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Claudia Carmassi,1 Virginia Pedrinelli,1,2 Corinna Antonini,1 Valerio Dell’Oste,1,2 Davide Gravina,1 Benedetta Nardi,1 Carlo Antonio Bertelloni,1 Gabriele Massimetti,1 Joaquín Nieto-Munuera,3 Liliana Dell’Osso1 1Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy; 2Department of Biotechnology, Chemistry and Pharmacy, University of Siena, Siena, Italy; 3Department of Psychiatry and Social Psychology, University of Murcia, Murcia, SpainCorrespondence: Virginia Pedrinelli, Department of Clinical and Experimental Medicine, University of Pisa, Via Roma 67, Pisa, 56100, Italy, Tel +39 050 2219760, Fax +39 050 2219787, Email virginiapedrinelli@gmail.comBackground: The present study aimed at reporting about the validity and reliability of the Spanish version of the Trauma and Loss Spectrum-Self Report (TALS-SR), an instrument based on a multidimensional approach to Post-Traumatic Stress Disorder (PTSD) and Prolonged Grief Disorder (PGD), including a range of threatening or traumatic experiences and significant losses, besides the spectrum of peri-traumatic stress reactions and post-traumatic stress symptoms that may occur.Methods: A sample of 87 Health Care Workers (HCWs) employed in the COVID-19 Emergency Department at the Virgen de la Arrixaca and Reina Sofia Hospitals (Murcia, Spain) during the pandemic, was consecutively recruited and fulfilled the TALS-SR. Assessments also included the Impact of Event Scale-Revised (IES-R), to examine post-traumatic stress symptoms and probable PTSD. Nineteen HCWs fulfilled the TALS-SR again after three weeks from baseline for test–retest reliability.Results: This study provides evidence of good internal consistency and test–retest reliability of the Spanish version of the TALS-SR. Strong support for the internal validity structure was obtained, with positive and significant correlations between the five symptomatologic domains and the symptomatologic total score. Significant and good correlations between the TALS-SR symptomatologic domains and the IES-R total and single domains’ scores were found. The Questionnaire also demonstrated to discriminate between subjects with and without PTSD, with subjects with PTSD showing significantly higher mean scores in each domain of the TALS-SR.Conclusion: This study validates the Spanish version of TALS-SR, providing a useful instrument for a spectrum approach to PTSD and confirms the potential utility of this psychometric tool in both clinical practice and research settings.Keywords: mental health, stress disorders, traumatic, PTSD, psychological distress, health personnel, psychological tests

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

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

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

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

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

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

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