Human Cytomegalovirus Inhibitor AL18 Also Possesses Activity against Influenza A and B Viruses

AL18, an inhibitor of human cytomegalovirus DNA polymerase, was serendipitously found to also block the interaction between the PB1 and PA polymerase subunits of influenza A virus. Furthermore, AL18 effectively inhibited influenza A virus polymerase activity and the overall replication of influenza A and B viruses. A molecular model to explain the binding of AL18 to both cytomegalovirus and influenza targets is proposed. Thus, AL18 represents an interesting lead for the development of new antivirals

Biomarkers, Inflammation, and Bipolar Disorder: Association Between the Improvement of Bipolar Disorder Severity and the Improvement in C-Reactive Protein Levels After 7 Days of Inpatient Treatment

Introduction: Compared to the general population, people with severe mental illness (SMI) have a poorer health status and a higher mortality rate, with a 10-20-year reduction in life expectancy. Excess mortality and morbidity in SMI have been explained by intertwined components. Inflammatory processes could increase the morbidity and mortality risk in patients with bipolar disorder (BD) because of a bidirectional interaction between BD and conditions related to inflammation. This pilot study aimed to evaluate the relationship between C-Reactive-Protein (CRP) and bipolar disorder severity.Methods: A retrospective observational study was conducted on 61 hospitalized patients with bipolar disorder. CRP was measured at admission to inpatient treatment (T0) and after seven days from the admission (T1). Clinical Global Impression for Depression, Mania and Overall Bipolar Illness were recorded at T0 and T1. Comparisons among the recorded CRP values were determined through the paired t-test. Correlations between CRP and CGI scores were determined through Spearman's correlation coefficient at T0 and T1.Results: A statistically significant decrease in CRP values was observed after 7 days of hospitalization (p < 0.001) and positive significant correlations emerged between CRP and CGI scores at T0 and T1.Conclusion: Patients admitted to the inpatient unit reported a statistically significant decrease of CRP values during the first 7 days of treatment. Although the direction of the relationship between BP severity and inflammation status continues to remain unclear, this study showed a relationship between the improvement of bipolar disease symptoms and the improvement of the inflammatory marker CRP

Radiofrequency echographic multispectrometry (REMS): an innovative technique for the assessment of bone status in young women with anorexia nervosa

Purpose Reduced bone mineral density (BMD) and increase risk of fragility fracture are common complication of anorexia nervosa (AN). BMD by dual-energy X-ray absorptiometry (DXA) present several limits in subjects with AN. This study aimed to evaluate the usefulness of the new Radiofrequency echographic multispectrometry (REMS) technique in the assessment of bone status in young women with AN. Methods In a cohort of 50 subjects with restrictive AN and in 30 healthy controls, we measured BMD at the lumbar spine (LS-BMD), at femoral neck (FN-BMD) and total hip (TH-BMD) using both DXA and REMS technique. Results BMD evaluated by DXA and REMS technique at all measurement sites were all significantly (p < 0.01) lower in subjects suffering from AN subjects than in controls. Good correlations were detected between BMD by DXA and BMD by REMS measurements at LS (r = 0.64, p < 0.01) at FN (r = 0.86, p < 0.01) and at TH (r = 0.84, p < 0.01) in subjects suffering from AN. Moreover, Bland-Altman analysis confirmed the good agreement between the two techniques. The subjects suffering from AN with previous vertebral fragility fractures presented lower values of both BMD-LS and BMD-TH by DXA and by REMS with respect to those without fractures; however, the difference was significant only for BMD-TH by REMS (p < 0.05). Conclusions Our data suggest that REMS technique due to its characteristic of precision and reproducibility may represent an important tool for the evaluation of the changes in bone status in AN young women, especially during the fertile age and in case of pregnancy and breastfeeding. © 2022, The Author(s)

Exploration of mood spectrum symptoms during a major depressive episode: The impact of contrapolarity-Results from a transdiagnostic cluster analysis on an Italian sample of unipolar and bipolar patients

Background Subthreshold hypomania during a major depressive episode challenges the bipolar-unipolar dichotomy. In our study we employed a cross-diagnostic cluster analysis - to identify distinct subgroups within a cohort of depressed patients. Methods A k-means cluster analysis- based on the domain scores of the Mood Spectrum Self-Report (MOODS-SR) questionnaire-was performed on a data set of 300 adults with either bipolar or unipolar depression. After identifying groups, between-clusters comparisons were conducted on MOODS-SR domains and factors and on a set of sociodemographic, clinical and psychometric variables. Results Three clusters were identified: one with intermediate depressive and poor manic symptomatology (Mild), one with severe depressive and poor manic symptomatology (Moderate), and a third one with severe depressive and intermediate manic symptomatology (Mixed). Across the clusters, bipolar patients were significantly less represented in the Mild one, while the DSM-5 "Mixed features" specifier did not differentiate the groups. When compared to the other patients, those of Mixed cluster exhibited a stronger association with most of the illness-severity, quality of life, and outcomes measures considered. After performing pairwise comparisons significant differences between "Mixed" and "Moderate" clusters were restricted to: current and disease-onset age, psychotic ideation, suicidal attempts, hospitalization numbers, impulsivity levels and comorbidity for Cluster B personality disorder. Conclusions In the present study, a clustering approach based on a spectrum exploration of mood symptomatology led to the identification of three transdiagnostic groups of patients. Consistent with our hypothesis, the magnitude of subthreshold (hypo)manic symptoms was related to a greater clinical severity, regardless of the main categorical diagnosis

Heterozygosity for Neuronal Ceroid Lipofuscinosis predisposes to Bipolar Disorder

Objective: Bipolar Disorder (BD) is an heritable chronic mental disorder causing psychosocial impairment, affecting patients with depressive/manic episodes. The familial transmission of BD does not follow any of the simple Mendelian patterns of inheritance. The aim of this study is to describe a new large family with twelve affected BD members: WES was performed in eight of them, three of which were diagnosed for BD, and one was reported as a "borderline" individual. Material and methods: WES data allowed us to select variants in common between the affected subjects, once including and once excluding a "borderline" subject with moderate anxiety and traits of obsessive-compulsive disorder. Results: Results were in favor of new predisposing BD genes, electing a heterozygous missense variant in CLN6 resulting in a "borderline" phenotype that if combined with a heterozygous missense variant in ZNF92 is responsible for the more severe BD phenotype. Both rare missense changes are predicted to disrupt the protein function. Conclusions: Loss of both alleles in CLN6 causes Neuronal Ceroid Lipofuscinosis, a severe progressive neurological disorder of childhood. Our results indicate that heterozygous CLN6 carriers, previously reported as healthy, may be susceptible to bipolar disorder late in life if associated with additional variants in ZNF92

Neuroticism and Conscientiousness Moderate the Effect of Oral Medication Beliefs on Adherence of People with Mental Illness during the Pandemic

Background. After the declaration of the pandemic status in several countries, the continuity of face-to-face visits in psychiatric facilities has been delayed or even interrupted to reduce viral spread. Little is known about the personality factors associated with medication beliefs and adherence amongst individuals with mental illness during the COVID-19 pandemic. This brief report describes a preliminary naturalistic longitudinal study that explored whether the Big Five personality traits prospectively moderate the effects of medication beliefs on changes in adherence during the pandemic for a group of outpatients with psychosis or bipolar disorder. Methods. Thirteen outpatients undergoing routine face-to-face follow-up assessments during the pandemic were included (41 observations overall) and completed the Revised Italian Version of the Ten-Item Personality Inventory, the Beliefs about Medicines Questionnaire, the Morisky Medication Adherence Scale-8-item and the Beck Depression Inventory-II. Results. Participants had stronger concerns about their psychiatric medications rather than beliefs about their necessity, and adherence to medications was generally low. Participants who had more necessity beliefs than concerns had better adherence to medications. People scoring higher in Conscientiousness and Neuroticism traits and more concerned about the medication side effects had poorer adherence. Conclusions. These preliminary data suggest the importance of a careful assessment of the adherence to medications amongst people with psychosis/bipolar disorder during the pandemic. Interventions aimed to improve adherence might focus on patients' medication beliefs and their Conscientiousness and Neuroticism personality traits

Insight in cognitive impairment assessed with the Cognitive Assessment Interview in a large sample of patients with schizophrenia

The Cognitive Assessment Interview (CAI) is an interview-based scale measuring cognitive impairment and its impact on functioning in subjects with schizophrenia (SCZ). The present study aimed at assessing, in a large sample of SCZ (n = 601), the agreement between patients and their informants on CAI ratings, to explore patients' insight in their cognitive deficits and its relationships with clinical and functional indices. Agreement between patient- and informant-based ratings was assessed by the Gwet's agreement coefficient. Predictors of insight in cognitive deficits were explored by stepwise multiple regression analyses. Patients reported lower severity of cognitive impairment vs. informants. A substantial to almost perfect agreement was observed between patients' and informants' ratings. Lower insight in cognitive deficits was associated to greater severity of neurocognitive impairment and positive symptoms, lower severity of depressive symptoms, and older age. Worse real-life functioning was associated to lower insight in cognitive deficit, worse neurocognitive performance, and worse functional capacity. Our findings indicate that the CAI is a valid co-primary measure with the interview to patients providing a reliable assessment of their cognitive deficits. In the absence of informants with good knowledge of the subject, the interview to the patient may represent a valid alternative

Treatment persistence with aripiprazole once monthly: a 4-year follow-up

Objectives: Treatment persistence refers to the act of continuing a treatment as prescribed and reflects the patient's or doctor's judgment about efficacy, tolerability, and acceptability. In patients with schizophrenia, antipsychotic persistence is often poor, because of issues such as lack or loss of efficacy, side effects, and poor adherence, which is often related to the degree to which patients find the medication and overall intervention to be helpful, tolerable, fair, reasonable, appropriate, and consistent with expectations of treatment. Despite the poor antipsychotic persistence that has been reported to date in patients with schizophrenia, we previously observed a relatively high (86%) 6 months persistence with aripiprazole once-monthly (AOM) in a group of patients with schizophrenia, treated in the real world Italian clinical practice. The present study explores the longer term persistence with AOM, over a mean follow-up period of 48 months. Methods: This was a multicenter, retrospective, non-interventional follow-up study, aimed at evaluating the longer term persistence with AOM in a group of patients with schizophrenia who had already shown persistence over a period of at least 6 months. The study included 161 individuals who had participated in our previous study, where 86% of participating individuals had shown persistence with AOM for at least 6 months. Non-persistence was defined as discontinuing the medication for any reason. Baseline demographic and clinical characteristics of patients who continued AOM were then compared to those of patients who discontinued the medication. Results: Study subjects were predominantly male (64.4%) and their mean age was 39.7 (SD: 12.24). Treatment persistence with AOM was 69.6% and 112 out of 161 patients were still receiving AOM treatment at the last follow-up visit. The mean duration of AOM treatment until the last recorded observation was 55.87 months (median 56.17, SD6.23) for the 112 persistent patients and 32.23 (median 28.68.SD 15.09) months for the 49 non-persistent individuals. The mean observation period for all patients (persistent and non-persistent) was 48.78 months (median 52.54, SD 14.64). For non-persistent subjects, the observation period ended with the discontinuation of AOM. Subjects treated with AOM at 400 mg presented a 69.6% lower risk of all-cause treatment discontinuation when compared with patients treated with 300 mg (HR: 0.314; 95% confidence interval [CI] 0.162-0.608; P = 0.001). The main reasons for discontinuation were lack of efficacy (30.6%), patient/caregiver choice (18.4%), physician's choice (16.3%), non-adherence (12.2%) and inconvenience (6.1%). Only 3 patients (6.1%) discontinued AOM for tolerability issues. Conclusions: In subjects with schizophrenia, who had already shown a 6 months persistence with AOM, a high number of patients (69.6%) continued to be persistent over a 4-year follow-up period. This may reflect a favourable profile of efficacy, tolerability, and acceptability. Larger and prospective studies are warranted to confirm our observations

Prevalence and Correlates of Vitamin D Deficiency in a Sample of 290 Inpatients With Mental Illness

Introduction: Vitamin D inadequacy or deficiency (VDID) has been reported in a high percentage of otherwise healthy individuals. Factors that may contribute to the high prevalence of VDID in people with mental disorders include diet low in vitamin D, poor sunlight exposure, decrease in cutaneous vitamin D synthesis, intake of certain medications, poor mobility, excessive alcohol intake, and tobacco smoking. VDID has been correlated to a host of adverse conditions, including rickets, osteoporosis, osteomalacia, muscle diseases, depression, cognitive dysfunction, and even certain cancers.Objectives: The purpose of this study was to report the prevalence and correlates of vitamin D inadequacy in a sample of 290 psychiatric patients admitted to inpatient or day hospital treatment at the University of Siena Medical Center.Methods: We retrospectively evaluated the prevalence of VDID in 290 psychiatric inpatients' medical records during the year 2017 and evaluated the correlates of VDID in patients with mental illness.Results: Two hundred and seventy two out of two hundred and ninety patients (94%) showed VDID. Physical activity and regular diet were positively correlated with vitamin D levels whereas age, tobacco smoking, PTH, alkaline phosphatase levels were negatively correlated. Statistically significant differences were found among smokers and non-smokers in all study groups.Conclusions: VDID was highly prevalent in our sample. In addition to vitamin D supplementation, psychosocial intervention able to promote and help sustain physical activity, appropriate diet, quitting smoking and sensible sun exposure to prevent and treat VDID in patients with mental health should be implemented, tested, and introduced in our clinical practice

Feasibility, Adherence and Efficacy of Liraglutide Treatment in a Sample of Individuals With Mood Disorders and Obesity

Background: Liraglutide is a once-daily injectable medication approved for the treatment of obesity. Hereby we report the feasibility, adherence and efficacy of liraglutide treatment in a sample of individuals with mood disorders and obesity.Methods and Sample: Twenty-nine patients with Bipolar or Major Depressive Disorder received liraglutide once daily subcutaneously at a dose gradually titrated from 0.6 to 3 mg. All patients were obese and had previously failed multiple healthy lifestyle interventions, including exercise and diet programs. Patients' weight was recorded before liraglutide treatment (T0) and then 1 (T1), 3 (T3), and 6 months (T6) following T0.Results: Mean baseline (T0) weight was 110.54 Kg (±24.95). Compared to baseline, the percentage of weight loss was 3.37% at T1, 7.85% at T3, and 10.20% at T6. Thirty-one percent (n = 9) of patients had no side effects, 34.48% (n = 10) had one, 24.14% (n = 7) had two, and 10.34% (n = 3) had three side effects. All 29 subjects were still on liraglutide at T1; 79.31 and 48.28% were on liraglutide at T3 and T6. No significant relationship was found between liraglutide dose and likelihood to continue the medication. No patient showed a worsening of the psychiatric condition due to liraglutide treatment. Acceptability and satisfaction with treatment were good for the 48% that completed the study.Conclusions: Liraglutide treatment was efficacious, accepted and tolerated by ~50% of our sample, followed up for a period of 180 days. Larger, longer, controlled, prospective studies are warranted