When a test is more than just a test: Findings from patient interviews and survey in the trial of a technology to measure antidepressant medication response (the PReDicT Trial).

BACKGROUND: A RCT of a novel intervention to detect antidepressant medication response (the PReDicT Test) took place in five European countries, accompanied by a nested study of its acceptability and implementation presented here. The RCT results indicated no effect of the intervention on depression at 8 weeks (primary outcome), although effects on anxiety at 8 weeks and functioning at 24 weeks were found. METHODS: The nested study used mixed methods. The aim was to explore patient experiences of the Test including acceptability and implementation, to inform its use within care. A bespoke survey was completed by trial participants in five countries (n = 778) at week 8. Semi-structured interviews were carried out in two countries soon after week 8 (UK n = 22, Germany n = 20). Quantitative data was analysed descriptively; for qualitative data, thematic analysis was carried out using a framework approach. Results of the two datasets were interrogated together. OUTCOMES: Survey results showed the intervention was well received, with a majority of participants indicating they would use it again, and it gave them helpful extra information; a small minority indicated the Test made them feel worse. Qualitative data showed the Test had unexpected properties, including: instigating a process of reflection, giving participants feedback on progress and new understanding about their illness, and making participants feel supported and more engaged in treatment. INTERPRETATION: The qualitative and quantitative results are generally consistent. The Test's unexpected properties may explain why the RCT showed little effect, as properties were experienced across both trial arms. Beyond the RCT, the qualitative data sheds light on measurement reactivity, i.e., how measurements of depression can impact patients.

Longitudinal investigation of patients receiving involuntary treatment for extremely severe anorexia nervosa.

INTRODUCTION: Involuntary treatment may be a life-saving option for extremely severe anorexia nervosa (AN) in the context of life-threatening conditions and refusal of care. The long-term outcomes of patients undergoing involuntary treatment for AN are poorly understood. This study aims to explore quality of life, long-term outcomes and attitudes towards involuntary treatment in patients involuntarily treated for extremely severe AN. METHODS: 23 patients involuntarily admitted for extremely severe AN (I-AN), and 25 voluntarily admitted patients (V-AN) were compared for body mass index (BMI), residual symptoms, quality of life, and attitudes towards treatment almost four years after discharge. In I-AN, clinical variables were also compared between admission and follow-up. RESULTS: At follow-up, weight restoration was higher in V-AN (p = 0.01), while differences in quality of life, BMI, and mortality rates were not significant between I-AN and V-AN (p > 0.05). In I-AN, BMI increased and weight-controlling strategies decreased at follow-up (p < 0.05). Despite negative experiences of involuntary treatment, the perception of the necessity of treatment increased from admission to follow-up (p < 0.01) and became comparable to V-AN (p > 0.05). DISCUSSION: Involuntary treatment for AN does not appear to be a barrier to weight gain and clinical improvement, nor to long-term attitudes towards treatment.

Body shape rather than facial emotion of others alters interpersonal distance in patients with anorexia nervosa.

OBJECTIVE: The study investigated interpersonal distance in patients with anorexia nervosa (AN), focussing on the role of other's facial expression and morphology, also assessing physiological and subjective responses. METHOD: Twenty-nine patients with AN and 30 controls (CTL) were exposed to virtual characters either with an angry, neutral, or happy facial expression or with an overweight, normal-weight, or underweight morphology presented either in the near or far space while we recorded electrodermal activity. Participants had to judge their preferred interpersonal distance with the characters and rated them in terms of valence and arousal. RESULTS: Unlike CTL, patients with AN exhibited heightened electrodermal activity for morphological stimuli only, when presented in the near space. They also preferred larger and smaller interpersonal distances with overweight and underweight characters respectively, although rating both negatively. Finally, and similar to CTL, they preferred larger interpersonal distance with angry than neutral or happy characters. DISCUSSION: Although patients with AN exhibited behavioural response to emotional stimuli similar to CTL, they lacked corresponding physiological response, indicating emotional blunting towards emotional social stimuli. Moreover, they showed distinct behavioural and physiological adjustments in response to body shape, confirming the specific emotional significance attached to body shape.

Trajectories and predictive factors of weight recovery in patients with anorexia nervosa completing treatment. A latent class mixed model approach.

BACKGROUND: Treatment of anorexia nervosa (AN) sometimes requires hospitalisation, which is often lengthy, with little ability to predict individual trajectory. Depicting specific profiles of treatment response and their clinical predictors could be beneficial to tailor inpatient management. The aim of this research was to identify clusters of weight recovery during inpatient treatment, and their clinical predictors. METHODS: A sample of 181 inpatients who completed a treatment programme for AN was included in a retrospective study. A latent class mixed model approach was used to identify distinct weight-gain trajectories. Clinical variables were introduced in a multinomial logistic regression model as predictors of the different classes. RESULTS: A four-class quadratic model was retained, able to correctly classify 63.7% of the cohort. It encompassed a late-rising, flattening, moderate trajectory of body mass index (BMI) increase (class 1), a late-rising, steady, high trajectory (class 2), an early-rising, flattening, high trajectory (class 3) and an early-rising, steady, high trajectory (class 4). Significant predictors of belonging to a class were baseline BMI (all classes), illness duration (class 2), and benzodiazepine prescription (class 3). CONCLUSION: Predicting different kinetics of weight recovery based on routinely collected clinical indicators could improve clinician awareness and patient engagement by enabling shared expectations of treatment response.

Clinical features and outcomes of COVID-19 patients hospitalized for psychiatric disorders: a French multi-centered prospective observational study.

BACKGROUND: Patients with psychiatric disorders are exposed to high risk of COVID-19 and increased mortality. In this study, we set out to assess the clinical features and outcomes of patients with current psychiatric disorders exposed to COVID-19. METHODS: This multi-center prospective study was conducted in 22 psychiatric wards dedicated to COVID-19 inpatients between 28 February and 30 May 2020. The main outcomes were the number of patients transferred to somatic care units, the number of deaths, and the number of patients developing a confusional state. The risk factors of confusional state and transfer to somatic care units were assessed by a multivariate logistic model. The risk of death was analyzed by a univariate analysis. RESULTS: In total, 350 patients were included in the study. Overall, 24 (7%) were transferred to medicine units, 7 (2%) died, and 51 (15%) patients presented a confusional state. Severe respiratory symptoms predicted the transfer to a medicine unit [odds ratio (OR) 17.1; confidence interval (CI) 4.9-59.3]. Older age, an organic mental disorder, a confusional state, and severe respiratory symptoms predicted mortality in univariate analysis. Age >55 (OR 4.9; CI 2.1-11.4), an affective disorder (OR 4.1; CI 1.6-10.9), and severe respiratory symptoms (OR 4.6; CI 2.2-9.7) predicted a higher risk, whereas smoking (OR 0.3; CI 0.1-0.9) predicted a lower risk of a confusional state. CONCLUSION: COVID-19 patients with severe psychiatric disorders have multiple somatic comorbidities and have a risk of developing a confusional state. These data underline the need for extreme caution given the risks of COVID-19 in patients hospitalized for psychiatric disorders.

Delphi panel to obtain clinical consensus about using long-acting injectable antipsychotics to treat first-episode and early-phase schizophrenia: treatment goals and approaches to functional recovery.

BACKGROUND: Schizophrenia is mostly a chronic disorder whose symptoms include psychosis, negative symptoms and cognitive dysfunction. Poor adherence is common and related relapse can impair outcomes. Long-acting injectable antipsychotics (LAIs) may promote treatment adherence and decrease the likelihood of relapse and rehospitalization. Using LAIs in first-episode psychosis (FEP) and early-phase (EP) schizophrenia patients could benefit them, yet LAIs have traditionally been reserved for chronic patients. METHODS: A three-step modified Delphi panel process was used to obtain expert consensus on using LAIs with FEP and EP schizophrenia patients. A literature review and input from a steering committee of five experts in psychiatry were used to develop statements about patient population, adverse event management, and functional recovery. Recruited Delphi process psychiatrists rated the extent of their agreement with the statements over three rounds (Round 1: paper survey, 1:1 interview; Rounds 2-3: email survey). Analysis rules determined whether a statement progressed to the next round and the level of agreement deemed consensus. Measures of central tendency (mode, mean) and variability (interquartile range) were reported back to help panelists assess their previous responses in the context of those of the overall group. RESULTS: The Delphi panelists were 17 psychiatrists experienced in treating schizophrenia with LAIs, practicing in seven countries (France, Italy, US, Germany, Spain, Denmark, UK). Panelists were presented with 73 statements spanning three categories: patient population; medication dosage, management, and adverse events; and functional recovery domains and assessment. Fifty-five statements achieved ≥ 80% agreement (considered consensus). Statements with low agreement (40-79%) or very low agreement (< 39%) concerned initiating dosage in FEP and EP patients, and managing loss of efficacy and breakthrough episodes, reflecting current evidence gaps. The panel emphasized benefits of LAIs in FEP and EP patients, with consensus that LAIs can decrease the risk of relapse, rehospitalization, and functional dysfunction. The panel supported links between these benefits and multidimensional longer-term functional recovery beyond symptomatic remission. CONCLUSIONS: Findings from this Delphi panel support the use of LAIs in FEP and EP schizophrenia patients regardless of disease severity, number of relapses, or social support status. Gaps in clinician knowledge make generating evidence on using LAIs in FEP and EP patients critical.

Magnesium in the treatment of alcohol withdrawal syndrome: a multicenter randomized controlled trial.

OBJECTIVE: Alcohol withdrawal syndrome (AWS) is a frequent and potentially life-threatening condition experienced in alcohol use disorder. Since hypomagnesemia is involved in AWS's severity, we conducted a multicenter double-blind randomized placebo-controlled trial to examine the efficacy of oral magnesium supplementation as an adjuvant therapy of AWS. MATERIAL AND METHODS: Inpatients were recruited in six different centers if they had a baseline score higher than eight on the Revised Clinical Institute Withdrawal Assessment for Alcohol (CIWA-Ar). The experimental treatment was magnesium lactate dehydrate, administrated three times per day providing a total of 426.6 mg per day and up to 15 days. The primary endpoint was the significant between-group difference of the CIWA-Ar total score change from baseline to 3 days later. The treatment group and baseline score were introduced as covariables in an analysis of covariance. RESULTS: A total of 98 inpatients were included {71.4% of men; mean age of 49.1 years [standard deviation (SD): 10.3]}. In the intention-to-treat population, the mean reduction of the CIWA-Ar score in the experimental group between baseline and 3 days later was 10.1 (SD: 5.2), whereas it was 9.2 (SD: 3.9) in the control group. The absolute difference of the adjusted mean in the experimental group compared with the control group was -0.69 (SD: 0.72), which did not correspond to a significant between-group difference (P = 0.34). Per-protocol analysis and sensitivity analyses also supported this result. Supplementary analyses found no significant difference regarding benzodiazepine consumption, magnesium blood concentration, and satisfaction to care. CONCLUSIONS: The present study does not support the rationale of systematic oral magnesium supplementation in patients with AWS.

Associated and intermediate factors between genetic variants of the dopaminergic D2 receptor gene and harmful alcohol use in young adults.

Dopamine receptor D2 (DRD2) and ankyrin repeat and kinase domain-containing protein 1 (ANKK1) genes have received considerable attention for their involvement in alcohol use disorder (AUD), but many questions remain on their exact role. We conducted a population-based case-control and genetic association study in a large sample of young adults. Our aim was to assess the association between DRD2 and ANKK1 single nucleotide polymorphisms (SNPs) and harmful alcohol use, disentangling associated and possible intermediate factors. A total of 1841 college students from the French region Champagne-Ardennes, aged between 18 and 21 years and who reported at least one lifetime alcohol consumption, were included in this study. Allele frequencies were analysed according to harmful alcohol use (assessed through the Alcohol Use Disorder Identification Test [AUDIT] questionnaire). Different substance use disorders, including nicotine and cannabis dependences, were also assessed through questionnaires, as was a list of potential associated factors (e.g., major depressive episode, conduct disorder, attention-deficit/hyperactivity disorder [ADHD], school failure, sugar consumption, sexual trauma, parents' use of alcohol, tobacco or cannabis). We found that DRD2 rs1800498 was associated with harmful alcohol use. Many factors were detected, but a global path analysis revealed that DRD2 rs1800498 had a significant direct effect on harmful alcohol use and that early age at first alcohol consumption and depressive symptoms moderated this effect. This study suggests an interplay between harmful alcohol use, DRD2 genotypes and other risk factors that, with a full understanding, could be useful for preventive purposes.

Transition from an adolescent to an adult eating disorder treatment centre: A qualitative investigation of the experience of inpatients with anorexia nervosa and their carers using interpretative phenomenological analysis.

AIMS: To capture the subjective experience of eating disorder patients and their immediate family members in the transition between adolescent and adult treatment services and to explore how both groups make sense of this specific experience. DESIGN: Qualitative study in the form of in-depth interviews using interpretative phenomenological analysis. SETTINGS: Participants were recruited from a university department of a large psychiatric hospital specialising in eating disorders between July 2021 and September 2022. PARTICIPANTS: A convenience sample of 18 participants was recruited, including 12 patients aged 19-30 years (m = 22.5, SD = 3.8) and six of their respective caregivers. RESULTS: Four main themes were identified in relation to the participants' experience of transition to adult care: (1) the detailed description of the transition process, (2) the emotions associated with this experience, (3) the challenges encountered and (4) recommendations for improving the process. Two fundamental meaning-making processes emerged: the feeling of being "lost in transition" and the opportunity to "become an adult". The results highlighted the factors that characterise this experience for patients and their families, and the need for practical and psychological support during the transition process. CONCLUSIONS: This study provides a unique insight into the experience of patients and their immediate family members regarding the transition from adolescent to adult care. It reveals the multidimensional impact of the transition experience and highlights the need for increased support for family members. These findings may provide new insights into interventions that promote successful transition and encourage rethinking the organisation of this crucial stage of the care pathway.

Characteristics and treatment outcome of suicidal depression: Two large naturalistic cohorts of depressed outpatients.

OBJECTIVE: The emergence of new drugs for managing suicidal ideation (e.g. ketamine) raises the question of whether suicidal depression (i.e. moderate to severe depression with concomitant suicidal ideation) is a specific depression phenotype. Therefore, this study characterized patients with suicidal depression (baseline clinical characteristics, suicidal ideation and depression evolutions, suicide risk) in two large cohorts of outpatients with depression. METHODS: LUEUR and GENESE are two large, prospective, naturalistic cohorts of French adult outpatients with depression (Diagnostic and Statistical Manual of Mental Disorders, fourth edition, criteria), treated and followed up for 6 weeks. Depression severity was assessed with the Hospital Anxiety and Depression Scale, and suicidal ideation with the suicidal item of the Montgomery-Åsberg Depression Rating Scale. Patients with moderate or severe depression (Hospital Anxiety and Depression Scale-Depression subscale score >11) were selected and classified as without suicidal ideation (suicidal item of the Montgomery-Åsberg Depression Rating Scale <2), with moderate suicidal ideation (suicidal item of the Montgomery-Åsberg Depression Rating Scale [2; 3]) and with severe suicidal ideation (suicidal item of the Montgomery-Åsberg Depression Rating Scale ⩾4). RESULTS: Baseline clinical features were more severe (e.g. higher anxiety and depression scores) in depressed patients with moderate/severe suicidal ideation. Depression remission after treatment was less frequent among patients with severe suicidal ideation. The risk of suicide attempt during the follow-up was threefold higher in patients with suicidal ideation among those 10% had persistent suicidal ideation. CONCLUSION: Suicidal depression could be a specific depression phenotype with more severe clinical characteristics, less frequent depression remission, suicidal ideation persistence and higher suicide attempt risk, despite antidepressant treatment. It seems that novel therapeutic strategies could be needed.

Time Devoted to Individual, Collective, and Two-Person Sports: Its Association with Risk of Exercise Addiction and Alcohol Use Disorder.

INTRODUCTION: Although sport activities have beneficial effects on health, excessive practice can lead to exercise addiction (EA), which can be associated with other addictive behaviors. However, results regarding the comorbidities between EA and alcohol use disorder (AUD) remain heterogeneous. This study aims to investigate the relationship between a proxy of AUD and different sport practices, more specifically focusing on EA. METHODS: One thousand nine hundred eighty-five (N = 1,985) participants were recruited online and selected to represent the French adult population. Participants were asked to answer questions regarding sport activity, with the EA inventory questionnaire investigating EA, and alcohol consumption, with the CAGE questionnaire investigating a proxy of AUD (score ≥2). RESULTS: AUD was associated with a higher risk of EA and with more time devoted to collective sports (such as football) and two-person sports (such as tennis). The risk of EA was higher for individual sports (such as running), and the risk of AUD seems to increase with the level of physical activity for collective sport but to decrease for individual sports. The type of sports partly but significantly mediated the relationship between AUD and EA. CONCLUSIONS: Results support the hypothesis that different types of sport have different risks for EA (individual sports being more concerned) and AUD (collective sports being more concerned). Results suggest that the type of sports may be a crucial variable to understand how physical activity can be a risk factor for alcohol disorders. The social dimension of collective sports should be further investigated to facilitate preventive approaches.

Clinical meaning of body temperatures in anorexia nervosa and bulimia nervosa.

OBJECTIVE: Bradycardia is one of the common cardiac abnormalities in patients with eating disorders. It ensues from hypometabolism, which results from reduced caloric intake and consequential weight loss. Hypothermia is another consequence of hypometabolism. While at-rest metabolism and body mass index (BMI) are typically used to assess hypometabolism and estimate potential bradycardia, we hypothesised that body temperature, which is easy to measure, could also capture the presence of this threatening cardiovascular condition. METHOD: We monitored heart rate continuously for 72 h, measured resting energy expenditure (REE) and assessed body temperature in 12 body parts for 58 patients with anorexia nervosa (AN) and 29 patients with bulimia nervosa (BN). RESULTS: Palm temperature reflects bradycardia in both AN and BN, explaining 18% of its variance (p < 0.001), capturing this aspect even more efficiently than BMI. We also observe different correlations between palm temperature, abdominal temperature, BMI, REE and levels of physical activity. CONCLUSION: Palm temperature could be used as a warning of bradycardia, a serious cardiovascular condition which can be difficult to detect in short visits with outpatients. Further studies are needed to determine how useful bradycardia and palm temperature could be to assess severity and prognosis of the disorder.

Pupil psychosensory reflex in response to own and standardised silhouettes in patients with anorexia nervosa.

OBJECTIVE: This study aimed to assess the physiological response of patients with anorexia nervosa (AN) to different types of silhouettes using pupillometry. METHODS: We measured the pupil psychosensory reflex (PSR) of 42 patients with AN and 35 healthy controls in response to standardised body silhouettes and to pictures of their own silhouettes digitally modified to represent different body mass indices (BMI). Perceptual distortion and body dissatisfaction were assessed using Anamorphic Micro Software©. Twenty-three of the recruited patients were tested up to four times during an inpatient treatment programme to assess the impact of weight gain. RESULTS: PSR correlated with the subjective rating of emotional arousal in controls but not in patients. Own silhouettes and standardised silhouettes triggered a different pupil response both in patients with AN and in controls. With pictures of their own silhouettes, pupil response to underweight stimuli differed from pupil response to normal weight or overweight stimuli in both groups. Weight gain was associated with an increase in PSR, an improvement of ideal BMI and a decrease of body dissatisfaction, but no change in perceptual distortion. CONCLUSION: Our findings support the idea that pupillometry could be a useful tool to assess the physiological state of patients with AN.

Experiencing eight psychotherapy approaches devoted to eating disorders in a single-day workshop increases insight and motivation to engage in care: a pilot study.

PURPOSE: For patients with eating disorders (EDs), early engagement in care is usually considered a positive prognostic factor. The aim of the study was to investigate how a single-day intervention devoted to early, brief, experiential exposure to a variety of psychotherapy approaches might support commitment to change and the decision to engage in care in patients with EDs. METHODS: One hundred and sixty-nine adult outpatients newly diagnosed with an ED took part in a single-day workshop for groups of up to ten patients, where they experienced eight psychotherapeutic approaches. Motivation to change care and level of insight were assessed at baseline and 10 days after the intervention. RESULTS: Motivation and commitment to take active steps toward change (expressed by the "Committed Action" composite score) significantly improved after the intervention (p < 0.001), and a significant number of patients specifically moved from "contemplation" to "action" stage (p < 0.001). The improvement of motivation to change was significantly associated with an increase in insight capacity (p < 0.001), and this increase was observed for almost all related dimensions such as recognition of illness or awareness of need for psychological treatment. CONCLUSION: A single-day session devoted to experiencing a range of group psychotherapies increased patients' insight and motivation to actively engage in care. To confirm potential longer-term benefits of this intervention, further studies are needed to explore the contribution of each approach and process specifically involved in patients' increased motivation for care, as well as the clinical characteristics of patients associated with better outcomes. LEVEL OF EVIDENCE: V: Opinions of respected authorities, based on descriptive studies, narrative reviews, clinical experience, or reports of expert committees.

Morphing analysis of facial emotion recognition in anorexia nervosa: association with physical activity.

PURPOSE: Anorexia Nervosa (AN) has been linked to emotion processing inefficiencies, social cognition difficulties and emotion dysregulation, but data on Facial Emotion Recognition (FER) are heterogenous and inconclusive. This study aims to explore FER in patients with AN using a dynamic and ecological evaluation, and its relationship with Physical Activity (PA), an important aspect of AN that could impact emotional processing. METHODS: Sixty-six participants (33 patients with AN and 33 healthy controls) performed a morphed facial emotional recognition task and 49 of them wore an accelerometer during seven days to assess PA. Axis-I disorders and depressive symptoms have been assessed. RESULTS: No difference was found regarding time to recognize facial emotions. However, patients with AN correctly recognize emotions more frequently than controls. This was specific to disgust, although there was also a tendency for sadness. Among patients, higher depressive scores are associated with a faster and more accurate recognition of disgust, while a higher level of PA is associated to decreased accuracy in recognizing sadness. CONCLUSION: Patients with AN are capable of recognizing facial emotions as accurately as controls, but could have a higher sensitivity in recognizing negative emotions, especially disgust and sadness. PA has opposite effects and, thus, could be considered as an emotional regulation strategy against negative affect. LEVEL OF EVIDENCE II: Controlled trial without randomization.

Outcome in depression (II): beyond the Hamilton Depression Rating Scale.

BACKGROUND: The Leuven Affect and Pleasure Scale (LAPS) was developed as an outcome measure in major depressive disorder (MDD) tha treflects patient treatment expectations. The present report investigates whether the LAPS negative affect, the LAPS positive affect, and the LAPS hedonic tone have added value on top of the Hamilton Depression Rating Scale (HAMD) in explaining generic as well as patient-centered outcomes. METHODS: A total of 109 outpatients with Diagnostic and Statistical Manual of Mental Disorders, fifth edition, criteria for MDD were assessed over 8 weeks of antidepressant treatment. At baseline and after 2, 4, and 8 weeks, the LAPS, HAMD, Snaith-Hamilton Pleasure Scale (SHAPS), Positive and Negative Affect Scale (PANAS), and Sheehan Disability Scale were administered. The Clinical Global Impression of Improvement (CGI-I) and the Patient Global Impression of Improvement (PGI-I) were also administered at endpoint. RESULTS: Changes in LAPS negative affect, LAPS positive affect, and LAPS hedonic tone explain 14% of the additional variance in CGI-I, 21% in PGI-I, 37% in cognitive functioning, 32% in overall functioning, 31% in "my life is meaningful," and 45% in "I feel happy." Compared to standard scales (PANAS and SHAPS), the LAPS negative affect, LAPS positive affect, and LAPS hedonic tone differentiate better between different levels of CGI-I or PGI-I. CONCLUSIONS: The LAPS has added value (on top of the HAMD) in explaining changes in both generic outcomes (CGI-I/PGI-I) and patient-centered dimensions. The LAPS negative and positive affects and the LAPS hedonic tone differentiate CGI-I and PGI-I scores better than corresponding scales supposed to cover the same domains.

Outcome in depression (I): why symptomatic remission is not good enough.

BACKGROUND: The Leuven Affect and Pleasure Scale (LAPS) is a depression outcome measure aiming to better reflect patient treatment expectations. We investigated the evolution of the LAPS and some comparator scales during antidepressant treatment and compared scores of remitters with scores of healthy controls. METHODS: A total of 109 outpatients with Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5) major depressive disorder were assessed over 8 weeks of antidepressant treatment. At baseline and after 2, 4, and 8 weeks, the LAPS as well as the Hamilton Depression Rating Scale (HAMD), the Snaith-Hamilton Pleasure Scale (SHAPS), the Positive and Negative Affect Scale (PANAS), and the Sheehan Disability Scale (SDS) were administered. Healthy controls consisted of 38 Italian adults and 111 Belgian students. RESULTS: Correlations between baseline positive and negative affect were only moderate (R between -0.20 and -0.41). LAPS positive affect and hedonic tone showed higher correlations with LAPS cognitive functioning, overall functioning, meaningfulness of life, and happiness than HAMD scores or PANAS negative affect. HAMD remission was associated with normal levels of LAPS negative affect but with significantly lower levels of LAPS positive affect, hedonic tone, cognitive functioning, overall functioning, meaningfulness of life, and happiness. The scores on the latter subscales only reached healthy control scores when the HAMD approached a score of 0 or 1. CONCLUSIONS: The standard definition of remission (HAMD cutoff of 7) is probably adequate for remitting negative mood, but not good enough for recovering positive mood, hedonic tone, functioning, or meaningfulness of life.

Physical exercise-related endophenotypes in anorexia nervosa.

BACKGROUND: The persistence of physical exercise in anorexia nervosa (AN) despite underweight and its maintaining factors are poorly understood. The aim of this study was to explore the attitudes toward physical exercise and its effects on emotions, cognitive functioning, and body image perception in patients with AN, and to search for exercise-related endophenotypes of the pathology. METHODS: Physical exercise dependence, quantity, and dysregulation were assessed by the Exercise Dependence Scale (EDS), the Godin Leisure Time Exercise Questionnaire (GLTEQ) and a standardized effort test in 88 patients with AN, 30 unaffected relatives and 89 healthy controls. Changes in positive and negative affect, cognitive rigidity, and body image distortion were measured before and after the effort test in the three groups. RESULTS: Patients with AN had higher scores on the EDS and the GLTEQ and used more effort in the standardized effort test. These three measures of physical exercise correlated with negative emotions at baseline. After the effort test, patients with AN had marked emotional improvement, a moderate increase in body image distortion and a small increase in cognitive rigidity compared to HC. Unaffected relatives also had a significant postexercise increase of positive emotion. DISCUSSION: The mood-related drive for physical exercise has the characteristics of an endophenotype of the disorder. Excessive and driven physical exercise may be state-associated features of AN, driven by the positive effect on emotional wellbeing.

The safety of agomelatine in standard medical practice in depressed patients: A 26-week international multicentre cohort study.

OBJECTIVE: The present observational cohort study documented the safety of agomelatine in current medical practice in out-patients suffering from major depressive disorder. METHOD: The 6-month evolution of agomelatine-treated patients was assessed with a focus on safety (emergent adverse events, liver acceptability), severity of depression using the Clinical Global Impression Severity (CGI-S) score, and functioning measured by the Sheehan Disability Scale (SDS). RESULTS: A total of 8453 depressed patients from 761 centres in 6 countries were analysed (female: 67.7%; mean age: 49.1 ± 14.8 years). Adverse events reported were in accordance with the known safety profile of agomelatine. Cutaneous events were reported in 1.7% of the patients and increased hepatic transaminases values were reported in 0.9 % of the patients. The incidence of events related to suicide/self-injury was 1.0%. Two completed suicides, not related to the study drug, were reported. CGI-S total scores and SDS sub-scores improved and numbers of days lost or underproductive decreased over the treatment period. CONCLUSIONS: In standard medical practice, agomelatine treatment was associated with a low incidence of side effects. No unexpected events were reported. A decrease in the severity of the depressive episode and improved functioning were observed. TRIAL REGISTRATION NAME: Observational cohort study to evaluate the safety of agomelatine in standard medical practice in depressed patients. A prospective, observational (non-interventional), international, multicentre cohort study. TRIAL REGISTRATION NUMBER: ISRCTN53570733.

Increased cognitive flexibility mediates the improvement of eating disorders symptoms, depressive symptoms and level of daily life functioning in patients with anorexia nervosa treated in specialised centres.

OBJECTIVE: Poor cognitive flexibility has been highlighted in patients with anorexia nervosa (AN), contributing to the development and maintenance of symptoms. The aim of the present study is to investigate how enhanced cognitive flexibility is involved in treatment outcomes in patients with AN. METHOD: One hundred thirty female out-patients treated for AN have been assessed at baseline and after 4 months of treatment. Path analyses were used to investigate the mediating role of cognitive flexibility, measured through the Brixton test, on a wide range of outcomes: body mass index, eating disorder symptoms, daily life functioning, anxiety, depression, emotions, self-rated silhouette. RESULTS: Cognitive flexibility was improved during treatment, and enhanced cognitive flexibility explains a significant part of level of the improvement in daily life functioning (26%), reduction of eating disorder symptoms (18%) and reduction of depressive symptoms (17%). Others outcomes were also improved, but these improvements were not mediated by cognitive flexibility. CONCLUSIONS: Results suggest that enhancing cognitive flexibility could help reduce rigid cognitive and behavioural patterns involved in AN, thus improving everyday functioning and clinical severity. Further studies combining different types of cognitive flexibility evaluation as well as neuroimaging may be necessary to better establish which of its aspects are involved in patients' improvement.