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 welldefined H/NS features with an adequate tool

Longitudinal assessment of brain-derived neurotrophic factor in Sardinian psychotic patients (LABSP): a protocol for a prospective observational study

Brain-derived neurotrophic factor (BDNF) plays a crucial role in neurodevelopment, synaptic plasticity and neuronal function and survival. Serum and plasma BDNF levels are moderately, but consistently, decreased in patients with schizophrenia (SCZ) compared with healthy controls. There is a lack of knowledge, however, on the temporal manifestation of this decline. Clinical, illness course and treatment factors might influence the variation of BDNF serum levels in patients with psychosis. In this context, we propose a longitudinal study of a cohort of SCZ and schizophrenic and schizoaffective disorder (SAD) Sardinian patients with the aim of disentangling the relationship between peripheral BDNF serum levels and changes of psychopathology, cognition and drug treatments

Therapeutic use of a cationic antimicrobial peptide from the spider Acanthoscurria gomesiana in the control of experimental candidiasis

<p>Abstract</p> <p>Background</p> <p>Antimicrobial peptides are present in animals, plants and microorganisms and play a fundamental role in the innate immune response. Gomesin is a cationic antimicrobial peptide purified from haemocytes of the spider <it>Acanthoscurria gomesiana</it>. It has a broad-spectrum of activity against bacteria, fungi, protozoa and tumour cells. <it>Candida albicans</it> is a commensal yeast that is part of the human microbiota. However, in immunocompromised patients, this fungus may cause skin, mucosal or systemic infections. The typical treatment for this mycosis comprises three major categories of antifungal drugs: polyenes, azoles and echinocandins; however cases of resistance to these drugs are frequently reported. With the emergence of microorganisms that are resistant to conventional antibiotics, the development of alternative treatments for candidiasis is important. In this study, we evaluate the efficacy of gomesin treatment on disseminated and vaginal candidiasis as well as its toxicity and biodistribution.</p> <p>Results</p> <p>Treatment with gomesin effectively reduced <it>Candida albicans </it>in the kidneys, spleen, liver and vagina of infected mice. The biodistribution of gomesin labelled with technetium-99 m showed that the peptide is captured in the kidneys, spleen and liver. Enhanced production of TNF-α, IFN-γ and IL-6 was detected in infected mice treated with gomesin, suggesting an immunomodulatory activity. Moreover, immunosuppressed and <it>C. albicans</it>-infected mice showed an increase in survival after treatment with gomesin and fluconazole. Systemic administration of gomesin was also not toxic to the mic</p> <p>Conclusions</p> <p>Gomesin proved to be effective against experimental <it>Candida albicans</it> infection. It can be used as an alternative therapy for candidiasis, either alone or in combination with fluconazole. Gomesin's mechanism is not fully understood, but we hypothesise that the peptide acts through the permeabilisation of the yeast membrane leading to death and/or releasing the yeast antigens that trigger the host immune response against infection. Therefore, data presented in this study reinforces the potential of gomesin as a therapeutic antifungal agent in both humans and animals.</p

The impact of MDQ positivity on quality of life impairment: Does it support the hypothesis of Dysregulation of Mood, Energy, and Social Rhythms Syndrome (DYMERS)?

Background: DSM-5 separates bipolar (BD) from depressive disorders, but some experts consider BD as part of a spectrum of mood disorders. The interpretation of numerous false positives of BD screened by the Mood Disorders Questionnaire (MDQ) is part of this debate. Recent study results suggest that the worsening of health-related quality of life (H-Qol) associated with MDQ positivity does not depend solely on mood disorders. This study aims to clarify whether the impairment may be due to other concomitant disorders, unrelated to mood disorders, leading to a worsening of H-Qol. Additionally, the study aims to explore if MDQ positivity itself observe clinical significance.Design and methods: The study involved pairs of cases (MDQ+) and controls (MDQ-) matched for sex, age, and absence of DSM-IV psychiatric comorbidity. The impact of MDQ positivity on the quality of life in a sample of MDQ+ comorbid with MDD was measured and compared to impact of MDD in other chronic disorders.Results: The H-Qol was significantly worse in MDQ+ than in controls (both groups without any psychiatric co-morbidity). The worsening was similar to severe chronic disorders The burden of worsening quality of life due to MDD was mild in another sample of MDQ positives with comorbid MDD.Conclusion:The study hypothesizes that MDQ positivity may be related to hyperactivation and dysregulation of rhythms typical of stress disorders. In fact, MDQ+ was found strongly related to sleep disturbances. Future studies could verify if a "Dysregulation of Mood, Energy, and Social Rhythms Syndrome" (DYMERS), causes worsening the H-Qol in MDQ+

A Recovery-Oriented Program for People with Bipolar Disorder through Virtual Reality-Based Cognitive Remediation: Results of a Feasibility Randomized Clinical Trial

Background: Cognitive impairment is a frequent consequence of bipolar disorder (BD) that is difficult to prevent and treat. In addition, the quality of the preliminary evidence on the treatment of BD through Cognitive Remediation (CR) with traditional methods is poor. This study aims to evaluate the feasibility of a CR intervention with fully immersive Virtual Reality (VR) as an additional treatment for BD and offers preliminary data on its efficacy. Methods: Feasibility randomized controlled cross-over clinical study, with experimental condition lasting three months, crossed between two groups. Experimental condition: CR fully immersive VR recovery-oriented program plus conventional care; Control condition: conventional care. The control group began the experimental condition after a three months period of conventional care (waiting list). After the randomization of 50 people with BD diagnosis, the final sample consists of 39 participants in the experimental condition and 25 in the control condition because of dropouts. Results: Acceptability and tolerability of the intervention were good. Compared to the waitlist group, the experimental group reported a significant improvement regarding cognitive functions (memory: p = 0.003; attention: p = 0.002, verbal fluency: p = 0.010, executive function: p = 0.003), depressive symptoms (p = 0.030), emotional awareness (p = 0.007) and biological rhythms (p = 0.029). Conclusions: The results are preliminary and cannot be considered exhaustive due to the small sample size. However, the evidence of efficacy, together with the good acceptability of the intervention, is of interest. These results suggest the need to conduct studies with larger samples that can confirm this data. Trial registration: ClinicalTrialsgov NCT05070065, registered in September 202

First-episode psychosis and migration in Italy (PEP-Ita migration): a study in the Italian mental health services

BACKGROUND: It has been frequently reported a higher incidence of psychotic disorders in immigrants than in native populations. There is, however, a lack of knowledge about risk factors which may explain this phenomenon. A better understanding of the causes of psychosis among first-generation migrants is highly needed, particularly in Italy, a country with a recent massive migration. METHODS/DESIGN: The "Italian study on first-episode psychosis and migration (PEP-Ita)" is a prospective observational study over a two-year period (1 January 2012-31 December 2013) which will be carried out in 11 Italian mental health centres. All participating centres will collect data about all new cases of migrants with first-episode psychosis. The general purpose ("core") of the PEP-Ita study is to explore the socio-demographic and clinical characteristics, and the pathways to care of a population of first-episode psychosis migrants in Italy. Secondary aims of the study will be: 1) to understand risk and protective factors for the development of psychotic disorders in migrants; 2) to evaluate the correlations between psychopathology of psychotic disorders in migrants and socio-demographic characteristics, migration history, life experiences; 3) to evaluate the clinical and social outcomes of first-episode psychoses in migrants. DISCUSSION: The results of the PEP-Ita study will allow a better understanding of risk factors for psychosis in first-generation migrants in Italy. Moreover, our results will contribute to the development of prevention programmes for psychosis and to the improvement of early intervention treatments for the migrant population in Italy

Exploring the association between brain-derived neurotrophic factor (BDNF) levels and longitudinal psychopathological and cognitive changes in Sardinian psychotic patients

Background and Hypothesis: Schizophrenia is among the most debilitating mental disorders and has complex pathophysiological underpinnings. There is growing evidence that brain-derived neurotrophic factor (BDNF) can play a role in its pathogenesis. The present study investigated the longitudinal variation of serum BDNF levels in a 24-month observational prospective cohort study of Sardinian psychotic patients and its relationship with psychopathological and cognitive changes. Further, we examined whether genetic variation within the BDNF gene could moderate these relationships. Study design: Every six months 105 patients were assessed for their BDNF serum levels, as well as for a series of psychopathological, cognitive, and social measures. We performed a targeted analysis of four tag single nucleotide polymorphisms (SNPs) within the BDNF gene that were selected and analyzed using Polymerase Chain Reaction (PCR). Longitudinal data were analyzed using mixed-effects linear regression models (MLRM). Study results: We observed a declining longitudinal trajectory of BDNF levels in psychotic patients in general, and in relation to the severity of depressive and negative symptoms. BDNF serum levels also declined in patients scoring lower in cognitive measures such as attention and speed of information processing and verbal fluency. The rs7934165 polymorphism moderated the significant association between verbal fluency and BDNF levels. Conclusions: These findings in patients from real-world settings suggest a plausible role of peripheral BDNF levels as a marker of illness burden in schizophrenia spectrum disorders

Converging Evidence Points to BDNF as Biomarker of Depressive Symptoms in Schizophrenia-Spectrum Disorders

Brain-derived neurotrophic factor (BDNF) is a key modulator of neuroplasticity and has an important role in determining the susceptibility to severe psychiatric disorder with a significant neurodevelopmental component such as major psychoses. Indeed, a potential association between BDNF serum levels and schizophrenia (SCZ) and schizoaffective disorder (SAD) has been tested in diverse studies and a considerable amount of them found reduced BDNF levels in these disorders. Here, we aimed at testing the association of BDNF serum levels with several demographic, clinical, and psychometric measures in 105 patients with SCZ and SAD, assessing the moderating effect of genetic variants within the BDNF gene. We also verified whether peripheral BDNF levels differed between patients with SCZ and SAD. Our findings revealed that BDNF serum levels are significantly lower in patients affected by SCZ and SAD presenting more severe depressive symptomatology. This finding awaits replication in future independent studies and points to BDNF as a possible prognostic indicator in major psychoses

Social cognition in people with schizophrenia: A cluster-analytic approach

Background The study aimed to subtype patients with schizophrenia on the basis of social cognition (SC), and to identify cut-offs that best discriminate among subtypes in 809 out-patients recruited in the context of the Italian Network for Research on Psychoses. Method A two-step cluster analysis of The Awareness of Social Inference Test (TASIT), the Facial Emotion Identification Test and Mayer-Salovey-Caruso Emotional Intelligence Test scores was performed. Classification and regression tree analysis was used to identify the cut-offs of variables that best discriminated among clusters. Results We identified three clusters, characterized by unimpaired (42%), impaired (50.4%) and very impaired (7.5%) SC. Three theory-of-mind domains were more important for the cluster definition as compared with emotion perception and emotional intelligence. Patients more able to understand simple sarcasm (14 for TASIT-SS) were very likely to belong to the unimpaired SC cluster. Compared with patients in the impaired SC cluster, those in the very impaired SC cluster performed significantly worse in lie scenes (TASIT-LI &lt;10), but not in simple sarcasm. Moreover, functioning, neurocognition, disorganization and SC had a linear relationship across the three clusters, while positive symptoms were significantly lower in patients with unimpaired SC as compared with patients with impaired and very impaired SC. On the other hand, negative symptoms were highest in patients with impaired levels of SC. Conclusions If replicated, the identification of such subtypes in clinical practice may help in tailoring rehabilitation efforts to the person's strengths to gain more benefit to the person

Social cognition in people with schizophrenia: A cluster-analytic approach

Background The study aimed to subtype patients with schizophrenia on the basis of social cognition (SC), and to identify cut-offs that best discriminate among subtypes in 809 out-patients recruited in the context of the Italian Network for Research on Psychoses. Method A two-step cluster analysis of The Awareness of Social Inference Test (TASIT), the Facial Emotion Identification Test and Mayer-Salovey-Caruso Emotional Intelligence Test scores was performed. Classification and regression tree analysis was used to identify the cut-offs of variables that best discriminated among clusters. Results We identified three clusters, characterized by unimpaired (42%), impaired (50.4%) and very impaired (7.5%) SC. Three theory-of-mind domains were more important for the cluster definition as compared with emotion perception and emotional intelligence. Patients more able to understand simple sarcasm (14 for TASIT-SS) were very likely to belong to the unimpaired SC cluster. Compared with patients in the impaired SC cluster, those in the very impaired SC cluster performed significantly worse in lie scenes (TASIT-LI <10), but not in simple sarcasm. Moreover, functioning, neurocognition, disorganization and SC had a linear relationship across the three clusters, while positive symptoms were significantly lower in patients with unimpaired SC as compared with patients with impaired and very impaired SC. On the other hand, negative symptoms were highest in patients with impaired levels of SC. Conclusions If replicated, the identification of such subtypes in clinical practice may help in tailoring rehabilitation efforts to the person's strengths to gain more benefit to the person