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INTRODUCTION:  For nearly 20% of patients diagnosed with Anorexia Nervosa (AN), the eating disorder (ED) is prolonged and becomes long-lasting. It has been reported that patients diagnosed with Severe Enduring Anorexia Nervosa (SE-AN) have worse ED symptoms, higher rates of lifetime hospitalization, and lower psychosocial well-being compared to patients with shorter disease duration. OBJECTIVES:  This review aims to describe the treatments proposed to date and their effectiveness on SE-AN-related outcomes. METHODS:  We conducted a PubMed search for studies addressing the issue of treatment approach to SE-AN adults, that were published between 2003 and 2023, peer-reviewed, written in the English language, and available in full-text. Next, we inductively created relevant macro-themes by synthesizing the data from the included articles. RESULTS:  Of 251 PubMed studies, 25 articles were considered for data extraction, all published between 2003 and 2022. We identified three macro-themes. The first macro-theme, "Psychotherapy", mostly takes into consideration treatment effectiveness of cognitive behavioral therapy (CBT). Various reports determined its greater effectiveness compared to Specialist Supportive Clinical Management (SSCM), and one study proved that outpatient CBT is a valid alternative to hospitalization. The second one involves "Pharmacological Treatments". Research on dronabinol, a synthetic orexigenic cannabinoid, antipsychotics (in particular, olanzapine and haloperidol), and ketamine showed some mixed results regarding the often-complementary areas of weight gain and improvement in ED-related symptoms. Regarding the third macro-theme, "Brain Stimulation Therapies," such as Repetitive Transcranial Magnetic Stimulation (rTMS) and Deep Brain Stimulation (DBS), we found promising results in improving ED-related psychological traits (such as mood and anxiety), affective regulation, and quality of life. However, we have observed divergent results regarding outcome measures such as BMI and weight gain. CONCLUSIONS:  SE-AN patients are predicted to encounter both medical complications and psychological distress of increasing severity that will inevitably affect their quality of life; to our knowledge, research evidence on treatment options for SE-AN remains limited, and the methodological quality of studies is generally low. These findings denote the need to focus future research efforts on effective treatment strategies specific to long-lasting EDs.

For nearly 20% of patients diagnosed with Anorexia Nervosa, the eating disorder is prolonged and becomes long-lasting. Those patients have worse ED symptoms, higher rates of lifetime hospitalization, and lower psychosocial well-being compared to patients with shorter disease duration. This review aims to describe the treatments proposed to date and their effectiveness on severe enduring anorexia nervosa related outcomes. The data obtained show how the intervention techniques primarily used in these patients are psychotherapy (in particular, cognitive behavioral therapy and Specialist Supportive Clinical Management), pharmacological treatments, and Brain Stimulation Therapies (such as Repetitive Transcranial Magnetic Stimulation and Deep Brain Stimulation). To our knowledge, research evidence on treatment options for SE-AN remains limited and these findings denote the need to focus future research efforts on effective treatment strategies specific to long-lasting eating disorders.

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PURPOSE: Treatment resistance is a significant challenge in addressing eating disorders (EDs). The Autonomous and Controlled Motivation for Treatment Questionnaire (ACMTQ) has been previously validated in ED populations to assess patients' motivation for treatment. This study aimed to validate the ACMTQ in the Italian language (ACMTQ-ITA) and evaluate its psychometric properties. METHODS: We recruited a clinical sample of adults aged 18 or older, diagnosed with EDs, proficient in the Italian language, and providing written informed consent. Participants with psychiatric comorbidities such as schizophrenia, bipolar disorder, and substance use disorder were excluded from the study. Validity of the ACMTQ-ITA was assessed using reliability analysis with Cronbach's α and McDonald's ω estimates, and Confirmatory Factor Analysis (CFA). RESULTS: Results from the reliability analysis confirmed the internal consistency of the Autonomous Motivation (AM) factor (α = 0.82, ω = 0.82), the Controlled Motivation (CM) factor (α = 0.76, ω = 0.77), and the ACMTQ-ITA overall score (α = 0.79). The CFA confirmed the two-factor solution (i.e., AM and CM) identified in the original validation of the ACMTQ (Comparative Fit Index = 0.92, Akaike Information Criterion = 3427.26, Bayesian Information Criterion = 3486.82; Root Mean Square Error of Approximation = 0.08, Standardized Root Mean Square Residual = 0.09). CONCLUSION: The ACMTQ-ITA emerged as a valid and reliable tool for measuring motivation for treatment in individuals with EDs. Its implementation may facilitate the comprehension of treatment motivation, offering valuable clinical insights and implications for health management practices. LEVEL OF EVIDENCE: Level V, descriptive studies.

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Narcolepsy type 1 is a chronic central disorder of hypersomnolence, and it is frequently accompanied by overweight, but the association between narcolepsy type 1 and eating disorders is controversial. Our study aims to compare patients with narcolepsy type 1 and controls on the symptomatology of eating disorders and to evaluate the association between clinical factors. This is a cross-sectional study, with consecutive recruitment of patients with narcolepsy type 1 attending the Outpatient Clinic for Narcolepsy at the IRCCS Istituto delle Scienze Neurologiche di Bologna (Italy) for routine follow-up visits. Healthy subjects from general populations were recruited as controls. Patients underwent a questionnaire-based assessment using the Eating Disorder Examination Questionnaire (EDE-Q), Binge Eating Scale (BES), Italian Night Eating Questionnaire (I-NEQ), Epworth Sleepiness Scale (ESS), and Narcolepsy Severity Scale (NSS). One hundred and thirty-eight patients with narcolepsy type 1 and 162 controls were enrolled. This study showed that individuals with narcolepsy type 1 reported higher scores on the EDE-Q, I-NEQ, and a higher body mass index (BMI) than the controls. The logistic regression analysis results, with EDE-Q positivity as a dependent variable, demonstrate a significant association with antidepressant drugs, female sex, and the use of sodium oxybate. We found an association between antidepressant drug consumption, the NSS total score, and female sex with BES positivity as the dependent variable. The logistic regression analysis for I-NEQ positivity found an association with antidepressant drug use. This study shows that patients with narcolepsy type 1 frequently present with comorbid eating disorder symptomatology, mainly night eating syndrome. Investigating the possible presence of eating disorders symptomatology through questionnaires is fundamental during the assessment of patients with narcolepsy type 1.

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OBJECTIVE: Healthcare workers (HCWs) were considered a population at risk for developing psychiatric symptoms during the COVID-19 pandemic, such as anxiety, depression, and post-traumatic stress disorder (PTSD). Peritraumatic distress is associated with post-traumatic psychopathological symptoms; however, little is known about how it may affect functioning. The study aimed at evaluating the level of peritraumatic distress in a sample of HCWs during the first wave of the COVID-19 pandemic and at examining the relationship between peritraumatic distress, mental health symptoms, and functioning impairment. METHODS: A sample of 554 frontline HCWs were consecutively enrolled in major university hospitals and community services in Italy. The PDI, IES-R, PHQ-9, and GAD-7 were used to assess peritraumatic distress, symptoms of PTSD, depression, and anxiety, respectively, and the WSAS to investigate functioning impairment. PDI scores were higher among females, community services, physicians, and nurses. Furthermore, the PDI correlated significantly with the GAD-7, PHQ-9, IES-R, and WSAS. RESULTS: In a mediation analysis, the direct effect of PDI on WSAS and the indirect effects through the PHQ-9 and IES-R were statistically significant (P < .001). CONCLUSION: Peritraumatic distress reported by HCWs was associated with symptoms of PTSD, depression, and anxiety, but the association with reduced functioning may be only partially mediated through symptoms of depression and PTSD.

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BACKGROUND: Anorexia Nervosa (AN) poses significant therapeutic challenges, especially in cases meeting the criteria for Severe and Enduring Anorexia Nervosa (SE-AN). This subset of AN is associated with severe medical complications, frequent use of services, and the highest mortality rate among psychiatric disorders. CASE PRESENTATION: In the present case series, 14 patients were selected from those currently or previously taken care of at the Eating Disorders Outpatients Unit of the Maggiore Hospital in Bologna between January 2012 and May 2023. This case series focuses on the effects of the disease, the treatment compliance, and the description of those variables that could help understand the great complexity of the disorder. CONCLUSION: This case series highlights the relevant issue of resistance to treatment, as well as medical and psychological complications that mark the life course of SE-AN patients. The chronicity of these disorders is determined by the overlapping of the disorder's ego-syntonic nature, the health system's difficulty in recognizing the problem in its early stages, and the presence of occupational and social impairment.

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INTRODUCTION: Liraglutide 3.0 mg, a glucagon-like peptide-1 (GLP-1) analogue, is a medication approved for obesity treatment. This study aimed to investigate the relationship between psychiatric symptoms, including depression, anxiety, and binge eating, and their impact on therapy adherence. METHODS: A clinical audit was carried out on a cohort of 54 adults with obesity treated with liraglutide 3.0 mg. We retrospectively analyzed the connection between psychiatric symptoms assessed through the State-Trait Anxiety Inventory (STAI), Beck Depression Inventory (BDI), and Binge Eating Scale (BES). Adherence to therapy was assessed by the maximum dosage (MD) and treatment duration (TD). RESULTS: Notably, a discontinuation rate of 59% was encountered. However, among those who continued the treatment, we observed a negative association between anxiety symptoms (STAI score) and MD, depression symptoms (BDI score) and TD, and a higher likelihood of binge eating (BES score > 17) and TD. Moreover, presence of psychiatric symptoms did not compromise drug's effectiveness in achieving weight loss, which was 4.43% (± 5.5 SD) in the whole sample and 5.3% (± 6.3 SD) in the subgroup evaluated at 12 weeks. CONCLUSION: We observed a high discontinuation rate in real-life clinical setting, where Liraglutide 3.0 therapy is paid out-of-pocket. While psychiatric symptoms might play a role in diminishing adherence to therapy, they do not prevent drug's effectiveness to promote weight loss. This finding underscores the potential advantages of liraglutide 3.0 mg therapy for individuals contending with obesity while simultaneously managing mental health challenges. LEVEL OF EVIDENCE: Level V, descriptive studies.

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This study aimed to characterize the prevalence of eating disorders (EDs), disturbed eating behaviors (DEBs), and emotional eating attitudes (EEAs) among patients affected by endometriosis in order to understand a potential crosslink between this impacting gynecological disease and a Body Mass Index shift. A total of 30 patients were recruited at an endometriosis outpatient clinic in Bologna and were assessed by using standardized instruments and specific questionnaires for EDs, DEBs, and EEAs. Sociodemographic information and endometriosis clinical features and history information were collected by adopting a specific questionnaire. Retrospective reports of lifetime Body Mass Index (BMI) changes, current BMI, peak pain severity during the last menstrual period, and the average of pain intensity during the last intermenstrual period were used for a correlation with the mean score from eating-behavior scales' assessment. The preliminary results indicate that, although only 3.33% of endometriosis patients are affected by ED, statistically significant differences at the mean scores of DEBs and EEAs assessment scales were found by stratifying patients on the basis of BMI levels at risk for infertility and coronary heart disease and on the basis of moderate/severe pain levels. The enrichment of the sample size and the recruitment of the control group to complete the study enrollment will allow us to investigate more complex and strong correlation findings and to assess the prevalence of EDs among endometriosis patients.

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Binge-eating (BE) symptoms are relatively common in major depressive disorder (MDD), but their prognostic role is not fully understood. This study compared two groups of patients with MDD experiencing or not BE symptoms to ascertain differences in terms of clinical manifestations, presence of bipolar features, and antidepressant treatment outcomes. The study involved 482 outpatients collected within the Combining Medications to Enhance Depression Outcomes (CO-MED) trial, who were assessed with scales for depressive and hypomanic symptomatology, suicidality, comorbid mental disorders, and childhood traumas. BE symptoms were reported in 95 patients (20%). Patients with MDD experiencing BE symptoms were characterized by higher scores of negative self-outlook ( P = 0.0018), negative outlook of future ( P = 0.0014), irritability ( P = 0.0043), comorbid anxiety disorders (generalized anxiety disorder: P = 0.0006; panic disorder: P < 0.0001; social phobia: P < 0.0001), obsessive-compulsive disorder ( P = 0.0053), hypomanic symptoms (increased talkativeness: P = 0.0029; reduced need for sleep: P = 0.0171), and suicidality (suicidal propensity: P = 0.0013; suicidal risk: P = 0.0148; lifetime suicidal behavior: P = 0.0052). BE symptoms (OR = 2.02; 95% CI = 1.06-3.84) and depression severity (OR = 1.04; 95% CI = 1.00-1.08) were independently associated with lifetime attempted suicide. The presence of BE symptoms might indicate higher severity of depressive disorder. Suicidal risk is a major issue in these patients, whereas the association between BE and bipolar features needs further research.

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BACKGROUND: Psychiatric disorders are complex, multifactorial illnesses with a demonstrated biological component in their etiopathogenesis. Epigenetic modifications, through the modulation of DNA methylation, histone modifications and RNA interference, tune tissue-specific gene expression patterns and play a relevant role in the etiology of psychiatric illnesses. OBJECTIVE: This review aims to discuss the epigenetic mechanisms involved in psychiatric disorders, their modulation by environmental factors and their interactions with genetic variants, in order to provide a comprehensive picture of their mutual crosstalk. METHODS: In accordance with the PRISMA guidelines, systematic searches of Medline, EMBASE, PsycINFO, Web of Science, Scopus, and the Cochrane Library were conducted. RESULTS: Exposure to environmental factors, such as poor socio-economic status, obstetric complications, migration, and early life stressors, may lead to stable changes in gene expression and neural circuit function, playing a role in the risk of psychiatric diseases. The most replicated genes involved by studies using different techniques are discussed. Increasing evidence indicates that these sustained abnormalities are maintained by epigenetic modifications in specific brain regions and they interact with genetic variants in determining the risk of psychiatric disorders. CONCLUSION: An increasing amount of evidence suggests that epigenetics plays a pivotal role in the etiopathogenesis of psychiatric disorders. New therapeutic approaches may work by reversing detrimental epigenetic changes that occurred during the lifespan.

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BACKGROUND: Healthcare workers (HCWs) deployed to the frontline during the COVID-19 pandemic are at risk for developing mental disorders, with a possible impact on their wellbeing and functioning. The present study aimed at investigating post-traumatic stress symptoms (PTSS), anxiety and depressive symptoms and their relationships with impairment in the functioning impairment among frontline HCWs from three Italian regions differently exposed to the first wave of the COVID-19 emergency: Tuscany (low), Emilia-Romagna (medium) and Lombardy (high). METHODS: 514 frontline HCWs were consecutively enrolled in hospital units devoted to the treatment of COVID-19 patients. They completed the IES-R, PHQ-9 and GAD-7 to assess PTSS, depressive and anxiety symptoms respectively, and the WSAS to investigate functioning impairment. RESULTS: A total of 23.5% of HCWs reported severe PTSS, 22.4% moderate-severe anxiety symptoms, 19.3% moderate-severe depressive symptoms and 22.8% impairment in global functioning. HCWs from the higher-exposure regions reported significantly higher scores in all instruments than those from lower-exposure regions. In a multiple linear regression model, PTSS, depressive and anxiety symptoms presented a significant positive association with the functioning impairment. Both PTSS and depression resulted to be independently related to functioning impairment. LIMITATIONS: The cross-sectional design and the use of self-report instruments. CONCLUSIONS: Depressive and PTSS appear to be the greatest contributors to functioning impairment in HCWs exposed to a massive stressful sanitary event as the COVID-19 pandemic. A more accurate assessment of work-related mental health outcomes in such population could help planning effective prevention strategies and therapeutic interventions.

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BACKGROUND: Few studies, so far, have been specifically designed to highlight the features related to Compulsory Admissions (CA) and Voluntary Admissions (VA) in Italian psychiatric emergency wards. AIMS: The main purpose of this observational study was to compare the sociodemographic and clinical characteristics of VA and CA and to explore possible predictors of re-admissions. METHODS: During a 6-month Index Period (February, the 1st-July, the 31st 2008) all psychiatric admissions were documented and then followed-up through all available informatic systems for the next 9 years. RESULTS: Out of 390 hospitalizations, 101 (25.9%) were compulsory (CA rate was 2.79 per 10,000 inhabitants per year, mean duration of hospitalizations of 7.33 ± 7.84 days). Diagnoses were recorded for the 325 patients who had been hospitalized during index period: schizophrenic psychoses ([p = .042], in particular schizophrenia [p = .027]), manic episode (p = .044), and delusional disorders (p = .009) were associated with CA; conversely, the diagnosis of unipolar major depression (p = .005) and personality disorders (p = .048) were significantly more frequent in VA. The 325 admitted patients were followed up for 1,801 person-years. No significant differences were found in terms of drop-outs, transferring, and discharge rates, and mortality rates due to both natural causes and suicides. Factors associated with at least one compulsory readmission were younger age and having had a previous CA (p = .011); conversely having been engaged with psychiatric services for over 1 year prior to index hospitalization was protective for a subsequent CA (p = .013). CONCLUSIONS: After a 40-year old political reform, the current study shows that, in a context of integrated outpatient and inpatient services, engagement with outpatient care may be protective for compulsory rehospitalization.

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BACKGROUND: The subsequent waves of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic have represented a dramatic health emergency characterized by significant consequences on mental health. Diachronic variations in the incidence rates of acute relapse of psychiatric disorders may represent significant "sentinel events" for assessing the mental health response to an unprecedented stressful event. AIM: To investigate the variation in psychiatric hospitalization rates and differences in sociodemographic and clinical-psychopathological peculiarities at Bologna "Maggiore" General Hospital Psychiatric Ward (GHPW) between the first two waves SARS-CoV-2 pandemic and the same periods of the previous 3 years. The secondary purpose of the study was to suggest a diachronic response pathway to stress by reporting additional literature data on coping strategies. METHODS: This observational and retrospective study collected information on admission to the GHPW at the "Maggiore" Hospital in Bologna in the index periods defined as follows: the first period between February 24, 2020 and April 30, 2020 (first epidemic wave) and the second period between October 8, 2020, and January 7, 2021 (second pandemic wave). Absolute numbers and proportion of admitted patients, their sociodemographic and clinical-psychopathological characteristics were compared with the same parameters recorded in the two same periods of the previous 3 years. No strict inclusion or exclusion criteria were provided in the data collection to collect information on all patients requiring acute psychiatric hospitalization. RESULTS: During the first wave, there was a significant reduction in hospitalization rates, although there was a simultaneous increase in compulsory hospitalizations and the acute relapse of schizophrenia spectrum and other psychotic disorders. During the second wave, hospitalization rates reached those recorded during the same period of the previous 3 years, mainly due to the rise of bipolar and related disorders, depressive disorders, anxiety disorders, trauma- and stressor-related disorders and suicidal behaviors. CONCLUSION: The coping strategies adopted during the first wave of the SARS-CoV-2 pandemic protected the vulnerable population from the general risk of clinical-psychopathological acute relapse, even if they increased the susceptibility to run into schizophrenia spectrum and other psychotic disorder relapses. In the medium-long term (as in the second pandemic wave), the same strategies do not play protective roles against the stress associated with the pandemic and social restriction measures. Indeed, during the second wave of the SARS-CoV-2 pandemic, an increase in total hospitalization rate, suicidal behaviors and the incidence rate of bipolar and related disorders, depressive disorders, anxiety disorders, trauma- and stressor-related disorders was observed.

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Anorexia Nervosa (AN) is a severe eating disorder which typically develops in younger females. Many studies focus on this specific population, a majority of which will eventually partially or fully recover. A minority will become chronic despite extensive treatment. These patients are treatment-resistant and may not necessarily benefit from usual treatment. In this article we will reflect on possible mechanisms which may explain the maintenance of disease, and especially on the possible role of affective and anxiety disturbances. We will use, due to the lack of large-scale studies, data from risk and prognostic factors, treatment options and neurobiological correlates in chronic AN patients. Lastly, we will propose how these elements may advise further research and treatments.

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INTRODUCTION: The aims of this systematic review and meta-analysis are to provide a summary of the current literature concerning compulsory treatments in patients with eating disorders (ED) and to understand whether compulsorily and involuntarily treated patients differ in terms of baseline characteristics and treatment outcomes. METHODS: Relevant articles were identified following the PRISMA guidelines by searching the following terms: "treatment refusal", "forced feeding", "compulsory/coercive/involuntary/forced treatment/admission", "eating disorders", "feeding and eating disorders", "anorexia nervosa", "bulimia nervosa". Research was restricted to articles concerning humans and published between 1975 and 2020 in English. RESULTS: Out of 905 articles retrieved, nine were included for the analyses allowing the comparisons between 242 compulsorily and 738 voluntarily treated patients. Mean body mass index (BMI) was slightly lower in patients compelled to treatments. Mean illness duration, BMI at discharge and BMI variation showed no significant differences between the two groups. Average length of hospitalization was 3 weeks longer among compulsory-treated patients, but this did not result in a higher increase in BMI. No significant risk difference on mortality was estimated (three studies). CONCLUSIONS: Compulsory treatments are usually intended for patients having worse baseline conditions than voluntary ones. Those patients are unlikely to engage in treatments without being compelled but, after the treatments, albeit with longer hospitalisations, they do achieve similar outcomes. Therefore, we can conclude that forcing patients to treatment is a conceivable option. LEVEL OF EVIDENCE: Level I, systematic review and meta-analysis.

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Interstitial pneumonia was the first manifestation to be recognized as caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2); however, in just a few weeks, it became clear that the coronavirus disease-2019 (COVID-19) overrun tissues and more body organs than just the lungs, so much so that it could be considered a systemic pathology. Several studies reported the involvement of the conjunctiva, the gut, the heart and its pace, and vascular injuries such as thromboembolic complications and Kawasaki disease in children and toddlers were also described. More recently, it was reported that in a sample of 214 SARS-CoV-2 positive patients, 36.4% complained of neurological symptoms ranging from non-specific manifestations (dizziness, headache, and seizures), to more specific symptoms such hyposmia or hypogeusia, and stroke. Older individuals, especially males with comorbidities, appear to be at the highest risk of developing such severe complications related to the Central Nervous System (CNS) involvement. Neuropsychiatric manifestations in COVID-19 appear to develop in patients with and without pre-existing neurological disorders. Growing evidence suggests that SARS-CoV-2 binds to the human Angiotensin-Converting Enzyme 2 (ACE2) for the attachment and entrance inside host cells. By describing ACE2 and the whole Renin Angiotensin Aldosterone System (RAAS) we may better understand whether specific cell types may be affected by SARS-CoV-2 and whether their functioning can be disrupted in case of an infection. Since clear evidences of neurological interest have already been shown, by clarifying the topographical distribution and density of ACE2, we will be able to speculate how SARS-CoV-2 may affect the CNS and what is the pathogenetic mechanism by which it contributes to the specific clinical manifestations of the disease. Based on such evidences, we finally hypothesize the process of SARS-CoV-2 invasion of the CNS and provide a possible explanation for the onset or the exacerbation of some common neuropsychiatric disorders in the elderly including cognitive impairment and Alzheimer disease.

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BACKGROUND: The high comorbidity between Eating Disorders (EDs) and Obsessive-Compulsive disorder (OCD) is well known, as well as its implications in terms of worse outcome and need to adapt treatment. Estimates of OCD comorbidities in EDs are variable in different studies and poorly informative for clinical purposes. In this study, we sought to derive more consistent estimates, taking into account potential methodological and sampling confounding factors. METHODS: We searched published studies reporting lifetime and current rates of comorbid OCD in ED samples based on recent diagnostic criteria. Comorbidity rates were meta-analyzed using a binary random effects model. Heterogeneity among the studies and publication bias were systematically checked. Potential confounding factors were tested by meta-regression analysis and adjusted by sensitivity analysis. RESULTS: Globally, respectively 18% and 15% of all patients with an ED had a lifetime and current comorbidity with OCD. Rates were slightly higher in anorexia (19% and 14%) than in bulimia nervosa (13% and 9%), although only the current comorbid OCD was significantly higher in anorexia than in bulimia. Prospective follow-up studies provided considerably higher lifetime estimates (EDs 38%, anorexia 44%, bulimia 19%). LIMITATIONS: Temporal/causal relationship between ED and OCD could not be defined. CONCLUSIONS: OCD comorbidity in EDs is a relevant phenomenon, affecting almost one fifth of the patients in cross-sectional observations and up to nearly 40% in prospective follow-up studies. These data indicate the need for focused attention to non-food or body-shape related OCD symptoms, for better diagnostic and prognostic accuracy, and targeted treatment.

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Patients suffering from major depression and related pathologies (feeding and eating disorders, obsessive-compulsive disorder, post-traumatic stress disorder, anxiety disorders, etc.) are usually treated with antidepressant agents belonging to several pharmacological and chemical classes; the most recent of these agents are collectively known as "new-generation antidepressants". In these patients, therapeutic drug monitoring (TDM) with the determination of drug and metabolite blood levels is one of the most useful procedures to optimise and personalise the treatment, enhancing both effectiveness and safety. A new approach is proposed in this study, based on microsampling of both blood and oral fluid by means of volumetric absorptive microsampling (VAMS). This approach makes sampling and storage much simpler and even self- and at-home-sampling possible, while retaining reliability, vastly increasing analyte stability and reducing overall expenses. The microsamples were pretreated by means of microextraction by packed sorbent (MEPS) on C2 sorbent and analysed by liquid chromatography with sequential spectrophotometric and spectrofluorimetric detection (HPLC-UV-FL). Method validation results were satisfactory (extraction yield >84%, precision RSD < 8.9%, stability>85.0% after 3 months). Application to blood and oral fluid VAMS from patients treated with four possible different antidepressants (sertraline, fluoxetine, citalopram and vortioxetine) provided results always in good agreement with those obtained from the corresponding fluid matrices, including the levels of drug metabolites.

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A systematic review was implemented according to PRISMA guidelines on Pubmed, Psychinfo, Medline, Embase to fill the existing literature gap on the effectiveness of using Positron Emission Tomography (PET) and Single Photon Emission Computed Tomography (SPECT) in Anorexia Nervosa (AN), Bulimia Nervosa (BN) and Binge Eating Disorder (BED). Twenty-two articles were included. Four studies reported an increased density in 5-hydroxytryptamine receptor (5-HT1A) in fronto-temporo-parietal regions in both affected and recovered AN as well as in BN. The 5-HT transporter (5-HTT) binding was increased or diminished in different specific cortical areas and in relation to Eating Disorder (ED) subtypes. Some evidences of blunted Dopamine (DA) release in the putamen in BN patients suggest that their DA function might be impaired as in addictive behaviours. Studies estimating the regional Cerebral Blood Flow (rCBF) with SPECT demonstrated that temporal areas seem to play a key role in ED corroborating the hypothesis of a cingulate-temporal cortical dysfunction in AN. In addition, alterations of both parietal and prefrontal cortex provide a possible common neural substrate in AN. Studies included in this review are heterogeneous preventing robust conclusions, however, our findings add knowledge on some of the neurotransmitters involved in ED.

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