The effects on children of depressed mothers' remission and relapse over 9 months.

BACKGROUND: The high rate of depression among children of depressed mothers is well known. Suggestions that improvement in maternal acute depression has a positive effect on the child have emerged. However, data on the mechanisms of change have been sparse. The aim was to understand how remission and relapse in the mother might explain the changes in the child's outcome. METHOD: Participants were 76 depressed mothers who entered into a medication clinical trial for depression and 135 of their eligible offspring ages 7-17 years. The mothers and children were assessed at baseline and periodically over 9 months by independent teams to understand the relationship between changes in children's symptoms and functioning and maternal remission or relapse. The main outcome measures were, for mothers, the Hamilton Depression Rating Scale (HAMD), the Social Adjustment Scale (SAS) and the Parental Bonding Instrument (PBI) and, for children, the Children's Depression Inventory (CDI), the Columbia Impairment Scale (CIS), the Multidimensional Anxiety Scale for Children (MASC) and the Children's Global Assessment Scale (CGAS). RESULTS: Maternal remission was associated with a decrease in the child's depressive symptoms. The mother's subsequent relapse was associated with an increase in the child's symptoms over 9 months. The effect of maternal remission on the child's improvement was partially explained by an improvement in the mother's parenting, particularly the change in the mother's ability to listen and talk to her child, but also reflected in her improvement in parental bonding. These findings could not be explained by the child's treatment. CONCLUSIONS: A depressed mother's remission is associated with her improvement in parenting and a decrease in her child's symptoms. Her relapse is associated with an increase in her child's symptoms.

Predictors of newly diagnosed atrial fibrillation in cryptogenic stroke: a cohort study.

BACKGROUND AND PURPOSE: A significant proportion of cryptogenic ischaemic strokes are due to paroxysmal atrial fibrillation (AF). As paroxysmal AF appears to inexorably progress to persistent or permanent AF, this study with long-term follow-up was designed to establish the profile of patients who developed AF after hospital discharge. METHODS: All patients with cryptogenic ischaemic stroke over a 1-year period were included (n = 164). Patients were prospectively followed up at the outpatient clinic. Information on long-term outcome included the presence of newly diagnosed AF (NDAF). A specific NDAF assessment was performed at least 2 years after the index stroke using a structured telephone interview. Baseline clinical, laboratory, and echocardiographic data of these patients were retrospectively recorded. Independent predictive factors were then used to produce a predictive grading score for NDAF, derived by logistic regression analysis. RESULTS: With a median follow-up of 854 days, 22 cases of NDAF (13%) were observed. On multivariate analysis, factors associated with NDAF were age ≥72 years (two points), history of coronary artery disease (one point) or stroke (one point), and left atrial area ≥16 cm(2) (two points) (total score ranging from 0 to 6). Patients with a score ≤1 point did not have NDAF during follow-up. CONCLUSIONS: In cryptogenic ischaemic stroke, the NDAF score can be used to target patients at high risk of developing AF after hospital discharge, as a score of 0-1 was highly predictive of the absence of NDAF during follow-up. These results need to be confirmed in prospective studies.

Dry powder inhalers: study of the parameters influencing adhesion and dispersion of fluticasone propionate.

Interactions between particles are dependent on the physicochemical characteristics of the interacting particles but it is also important to consider the manufacturing process. Blending active pharmaceutical ingredient (API) with carrier is a critical stage that determines the blend homogeneity and is the first step towards obtaining the final quality of the powder blend. The aim of this work was to study parameters that influence the interactions between API and carrier in adhesive mixtures used in DPI and their effect on API dispersion. The study was done with fluticasone propionate blended with lactose 'Lactohale 200'. The study was based on the influence of the operating conditions (speed, mixing time, resting steps during mixing), the size of the carrier and the storage conditions on the blend properties and on the API dispersion. The quality of the blends was examined by analysing the API content uniformity. Adhesion characteristics were evaluated by submitting mixtures to a sieving action by air depression with the Alpine air-jet sieve. Aerodynamic evaluation of fine particle fraction (FPF) was obtained using a Twin Stage Impinger; the FPF being defined as the mass percentage of API below 6.4 µm. For good dispersion and therefore good homogeneity of the API in the carrier particles, speed and powder blending time have to be sufficient, but not too long to prevent the appearance of static electricity, which is not favourable to homogeneity and stability. The FPF increases with the decrease in the carrier size. The storage conditions have also to be taken into consideration. Higher humidity favours the adhesion of API on the carrier and decreases the FPF.

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.

Non-coated multiparticulate matrix systems for colon targeting.

BACKGROUND: Colon specific drug delivery can significantly improve the efficacy of local treatments of inflammatory bowel diseases. Film coatings containing the starch derivative Nutriose have recently been reported to minimize 5-ASA release in media simulating the upper gastro intestinal tract (GIT), while releasing the drug in a time-controlled manner upon contact with feces from Crohn's Disease and Ulcerative Colitis patients. It was the aim of this study to prepare Nutriose-containing matrix pellets and mini tablets in order to avoid a film coating step. METHODS: Highly dosed matrix pellets were prepared by extrusion-spheronization, highly dosed mini tablets by compression. Various types of lipids were added and drug release measured in 0.1 N HCl and phosphate buffer pH 6.8, optionally containing pepsin and pancreatin. RESULTS: The type of added lipid and the preparation technique, in particular the curing conditions, significantly affected the resulting drug release kinetics. Glyceryl palmitostearate containing pellets and mini tablets showed the most promising results upon appropriate curing, minimizing premature drug release in media simulating the upper GIT. CONCLUSION: The proposed novel multiparticulates do not require a film coating step and show an interesting potential for site-specific drug delivery to the colon of inflammatory bowel disease patients.

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.

Nandrolone excretion in sedentary vs physically trained young women.

We investigated the effects of the menstrual cycle, oral contraception and physical training on exhaustive exercise-induced changes in the excretion of nandrolone metabolites [19-norandrosterone (19-NA), and 19-noretiocholanolone (19-NE)] in young women. Twenty-eight women were allocated to an untrained group (n=16) or a trained group (n=12), depending on their physical training background. The untrained group was composed of nine oral contraceptive users (OC+) and seven eumenorrheic women (OC-), while the trained group was entirely composed of OC+ subjects. Three laboratory sessions were conducted in a randomized order: a prolonged exercise test, a short-term exercise test and a control session. Urine specimens were collected before and 30, 60 and 90 min after the exercise test and at the same times of the day during the control session. Urinary concentrations of nandrolone metabolites were determined by gas chromatography coupled to mass spectrometry. Urinary concentrations of 19-NA and 19-NE ranged from undetectable levels to 1.14 and 0.47 ng/mL, respectively. Nandrolone excretion was not affected by the menstrual cycle phase (early follicular vs mid-luteal), prior physical training, oral contraception or acute physical exercise. Therefore, a urinary concentration of 2 ng/mL of 19-NA appears to be fair as the upper acceptable limit in doping control tests for female athletes.

Comorbidity studies of eating disorders and mood disorders. Critical review of the literature.

OBJECTIVE: We conducted a critical literature review of studies assessing the prevalence of mood disorders (MD) in subjects with eating disorders (ED; anorexia nervosa and bulimia nervosa). In the first part of this article, we discuss methodological issues relevant to comorbidity studies between ED and MD. In the second part, we summarize the findings of these studies in light of the methodological considerations raised. METHOD: A manual computerised search (Medline) was performed for all published studies on comorbidity between ED and MD. In order to have sufficiently homogeneous diagnostic criteria for both categories of disorders, this search was limited to articles published between 1985 and 2006. RESULTS: Too few studies include control groups, few studies compared diagnostic subgroups of ED subjects, and results are scarce or conflicting. DISCUSSION: The results are discussed in the light of the methodological problems observed. The implications when reviewing the results of published studies and planning future research are set out.

Influence of carrier on the performance of dry powder inhalers.

The aim of this work is to study carriers which can become alternatives to monohydrate lactose in dry powder inhalers and to consider particle parameters that influence adhesion between drug and carrier in dry powder inhalers. Different forms of mannitol, lactose and maltitol were mixed with either terbutaline sulphate or formoterol fumarate. The blends were submitted to different adhesion tests where drug detachment from the carrier was obtained either through mechanical vibration or by aspiration. Parameters like particle shape, roughness, amorphous content and cristalline form may affect interactions between drug and carrier. In our case, crystallized forms of the carrier offered lower adhesion but better release of the active ingredient than spray-dried forms. The crystallized mannitol produced maximal fine particle dose. The blends of the mannitols and the two active ingredients gave different results. The two techniques used to assess the adhesion of drugs to carrier particles provide complementary information about drug/carrier interactions and detachment. The mechanical sieving allows to assess blend stability and the air-jet sieving makes it possible to determine how easily the drug separates from carrier. For the drugs tested, the results of fine particle doses are in agreement with the Alpine air-jet sieve results. The tests used are helpful for the choice of a new carrier in the field of the development of new carriers for dry powder inhalers.

Preparation and investigation of P28GST-loaded PLGA microparticles for immunomodulation of experimental colitis.

The aim of this work was to prepare and characterize (in vitro and in vivo) PLGA-based microparticles loaded with an enzymatic protein derived from the helminth parasite Schistosoma haematobium: glutathione S-transferase P28GST (P28GST). This protein is not only a promising candidate vaccine against schistosomiasis, it also exhibits interesting immunomodulating effects, which can be helpful for the regulation of inflammatory diseases. Helminths express a regulatory role on intestinal inflammation, and immunization by P28GST has recently been shown to be as efficient as infection to reduce inflammation in a murine colitis model. As an alternative to the combination with a classical adjuvant, long acting P28GST microparticles were prepared in order to induce colitis prevention. PLGA was used as biodegradable and biocompatible matrix former, and a W/O/W emulsion/solvent extraction technique applied to prepare different types of microparticles. The effects of key formulation and processing parameters (e.g., the polymer molecular weight, drug loading, W/O/W phase volumes and stirring rates of the primary/secondary emulsions) on the systems' performance were studied. Microparticles providing about constant P28GST release during several weeks were selected and their effects in an experimental model of colitis evaluated. Mice received P28GST-loaded or P28GST-free PLGA microparticles (s.c.) on Day 0, and optionally also on Days 14 and 28. Colitis was induced on Day 35, the animals were sacrificed on Day 37. Interestingly, the Wallace score (being a measure of the severity of the inflammation) was significantly lower in mice treated with P28GST microparticles compared to placebo after 1 or 3 injections. As immunogenicity markers, increased anti-P28GST IgG levels were detected after three P28GST PLGA microparticle injections, but not in the control groups. Thus, the proposed microparticles offer an interesting potential for the preventive treatment of experimental colitis, while the underlying mechanism of action is still to be investigated.

Influence of granulation and compaction on the particle size of ibuprofen--development of a size analysis method.

The aim of this work was to study the impact of the process on drug particle size. We chose ibuprofen, practically insoluble in water, as granulometry greatly influences its dissolution rate. We developed an original method using a laser granulometer to assess the size of ibuprofen within a blend before and after granulation and then compression. Wet granulation was performed with a Lodige and a Diosna granulator. The granules were then compressed. The evolution of ibuprofen particle size after these operations was checked. Two grades of ibuprofen differing in size were studied: ibuprofen 25 and ibuprofen 50. After the wet granulation of ibuprofen 50 with a Lodige or a Diosna granulator, a decrease in size was observed. This could be caused by shocks occurring in the granulator. On the other hand, after compression of the granules, ibuprofen particle size increased and was greater than that measured before granulation. Compression could induce some fragmentation of ibuprofen associated with the plastic deformation and then, under pressure, a closeness of the fragments or deformed particles which could bind or associate with one another because the melting point of ibuprofen is not very high. In the case of ibuprofen 25, the same phenomena were observed after compression. But, after granulation, particle size was not modified. There was little breaking of ibuprofen particles in the granulator because they are much smaller than those of ibuprofen 50. This work shows the impact of the process on drug particle size when producing tablets. The method developed made it possible to differentiate and measure the size of ibuprofen particles in a blend.

Controlled drug release from Gelucire-based matrix pellets: experiment and theory.

The aim of this work was to elucidate the underlying drug release mechanisms from lipidic matrix pellets, using theophylline and Gelucire 50/02 as model drug and carrier material, respectively. Pellets were prepared by two different techniques: melt-solidification and extrusion-spheronization. The effects of different formulations and processing parameters on the resulting drug release kinetics in 0.1N HCl and phosphate buffer pH 7.4 were studied and the obtained results analyzed using adequate mathematical models in order to get further insight into the underlying mass transport mechanisms. The type of preparation technique was found to strongly affect the underlying drug release mechanisms. Drug release from pellets prepared by the melt-solidification method was primarily controlled by pure diffusion, whereas drug release from pellets prepared by the extrusion-spheronization method was purely diffusion-controlled only at early time points. After approximately 2h, the pellets started to disintegrate, resulting in decreased diffusion pathway lengths and, thus, increased drug release rates. Furthermore, the curing conditions significantly affected the theophylline release kinetics, whereas varying the initial drug loading from 20 to 50% (w/w) resulted only in a slight increase in the relative drug release rate. Interestingly, the effects of the size of pellets prepared by the melt-solidification method on the resulting drug release kinetics could be quantitatively predicted using an analytical solution of Fick's second law of diffusion. These predictions could be verified by independent experiments.

Resolving a disagreement in a clinical team: overcoming conflicting views about the role of family therapy in an outpatient treatment programme for anorexia nervosa.

In the Adolescent Psychiatry Department at the Institut Mutualiste Montsouris, Paris, as is also observed in the literature, the outcome for anorexic patients can sometimes be catastrophic, regardless of treatments proposed. This disturbing finding led us to reassess our therapeutic treatment strategies, in an effort to improve patient outcome. The multidimensional treatment program implemented in the Department includes parent counselling, but not the whole family in a family therapy procedure. It has been demonstrated better outcome for patients who underwent family therapy in comparison to patients who underwent individual therapy. This raised the question of whether family therapy could improve our outpatient programme. This paper describes here how a research programme was developed to resolve a disagreement in our clinical team as to whether family therapy should be added to the existing care programme. The paper describes the difficulties encountered by our team, and the experimental design chosen to resolve the debate. Data will not be set out here.

Aerosolization potential of cyclodextrins--influence of the operating conditions.

The aim of this work is to characterize the aerosols obtained by jet nebulization with cyclodextrin solutions and to study the influence of operating conditions on nebulization efficiency. Two cyclodextrins, an hydroxypropyl cyclodextrin (Kleptose HP) and a polydisperse methyl beta cyclodextrin (Crysmeb), were tested with 14 nebulizers that differ geometrically. We first determined the physicochemical properties of density, viscosity, and surface tension for the cyclodextrin solutions. Nebulization efficiency was evaluated by measuring droplet size, nebulization rate, quantity of solution nebulized, and nebulization time. We studied the influence of the technological parameters of pressure and nebulizer type and the influence of the formulation on performance efficiency. The use of different nebulizers and different pressure conditions results in variable efficiency. Regardless of the type of nebulizer, an increase in pressure decreases droplet size and increases nebulization rate. The influence of the nebulizer design is considerable. The aqueous cyclodextrin solutions studied can generate aerosols in particle size ranges suitable for pulmonary deposition. Large quantities of aerosol can be nebulized in acceptable nebulization times. The cyclodextrin concentration does not modify nebulization efficiency in the range tested.

Biochemical changes during clomipramine treatment of childhood obsessive-compulsive disorder.

Peripheral measures of serotonergic and noradrenergic function were obtained in 29 obsessive-compulsive adolescents and 31 age- and sex-matched controls, as well as in a subsample of 22 patients after five weeks of treatment with clomipramine hydrochloride (134 +/- 33 mg/d) (mean +/- SD) given in a double-blind placebo-controlled trial. Drug-free obsessive-compulsive subjects did not differ from controls on measures of platelet serotonin and monoamine oxidase (MAO) activity, nor on plasma epinephrine or norepinephrine concentrations at rest and after a standard orthostatic challenge procedure. Compared with placebo, treatment with clomipramine was clinically effective and produced a marked decrease in platelet serotonin concentration, a trend toward a reduction in platelet MAO activity, and a rise in standing plasma norepinephrine. Clinical improvement during drug therapy was closely correlated with pretreatment platelet serotonin concentration and MAO activity, as well as with the decrease in both measures during clomipramine administration. This suggests that the effects of clomipramine on serotonin uptake may be essential to the antiobsessional action observed.

Clomipramine treatment of childhood obsessive-compulsive disorder. A double-blind controlled study.

Nineteen children (mean [+/- SD] age, 14.5 +/- 2.3 years) with severe, primary obsessive-compulsive disorder completed a ten-week, double-blind, controlled trial of clomipramine hydrochloride (mean dosage, 141 mg/day) or placebo, each of which was administered for five weeks. Half of the subjects had not responded to previous treatment with other tricyclic antidepressants. There was a significant improvement in observed and self-reported obsessions and compulsions that was independent of the presence of depressive symptoms at baseline. Improvement in obsessive-compulsive symptoms did not correlate significantly with plasma concentrations of the drug or its metabolites. Clomipramine appears to be effective in the treatment of children with obsessive-compulsive disorder and the treatment seems to be independent of an antidepressant effect.

Influence of the morphogranulometry and hydrophobicity of talc on its antisticking power in the production of tablets.

Antisticking power varies according to the talc considered. It is difficult to define the physical properties of talc implicated in its antisticking power. In this work, different talcs were characterized and an evaluation made of their performance in reducing sticking in tablet manufacturing. Determination of the specific surface area was made by permeametry, morphogranulometric analysis by laser diffractometry using a method, which made it possible to assess the mean thickness of talc particles, and measurement of water absorption kinetics was taken to assess hydrophobicity. The relationship between the characteristics of talcs and their antisticking power was then considered. There is a correlation between the particle size of talc and surface hydrophobicity. The detaching force of tablets appears to be dependent on the basal dimension of talc.

[Comorbidity between eating disorders and anxiety disorders. First part: methodological review]. / Comorbidité entre les troubles du comportement alimentaire et les troubles anxieux. Première partie: revue méthodologique.

UNLABELLED: The objective of our work is to conduct a critical literature review on studies assessing the prevalence of anxiety disorders (AD) in subjects with eating disorders (ED) (anorexia nervosa and bulimia nervosa). In the first part (this paper), we will discuss methodological issues relevant to comorbidity studies between ED and AD. METHOD: We performed a manual and computerised search (Medline) for all published studies on comorbidity between ED and AD, limiting our search to the 1985-2002 period, in order to get sufficiently homogeneous diagnostic criteria for both categories of disorders (most often RDC, DSM III, DSM Ill-R, or DSM IV criteria). RESULTS: We review methodological issues regarding population sources, general methodological procedures, diagnostic criteria for ED and AD, diagnostic instruments, age of subjects and course of the eating disorder. DISCUSSION: We give implications for reviewing the results of published studies and planing future research.

[Comorbidity between eating disorders and anxiety disorders: results]. / Comorbidité des troubles du comportement alimentaire et des troubles anxieux. Deuxième partie: résultats.

Taking into account the methodological problems underlined in the first part of this paper, the current review aims to answer three questions: 1) Is there convincing evidence that anxiety disorders (AD) are more frequent among women with eating disorders (ED) than among women from the community? 2) Is there convincing evidence that prevalence of AD differs across diagnostic types or subtypes of ED? 3) What is the chronology of appearance of the two disorders? We performed a manual and computerized search (Medline) for all published studies on comorbidity between ED and AD (1985-2002 period), and selected the most relevant studies. An increased risk for AD in subjects with ED has been shown in several community studies, but studies conducted in referred subjects have led to inconstant findings. The answer to the questions remains uncertain, because too few studies included control groups and few studies have compared diagnostic subgroups of ED subjects, with scarce or conflicting results.

[Comorbidity between eating disorders and mood disorders: review]. / Comorbidité des troubles alimentaires et des troubles de l'humeur. Revue de la littérature: problèmes méthodologiques et données.

OBJECTIVE: Comorbidity between eating disorders (ED) and mood disorders is a major issue when evaluating and treating patients with anorexia nervosa (AN) or bulimia nervosa (BN). In the literature, estimated comorbidity rates of mood disorders in subjects with ED differ widely across studies. Obviously, it is difficult to compare results from various sources because of differences in methods of assessment of depressive symptoms and in diagnostic criteria for both ED and mood disorders. Furthermore, few studies have included control groups, and, since mood disorders are among the most frequent psychiatric disorders in women--with an average estimated lifetime prevalence of 23.9 % (Kessleret al., 1994)--, it is not clear, yet, whether mood disorders are more common among women with an ED (AN or BN) than among women from the community. The only review articles we found on the relationships between ED and mood disorders survey different types of arguments in favour of a link between both categories of disorders, including symptoms, personal and family comorbidity, overlap in biological findings, and treatment results, but do not review in detail available comorbidity data. The aim of this paper is to conduct a critical literature review on studies assessing the prevalence of mood disorders in subjects with an ED (AN or BN). In the first part, we will discuss methodological issues relevant to comorbidity studies between ED and mood disorders, and select the most reliable studies. In the second part, taking into account these methodological considerations raised, we summarize the findings of these studies. METHOD: We performed a manual and computerized search (Medline) for all published studies on comorbidity between ED and AD, limiting our search to the 1985-2002 period, in order to get sufficiently homogeneous diagnostic criteria for both categories of disorders. RESULTS: Too few studies include control groups and few studies have compared diagnostic subgroups of ED subjects, with scarce or conflicting results. DISCUSSION: We reviewed numerous studies here and conclude simply that there are many arguments in favor of elevated rates of MD in ED subjects, but there is no convincing evidence yet. Many questions are left unanswered or have conflicting responses. Our review highlights the need for further studies, which should address several requisites: comorbidity studies should be designed with this as a specific goal, rather than as a secondary aim within other types of studies (such as treatment studies, follow-up studies, etc.). Kendler et al. (1991) state that individuals with two disorders are more likely to present for treatment than individuals with one, therefore, comorbidity rates (which are not in agreement with a special etiologic relationship between BN and depression) may be exaggerated in clinical population results. New studies should include control subjects, matched (at least) for sex and age with ED subjects. Studies should evaluate prevalence of all types of MD in order to yield comparable estimates of MD in general. Comorbidity studies should be conducted on both current and recovered patients, compared to subjects from the community. It is still necessary to demonstrate specificity of findings, i.e. that early onset MD are of specific etiological importance to ED and do not simply increase the risk of later psychopathology in general. Studies should be conducted on larger samples, and all diagnostic subgroups should be considered (restrictive and bulimic anorexics, bulimics with and without history of AN, with or without purging). Multivariate comparisons should be performed, taking into account subject age, sex (if men are included), in- and outpatient status, course of illness, and other possibly relevant variables. Thus, more reliable estimates of the frequency of MD in subjects with ED could provide us with valuable etiologic, therapeutic and prognostic information.