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Background Mental disorders are a major public health problem. However, over the last few years, there have been few studies aimed at evaluating their diffusion. Therefore, this study aimed at evaluating: the prevalence of the most frequent psychiatric disorders in the general population residing in Tuscany using a clinical scale administered by trainee in psychiatry. Methods The study was carried out on a representative sample of the general population aged > 18 years, randomly extracted from the register of patients in the Tuscany region, adopting a proportional sampling method stratified by gender, age group and Local Health Units (LHU). Each person was contacted by letter followed by a phone call from an operator who makes an appointment with the trainee in psychiatry. The diagnostic interview conducted was the Mini-International Neuropsychiatric Interview (MINI). Point and lifetime prevalence by gender and age group were calculated. Differences and associations were considered statistically significant if their p-values were less than 0.05. Results Of the 408 people involved, 390 people were enrolled (of which 52.6% female). The 28.5% of the sample had been affected by a psychiatric disorder during their lifetime. In their lifetime, the most represented psychiatric disorders were major depressive episode (20.4%), major depressive disorder (17.0%) and panic disorder (10.3%), more frequent in the female than the male group. Current conditions were predominantly major depressive episode (3.1%) and agoraphobia (2.8%). A 5.9% rate of current suicidal ideation was also found. Conclusions In the general population, 28.5% of people reported a psychiatric disorder during their lifetime. This prevalence is considerably higher than that reported in a previous study carried out in central Italy.

Aims of the present study are to test the efficacy of a lifestyle group intervention, compared to a brief psychoeducational intervention, on levels of physical activity and dietary habits in a real-world sample of patients with severe mental disorders. The study, funded by the Italian Ministry of Education, has been carried out in six Italian University psychiatric outpatient units. All patients were randomly assigned to the experimental or control group and were assessed through standardized assessment instruments at baseline and six months after randomization. Of the 401 recruited patients, 43.3% had a diagnosis of bipolar disorder, 29.9% of psychosis and 26.9% of major depression. Patients were mainly female (57%), with a mean age of 45.6 +/- 11.8 years. Treated patients have almost 8 times the likelihood to show an increase of the total MET (OR: 8.02; p < .001) and of the walking MET (OR: 7.68; p < .001) and are more likely to increase the weekly consumption of vegetables (OR= 1.98, p < .05) and to reduce that of junk food (OR:0.23; p < .05). The present study support the notion that patients with severe mental disorders can improve their lifestyle behaviours and that, with appropriate support, they can achieve a healthy living.

Literature shows high rates of comorbidity between fibromyalgia (FM) and mood disorders, especially major depressive disorder (MMD), reported in more than half of the cases. Consistently, patients with FM also present high rates of mood spectrum symptoms, despite scant data are still available on the relationship with antidepressant treatment outcomes. The present study was aimed at exploring the clinical outcome of patients with FM-MDD comorbidity naturalistically treated with antidepressant drugs, besides the relationships between mood spectrum symptoms and the treatment response.A total sample of 40 patients with FM and MDD, who started a treatment with an antidepressant drug, was recruited at the Rheumatology Unit of the University of Pisa, Italy. Patients were evaluated at baseline and after 1 (T1) and 6 months (T2) of the treatment with an antidepressant drug. Assessments included: the Mood Spectrum-Self Report (MOODS-SR) for mood spectrum symptoms, the Short Form Health Survey (SF-36) for the global functioning and the Clinical Global Impression (CGI) for the clinical severity and improvement. All instruments were administered at baseline and the SF-36 and CGI were repeated at T1 and T2.Twenty-eight (70%) patients reported an improvement at the CGI at T2. At T1 and T2 the CGI item-1 and most of the SF-36 domain scores significantly improved with respect to the T0, with the exception of the "role physical" and "role emotional" subscales. Improved patients reported higher scores in the energy depressive MOODS-SR domain. Furthermore, correlations emerged between several MOODS-SR domains and the CGI or SF-36 subscales scores at T0.Our results corroborate previous findings on the role of antidepressant drugs in the management not only of MDD symptoms, but also of the painful component of FM. FM patients should be investigated for Mood Spectrum symptomatology considering its prominent role on the manifestations of the disorder and treatment outcome.

Importance: The goal of schizophrenia treatment has shifted from symptom reduction and relapse prevention to functional recovery; however, recovery rates remain low. Prospective identification of variables associated with real-life functioning domains is essential for personalized and integrated treatment programs. Objective: To assess whether baseline illness-related variables, personal resources, and context-related factors are associated with work skills, interpersonal relationships, and everyday life skills at 4-year follow-up. Design, Setting, and Participants: This multicenter prospective cohort study was conducted across 24 Italian university psychiatric clinics or mental health departments in which 921 patients enrolled in a cross-sectional study were contacted after 4 years for reassessment. Recruitment of community-dwelling, clinically stable persons with schizophrenia was conducted from March 2016 to December 2017, and data were analyzed from January to May 2020. Main Outcomes and Measures: Psychopathology, social and nonsocial cognition, functional capacity, personal resources, and context-related factors were assessed, with real-life functioning as the main outcome. Structural equation modeling, multiple regression analyses, and latent change score modeling were used to identify variables that were associated with real-life functioning domains at follow-up and with changes from baseline in these domains. Results: In total, 618 participants (427 male [69.1%]; mean [SD] age, 45.1 [10.5] years) were included. Five baseline variables were directly associated with real-life functioning at follow-up: neurocognition with everyday life (β, 0.274; 95% CI, 0.207-0.341; P

Objectives People with schizophrenia (SCZ) present serious and generalised deficits in social cognition (SC), which affect negatively patients' functioning and treatment outcomes. The genetic background of SC has been investigated in disorders other than SCZ providing weak and sparse results. Thus, our aim was to explore possible genetic correlates of SC dysfunctions in SCZ patients with a genome-wide study (GWAS) approach. Methods We performed a GWAS meta-analysis of data coming from two cohorts made of 242 and 160 SCZ patients, respectively. SC was assessed with different tools in order to cover its different domains. Results We found GWAS significant association between the TMEM74 gene and the patients' ability in social inference as assessed by The Awareness of Social Inference Test; this association was confirmed by both SNP-based analysis (lead SNP rs3019332 p-value = 5.24 × 10-9) and gene-based analysis (p-value = 1.09 × 10-7). Moreover, suggestive associations of other genes with different dimensions of SC were also found. Conclusions Our study shows for the first time GWAS significant or suggestive associations of some gene variants with SC domains in people with SCZ. These findings should stimulate further studies to characterise the genetic underpinning of SC dysfunctions in SCZ.

Compared with the general population, people with severe mental disorders have significantly worse physical health and a higher mortality rate, which is partially due to the adoption of unhealthy lifestyle behaviors, such as heavy smoking, use of alcohol or illicit drugs, unbalanced diet, and physical inactivity. These unhealthy behaviors may also play a significant role in the personal and functional recovery of patients with severe mental disorders, although this relationship has been rarely investigated in methodologically robust studies. In this paper, we aim to: a) describe the levels of physical activity and recovery style in a sample of patients with severe mental disorders; b) identify the clinical, social, and illness-related factors that predict the likelihood of patients performing physical activity. The global sample consists of 401 patients, with a main psychiatric diagnosis of bipolar disorder (43.4%, N = 174), psychosis spectrum disorder (29.7%; N = 119), or major depression (26.9%; N = 118). 29.4% (N = 119) of patients reported performing physical activity regularly, most frequently walking (52.1%, N = 62), going to the gym (21.8%, N = 26), and running (10.9%, N = 13). Only 15 patients (3.7%) performed at least 75 min of vigorous physical activity per week. 46.8% of patients adopted sealing over as a recovery style and 37.9% used a mixed style toward integration. Recovery style is influenced by gender (p < 0.05) and age (p < 0.05). The probability to practice regular physical activity is higher in patients with metabolic syndrome (Odds Ratio - OR: 2.1; Confidence Interval - CI 95%: 1.2-3.5; p < 0.050), and significantly lower in those with higher levels of anxiety/depressive symptoms (OR: 0.877; CI 95%: 0.771-0.998; p < 0.01). Globally, patients with severe mental disorders report low levels of physical activities, which are associated with poor recovery styles. Psychoeducational interventions aimed at increasing patients' motivation to adopt healthy lifestyle behaviors and modifying recovery styles may improve the physical health of people with severe mental disorders thus reducing the mortality rates.

Background People with severe mental illnesses (SMI) have a mortality rate two times higher compared to the general population, with a decade of years of life lost. In this randomized controlled trial (RCT), we assessed in a sample of people with bipolar disorder, major depressive disorder, and schizophrenia spectrum disorder, the efficacy of an innovative psychosocial group intervention compared to a brief psychoeducational group intervention on patients’ body mass index (BMI), body weight, waist circumference, Framingham and HOMA-IR indexes. Methods This is a multicentric RCT with blinded outcome assessments carried out in six Italian university centers. After recruitment patients were randomized to receive a 6-month psychosocial intervention to improve patients’ physical health or a brief psychoeducational intervention. All recruited patients were assessed with standardized assessment instruments at baseline and after 6 months. Anthropometric parameters and blood samples have also been collected. Results Four-hundred and two patients with a diagnosis of bipolar disorder (43.3%), schizophrenia or other psychotic disorder (29.9%), or major depression (26.9%) were randomly allocated to the experimental (N = 206) or the control group (N = 195). After 6 months, patients from the experimental group reported a significant reduction in BMI (odds ratio [OR]: 1.93, 95% confidence intervals [CI]: 1.31–2.84; p p p Conclusions The experimental group intervention was effective in improving the physical health in SMI patients. Further studies are needed to evaluate the feasibility of this intervention in real-world settings.

First generation antipsychotics (FGAs) are more likely to induce extrapyramidal side-effects (EPS) than second generation antipsychotics (SGAs), and EPS have been shown associated to cognitive deficits in schizophrenia. So far, no study has explored the relationships between EPS and social cognition (SC) in people with schizophrenia. Therefore, we assessed the prevalence of EPS in a large sample of drug-treated community-dwelling persons with schizophrenia and explored their relationships with patients' neurocognitive and SC abilities. 875 patients underwent EPS, psychopathological, neurocognitive and SC assessments by means of standardized measures. Relationships between EPS, psychopathology and neurocognitive and SC measures were investigated by correlation tests. Moreover, a partial correlation network was computed by means of a network analysis. 256 patients were treated with FGAs alone or in combination with SGA and 619 with SGAs. EPS were significantly more frequent in FGA-treated group than in the SGA-treated one. Patients with EPS disclosed a more severe psychopathology and were more impaired in neurocognitive and SC measures compared to those without EPS. Disorganization, expressive deficit, and duration of illness were significantly associated to both neurocognitive and SC measures while EPS were associated to neurocognitive measures only. The network analysis showed that parkinsonism was the sole EPS directly connected to both psychopathological and neurocognitive indices whereas no direct connection emerged between EPS and SC measures. Present findings confirm that EPS are still present in the era of SGAs and contribute, together with other clinical variables, to the neurocognitive but not to the SC impairment of patients with schizophrenia.

Background. Greater levels of insight may be linked with depressive symptoms among patients with schizophrenia, however, it would be useful to characterize this association at symptom-level, in order to inform research on interventions. Methods. Data on depressive symptoms (Calgary Depression Scale for Schizophrenia) and insight (G12 item from the Positive and Negative Syndrome Scale) were obtained from 921 community-dwelling, clinically-stable individuals with a DSM-IV diagnosis of schizophrenia, recruited in a nationwide multicenter study. Network analysis was used to explore the most relevant connections between insight and depressive symptoms, including potential confounders in the model (neurocognitive and social-cognitive functioning, positive, negative and disorganization symptoms, extrapyramidal symptoms, hostility, internalized stigma, and perceived discrimination). Bayesian network analysis was used to estimate a directed acyclic graph (DAG) while investigating the most likely direction of the putative causal association between insight and depression. Results. After adjusting for confounders, better levels of insight were associated with greater self-depreciation, pathological guilt, morning depression and suicidal ideation. No difference in global network structure was detected for socioeconomic status, service engagement or illness severity. The DAG confirmed the presence of an association between greater insight and self-depreciation, suggesting the more probable causal direction was from insight to depressive symptoms. Conclusions. In schizophrenia, better levels of insight may cause self-depreciation and, possibly, other depressive symptoms. Person-centered and narrative psychotherapeutic approaches may be particularly fit to improve patient insight without dampening self-esteem., Highlights Better insight seems associated with depressive symptoms in schizophrenia.Network analyses were used to explore this association in a large sample.Insight was associated with self-depreciation, guilt, and suicidal ideation.Although cross-sectional, data suggest causal direction from insight to depression.

Claudia Carmassi,1 Valerio Dell’Oste,1 Diana Ceresoli,1 Stefano Moscardini,2 Enrico Bianchi,3 Roberto Landi,4 Gabriele Massimetti,1 Cristiana Nisita,1 Liliana Dell’Osso1 1Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy; 2General Medicine Outpatient Clinic, ASL 5 Tuscany, Pisa, Italy; 3General Medicine Outpatient Clinic, ASL 6 Tuscany, Livorno, Italy; 4General Medicine Outpatient Clinic, ASL 2 Tuscany, Lucca, Italy Background: Frequent attenders (FAs), defined as patients reporting a disproportionate number of visits to general practitioners (GPs), may represent up to one-third of GP patients responsible for a high burden of care not always justified by the severity of the medical condition. The aim of this study was to explore sociodemographic and clinical characteristics of FAs of GP in Italy with particular attention to functional impairment. Methods: A total sample of 75 FAs (defined as individuals who had consulted GPs 15 times or more during 2015) of GPs of three primary care centers (Pisa, Livorno, and Lucca) in Italy were enrolled and assessed by sociodemographic scale, Structured Clinical Interview for DSM-5 (SCID-5), global functioning (Global Assessment of Functioning [GAF]), illness behavior and perceived health (Illness Behavior Inventory), and somatic comorbidity (Cumulative Illness Rating Scale). Results: Most of the sample were females, middle aged, married, or cohabiting, with low levels of education. One-third of FAs was low functioning (LF; GAF score

Objective The study aimed to explore premorbid academic and social functioning in patients with schizophrenia, and its associations with the severity of negative symptoms and neurocognitive impairment. Method Premorbid adjustment (PA) in patients with schizophrenia was compared to early adjustment in unaffected first-degree relatives and healthy controls. Its associations with psychopathology, cognition, and real-life functioning were investigated. The associations of PA with primary negative symptoms and their two factors were explored. Results We found an impairment of academic and social PA in patients (P ≤ 0.000001) and an impairment of academic aspects of early adjustment in relatives (P ≤ 0.01). Patients with poor PA showed greater severity of negative symptoms (limited to avolition after excluding the effect of depression/parkinsonism), working memory, social cognition, and real-life functioning (P ≤ 0.01 to ≤0.000001). Worse academic and social PA were associated with greater severity of psychopathology, cognitive impairment, and real-life functioning impairment (P ≤ 0.000001). Regression analyses showed that worse PA in the academic domain was mainly associated to the impairment of working memory, whereas worse PA in the social domain to avolition (P ≤ 0.000001). Conclusion Our findings suggest that poor early adjustment may represent a marker of vulnerability to schizophrenia and highlight the need for preventive/early interventions based on psychosocial and/or cognitive programs.

Fibromyalgia (FM) is an increasingly prevalent disorder that usually shows a chronic course and a disappointing therapeutic response in which psychiatric features seem to play a relevant role. Most recently, the relationship between FM and Post-traumatic Stress Disorder (PTSD) has gained interest since several studies demonstrated a higher rate of PTSD, both full blown and partial, and Post-traumatic Stress spectrum symptoms. While the relationship between higher burden of autistic symptoms and PTSD is reported in literature, the relationship between FM and autism spectrum symptoms is still unexplored. In this study we investigated both post-traumatic and autistic spectrum in a sample of FM patients with the aim of exploring the relationships between these dimensions.One hundred and nineteen patients with FM, diagnosed according the American College of Rheumatology 2010 criteria, were consecutively enrolled at the Unit of Rheumatology, University of Pisa, Italy. Assessments included: the Trauma And Loss Spectrum-Self Report (TALS-SR), for the post-traumatic stress spectrum symptomatology, the Adult Autism Subthreshold spectrum (AdAS spectrum) for the assessment of subthreshold autism spectrum. The scores reported to AdAS (total and per domain) by the entire sample and subgroups with PTSD diagnosis, partial PTSD and no PTSD were compared in order to detect a relation between Autistic Traits (ATs) and post-traumatic spectrum in this clinical sample.Our results show that FM patients with PTSD report an AdAS total score significantly higher than those reported by patients without PTSD. Moreover, through an examination of the correlation between AdAS spectrum and TALS-SR scores, significant correlations between the total score of the two instruments has emerged. The correlation resulted to be particularly significant between TALS-SR scores and non-verbal communication domain of the AdAS and between hyper-hypo reactivity to sensory input domain and several TALS-SR domains.These results highlight the clinical relevance of autistic traits in FM patients with PTSD. In this regard, we may claim a potential role of abnormal processing of sensory input and deficits in non-verbal communication in explaining this association.

Recently, increasing research stressed the presence of subthreshold autistic traits in patients with other psychiatric conditions. In this framework, a significant relationship between anorexia nervosa (AN) and the autism spectrum has been frequently reported, in particular among female samples, to the point that AN has been hypothesized to be a female phenotype of autism spectrum disorder (ASD). On the other hand, among subjects with ASD has been reported a higher prevalence of immune diseases and altered immune functions. While these reports seem to support an association between neurodevelopmental and immune system alterations in ASD, the relationship between the immune system and the broader autism spectrum, including its subthreshold manifestations, remains poorly investigated. In this report, we described the presence of autistic traits in a male inpatient with AN and separation anxiety disorder, who also show a diagnosis of Behçet’s syndrome (BS). This case seems to further stress the association between AN and the autism spectrum, which may not be limited to the female gender. Moreover, it further suggests a deeper link between neurodevelopmental and immune system alterations. Implications are discussed in light of the more recent neurobiological and psychopathological hypothesis about the autism spectrum.

Claudia Carmassi,1 Martina Corsi,1 Carlo Antonio Bertelloni,1 Barbara Carpita,1 Camilla Gesi,1 Virginia Pedrinelli,1 Gabriele Massimetti,1 Diego Giampietro Peroni,2 Alice Bonuccelli,2 Alessandro Orsini,2 Liliana Dell’Osso1 1Psychiatric Clinic, 2Pediatric Clinic, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy Background: Post-traumatic stress disorder (PTSD) and post-traumatic stress spectrum have been recently applied to understand the impact of life-threatening disease or injury in one’s child; nevertheless, scant data are available on a particular chronic illness such as epilepsy whose phenotypic expression is seizures, which are acute, sudden, and unpredictable manifestations. Subjects with bipolar disorders or with mood spectrum symptoms demonstrated to be more vulnerable to develop PTSD in the aftermath of a trauma. Objectives: The main aim of this study was to evaluate post-traumatic symptoms among 134 parents of children with a diagnosis of epilepsy, followed at the outpatient neurologic unit of Department of Pediatrics in Santa Chiara Hospital in Pisa, as well as gender differences. The second aim of this study was to estimate the impact of lifetime mood spectrum on post-traumatic stress symptoms in the same study sample after fulfillment of the Trauma and Loss Spectrum-Self Report (TALS-SR) and the Mood Spectrum-Self Report (MOODS-SR) lifetime version. Results: Results showed 10.4% and 37.3% of PTSD full and partial, respectively. Demographic characteristics and clinical features of the study sample did not show any impact on stress symptomatology. Mothers presented higher rates at all Diagnostic and Statistical Manual of Mental Disorders (DSM)-5 PTSD symptoms’ clusters except avoidance. Nevertheless, noteworthy correlations between post-traumatic symptomatology and mood spectrum symptoms detected with the self-report tools, emerged only in the subgroup of the fathers. Conclusion: These findings corroborate the need to provide assistance to caregivers of pediatric patients and confirm the hypothesis that lifetime mood spectrum may have an impact on reaction to traumas. Keywords: PTSD, post-traumatic stress spectrum, mood spectrum, DSM-IV, DSM-5, caregivers, children with epilepsy

BackgroundThe increased use of the MATRICS Consensus Cognitive Battery (MCCB) to investigate cognitive dysfunctions in schizophrenia fostered interest in its sensitivity in the context of family studies. As various measures of the same cognitive domains may have different power to distinguish between unaffected relatives of patients and controls, the relative sensitivity of MCCB tests for relative–control differences has to be established. We compared MCCB scores of 852 outpatients with schizophrenia (SCZ) with those of 342 unaffected relatives (REL) and a normative Italian sample of 774 healthy subjects (HCS). We examined familial aggregation of cognitive impairment by investigating within-family prediction of MCCB scores based on probands’ scores.MethodsMultivariate analysis of variance was used to analyze group differences in adjusted MCCB scores. Weighted least-squares analysis was used to investigate whether probands’ MCCB scores predicted REL neurocognitive performance.ResultsSCZ were significantly impaired on all MCCB domains. REL had intermediate scores between SCZ and HCS, showing a similar pattern of impairment, except for social cognition. Proband's scores significantly predicted REL MCCB scores on all domains except for visual learning.ConclusionsIn a large sample of stable patients with schizophrenia, living in the community, and in their unaffected relatives, MCCB demonstrated sensitivity to cognitive deficits in both groups. Our findings of significant within-family prediction of MCCB scores might reflect disease-related genetic or environmental factors.

Self-reported 'personal recovery' and clinical recovery in schizophrenia (SRPR and CR. respectively) reflect different perspectives in schizophrenia outcome, not necessarily concordant with each other and usually representing the consumer's or the therapist's point of view. By means of a cluster analysis on SRPR related variables, we identified three dusters. The first and third cluster included subjects with the best and the poorest clinical outcome respectively. The second cluster was characterized by better insight, higher levels of depression and stigma, lowest self-esteem and personal strength, and highest emotional coping. The first duster showed positive features of recovery, while the third duster showed negative features. The second cluster, with the most positive insight, showed a more complex pattern, a some-what 'paradoxical' mixture of positive and negative personal and clinical features of recovery. The present results suggest the need for a characterization of persons with schizophrenia along SRPR and CR dimensions to design individualized and integrated treatment programs aimed to improve insight and coping strategies, reduce stigma and shape recovery styles. (C) 2017 Elsevier B.V. All rights reserved.

Liliana Dell’Osso,1 Ivan M Cremone,1 Barbara Carpita,1 Valerio Dell’Oste,1 Dario Muti,1 Gabriele Massimetti,1 Stefano Barlati,2 Antonio Vita,2 Andrea Fagiolini,3,4 Claudia Carmassi,1 Camilla Gesi11Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy; 2Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy; 3Department of Mental Health, University of Siena, Siena, Italy; 4Department of Molecular Medicine, University of Siena, Siena, ItalyBackground: The interrelationship between mood disorders and borderline personality disorder (BPD) has been long debated in the literature. Increasing attention has also been paid to the relationship between posttraumatic stress disorder (PTSD) and BPD, as well as to the role of rumination in the development and severity of BPD. This study aims to evaluate the association of rumination, PTSD, and mood spectrum among patients with BPD with or without comorbid mood disorders.Methods: Fifty patients with BPD and 69 healthy controls were assessed with the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders 5, MoodSpectrum Self-Report (MOODS-SR), and Ruminative Response Scale (RRS).Results: The BPD group was split into subjects with BPD+ mood disorder (MD) or BPD only) . PTSD-criteria fulfillment, MOODS, and RRS scores were significantly higher in both BPD subgroups than in controls, while BPD+MD patients scored significantly higher than the BPD-only group. RRS scores and PTSD-criteria fulfillment were significantly related to the presence of both BPD and BPD+MD, with no effect of MOODS-SR scores.Conclusion: Our findings confirm the presence of a relationship between BPD and the PTSD spectrum, highlighting also a possible role of rumination in BPD psychopathology. Rumination and PTSD symptoms seem to prevail in the effect of mood spectrum in predicting BPD.Keywords: ruminative thinking, borderline personality disorder, post-traumatic stress disorder, mood disorders

Objective: The objective of this study was to characterise international trends in the use of psychotropic medication, psychological therapies, and novel therapies used to treat obsessive–compulsive disorder (OCD). Methods: Researchers in the field of OCD were invited to contribute summary statistics on the characteristics of their samples. Consistency of summary statistics across countries was evaluated. Results: The study surveyed 19 expert centres from 15 countries (Argentina, Australia, Brazil, China, Germany, Greece, India, Italy, Japan, Mexico, Portugal, South Africa, Spain, the United Kingdom, and the United States) providing a total sample of 7,340 participants. Fluoxetine (n = 972; 13.2%) and fluvoxamine (n = 913; 12.4%) were the most commonly used selective serotonin reuptake inhibitor medications. Risperidone (n = 428; 7.3%) and aripiprazole (n = 415; 7.1%) were the most commonly used antipsychotic agents. Neurostimulation techniques such as transcranial magnetic stimulation, deep brain stimulation, gamma knife surgery, and psychosurgery were used in less than 1% of the sample. There was significant variation in the use and accessibility of exposure and response prevention for OCD. Conclusions: The variation between countries in treatments used for OCD needs further evaluation. Exposure and response prevention is not used as frequently as guidelines suggest and appears difficult to access in most countries. Updated treatment guidelines are recommended. © 2019 John Wiley & Sons, Ltd.

Rationale Variables influencing real-life functioning have repeatedly been modeled in schizophrenia subjects but not systematically investigated in their unaffected first-degree relatives (SRs), in whom milder forms of deficits reported in schizophrenia have been observed, but confounders of clinical cohorts are not in play. Demonstrating that pathways to functional outcome are similar between patients and SRs would validate structural models developed in schizophrenia subjects. The present multicenter study aimed to explore whether variables associated with real-life functioning are similar in schizophrenia patients and their unaffected relatives. Methods The study sample included 921 schizophrenia patients, 379 SRs and 780 healthy controls. Structural Equation Models (SEMs) were used in patients and SRs to test associations of psychopathological dimensions, neurocognition, social cognition, resilience, perceived stigma and functional capacity with real-life functioning domains, impaired in both patients and SRs. Results Interpersonal Relationships and Work Skills were the only functional domains impaired in both patients and SRs. For both domains, functional impairment in patients was found to predict impairment in unaffected relatives, suggesting the involvement of similar illness-related vulnerability factors. In both groups variables significantly associated with Interpersonal Relationships included Social Cognition, Neurocognition, Avolition, Resilience, Disorganization, Perceived Stigma and Gender, and those significantly associated with Work Skills included Social Cognition, Neurocognition and Disorganization. Conclusions Pathways to functional outcome for Interpersonal relationships and Work skills are similar between schizophrenia patients and their unaffected first-degree relatives. These findings validate, in the absence of confounders of clinical cohorts, structural models of determinants of functional outcome in people with schizophrenia.

Liliana Dell’Osso, Claudia Del Grande, Camilla Gesi, Claudia Carmassi, Laura Musetti Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy Abstract: Increasing evidence highlights bipolar disorder as being associated with impaired neurogenesis, cellular plasticity, and resiliency, as well as with cell atrophy or loss in specific brain regions. This has led most recent research to focus on the possible neuroprotective effects of medications, and particularly interesting findings have emerged for lithium. A growing body of evidence from preclinical in vitro and in vivo studies has in fact documented its neuroprotective effects from different insults acting on cellular signaling pathways, both preventing apoptosis and increasing neurotrophins and cell-survival molecules. Furthermore, positive effects of lithium on neurogenesis, brain remodeling, angiogenesis, mesenchymal stem cells functioning, and inflammation have been revealed, with a key role played through the inhibition of the glycogen synthase kinase-3, a serine/threonine kinase implicated in the pathogenesis of many neuropsychiatric disorders. These recent evidences suggest the potential utility of lithium in the treatment of neurodegenerative diseases, neurodevelopmental disorders, and hypoxic–ischemic/traumatic brain injury, with positive results at even lower lithium doses than those traditionally considered to be antimanic. The aim of this review is to briefly summarize the potential benefits of lithium salts on neuroprotection and neuroregeneration, emphasizing preclinical and clinical evidence suggesting new therapeutic potentials of this drug beyond its mood stabilizing properties. Keywords: bipolar disorder, GSK-3, neurodegeneration, neurogenesis, neurodevelopmental disorders

Liliana Dell’Osso,1 Marianna Abelli,1 Barbara Carpita,1 Stefano Pini,1 Giovanni Castellini,2 Claudia Carmassi,1 Valdo Ricca2 1Psychiatry Section, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, 2Department of Neuroscience, Psychology, Drug Research and Child Health (NEUROFARBA), University of Florence, Florence, Italy Abstract: Eating disorders have been defined as “characterized by persistence disturbance of eating or eating-related behavior that results in the altered consumption or absorption of food and that significantly impairs health or psychosocial functioning”. The psychopathology of eating disorders changed across time under the influence of environmental factors, determining the emergence of new phenotypes. Some of these conditions are still under investigation and are not clearly identified as independent diagnostic entities. In this review, the historic evolution of the eating disorder concept up to the recent Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, has been evaluated. We also examined literature supporting the inclusion of new emergent eating behaviors within the eating disorder spectrum, and their relationship with anorexia, autism, and obsessive–compulsive disorder. In particular, we focused on what is known about the symptoms, epidemiology, assessment, and diagnostic boundaries of a new problematic eating pattern called orthorexia nervosa that could be accepted as a new psychological syndrome, as emphasized by an increasing number of scientific articles in the last few years. Keywords: anorexia nervosa, autism spectrum disorders, eating disorders spectrum, obsessive–compulsive spectrum, orthorexia nervosa, DSM-5

Claudia Carmassi,1 Camilla Gesi,1 Marly Simoncini,1 Luca Favilla,1 Gabriele Massimetti,1 Maria Cristina Olivieri,1 Ciro Conversano,2 Massimo Santini,2 Liliana Dell’Osso1 1Department of Clinical and Experimental Medicine, Section of Psychiatry, University of Pisa, Pisa, Italy; 2Emergency Medicine and Emergency Room Unit, Azienda Ospedaliero-Universitaria Pisana (AOUP), Pisa,Italy Abstract: The Diagnostic and Statistical Manual of Mental Disorders Fifth Edition (DSM-5) has recently recognized a particular risk for posttraumatic stress disorder (PTSD) among first responders (criterion A4), acknowledging emergency units as stressful places of employment. Little data is yet available on DSM-5 among emergency health operators. The aim of this study was to assess DSM-5 symptomatological PTSD and posttraumatic stress spectrum, as well as their impact on work and social functioning, in the emergency staff of a major university hospital in Italy. One hundred and ten subjects (doctors, nurses, and health-care assistants) were recruited at the Emergency Unit of the Azienda Ospedaliero-Universitaria Pisana (Italy) and assessed by the Trauma and Loss Spectrum-Self Report (TALS-SR) and Work and Social Adjustment Scale (WSAS). A 15.7% DSM-5 symptomatological PTSD prevalence rate was found. Nongraduated persons reported significantly higher TALS-SR Domain IV (reaction to loss or traumatic events) scores and a significantly higher proportion of individuals presenting at least one maladaptive behavior (TALS-SR Domain VII), with respect to graduate ones. Women reported significantly higher WSAS scores. Significant correlations emerged between PTSD symptoms and WSAS total scores among health-care assistants, nongraduates and women. Our results showed emergency workers to be at risk for posttraumatic stress spectrum and related work and social impairment, particularly among women and nongraduated subjects. Keywords: posttraumatic stress disorder (PTSD), emergency, emergency care workers, work and social functioning/adjustment, maladaptive behaviors, gender, education

Liliana Dell’Osso,1 Marianna Abelli,1 Stefano Pini,1 Marina Carlini,1 Barbara Carpita,1 Elisabetta Macchi,2 Federica Gorrasi,2 Francesco Mengali,1 Rosalba Tognetti,2 Gabriele Massimetti1 1Department of Clinical and Experimental Medicine, Section of Psychiatry, 2Prorectorate to Students Affairs and Right to Education, University of Pisa, Pisa, Italy Abstract: Social anxiety disorder is a common condition often associated with severe impairment in educational career. The aim of this paper was to evaluate prevalence rates and correlates of mild, moderate, and severe forms of social anxiety spectrum in a large sample of university students. Overall, 717 university students were assessed with the Social Anxiety Spectrum Self-Report questionnaire. Using two cut-off scores, 61.4% of subjects were classified as low scorers, 10% as medium scorers, and 28.6% as high scorers. Both high and medium scorers reported fears related to social situations. Interpersonal sensitivity and specific phobias were more common among women with low scores. Childhood/adolescence social anxiety features were more common among males with medium scores. Behavioral inhibition was more common among males with high scores. Functional impairment was severe among high scorers and, to a lesser extent, among medium scorers. Social anxiety spectrum is largely represented among university students. Future studies should investigate whether sufferers of social phobia underachieve or end their professional objectives prematurely. Keywords: social anxiety spectrum, behavioral inhibition, gender, subthreshold, self-rating, DSM-5

In people suffering from schizophrenia, major areas of everyday life are impaired, including independent living, productive activities and social relationships. Enhanced understanding of factors that hinder real-life functioning is vital for treatments to translate into more positive outcomes. The goal of the present study was to identify predictors of real-life functioning in people with schizophrenia, and to assess their relative contribution. Based on previous literature and clinical experience, several factors were selected and grouped into three categories: illness-related variables, personal resources and context-related factors. Some of these variables were never investigated before in relationship with real-life functioning. In 921 patients with schizophrenia living in the community, we found that variables relevant to the disease, personal resources and social context explain 53.8% of real-life functioning variance in a structural equation model. Neurocognition exhibited the strongest, though indirect, association with real-life functioning. Positive symptoms and disorganization, as well as avolition, proved to have significant direct and indirect effects, while depression had no significant association and poor emotional expression was only indirectly and weakly related to real-life functioning. Availability of a disability pension and access to social and family incentives also showed a significant direct association with functioning. Social cognition, functional capacity, resilience, internalized stigma and engagement with mental health services served as mediators. The observed complex associations among investigated predictors, mediators and real-life functioning strongly suggest that integrated and personalized programs should be provided as standard treatment to people with schizophrenia. In people suffering from schizophrenia, major areas of everyday life are impaired, including independent living, productive activities and social relationships. Enhanced understanding of factors that hinder real-life functioning is vital for treatments to translate into more positive outcomes. The goal of the present study was to identify predictors of real-life functioning in people with schizophrenia, and to assess their relative contribution. Based on previous literature and clinical experience, several factors were selected and grouped into three categories: illness-related variables, personal resources and context-related factors. Some of these variables were never investigated before in relationship with real-life functioning. In 921 patients with schizophrenia living in the community, we found that variables relevant to the disease, personal resources and social context explain 53.8% of real-life functioning variance in a structural equation model. Neurocognition exhibited the strongest, though indirect, association with real-life functioning. Positive symptoms and disorganization, as well as avolition, proved to have significant direct and indirect effects, while depression had no significant association and poor emotional expression was only indirectly and weakly related to real-life functioning. Availability of a disability pension and access to social and family incentives also showed a significant direct association with functioning. Social cognition, functional capacity, resilience, internalized stigma and engagement with mental health services served as mediators. The observed complex associations among investigated predictors, mediators and real-life functioning strongly suggest that integrated and personalized programs should be provided as standard treatment to people with schizophrenia.

Background The study aimed to assess the construct validity, internal consistency and factor structure of the Specific Levels of Functioning Scale (SLOF), a multidimensional instrument assessing real life functioning. Methods The study was carried out in 895 Italian people with schizophrenia, all living in the community and attending the outpatient units of 26 university psychiatric clinics and/or community mental health departments. The construct validity of the SLOF was analyzed by means of the multitrait–multimethod approach, using the Personal and Social Performance (PSP) Scale as the gold standard. The factor structure of the SLOF was examined using both an exploratory principal component analysis and a confirmatory factor analysis. Results The six factors identified using exploratory principal component analysis explained 57.1% of the item variance. The examination of the multitrait–multimethod matrix revealed that the SLOF factors had high correlations with PSP factors measuring the same constructs and low correlations with PSP factors measuring different constructs. The confirmatory factor analysis (CFA) corroborated the 6-factor structure reported in the original validation study. Loadings were all significant and ranged from a minimum of 0.299 to a maximum of 0.803. The CFA model was adequately powered and had satisfactory goodness of fit indices (comparative fit index = 0.927, Tucker–Lewis index = 0.920 and root mean square error of approximation = 0.047, 95% CI 0.045–0.049). Conclusion The present study confirms, in a large sample of Italian people with schizophrenia living in the community, that the SLOF is a reliable and valid instrument for the assessment of social functioning. It has good construct validity and internal consistency, and a well-defined factor structure.

Matteo Preve,1 Cristiana Nisita,1 Massimo Bellini,2 Liliana Dell'Osso1 1Department of Psychiatry, Neurobiology, Pharmacology and Biotechnology, 2Department of Gastroenterology, Gastrointestinal Unit, University of Pisa, Pisa, Italy Abstract: Panic disorder is the most common type of anxiety disorder, and its most common expression is panic attacks characterized with sudden attacks of anxiety with numerous symptoms, including palpitations, tachycardia, tachypnea, nausea, and vertigo: ie, cardiovascular, gastroenterologic, respiratory, and neuro-otologic symptoms. In clinical practice, panic disorder manifests with isolated gastroenteric or cardiovascular symptoms, requiring additional clinical visits after psychiatric intervention. The first-line treatment for anxiety disorders, and in particular for panic disorder, is the selective serotonin reuptake inhibitors. However, these drugs can have adverse effects, including sexual dysfunction, increased bodyweight, and abnormal bleeding, that may be problematic for some patients. Here we report the case of a 29-year-old Caucasian woman affected by panic disorder with agoraphobia who was referred to our clinic for recurrent gastroenteric panic symptoms. The patient reported improvement in her anxiety symptoms and panic attacks while on a selective serotonin reuptake inhibitor, but not in her gastric somatic problems, so the decision was taken to start her on duloxetine, a serotonin-norepinephrine reuptake inhibitor. After 6 months of treatment, the patient achieved complete remission of her gastric and panic-related symptoms, and was able to stop triple gastric therapy. Other authors have hypothesized and confirmed that duloxetine has greater initial noradrenergic effects than venlafaxine and is effective in patients with panic disorder. This case report underscores the possibility of tailoring therapeutic strategies for the gastroenteric expression of panic disorder. Keywords: anxiety disorder, panic attacks, palpitations, tachycardia, tachypnea, nausea, vertigo

We aimed at investigating the impact of lifetime manic spectrum symptoms on the severity of pain and the health-related quality of life (HRQoL) in patients with fibromyalgia (FM).One hundred and sixty-seven patients with FM, assessed according to the ACR criteria, were consecutively enrolled. Psychiatric diagnoses were carried out following the Diagnostic and Statistical Manual for Mental Disorders (DSM-IV-TR). The severity of pain and the HRQoL of FM patients was measured by means of the Fibromyalgia Impact Questionnaire (FIQ) and the Medical Outcomes Study Short Form-36 Health Survey (MOS SF-36); the mood spectrum symptomatology by means of the Mood Spectrum-Self Report (MOODS-SR).A high rate of lifetime manic symptoms was detected and resulted as related to the Pain Visual Analogic Scale ("pain VAS") of the FIQ and the FIQ total scores as well as to the "bodily pain", and to the physical and mental component summary scores of the MOS SF-36, both in the whole sample (n=167) and in FM patients without bipolar disorder (n=160).Our results highlight the need to pay more attention to manic spectrum symptoms and features in FM patients, because of their relationship with the severity of pain and with a worse HRQoL.