Introduction Bipolar disorder has been repeatedly associated with abnormalities of white matter. However, DTI is intrinsically limited and the precise cellular mechanisms that underlie these alterations remains unknown. Objectives Our aim was to investigate microscopical characteristics of white matter using MRI in patients with bipolar and healthy controls. Methods 77 patients and 71 controls from 3 sites had a T1 structural MRI, a multi-shell HARDI MRI and at one site with a T1-weighted VFA-SPGR acquisition, and a T2 MSME acquisition. The volume fraction and the orientation dispersion was extracted using NODDI from DW images in each site. Myelin Water Fraction was extracted in 33 patients and 36 controls to probe myelin characteristics. White matter bundles were reconstructed using deterministic tractography. Statistical analyses were performed after harmonization by the ComBat algorithm and controlled for age, gender and handedness. Results We found significant lower axonal density in patients along the short fibers of the left cingulum, the left anterior arcuate and the left inferior fronto-occipital fasciculus. We found lower mean MWF in patients along the short fibers of the right cingulum, the left inferior fronto-occipital fasciculus, the left anterior arcuate and the splenium of the corpus callosum. We found higher mean orientation dispersion in patients only along the left uncinate fasciculus. Conclusions We report alterations of limbic and inter-hemispheric white matter tracts in patients with bipolar disorder reflecting axonal loss, demyelination and architecture alterations. These results contribute to better capture the plurality of the mechanisms involved in bipolar disorder that cannot be deciphered with classical diffusion MRI. Disclosure No significant relationships.

Background: Mental disorders are at-risk of severe COVID-19 outcomes. There is limited and heterogeneous national data in hospital settings evaluating the risks associated with any pre-existing mental disorder, and susceptible subgroups. Our study aimed to investigate the association between pre-existing psychiatric disorders and outcomes of adults hospitalised for COVID-19. Method: We used data obtained from the French national hospital database linked to the state-level psychiatric registry. The primary outcome was 30-days in-hospital mortality. Secondary outcomes were to compare the length of hospital stay, Intensive Care Unit (ICU) admission and ICU length. Propensity score matching analysis was used to control for COVID-19 confounding factors between patients with or without mental disorder and stratified by psychiatric subgroups. Results: Among 97 302 adults hospitalised for COVID-19 from March to September 2020, 10 083 (10.3%) had a pre-existing mental disorder, mainly dementia (3581 [35.5%]), mood disorders (1298 [12.9%]), anxiety disorders (995 [9.9%]), psychoactive substance use disorders (960 [9.5%]), and psychotic disorders (866 [8.6%]). In propensity-matched analysis, 30-days in-hospital mortality was increased among those with at least one preexisting mental disorder (hazard ratio (HR) 1.15, 95% CI 1.08-1.23), psychotic disorder (1.90, 1.24-2.90), and psychoactive substance disorders (1.53, 1.10-2.14). The odds of ICU admission were consistently decreased for patients with any pre-existing mental disorder (OR 0.83, 95% CI 0.76-0.92) and for those with dementia (0.64, 0.53-0.76). Conclusion: Pre-existing mental disorders were independently associated with in-hospital mortality. These findings underscore the important need for adequate care and targeted interventions for at-risk individuals with severe mental illness.

Ecotoxicological studies that try to describe the effects of particulate matter (PM) on human health are important in order to gain a deeper understanding of their effects in disease outcomes. Because exposure protocols are not easily comparable, evaluating human PM exposure is a difficult task. Thus, interpreting ambiguous or conflicting results from different experiments could lead to misleading conclusions about the true nature of PM effects. To address these issues, we compiled a collection of relevant research articles in order to compare present PM exposure methods and extract data related to concentration, inhalation rates (IR), and doses. We also compare the experimental exposure levels reported in these articles to PM levels around the world. In particular, our dataset covers reported results from 75 research articles. To allow for comparison between protocols, we used this data to fit a normalization equation that depends upon concentration, exposure time, dose, inhalability, and physiological parameters. Based on the collected research papers, instillation is the prevalent exposure method. Also, the median PM IR from these experiments is three orders of magnitude higher than the PM IR found in environmental conditions (EAP). Experiments employing inhalation of concentrated PM show IR results that are two orders of magnitude higher than EAP; these results are cause for concerns, since the PM exposure were acute, sudden, and higher than the worst-case exposure scenarios reported by the world megacities. We also found that different PM exposure protocols are sources for the observed variability in physiological response results found from animal models. We discuss these findings and make suggestions for future exposure methodologies. Such considerations should be valuable for quantifying PM exposure in disease outcomes.

OBJECTIVE:The cerebellum is involved in cognitive processing and emotion control. Cerebellar alterations could explain symptoms of schizophrenia spectrum disorder (SZ) and bipolar disorder (BD). In addition, literature suggests that lithium might influence cerebellar anatomy. Our aim was to study cerebellar anatomy in SZ and BD, and investigate the effect of lithium.METHODS:Participants from 7 centers worldwide underwent a 3T MRI. We included 182 patients with SZ, 144 patients with BD, and 322 controls. We automatically segmented the cerebellum using the CERES pipeline. All outputs were visually inspected.RESULTS:Patients with SZ showed a smaller global cerebellar gray matter volume compared to controls, with most of the changes located to the cognitive part of the cerebellum (Crus II and lobule VIIb). This decrease was present in the subgroup of patients with recent-onset SZ. We did not find any alterations in the cerebellum in patients with BD. However, patients medicated with lithium had a larger size of the anterior cerebellum, compared to patients not treated with lithium.CONCLUSION:Our multicenter study supports a distinct pattern of cerebellar alterations in SZ and BD.

Neurons in the supragranular layers of the human cerebral cortex play an important role in long-range cortico-cortical connections. Alterations to these layers are of special interest in autism spectrum disorder (ASD) as they could play a significant role in altered connectivity between distal regions of cortex. The present study isolated sampling boxes through the use of an automated boundary identification technique. A two-dimensional analysis of the Nissl-stained tissue was then performed to examine whether differences in cell size and number are present in ASD tissue. The analysis focused on layers II and III of association cortex sampled from frontal (BA9), temporal (BA21), and parietal (BA7) regions. In previous studies, both BA9 and BA21 have been linked to alterations in cortical connectivity in ASD. Aside from the expected differences between cortical layers and regions, data analysis revealed that ASD tissue possessed a higher density of cells, the magnitude of which was layer dependent, and that the cell profiles were of a smaller size. The results of this study suggest that cellular abnormalities with respect to cell size and number are present in multiple areas of association cortex, specifically within layers that are involved in long-range connectivity. Additionally, the results comport with previous findings of altered cortical minicolumns in frontal and temporal areas and further suggest that similar irregularities may also be present in parietal areas.

Disruptions in affective processing characterize mood disorders, yet the neural mechanisms underlying internal state dependency in affective processes are not well understood. The present work presents a pilot investigation into state dependency among neural circuits known to be involved in processing affective information, by examining acute manic and depressive mood phases in adults with bipolar disorder and major depressive disorder.The present study probed affective processes with a well-validated passive picture-viewing task amongst acutely manic (n = 8) or acutely depressed (bipolar depression: n = 11; major depression: n = 15) mood-disordered adults during functional magnetic resonance imaging .Beta-series correlation analyses seeded from the amygdala revealed distinct neural circuits distinguished across current mood state rather than diagnostic boundaries. We delineated an amygdala-striatum pathway that distinguished depressed from manic mood phase, rather than between diagnostic boundaries, in processing valenced information. Specifically, we found differences in this neural response to negative, but not positive, images across clinical mood states.As a preliminary investigation of state-dependent affective processes, the current investigation is predominantly limited by the small sample size. While it provides direction and generates hypotheses for further work, future studies need to replicate and expand the reported effects with larger samples.These findings demonstrate the conditions under which mood state-dependent affective processes cut cross traditional diagnostic boundaries, speaking to recent advances in transdiagnostic disease mechanisms, and can guide future work examining the neural mechanisms driving symptomatology in affective disorders.

Medium-range order structure is the one of the important local structural units in the field of bulk metallic glasses. The rapid solidification of Cu50Zr40Al10 ternary alloy is investigated by molecular dynamics simulation. Simultaneously, the connections between the full icosahedral and defective icosahedral clusters in medium-range order structures of Cu50Zr40Al10 alloy are characterized systematically by the quantitative method and visualization analysis. The results reveal that the icosahedral clusters as the main structures with high structural stability are bonded with each other by interpenetrating connection, and form the triangle, double triangle, triple triangle, tetrahedron and chain connected icosahedral medium-range order clusters. Moreover, the icosahedral and defective icosahedral clusters prefer to link with each other and form the bigger medium-range order clusters with different configurations in this system. These structures keep the high structural stability of icosahedral medium-range order section and the structural variability of chain-like medium-range order structures.

ObjectiveStructural MRI (sMRI) increasingly offers insight into abnormalities inherent to schizophrenia. Previous machine learning applications suggest that individual classification is feasible and reliable and, however, is focused on the predictive performance of the clinical status in cross‐sectional designs, which has limited biological perspectives. Moreover, most studies depend on relatively small cohorts or single recruiting site. Finally, no study controlled for disease stage or medication's effect. These elements cast doubt on previous findings’ reproducibility.MethodWe propose a machine learning algorithm that provides an interpretable brain signature. Using large datasets collected from 4 sites (276 schizophrenia patients, 330 controls), we assessed cross‐site prediction reproducibility and associated predictive signature. For the first time, we evaluated the predictive signature regarding medication and illness duration using an independent dataset of first‐episode patients.ResultsMachine learning classifiers based on neuroanatomical features yield significant intersite prediction accuracies (72%) together with an excellent predictive signature stability. This signature provides a neural score significantly correlated with symptom severity and the extent of cognitive impairments. Moreover, this signature demonstrates its efficiency on first‐episode psychosis patients (73% accuracy).ConclusionThese results highlight the existence of a common neuroanatomical signature for schizophrenia, shared by a majority of patients even from an early stage of the disorder.

ObjectiveThe posterior superior temporal sulcus (pSTS) plays a critical role in the ‘social brain’. Its neurodevelopment and relationship with the social impairment in autism spectrum disorders (ASD) are not well understood. We explored the relationship between social cognition and the neurodevelopment of the pSTS in ASD.MethodWe included 44 adults with high‐functioning ASD and 36 controls. We assessed their performances on the ‘Reading the mind in the eyes’ test (for 34 of 44 subjects with ASD and 30 of 36 controls), their fixation time on the eyes with eye tracking (for 35 of 44 subjects with ASD and 30 of 36 controls) and the morphology of the caudal branches of the pSTS (length and depth), markers of the neurodevelopment, with structural MRI.ResultsThe right anterior caudal ramus of the pSTS was significantly longer in patients with ASD compared with controls (52.6 mm vs. 38.3 mm; P = 1.4 × 10−3; Cohen's d = 0.76). Its length negatively correlated with fixation time on the eyes (P = 0.03) in the ASD group and with the ‘Reading the mind in the eyes’ test scores in both groups (P = 0.03).ConclusionOur findings suggest that the neurodevelopment of the pSTS is related to the ASD social impairments.

Objective There is growing evidence that cerebellum plays a crucial role in cognition and emotional regulation. Cerebellum is likely to be involved in the physiopathology of both bipolar disorder and schizophrenia. The objective of our study was to compare cerebellar size between patients with bipolar disorder, patients with schizophrenia, and healthy controls in a multicenter sample. In addition, we studied the influence of psychotic features on cerebellar size in patients with bipolar disorder. Method One hundred and fifteen patients with bipolar I disorder, 32 patients with schizophrenia, and 52 healthy controls underwent 3 Tesla MRI . Automated segmentation of cerebellum was performed using FreeSurfer software. Volumes of cerebellar cortex and white matter were extracted. Analyses of covariance were conducted, and age, sex, and intracranial volume were considered as covariates. Results Bilateral cerebellar cortical volumes were smaller in patients with schizophrenia compared with patients with bipolar I disorder and healthy controls. We found no significant difference of cerebellar volume between bipolar patients with and without psychotic features. No change was evidenced in white matter. Conclusion Our results suggest that reduction in cerebellar cortical volume is specific to schizophrenia. Cerebellar dysfunction in bipolar disorder, if present, appears to be more subtle than a reduction in cerebellar volume.