An e-Health Psychoeducation Program for Managing the Mental Health of People with Bipolar Disorder during the COVID-19 Pandemic: A Randomized Controlled Study.

Background: Social rhythm dysregulation has been identified as a determining factor in bipolar disorder (BD) relapses. It directly impacts individuals' quality of life (QoL). This study aims to present preliminary data on the efficacy of an e-health psychoeducational intervention for BD for improving clinical outcomes. Methods: This study used an open-label, crossover, randomized controlled trial design. The inclusion criteria consisted of a BD diagnosis, affiliation with the Consultation Psychiatry and Psychosomatic Center at the University Hospital in Cagliari, Italy, age over 18, and the obtaining of informed consent. Anxiety and depressive symptoms, QoL, and social and biological rhythms were measured using standardized instruments validated in Italian. Results: A total of 36 individuals were included in the experimental group (EG) and 18 in the control group (CG). The final sample consisted of 25 in the EG and 14 in the CG. A statistically significant improvement in QoL was found in the EG post-treatment (p = 0.011). Significant correlations were found between QoL and the dysregulation of biorhythms in the EG at T0 (p = 0.0048) and T1 (p = 0.0014). Conclusions: This study shows that, during extreme distress, an e-health group psychoeducation intervention for people with BD could significantly improve the perception of QoL. The results must be confirmed by studies conducted with larger-sized samples.

Temporomandibular Disorders Management-What's New? A Scoping Review.

Temporomandibular disorders include various conditions that impact the masticatory system, affecting its structure, function, or physiology. Clinicians face a complex array of therapeutic options when treating this group of diseases, emphasizing the importance of evaluating the current evidence to guide decisions in patient care. The main objective of this article is to conduct a scoping review on the available treatment approaches to manage temporomandibular disorders (TMDs). An extensive search of the literature was performed on Scopus, Pubmed, Embase, and Web of Science. Systematic reviews published in the last 5 years were considered. Out of the 2183 publications identified, 109 studies were included in this review. Among them, 39 articles focused on the non-invasive approach, while 120 delved into the minimally invasive approach, and 15 explored the surgical approach. Non-invasive or conservative approaches like cognitive-behavioral therapy, physical therapy, and acupuncture offer effective pain management and functional improvements in TMDs. Emerging treatments offer promising alternatives for treating these disorders. Surgery should be reserved for severe cases, with conservative therapies used in conjunction with invasive procedures for optimal patient outcomes.

Effectiveness of Highly Purified Cannabidiol in Refractory and Super-Refractory Status Epilepticus: A Case Series.

INTRODUCTION: Refractory and super-refractory status epilepticus are medical emergencies that must be promptly treated in consideration of their high mortality and morbidity rate. Nevertheless, the available evidence of effective treatment of these conditions is scarce. Among novel antiseizure medications (ASMs), highly purified cannabidiol (hpCBD) has shown noteworthy efficacy in reducing seizures in Lennox-Gastaut syndrome (LGS), Dravet syndrome (DS), and Tuberous Sclerosis Complex (TSC). CASE PRESENTATION: Here, we present two cases of effective use of hpCBD in both refractory and super- refractory status epilepticus. The administration of the nasogastric tube permitted the resolution of status epilepticus without adverse events. At 6-month follow-up, both patients were on hpCBD treatment, which continued to be efficacious for treating seizures. CONCLUSION: According to our experience, hpCBD should be taken into consideration as an add-on therapy of RSE and SRSE while also considering the possibility of maintaining this treatment during the follow-up of patients. However, more studies and real-world experiences are needed to better understand its effectiveness in this setting and the interaction with other ASMs.

Implementation of the World Health Organization's QualityRights initiative in Ghana: an overview.

BACKGROUND: Globally, human rights violations experienced by persons with psychosocial, intellectual or cognitive disabilities continue to be a concern. The World Health Organization's (WHO) QualityRights initiative presents practical remedies to address these abuses. This paper presents an overview of the implementation of the initiative in Ghana. AIMS: The main objective of the QualityRights initiative in Ghana was to train and change attitudes among a wide range of stakeholders to promote recovery and respect for human rights for people with psychosocial, intellectual and cognitive disabilities. METHOD: Reports of in-person and online training, minutes of meetings and correspondence among stakeholders of the QualityRights initiative in Ghana, including activities of international collaborators, were analysed to shed light on the implementation of the project in Ghana. RESULTS: In-person and online e-training on mental health were conducted. At the time of writing, 40 443 people had registered for the training, 25 416 had started the training and 20 865 people had completed the training and obtained a certificate. The team conducted 27 in-person training sessions with 910 people. The successful implementation of the project is underpinned by a committed partnership among stakeholders, strong leadership from the coordinating agency, the acceptance of the initiative and the outcome. A few challenges, both in implementation and acceptance, are discussed. CONCLUSIONS: The exposure of the WHO QualityRights initiative to a substantial number of key stakeholders involved in mental healthcare in Ghana is critical to reducing human rights abuses for people with psychosocial, intellectual and cognitive disabilities.

The long-term adherence following the end of Community Treatment Order: A systematic review.

BACKGROUND: The community treatment order (CTO) is designed to deliver mental healthcare in the community and has been introduced in around 75 jurisdictions worldwide. It constitutes a legal obligation in which individuals with severe mental illness must adhere to out-of-hospital treatment plans. Despite intense criticism and the debated nature of published evidence, it has emerged as a clinical and policy response to frequent hospital readmissions and to enhance adherence in cases where there is refusal of pharmacological treatments. This systematic review outlines findings on CTO long-term adherence, after mandatory outpatient treatment has ended, in studies that include people with psychiatric disorders. METHOD: Following PRISMA guidelines, we performed a review of published articles from PubMed, PsycINFO, EMBASE, and CINAHL up to January 15, 2023. We included studies that assessed adherence after CTO ends. The study is registered with PROSPERO number CRD42022360879. RESULTS: Six independent studies analyzing the main indicators of long adherence: engagement with services and medication adherence, were included. The average methodological quality of the studies included is fair. Long-term adherence was assessed over a period ranging from 11 to 28 months. Only two studies reported a statistically significant improvement. Regarding the remaining studies, no positive correlation was observed, except for certain subgroup samples, while in one study, medication adherence decreased. CONCLUSION: Scientific evidence supporting the hypothesis that CTO has a positive role on long-term adherence post-obligation is currently not sufficient. Given the importance of modern recovery-oriented approaches and the coercive nature of compulsory outpatient treatment, it is necessary that future studies ensure the role of CTO in effectively promoting adherence.

Stress, Dysregulation of Rhythms, and Bipolar Disorder: A Challenging Field of Research.

Clarifying the mechanisms by which circadian rhythms regulate biology is a central issue in directing life choices in the immediate future and presents an interesting challenge for current scientific research [...].

The efficacy of heart rate variability biofeedback training on sleep disorders and impact of fibromyalgia: Results of a phase II randomized controlled trial.

OBJECTIVE: Fibromyalgia syndrome (FMs) is a chronic, musculoskeletal pain disorder characterized by sleep disturbances, fatigue, and cognitive dysfunction. Heart rate variability biofeedback (HRV-BF) aiming to improve self-regulation and strengthen the parasympathetic nervous system has been shown to be effective in several pain syndromes, but its efficacy in FMs has not been adequately investigated. This Phase II trial aimed to assess the feasibility and preliminary measurement of the improvement induced by HRV-BF in FMs. METHODS: Sixty-four patients with FMs were recruited. Patients were randomly assigned to either the experimental group (EG) or the control group (CG). The EG received 10 HRV-BF training sessions in addition to pharmacological standard therapy. The CG received standard therapies for 10 weeks. The FMs impact on daily life, sleep regularity, sense of coherence, depression symptoms and pain has been assessed as primary outcomes, quality of life as secondary. RESULT: 23 (71.9%) of EG patients completed the intervention and 20 (62.5%) of the CG were re-evaluated at time T1. No side effects were reported. It was not found any statistical differences between groups over time in primary and secondary outcomes. CONCLUSIONS: The HRV-BF intervention did not demonstrate efficacy in both primary and secondary outcomes. However, it is quite feasible in terms of drop-out rate and side effects. Further studies with larger sample sizes are needed to determine its actual efficacy. CLINICALTRIALS: gov with code: NCT04121832.

The Stability of Social and Behavioral Rhythms and Unexpected Low Rate of Relevant Depressive Symptoms in Old Adults during the COVID-19 Pandemic.

Background: The disruption of social rhythms was found to be associated with depressive disorders during the COVID-19 pandemic; lower rates of these disorders were surprisingly found in old adults. The present study aims to verify the stability of social rhythms during lockdown in a sample of elderly people. Methods: Controlled cohort study (secondary analyses) of a previous randomized-controlled trial with the first evaluation in April 2019 (T0) and then 48 weeks later (T1) during the lockdown. The regulation of social and behavioral rhythms was measured through the Brief Social Rhythms Scale (BSRS); the Patient Health Questionnaire-9 (PHQ9) was adopted to detect relevant depressive symptoms. Results: 93 elderlies (73.36 ± 4.97 years old, 50.5% females) were evaluated at T0 and T1. Neither the total score of BSRS nor any of the 10 items showed a statistically significant difference comparing the two survey periods. The frequency of relevant depressive symptoms was 5.3% at T0 and 6.4% at T1 (OR = 0.8, CI95% 0.2-24). Conclusions: Among elderlies who did not show an increased risk of depression during the lockdown, social and behavioral rhythms remained exceptionally stable during the same period. Considering previous evidence about rhythms dysregulation preceding depression, their stability may be considered a factor of resilience.

Dysregulation of mood, energy, and social rhythms syndrome (DYMERS): A working hypothesis.

A syndrome centered on the dysregulation of behavioral rhythms (DBR) is discussed. Recent pandemic brought to observe: (1) Having a DBR affecting sleep patterns, eating habits, and social interactions, before the lockdown period, was a determinant for depressive episodes during the lockdown; (2) In tighter lockdowns, DBR triggered depressive episodes in bipolar patients; (3) DBR in healthcare workers under pressure was a determinant of burnout; (4) DBR influenced the course of chronic diseases by altering immune responses. In addition, it was found that scoring positive on the Mood Disorder Questionnaire (MDQ) was closely associated with the dysregulation of sleep rhythms. MDQ is a screening tool for bipolar disorder (BD), criticized for detecting too many false positives. Studies showed that positivity to the MDQ implied a severe impairment of quality of life even in people without psychiatric diagnoses. According to this evidence, three different hyperactivation levels could be proposed (from normality to pathology): firstly, an adaptive increase in energy (e.g. athletes performing well); secondly, a DBR determined from the continuous stimulation of stress hormones, with possible positive scores on the MDQ without a diagnosis of bipolar disorder, like in burnout syndromes and, thirdly, hyperactivity during manic episodes. The Dysregulation of Mood, Energy, and Social Rhythms Syndrome (DYMERS), the second level of the scale, is proposed as a working hypothesis. DYMERS is also seen as a vulnerable condition that may evolve in other disorders (including BD) according to the individual susceptibility (including genetic predisposition) and the specific nature/level of the stressor.

Mental Health Professionals' Perception of Respect for Human Rights and Organizational Well-Being in Three Countries of South America.

The respect for human rights in mental health care services significantly contributes to organizational well-being and is evolving into an actual benchmark of quality standards. This study assesses the perception of the respect for human rights for users and staff, as well as organizational and job satisfaction among mental health professionals in three South American countries, through the well-being at work and respect for human rights (WWRR) questionnaire and assesses whether there are significant differences. Seven mental health facilities in Argentina, Colombia, and Peru were involved in this observational study. The sample comprised 310 mental health professionals. The three countries exhibited differences in WWRR, particularly in the staff's satisfaction with resources for care (η2 = 0.166) and staff's satisfaction with organizational aspects (η2 = 0.113). Colombia had the lowest scores in these factors but the highest in the perception of the respect for human rights for users and staff, although this difference did not reach a statistical significance. Despite the progress made in recent years towards coercion-free medical standards and an increased focus on mental health polices in Latin American countries, there is a need to enhance the quality standards of mental health services, recognizing the value that the respect for human rights holds for the organizational well-being of both mental health users and professionals.

Quality of Life in Systemic Lupus Erythematosus and Other Chronic Diseases: Highlighting the Amplified Impact of Depressive Episodes.

BACKGROUND: Extensive research has explored SLE's impact on health-related quality of life (H-QoL), especially its connection with mental wellbeing. Recent evidence indicates that depressive syndromes significantly affect H-QoL in SLE. This study aims to quantify SLE's impact on H-QoL, accounting for comorbid depressive episodes through case-control studies. METHODS: A case-control study was conducted with SLE patients (meeting the ACR/EULAR 2019 criteria of age ≥ 18). The control group was chosen from a community database. H-QoL was measured with the SF-12 questionnaire, and PHQ-9 was used to assess depressive episodes. RESULTS: SLE significantly worsened H-QoL with an attributable burden of 5.37 ± 4.46. When compared to other chronic diseases, only multiple sclerosis had a worse impact on H-QoL. Major depressive episodes had a significant impact on SLE patients' H-QoL, with an attributable burden of 9.43 ± 5.10, similar to its impact on solid cancers but greater than its impact on other diseases. CONCLUSIONS: SLE has a comparable impact on QoL to serious chronic disorders. Concomitant depressive episodes notably worsened SLE patients' QoL, exceeding other conditions, similar to solid tumors. This underscores the significance of addressing mood disorders in SLE patients. Given the influence of mood disorders on SLE outcomes, early identification and treatment are crucial.

A quantitative analysis of human rights-related attitude changes towards people with mental health conditions and psychosocial, intellectual, or cognitive disabilities following completion of the WHO QualityRights e-training in Ghana.

BACKGROUND: Despite growing recognition of essential human rights, people with mental health conditions and psychosocial, intellectual, or cognitive disabilities' rights are known to be frequently violated in mental healthcare worldwide, with common use of coercive practices and limited recognition of people's right to exercise their legal capacity and make decisions for themselves on treatment and other issues affecting them. To tackle this issue, Ghana adopted the WHO QualityRights Initiative in 2019. This aims to introduce a right-based, person-centred recovery approach within the mental health care system, protecting and promoting the rights of people with mental health conditions, psychosocial, cognitive, and intellectual disabilities in the healthcare context and community. METHODS: E-training (capacity-building) was provided in Ghana across a broad array of stakeholder groups including healthcare professionals, carers, and people with lived experience. The training covered legal capacity, coercion, community inclusion, recovery approach, service environment, and the negative attitudes commonly held by stakeholder groups; it was completed by 17,000 people in Ghana as of December 2021. We assessed the impact of the e-training on attitudes through comparing trainees' pre- and post-questionnaire responses on 17 items, each measured on a 5-point Likert scale (strongly disagree to strongly agree), such that higher scores indicated negative attitudes towards persons with mental health conditions and psychosocial disabilities as rights holders. Analyses were conducted on two main groups: matched pairs (417 pairs of baseline and follow-up questionnaire responses matched to a high degree of certainty), and the unmatched group (4299 individual completed questionnaire responses). RESULTS: We assessed the impact of the WHO QualityRights e-training on attitudes: training resulted in highly significant attitude changes towards alignment with human rights, with scores changing by approximately 40% between baseline and follow-up. In particular, attitude changes were seen in items representing treatment choice, legal capacity, and coercion. This change was not affected by age, gender, or background experience. CONCLUSIONS: The QualityRights e-training programme is effective in changing people's (especially healthcare professionals') attitudes towards people with mental health conditions and psychosocial, intellectual, or cognitive disabilities: this is a step towards mental healthcare being more with human rights-based worldwide.

Is a Genetic Variant associated with Bipolar Disorder Frequent in People without Bipolar Disorder but with Characteristics of Hyperactivity and Novelty Seeking?

Objective: The objective is to verify whether a genetic condition associated with bipolar disorder (BD) is frequent in old adults adapted to their environment, without BD, but with aptitudes for hyperactivity and novelty seeking (H/NS). Methods: In this cross-sectional study, the study sample included healthy elderly people (40 participants, aged 60 or older) living in an urban area and recruited from a previous study on physical exercise and active aging, who were compared with 21 old adults with BD from the same area. The genetic methodology consisted of blood sampling, DNA extraction, real-time PCR jointly with FRET probes, and the SANGER sequencing method. The genetic variant RS1006737 of CACNA1C, found to be associated with bipolar disorder diagnosis, was investigated. Results: The frequency of the RS1006737 genetic variant in the study group (H/NS) is not higher than in the BD group and is statistically significantly higher than in all the control groups found in the literature. However, the familiarity for BD is higher in old adults with BD than in the H/NS sample without BD. The risk of BD in the family (also considering those without BD but with family members with BD) is not associated with the presence of the genetic variant examined. Conclusion: The study suggests that the gene examined is associated with characteristics of hyperactivity rather than just BD. Nevertheless, choosing to participate in an exercise program is an excessively general way to identify H/NS. The next step would be to identify the old adults with well-defined H/NS features with an adequate tool.

Why is it Important to Assess and Treat Alexithymia in the Cardiologic Field? An Overview of the Literature.

Background: Alexithymia has been found to be associated with several somatic illnesses, such as cardiovascular, indicating that it might be a risk factor for early death in the long-term course of post-myocardial infarction. From the cardiology perspective, the aim was to collect current evidence about the relationship between alexithymia and somatic illness. Methods: The literature was synthesized and summarized in a narrative format. The literature search was carried out in PubMed. Pertinent studies published in the last 50 years written in English were included and organized by three main topics ("The relation between alexithymia and somatic illness from the cardiology perspective"; "How do assess alexithymia?"; "Treating alexithymia") to be discussed. Results: High alexithymia is a dimensional trait that affects around 10% of the general population and up to 55% of people with essential hypertension. Also, the link between alexithymia and cardiovascular activity has been pointed out. There are several validated tools to assess alexithymia, as well as treatment options. Conclusion: Knowledge about the main features of alexithymia, as well as its assessment and treatment, can promote a multifactorial approach to the primary, secondary, and tertiary prevention of cardiac diseases.

Effect of anti-P ribosomal and anti-NR2 antibodies on depression and cognitive processes in SLE: an integrated clinical and functional MRI study.

OBJECTIVES: To explore the effects of anti-ribosomal P protein (anti-P) and anti-N-methyl-D-aspartic acid receptor subunit 2 (anti-NR2) autoantibodies on depression and cognitive dysfunction and their relationships with functional brain connectivity in SLE. METHODS: This cross-sectional study included adult patients who fulfilled the American College of Rheumatology/European Alliance of Associations for Rheumatology 2019 SLE criteria. Anti-P and anti-NR2 were quantified using ELISA. A 1-hour battery of neuropsychological testing interpreted by a neuropsychologist explored depressive symptoms (Center for Epidemiologic Studies Depression Scale, CES-D), cognitive domains and quality of life (SF-12). Resting-state functional connectivity (rs-fc) MRI analysis was performed within 1 month, and region-of-interest to region-of-interest (ROI-to-ROI) analyses with the graph theory were performed. RESULTS: Thirty-three patients with SLE (9% male) were enrolled, mean age (SD) of 43.5 (14) years and median disease duration of 10.4 years (2.9-25.4). Anti-P was positive in 6 (18.2%) and anti-NR2 in 14 (42.4%) patients. Depressive symptoms were found in 14 (42.4%) patients using the CES-D (range 0-51). After correction for age, disease duration, disease activity and white matter lesion load, the CES-D score was independently associated with anti-P serum level (ß=0.32; p=0.049) and prednisone daily dose (ß=0.38; p=0.023). Nineteen patients (57.6%) showed at least a cognitive test alteration, but no significant association with autoantibodies was found. The rs-fc MRI analysis revealed an independent association between the anti-P serum levels and many altered brain ROI properties but no anti-NR2 and prednisone effects on the cerebral network. CONCLUSIONS: Anti-P was associated with brain network perturbation, which may be responsible for depressive symptoms in patients with SLE.

Screening, Genetic Variants, and Bipolar Disorders: Can Useful Hypotheses Arise from the Sum of Partial Failures?

Bipolar disorder (BD) is a relevant public health issue, therefore accurate screening tools could be useful. The objective of this study is to verify the accuracy of the Mood Disorder Questionnaire (MDQ) and genetic risk as screeners, and their comparison in terms of reliability. Older adults (N = 61, ≥60 years) received a clinical psychiatric evaluation, the MDQ, and were evaluated according to the presence of the genetic variant RS1006737 of CACNA1C. MDQ+ versus the diagnosis of BD as a gold standard shows a sensitivity of 0.286 (Cl 95% 0.14-0.39); a specificity of 0.925 (Cl 95% 0.85-0.08); a predictive positive value (PPV) of 0.667 (Cl 95% 0.33-0.91); and a predictive negative value (PNV) of 0.702 (Cl 95% 0.65-0.75). The positivity for the variant RS1006737 of the CACNA1C against the diagnosis of BD as a gold standard shows a sensitivity of 0.750 (Cl 95% 0.55-0.90); a specificity of 0.375 (Cl 95% 0.28-0.45); a PPV of 0.375 (Cl 95% 0.28-0.45); and a PNV of 0.750 (Cl 95% 0.55-0.90). The reliability between the MDQ+ and positivity for the variant RS1006737 of the CACNA1C was very low (K = -0.048, Cl 95% -0.20-0.09). The study found that both the genetic and the paper and pencil test were quite accurate, but were not reliable in case finding. In fact, despite some validity, albeit specular (in the case of a positive genetic test, the probability of having the disorder is very high, whereas in the case of a negative score on the paper and pencil test, the probability of not having the disorder is very high), the unreliability of the two tests (i.e., they certainly do not measure the same underlying dimension) opens the door to the need for an interpretation and the possibility of a synergistic use for screening. From a heuristic perspective, which obviously requires all of the necessary verifications, this study seems to suggest the hypothesis that a condition of hyperactivation common to disorders and stress conditions, and identified by a positive score on the MDQ (which is common to BD, post-traumatic stress disorder (PTSD), and anxiety disorders and whose genetic basis has not yet been clarified) can trigger BD in people with a predisposition to hyperactivity (i.e., in people with the condition identified by the analyzed genetic variant).

Does Screening for Bipolar Disorders Identify a "Dysregulation of Mood, Energy, and Social Rhythms Syndrome" (DYMERS)? A Heuristic Working Hypothesis.

The aim of this paper is to verify if people with a positive score on the Mood Disorder Questionnaire (MDQ) without comorbidity of mood disorders showed a worse level of Health-related Quality of life (HRQol) compared to a control-matched sample of MDQ negatives, identifying a specific syndrome. This is a case-control study based on a database from a community survey. Cases: MDQ-positive without mood disorders; Controls: MDQ negatives matched by sex, age, and psychiatric diagnosis according to the Diagnostic and Statistical Manual of Mental Disorders IV (DSM-IV) criteria. Tools: MDQ, the Advanced Neuropsychiatric Tools and Assessment Schedule (ANTAS) semi-structured interview for psychiatric diagnosis, and the Health Survey Short Form (SF-12) for measuring HRQol. People scoring positive on the MDQ without a diagnosis of mood disorders showed significantly lower scores on the SF-12 compared to people of the same age and of the same sex with an equal diagnosis of psychiatric disorders not related to mood disorders (35.21 ± 6.30 vs. 41.48 ± 3.39, p < 0.0001). In the debate whether a positive score on the MDQ selects an area of "malaise" due to the presence of disorders differing from Bipolar Disorders, or if a positive score on the MDQ may be considered a "subthreshold" form of bipolar disorder in people who may later develop bipolar disorder, a third hypothesis can be advanced, i.e., that a positive score on the MDQ identifies a specific "Dysregulation of Mood, Energy, and Social Rhythms Syndrome" (DYMERS), characterized by a considerable amount of suffering and not attributable to other disorders, and which might represent a trigger for the previously mentioned disorders with which a positive score on the MDQ is associated, probably including, in severe conditions, bipolar disorder.

Mobility constraints in segregation models.

Since the development of the original Schelling model of urban segregation, several enhancements have been proposed, but none have considered the impact of mobility constraints on model dynamics. Recent studies have shown that human mobility follows specific patterns, such as a preference for short distances and dense locations. This paper proposes a segregation model incorporating mobility constraints to make agents select their location based on distance and location relevance. Our findings indicate that the mobility-constrained model produces lower segregation levels but takes longer to converge than the original Schelling model. We identified a few persistently unhappy agents from the minority group who cause this prolonged convergence time and lower segregation level as they move around the grid centre. Our study presents a more realistic representation of how agents move in urban areas and provides a novel and insightful approach to analyzing the impact of mobility constraints on segregation models. We highlight the significance of incorporating mobility constraints when policymakers design interventions to address urban segregation.

Multidisciplinary contributions towards an evolutive interpretation of bipolar disorders: Could it be the pathological drift of a potentially adaptive condition?

This paper tries to summarize the results of studies from different disciplines supporting the idea that temperamental traits, such as "reckless/hyper-exploratory" attitudes, commonly believed to be associated with psychopathology, surprisingly turn out as adaptive under specific stress conditions. In particular, this paper analyzes an ethologic line of research on primates suggesting models for a sociobiological interpretation of mood disorders in humans; a study that found high frequencies of a genetic variance associated with bipolar disorder in people without bipolar disorder but with hyperactivity/novelty-seeking traits; the outcomes of socio-anthropologicalhistorical surveys on the evolution of mood disorders in Western countries in the last centuries; surveys on changing societies in Africa and African migrants in Sardinia; and studies that found higher frequencies of mania and subthreshold mania among Sardinian immigrants in Latin American megacities. Although it is not unequivocally accepted that an increase in the prevalence of mood disorders has occurred, it would be logical to suppose that a nonadaptive condition should have disappeared over time; mood disorders, on the contrary, persist and their prevalence might have even increased. This new interpretation could lead to counter-discrimination and stigma towards people suffering from the disorder, and it would be a central point in psychosocial treatments in addition to drugs. The aim is to hypothesize that bipolar disorder, strongly characterized by these traits, may be the result of the interaction between genetic characteristics, not necessarily pathological, and specific environmental conditions, rather than a mere product of an aberrant genetic profile. If mood disorders were mere nonadaptive conditions, they would have disappeared over time, however, their prevalence, paradoxically, persists if not even increases over time. The hypothesis that bipolar disorder may result from the interaction between genetic characteristics, not necessarily pathological, and specific environmental factors, seem more credible than considering bipolar disorder as a mere product of an aberrant genetic profile.

A review of the main genetic factors influencing the course of COVID-19 in Sardinia: the role of human leukocyte antigen-G.

Introduction: A large number of risk and protective factors have been identified during the SARS-CoV-2 pandemic which may influence the outcome of COVID-19. Among these, recent studies have explored the role of HLA-G molecules and their immunomodulatory effects in COVID-19, but there are very few reports exploring the genetic basis of these manifestations. The present study aims to investigate how host genetic factors, including HLA-G gene polymorphisms and sHLA-G, can affect SARS-CoV-2 infection. Materials and Methods: We compared the immune-genetic and phenotypic characteristics between COVID-19 patients (n = 381) with varying degrees of severity of the disease and 420 healthy controls from Sardinia (Italy). Results: HLA-G locus analysis showed that the extended haplotype HLA-G*01:01:01:01/UTR-1 was more prevalent in both COVID-19 patients and controls. In particular, this extended haplotype was more common among patients with mild symptoms than those with severe symptoms [22.7% vs 15.7%, OR = 0.634 (95% CI 0.440 - 0.913); P = 0.016]. Furthermore, the most significant HLA-G 3'UTR polymorphism (rs371194629) shows that the HLA-G 3'UTR Del/Del genotype frequency decreases gradually from 27.6% in paucisymptomatic patients to 15.9% in patients with severe symptoms (X2 = 7.095, P = 0.029), reaching the lowest frequency (7.0%) in ICU patients (X2 = 11.257, P = 0.004). However, no significant differences were observed for the soluble HLA-G levels in patients and controls. Finally, we showed that SARS-CoV-2 infection in the Sardinian population is also influenced by other genetic factors such as ß-thalassemia trait (rs11549407C>T in the HBB gene), KIR2DS2/HLA-C C1+ group combination and the HLA-B*58:01, C*07:01, DRB1*03:01 haplotype which exert a protective effect [P = 0.005, P = 0.001 and P = 0.026 respectively]. Conversely, the Neanderthal LZTFL1 gene variant (rs35044562A>G) shows a detrimental consequence on the disease course [P = 0.001]. However, by using a logistic regression model, HLA-G 3'UTR Del/Del genotype was independent from the other significant variables [ORM = 0.4 (95% CI 0.2 - 0.7), PM = 6.5 x 10-4]. Conclusion: Our results reveal novel genetic variants which could potentially serve as biomarkers for disease prognosis and treatment, highlighting the importance of considering genetic factors in the management of COVID-19 patients.