MULTICENTER NATIONAL STUDY IN PATIENTS WITH POST-TRAUMATIC STRESS DISORDER AND/OR COMPLICATED GRIEF VERSUS CONTROLS: VALIDATION OF THE STRUCTURED CLINICAL INTERVIEW FOR TRAUMA AND LOSS SPECTRUM(SCI-TALS) AND NEUROBIOLOGICAL CORRELATIONS TO MOOD SPECTRUM

Post-Traumatic Stress Disorder (PTSD) is an invaliding psychiatric condition with typical onset following traumatic and stressful situations. Recently, nvestigators have emphasized the importance of a revision of current diagnostic criteria in order to include both a broaden spectrum of events among potential trauma,including the so called “low-magnitude” events, and subthreshold and subsyndromal forms of the disorder that are progressively showing to be as disruptive and invalidating as the full blown. In line With these studies, researchers from the University of Pisa (Italy), as part of the international collaboration project named “Spectrum Project”, have developed a new instrument to assess the trauma and loss spectrum: the Structured Clinical Interview for the Trauma and Loss Spectrum (SCI-TALS). The instrument is based on a spectrum model that emphasizes soft signs, low-grade symptoms, subthreshold syndromes, as well as temperamental and personality traits comprising the clinical and subsyndromal manifestations of Post-Traumatic Stress Disorder (PTSD) and prolonged grief disorder. This latest, also sometimes called Complicated Grief (CG), has been recently explored as an independent form of stress response. The items of the interview include, in addition to a subset of the DSM-IV criteria for PTSD, a number of features derived from clinical experience and from a review of the phenomenological descriptions of post-traumatic syndromes including CG. TheSCI-TALS also includes two specific sections that apply the “spectrum” concept to the definition of the trauma including losses and traumatic events, exploring both the exposure to DSM-IV qualifying traumas and less severe experiences. Primary aim of the present thesis is to describe the SCI-TALS, and to evaluate its acceptability, validity and reliability that was assessed through a national multicenter validation study. Study participants were enrolled at 6I talian Academic Departments of Psychiatry coordinated by the University of Pisa, and included 48 consecutive patients with PTSD (DSM-IV), 44 with CG, and 48 healthy controls, with outcurrent or lifetime psychiatric history. Assessments included: SCID (DSM-IV-TR), IES, ICG. The SCI-TALS significantly discriminated subjects with PTSD or CG from controls. As expected, the instrument did not discriminate between those with PTSD and CG, except on the domain of grief reactions. Validity and reliability of the instrument were proved to be substantial and acceptability was excellent. Besides progresses in clinical assessments, recent studies attempting to delineate clear-cut diagnostic criteria for PTSD, have suggested the relevance of biological markers of PTSD. Although the findings have been highly variable, a great number of data have suggested the presence of characteristic alterations in the function of hypothalamic -pituitary-adrenal (HPA) axis and some reported alterations in the mitochondrial translocator protein (Peripheral Benzodiazepine Receptor, PBR), that is a protein complexessential for steroid synthesis. PBR has been found decreased in combat-related PTSD but no data have been reported in non-combat related PTSD. Secondary aim of the present thesis was to assess mitochondrial PBR density in lymphomonocytes from civilian patients with PTSD (DSM-IV), exposed to non¬ combat related traumas versus controls. Moreover, in psychiatric literature, the presence of a manic/hypomanic state has been recently hypothesized as the most critical risk factor for PTSD onset after trauma exposure in patients with Bipolar Disorder. Secondary aim of the present thesis was also to explore the correlation between PBR density and the presence of lifetime manic/hypomanic spectrum symptoms. Assessments for this second phase of the study included the MOOD Spectrum Self Report (MOODS-SR) lifetime version, as harpened instrument assessing mood spectrum symptomatology, that was administered to those patients with PTSD and controls that, enrolled for the multicenter national validation study at the Pisa site, accepted to complete this second phase of thestudy after procedures and possible side effects were explained to them. Blood samples (16 ml) were processed to assess PBR binding parameters in lymphomonocyte mitochondrial membranes. Results show that PTSD patients presented significant PBR density decrease with respect to controls. No correlation resulted between PBR density and IES scores. Significant correlation was found between PBR density and the number of lifetime MOODS-SR manic/hypomanic symptoms. In conclusion,data from the present thesis show that the SCI-TALS is a userfriendly instrument to both clinicians and patients that provides information on a broads pectrum of trauma, loss events and related symptoms beyond those covered by existing instruments and maybe used in research settings. Moreover, for the first time, PBR density decrease has been reported in PTSD patients with not war-related traumas, supporting the potential role of this biochemical marker in PTSD diagnosis. A significant correlation between this alteration and the presence of lifetime manic spectrum symptoms was found, corroborating the relevance of an accurate assessment of subthreshold mania as risk factor for PTSD

A new look at an old drug: Neuroprotective effects and therapeutic potentials of lithium salts

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

Psychotic spectrum symptoms across the lifespan are related to lifetime suicidality among 147 patients with bipolar I or major depressive disorder

BACKGROUND: Conflicting evidence exists about the relationship between psychotic symptoms and suicidality in mood disorders. We aimed to investigate the lifetime suicidality and its relationship with dimensions of the psychotic spectrum over the lifespan among subjects with bipolar I (BD I) or major depressive disorder (MDD). METHODS: 147 Consecutive out- and inpatients with BD I or MDD presenting for treatment at 11 Italian Departments of Psychiatry were administered the Structured Clinical Interview for DSM-IV Axis I Disorders, the Structured Clinical Interview for the Psychotic Spectrum (SCI-PSY, lifetime version) and the Mood Spectrum Self-Report (MOODS-SR, lifetime version). RESULTS: Subjects with psychotic features did not differ from those without for MOODS-SR suicidality score. Controlling for age, gender and diagnosis (MDD/BD I), the SCI-PSY total score (p = .007) and Paranoid (p = .042), Schizoid (p = .007) and Interpersonal Sensitivity (p < .001) domain scores independently predicted lifetime MOODS-SR suicidality score in the overall sample. CONCLUSIONS: Psychotic features, as evaluated upon the presence of delusions or hallucinations, are not associated with suicidality among subjects with BD I or MDD. However, more subtle dimensions of the psychotic spectrum, such as Interpersonal Sensitivity, Paranoid and Schizoid symptoms, show a significant relationship with lifetime suicidality. Our findings highlight the potential usefulness of a spectrum approach in the assessment of psychotic symptoms and suicide risk among subjects with BD I or MDD

Comparing re‐hospitalisation rates in a real‐world naturalistic 24‐month follow‐up of psychotic patients with different treatment strategies: Oral versus LAI antipsychotics

AIM & BACKGROUND Non-adherence to antipsychotic treatment is a major issue in the management of severe psychiatric disorders, because it is usually related to future relapses and re-hospitalisations. Long-Acting-Injection (LAI) antipsychotics can be useful to increase treatment adherence in these patients. The aim of the present study was to compare the re-hospitalisation rates of psychotic patients discharged from a psychiatric ward and then, divided into three groups upon the treatment received: LAI antipsychotic, oral antipsychotic at home or oral antipsychotic administered daily by psychiatric nurse staff as patients lived in a long-term care facility. METHODS Data on all inpatients consecutively admitted to the Psychiatric Unit of the Nuovo Ospedale Apuano (Massa, Italy), between January 2017 and December 2018, were obtained by the registration record system. Information about eventual re-hospitalisations of these patients, occurred within a 24-month timeframe since discharge, were collected from the same database. RESULTS In a Kaplan-Meyer analysis, patients treated with LAI antipsychotics showed significantly lower re-hospitalisation rates in the first 24 months after discharge than those treated with oral ones. CONCLUSIONS This study highlights the impact of LAI antipsychotics in preventing re-hospitalisation in severe psychotic patients at high risk in a naturalistic setting. The benefits appear relevant also with respect to a controlled long-term oral antipsychotic treatment, however, further studies are needed to develop more tailored intervention strategies in such complex psychiatric population

Adult separation anxiety in patients with complicated grief versus healthy control subjects: relationships with lifetime depressive and hypomanic symptoms

<p>Abstract</p> <p>Background</p> <p>Around 9% to 20% of bereaved individuals experience symptoms of complicated grief (CG) that are associated with significant distress and impairment. A major issue is whether CG represents a distinctive nosographic entity, independent from other mental disorders, particularly major depression (MD), and the role of symptoms of adult separation anxiety. The purpose of this study was to compare the clinical features of patients with CG versus a sample of healthy control subjects, with particular focus on adult separation anxiety and lifetime mood spectrum symptoms.</p> <p>Methods</p> <p>A total of 53 patients with CG and 50 healthy control subjects were consecutively recruited and assessed by means of the Structured Clinical Interview for DSM-IV Axis-I disorders (SCID-I/P), Inventory of Complicated Grief (ICG), Adult Separation Anxiety Questionnaire (ASA-27), Work and Social Adjustment Scale (WSAS) and Mood Spectrum-Self Report (MOODS-SR) lifetime version.</p> <p>Results</p> <p>Patients with CG reported significantly higher scores on the MOODS-SR, ASA-27, and WSAS with respect to healthy control subjects. The scores on the ASA-27 were significantly associated with the MOODS-SR depressive and manic components amongst both patients and healthy control subjects, with a stronger association in the latter.</p> <p>Conclusions</p> <p>A major limitation of the present study is the small sample size that may reduce the generalizability of the results. Moreover, lifetime MOODS-SR does not provide information about the temporal sequence of the manic or depressive symptoms and the loss. The frequent comorbidity with MD and the association with both depressive and manic lifetime symptoms do not support the independence of CG from mood disorders. In our patients, CG is associated with high levels of separation anxiety in adulthood. However, the presence of lifetime mood instability, as measured by the frequent presence of depressive and hypomanic lifetime symptoms, suggests that cyclothymia might represent the common underlying feature characterizing the vulnerability to both adult separation anxiety and CG.</p

An attempted "suicide pact" in Covid-19 era - psychiatric perspectives

Background A "suicide pact" is a joint and actively induced death of two individuals with the essential and unavoidable characteristic of a mutual consent. One of the partners (dominant in the relationship, commonly male) usually induces the action and in most cases, it is the one who actively carries it out. Undiagnosed psychopathological dimension or pathological subthreshold traits are found in those who enter into suicide agreements, the presence of cluster B personality traits such as narcissistic or borderline is of particular relevance in the dominant partner, while in the submissive one dependent personality traits are more frequent. As in the case of other similar health emergencies, COVID-19 pandemic seems to lead to greater suicidality, including the "suicide pacts" of couples whose motivation varies including firstly financial problems, strictly followed by fear of infection and not being able to return home from abroad. Case presentation We reported a case of a couple who entered a suicide agreement consequently to the economic difficulties caused by COVID-19 pandemic, hospitalized in our department. Both partners were assessed with Adult Autism Subthreshold Spectrum (AdAS Spectrum) and both crossed the threshold for clinically relevant autistic traits (M = 67; F = 49). Conclusion This case further confirms the link between COVID-19 pandemics and suicidality. The role of autism spectrum traits as a vulnerability factor towards the development of severe psychopathological consequences after traumatic events is also stressed

Autism Spectrum Disorder and Fetal Alcohol Spectrum Disorder: A Literature Review

Fetal alcohol spectrum disorders (FASD) are a group of conditions associated with the effects of prenatal alcohol exposure and characterized by somatic and neuropsychological alterations. On the other hand, autism spectrum disorder (ASD) is characterized by a multifaceted neurobehavioral syndrome. Since alcohol can affect every stage of brain development, some authors hypothesized that in utero alcohol exposure might be linked to an increased risk of ASD in subjects with genetic vulnerability. The present review aimed to summarize the available literature on the possible association between FASD and ASD, also focusing on the reported clinical overlaps and on the possible shared pathogenic mechanisms. Studies in this field have stressed similarities and differences between the two conditions, leading to controversial results. The available literature also highlighted that both the disorders are often misdiagnosed or underdiagnosed, stressing the need to broaden the perspective, paying specific attention to milder presentations and sub-syndromic traits

The Broad Autism (Endo)Phenotype: Neurostructural and Neurofunctional Correlates in Parents of Individuals with Autism Spectrum Disorders

Autism Spectrum Disorders (ASD) are a set of neurodevelopmental disorders with an early-onset and a strong genetic component in their pathogenesis. According to genetic and epidemiological data, ASD relatives present personality traits similar to, but not as severe as the defining features of ASD, which have been indicated as the "Broader Autism Phenotype" (BAP). BAP features seem to be more prevalent in first-degree relatives of individuals with ASD than in the general population. Characterizing brain profiles of relatives of autistic probands may help to understand ASD endophenotype. The aim of this review was to provide an up-to-date overview of research findings on the neurostructural and neurofunctional substrates in parents of individuals with ASD (pASD). The primary hypothesis was that, like for the behavioral profile, the pASD express an intermediate neurobiological pattern between ASD individuals and healthy controls. The 13 reviewed studies evaluated structural magnetic resonance imaging (MRI) brain volumes, chemical signals using magnetic resonance spectroscopy (MRS), task-related functional activation by functional magnetic resonance imaging (fMRI), electroencephalography (EEG), or magnetoencephalography (MEG) in pASD.The studies showed that pASD are generally different from healthy controls at a structural and functional level despite often not behaviorally impaired. More atypicalities in neural patterns of pASD seem to be associated with higher scores at BAP assessment. Some of the observed atypicalities are the same of the ASD probands. In addition, the pattern of neural correlates in pASD resembles that of adult individuals with ASD, or it is specific, possibly due to a compensatory mechanism. Future studies should ideally include a group of pASD and HC with their ASD and non-ASD probands respectively. They should subgrouping the pASD according to the BAP scores, considering gender as a possible confounding factor, and correlating these scores to underlying brain structure and function. These types of studies may help to understand the genetic mechanisms involved in the various clinical dimension of ASD

DSM-5 PTSD and posttraumatic stress spectrum in Italian emergency personnel: correlations with work and social adjustment

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, educatio