Naturalistic and Uncontrolled Pilot Study on the Efficacy of Vortioxetine in Binge Eating Disorder With Comorbid Depression.

Background: Binge eating disorder (BED) is clinically relevant by virtue of the global impairment, poor quality of life, and increased overall medical morbidity. The high comorbidity with psychiatric disorders, particularly depression, has received attention as a possible mediator of the poor outcome. Further, BED and depression share cognitive dysfunctions. This naturalistic and uncontrolled pilot study aimed at evaluating the efficacy of vortioxetine (VTX) on depressive symptoms in patients with BED, secondly the efficacy in improving a broad array of executive functions, and third to explore the effect on eating behavior and body weight. Methods: This pilot study involved 30 patients with BED and comorbid MDD, treated with VTX for 24 weeks. Assessments were run at baseline (t 0), 4 (t 1), 8 (t 2), 12 (t 3), and 24 (t 4) weeks. Changes in depressive symptoms (HDRS and BDI), executive functions, eating behaviors (binge frequency and severity, night eating, food addiction), and body weight were estimated after treatment with VTX through GLM. Results: Significant improvements emerged after treatment with VTX in: depression (HDRS p < 0.001; BDI p = 0.002) regardless the dose of VTX and first diagnosis (BED/MDD), working memory (RAVLT acquisition p = 0.01, delay recall p < 0.001, RCFT percentage of recall p = 0.01, and Attentional Matrices p = 0.05), binge days frequency (p < 0.001), binge eating severity (BES p < 0.001), night eating (p = 0.001), food addiction (YFAS 2.0 p = 0.039), and body weight (p = 0.039). The improvement in depressive symptoms was associated with the concurrent improvement in night eating as assessed by the I-NEQ. Conclusions: VTX can be a valid therapeutic choice for patients with BED with comorbid depression in controlling the depressive symptoms, working memory, and eating behavior. Indeed, by acting on affective symptoms, neurocognitive functioning, and eating behaviors, it confirms the results already obtained with VTX in other disorders, expanding them to BED.

Antisocial Personality Disorder in Bipolar Disorder: A Systematic Review.

Background and Objectives: Bipolar Disorder (BD) is a severe psychiatric disorder that worsens quality of life and functional impairment. Personality disorders (PDs), in particular Cluster B personality, have a high incidence among BD patients and is considered a poor prognostic factor. The study of this co-morbidity represents an important clinical and diagnostic challenge in psychiatry. Particularly, clinical overlap has been shown between antisocial personality disorder (ASPD) and BD that could worsen the course of both disorders. We aimed to detect the frequency of ASPD in bipolar patients with greater accuracy and the impact of ASPD on the clinical course of BD. Materials and Methods: A systematic literature search was conducted in PubMed, Embase, MEDLINE and the Cochrane Library through December 2020 without language or time restriction, according to PRISMA statement guidelines. Results: Initially, 3203 items were identified. After duplicates or irrelevant paper deletion, 17 studies met the inclusion criteria and were included in this review. ASPD was more frequent among BD patients, especially in BD type I. BD patients with ASPD as a comorbidity seemed to have early onset, higher number and more severe affective episodes, higher levels of aggressive and impulsive behaviors, suicidality and poor clinical outcome. ASPD symptoms in BD seem to be associated with a frequent comorbidity with addictive disorders (cocaine and alcohol) and criminal behaviors, probably due to a shared impulsivity core feature. Conclusions: Considering the shared symptoms such as impulsive and dangerous behaviors, in patients with only one disease, misdiagnosis is a common phenomenon due to the overlapping symptoms of ASPD and BD. It may be useful to recognize the co-occurrence of the disorders and better characterize the patient with ASPD and BD evaluating all dysfunctional aspects and their influence on core symptoms.

Clinical Impact of Psychopathy on Bipolar Disorder.

Background and Objectives. Bipolar disorder (BD) is associated with a significant burden due to affective symptoms and behavioral manifestations, but also cognitive and functional impairment. Comorbidity with other psychiatric conditions, including personality disorders, is frequent. The comorbidity with psychopathy deserves special consideration given that both disorders share some clinical characteristics, such as grandiosity, risky behavior or poor insight, among others, that can worsen the outcome of BD. Therefore, this study aimed to evaluate the prevalence of psychopathy in a sample of clinically stabilized patients with BD and its impact on the severity of BD. Materials and Methods. A sample of 111 patients with BD (38 type I and 73 type II) was studied. The Hamilton Depression Rating Scale (HAM-D) and the Young Mania Rating Scale (YMRS) served to assess the severity of BD. Psychopathy was measured by means of the Psychopathic Personality Inventory-Revised (PPI-R). Patients were divided into three groups according to the severity of psychopathy (Group 1: no psychopathy; Group 2: "psychopathic" trait; Group 3: clinical psychopathy). Other measures regarded impulsiveness (Barratt Impulsiveness Scale-11, BIS-11) and empathy (Empathy Quotient, EQ). Comparisons of mania, depression, impulsivity and empathy scores were run with MANOVA considering psychopathy and diagnosis as independent variables. Results. The prevalence of psychopathy was 5.4%. A significant association between the level of psychopathy and YMRS, attentional/cognitive impulsivity and motor impulsivity scores emerged. No interaction between psychopathy and BD diagnosis was found. Post hoc analysis demonstrated significantly higher YMRS scores in Group 3 than in Group 1; that is, patients with psychopathy have more manic symptoms. Conclusion. Psychopathy seems quite frequent among patients with BD. The association of psychopathy with BD results in higher impulsivity and manic symptoms. In light of this, psychopathy should be investigated when assessing patients with BD, regardless of the comorbidity of BD with other personality disorders.

Metacognition and emotion regulation as treatment targets in binge eating disorder: a network analysis study.

BACKGROUND: This study aims to examine the underlying associations between eating, affective and metacognitive symptoms in patients with binge eating disorder (BED) through network analysis (NA) in order to identify key variables that may be considered the target for psychotherapeutic interventions. METHODS: A total of 155 patients with BED completed measures of eating psychopathology, affective symptoms, emotion regulation and metacognition. A cross-sectional network was inferred by means of Gaussian Markov random field estimation using graphical LASSO and the extended Bayesian information criterion (EBIC-LASSO), and central symptoms of BED were identified by means of the strength centrality index. RESULTS: Impaired self-monitoring metacognition and difficulties in impulse control emerged as the symptoms with the highest centrality. Conversely, eating and affective features were less central. The centrality stability coefficient of strength was above the recommended cut-off, thus indicating the stability of the network. CONCLUSIONS: According to the present NA findings, impaired self-monitoring metacognition and difficulties in impulse control are the central nodes in the psychopathological network of BED whereas eating symptoms appear marginal. If further studies with larger samples replicate these results, metacognition and impulse control could represent new targets of psychotherapeutic interventions in the treatment of BED. In light of this, metacognitive interpersonal therapy could be a promising aid in clinical practice to develop an effective treatment for BED.

An open-label trial on the efficacy and tolerability of naltrexone/bupropion SR for treating altered eating behaviours and weight loss in binge eating disorder.

PURPOSE: Binge eating disorder (BED) has a considerable clinical relevance by virtue of its high numerous psychiatric and medical comorbidities; among the latter, the most frequent is obesity. Available treatments for BED have shown frequent relapse of binges or weight regain in the long term. The new combination of naltrexone and bupropion sustained release (NB) has proved to be effective for weight loss among obese patients. As NB acts on hypothalamic and reward circuits, that seem involved in the pathogenesis and maintenance of BED symptoms, this study aims to evaluate the efficacy of NB in improving pathological eating behavior and losing weight in BED patients. METHODS: In this preliminary study, 23 obese-BED patients and a control group of 20 obese non-BED patients (respectively, Groups 1 and 2) who had previously undergone at least 5 unsuccessful weight-loss programs were treated with NB in addition to modified life style. Evaluation at t0 and after 16 weeks of treatment (t1) included anthropometric measurement, eating behavior assessment and psychopathological questionnaires (EDE-Q, BES, YFAS, BDI and STAI). RESULTS: A significant and similar weight loss (ΔBMI% ≈ 8%) was evident for both groups. Pathological eating behavior (i.e., binge, grazing, emotional eating, craving for carbohydrates, and post-dinner eating), BES score and YFAS severity significantly improved, especially among BED. NB was well tolerated and drop-out rate was low. CONCLUSION: Treatment with NB, in addition to a reduced-calorie diet and increased physical activity, seems an effective and well-tolerated option for improving pathological eating behavior and losing weight in obese-BED patients. LEVEL OF EVIDENCE: Level III case-control study.

The role of self-monitoring metacognition sub-function and negative urgency related to binge severity.

OBJECTIVE: This study aims to test a model where low self-monitoring (a sub-function of first-person domain of metacognition) and high negative urgency lead to a worsening of binge severity through the mediation of emotional dysregulation in patients with binge eating disorder (BED). METHOD: Forty non-BED-obese and 46 BED-obese patients completed a battery of tests assessing metacognition and psychopathology. To test our hypothesized model, a structural equation model (SEM) using maximum likelihood estimation was conducted. RESULTS: BED-obese patients had significantly higher scores in BES, UPPS-P Negative urgency, and DERS total score, and lower MSAS self-monitoring than non-BED-obese, while no differences emerged in the MSAS others-monitoring subscale. The structural model demonstrated very good fit indexes (χ2 = 1.377, df = 2; p = .502, CMIN/DF = 0.688, CFI = 1.000, RMSEA = 0.000, TLI = 1.047) and all paths were significant in the predicted directions. CONCLUSIONS: These preliminary findings show that, low self-monitoring and high negative urgency lead BED-obese patients to express the worsening of binge severity through the mediation of emotional dysregulation. This knowledge may be helpful in the clinical practice to develop a tailor-made treatment. Accordingly, an approach through Metacognitive Interpersonal Therapy could be attempted in BED-obese patients with these characteristics. Highlights Patients with BED exhibited low self-monitoring and high negative urgency. Binge severity was mediated by high level of emotional dysregulation. Metacognitive Interpersonal Therapy may be useful for BED patients.

'Impaired Autonomy and Performance' predicts binge eating disorder among obese patients.

PURPOSE: The present study examined the predictive value of early maladaptive schema (EMS) domains on the diagnosis of binge eating disorder (BED). METHODS: Seventy obese patients seeking treatment for weight loss were recruited and allocated to either group 1 (obese) or group 2 (BED-obese) according to clinical diagnosis. Both groups underwent psychometric assessment for EMS (according to the latest four-factor model), eating and general psychopathologies. Logistic regression analysis was performed on significant variables and BED diagnosis. RESULTS: In addition to showing higher values on all clinical variables, BED-obese patients exhibited significantly higher scores for all four schema domains. Regression analysis revealed a 12-fold increase in risk of BED with 'Impaired Autonomy and Performance'. Depression did not account for a higher risk. CONCLUSIONS: Impaired Autonomy and Performance is associated with BED in a sample of obese patients. Schema therapy should be considered a potential psychotherapy strategy in the treatment of BED. LEVEL OF EVIDENCE: Level III, case-control study.

Adverse childhood experiences and clinical severity in bipolar disorder and schizophrenia: A transdiagnostic two-step cluster analysis.

BACKGROUND: Adverse childhood experiences (ACEs) are risk factors for psychiatric disorders, but evidence about their relationship with clinical severity is limited. We aimed to classify patients according to ACEs and to compare these clusters with regards to the clinical severity. METHODS: Seventy-four patients with Bipolar Disorder (BD) and 91 patients with a diagnosis within the Schizophrenia Spectrum Disorders (SSDs) were interviewed. The Childhood Experience of Care and Abuse scale (CECA) and the Positive and Negative Symptoms Scale (PANSS) were administered. A two-step cluster analysis was run to identify clusters according to ACEs. PANSS average scores were compared between clusters. RESULTS: Three clusters emerged; significant differences in ACEs distribution were evident. Cluster 1 was characterized by very low frequency of ACEs. ACEs related to lack of support/isolation were more frequent within Cluster 2, instead ACEs related to abuse/neglect were over represented in Cluster 3. The comparison of PANSS through ANOVA demonstrated that Cluster 3 not only had significantly higher scores in all dimensions than Cluster 1 and 2 but also a higher average number of ACEs. LIMITATIONS: CECA is a self-report scale and is subject to recall bias. CONCLUSIONS: Specific ACEs are related to clinical severity among BD and SSD patients. Early life adversities related to abuse and neglect are associated to greater symptomatic severity than those related to lack of support/isolation. Our findings suggest that a history of ACEs could be used to identify patients at higher risk of unfavorable clinical features.

Maternal stress, prenatal medical illnesses and obstetric complications: Risk factors for schizophrenia spectrum disorder, bipolar disorder and major depressive disorder.

Maternal stress and medical illnesses during early life are well-documented environmental indicators of an increased risk of schizophrenia. Few studies, conversely, have confirmed an association with major affective disorders. The present study examined the impact of maternal stress, medical illnesses and obstetric complications on the development of severe mental disorder in 240 patients with a diagnosis of schizophrenia spectrum disorder, bipolar disorder, or major depressive disorder and matched with 85 controls. Mothers of participants were asked about stressful events during pregnancy using the Social Readjustment Scale; information on prenatal/perinatal illnesses were acquired from medical records. Schizophrenia spectrum disorder was positively associated with maternal stress (OR = 2.16), infections (OR = 7.67), inadequate weight gain (OR = 9.52) during pregnancy, and peripartum asphyxia (OR = 4.00). An increased risk of bipolar disorder was associated with head circumference < 32 cm at birth (OR = 5.40) and inversely with inadequate weight gain (OR = 0.29). Major depressive disorder diagnosis was inversely related to inadequate weight gain (OR = 0.22). These results support a role for maternal stress, medical illnesses and obstetric complications as risk factors for subsequent severe mental illness in adulthood. Further research is needed, especially with regard to affective disorders.

Childhood adversities are different in Schizophrenic Spectrum Disorders, Bipolar Disorder and Major Depressive Disorder.

BACKGROUND: Research has shown that a history of childhood adversities is common in patients with psychiatric disorders but few studies have investigated links between specific types of adversity and specific psychiatric disorders. METHODS: We investigated the frequency of early childhood adversities in a sample consisting of 91 patients with diagnosis of schizophrenic spectrum disorders (SSD), 74 patients with bipolar disorder (BD), 83 patients with major depressive disorder (MDD) and 85 healthy controls and sought to identify adverse early childhood life events that predict the development of major psychiatric disorders. The Childhood Experiences of Care and Abuse questionnaire was used to collect data on traumatic experiences occurring before the age of 17 years and comprehensive demographic data were also collected. The data were analyzed with chi-squared tests, t-tests, post-hoc and logistic regression. RESULTS: Maternal absence/loss and economic difficulties in the early life were more prevalent in the BD group than other groups. Escape from home, cannabis abuse, psychological abuse, physical abuse and loneliness were more frequent in the SSD group than in other groups. Paternal absence, neglect of core needs, serious familial tension and absence of adult and peer confidants were all less common in the HC group than in the other groups. The regression model confirmed that different types of adversities play a crucial role in the development of the three investigated disorders. CONCLUSIONS: Our results support that SSD, BD and MDD are associated to different childhood adversities. This suggests that psychosocial interventions that reduce the incidence of these early life adversities might reduce the incidence of severe and disabling psychiatric disorders.

Unemployment, perceived health status and coping: A study in Southern Italy.

BACKGROUND: Unemployment is a very stressful experience that significantly impairs an individual's perception of their overall wellbeing. Interaction between unemployment and physical health is complex. OBJECTIVE: To analyze how specific coping strategies and socio-demographic variables may influence the level of physical and mental health perceived by those searching for work at an employment centre in Catanzaro, Italy. METHODS: Participants completed a set of self-administrated questionnaires including a socio-demographic questionnaire, the Coping Inventory for Stressful Situations (CISS) and the SF-12 Health Survey (SF-12). A forward stepwise multiple regression analysis was used to ascertain those coping strategies significantly associated with participants' perceived health status. RESULTS: Complete documentation was received from 113 registered unemployed participants, (61 men and 52 women) giving a response rate of 45% .Physical health status was significantly and positively associated with age and task-oriented coping, while the perception of mental health was associated not only with age, but also by lower emotion-oriented coping and a low number of previous job losses. CONCLUSION: The perception of health status is reduced among unemployed. Age is the only socio demographic variable that influences the perception of health status. Adaptive Task-oriented coping strategies are related to better physical health perception, whereas Emotion-oriented coping makes people prone to poorer mental health perception.

Phenobarbital/Lamotrigine coadministration-induced blood dyscrasia in a patient with epilepsy.

OBJECTIVE: To report on a patient with epilepsy who developed leukopenia and thrombocytopenia during phenobarbital/lamotrigine treatment. CASE REPORT: A 45-year-old woman with a 10-year history of complex partial seizures being treated with phenobarbital 100 mg/day presented due to the development of complex partial seizure episodes (8 episodes/month in the last 6 months). Results of laboratory tests on admission showed normal platelets (250 x 10³/µL) and white blood cells (8.2 x 10³/µL). After clinical evaluation, lamotrigine titrated to a final dose of 100 mg twice daily was added to the phenobarbital. About 2 months later no epileptic manifestations were reported, but hematologic tests revealed a decrease in both platelets (36 x 10³/µL) and white blood cells (2.0 x 10³/µL). One day later, phenobarbital was discontinued and the patient developed 2 episodes of complex partial seizure. Levetiracetam titrated to 1500 mg/day was added to lamotrigine, with a normalization of platelets (260 x 10³/µL) and white blood cell (7.9 x 10³/µL) counts about 20 days later. After a few days, levetiracetam was discontinued and phenobarbital rechallenge during lamotrigine treatment induced a new blood dyscrasia in about 2 weeks (platelets 80 x 10³/µL; white blood cells 3.2 x 10³/µL). Phenobarbital was discontinued and levetiracetam was restarted, with a recovery of normal hematopoiesis in 25 days. The patient is presently receiving treatment with both lamotrigine 200 mg/day and levetiracetam 1500 mg/day and shows no seizure symptoms, blood abnormalities, or other adverse effects. DISCUSSION: Using the Horn Drug Interaction Probability Scale, we estimated a probable relationship between the drug-drug interaction and blood dyscrasia. The underlying mechanism of this interaction has not been well characterized. Cytochrome P450 enzyme induction by phenobarbital could be responsible for the production of reactive metabolites of lamotrigine that might be causative for the observed hematologic effects. A pharmacodynamic interaction between the 2 drugs is also a possible mechanism of this interaction. CONCLUSIONS: Our patient with epilepsy developed blood dyscrasia during lamotrigine/phenobarbital treatment. Clinicians should carefully monitor hematologic parameters during lamotrigine/phenobarbital treatment.