The potential use of daridorexant in eating disorders: beyond the treatment of insomnia?

A strong interplay exists between sleep and dietary habits, and sleep disturbances have been repeatedly documented in individuals with eating disorders (EDs). The orexin system - implicated in sleep regulation, energy homeostasis, and food reward - may represent a mechanist link between sleep alterations and disordered eating behaviors. Daridorexant is a dual orexin receptor antagonist (DORA) recently approved for the treatment of insomnia, with demonstrated efficacy and tolerability. Owing to its action on orexin neurons, the compound represents an intriguing option for addressing both sleep-related and core symptoms of EDs. By inhibiting motor hyperactivity, daridorexant may reduce excessive physical exercise in individuals with anorexia nervosa (AN) restricting type. Additionally, the compound may exert anti-binge effects, suggesting broad applicability in binge ED, bulimia nervosa, and binge/purging AN. In this framework, daridorexant emerges as a promising therapeutic option, offering a multifaceted approach to improving circadian rhythms, energy balance, and overall quality of life in individuals with diverse ED subtypes.

Which Factors Are Associated With Comorbid Psychiatric Conditions in Patients Affected by Substance Use Disorders? The Impact of COVID-19 Pandemic on Dual-Diagnosis Subjects.

Objective: To investigate demographic/cinical variables associated to dual diagnosis and the psychological reaction of dual-diagnosis patients to COVID-19 pandemic. Methods: Information was collected at the Addiction Service of Monza, Italy. The Impact of Event Scale-Revised (IES-R), a self-report questionnaire measuring the subjective response to a traumatic event, was administered. Univariate analyses and binary logistic regression were performed. IES-R scores were compared between groups defined by qualitative variables through one-way analyses of variance (ANOVA). Results: 118 outpatients were included, 48.3% with dual diagnosis. Alcohol use disorder and being female were associated to dual diagnosis. IES-R scores were significantly higher in the dual-diagnosis group, especially for personality disorders (PDs). IES-R scores were higher in patients taking treatment for substance use disorder (SUD). Conclusions: Females and alcohol abusers were at-risk subjects for dual diagnosis. Patients with SUD and PDs may benefit from additional support, especially when traumatic life events occur. Trial Registration: ClinicalTrials.gov Identifier: NCT04694482.

The challenge of diagnosing cultural syndromes: A narrative review.

BACKGROUND: In 2022 the total world migrant population was 281 million (an increase of approximately 62% compared to year 2000), of whom 169 million were migrant workers. The number of refugees, asylum seekers and others in need of international protection increased by 22% compared to 2021. Research has shown that the forcibly displaced have high rates of mental disorders (including depression, post-traumatic stress disorder (PTSD) and anxiety), with an estimated prevalence almost 6 to 7 times higher than the general population. Given the increase of the overall migration phenomenon and the challenge raised by the cultural features concerning mental health, we consider that this is an area that requires close attention to ensure that culturally sensitive health services be available to the migrant and displaced population. AIMS: The aim of this narrative review is to provide a background to the issue and take stock of what is currently available in the literature regarding culture-bound illnesses and the relevant diagnostic tools. METHODS: A comprehensive search was performed in PubMed, Psychinfo, Embase, Google Scholar, organized in stages to assure inclusion of all the relevant studies. Of the 703 papers initially identified, only 30 papers finally satisfied the inclusion criteria. RESULTS: Eleven diagnostic scales were found, only two of which are being used for displaced people. CONCLUSIONS: Further work is required in this field, including a debate as to whether scales are indeed an appropriate tool for use with this population.

The Impact of Clinical Factors, Vitamin B12 and Total Cholesterol on Severity of Anorexia Nervosa: A Multicentric Cross-Sectional Study.

Severe forms of Anorexia Nervosa (AN) are characterized by medical complications, psychiatric comorbidity, and high mortality. This study investigated potential associations between clinical/biological factors and the severity of AN, measured by the Body Mass Index (BMI). Red and white blood cells, hemoglobin, platelets, iron, vitamins D and B12, folate, and total cholesterol were measured in a mixed sample of 78 inpatients and outpatients. Linear regressions and one-way analyses of variance (ANOVAs) were carried out to evaluate the relationship between BMI and clinical/biochemical variables. BMI was significantly lower in hospitalized patients (F = 4.662; p = 0.034) and in those under pharmacological treatment (F = 5.733; p = 0.019) or poly-therapy (F = 5.635; p = 0.021). Higher vitamin B12 (ß = -0.556, p < 0.001), total cholesterol (ß = -0.320, p = 0.027), and later age at onset (with a trend towards significance) (ß = -0.376, p = 0.058) were associated with a lower BMI. Increased total cholesterol and vitamin B12, later age at onset, current pharmacological treatment, and poly-therapy might be distinctive in patients with a lower BMI. In clinical practice, these findings may contribute to the early identification of AN patients at higher risk of developing complicated or chronic forms of the disorder. Further studies on larger samples are needed to identify potential predictive factors of AN severity in the framework of precision medicine.

The Impact of the COVID-19 Pandemic on Binge Eating Disorder: A Systematic Review.

The aim of this systematic review was to synthesise the impact of the COVID-19 pandemic on binge eating disorder (BED) the new onset and course. Inclusion criteria: original articles and BED diagnosis; and the main outcomes: relationships between the COVID-19 pandemic and the new onset/clinical changes in BED, and specific results for BED. Exclusion criteria: mixed/inaccurate diagnoses and articles not written in English. We searched four databases and one registry until 5 May 2023. The quality appraisal was conducted using the Effective Public Health Practice Project (EPHPP) tool. Twelve studies with 4326 participants were included. All studies were observational with nine cross-sectional and three longitudinal. Four of the included studies investigated new-onset BED, while eight examined the BED clinical course of patients with a previous diagnosis. With the exception of one study, the available literature indicates both an increase in BED diagnoses and a clinical worsening during COVID-19. Major limitations include study quality (weak-to-moderate) and high heterogeneity in terms of pandemic phase, population, geographical areas, and psychometric tools. Our findings indicate that BED patients are particularly vulnerable to events characterised by social distancing and over-worry, and should be, therefore, carefully monitored. Further studies are needed to corroborate our findings, implement preventive strategies, and promote personalised treatments. PROSPERO registration number: CRD42023434106.

Air Pollution and Perinatal Mental Health: A Comprehensive Overview.

BACKGROUND: The aim of the present study was to summarise the available data about the link between air pollution exposure and the new-onset and severity of psychiatric disorders in pregnant women during the perinatal period. MATERIALS AND METHODS: We selected articles published until June 2022 on PubMed and the Web of Science. Pollutants included were PM2.5 (particulate matter 2.5 micrometres and smaller), PM10 (particulate matter 10 micrometres and smaller), NO2 (nitrogen dioxide), O3 (ozone), SO2 (sulphur dioxide), CO (carbon monoxide), PBDEs (polybrominated diphenyl ethers), PFAS (per- and polyfluoroalkyl substances), lead, and cadmium. The perinatal period was considered as the time of pregnancy until one year after childbirth. RESULTS: Nine studies were included; most of them evaluated the association between exposure to air pollutants and the onset of Postpartum Depression (PPD). Two studies showed an association between, respectively, only PM2.5 and both PM2.5 and NO2 exposure and PPD onset 12 months after childbirth, while another study found a significant association between NO2 exposure and PPD occurrence 6 months after childbirth. PBDE blood levels were associated with more severe depressive symptoms. Lastly, one study observed a link between stressful symptoms and exposure to PM2.5, PM10 during pregnancy. CONCLUSION: More comprehensive and uniform studies are required to make a roadmap for future interventions, given the growing relevance of issues such pollution and mental health, particularly during the perinatal period.

Clinical and Peripheral Biomarkers in Female Patients Affected by Anorexia: Does the Neutrophil/Lymphocyte Ratio (NLR) Affect Severity?

Anorexia Nervosa (AN) is a disabling disorder characterized by extreme weight loss and frequent chronicization, especially in its most severe forms. This condition is associated with a pro-inflammatory state; however, the role of immunity in symptom severity remains unclear. Total cholesterol, white blood cells, neutrophils, lymphocytes, platelets, iron, folate, vitamin D and B12 were dosed in 84 female AN outpatients. Mildly severe (Body Mass Index-BMI ≥ 17) versus severe (BMI < 17) patients were compared using one-way ANOVAs or χ2 tests. A binary logistic regression model was run to investigate the potential association between demographic/clinical variables or biochemical markers and the severity of AN. Patients with severe anorexia (compared to mild forms) were older (F = 5.33; p = 0.02), engaged in more frequent substance misuse (χ2 = 3.75; OR = 3.86; p = 0.05) and had a lower NLR (F = 4.12; p = 0.05). Only a lower NLR was predictive of severe manifestations of AN (OR = 0.007; p = 0.031). Overall, our study suggests that immune alterations may be predictive of AN severity. In more severe forms of AN, the response of the adaptive immunity is preserved, while the activation of the innate immunity may be reduced. Further studies with larger samples and a wider panel of biochemical markers are needed to confirm the present results.

Clinical Markers of Panic and Generalized Anxiety Disorder: Overlapping Symptoms, Different Course and Outcome.

Generalized Anxiety Disorder (GAD) and Panic Disorder (PD) share underlying neurobiological mechanisms and several clinical features which, with medical comorbidities, may increase misdiagnosis and delay proper treatment. The aim of the study was to evaluate the association between clinical/socio-demographic markers and GAD/PD diagnosis. Outpatients (N = 290) with PD or GAD were identified in mental health services in Monza and Milan (Italy). Descriptive analyses and a binary logistic regression model were performed. Post-onset psychiatric (p = 0.05) and medical (p = 0.02) multiple co-morbidities were associated with GAD; treatment with selective serotonin reuptake inhibitors (SSRIs) was associated with PD, while GAD diagnosis was associated with treatment with atypical antipsychotics or GABAergic drugs (p = 0.03), as well as psychodynamic psychotherapy (p < 0.01). Discontinuation of the last pharmacological treatment was associated with GAD diagnosis rather than the PD one (p = 0.02). GAD patients may have a worse prognosis than PD patients because of more frequent multiple co-morbidities, relapses and poorer treatment compliance. The different treatment approaches were consistent with the available literature, while the association between GAD and psychodynamic psychotherapy is an original finding of our study. Further studies on larger samples are necessary to better characterize clinical factors associated with GAD or PD.

Instagram Use and Mental Well-Being: The Mediating Role of Social Comparison.

ABSTRACT: Instagram has grown in popularity among young adults and adolescents and is currently the second-favorite social network in the world. Research on its relationship to mental well-being is still relatively small and has yielded contradictory results. This study explores the relationship between time spent on Instagram and depressive symptoms, self-esteem, and disordered eating attitudes in a nonclinical sample of female Instagram users aged 18-35 years. In addition, it explores the mediating role of social comparison. A total of 1172 subjects completed a one-time-only online survey. Three different mediation analyses were performed to test the hypotheses that social comparison on Instagram mediates the association time spent on Instagram with depressive symptoms (model 1), self-esteem (model 2), and disordered eating attitudes (model 3). All three models showed that the relationship between intensity of Instagram use and the respective mental health indicator is completely mediated by the tendency for social comparison on Instagram.

Possible Use of Minocycline in Adjunction to Intranasal Esketamine for the Management of Difficult to Treat Depression following Extensive Pharmacogenomic Testing: Two Case Reports.

The advent of intra-nasal esketamine (ESK), one of the first so called fast-acting antidepressant, promises to revolutionize the management of treatment resistant depression (TRD). This NMDA receptor antagonist has proven to be rapidly effective in the short- and medium-term course of the illness, revealing its potential in targeting response in TRD. Although many TRD ESK responders are able to achieve remission, a considerable portion of them undergo a metamorphosis of their depression into different clinical presentations, characterized by instable responses and high recurrence rates that can be considered closer to the concept of Difficult to Treat Depression (DTD) than to TRD. The management of these DTD patients usually requires a further complex multidisciplinary approach and can benefit from the valuable contribution of new personalized medicine tools such as therapeutic drug monitoring and pharmacogenetics. Despite this, these patients usually come with long and complex previous treatments history and, often, advanced and sophisticated ongoing pharmacological schemes that can make the finding of new alternative options to face the current recurrences extremely challenging. In this paper, we describe two DTD patients-already receiving intranasal ESK but showing an instable course-who were clinically stabilized by the association with minocycline, a semisynthetic second-generation tetracycline with known and promising antidepressant properties.

Therapeutic termination of pregnancy and major psychiatric outcomes in parents.

OBJECTIVES: Therapeutic termination of pregnancy (TToP) may have psychiatric outcomes like depression, anxiety and post-traumatic-stress disorder (PTSD). MATERIAL AND METHODS: 45 couples had psychiatric evaluation before TToP and after one-year period. RESULTS: TToP is linked to acute development of depressive symptoms that recover with time and professional support. Twelve percent of women developed PTSD (but 29.5% refused one-year evaluation due to mental distress at recalling TToP). Fathers showed no psychiatric outcomes. CONCLUSIONS: Acute depressive symptoms after TToP improve with professional support but PTSD rate is concerning and stress importance of mental health implications and need for adequate related treatments.

[Ketamine's fast-acting antidepressant mechanisms: state of the art and new research perspectives]. / I meccanismi antidepressivi ad azione rapida della ketamina: stato dell'arte e nuove prospettive di ricerca.

About a third of patients with major depressive disorder (MDD) do not have an adequate response to first-line antidepressant treatment, i.e., develop a treatment-resistant depression (TRD). The partial understanding of MDD pathophysiology currently constitutes the major barrier to clinical and research progress on this topic. However, recent advances in genome editing techniques as well as in induced pluripotent stem cells (iPSC) technology are offering unprecedented opportunities in both human disease modelling and drug discovery. These technology progresses have been enabling to set up disease-relevant patient-specific in vitro disease modeling for various mental disorders. The resulting models have the potential to significantly improve pathophysiologic understanding of MDD and then overcome some limitations inherent to animal and post-mortem models. More recently, psychiatry started to deal with the fast acting antidepressant ketamine and its derivates. Although ketamine appears to have the potential to transform the treatment of depression, its specific mechanisms of action are only partially known. Such knowledge is necessary to develop a model to understand the mechanisms behind fast-acting antidepressants, which may enable the discovery of novel glutamatergic compounds for the treatment of MDD. After discussing both the current understanding of ketamine's mechanisms of action, and the state of the art of human iPSC technology, the authors will introduce the implementation of a TRD model based on iPSC human technology and aimed at studying the ketamine's fast acting antidepressant mechanisms of action.

Clinical and Biological Factors Are Associated with Treatment-Resistant Depression.

BACKGROUND: Treatment-resistant depression (TRD) is a debilitating condition associated with unmet clinical needs. Few studies have explored clinical characteristics and serum biomarkers associated with TRD. AIMS: We investigated whether there were differences in clinical and biochemical variables between patients affected by TRD than those without. METHODS: We recruited 343 patients (165 males and 178 females) consecutively hospitalized for MDD to the inpatient clinics affiliated to the Fondazione IRCCS Policlinico, Milan, Italy (n = 234), and ASST Monza, Italy (n = 109). Data were obtained through a screening of the clinical charts and blood analyses conducted during the hospitalization. RESULTS: TRD versus non-TRD patients resulted to be older (p = 0.001), to have a longer duration of illness (p < 0.001), to be more currently treated with a psychiatric poly-therapy (p < 0.001), to have currently more severe depressive symptoms as showed by the Hamilton Depression Rating Scale (HAM-D) scores (p = 0.016), to have lower bilirubin plasma levels (p < 0.001). In addition, more lifetime suicide attempts (p = 0.035), more antidepressant treatments before the current episode (p < 0.001), and a lower neutrophil to lymphocyte ratio at borderline statistically significant level (p = 0.060) were all associated with the TRD group. CONCLUSION: We identified candidate biomarkers associated with TRD such as bilirubin plasma levels and NLR, to be confirmed by further studies. Moreover, TRD seems to be associated with unfavorable clinical factors such as a predisposition to suicidal behaviors. Future research should replicate these results to provide robust data in support of the identification of new targets of treatment and implementation of prevention strategies for TRD.

Disentangling binge eating disorder and food addiction: a systematic review and meta-analysis.

BACKGROUND AND AIMS: The concept of "Food Addiction" has been based on criteria of Substance Use Disorder. Several studies suggested a relationship between food addiction and eating disorders, but little is known about its extent or role. We aim at exploring if food addiction is coincident with a specific eating disorder (binge eating disorder appears the closest) or it is a separate diagnostic entity that afflicts in comorbidity with eating disorders or other conditions like obesity or even in the general population. METHODS: This systematic review and meta-analysis analyzed observational studies with a comparative estimation on rates of subjects affected by binge eating disorder and food addiction. RESULTS: Binge eating disorder shows higher comorbidity with food addiction compared to other eating disorders (OR = 1.33, 95% CI, 0.64-2.76; c2 = 4.42; p = 0.44;I2 = 0%), or each eating disorder [anorexia nervosa purging type (OR = 1.93, 95% CI, 0.20-18.92; p = 0.57) and restrictive type (OR = 8.75, 95% CI, 1.08-70.70; p = 0.04)], obese patients (OR = 5.72, 95% CI, 3.25-10.09; p = < 0.0001) and individuals from the general population (OR = 55.41, 95% CI, 8.16-376.10; c2 = 18.50; p < 0.0001; I2 = 0%)but has decreased prevalence when compared to bulimia nervosa (OR = 0.85, 95% CI, 0.33-2.22; c2 = 0.35; p = 0.74; I2 = 0%). DISCUSSION AND CONCLUSIONS: Our data show that the prevalence of food addiction in binge eating disorder is higher than in other eating disorders except in bulimia nervosa. Moreover, it is a separate diagnostic reality and can be detected in people without mental illness and in the general population. Food addiction might have a prognostic value, since in comorbidity, and should be addressed to boost treatment efficacy and patient's recovery. LEVEL OF EVIDENCE: I: Evidence obtained systematic reviews and meta-analyses.

Profile of patients attending psychiatric emergency care during the coronavirus 2019 (COVID 19) pandemic: a comparative cross-sectional study between lockdown and post-lockdown periods in Lombardy, Italy.

OBJECTIVE: To assess the long-term impact of early COVID-19 lockdown phase on emergency psychiatric consultations in two psychiatric emergency departments located in Italy. METHODS: We conducted a cross-sectional study comparing the number and characteristics of emergency psychiatric consultations during post-lockdown with respect to the lockdown period. Sociodemographic data, clinical characteristics, referred symptoms, diagnosis, information on multiple psychiatric consultations and hospitalisation were collected. RESULTS: A rise of almost 60% in emergency psychiatric consultations during the post-lockdown compared to the lockdown period was observed. Emergency psychiatric consultations in the post-lockdown period were associated with lower rates of cannabis (aOR = 0.42, p = 0.011) and cocaine use (aOR = 0.39, p = 0.011). Despite a lower occurrence of two or more psychiatric consultations was observed during post-lockdown phase (aOR = 0.44, p = 0.008), subjects who had anxiety disorders (aOR = 3.91, p = 0.000) and substance intoxication or withdrawal (aOR = 6.89, p = 0.000) were more likely to present to emergency psychiatric consultations during post-lockdown period compared to the lockdown one. CONCLUSIONS: Substance intoxication or withdrawal and anxiety disorders increased after the COVID-19 lockdown. The findings of this study suggest to address more economic and professional sources to the mental health areas potentially more affected by the different phases of a pandemic.KEYPOINTSCOVID-19 pandemic and lockdown measures increased mental health unmet needs.According to our findings, a rise in emergency psychiatric consultations during the post-lockdown compared to the lockdown period was observed.Patients with substance intoxication or withdrawal syndrome and anxiety disorders were significantly more likely to present to emergency psychiatric consultations during post-lockdown.Lockdown was associated with higher rates of both cannabis and cocaine use disorders as well as of multiple psychiatric consultations.Alternative strategies to improve mental health such as e-health technologies should be promoted.

The psychopathological impact of the SARS-CoV-2 epidemic on subjects suffering from different mental disorders: An observational retrospective study.

SARS-CoV-2 infection causes a pulmonary disease (COVID-19) which spread worldwide generating fear, anxiety, depression in the general population as well as among subjects affected by mental disorders. Little is known about which different psychopathological changes the pandemic caused among individuals affected by different psychiatric disorders, which represents the aim of the present study. Specific psychometric scales were administered at three time points: T0 as outbreak of pandemic, T1 as lockdown period, T2 as reopening. Descriptive analyses and linear regression models were performed. A total of 166 outpatients were included. Overall, psychometric scores showed a significant worsening at T1 with a mild improvement at T2. Only psychopathology in schizophrenia (SKZ) patients and obsessive-compulsive (OC) symptoms did not significantly improve at T2. Subjects affected by personality disorders (PDs) resulted to be more compromised in terms of general psychopathology than depressed and anxiety/OC ones, and showed more severe anxiety symptoms than SKZ patients. In conclusion, subjects affected by PDs require specific clinical attention during COVID-19 pandemic. Moreover, the worsening of SKZ and OC symptoms should be strictly monitored by clinicians, as these aspects did not improve with the end of lockdown measures. Further studies on larger samples are needed to confirm our results. ClinicalTrials.gov Identifier: NCT04694482.