN). Depression, anxiety and obsessive-compulsive symptoms and comorbidity were evaluated using psychometric scales and CIDI-SF. BMD was measured by dual-energy X-ray absorptiometry. RESULTS: According to the CIDI-SF, 56% of participants (n = 70) had a lifetime major depressive disorder, 27.2% (n = 34) had a lifetime obsessive-compulsive disorder, 32.8% (n = 41) had a lifetime generalized anxiety disorder and 25.6% (n = 32) had a lifetime social phobia disorder. Half of the sample (50.7%; n = 72) had a low BMD (Z score ≤ - 2). In multivariate analysis, lifetime lowest BMI was the only determinant significantly associated with low BMD (OR = 0.56, p = 0.0008) during hospitalization. A long duration of AN (OR = 1.40 (0.003-3.92), p = 0.03), the AN-R subtype (OR = 4.95 (1.11-26.82), p = 0.04), an increase of BMI between the admission and 1 year (OR = 1.69 (1.21-2.60), p = 0.005) and a gain of BMD 1 year after the discharge explained BMD change. CONCLUSION: We did not find any association between depression and anxiety or SSRI treatment and a low BMD or variation of BMD. LEVEL OF EVIDENCE: Level III, cohort study.

Impact of bipolar disorder on eating disorders severity in real-life settings.

BACKGROUND: Comorbidity of bipolar disorder (BD) and eating disorders (ED) is common and increases the course and severity of BD. However, the impact of comorbid BD on the clinical profile of ED patients remains unclear. Most studies have focused on patients primarily assessed for BD and data on patients with a primary diagnosis of ED are sparse. We investigated the association between a dual diagnosis and severity in terms of clinical, neuropsychological dimensions and daily functioning. METHOD: Two hundred and sixty-one patients with ED were consecutively recruited. BD was screened with the MINI and further confirmed in the French expert centre network. The severity of ED symptoms was assessed with the EDE-Q and EDI-2, daily functioning with the FAST. The neurocognitive assessment targeted attention, set-shifting and decision-making. RESULTS: Forty-nine patients screened positive for BD, but diagnosis was confirmed in only thirty patients (11.5% of the cohort). After multiple adjustments, comorbidity was associated with greater severity on the total score and three subscales of the EDE-Q and on four of the ten dimensions of the EDI-2. Comorbid BD was associated with lower daily functioning but not with lower neuropsychological performance. LIMITATIONS: Sample referred to specialist clinics not large enough to authorize an analysis by subtype and cross-sectional evaluation. CONCLUSION: The association between ED and BD increases ED severity for most of these core features. It negatively impacts daily functioning. The results also highlight issues about the validity of screening tools to detect BD in patients with ED.

Crossed prevalence results between subtypes of eating disorder and bipolar disorder: A systematic review of the literature.

OBJECTIVE: To assess the association between sub-types of bipolar disorder (BD) (types I and II) and sub-types of eating disorders (EDs) (Anorexia Nervosa, Bulimia Nervosa, Binge-eating disorders) as well as their relative order of occurrence. METHODOLOGY: A systematic review of articles estimating prevalence rates for BD among patients with ED and vice versa. We also analysed all articles assessing their relative order of occurrence. RESULTS: Comorbid BD is common among patients with an ED. From 0.6 to 33.3% of bipolar subjects have an eating disorder. Conversely, from 0 to 35.8% of subjects with an ED can present a BD. This co-occurrence has mostly been observed among patients with anorexia of the bulimic/purging type, with bulimia or with binge-eating disorders. The association is less frequent in cases of anorexia of the restrictive type. In contrast, the BD sub-type does not seem to have an impact on the association with EDs. Whilst age at BD onset is earlier in case of a comorbid ED, age at ED onset does not seem to be impacted by the presence of an associated BD. There has been little data on the relative order of occurrence of the two disorders or on the impact of the thymic phase on the expression of EDs. CONCLUSIONS: EDs and BD are frequently comorbid, suggesting the need for crossed screening of these pathologies, in particular for EDs with purging behaviours and for patients with early BD onset.

[Bipolar disorders and anorexia nervosa: A clinical study]. / Troubles bipolaires et anorexie mentale : une étude clinique.

PURPOSE: Anorexia nervosa is often accompanied by comorbid mood disorders, in particular depression, but individual or family history of bipolar disorders has not frequently been explored in anorexia nervosa. The objectives of the present study were: (1) to assess the frequency of bipolar disorders in patients with anorexia nervosa hospitalized in adolescence and in their parents, (2) to determine whether the patients with a personal or family history of bipolar disorders present particular characteristics in the way in which anorexia nervosa manifests itself, in their medical history, in the secondary diagnoses established, and in the treatments prescribed. METHOD: Overall, 97 female patients aged 13 to 20 hospitalized for anorexia nervosa and their parents were assessed. The diagnoses of anorexia nervosa and bipolar disorders were established on the basis of DSM-IV-TR criteria. RESULTS: A high frequency of type II and type V bipolar disorders was observed. The patients with anorexia nervosa and presenting personal or family histories of bipolar disorder had an earlier onset of anorexia nervosa, more numerous hospitalizations, a longer time-lapse between anorexia nervosa onset and hospitalization, more suicide attempts and more psychiatric comorbidities. CONCLUSION: The occurrence of anorexia nervosa-bipolar disorders comorbidity appears to be considerable and linked to the severity of anorexia nervosa, raising the issue of the relationship between anorexia nervosa and bipolar disorders.

Are lifetime affective disorders predictive of long-term outcome in severe adolescent anorexia nervosa?

Depression and anxiety are commonly associated with anorexia nervosa (AN) and contribute to difficulties in social integration, a negative factor for outcome in AN. The link between those disorders and AN has been poorly studied. Thus, our objective was to investigate (1) the link between outcome nine years after hospitalisation for AN and the occurrence of lifetime anxious or depressive comorbidities; (2) the prognostic value of these comorbidities on patient outcome; 181 female patients were hospitalised for AN (between 13 and 22 years old), and were re-evaluated for their psychological, dietary, physical and social outcomes, from 6 to 12 years after their hospitalisation. The link between anxious and depressive disorders (premorbid to AN and lifetime) and the outcome assessment criteria were tested through multivariate analyses; 63% of the participants had good or intermediate outcome, 83% had presented at least one anxiety or depression disorder in the course of their lives, half of them before the onset of AN. Premorbid obsessive compulsive disorders (OCD), BMI at admission, and premenarchal AN all contribute to poor prognosis. Social phobia and agoraphobia affect the subjects' quality of life and increase eating disorder symptoms. These results encourage a systematic assessment of, and care for, anxiety and depression comorbidities among female adolescent patients with a particular focus on premorbid OCD.

[Depressive symptoms during anorexia nervosa: State of the art and consequences for an appropriate use of antidepressants]. / Manifestations dépressives au cours de l'anorexie mentale : données de la littérature et implications pour une utilisation adaptée des antidépresseurs.

OBJECTIVE: Depressive comorbidity is often associated with anorexia nervosa (AN), and antidepressant medication is widely used although it does not rely on any convincing data in the scientific literature. Our objectives were: to summarize the epidemiological, physiological, psychopathological literature about the relation between AN and manifestations of depression, and to focus on the clinical trial data assessing the use of antidepressant medication in AN in order to clarify the strategy for the use of antidepressant in AN during adolescence. METHOD: A manual computerised search (Medline) was performed for relevant published studies assessing the association between depressive signs or Major Depressive Disorder (MDD) and AN. Another manual computerised search (Medline) listed clinical trials assessing antidepressant in AN. RESULTS: On the one hand, depressive symptoms are common during the course of AN and could have different meaning. Indeed, firstly, we can distinguish symptoms that are inherent to AN and which can be mistaken for depressive signs (for instance: low self-esteem, reduced social contacts). Secondly, long-term undernourishment can be held responsible for numerous psychological distortions, including anxiety and depression symptoms such as insomnia, impaired concentration, or social isolation. Thirdly, the natural course of AN can also lead to "depressive moments", in particular when switching to a "purging type" AN, or when recovery mobilizes control and narcissistic issues. On the other hand, MDD is also highly prevalent among AN patients and is a negative prognosis factor. Thus, it is complex to differentiate MDD from isolated depressive symptoms that could be inherent of the AN symptomatology which raises the question of the role of antidepressant medication in treatment of depression in AN. No significant benefit of antidepressant medication in AN has been shown in clinical trials, and according to international guidelines it should be prescribed only as a second-line treatment, after appropriate refeeding, and in case of an authentic depressive disorder. Those data appear to be in contradiction with the frequent use of those drugs in clinical practice. DISCUSSION: Nevertheless, clinical trials assessing antidepressant treatment in AN suffer from methodological weakness concerning the size of the sample, the choice of the population or the evaluation criterion. This lack of proof must raise our vigilance concerning antidepressant medication in AN but should not categorically prevent the clinician from using it when necessary. We do believe that there are some indications for prescribing antidepressant in patients with AN. The clinical challenge lies in the differentiation of the depressive symptoms that are transitory and likely to improve without medication from those that signal the presence of an MDD. Three criterion could be indicative of MDD: familial history of mood disorder, as it is a major risk factor for MDD among relatives; the chronology of appearance of both disorders, when MDD pre-exists AN; a few specific symptoms cannot be attributed to undernourishment or reactive depressive signs, such as morning insomnia, daily variation of depressive symptoms, suicidal attempts or ideation and guilt ideation. Thus, in integrating the data from the literature review, we propose a pragmatic therapeutic strategy for the use of an antidepressant in AN during adolescence that lies in 3 main categories for depressive manifestations in AN: therapeutic emergencies: when an obvious and severe MDD is comorbid to AN, immediate antidepressant would be required; isolated and non-specific depressive sign: no medication would be relevant as they are supposed to improve with refeeding and psychotherapeutic support; intermediary patterns which is probably the most frequent situation. In the last case, it would be relevant to abstain from prescribing medication in first line, but an antidepressant medication should be quickly considered in the presence of one (or several) criterion listed above and its persistence despite refeeding. The general medical state of this fragile population of patients should be evaluated (standard blood test, ECG) before and during treatment.

[Guidelines for the prescription of mood stabilizers for adolescents: A literature review]. / Bonnes pratiques pour la prescription de thymorégulateurs à l'adolescence : une revue de la littérature.

INTRODUCTION: Adolescence is a unique phase of the human developmental process. In adolescents, psychotropic medications may have different efficacy and tolerance profiles compared to those at other stages of the lifespan. Mood stabilizers are a complex pharmacological category including lithium, some anticonvulsants, and some second generation antipsychotics. Focusing on this class of pharmacological agents, we aim to answer the following questions: in which indications and according to which modalities should mood stabilizers be prescribed during adolescence? METHODS: Information was sought from the websites of the French Haute Autorité de santé (HAS) and Agence nationale de sécurité du médicament et des produits de santé (ANSM), the American Food and Drug Administration (FDA) and the British National Institute for Health and Clinical Excellence (NICE). Guidelines from the American Academy of Child and Adolescent Psychiatry (AACAP) were also reviewed. Additional articles were found using PubMed and Google Scholar. We assumed that guidelines published by a national institute were the most relevant, second information from medical academies, then literature reviews, and finally single studies. Practical prescription data were also sought from the French Vidal Drug Dictionary. RESULTS: For bipolar disorder in adolescents, lithium has been the first drug licensed in France (from the age of 16) and in the USA (from the age of 12), with indications for acute mania and preventive treatment. Benefits for impulsive and self-aggressive behaviour disorders (especially relevant in case of borderline personality disorder) have also been documented, although lithium has not been licensed in any country for those indications. Extended-release tablets are usually used, at doses targeting for a lithiemia between 0.8 and 1.2mEq/L 12hours after last intake. Because of a narrow therapeutic window and potential side effects (especially nephrotoxicity), lithium prescription requires regular blood tests and good treatment compliance. None of the anticonvulsants has been licensed by a national drug administration as a mood stabilizer in adolescents. However, the AACAP recommends valproate as a first line treatment for mania, even though the NICE and the ANSM caution that valproate should not be used by women of child bearing age. Besides its teratogenic and endocrine side effects, valproate exposes one to the risk of hepatic toxicity. That is why regular liver function tests should be prescribed when valproate is chosen. According to the AACAP, carbamazepine (which is licensed for the treatment of mania in adults) is not a first line treatment for adolescents. Indeed, no clinical study has demonstrated its efficacy on manic episodes in adolescents. Moreover, carbamazepine exposes one to the risk of agranulocytosis. Lamotrigine has not been approved for adolescents, but some studies suggest its efficacy for bipolar depression (often a treatment-resistant phase) in this age group. Major side effects are the risk of Lyell or Stevens-Johnsons syndrome (which usually occur within the first eight weeks of treatment). There is no need for biological tests, just clinical monitoring. Pharmacological interactions between lamotrigine and oral contraceptives require caution. Finally, the use of some second generation antipsychotics for bipolar disorder in adolescents has been approved by national drug administrations. In France, only aripiprazole is licensed for acute mania (from the age of 13). In the USA, aripiprazole is licensed from the age of 10 for acute mania and preventive treatment, while risperidone and quetiapine are licensed from the age of 10 for acute mania, and olanzapine is licensed from the age of 13 for acute mania. The AACAP recommends second generation antipsychotics as a first line treatment for bipolar disorder. Moreover, the AACAP and the NICE recommend second generation antipsychotics for behavioural disorders in adolescents. Recommended doses are usually lower and titration slower than for adults. As in adults, adverse effects are metabolic, motor and cognitive disorders. Moreover, hyperprolactinemia, sedation and weight gain are more frequent than in adults. DISCUSSION: Epidemiologic data for prescription of mood stabilizers in adolescents only partially concord with recommendations from drug administrations and scientific societies. On the one hand, there is a trend toward preferential prescription of second generation antipsychotics, on the other hand lithium is hardly prescribed to adolescents, less often than anticonvulsants. Thus, without approval from any drug administration, the anticonvulsants are often preferred to lithium (because of lithium's potential risks due to noncompliance or voluntary poisoning) and to second generation antipsychotics (because of their tolerance profile). Nevertheless, for prescribers it is a complex matter to compare side effects: the frequency and intensity of adverse effects is quite variable from one mood stabilizer to another, and such a thing as an expected value is therefore hard to define. Regardless of the medication chosen, compliance and therapeutic alliance are major issues. Compliance is especially low during adolescence (less than 40% according to a study on bipolar disorder). This lack of compliance has multiple determinants: poor acceptance or misunderstanding of the psychiatric disorder, indirect effects of bad relationships with parents and more generally adults, but also reckless behaviour or death wishes. Improving therapeutic alliance appears as a major challenge for health practitioners dealing with youth. One interesting path of research could be the therapeutic education programs using humanistic communication techniques (addressing both adolescents and their parents) which have already produced encouraging results.

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.

[Epidemiology of anorexia nervosa: a review]. / Épidémiologie de l'anorexie mentale : revue de la littérature.

UNLABELLED: A critical review of the literature was conducted to provide answers to three questions: firstly, are we facing a national and/or international epidemic of anorexia nervosa (AN) as claimed in the media by certain professionals? Secondly, is AN simply an ordinary crisis of adolescence? Thirdly, is it a pathology that solely affects the higher socio-professional categories? METHOD: A Medline search was conducted and backed up by a manual search to find all the studies or literature reviews published on prevalence, incidence rates, outcomes, morbidity and mortality in AN and its links with social class, covering the period 2000-2011. RESULTS: The differing methodologies of the studies on these themes have a considerable impact on the interpretation of results. For each indicator retained, the results observed in the different studies are detailed and commented in the light of these differences. The prevalence of AN in women aged 11 to 65 in non-clinical population ranges from 0 to 2.2 %. It varies in particular with the age of the studied subjects, the measurements used, and the definition criteria for AN. Among men, the lifetime prevalence is around 0.3%. The marked disparities in incidence rates observed are related to the nature of the samples considered: subjects consulting in hospital, whether in a specialised department or in any department, those consulting general practitioners (GPs), or subjects from general population samples recruited in different surveys (girls in schools for example). The incidence of female cases is low in general medicine or specialised consultation in town (whatever the speciality): from 4.2 and 8.3/100,000 individuals per year. It is much higher in the general population, ranging from 109 to 270/100,000 individuals per year. In fact, the studies reporting variations in the incidence of AN were conducted on samples from clinical populations in certain countries (United States and United Kingdom). They are probably more a reflection of variations in detection rates and use of healthcare, than of variations in the incidence in the general population. The mean duration of AN appears shorter in the general population than in clinical populations. On average, 47% of the individuals treated for AN recovered, 34% improved, 21% had a chronic eating disorder, and 5% died. The outcome is better for subjects treated during adolescence. Mortality is frequently expressed in crude mortality rate (CMR), which is not very informative on account of the heterogeneous natures of the cohorts followed; only the studies reporting standardised mortality rate (SMR) are informative. AN appears as having one of the highest mortality rates among psychiatric pathologies. Mortality varies according to the population considered. Rates observed are 6.2 to 10.6 times greater than that observed in the general population for a follow-up duration ranging respectively from 13 to 10 years. It is lower for longer follow-up periods, only 3.7 times more frequent than in the general population for follow-up periods of 20 to 40 years. It appears lower for subjects treated before the age of 20. The main causes of death are eating disorder complications, suicide and cancer. One review of the literature concluded in the absence of any significant link between this pathology and social class. DISCUSSION: There is nothing in the incidence and prevalence data to back up the notion of a recent "epidemic" of AN. AN is not simply a crisis of adolescence: morbidity and mortality are considerable in this pathology. The relationship between AN and social class is not established.

The Attitudes and Patterns of Eating (APE) Questionnaire: development and factor analysis in a U.S. adolescent community sample.

OBJECTIVE: This paper describes the creation and demonstrates the internal consistency of the Attitudes and Patterns of Eating (APE) Questionnaire, English version, which assesses adolescent food beliefs and eating habits and can be used for comparative studies on various cultures and lifestyles. The questionnaire is intended for use in a study comparing French and U.S. adolescents, the details of which will be presented in a future article. METHOD: A research team composed of French and American researchers observed eating behaviors in community samples from each country and reviewed previous studies comparing Europe and North America regarding eating attitudes/practices. Common eating-related themes were identified and corresponding questionnaire items were constructed, then a group of U.S. high school students (N=1230) was administered the questionnaire. RESULTS: A principal components analysis (PCA) identified 5 components: "Eating Diet/Light Foods," "Unhealthy/Increased Eating," "Homemade Meals," "Skipping Meals" and "Healthy Eating". DISCUSSION: The testing and factor analysis of the APE (English) Questionnaire demonstrated its internal consistency. Further validity and reliability studies will be needed to complete the global validation process for both the French and English versions.

Can birth weight predict later body composition in anorexia nervosa?

BACKGROUND/OBJECTIVES: The relationship between birth weight and body composition at later stages in life was not studied previously in anorexia nervosa (AN). The aim of the following brief report is to present results concerning the relationship between birth weight and later body composition specifically in AN, and to check if the programming of body composition from birth weight is still detected in severely emaciated AN patients. SUBJECTS/METHODS: One hundred and fifty-one female AN patients aged between 13 and 44 were recruited from 11 inpatient treatment facilities in France. Birth weight, body weight and height were obtained. Body composition was measured using bioelectrical impedance. Birth weight was significantly correlated to lifetime maximum body mass index (BMI; r=0.211, P=0.009) and significantly correlated to fat-free mass index (r=0.190, P=0.027) but not to fat mass index (FMI). RESULTS: This report confirms that even in AN when patients are severely emaciated and where fat-free mass (FFM) and fat mass (FM) are low, a link between birth weight and FFM and BMI can still be identified, independently from age. CONCLUSION: Further studies are needed on larger samples exploring other factors, such as gender, puberty and ethnicity.

Expressed emotion measure adaptation into a foreign language.

Expressed emotion (EE) measures have been created in English; adaptation into a foreign language is difficult. The aim of this study was to adapt the five minutes speech sample (FMSS), with a designed procedure ensuring optimum quality of the adaptation, and thus better trans-cultural validity. A strategy for improving inter-rater agreement comprised three phases: (1) phase of initial ratings (70 French samples), (2) experimental phase in two steps: ratings of 40 other samples in French, followed by analysis of differences between the French-language ratings and English-language ratings and (3) final rating phase of the initial 70 samples. For each phase, the κ coefficients measuring inter-rater agreement were calculated and compared using a bootstrap procedure. The improvements between these scorings were significant at p < 0.05 (phase 2 initial versus phase 2 final and phases 1 versus 3). The French inter-rater agreement significantly improved after this procedure.

Factors predictive of ten-year mortality in severe anorexia nervosa patients.

OBJECTIVE: Little is known concerning mortality and predictive factors for anorexia nervosa in-patients. This study aimed to establish mortality rates and identify predictors in a large sample of adults through a 10-year post in-patient treatment follow-up. METHOD: Vital status was established for 601 anorexia nervosa (DSM-IV) consecutive in-patients with initial evaluation at admission. Standardized mortality ratio (SMR) was calculated. Cox analyses for hypothesized predictors of mortality were performed. RESULTS: Forty deaths were recorded. SMR was 10.6 [CI 95% (7.6-14.4)]. Six factors at admission were associated with death: older age, longer eating disorder duration, history of suicide attempt, diuretic use, intensity of eating disorder symptoms, and desired body mass index at admission. CONCLUSION: Anorexia nervosa in-patients are at high risk of death. This risk can be predicted by both chronicity and seriousness of illness at hospitalization. These elements should be considered as warnings to adapt care provision and could be targeted by treatment.