Delirium in COVID-19 patients: a multicentric observational study in Italy.

INTRODUCTION: Although recent data show that SARS-CoV-2 infection seems to affect the central nervous system (CNS), little is known about the neuropsychiatric effects resulting from this condition. In addition to the well-known neurotrophism of coronaviruses, recent evidence shows also that the "cytokine storm" induced by the infection is at the basis of the neuroinflammation of the CNS. Furthermore, prolonged hospitalization, polypharmacotherapy, and isolation could be at the basis of the onset of delirium in hospitalized COVID patients. This multicentric observational study explores the incidence of the onset of delirium in an Italian cohort of SARS-CoV-2 positive inpatients. METHODS: Data were collected in the COVIDhospitals of Brescia, Bergamo, Chieti, and Genova. Different socio-demographic, medical, neurological, and pharmacological parameters were collected. As a rapid screening for delirium, the 4AT scale was used. Eighty COVID-19 inpatients (mean age 74.7 ± 14.5 years) met the inclusion criteria (confirmed positivity to the SARS-CoV-2 virus; the presence of delirium and/or psychomotor agitation and/or new onset of other neuropsychiatric symptoms during hospitalization). RESULTS: The majority of these patients (68.8%) had "hyperactive delirium" subtype. Polypharmacotherapy, current treatment with corticosteroids, and higher age were associated with delirium severity. CONCLUSION: These data provide an insight into the onset of delirium among COVID-19 patients underlining the need for monitoring, especially in elderly patients, the neuropsychiatric symptoms, and the therapy in order to have shorter hospitalization times and better outcomes.

Commentary on the study of Roy et al. Amygdala Based Altered mir-128-3p in Conferring Susceptibility to Depression-like Behavior via Wnt Signalling.

The study of Roy and colleagues recently accepted for publication in International Journal of Neuropsychopharmacology is a very interesting report investigating the role of specific microRNAs (miRNAs) in vulnerability or resistance to major depressive disorder in a specific brain region (e.g., amygdala). MiRNAs may act as a mega-controller of gene expression being involved in the pathogenesis of major neuropsychiatric conditions. Interestingly, some of the altered miRNAs (e.g., hsa-miR-425-3p, miR-425, miR-674-3p, and miR-873-3p) identified in this study were found to be dysregulated even in existing studies, but several methodological issues may hamper the translation of basic research findings in clinical studies. MiRNAs are proposed as possible biomarkers of disease and treatment response to disentangle the biological complexity underlying major affective disorders. The main implications regarding the present findings are discussed.

The Role of Inflammation in the Pathophysiology of Depression and Suicidal Behavior: Implications for Treatment.

Depression and suicidal behavior are 2 complex psychiatric conditions of significant public health concerns due to their debilitating nature. The need to enhance contemporary treatments and preventative approaches for these illnesses not only calls for distillation of current views on their pathogenesis but also provides an impetus for further elucidation of their novel etiological determinants. In this regard, inflammation has recently been recognized as a potentially important contributor to the development of depression and suicidal behavior. This review highlights key evidence that supports the presence of dysregulated neurometabolic and immunologic signaling and abnormal interaction with microbial species as putative etiological hallmarks of inflammation in depression as well as their contribution to the development of suicidal behavior. Furthermore, therapeutic insights addressing candidate mechanisms of pathological inflammation in these disorders are proposed.

"Surrounded, detached": the relationship between defensive peripersonal space and personality.

Introduction: Personality shapes the cognitive, affective, and behavioral interactions between individuals and the environment. Defensive peripersonal space (DPPS) is the projected interface between the body and the world with a protective function for the body. Previous studies suggest that DPPS displays inter-individual variability that is associated with psychiatric symptoms, such as anxiety. However, DPPS may share a link with personality traits. Methods: Fifty-five healthy participants were assessed with the Personality Inventory for DSM-5 (PID-5)-Adult to evaluate personality dimensions. Subjects underwent the Hand Blink Reflex (HBR) task that estimates the DPPS limits by assessing the modulation of blink intensity in response to the median nerve stimulation. Data of the HBR was analyzed with Bayesian multilevel models, while the relationship between DPPS and personality traits was explored using network analysis. Results: HBR was best modeled using a piecewise linear regression model, with two distinct slope parameters for electromyographic data. Network analyzes showed a positive correlation between the proximal slope and detachment personality trait, suggesting that individuals with higher scores in the detachment trait had an increased modulation of HBR, resulting in a larger extension of the DPPS. Discussion: Features of the detachment personality trait include avoidance of interpersonal experiences, restricted affectivity, and suspiciousness, which affect interpersonal functioning. We suggest that DPPS may represent a characteristic feature of maladaptive personality traits, thus constitute a biomarker or a target for rehabilitative interventions.

Sociodemographic and Clinical Correlates Associated with the Frequent Service Users in an Italian Psychiatric Emergency Department.

BACKGROUND: The aim of the present study is to identify the main sociodemographic and clinical correlates associated with frequent service users (FSUs) in an Italian psychiatric emergency department. METHODS: This study is an observational and prospective clinical investigation. All subjects (N = 549) consecutively admitted to the Psychiatric Inpatient Unit of the IRCCS Ospedale Policlinico San Martino ((Genoa, Italy) were recruited over a period of 18 months. RESULTS: On average, FSUs were more likely to be single (75.0% vs. 64.0, p = 0.001), younger (38.79 years ± 14.68 vs. 45.94 years ± 16.94, p = 0.028), with an earlier onset (20.15 years ± 7.22 vs. 29.33 years ± 15.96, p < 0.001), and longer length of hospitalisation (13.65 days ± 12.40 vs. 9.89 ± 10.15, p = 0.006) compared to non-FSUs. While bipolar disorder was the most common primary diagnosis in both FSUs and non-FSUs, cluster B personality disorder was particularly elevated in FSUs (30.3% vs. 10.4%, p < 0.001). Furthermore, FSUs were more prone to substance use disorder (63.6% vs. 40.0%, p < 0.001), particularly cannabis (45.5% vs. 15.3%, p < 0.001), cocaine (33.3% vs. 10.4%, p < 0.001), and heroin (19.7% vs. 5.8%, p < 0.001), and were more likely to have non-suicidal self-injuries (21.2% vs. 6.8%, p < 0.001). FSUs were significantly more likely to be discharged against medical advice (18.2% vs. 5.6%, p < 0.001) or to have at least one escape attempt from the psychiatric ward (12.1% vs. 0.8%, p < 0.001). CONCLUSIONS: Specific clinical and social profiles of patients who repeatedly utilised the services of a psychiatric emergency department have been identified. Our findings can be used to develop suitable structures to support and reintegrate FSUs into society and work life.

Sensation seeking correlates with increased white matter integrity of structures associated with visuospatial processing in healthy adults.

Introduction: The ability to process sensory information is an essential adaptive function, and hyper- or hypo-sensitive maladaptive profiles of responses to environmental stimuli generate sensory processing disorders linked to cognitive, affective, and behavioral alterations. Consequently, assessing sensory processing profiles might help research the vulnerability and resilience to mental disorders. The research on neuroradiological correlates of the sensory processing profiles is mainly limited to the young-age population or neurodevelopmental disorders. So, this study aims to examine the structural MRI correlates of sensory profiles in a sample of typically developed adults. Methods: We investigated structural cortical thickness (CT) and white matter integrity, through Diffusion Tensor Imaging (DTI), correlates of Adolescent/Adult Sensory Profile (AASP) questionnaire subscales in 57 typical developing subjects (34F; mean age: 32.7 ± 9.3). Results: We found significant results only for the sensation seeking (STS) subscale. Positive and negative correlations emerged with fractional anisotropy (FA) and radial diffusivity (RD) in anterior thalamic radiation, optic radiation, superior longitudinal fasciculus, corpus callosum, and the cingulum bundle. No correlation between sensation seeking and whole brain cortical thickness was found. Discussion: Overall, our results suggest a positive correlation between sensation seeking and higher white matter structural integrity in those tracts mainly involved in visuospatial processing but no correlation with gray matter structure. The enhanced structural integrity associated with sensation seeking may reflect a neurobiological substrate linked to active research of sensory stimuli and resilience to major psychiatric disorders like schizophrenia, bipolar disorder, and depression.

Linguistic profile automated characterisation in pluripotential clinical high-risk mental state (CHARMS) conditions: methodology of a multicentre observational study.

INTRODUCTION: Language is usually considered the social vehicle of thought in intersubjective communications. However, the relationship between language and high-order cognition seems to evade this canonical and unidirectional description (ie, the notion of language as a simple means of thought communication). In recent years, clinical high at-risk mental state (CHARMS) criteria (evolved from the Ultra-High-Risk paradigm) and the introduction of the Clinical Staging system have been proposed to address the dynamicity of early psychopathology. At the same time, natural language processing (NLP) techniques have greatly evolved and have been successfully applied to investigate different neuropsychiatric conditions. The combination of at-risk mental state paradigm, clinical staging system and automated NLP methods, the latter applied on spoken language transcripts, could represent a useful and convenient approach to the problem of early psychopathological distress within a transdiagnostic risk paradigm. METHODS AND ANALYSIS: Help-seeking young people presenting psychological distress (CHARMS+/- and Clinical Stage 1a or 1b; target sample size for both groups n=90) will be assessed through several psychometric tools and multiple speech analyses during an observational period of 1-year, in the context of an Italian multicentric study. Subjects will be enrolled in different contexts: Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DINOGMI), Section of Psychiatry, University of Genoa-IRCCS Ospedale Policlinico San Martino, Genoa, Italy; Mental Health Department-territorial mental services (ASL 3-Genoa), Genoa, Italy; and Mental Health Department-territorial mental services (AUSL-Piacenza), Piacenza, Italy. The conversion rate to full-blown psychopathology (CS 2) will be evaluated over 2 years of clinical observation, to further confirm the predictive and discriminative value of CHARMS criteria and to verify the possibility of enriching them with several linguistic features, derived from a fine-grained automated linguistic analysis of speech. ETHICS AND DISSEMINATION: The methodology described in this study adheres to ethical principles as formulated in the Declaration of Helsinki and is compatible with International Conference on Harmonization (ICH)-good clinical practice. The research protocol was reviewed and approved by two different ethics committees (CER Liguria approval code: 591/2020-id.10993; Comitato Etico dell'Area Vasta Emilia Nord approval code: 2022/0071963). Participants will provide their written informed consent prior to study enrolment and parental consent will be needed in the case of participants aged less than 18 years old. Experimental results will be carefully shared through publication in peer-reviewed journals, to ensure proper data reproducibility. TRIAL REGISTRATION NUMBER: DOI:10.17605/OSF.IO/BQZTN.

COVID-19 and psychiatric disorders: The impact of face masks in emotion recognition face masks and emotion recognition in psychiatry.

Since the outbreak of the COVID-19 pandemic, reading facial expressions has become more complex due to face masks covering the lower part of people's faces. A history of psychiatric illness has been associated with higher rates of complications, hospitalization, and mortality due to COVID-19. Psychiatric patients have well-documented difficulties reading emotions from facial expressions; accordingly, this study assesses how using face masks, such as those worn for preventing COVID-19 transmission, impacts the emotion recognition skills of patients with psychiatric disorders. To this end, the current study asked patients with bipolar disorder, major depressive disorder, schizophrenia, and healthy individuals to identify facial emotions on face images with and without facial masks. Results demonstrate that the emotion recognition skills of all participants were negatively influenced by face masks. Moreover, the main insight of the study is that the impairment is crucially significant when patients with major depressive disorder and schizophrenia had to identify happiness at a low-intensity level. These findings have important implications for satisfactory social relationships and well-being. If emotions with positive valence are hardly understood by specific psychiatric patients, there is an even greater requirement for doctor-patient interactions in public primary care.

Evidence of alterations of Beta-endorphin levels and Mu-opioid receptor gene expression in bipolar disorder.

Despite the well-recognized effects of endogenous opioids on mood and behavior, research on its role in bipolar disorder (BD) is still limited to small or anecdotal reports. Considering that Beta-endorphins (ß-END) and Mu-opioid receptors (MOR), in particular, have a crucial activity in affective modulation, we hypothesized their alteration in BD. A cross-sectional study was conducted. We compared: (1) BD type I (BD-I) patients (n = 50) vs healthy controls (n = 27), (2) two BD-I subject subgroups: manic (MAN; n = 25) vs depressed (DEP; n = 25) subjects. Plasma levels of ß-END and MOR gene expression in peripheral blood mononuclear cells were analyzed using ELISA Immunoassay qRT-PCR. We found that subjects with BD exhibited a significant upregulation of MOR gene expression and a decrease of ß-END (p<0.0001 for both). MAN display higher MOR levels than DEP (p<0.001) and HC (p<0.0001). Plasma levels of ß-END were lower in DEP compared to MAN (p<0.05) and HC (p<0.0001). The main limitations are the cross-sectional design and the lack of a group of euthymic subjects. Although preliminary, our results suggest a dysregulation of the endogenous opioid systems in BD. In particular, both MAN and DEP showed a reduction of ß-END levels, whereas MAN was associated with MOR gene overexpression.

Expression of type 1 cannabinoid receptor gene in bipolar disorder.

BACKGROUND: The Endocannabinoid System (ECBs) may have a crucial role in bipolar disorder (BD). Previous reports have not detected abnormalities in the expression of the cannabinoid receptor gene CNR1, encoding for CB1. However, we hypothesized that differentiating between mania and depression may uncover differences in CNR1 expression levels. METHODS: We recruited 44 subjects with BD type I (BD-I), in mania (n = 22) and depression (n = 22) and 25 Healthy Controls (HC). CNR1 gene expression was analyzed using a quantitative real-time polymerase chain reaction from peripheral blood mononuclear cells. Data were analyzed using frequentist non-parametric and Bayesian approaches (generalized location-scale model based on lognormal and gamma distributions). RESULTS: Using the frequentist non-parametric approach, the depression group had lower CNR1 expression compared to the mania group (p = 0.004). In addition, there was a negative correlation between CNR1 expression and Hamilton Depression Scale score (rho = -0.37; p = 0.007). Bayesian analyses further revealed that CNR1 expression in the mania group was higher and less variable than among HC (>95% probability), while CNR1 expression in the depression group was lower and more variable than among HC (100% probability). LIMITATIONS: Lack of participants with bipolar disorder in the euthymic phase, lack of toxicology screening and evaluation of CNR1 variants. CONCLUSION: CNR1 expression is higher and less variable in mania than in depression. It is highly probable that these differences also distinguish individuals in different illness phases from healthy controls. Future studies are needed to clarify the role of the endocannabinoid system in bipolar disorder.

COVID-19 pandemic impact on the therapeutic setting in Mental Health Services.

BACKGROUND: The new 2019 coronavirus disease (COVID-19) outbreak forced mental health providers to overcome their general reluctance about telematic assistance, shifting from a face-to-face approach to online therapy to promote continuity of care for psychiatric patients. METHODS: An ad-hoc web-based survey questionnaire assessing the impact of the COVID-19 pandemic on therapeutic setting in Mental Health Services was sent via email from March 15, 2021 to June 15, 2021 to mental health providers in Genova, Italy. The survey was anonymous and a free Google Forms® software was used. RESULTS: Two hundred nineteen mental health providers completed the survey, and the overall response rate (ORR) was 65%. During the COVID-19 pandemic period, the continuity of care was mainly guaranteed using electronic devices. Psychologists reported a higher availability of video call assistance service to guarantee continuity of care for psychiatric patients compared to psychiatrists and psychotherapists (p<0,001). Psychiatrists reported the lowest degree of satisfaction about this new telematic approach (p<0,01), while psychologists and to a lesser extent psychotherapists speculated to use it even in non-pandemic times (p=0,02). CONCLUSIONS: COVID-19 pandemic creates an opportunity to overcome normative, technological and cultural barriers to the use of online psychotherapy, showing the importance of adapting the therapeutic setting to both collective and individual needs. Despite initial concerns about its effectiveness and efficacy, a general degree of satisfaction was expressed by the majority of the mental health providers. Further efforts will be needed to enhance this new way of working and to train therapists with particular regard to those employed in the public health system.

High-lethality of suicide attempts associated with platelet to lymphocyte ratio and mean platelet volume in psychiatric inpatient setting.

OBJECTIVES: A wide range of potential psychosocial, biological, genetic and environmental factors may interact with each other in determining suicidal behaviours. The aim of this study was to evaluate several biological parameters referred to the complete blood count values in 259 suicide attempters (SA) and 164 non-suicide attempters (control group), according to the lethality of suicidal behaviour. METHODS: After attempting suicide, subjects were admitted to the emergency ward of the IRCCS Ospedale Policlinico San Martino and later to the section of Psychiatry from 1 January 2014 to 31 June 2019. Socio-demographic and clinical characteristics, as well as blood cells, were collected. RESULTS: Individuals with high-lethality suicide attempts had a higher number of neutrophils, mean platelet volume, neutrophil-lymphocyte ratio, platelet-lymphocyte ratio, and lower number of lymphocytes relative to both those with low-lethality suicide attempts and control group. After regression analysis, only the mean platelet volume and platelet to lymphocyte ratio resulted associated with a high-lethality suicide attempt (HLSA). CONCLUSIONS: Our findings provide potential and useful peripheral biological markers able to help clinicians in understanding the complex phenomenon of suicide. However, further studies are needed to confirm the present findings.

Cannabinoid use and self-injurious behaviours: A systematic review and meta-analysis.

BACKGROUND: The increasing availability of high-potency cannabis-derived compounds and the use of synthetic cannabinoids may be responsible for severe side effects like cognitive impairment, psychosis or self-injurious behaviours (SIB). In particular, SIB like non-suicidal self-injury (NSSI) and deliberate self-harm (DSH) raise growing concern as a possible consequence of cannabis use. However, the research to date has not addressed the relationship between cannabinoid use and SIB systematically. METHODS: We conducted a systematic review on PubMed up to March 2020, using search terms related to cannabinoids and SIB. RESULTS: The search yielded a total of 440 abstracts. Of those, 37 studies published between 1995 and 2020 were eligible for inclusion. Cannabinoid use was significantly associated with SIB at the cross-sectional (OR=1.569, 95%CI [1.167-2.108]) and longitudinal (OR=2.569, 95%CI [2.207-3.256]) level. Chronic use, presence of mental disorders, depressive symptoms, emotional dysregulation and impulsive traits might further increase the likelihood of self-harm in cannabis users. Synthetic cannabinoids may trigger highly destructive SIB mainly through the psychotomimetic properties of these compounds. CONCLUSION: Cannabinoid use was associated with an increased prevalence of self-injury and may act as a causative factor with a duration-dependent manner. Emotional regulation and behavioural impulsivity functions might crucially moderate this association. Future studies should further investigate the mechanisms underlying this association, while exploring potential therapeutic applications of substances modulating the endocannabinoid system.

Predictors of relapse in high lethality suicide attempters: a six-month prospective study.

BACKGROUND: This study is aimed to investigate the association between clinical, metabolic, inflammatory and environmental (photoperiod defined as daily sunlight exposure) parameters and suicide re-attempts after the index suicide attempt. Possible predictors of suicide re-attempts were also explored. METHODS: Overall, 432 subjects with suicide attempts, of which 79 relapsed within the following six months were included in this prospective study. We adopted the Joiner's definition of suicide lethality, as "the acquired ability to enact lethal self-injury". The Cox regression was used to test the association between the mentioned variables and Kaplan-Meier plots showed the trend of suicide re-attempts. RESULTS: Among participants, 30.8% committed a high-lethality suicide attempt. Cox regression confirmed the association between lifetime suicide attempts and number of suicide attempts in the study time-frame and suicide-reattempts. The longer photoperiod (Spring/Summer) was associated with suicide re-attempts, particularly patients with admission in June/July for the index event. Total cholesterol (TC), low-density lipo-protein cholesterol and c-reactive protein serum levels were significantly associated with suicide re-attempts but Cox regression confirmed only the association between lower TC serum levels and suicide re-attempt. LIMITATIONS: Patients' seasonal environment, psychological factors, presence of acute life-events fostering the suicidal crisis and detailed medical history have been not investigated. Findings were derived from a single psychiatric unit. CONCLUSIONS: Lifetime suicide attempts, higher number of previous suicide attempts, lower total cholesterol levels, and suicide attempt during longer photoperiod were significant predictors of suicide re-attempts. Further studies are needed in order to better characterize single- vs. multiple suicide attempter's profiles.

Tabagism and its management in Italian Psychiatric Intensive Care General Hospital Units / La gestione del tabagismo nei Servizi Psichiatrici di Diagnosi e Cura.

Aim: The aim of this paper was to survey the current management of the problem of smoking in our Mental Health Units, the structural characteristics of the units and how a total smoking ban would be perceived by doctors and nurses. Method: An 18 items survey about smoking habits of inpatients and department inner regulations was sent to the Head Physician and the Charge Nurse of all the Intensive Psychiatric Care General Hospital Units in Italy (228 units), in order to increase the answer rate and to investigate if the perception of the problem is eventually different between the two groups. Results: We collected 65 answers from Head Physician and 79 from Nurses. Both groups think that the smoking rates for inpatients are between 50-100%. Most of the units is locked, with or without an external space, so that a total smoking ban is considered difficult to achieve by both groups. A very high rate of units has no specific rooms for smokers. In most cases the issue management is solved by a self-regulation, based on collecting cigarettes and lighters and granting a limited number of cigarettes per day. Anyway, an institutional intervention would be appreciated especially by nurses, who seem to be even more involved in the issue management and both of groups seem to badly judge the lack of sources to face the eventual ban: particularly the possibility to offer nicotine replacement therapy, a cognitive-behavioural support and providing more staff education would all be considered useful to implement the success rate of the ban. By the way, both of groups seem skeptical about the possibility of a total smoking-free policy in Acute Psychiatric Hospital Units. Though, a difference in the problem's perception between the two groups has been noticed. Discussion: Smoking cessation remains a neglected area in psychiatry, in part due to misconceptions about smoking in the mentally ill, i.e. the idea that smoking cessation will exacerbate mental illness, aggression and suicide risk, even though these believes are not supported by evidence; in part due to the lack of institutional intervention and the structural deficiencies of the units.