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Major depressive disorder (MDD) is a psychiatric disorder characterized by abnormal resting state functional connectivity (rsFC) in various neural networks and especially in default-mode network (DMN). However, inconsistent findings, i.e., increased and decreased DMN rsFC, have been reported, which raise the question for the source of DMN changes in MDD. Testing whether the DMN abnormalities in MDD can be traced to either a local, i.e., intra-network, or a global, i.e., inter-network, source, we conducted a novel sequence of rsFC analyses, i.e., global FC, intra-network FC, and inter-network FC. Moreover, all analyses were conducted without global signal regression (non-GSR) and with GSR in order to identify the impact of specifically the global component of functional connectivity on within-network functional connectivity within specifically the DMN. In MDD our findings demonstrate (i) increased representation of global signal correlation (GSCORR) in DMN regions, as confirmed independently by degree of centrality (DC) and by an independent DMN template, (ii) increased within-network DMN rsFC, (iii) highly increased inter-network rsFC of both lower- and higher order non-DMN networks with DMN, (iv) high accuracy in classifying MDD vs. healthy subjects by using GSCORR as predictor. Further supporting the global, i.e., non-DMN source of within-network rsFC of the DMN, all results were obtained only when including the global signal, i.e., non-GSR, but not when conducting GSR. Together, we show for the first time increased global signal representation within rsFC of DMN as stemming from inter-network sources as distinguished from local sources, i.e., within- or intra-DMN.

Diagnosing autism spectrum disorder (ASD) in adulthood often represents a challenge in clinical practice. The aim of the present study was to evaluate the sensitivity and specificity of the ADOS and ADI-R in diagnosing ASD in adults. 113 subjects with an IQ of 70 or above were assessed through an extensive clinical evaluation. The ADOS-2 Module 4 and the ADI-R were separately administered by staff members blind to clinical judgment. Our results cautiously confirm the accuracy of ADOS-2 Module 4, while suggest that ADI-R might not be reliable in adults without intellectual disability. Clinicians’ training and experience remains of primary importance while assessing adults who could potentially belong to the autism spectrum.

Attention-Deficit/Hyperactivity Disorder (ADHD) comprises disturbances in attention, emotional regulation, and reward-related processes. In spite of the active efforts in researching neurofunctional correlates of these symptoms, how the activity of subcortical regions—such as basal ganglia—is related to ADHD has yet to be clarified. More specifically, how age may influence the critical changes observed in functional dynamics from childhood to adulthood remains relatively unexplored. We hence selected five core subcortical regions (amygdala, caudate, putamen, pallidum and hippocampus) as regions of interest from the previous literature, measuring their whole-brain voxel-wise rsFC in a sample of 95 ADHD and 90 neurotypical children and adolescents aged from 7 to 18. The only subcortical structure showing significant differences in rsFC was the caudate nucleus. Specifically, we measured increased rsFC with anterior cingulate and right insula, two mesolimbic regions pertaining to the Salience Network. The degree of hyper-rsFC positively correlated with ADHD symptomatology, and showed different patterns of evolution in ADHD vs neurotypical subjects. Finally, the rsFC scores allowed a fair discrimination of the ADHD group (Area Under the Curve ≥ 0.7). These findings shed further light on the fundamental role covered by subcortical structures in ADHD pathogenesis and neurodevelopment, providing new evidence to fill the gap between neurofunctional and clinical expressions of ADHD.

•From rest to task, GSCORR reduces in sensory but increases in associative areas.•Reallocation of functional resources from sensory to associative regions at task.•Two distinct clusters of areas are recruited during GO and STOP trials.•GSCORR correlates with deactivation rather than activation.•GSCORR, activation and deactivation reflect distinct neurofunctional processes. The dynamics of global, state-dependent reconfigurations in brain connectivity are yet unclear. We aimed at assessing reconfigurations of the global signal correlation coefficient (GSCORR), a measure of the connectivity between each voxel timeseries and the global signal, from resting-state to a stop-signal task. The secondary aim was to assess the relationship between GSCORR and blood-oxygen-level-dependent (BOLD) activations or deactivation across three different trial-conditions (GO, STOP-correct, and STOP-incorrect). As primary analysis we computed whole-brain, voxel-wise GSCORR during resting-state (GSCORR-rest) and stop-signal task (GSCORR-task) in 107 healthy subjects aged 21–50, deriving GSCORR-shift as GSCORR-task minus GSCORR-rest. GSCORR-tr and trGSCORR-shift were also computed on the task residual time series to quantify the impact of the task-related activity during the trials. To test the secondary aim, brain regions were firstly divided in one cluster showing significant task-related activation and one showing significant deactivation across the three trial conditions. Then, correlations between GSCORR-rest/task/shift and activation/deactivation in the two clusters were computed. As sensitivity analysis, GSCORR-shift was computed on the same sample after performing a global signal regression and GSCORR-rest/task/shift were correlated with the task performance. Sensory and temporo-parietal regions exhibited a negative GSCORR-shift. Conversely, associative regions (ie. left lingual gyrus, bilateral dorsal posterior cingulate gyrus, cerebellum areas, thalamus, posterolateral parietal cortex) displayed a positive GSCORR-shift (FDR-corrected p < 0.05). GSCORR-shift showed similar patterns to trGSCORR-shift (magnitude increased) and after global signal regression (magnitude decreased). Concerning BOLD changes, Brodmann area 6 and inferior parietal lobule showed activation, while posterior parietal lobule, cuneus, precuneus, middle frontal gyrus showed deactivation (FDR-corrected p < 0.05). No correlations were found between GSCORR-rest/task/shift and beta-coefficients in the activation cluster, although negative correlations were observed between GSCORR-task and GO/STOP-correct deactivation (Pearson rho=-0.299/-0.273; Bonferroni-p < 0.05). Weak associations between GSCORR and task performance were observed (uncorrected p < 0.05). GSCORR state-dependent reconfiguration indicates a reallocation of functional resources to associative areas during stop-signal task. GSCORR, activation and deactivation may represent distinct proxies of brain states with specific neurofunctional relevance.

Human navigation of social interactions relies on the processing of emotion on faces. This meta-analysis aimed to produce an updated brain atlas of emotional face processing from whole-brain studies based on a single emotional face–viewing paradigm (PROSPERO CRD42022251548). We conducted a systematic literature search of Embase, MEDLINE and PsycINFO from May 2008 to October 2021. We used seed-based d mapping with permutation of subject images to conduct a quantitative meta-analysis of functional neuroimaging contrasts between emotional (e.g., angry, happy) and neutral faces. We conducted agglomerative hierarchical clustering of meta-analytic map contrasts of emotional faces relative to neutral faces. We investigated lateralization of emotional face processing. From 5549 studies identified, 55 data sets (1489 healthy participants) met our inclusion criteria. Relative to neutral faces, we found extensive activation clusters by fearful faces in the right inferior temporal gyrus, right fusiform area, left putamen and amygdala, right parahippocampalgyrus and cerebellum; we found smaller activation clusters by angry faces in the right cerebellum and right middle temporal gyrus (MTG) and by disgusted faces in the left MTG. Happy and sad faces did not reach statistical significance. Clustering analyses showed similar activation patterns of fearful and angry faces; activation patterns of happy and sad faces showed the least correlation with other emotional faces. Emotional face processing was predominantly left-lateralized in the amygdala and anterior insula, and right-lateralized in the ventromedial prefrontal cortex. Reliance on discretized effect sizes based on peak coordinate location instead of statistical brain maps, and the varying level of statistical threshold reporting from original studies, could lead to underdetection of smaller clusters of activation. Processing of emotional faces appeared to be oriented toward identifying threats on faces, from highest (i.e., angry or fearful faces) to lowest level (i.e., happy or sad faces), with a more complex lateralization pattern than previously theorized. Emotional faces may be processed in latent grouping but organized by threat content rather than emotional valence.

Abstract RationaleThe use of intravenous valproate is not approved for clinical practice in psychiatry. Literature data pointed out for a potential usefulness of this route of administration for valproate, but there is no actual consensus.ObjectivesThe aim of the present systematic review is to assess the effectiveness of intravenous valproate in agitation as well as general safety.MethodsA systematic review of studies evaluating the use of intravenous valproate in agitation was conducted. Additionally, safety was evaluated in all randomized trials involving the use of intravenous valproate in all medical conditions (epilepsy, migraine and psychiatric conditions).ResultsFor the systematic review on effectiveness in agitation, the search yielded 965 articles overall. After removing duplicates, 9411 articles were screened by title and abstract, and 39 of these were evaluated at a full-text level. Six studies were considered eligible for qualitative synthesis: one RCT and case report (n = 3), followed by cohort studies (n = 2). For the systematic review on safety, twenty-two RCTs were considered eligible for quantitative synthesis.ConclusionIntravenous valproate seems efficacious in reducing agitation in psychiatric patients; it generally appears safe compared to other neuroleptics or antiepileptics. However, the evidence is still not strong as it relies mainly on open-label studies or case series.

The COVID-19 pandemic has posed a serious challenge for the life and mental health of people with autism spectrum disorder (ASD). COVID-19 sanitary restrictions led to significant changes in the lives of people with ASD, including their routines; similarly, these modifications affected the daily activities of the daycare centers which they attended. The present retrospective study evaluated the impact of COVID-19 restrictions on challenging behaviors in a cohort of people with severe ASD attending a daycare center in Italy at the beginning of the pandemic. During the first two weeks of the pandemic, we did not observe variations in challenging behaviors. This suggests that adaptations used to support these individuals with ASD in adapting to the COVID-19 emergency restrictions were effective for managing their behavior.

In spite of the growing awareness on medical students’ mental health in recent years, epidemiologic literature about the topic is scarce, particularly for what concerns suicide. Here, we collected cases of suicides among medical students enrolled at a local University in Italy and compared it to the general population of the same age group. Our sample was collected using records of suicides in the city of Pavia, Italy between the years of 2014 and 2019. This record was cross-referenced with enrolment numbers to the Medical Faculty of the city in order to select cases that involved medical students A time-window of 6 years was chosen for the evaluation. The odds ratio of suicide in medical students in comparison to the general population was of 14.58 (p value at the exact Poisson test <0.001). We then differentiated between native Italians and students from abroad. In this case, an odds ratio of 6.81 was observed (p value at the exact Poisson test 0.011). Our estimated suicide rates exceeded what was previously reported for the general population. We call for a closer attention on mental health in medical students, and an increased effort in collecting objective data on the topic.

Background: The clinical high risk for psychosis (CHR-P) phase represents an opportunity for prevention and early intervention in young adults, which also could focus on improving physical health trajectories. Methods: We conducted a RECORD-compliant clinical register-based cohort study. The primary outcome was to describe the physical health of assessed CHR-P individuals, obtained via Electronic Health Records at the South London and Maudsley (SLaM) NHS Foundation Trust, UK (January 2013–October 2020). Results: The final database included 194 CHR-P subjects (46% female). Mean age was 23.70 ± 5.12 years. Percentage of tobacco smokers was 41% (significantly higher than in the age-matched general population [24%]). We found that 49% of subjects who consumed alcohol had an AUDIT-C (Alcohol Use Disorder Identification Test) score above 5 (hazardous drinking), with an average score of 4.94 (significantly higher than in the general population [2.75]). Investigating diet revealed low fiber intake in most subjects and high saturated fat intake in 10% of the individuals. We found that 47% of CHR-P subjects met the UK recommended physical activity guidelines (significantly lower than in the general population [66%]). Physical parameters (e.g., weight, heart rate, blood pressure) were not significantly different from the general population. Conclusions: This evidence corroborates the need for monitoring physical health parameters in CHR-P subjects, to implement tailored interventions that target daily habits.