Clinical and psychological factors associated with resilience in patients with schizophrenia: data from the Italian network for research on psychoses using machine learning.

BACKGROUND: Resilience is defined as the ability to modify thoughts to cope with stressful events. Patients with schizophrenia (SCZ) having higher resilience (HR) levels show less severe symptoms and better real-life functioning. However, the clinical factors contributing to determine resilience levels in patients remain unclear. Thus, based on psychological, historical, clinical and environmental variables, we built a supervised machine learning algorithm to classify patients with HR or lower resilience (LR). METHODS: SCZ from the Italian Network for Research on Psychoses (N = 598 in the Discovery sample, N = 298 in the Validation sample) underwent historical, clinical, psychological, environmental and resilience assessments. A Support Vector Machine algorithm (based on 85 variables extracted from the above-mentioned assessments) was built in the Discovery sample, and replicated in the Validation sample, to classify between HR and LR patients, within a nested, Leave-Site-Out Cross-Validation framework. We then investigated whether algorithm decision scores were associated with the cognitive and clinical characteristics of patients. RESULTS: The algorithm classified patients as HR or LR with a Balanced Accuracy of 74.5% (p < 0.0001) in the Discovery sample, and 80.2% in the Validation sample. Higher self-esteem, larger social network and use of adaptive coping strategies were the variables most frequently chosen by the algorithm to generate decisions. Correlations between algorithm decision scores, socio-cognitive abilities, and symptom severity were significant (pFDR < 0.05). CONCLUSIONS: We identified an accurate, meaningful and generalizable clinical-psychological signature associated with resilience in SCZ. This study delivers relevant information regarding psychological and clinical factors that non-pharmacological interventions could target in schizophrenia.

Metabolomics signatures of acutely ill and short-term weight recovered women with anorexia nervosa.

Although metabolomics studies are recently spreading and have allowed the characterization of putative biomarkers in many diseases, they are relatively scanty in anorexia nervosa (AN). In this explorative study we analyzed the fecal metabolomics profiles of women with AN in the underweight phase (n = 24) and after short-term weight restoration (n = 16) and compared them with 20 healthy women. An untargeted metabolomic procedure allowed the characterization of 224 metabolites involved in energy, lipid, and amino acid metabolism. A partial least square discriminant analysis identified 14 metabolites with a variable importance in projection score >1.5 that clearly differentiated underweight from weight-restored patients from healthy women. Compared with healthy women, fecal concentrations of valeric acid and 3-methyl,2-ketobutyric acid were increased in both underweight and weight-restored patients; fecal concentrations of propionic acid, stearic acid, linolenic acid, methyl-galactoside, coprosterol, cycloserine, and lauric acid were increased while fecal levels of xylose, fucose, and rhamnose were decreased in underweight patients and normalized after weight-restoration; fecal concentrations of piperine, phenylalanine, butyric acid, and meso-erythritol-1 were decreased while fecal levels of hydroxystearic acid were increased in weight-restored but normal in underweight AN patients. All these changes point to peculiar fecal metabolomics profiles of acute and short-term weight restored AN patients. The value of these changes to improve our understanding of the pathophysiology of AN and to characterize potential biomarker targets for developing new treatment strategies needs further studies to be clarified.

At the Core of Depression: A Diagnostic Interview of the Core Features of Depression.

INTRODUCTION: Valid and reliable methods for diagnosing depression are essential. The present study aimed to test the performance of a new diagnostic interview for depression focusing on the core symptoms of depression. METHOD: We developed a diagnostic interview for depression: the CORE Diagnostic Interview, CORE-DI, which assesses each of the core features of depression on the four dimensions: quality, reactivity, globality, and fluctuations over time. The diagnostic performance of this interview was tested in a clinical study including 83 individuals presenting with various depressive symptoms, who were interviewed independently (1) by means of the CORE-DI and the Mini-International Neuropsychiatric Interview (M.I.N.I.), and (2) by highly skilled specialists in depression representing gold standard diagnoses. RESULTS: We compared the outcome of the CORE-DI, the M.I.N.I., and the diagnosis made by clinicians, respectively, versus the gold standard diagnosis, using diagnostic efficiency statistics. The CORE-DI diagnosed depression with a high specificity (0.91, 95% CI: 0.85-0.97, for International Classification of Diseases [ICD]-10 criteria and 0.88, 95% CI: 0.81-0.95, for Diagnostic and Statistical Manual of Mental Disorders [DSM-5] criteria) compared to both M.I.N.I (specificity 0.44, 95% CI: 0.33-0.55) and clinical diagnoses (specificity 0.76, 95% CI: 0.67-0.85). The sensitivity of the CORE-DI was 0.61 (95% CI: 0.55-0.72) for ICD-10 criteria and 0.67 (95% CI: 0.57-0.77) for DSM-5 criteria. DISCUSSION/CONCLUSION: The CORE-DI increased the specificity of the depression diagnosis substantially compared to clinical diagnoses and the diagnoses obtained by M.I.N.I. The results point to the usefulness of an elaborated and systematic assessment of the core symptoms in the examination of patients with depressive symptoms and thereby indicate a way for further development of specific diagnostic tools for depression in both clinical and research settings. However, it should be noted that the sensitivity of the CORE-DI was modest, and the psychometric properties of the CORE-DI might be different in other settings with higher or lower prevalence or severity of depressive symptoms.

Autism spectrum in patients with schizophrenia: correlations with real-life functioning, resilience, and coping styles.

BACKGROUND: Previous researches highlighted among patients with schizophrenia spectrum disorders (SSD) a significant presence of autistic traits, which seem to influence clinical and functional outcomes. The aim of this study was to further deepen the investigation, evaluating how patients with SSD with or without autistic traits may differ with respect to levels of functioning, self-esteem, resilience, and coping profiles. METHODS: As part of the add-on autism spectrum study of the Italian Network for Research on Psychoses, 164 outpatients with schizophrenia (SCZ) were recruited at eight Italian University psychiatric clinics. Subjects were grouped depending on the presence of significant autistic traits according to the Adult Autism Subthreshold Spectrum (AdAS Spectrum) instrument ("AT group" vs "No AT group"). Other instruments employed were: Autism Spectrum Quotient (AQ), Specific Levels of Functioning (SLOF), Self-Esteem Rating scale (SERS), Resilience Scale for Adults (RSA), and brief-COPE. RESULTS: The "AT group" reported significantly higher scores than the "No AT group" on SLOF activities of community living but significantly lower scores on work skills subscale. The same group scored significantly lower also on SERS total score and RSA perception of the self subscale. Higher scores were reported on COPE self-blame, use of emotional support and humor domains in the AT group. Several correlations were found between specific dimensions of the instruments. CONCLUSION: Our findings suggest the presence of specific patterns of functioning, resilience, and coping abilities among SSD patients with autistic traits.

Childhood maltreatment and clinical response to mood stabilizers in patients with bipolar disorder.

OBJECTIVE: The association between childhood maltreatment (CM) and clinical response to mood stabilizers has been scarcely investigated in bipolar disorder (BD). Therefore, we assessed whether CM affects the response to lithium or anticonvulsant treatments in BD patients. METHODS: A retrospective assessment of clinical response to mood stabilizers was conducted in 97 euthymic patients with BD by means of the Alda scale. History of CM was investigated through the Childhood Trauma Questionnaire. RESULTS: Thirty-seven patients (24 with a history of CM and 13 without CM) were on stable lithium treatment while sixty (35 with a history of CM and 25 without CM) were on stable anticonvulsant treatment. Clinical response to drug treatment did not differ between BD with CM and those without CM in the whole sample as well as in the anticonvulsant-treated subgroup. In the lithium-treated subgroup, a significant negative correlation emerged between childhood physical abuse and clinical response and patients with CM showed a significantly reduced Alda score. CONCLUSIONS: In BD patients, CM did not influence the clinical response to anticonvulsant mood stabilizers whereas it was associated with a poorer response to lithium with childhood physical abuse playing a major role in this effect.

Emotional traumatic experiences significantly contribute to identify a maltreated ecophenotype sub-group in eating disorders: Experimental evidence.

OBJECTIVE: Eating disorders (EDs) are associated with a high prevalence of childhood maltreatment (CM). We aimed to experimentally assess if people with EDs and history of CM show altered biological, emotional and behavioural responses to the Trier Social Stress Test (TSST). METHODS: According to Childhood Trauma Questionnaire cut-off scores, 29 participants (14 with anorexia nervosa [AN] and 15 with bulimia nervosa [BN]) were classified as maltreated (Mal) ED participants while 19 participants (11 with AN and eight with BN) without CM were identified as no maltreated (noMal) ED participants. Cortisol, anxiety and hunger responses to TSST and post-stress body dissatisfaction were measured. RESULTS: Mal ED people showed heightened emotional reactivity, lower levels of hunger and more severe post-stress body dissatisfaction in comparison with noMal ones. Higher cortisol production was observed in people with AN, regardless of CM history, and in those with BN and emotional CM. Emotional trauma was the main CM type contributing to the experimental differences observed in Mal ED people. CONCLUSIONS: This is the first study providing experimental and multi-level support to the maltreated ecophenoptype hypothesis in people with EDs. These findings may promote new insights into the biological bases of EDs and provide novel therapeutic implications.

Mental, behavioral and neurodevelopmental disorders in the ICD-11: an international perspective on key changes and controversies.

An update of the chapter on Mental, Behavioral and Neurodevelopmental Disorders in the International Classification of Diseases and Related Health Problems (ICD) is of great interest around the world. The recent approval of the 11th Revision of the ICD (ICD-11) by the World Health Organization (WHO) raises broad questions about the status of nosology of mental disorders as a whole as well as more focused questions regarding changes to the diagnostic guidelines for specific conditions and the implications of these changes for practice and research. This Forum brings together a broad range of experts to reflect on key changes and controversies in the ICD-11 classification of mental disorders. Taken together, there is consensus that the WHO's focus on global applicability and clinical utility in developing the diagnostic guidelines for this chapter will maximize the likelihood that it will be adopted by mental health professionals and administrators. This focus is also expected to enhance the application of the guidelines in non-specialist settings and their usefulness for scaling up evidence-based interventions. The new mental disorders classification in ICD-11 and its accompanying diagnostic guidelines therefore represent an important, albeit iterative, advance for the field.

Clinical and neuroendocrine correlates of childhood maltreatment history in adults with bipolar disorder.

OBJECTIVES: Childhood maltreatment has been associated to an increased risk of developing bipolar disorder (BD). A role of the hypothalamus-pituitary-adrenal (HPA) axis in mediating trauma-related risk for adult psychopathology has been suggested but scarcely investigated in BD. Therefore, we explored the impact of childhood maltreatment on clinical features of BD and on the activity of the HPA axis. METHODS: One hundred and six patients participated in the study. On the basis of their history of childhood trauma, as assessed by the Childhood Trauma Questionnaire (CTQ), they were divided into a group with a history of childhood maltreatment (CM+) and a group without (CM-). Twenty-nine participants (16 with a history of childhood trauma and 13 without) underwent the cortisol awakening response (CAR) test. RESULTS: Sixty-two patients had a history of childhood maltreatment and 44 had not. Maltreatment was significantly more frequent in females than males. CM+ patients showed a significant higher body mass index, a significant higher number of suicide attempts, and more severe mania symptoms than CM- ones. Logistic regression indicated a significant association between lifetime suicide attempts and any type of childhood maltreatment and between emotional abuse and the presence of psychotic symptoms or mixed mood episodes. CM+ individuals with BD exhibited a significantly reduced CAR with respect to CM- ones. DISCUSSION: Our results add to literature findings showing a worse clinical course in BD patients with a history of childhood maltreatments and show for the first time that childhood trauma exposure is associated to an impaired CAR in adults with BD.

Beyond diagnosis in psychiatric practice.

In psychiatry, the information conveyed by diagnosis (i.e., the "type" to which the individual patient is reconducted) is in itself insufficient for therapeutic and prognostic purposes. Hence the need for a more detailed characterization of the individual case, with a special focus on the assessment of low-order and high-order psychopathological dimensions, the evaluation of the severity of the clinical picture, the assessment of the stage of development of the disorder, and the exploration of a series of antecedent and concomitant variables. We should start to promote the construction and validation of tools guiding the clinician systematically in this characterization, trying to incorporate in this effort elements of the approaches that are currently presented as "alternative" to the ICD and DSM.

Defining the Optimal Threshold Scores for Adult Autism Subthreshold Spectrum (AdAS Spectrum) in Clinical and General Population.

BACKGROUND: The Adult Autism Subthreshold Spectrum (AdAS Spectrum) is a recently developed instrument tailored to assess the broad range of full-threshold as well as sub-threshold manifestations related to the autism spectrum. Although it has proved to be a valuable instrument for quantitative assessment of autistic symptoms, the AdAS Spectrum still lacks validated diagnostic thresholds. OBJECTIVE: The aim of this study was to define the best cut-off scores of the AdAS Spectrum for determining the presence of subthreshold autistic traits as well as a clinically significant autism spectrum disorder (ASD). METHODS: Our sample was composed of 39 patients with full-blown ASD, 73 subjects with autistic traits, and 150 healthy controls. Subjects were evaluated by trained psychiatrists, who performed a clinical diagnosis according to DSM-5 and then assessed with the AdAS Spectrum and the Autism Spectrum Quotient. RESULTS: Our results showed that the most discriminant cut-off scores were 70 for identifying subjects with full-blown ASD, and 43 for determining the presence of significant autistic traits. CONCLUSION: The threshold values proposed here showed satisfying levels of specificity and sensibility, as well as a good agreement with the diagnosis according to DSM-5 criteria, confirming the validity of the AdAS Spectrum as a psychometric tool for measuring ASD-related conditions in the clinical and general population.

Parental bonding, childhood maltreatment and eating disorder psychopathology: an investigation of their interactions.

PURPOSE: Childhood trauma and parental bonding have been widely recognized as risk factors for eating disorders (EDs). However, their interplay in determining ED psychopathology has been poorly investigated. Consequently, we have assessed their interaction with core ED psychopathological symptoms. METHODS: Fifty-seven patients with anorexia nervosa, 43 with bulimia nervosa and 77 healthy women completed the Childhood Trauma Questionnaire, the Parental Bonding Instrument and the Eating Disorder Inventory-2. Chi square test and regression analyses with a moderation model were performed to investigate the interplay between childhood trauma, parental bonding and ED symptoms such as ineffectiveness, social insecurity, drive to thinness, interoceptive awareness, impulsivity and perfectionism. RESULTS: Compared to controls, patients with EDs showed higher levels of trauma and parental control perception and lower levels of parental care. Childhood maltreatment was more prevalent in patients with the affectionless control parental style. Moderation analyses revealed that higher maternal control significantly predicted the ED symptom of social insecurity only when participants experienced lower levels of emotional abuse. CONCLUSIONS: These findings demonstrate an interplay between deranged problematic parental bonding and childhood trauma in promoting a possible vulnerability to social insecurity, one of the most central dimensions of ED psychopathology. This interaction might have psychotherapeutic implications. LEVEL OF EVIDENCE: Level V, cross-sectional descriptive study.

Questionnaire on Attitude towards Research and Care (QuARC): a survey of patients with psychosis.

Background: The patients' appraisal, satisfaction and attitude toward research is crucial to obtain reliable information, in psychiatry frequently not objective.Aim: We operationalised the information derived from studies on satisfaction and attitude towards research and developed a standardized measure, whose internal consistency and factor structure was investigated.Method: The Questionnaire on Attitude towards Research and health Care (QuARC) is a 10-item self-report scale, administered to 116 patients with psychotic disorders participating in research protocols. Exploratory factor analysis was conducted and internal consistency evaluated.Results: Two factors have been identified: one labelled External Factor, including items related to information on the received treatment, relationship with third parties, and one labelled Internal Factor with items related to the disorder, perceived well-being and contribution to scientific knowledge. Cronbach's alpha internal consistencies were good.Conclusions: The QuARC is easy to use, well accepted, with good psychometric properties. The constructs identified are different from the original issues addressed (i.e. attitude and satisfaction), prevailing different constructs closer to the patient opinion on the research and personal condition. These constructs identify dimensions useful to delineate and understand the patients' experience of participating in a scientific project as well as their satisfaction.

Pathways to specialist care for eating disorders: An Italian multicentre study.

Two hundred forty six patients with eating disorders (EDs) recruited from eight Italian specialized treatment centres were administered with the World Health Organization "Encounter Form," a standardized schedule that makes it possible to characterize the clinical pathways that patients follow to reach specialized care. The median time from symptoms onset to specialized care was 114 weeks. Primary "points of access to care" were general practitioners (25%), psychiatrists (18%), and clinical nutritionists (17%), followed by various other carers. All patients received specific psychotherapy, whereas only 11% of them were given psychotropic drugs. EDs are characterized by complex care pathways, with low rates of direct access to specialized care. Although the role of general practitioners remains crucial, they tend to follow different clinical routes to refer ED patients. Educational programmes on EDs should be addressed to general practitioners and clinical nutritionists, in order to ease the transition of ED patients to a mental health care setting.

Insecure Attachment and Hypothalamus-Pituitary-Adrenal Axis Functioning in People With Eating Disorders.

OBJECTIVE: Childhood attachment experiences affect adult emotion regulation and ability to cope with stressors. Therefore, insecure attachment may influence the functioning of the hypothalamic-pituitary-adrenal (HPA) axis and a dysregulation of HPA axis has been found in insecure attached healthy individuals. The effects of attachment on HPA axis activity have never been investigated in eating disorders (EDs). Therefore, we assessed the relationships between insecure attachment and the cortisol awakening response (CAR) in adults with EDs. METHODS: Seventy-eight patients with EDs (43 with anorexia nervosa, 35 with bulimia nervosa) were recruited. They completed the Experience in Close Relationships questionnaire, which provides a rating of two insecure attachment dimensions (anxiety and avoidance) and collected saliva samples to measure the CAR. Differences in the CAR between groups with high and low attachment anxiety and between groups with high and low attachment avoidance were evaluated by repeated measures two-way analysis of variance. RESULTS: Patients with high attachment anxiety showed a reduced CAR compared with those with low attachment anxiety (F1,76 = 7.31, p = .008). The CAR did not differ between the groups with high and low attachment avoidance (F1,76 = 0.01, p = .93). Patients with high levels of insecure attachment showed a more severe eating-related psychopathology. CONCLUSIONS: Our data show, for the first time, a specific association of the anxious attachment with the HPA axis activity in EDs and suggest a possible role of attachment in the biological vulnerability to stress of adult patients with EDs.

Interhemispheric functional connectivity in anorexia and bulimia nervosa.

The functional interplay between hemispheres is fundamental for behavioral, cognitive, and emotional control. Anorexia nervosa (AN) and bulimia nervosa (BN) have been largely studied with brain magnetic resonance imaging (MRI) in relation to the functional mechanisms of high-level processing, but not in terms of possible inter-hemispheric functional connectivity anomalies. Using resting-state functional MRI (fMRI), voxel-mirrored homotopic connectivity (VMHC) and regional inter-hemispheric spectral coherence (IHSC) were studied in 15 AN and 13 BN patients and 16 healthy controls (HC). Using T1-weighted and diffusion tensor imaging MRI scans, regional VMHC values were correlated with the left-right asymmetry of corresponding homotopic gray matter volumes and with the white matter callosal fractional anisotropy (FA). Compared to HC, AN patients exhibited reduced VMHC in cerebellum, insula, and precuneus, while BN patients showed reduced VMHC in dorso-lateral prefrontal and orbito-frontal cortices. The regional IHSC analysis highlighted that the inter-hemispheric functional connectivity was higher in the 'Slow-5' band in all regions except the insula. No group differences in left-right structural asymmetries and in VMHC vs. callosal FA correlations were significant in the comparisons between cohorts. These anomalies, not explained by structural changes, indicate that AN and BN, at least in their acute phase, are associated with a loss of inter-hemispheric connectivity in regions implicated in self-referential, cognitive control and reward processing. These findings may thus gather novel functional markers to explore aberrant features of these eating disorders.

The relationships of personal resources with symptom severity and psychosocial functioning in persons with schizophrenia: results from the Italian Network for Research on Psychoses study.

The relationships of personal resources with symptom severity and psychosocial functioning have never been tested systematically in a large sample of people with schizophrenia. We applied structural equation models to a sample of 921 patients with schizophrenia collected in a nationwide Italian study, with the aim to identify, among a large set of personal resources, those that may have an association with symptom severity or psychosocial functioning. Several relevant demographic and clinical variables were considered concurrently. Poor service engagement and poor recovery style, as well as older age and younger age at onset, were related to greater symptom severity and poorer social functioning. Higher resilience and higher education were related to better social functioning only. Poor problem-focused coping and internalized stigma, as well as male gender and depression, were related to symptom severity only. The explored variables showed distinctive and partially independent associations with symptom severity and psychosocial functioning. A deeper understanding of these relationships may inform treatment decisions.

How do relatives cope with eating disorders? Results from an Italian multicentre study.

OBJECTIVE: This paper aims to: (1) describe coping strategies in relatives of patients with eating disorders (EDs); (2) analyze coping strategies according to the different EDs; (3) identify correlations between patients' clinical characteristics, relatives' socio-demographic characteristics and coping strategies. METHODS: Patients and their relatives consecutively attending three outpatient units for EDs at the Universities of Naples SUN, Salerno and Catanzaro were recruited. Coping strategies were assessed through the Family Coping Questionnaire for Eating Disorders (FCQ-ED). It consists of 32 items, grouped into two factors: problem-oriented ("seek for information", "positive communication") and emotion-focused ("avoidance," "collusion," "coercion") strategies, plus one item on seeking for spiritual help. RESULTS: Seventy-two patients and 127 relatives were recruited. The most frequently reported coping strategies by relatives were seeking for information, positive communication, seeking for spiritual help; the first two coping strategies were positively correlated with the level of education of both patients and relatives. Mothers reported avoidance less frequently than other relatives. Relatives of patients with BN reported collusion and coercion more frequently compared to relatives of patients with AN. DISCUSSION: This report represents an initial attempt to understand the complex relationship among clinical, social and personal variables involved in the development of coping strategies. © 2016 Wiley Periodicals, Inc.(Int J Eat Disord 2017; 50:587-592).

Differences in Cortisol Awakening Response between Binge-Purging and Restrictive Patients with Anorexia Nervosa.

Malnutrition and childhood trauma were shown to affect in opposite way the cortisol awakening response (CAR) of patients with anorexia nervosa (AN). To assess the influence of binge-purging behaviour on the CAR of AN patients, we measured the CAR of restrictive AN (ANR) or binge-purging AN (ANBP) patients without history of childhood maltreatment. Seventeen ANBP women, 18 ANR women and 42 healthy women collected saliva samples at awakening and after 15, 30 and 60 min, and filled in the Eating Disorder Inventory-2 (EDI-2). ANR and ANBP patients exhibited a CAR significantly higher than healthy women. Moreover, the CAR of ANBP women was even higher than that of ANR women and positively correlated with the bulimia subitem scores of the EDI-2. Present findings show, for the first time, differences in the CAR between ANBP and ANR subtypes, which may suggest a possible connection between the HPA axis functioning and binge-purging. Copyright © 2016 John Wiley & Sons, Ltd and Eating Disorders Association.