Total Synthesis of 4-epi-Bengamide E.

Bengamide E is a bioactive natural product that was isolated from Jaspidae sponges by Crews and co-workers in 1989. It displays a wide range of biological activities, including antitumor, antibiotic, and anthelmintic properties. With the aim of investigating the structural feature essential for their activity, several total syntheses of Bengamide E and its analogues have been reported in the literature. Nevertheless, no synthesis of the stereoisomer with modification of its configuration at C-4 carbon has been reported so far. Here, we report the first total synthesis of the 4-epi-Bengamide E. Key reactions in the synthesis include a chemoenzimatic desymmetrization of biobased starting materials and a diastereoselective Passerini reaction using a chiral, enantiomerically pure aldehyde, and a lysine-derived novel isocyanide.

The mediating effect of mood spectrum on the relationship between autistic traits and catatonia spectrum.

Background: In the recent years, several studies have shown a correlation between autism spectrum disorder (ASD) and catatonia. It is also known that both conditions are found to be associated with mood disorders. This study aimed to investigate the relationship between autistic traits and catatonic symptoms, as well as the potential mediating role of mood disorder spectrum in the relationship between them. Methods: The total sample of 514 subjects was composed by four diagnostic groups, composed by patients affected by catatonia (CTN), borderline personality disorder (BPD), major depressive disorder (MDD) and healthy controls (HC). Subjects were assessed with the SCID-5-RV, the Adult Autism Subthreshold Spectrum (AdAS Spectrum) and the Catatonia Spectrum (CS) and the Mood Spectrum Self-Report (MOODS-SR). Statistical analyses included Pearson's coefficient calculation, multiple linear regression, and mediation analysis. Results: all the correlations appear to be strongly positive and significant with the strongest coefficient emerging between AdAS Spectrum total score and CS total score (r = 0.762, p < 0.001). The Mediation Analysis showed that AdAS Spectrum total score showed a significant indirect effect on CS total score through MOODS-SR total score (b = 0.168, 95% bootstrapped CI [0.127:0.207]). Conclusion: The present study highlights the presence of a mediating role of the mood disorder spectrum in the relationship between autistic traits and the catatonia spectrum.

Epigenetics of Autism Spectrum Disorders: A Multi-level Analysis Combining Epi-signature, Age Acceleration, Epigenetic Drift and Rare Epivariations Using Public Datasets.

BACKGROUND: Epigenetics of Autism Spectrum Disorders (ASD) is still an understudied field. The majority of the studies on the topic used an approach based on mere classification of cases and controls. OBJECTIVE: The present study aimed at providing a multi-level approach in which different types of epigenetic analysis (epigenetic drift, age acceleration) are combined. METHODS: We used publicly available datasets from blood (n = 3) and brain tissues (n = 3), separately. Firstly, we evaluated for each dataset and meta-analyzed the differential methylation profile between cases and controls. Secondly, we analyzed age acceleration, epigenetic drift and rare epigenetic variations. RESULTS: We observed a significant epi-signature of ASD in blood but not in brain specimens. We did not observe significant age acceleration in ASD, while epigenetic drift was significantly higher compared to controls. We reported the presence of significant rare epigenetic variations in 41 genes, 35 of which were never associated with ASD. Almost all genes were involved in pathways linked to ASD etiopathogenesis (i.e., neuronal development, mitochondrial metabolism, lipid biosynthesis and antigen presentation). CONCLUSION: Our data support the hypothesis of the use of blood epi-signature as a potential tool for diagnosis and prognosis of ASD. The presence of an enhanced epigenetic drift, especially in brain, which is linked to cellular replication, may suggest that alteration in epigenetics may occur at a very early developmental stage (i.e., fetal) when neuronal replication is still high.

Investigating suicidality across the autistic-catatonic continuum in a clinical sample of subjects with major depressive disorder and borderline personality disorder.

Background: Recent literature has highlighted that catatonia may be more prevalent among psychiatric patients than previously thought, beginning from autism spectrum disorders (ASD), for which it has been suggested to represent a severe late consequence, but also among individuals with mood disorders and borderline personality disorder (BPD). Interestingly, one critical point shared by these conditions is the increased risk of suicidality. The aim of this study was to evaluate how the presence and the prevalence of catatonic symptoms may shape and correlate with suicidal risk in a sample of individuals with major depressive disorder (MDD) or BPD. Methods: We recruited two clinical samples of subjects (BPD and MDD) and a control group without a diagnosis according to DSM-5 (CTL). Subjects were assessed with the catatonia spectrum (CS) and the MOODS-SR for evaluating suicidality. Results: In the total sample, suicidality score was significantly and positively correlated with all CS domains and CS total score. Correlation and regression analyses highlighted specific patterns of association among Catatonia spectrum domains and suicidality in the MDD and BPD group and in the total sample. Conclusion: In both disorders, higher catatonic traits are linked to higher suicidal tendencies, confirming the high risk of suicide for this population. However, different patterns of association between catatonic symptoms and suicidality were highlighted in the two disorders.

Not a matter of quantity: quality of relationships and personal interests predict university students' resilience to anxiety during CoViD-19.

During the CoViD-19 pandemic, University students may have suffered from increased anxiety due to interferences in their relationships and in academic requirements, as didactic activities have moved to distance learning systems. However, being surrounded by supportive relationships and being motivated to cultivate personal interests might have decreased anxiety. In this pilot study, we collected the responses of 174 students from Italian University merit colleges to an online questionnaire, investigating their perceived anxiety, the quality of surrounding relationships, whether they were cultivating any personal interests and whether they had spent the period of lockdown in college or at home. Regression analyses indicated that both quality of relationships and personal interests predicted low levels of anxiety (p < 0.001). However, simple slope analyses showed that personal interests were negatively related to anxiety only at medium and high quality of relationships (p < 0.001), while no association was found at low quality of relationships. No differences were found between students who stayed in college or at home. These results suggest that Universities should promote accessibility to relationships and cultivation of personal interests to protect students' mental health during mass emergencies such as the current pandemic, in the perspective of improving community resilience.

Catatonia Spectrum: Validation of a Questionnaire Investigating Catatonia Spectrum.

Aim: A growing body of literature has demonstrated the utility of a dimensional perspective on mental disorders. The current study aims to determine the psychometric properties of the Catatonia Spectrum (CS), a new questionnaire specifically tailored to assess the spectrum of catatonia, from full blown forms to subthreshold ones. Methods: 86 adults with at least three symptom criteria for catatonia according to the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), 81 adults affected by borderline personality disorder (BPD), 104 adults with a diagnosis of major depressive disorder (MDD), and 105 subjects without mental disorders (CTL), were recruited from six Italian University Departments of Psychiatry and administered the: Bush-Francis Catatonia Rating Scale (BFCRS), Bush-Francis Catatonia Screening Instrument (BFCSI), and CS. Results: CS scale demonstrated a high level of internal consistency and excellent test-retest reliability for total and domain scores. CS domain scores were positively and significantly correlated with each other (p < 0.001) with Pearson's coefficients ranging from 0.337 to 0.663. All the CS domain scores were highly correlated with the CS total score. The correlation coefficients between CS and alternative measures of catatonia appeared all significant and positive. Significant differences among diagnostic groups on both CS domains and total scores were found. CS total scores increased significantly and progressively from the CTL, to the MDD and the BDP group, up to the catatonia group, which reported the highest value. Conclusion: The CS showed excellent internal consistency and test-retest reliability and strong convergent validity with alternative dimensional measures of catatonia. The questionnaire performed differently across the four diagnostic groups, with an increasing score gradient from healthy controls to patients with MDD, BPD and up to the catatonia group.

A Pilot Study on Covid and Autism: Prevalence, Clinical Presentation and Vaccine Side Effects.

Background: Several neurobiological mechanisms have been proposed to support the hypothesis of a higher COVID-19 risk in individuals with autism spectrum disorder (ASD). However, no real-world data are available on this population. Methods: We compared the period prevalence (March-May 2020) and symptom presentation of COVID-19 infections between a sample of individuals with severe ASD (n = 36) and the staff personnel (n = 35) of two specialized centers. Anti-SARS-Cov-2 antibody positivity was used as a proxy of infection. Additionally, we evaluated vaccine side effects in the same groups. Results: No significant difference was found between the prevalence of COVID-19 positivity between autistic participants and staff personnel. Levels of antibodies against the spike protein and the receptor binding domain were not significantly different between autistic and staff participants. The level of antibodies against the N-terminal domain were higher in autistic individuals. There was a significant difference between the prevalence of symptomatic COVID-19 in autistic participants (9.1%) compared to staff personnel (92.3%). The most frequent side effect among autistic participants was light fever. Conclusions: The present study provides preliminary data on COVID-19 transmission and presentation in ASD. Our data do not support the hypothesis of a higher susceptibility and severity of COVID-19 in people with ASD.

Two Faces of a Coin? A Systematic Review of Source Monitoring and Its Relationship with Memory in Autism.

The ability to discriminate the origin of stimuli, known as source monitoring, is crucial for self-other distinction and the integration of internally generated and externally generated experiences. Despite its valence, evidence on source monitoring in autism is yet scarce and unclear. We systematically reviewed literature concerning source monitoring in autism and its relationship with other constructs, such as memory type, encoding effects, social cognition, general intelligence, and clinical factors. Source-monitoring performance (operationalized as error or accuracy) was reduced in autistic participants in 9 of the 15 studies that met the inclusion criteria. When explicitly investigated, free-recall memory impairments in autism were shown to influence source monitoring deficits. General intelligence was another important factor linked to source-monitoring performance. Conversely, other memory types or encoding effects were not impaired in autism, and no univocal association could be found with source monitoring. Social cognition and clinical symptoms were rarely assessed in spite of their possible involvement in source monitoring. The heterogeneity of the task design, outcome measures and demographical factors limited study comparability. As a research framework on source monitoring as a construct of primary interest in autism is still lacking, we propose preliminary indications for future investigations based on the collected findings.

Prosocial behavior in aging: which factors can explain age-related differences in social-economic decision making?

OBJECTIVES: Older adults tend to exhibit more prosocial behavior than younger adults. However, little research has focused on understanding the factors that may explain such differences in the social decision-making process. The first aim was to examine if, and to what degree, the content of social information about a recipient has an impact on young vs. older adults' prosocial behavior. The second aim was to understand if empathic concern, Theory of Mind, and reasoning explain the (expected) age differences in prosociality. DESIGN: Cross-sectional study. SETTING: The study was conducted in northern Italy in a laboratory setting. PARTICIPANTS: Forty-eight younger adults (Mage = 23.29; SD = 2.20) and 48 older adults (Mage = 70.19; SD = 5.13). MEASUREMENTS: Prosocial behavior was measured using the Dictator Game in which participants split a sum of money with recipients presented with four levels of description: no information, physical description, positive psychological description, and negative psychological description. In addition, participants performed tasks on emphatic concern, Theory of Mind, and reasoning. RESULTS: Results showed that older adults are more prosocial than younger adults in the Dictator Game. This finding was evident when the recipient was described with positive psychological and physical features. This pattern of results was statistically explained by the reduction in reasoning ability. CONCLUSION: These findings suggest a relationship between age-related reduction in reasoning ability and older adults' prosocial behavior. The theoretical and practical implication of the empirical findings are discussed.

Children's giving: moral reasoning and moral emotions in the development of donation behaviors.

This study investigated the role of moral reasoning and moral emotions (i.e., sympathy and guilt) in the development of young children's donating behavior (N = 160 4- and 8-year-old children). Donating was measured through children's allocation of resources (i.e., stickers) to needy peers and was framed as a donation to "World Vision." Children's sympathy was measured with both self- and primary caregiver-reports and participants reported their anticipation of guilt feelings following actions that violated prosocial moral norms, specifically the failure to help or share. Participants also provided justifications for their anticipated emotions, which were coded as representing moral or non-moral reasoning processes. Children's moral reasoning emerged as a significant predictor of donating behavior. In addition, results demonstrated significant developmental and gender effects, with 8-year-olds donating significantly more than 4-year-olds and 4-year-old girls making higher value donations than boys of the same age. We discuss donation behaviors within the broader context of giving and highlight the moral developmental antecedents of giving behaviors in childhood.