Prenatal insomnia disorder may predict concurrent and postpartum psychopathology: A longitudinal study.

While insomnia symptoms may be a risk factor for mental disturbances, few studies evaluated "Insomnia Disorder" and its relationship with perinatal psychopathology. Pregnant women were recruited during their last routine assessment before being hospitalized for delivery during the 3rd trimester at the Gynaecological Unit of the University Hospital of Ferrara and Udine, Italy, from January 2022 to January 2023. Our assessment included baseline evaluation (T0), and evaluations at 1 month (T1) and 3 months (T2) in the postpartum period, with specific questionnaires for insomnia disorder, such as Sleep Condition Indicator, mood and anxiety symptoms and psychosocial functioning, such as Edinburgh Postnatal Depression Scale, Mood Disorder Questionnaire, State-Trait Anxiety Inventory, Work and Social Adjustment Scale. At T0, 181 pregnant women were included. Insomnia disorder affected 22.3% at T0, 23.5% at T1 and 16.2% at T2. Women with insomnia disorder at baseline were significantly more affected by concurrent anxiety and depressive symptoms, had higher bipolar diathesis and poorer psychosocial functioning in the perinatal period. Prenatal insomnia disorder predicted anxiety (T0: odds ratio 4.44, p << 0.001; T1: odds ratio 4.009, p = 0.042) and depressive symptoms (T0: odds ratio 2.66, p = 0.015; T1: odds ratio 11.20, p = 0.001; T2: odds ratio 12.50 p = 0.049) in both the prenatal and postnatal period. It also predicted poor psychosocial function during the prenatal (odds ratio 3.55, p = 0.003) and postpartum periods (T1: odds ratio 2.33, p = 0.004). Insomnia disorder is emerging as an important prenatal factor that may contribute to concurrent and postpartum psychopathology.

COVID-19-induced neuropsychiatric symptoms can persist long after acute infection: a 2-year prospective study of biobehavioral risk factors and psychometric outcomes.

OBJECTIVES: To assess the prevalence of neuropsychiatric symptoms 2 years after the COVID-19 acute phase and to identify biobehavioral risk factors. METHODS: This 2-year prospective study assessed adult individuals with COVID-19 via face-to-face interview and laboratory testing at onset, and via telephone interview at 2-year follow-up. Data collected included COVID-19 severity and management at onset, as well as depression, anxiety, insomnia, cognitive failure, and fatigue at follow-up using standardized assessment tools. RESULTS: Out of 1,067 screened COVID-19 patients, 230 completed the 2-year follow-up (female, 53.5%; aged>40, 80.9%; native Italian, 94.9%; medical comorbidity, 53.5%; chronic medication, 46.3%; moderate to severe COVID-19, 24.9%; hospital admission, 28.7%; ICU, 5.2%). At follow-up, 9.1% had anxiety, 11.3% depression, 9.1% insomnia, 18.3% cognitive failure, and 39.1% fatigue, of clinical relevance. Headache (OR = 2.49, 95% CI = 1.01-6.16, p = 0.048), dyspnea (OR = 2.55, 95% CI = 1.03-6.31, p = 0.043), and number of symptoms (OR = 1.23, 95% CI = 1.01-1.51, p = 0.047) at onset were associated with anxiety at follow-up; dyspnea at onset was associated with depression at follow-up (OR = 2.80, 95% CI = 1.22-6.41, p = 0.015); number of comorbidities at onset was associated with insomnia at follow-up (OR = 1.48, 95% CI = 1.06-2.08, p = 0.022); female gender (OR = 2.39, 95% CI = 1.14-5.00, p = 0.020) and number of symptoms (OR = 1.20, 95% CI = 1.02-1.42, p = 0.026) at onset was associated with cognitive failure at follow-up; number of comorbidities (OR = 1.33, 95% CI = 1.03-1.73, p = 0.029) and symptoms (OR = 1.19, 95% CI = 1.04-1.37, p = 0.013) and raised interleukin 6 levels (OR = 4.02, 95% CI = 1.42-11.36, p = 0.009) at onset was associated with fatigue at follow-up. CONCLUSIONS: COVID-19 survivors, especially if female, with preexisting health problems, and with a more severe acute phase, may present with long-lasting neuropsychiatric sequalae, urging interventions to sustain recovery particularly in these higher risk individuals.

Biobehavioral Interactions between Endocannabinoid and Hypothalamicpituitary- adrenal Systems in Psychosis: A Systematic Review.

BACKGROUND: The diathesis-stress paradigm and the cannabinoid-hypothesis have been proposed as possible pathophysiological models of schizophrenia. However, they have historically been studied independently of each other. OBJECTIVE: This PRISMA 2020-compliant systematic review aimed at reappraising the interplay between the hypothalamic-pituitary-adrenal (HPA) axis and the endocannabinoid (eCB) system in psychosis- spectrum disorder risk and outcome. METHODS: All pathophysiological and outcome clinical studies, concomitantly evaluating the two systems in psychosis-spectrum disorder risk and different stages of illness, were gathered from electronic databases (Pubmed, Web of Science, and Scopus), and discussed. RESULTS: 41 eligible outputs were extracted, focusing on at least a biological measure (9 HPA-related studies: 4 eCB-interventional, 1 HPA-interventional, 1 both HPA-interventional and non-interventional, 3 non-interventional; 2 eCB-related studies: non-interventional), environmental measures only (29 studies: 1 eCB- interventional, 28 non-interventional), and genetic measures (1 study: non-interventional). Independent contributions of aberrancies in the two systems to the physiopathology and outcome of psychosis were confirmed. Also, concomitant alterations in the two systems, either genetically defined (e.g., CNR1 genetic variation), biologically determined (e.g., dysfunctional HPA axis or endocannabinoid signaling), or behaviorally imputed (e.g., cannabis use, stress exposure, and response), were consistently reported in psychosis. Further, a complex biobehavioral perturbation was revealed not only within each system (e.g., cannabis use affecting the eCB tone, stress exposure affecting the HPA axis), but also across the two systems (e.g., THC affecting the HPA axis, childhood trauma affecting the endocannabinoid signaling). CONCLUSION: There is a need to concomitantly study the two systems' mechanistic contribution to psychosis in order to establish more refined biological relevance.

Lessons learnt while designing and conducting a longitudinal study from the first Italian COVID-19 pandemic wave up to 3 years.

BACKGROUND: Several scientific contributions have summarized the "lessons learnt" during the coronavirus disease 2019 (COVID-19) pandemic, but only a few authors have discussed what we have learnt on how to design and conduct research during a pandemic. The main intent of this study was to summarize the lessons learnt by an Italian multidisciplinary research group that developed and conducted a longitudinal study on COVID-19 patients infected during the first wave in March 2020 and followed-up for 3 years. METHODS: A qualitative research approach embedded into the primary CORonavirus MOnitoRing study (CORMOR) study was developed, according to the the consolidated criteria for reporting qualitative research. Multiple data collection strategies were performed: each member was invited to report the main lessons learnt according to his/her perspective and experience from the study design throughout its conduction. The narratives collected were summarized and discussed in face-to-face rounds. The narratives were then thematically analysed according to their main topic in a list that was resent to all members to check the content and their organization. The list of the final "lessons learnt" has been agreed by all members, as described in a detailed fashion. RESULTS: Several lessons were learnt while designing and conducting a longitudinal study during the COVID-19 pandemic and summarised into ten main themes: some are methodological, while others concern how to conduct research in pandemics/epidemics/infectious disease emergencies. CONCLUSIONS: The multidisciplinary approach, which also included patients' perspective, helped us to protect the consistency and quality of the research provided in pandemic times. The lesson learnt suggest that our research approach may benefit from changes in education, clinical practice and policies.

Psychological factors associated with vaccination hesitancy: an observational study of patients hospitalized for COVID-19 in a later phase of the pandemic in Italy.

Introduction: Vaccination against SARS-CoV-2 has been used to reduce the severity of COVID-19 disease and the incidence of new cases. However, a significant proportion of people have shown vaccination hesitancy. Methods: This study explored psychological factors related to vaccination hesitancy in a sample of Italian COVID-19 patients (N = 54), hospitalized during 2021, after vaccines had been made available and while the vaccination campaign was on-going. Consecutive patients, aged 18 or older, admitted to the hospital with a diagnosis of COVID-19 were assessed with a set of standardized measures. Results: In our sample, 48.1% was not vaccinated and 7.4% died within 6months after hospitalization, with a preponderance of deaths among non-vaccinated patients. Non-vaccinated participants had higher resilience scores at the CD-RISC-10 scale than vaccinated ones (33.6 ± 5.50 vs 28.6 ± 6.61; t40.2=+ 2.94, p = 0.005). No statistically significant differences were found between the two groups for any other measures. Discussion: Higher levels of resilience among non-vaccinated patients may reflect greater identity worth and self-esteem, in turn resulting in a decrease in vaccination likelihood. This finding may have important public health implications, as it indicates that specific psychological aspects, such as resilience, may result in vaccination hesitancy, with implications for hospitalization rates, and thus healthcare costs, as well as loss of lives.

Risk of psychosis in autism spectrum disorder individuals exposed to psychosocial stressors: A 9-year chart review study.

Psychosocial stressors have been suggested to precipitate psychotic episodes in patients with pre-existing psychosis and otherwise healthy subjects. However, such a risk has never been formally investigated in individuals with autism spectrum disorder (ASD). Sixty-nine autistic adolescents hospitalized for psychotic/manic symptoms (PSY) and other mental health issues (NPSY) over a 9-year period were compared with reference to their previous exposure to psychosocial stressors. ASD diagnoses satisfied the International Classification of Diseases (ICD)-10 criteria. Psychotic/manic symptom assessment followed the Kiddie Schedule for Affective Disorders and Schizophrenia (K-SADS). Psychosocial stressor exposure was collected separately at each admission. Preliminarily, univariate between-group comparisons were conducted. Then, a binomial model was adopted to investigate associations with previous exposure to psychosocial stressors. Results were reported with a change in AIC (ΔAIC). PSY patients presented with higher previous exposure to adverse life events (30.43% vs. 6.52%, OR = 6.079 [1.209, 40.926], p = 0.013) and school/work difficulties (30.43% vs. 8.70%, OR = 4.478 [0.984, 23.846], p = 0.034) than NPSY ones. Admissions for psychotic/manic symptoms occurred more likely in the context of family disturbances (OR = 2.275 [1.045, 5.045], p = 0.030) and adverse life events (OR = 3.489 [1.194, 11.161], p = 0.014). The fitted binomial model was found to be significant compared to the random effects model (ΔAIC = -1.962; χ2 10 = 21.96, p = 0.015), with the risk of presenting psychotic/manic symptoms being increased by family disturbances (z = +4.118) and school/work difficulties (z = +2.455). The results suggest a potential psychosis-inducing effect of psychosocial stressors in ASD, which has clinical and policy implications.

Consensus Panel Recommendations for the Pharmacological Management of Pregnant Women with Depressive Disorders.

INTRODUCTION: The initiative of a consensus on the topic of antidepressant and anxiolytic drug use in pregnancy is developing in an area of clinical uncertainty. Although many studies have been published in recent years, there is still a paucity of authoritative evidence-based indications useful for guiding the prescription of these drugs during pregnancy, and the data from the literature are complex and require expert judgment to draw clear conclusions. METHODS: For the elaboration of the consensus, we have involved the scientific societies of the sector, namely, the Italian Society of Toxicology, the Italian Society of Neuropsychopharmacology, the Italian Society of Psychiatry, the Italian Society of Obstetrics and Gynecology, the Italian Society of Drug Addiction and the Italian Society of Addiction Pathology. An interdisciplinary team of experts from different medical specialties (toxicologists, pharmacologists, psychiatrists, gynecologists, neonatologists) was first established to identify the needs underlying the consensus. The team, in its definitive structure, includes all the representatives of the aforementioned scientific societies; the task of the team was the evaluation of the most accredited international literature as well as using the methodology of the "Nominal Group Technique" with the help of a systematic review of the literature and with various discussion meetings, to arrive at the drafting and final approval of the document. RESULTS: The following five areas of investigation were identified: (1) The importance of management of anxiety and depressive disorders in pregnancy, identifying the risks associated with untreated maternal depression in pregnancy. (2) The assessment of the overall risk of malformations with the antidepressant and anxiolytic drugs used in pregnancy. (3) The evaluation of neonatal adaptation disorders in the offspring of pregnant antidepressant/anxiolytic-treated women. (4) The long-term outcome of infants' cognitive development or behavior after in utero exposure to antidepressant/anxiolytic medicines. (5) The evaluation of pharmacological treatment of opioid-abusing pregnant women with depressive disorders. CONCLUSIONS: Considering the state of the art, it is therefore necessary in the first instance to frame the issue of pharmacological choices in pregnant women who need treatment with antidepressant and anxiolytic drugs on the basis of data currently available in the literature. Particular attention must be paid to the evaluation of the risk/benefit ratio, understood both in terms of therapeutic benefit with respect to the potential risks of the treatment on the pregnancy and on the fetal outcome, and of the comparative risk between the treatment and the absence of treatment; in the choice prescription, the specialist needs to be aware of both the potential risks of pharmacological treatment and the equally important risks of an untreated or undertreated disorder.

Questioning the role of palmitoylethanolamide in psychosis: a systematic review of clinical and preclinical evidence.

Introduction: The endocannabinoid (eCB) system disruption has been suggested to underpin the development of psychosis, fueling the search for novel, better-tolerated antipsychotic agents that target the eCB system. Among these, palmitoylethanolamide (PEA), an N-acylethanolamine (AE) with neuroprotective, anti-inflammatory, and analgesic properties, has drawn attention for its antipsychotic potential. Methods: This Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020-compliant systematic review aimed at reappraising all clinical and preclinical studies investigating the biobehavioral role of PEA in psychosis. Results: Overall, 13 studies were eligible for data extraction (11 human, 2 animal). Observational studies investigating PEA tone in psychosis patients converged on the evidence for increased PEA plasma (6 human) and central nervous system (CNS; 1 human) levels, as a potential early compensatory response to illness and its severity, that seems to be lost in the longer-term (CNS; 1 human), opening to the possibility of exogenously supplementing it to sustain control of the disorder. Consistently, PEA oral supplementation reduced negative psychotic and manic symptoms among psychosis patients, with no serious adverse events (3 human). No PEA changes emerged in either preclinical psychosis model (2 animal) studied. Discussion: Evidence supports PEA signaling as a potential psychosis biomarker, also indicating a therapeutic role of its supplementation in the disorder. Systematic review registration: https://doi.org/10.17605/OSF.IO/AFMTK.

COVID-19 Survivors Are Still in Need of Neuropsychiatric Support Two Years after Infection.

COVID-19 survivors have been reported to be at risk of long-term neuropsychiatric sequalae; however, prospective evidence in this regard is lacking. We prospectively assessed the occurrence of mental-health-domain-related symptoms over a 24-month period following COVID-19 onset in a cohort of 230 patients. Of them, 36.1% were still presenting with at least one symptom 24 months later. Across the study period, a significant reduction in overall symptoms from the onset was observed (p < 0.001); however, symptom prevalence was unchanged between the 12- and 24-month follow-ups across most symptomatic domains. At the 24-month follow-up, mental-health-domain-related symptoms only were higher than at the onset and were the most frequently reported symptoms. Dyspnea at the onset predicted both symptoms of psychiatric disorders (OR = 3.26, 95% CI = 1.22-8.70, and p = 0.019) and a lack of concentration and focus (OR = 3.17, 95% CI = 1.40-7.16, and p = 0.005) 24 months post-infection, with the number of comorbidities at the onset also predicting the occurrence of a lack of concentration and focus (OR = 1.52, 95% CI = 1.12-2.08, and p = 0.008). The findings of this study may have important public health implications, as they underlie the fact that COVID-19 survivors are still in need of neuropsychiatric support two years after infection.

On the O2 "Surfactant" Effect during Ag/SiO2 Magnetron Sputtering Deposition: The Point of View of In Situ and Real-Time Measurements.

The use of gaseous species has been proposed in the literature to counteract the three-dimensional growth tendency of noble metals on dielectric substrates and favor an earlier percolation without compromising electrical properties. This "surfactant" effect is rationalized herein in the case of O2 presence during magnetron sputtering deposition of Ag films on SiO2. In situ and real-time techniques (X-ray photoemission, film resistivity, UV-visible optical spectroscopy) and ex situ characterizations (X-ray diffraction and transmission electron microscopy) were combined to scrutinize the impact of O2 addition in the gas flow (%O2), revealing three regimes of evolution of film resistivity, morphology, structure, and chemical composition. At low oxygen flow conditions (%O2 < 4), the observed drastic decrease of the percolation threshold is assigned to a combination of (i) a change in nanoparticle density, wetting, and crystallographic texture and (ii) a delayed coalescence effect. The driving force is ascribed to the presence of specific adsorbed oxygen moieties, the nature of which starts evolving at intermediate oxygen flow conditions (10 ≤ %O2 < 20). At high oxygen flow (20 ≤ %O2 < 40), the found detrimental impact on film resistivity is assigned to an actual oxidation in the form of a Ag2O-like poorly crystallized compound. For all %O2, a composition gradient is observed across the film thickness, with a more metallic Ag at the substrate interface. A correlation between percolation and the nature of the detected O moieties is observed. In parallel to an oxygen spillover mechanism, this gradient can be explained by the competition between different surface processes occurring before percolation, namely, aggregation, metal oxidation, and substrate reactivity. Such findings pave the way to a rational use of O2 as a modifier for Ag growth.

Mentalization in young patients undergoing opioid agonist treatment: Implications for clinical management.

Background: Mentalization is the ability to use internal mental states to manage and understand one's own and others' behavior. Inefficient mentalization has been associated to poor neuropsychological outcomes, including substance use disorder (SUD) and addiction. However, studies primarily investigating mentalization in SUD are lacking. Methods: Using the Reflective Functioning Questionnaire (RFQ), the Measurements in the Addictions for Triage and Evaluation, version 2.1 (MATE-IT-2.1), and the Mini International Neuropsychiatric Interview, 7th edition (MINI-7), an outpatient assessment investigated inefficient mentalization (i.e., 'hypo-mentalization' or 'uncertainty': concrete thinking with poor attribution of mental states; 'hyper-mentalization' or 'certainty': rigid and biased attribution of mental states) and socio-demographic and clinical characteristics, including SUD-related symptoms and any other psychiatric comorbidity, among opioid addiction (OA) patients in Opioid Agonist Treatment (OAT). Results: Thirty-seven consecutive OA patients in OAT (female, 45.9 %; age, M ± SD, 24.3 ± 3.55) were recruited. Patients' mentalization differed from normative data, in terms of higher uncertainty and lower certainty scores. Also, higher uncertainty score was found among younger patients and in those with the most severe SUD in terms of craving and need for care. Finally, lower certainty score was found in those with a more severe substance abuse, previous contacts with pediatric mental-health services, and receiving a therapeutic community support. Conclusions: OA patients with inefficient mentalization present with a higher burden in terms of SUD severity, comorbidities, psychosocial disabilities, and service use, with important public health implications. Interventions targeting mentalization may have positive repercussions in preventing SUD, mitigating its severity, and containing its healthcare and social costs.

Changes in Revolving-Door Mental Health Hospitalizations during the COVID-19 Pandemic: A 5-Year Chart Review Study.

This study assessed changes in revolving-door (RD) mental health hospitalizations during the COVID-19 pandemic. A 5-year retrospective hospital chart review was performed, collecting revolving-door hospitalization, sociodemographic, and clinical data. Out of 1036 patients, 5.69% had RD hospitalizations, which accounted for 10.38% of all recorded hospitalizations. Further, a higher number of RD hospitalizations occurred following the pandemic outbreak, which is unlikely to have been a result of the confounding effect of trimester and month of hospitalization. Finally, several sociodemographic and clinical characteristics recurred more frequently in the context of RD hospitalizations, such as being younger, being compulsorily admitted, being an absconding patient, and being referred by a public service. Certain diagnostic categories occurred more frequently among RD hospitalizations, including psychotic, personality, and substance use disorders, as well as intellectual disability. Patients with specific characteristics are more likely to incur in RD hospitalizations, requiring the implementation of supportive treatment plans, especially following the pandemic outbreak.

Confirmation of increased and more severe adolescent mental health-related in-patient admissions in the COVID-19 pandemic aftermath: A 2-year follow-up study.

COVID-19 pandemic may have affected youth's mental wellbeing. Youth admissions for mental health emergencies over the 2-year period following the COVID-19 outbreak (March 2020-February 2022) were compared to those occurring in the same period of 2018-2020, with reference to individual and clinical data. The study identified 30 admissions in the pre-pandemic period and 65 (+116.7%) in the post-pandemic period, with the latter being younger, less likely to have a personal psychiatric history, and more likely to receive psychopharmacological treatment. A higher likelihood of earlier, ex novo psychiatric manifestations, requiring medication to reach clinical stability, in the post-COVID era, is suggested.

Current models of insomnia disorder: a theoretical review on the potential role of the orexinergic pathway with implications for insomnia treatment.

Insomnia disorder is considered as a stress-related disorder associated with hyperarousal, stress and emotion dysregulation and the instability of the 'flip-flop' switch system. The orexinergic system is well known for its key role in sleep and arousal processes but also in the allostatic system regulating stress and emotions and may thus be of major interest for insomnia and its treatment. Accordingly, we discuss the potential role of orexins on sleep processes, brain systems modulating stress and emotions with potential implications for insomnia pathophysiology. We reviewed available data on the effect of dual orexin receptor antagonists (DORAs) on sleep and brain systems modulating stress/emotions with implications for insomnia treatment. We present our findings as a narrative review. Few data in animals and humans have reported that disrupted sleep and insomnia may be related to the overactivation of orexinergic system, while some more consistent data in humans and animals reported the overactivation of orexins in response to acute stress and in stress-related disorders. Taken together these findings may let us hypothesise that an orexins overactivation may be associated with stress-related hyperarousal and the hyperactivation of arousal-promoting systems in insomnia. On the other hand, it is possible that by rebalancing orexins with DORAs we may regulate both sleep and allostatic systems, in turn, contributing to a 'switch off' of hyperarousal in insomnia. Nevertheless, more studies are needed to clarify the role of the orexin system in insomnia and to evaluate the effects of DORAs on sleep, stress and emotions regulating systems.

Prevalence and Risk Factors for Absconding from an Open-Door, No-Restraint Inpatient Psychiatric Unit: A Single-Center Study in Italy.

Absconding from inpatient psychiatric services has been associated with poor outcomes, putting the patient and community at risk and prolonging the recovery process. A retrospective study investigated the absconding rates and risk factors among patients admitted to an open-door, no-restraint inpatient psychiatric unit. Overall, the absconding rate was 4.5%, and the relative risk of absconding was higher for male, younger, and non-Caucasian patients as well as for those who had already absconded, were unknown to health services, compulsorily admitted, admitted for substance abuse, and in the first days of hospitalization. The findings of this study may have important public health implications.

A machine learning approach on whole blood immunomarkers to identify an inflammation-associated psychosis onset subgroup.

Psychosis onset is a transdiagnostic event that leads to a range of psychiatric disorders, which are currently diagnosed through clinical observation. The integration of multimodal biological data could reveal different subtypes of psychosis onset to target for the personalization of care. In this study, we tested the existence of subgroups of patients affected by first-episode psychosis (FEP) with a possible immunopathogenic basis. To do this, we designed a data-driven unsupervised machine learning model to cluster a sample of 127 FEP patients and 117 healthy controls (HC), based on the peripheral blood expression levels of 12 psychosis-related immune gene transcripts. To validate the model, we applied a resampling strategy based on the half-splitting of the total sample with random allocation of the cases. Further, we performed a post-hoc univariate analysis to verify the clinical, cognitive, and structural brain correlates of the subgroups identified. The model identified and validated two distinct clusters: 1) a FEP cluster characterized by the high expression of inflammatory and immune-activating genes (IL1B, CCR7, IL12A and CXCR3); 2) a cluster consisting of an equal number of FEP and HC subjects, which did not show a relative over or under expression of any immune marker (balanced subgroup). None of the subgroups was related to specific symptoms dimensions or longitudinal diagnosis of affective vs non-affective psychosis. FEP patients included in the balanced immune subgroup showed a thinning of the left supramarginal and superiorfrontal cortex (FDR-adjusted p-values < 0.05). Our results demonstrated the existence of a FEP patients' subgroup identified by a multivariate pattern of immunomarkers involved in inflammatory activation. This evidence may pave the way to sample stratification in clinical studies aiming to develop diagnostic tools and therapies targeting specific immunopathogenic pathways of psychosis.

Using Metaphors to Understand Suffering in COVID-19 Survivors: A Two Time-Point Observational Follow-Up Study.

Accumulating evidence indicates that the COVID-19 pandemic carries risks to psychological health and represents a collective traumatic experience with consequences at the social, economic, and health levels. The primary aim of this study was to collect ongoing COVID-19 survivors' pandemic-related experiences as expressed through the use of metaphors; the secondary aim was to explore socio-demographic variables associated with the metaphor orientation as negative, positive or neutral. An observational follow-up survey was conducted and reported according to the STROBE guidelines. Patients ≥ 18 years, who were treated for COVID-19 during the first wave (March/April 2020) and who were willing to participate in a telephone interview were involved and asked to summarize their COVID-19 experience as lived up to 6 and 12 months in a metaphor. A total of 339 patients participated in the first (6 months) and second (12 months) data collection. Patients were mainly female (51.9%), with an average age of 52.9 years (confidence interval, CI 95% 51.2−54.6). At 6 months, most participants (214; 63.1%) used a negative-oriented metaphor, further increasing at 12 months (266; 78.5%), when they used fewer neutral-/positive-oriented metaphors (p < 0.001). At the 6-month follow-up, only three individual variables (female gender, education, and experiencing symptoms at the COVID-19 onset) were significantly different across the possible metaphor orientation; at 12 months, no individual variables were significantly associated. This study suggests increasingly negative lived experiences over time and the need for personalized healthcare pathways to face the long-term traumatic consequences of COVID-19.

Poor sleep quality may contribute to dysfunctional illness perception, physical and emotional distress in hospitalised patients: results of a national survey of the Italian Society of Consultation-Liaison Psychiatry.

Distress associated with physical illness is a well-known risk factor for adverse illness course in general hospitals. Understanding the factors contributing to it should be a priority and among them dysfunctional illness perception and poor sleep quality may contribute to it. As poor sleep quality is recognised as a major risk factor for health problems, we aimed to study its association with illness perception and levels of distress during hospitalisation. This cross-sectional study included a consecutive series of 409 individuals who were hospitalised in medical and surgical units of different hospitals located throughout the Italian national territory and required an assessment for psychopathological conditions. Sleep quality was assessed with the Pittsburgh (Sleep Quality Index), emotional and physical distress with the Edmonton Symptom Assessment System (ESAS), and illness perception with the Brief Illness Perception Questionnaire (BIPQ). Differences between groups, correlations and mediations analyses were computed. Patients with poor sleep quality were more frequently females, with psychiatric comorbidity, with higher scores in the ESAS and BIPQ. Poor sleep quality was related to dysfunctional illness perception, and to both emotional and physical distress. In particular, by affecting cognitive components of illness perception, poor sleep quality may, directly and indirectly, predict high levels of distress during hospitalisation. Poor sleep quality may affect >70% of hospitalised patients and may favour dysfunctional illness perception and emotional/physical distress.Assessing and treating sleep problems in hospitalised patients should be included in the routine of hospitalised patients.

Mental health symptoms one year after acute COVID-19 infection: Prevalence and risk factors.

Introduction: Emerging evidence suggests that mental health symptoms in COVID-19 survivors are higher than expected, possibly indicating that such symptoms are more likely to develop post-infection than just persist as a residual component of the acute phase. It is thus imperative to investigate the potential development of a post-COVID mental health syndrome in the longer-term and identify its risk factors. Material and methods: A prospective study investigated mental health symptoms associated with COVID-19 and its determinants over a 12-month period following the disease onset in all consecutive adult inpatients and outpatients with COVID-19 attending a tertiary referral hospital from March to May 2020. Results: A total of 479 patients (female, 52.6%) were followed-up for 12 months after COVID-19 onset. Of them, 47.2% were still presenting with at least one symptom. While most symptoms subsided as compared to COVID-19 onset (all p < 0.001), a significant increase was observed only for symptoms of psychiatric disorders (10.2%) and lack of concentration and focus (20%; all p < 0.001). Patients presenting with symptoms related to multiple body systems 12 months after contracting COVID-19 (all p ≤ 0.034) were more likely to suffer from mental health domain-related symptoms at follow-up. Also, a higher risk of presenting with lack of concentration and focus 12 months post infection was found in those suffering of psychiatric symptoms at COVID-19 onset (p = 0.005). Conclusions: Findings of this study may have important public health implications, as they underlie the increased need for mental health support in COVID-19 survivors.

Introducción: Nuevas evidencias sugieren que los síntomas de salud mental en los supervivientes de COVID-19 son mayores de lo esperado, lo que posiblemente indica que es más probable que dichos síntomas se desarrollen después de la infección en vez de sólo persistir como componente residual de la fase aguda. Por lo tanto, es imperativo investigar el posible desarrollo de un síndrome de salud mental post-COVID a largo plazo e identificar sus factores de riesgo. Materiales y métodos: Un estudio prospectivo investigó los síntomas de salud mental asociados a la COVID-19 y sus determinantes durante un periodo de 12 meses tras el inicio de la enfermedad en todos los pacientes adultos consecutivos con COVID-19, hospitalizados y ambulatorios, que acudieron a un hospital de tercer nivel entre marzo y mayo de 2020. Resultados: Un total de 479 pacientes (mujeres, 52,6%) fueron seguidos durante 12 meses después del inicio de COVID-19. De ellos, el 47,2% seguía presentando al menos un síntoma. Mientras que la mayoría de los síntomas disminuyeron en comparación con el inicio de la COVID-19 (todos p < 0,001), se observó un aumento significativo solamente de los síntomas de los trastornos psiquiátricos (10,2%) y la falta de concentración y enfoque (20%; todos p < 0,001). Los pacientes que presentaban síntomas relacionados con múltiples sistemas del cuerpo 12 meses después de contraer la COVID-19 (todos p ≤ 0,034) tenían más probabilidades de sufrir síntomas relacionados con el dominio de la salud mental en el seguimiento. Además, se encontró un mayor riesgo de presentar falta de concentración y enfoque 12 meses después de la infección en los que sufrían síntomas psiquiátricos al inicio de COVID-19 (p = 0,005). Conclusiones: Los resultados de este estudio pueden tener importantes implicaciones para la salud pública, ya que subyacen a la mayor necesidad de apoyo a la salud mental de los supervivientes de COVID-19.

Therapeutic effect of palmitoylethanolamide in cognitive decline: A systematic review and preliminary meta-analysis of preclinical and clinical evidence.

Cognitive decline is believed to be associated with neurodegenerative processes involving excitotoxicity, oxidative damage, inflammation, and microvascular and blood-brain barrier dysfunction. Interestingly, research evidence suggests upregulated synthesis of lipid signaling molecules as an endogenous attempt to contrast such neurodegeneration-related pathophysiological mechanisms, restore homeostatic balance, and prevent further damage. Among these naturally occurring molecules, palmitoylethanolamide (PEA) has been independently associated with neuroprotective and anti-inflammatory properties, raising interest into the possibility that its supplementation might represent a novel therapeutic approach in supporting the body-own regulation of many pathophysiological processes potentially contributing to neurocognitive disorders. Here, we systematically reviewed all human and animal studies examining PEA and its biobehavioral correlates in neurocognitive disorders, finding 33 eligible outputs. Studies conducted in animal models of neurodegeneration indicate that PEA improves neurobehavioral functions, including memory and learning, by reducing oxidative stress and pro-inflammatory and astrocyte marker expression as well as rebalancing glutamatergic transmission. PEA was found to promote neurogenesis, especially in the hippocampus, neuronal viability and survival, and microtubule-associated protein 2 and brain-derived neurotrophic factor expression, while inhibiting mast cell infiltration/degranulation and astrocyte activation. It also demonstrated to mitigate ß-amyloid-induced astrogliosis, by modulating lipid peroxidation, protein nytrosylation, inducible nitric oxide synthase induction, reactive oxygen species production, caspase3 activation, amyloidogenesis, and tau protein hyperphosphorylation. Such effects were related to PEA ability to indirectly activate cannabinoid receptors and modulate proliferator-activated receptor-α (PPAR-α) activity. Importantly, preclinical evidence suggests that PEA may act as a disease-modifying-drug in the early stage of a neurocognitive disorder, while its protective effect in the frank disorder may be less relevant. Limited human research suggests that PEA supplementation reduces fatigue and cognitive impairment, the latter being also meta-analytically confirmed in 3 eligible studies. PEA improved global executive function, working memory, language deficits, daily living activities, possibly by modulating cortical oscillatory activity and GABAergic transmission. There is currently no established cure for neurocognitive disorders but only treatments to temporarily reduce symptom severity. In the search for compounds able to protect against the pathophysiological mechanisms leading to neurocognitive disorders, PEA may represent a valid therapeutic option to prevent neurodegeneration and support endogenous repair processes against disease progression.