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Autism spectrum disorder (ASD) is a developmental disorder under-diagnosed in adults. To date, no consistent evidence of alterations in brain structure has been reported in adults with ASD and few studies were conducted at that age. We analyzed structural magnetic resonance imaging data from 167 high functioning adults with ASD and 195 controls. We ran our analyses on a discovery (n = 301) and a replication sample (n = 61). The right caudal anterior cingulate cortical thickness was significantly thinner in adults with ASD compared to controls in both the discovery and the replication sample. Our work underlines the relevance of studying the brain anatomy of an adult ASD population.

Background: Abnormal maturation of brain connectivity is supposed to underlie the dysfunctional emotion regulation in patients with bipolar disorder (BD). To test this hypothesis, white matter integrity is usually investigated using measures of water diffusivity provided by MRI. Here we consider a more intuitive aspect of the morphometry of the white matter tracts: the shape of the fibre bundles, which is associated with neurodevelopment. We analyzed the shape of 3 tracts involved in BD: the cingulum (CG), uncinate fasciculus (UF) and arcuate fasciculus (AF). Methods: We analyzed diffusion MRI data in patients with BD and healthy controls. The fibre bundles were reconstructed using Q-ball-based tractography and automated segmentation. Using Isomap, a manifold learning method, the differences in the shape of the reconstructed bundles were visualized and quantified. Results: We included 112 patients and 82 controls in our analysis. We found the left AF of patients to be further extended toward the temporal pole, forming a tighter hook than in controls. We found no significant difference in terms of shape for the left UF, the left CG or the 3 right fasciculi. However, in patients compared with controls, the ventrolateral branch of the left UF in the orbitofrontal region had a tendency to be larger, and the left CG of patients had a tendency to be smaller in the frontal lobe and larger in the parietal lobe. Limitations: This was a cross-sectional study. Conclusion: Our results suggest neurodevelopmental abnormalities in the left AF in patients with BD. The statistical tendencies observed for the left UF and left CG deserve further study., Introduction Models of bipolar disorder (BD) assume that an altered neurodevelopment leads to a dysfunctional corticolimbic connectivity, causing an emotional dysregulation. (1) The corticolimbic communication largely relies on structural brain [...]

Background: Previous studies have reported MRI abnormalities of the corpus callosum (CC) in patients with bipolar disorder (BD), although only a few studies have directly compared callosal areas in psychotic versus nonpsychotic patients with this disorder. We sought to compare regional callosal areas in a large international multicentre sample of patients with BD and healthy controls. Methods: We analyzed anatomic [T.sub.1] MRI data of patients with BD-I and healthy controls recruited from 4 sites (France, Germany, Ireland and the United States). We obtained the mid-sagittal areas of 7 CC subregions using an automatic CC delineation. Differences in regional callosal areas between patients and controls were compared using linear mixed models (adjusting for age, sex, handedness, brain volume, history of alcohol abuse/dependence, lithium or antipsychotic medication status, symptomatic status and site) and multiple comparisons correction. We also compared regional areas of the CC between patients with BD with and without a history of psychotic features. Results: We included 172 patients and 146 controls in our study. Patients with BD had smaller adjusted mid-sagittal CC areas than controls along the posterior body, the isthmus and the splenium of the CC. Patients with a positive history of psychotic features had greater adjusted area of the rostral CC region than those without a history of psychotic features. Limitations: We found small to medium effect sizes, and there was no calibration technique among the sites. Conclusion: Our results suggest that BD with psychosis is associated with a different pattern of interhemispheric connectivity than BD without psychosis and could be considered a relevant neuroimaging subtype of BD., Introduction Bipolar disorder (BD) is associated with widespread abnormalities of white matter tracts, including the corpus callosum (CC). (1-3) Microstructural impairments of white matter are increasingly considered a relevant endophenotype [...]

Cerebellar abnormalities have been reported in autism spectrum disorder (ASD). Beyond its role in hallmark features of ASD, the cerebellum and its connectivity with forebrain structures also play a role in navigation. However, the current understanding of navigation abilities in ASD is equivocal, as is the impact of the disorder on the functional anatomy of the cerebellum. In the present study, we investigated the navigation behavior of a population of ASD and typically developing (TD) adults related to their brain anatomy as assessed by structural and functional MRI at rest. We used the Starmaze task, which permits assessing and distinguishing two complex navigation behaviors, one based on allocentric learning and the other on egocentric learning of a route with multiple decision points. Compared to TD controls, individuals with ASD showed similar exploration, learning, and strategy performance and preference. In addition, there was no difference in the structural or functional anatomy of the cerebellar circuits involved in navigation between the two groups. The findings of our work suggest that navigation abilities, spatio‐temporal memory, and their underlying circuits are preserved in individuals with ASD. Lay Summary: In our study, adults with autism spectrum disorders (ASD) were able to learn and use different navigation strategies, similar to typically developing adults. Specific cerebellum regions needed for these abilities are thought to be affected in ASD. However, we found no difference in their volume or in their functioning at rest. Navigation and its associated brain circuits seem to be preserved in adults with ASD. [ABSTRACT FROM AUTHOR]

According to global neuronal workspace (GNW) theory, conscious access relies on long-distance cerebral connectivity to allow a global neuronal ignition coding for conscious content. In patients with schizophrenia and bipolar disorder, both alterations in cerebral connectivity and an increased threshold for conscious perception have been reported. The implications of abnormal structural connectivity for disrupted conscious access and the relationship between these two deficits and psychopathology remain unclear. The aim of this study was to determine the extent to which structural connectivity is correlated with consciousness threshold, particularly in psychosis. We used a visual masking paradigm to measure consciousness threshold, and diffusion MRI tractography to assess structural connectivity in 97 humans of either sex with varying degrees of psychosis: healthy control subjects (n = 46), schizophrenia patients (n = 25), and bipolar disorder patients with (n = 17) and without (n = 9) a history of psychosis. Patients with psychosis (schizophrenia and bipolar disorder with psychotic features) had an elevated masking threshold compared with control subjects and bipolar disorder patients without psychotic features. Masking threshold correlated negatively with the mean general fractional anisotropy of white matter tracts exclusively within the GNW network (inferior frontal-occipital fasciculus, cingulum, and corpus callosum). Mediation analysis demonstrated that alterations in longdistance connectivity were associated with an increased masking threshold, which in turn was linked to psychotic symptoms. Our findings support the hypothesis that long-distance structural connectivity within the GNW plays a crucial role in conscious access, and that conscious access may mediate the association between impaired structural connectivity and psychosis. [ABSTRACT FROM AUTHOR]

Autism spectrum disorder (ASD) is a developmental disorder underdiagnosed in adults. To date, no consistent evidence of alterations in brain structure has been reported in adults with ASD and few studies were conducted at that age. We analyzed structural magnetic resonance imaging data from 167 high functioning adults with ASD and 195 controls. We ran our analyses on a discovery (n = 301) and a replication sample (n = 61). The right caudal anterior cingulate cortical thickness was significantly thinner in adults with ASD compared to controls in both the discovery and the replication sample. Our work underlines the relevance of studying the brain anatomy of an adult ASD population. [ABSTRACT FROM AUTHOR]

The current theory implying local, short-range overconnectivity in autism spectrum disorder, contrasting with long-range underconnectivity, is based on heterogeneous results, on limited data involving functional connectivity studies, on heterogeneous paediatric populations and non-specific methodologies. In this work, we studied short-distance structural connectivity in a homogeneous population of males with high-functioning autism spectrum disorder and used a novel methodology specifically suited for assessing U-shaped short-distance tracts, including a recently developed tractography-based atlas of the superficial white matter fibres. We acquired diffusion-weighted MRI for 58 males (27 subjects with high-functioning autism spectrum disorder and 31 control subjects) and extracted the mean generalized fractional anisotropy of 63 short-distance tracts. Neuropsychological evaluation included Wechsler Adult Intelligence Scale IV (WAIS-IV), Communication Checklist-Adult, Empathy Quotient, Social Responsiveness Scale and Behaviour Rating Inventory of Executive Function-Adult (BRIEF-A). In contradiction with the models of short-range over-connectivity in autism spectrum disorder, we found that patients with autism spectrum disorder had a significantly decreased anatomical connectivity in a component comprising 13 short tracts compared to controls. Specific short-tract atypicalities in temporal lobe and insula were significantly associated with clinical manifestations of autism spectrum disorder such as social awareness, language structure, pragmatic skills and empathy, emphasizing their importance in social dysfunction. Short-range decreased anatomical connectivity may thus be an important substrate of social deficits in autism spectrum disorder, in contrast with current models. [ABSTRACT FROM AUTHOR]

Objectives: Brain sulcation is an indirect marker of neurodevelopmental processes. Studies of the cortical sulcation in bipolar disorder have yielded mixed results, probably due to high variability in clinical phenotype. We investigated whole‐brain cortical sulcation in a large sample of selected patients with high neurodevelopmental load. Methods: A total of 263 patients with bipolar disorder I and 320 controls were included in a multicentric magnetic resonance imaging (MRI) study. All subjects underwent high‐resolution T1‐weighted brain MRI. Images were processed with an automatized pipeline to extract the global sulcal index (g‐SI) and the local sulcal indices (l‐SIs) from 12 a priori determined brain regions covering the whole brain. We compared l‐SI and g‐SI between patients with and without early‐onset bipolar disorder and between patients with and without a positive history of psychosis, adjusting for age, gender and handedness. Results: Patients with early‐onset bipolar disorder had a higher l‐SI in the right prefrontal dorsolateral region. Patients with psychotic bipolar disorder had a decreased l‐SI in the left superior parietal cortex. No group differences in g‐SI or l‐SI were found between healthy subjects and the whole patient cohort. We could replicate the early‐onset finding in an independent cohort. Conclusions: Our work suggests that bipolar disorder is not associated with generalized abnormalities of sulcation, but rather with localized changes of cortical folding restricted to patients with a heavy neurodevelopmental loading. These findings support the hypothesis that bipolar disorder is heterogeneous but may be disentangled using MRI, and suggest the need for investigations into neurodevelopmental deviations in the disorder. [ABSTRACT FROM AUTHOR]

The synaptosomal-associated protein SNAP25 is a key player in synaptic vesicle docking and fusion and has been associated with multiple psychiatric conditions, including schizophrenia, bipolar disorder, and attention-deficit/hyperactivity disorder. We recently identified a promoter variant in SNAP25, rs6039769, that is associated with early-onset bipolar disorder and a higher gene expression level in human prefrontal cortex. In the current study, we showed that this variant was associated both in males and females with schizophrenia in two independent cohorts. We then combined in vitro and in vivo approaches in humans to understand the functional impact of the at-risk allele. Thus, we showed in vitro that the rs6039769 C allele was sufficient to increase the SNAP25 transcription level. In a postmortem expression analysis of 33 individuals affected with schizophrenia and 30 unaffected control subjects, we showed that the SNAP25b/SNAP25a ratio was increased in schizophrenic patients carrying the rs6039769 at-risk allele. Last, using genetics imaging in a cohort of 71 subjects, we showed that male risk carriers had an increased amygdala-ventromedial prefrontal cortex functional connectivity and a larger amygdala than non-risk carriers. The latter association has been replicated in an independent cohort of 121 independent subjects. Altogether, results from these multilevel functional studies are bringing strong evidence for the functional consequences of this allelic variation of SNAP25 on modulating the development and plasticity of the prefrontal-limbic network, which therefore may increase the vulnerability to both early-onset bipolar disorder and schizophrenia. [ABSTRACT FROM AUTHOR]

Background: Abnormal maturation of brain connectivity is supposed to underlie the dysfunctional emotion regulation in patients with bipolar disorder (BD). To test this hypothesis, white matter integrity is usually investigated using measures of water diffusivity provided by MRI. Here we consider a more intuitive aspect of the morphometry of the white matter tracts: the shape of the fibre bundles, which is associated with neurodevelopment. We analyzed the shape of 3 tracts involved in BD: the cingulum (CG), uncinate fasciculus (UF) and arcuate fasciculus (AF). Methods: We analyzed diffusion MRI data in patients with BD and healthy controls. The fibre bundles were reconstructed using Q-ball-based tractography and automated segmentation. Using Isomap, a manifold learning method, the differences in the shape of the reconstructed bundles were visualized and quantified. Results: We included 112 patients and 82 controls in our analysis. We found the left AF of patients to be further extended toward the temporal pole, forming a tighter hook than in controls. We found no significant difference in terms of shape for the left UF, the left CG or the 3 right fasciculi. However, in patients compared with controls, the ventrolateral branch of the left UF in the orbitofrontal region had a tendency to be larger, and the left CG of patients had a tendency to be smaller in the frontal lobe and larger in the parietal lobe. Limitations: This was a cross-sectional study. Conclusion: Our results suggest neurodevelopmental abnormalities in the left AF in patients with BD. The statistical tendencies observed for the left UF and left CG deserve further study. [ABSTRACT FROM AUTHOR]

Dear Editor, The biological mechanisms underlying the efficacy of lithium therapy remain largely unknown. Here, we report a replication of our previous results - higher neurite density within the left frontal cortex - in patients under lithium therapy compared with patients without lithium therapy, in a completely independent sample. [Extracted from the article]

Cerebellar abnormalities have been reported in autism spectrum disorder (ASD). Beyond its role in hallmark features of ASD, the cerebellum and its connectivity with forebrain structures also play a role in navigation. However, the current understanding of navigation abilities in ASD is equivocal, as is the impact of the disorder on the functional anatomy of the cerebellum. In the present study, we investigated the navigation behavior of a population of ASD and typically developing (TD) adults related to their brain anatomy as assessed by structural and functional MRI at rest. We used the Starmaze task, which permits assessing and distinguishing two complex navigation behaviors, one based on allocentric learning and the other on egocentric learning of a route with multiple decision points. Compared to TD controls, individuals with ASD showed similar exploration, learning, and strategy performance and preference. In addition, there was no difference in the structural or functional anatomy of the cerebellar circuits involved in navigation between the two groups. The findings of our work suggest that navigation abilities, spatio-temporal memory, and their underlying circuits are preserved in individuals with ASD., (© 2022 The Authors. Autism Research published by International Society for Autism Research and Wiley Periodicals LLC.)

Background: Lithium (Li) is the gold standard treatment for bipolar disorder (BD). However, its mechanisms of action remain unknown but include neurotrophic effects. We here investigated the influence of Li on cortical and local grey matter (GM) volumes in a large international sample of patients with BD and healthy controls (HC)., Methods: We analyzed high-resolution T1-weighted structural magnetic resonance imaging scans of 271 patients with BD type I (120 undergoing Li) and 316 HC. Cortical and local GM volumes were compared using voxel-wise approaches with voxel-based morphometry and SIENAX using FSL. We used multiple linear regression models to test the influence of Li on cortical and local GM volumes, taking into account potential confounding factors such as a history of alcohol misuse., Results: Patients taking Li had greater cortical GM volume than patients without. Patients undergoing Li had greater regional GM volumes in the right middle frontal gyrus, the right anterior cingulate gyrus, and the left fusiform gyrus in comparison with patients not taking Li., Conclusions: Our results in a large multicentric sample support the hypothesis that Li could exert neurotrophic and neuroprotective effects limiting pathological GM atrophy in key brain regions associated with BD.

The synaptosomal-associated protein SNAP25 is a key player in synaptic vesicle docking and fusion and has been associated with multiple psychiatric conditions, including schizophrenia, bipolar disorder, and attention-deficit/hyperactivity disorder. We recently identified a promoter variant in SNAP25 , rs6039769 , that is associated with early-onset bipolar disorder and a higher gene expression level in human prefrontal cortex. In the current study, we showed that this variant was associated both in males and females with schizophrenia in two independent cohorts. We then combined in vitro and in vivo approaches in humans to understand the functional impact of the at-risk allele. Thus, we showed in vitro that the rs6039769 C allele was sufficient to increase the SNAP25 transcription level. In a postmortem expression analysis of 33 individuals affected with schizophrenia and 30 unaffected control subjects, we showed that the SNAP25b / SNAP25a ratio was increased in schizophrenic patients carrying the rs6039769 at-risk allele. Last, using genetics imaging in a cohort of 71 subjects, we showed that male risk carriers had an increased amygdala-ventromedial prefrontal cortex functional connectivity and a larger amygdala than non-risk carriers. The latter association has been replicated in an independent cohort of 121 independent subjects. Altogether, results from these multilevel functional studies are bringing strong evidence for the functional consequences of this allelic variation of SNAP25 on modulating the development and plasticity of the prefrontal-limbic network, which therefore may increase the vulnerability to both early-onset bipolar disorder and schizophrenia. SIGNIFICANCE STATEMENT Functional characterization of disease-associated variants is a key challenge in understanding neuropsychiatric disorders and will open an avenue in the development of personalized treatments. Recent studies have accumulated evidence that the SNARE complex, and more specifically the SNAP25 protein, may be involved in psychiatric disorders. Here, our multilevel functional studies are bringing strong evidence for the functional consequences of an allelic variation of SNAP25 on modulating the development and plasticity of the prefrontal-limbic network. These results demonstrate a common genetically driven functional alteration of a synaptic mechanism both in schizophrenia and early-onset bipolar disorder and confirm the shared genetic vulnerability between these two disorders., (Copyright © 2017 the authors 0270-6474/17/3710390-09$15.00/0.)

The Kraepelinian dichotomy between schizophrenia (SZ) and bipolar disorder (BD) is being challenged by recent epidemiological and biological studies. We performed a comparative review of neuroimaging features in both conditions at several scales: whole-brain and regional volumes, brain activity, connectivity, and networks. Structural volumetric neuroimaging studies suggest a common pattern of volume decreases, but networks studies reveal a clearer distinction between BD and SZ with an altered connectivity generalized to all brain networks in SZ and restricted to limbic, paralimbic, and interhemispheric networks in BD., (© The Author 2014. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

There is an urgent need to identify objective biomarkers for the assessment of bipolar disorder, to improve diagnosis and prognostic evaluation. Neuroimaging is a particularly promising approach. We review here the structural and functional neuroimaging studies carried out on bipolar disorder. These studies have led to the development of neurobiological models of bipolar disorder assuming cortical-limbic dysregulation. Dorsal brain structures are thought to decrease in volume and activity in bipolar disorder, reducing inhibition of the ventral-limbic network and enhancing emotional responses. These models also assume abnormal prefrontal-subcortical limbic connectivity. This abnormal connectivity has been identified by both diffusion tensor imaging studies (anatomical connectivity) and functional MRI (functional connectivity). However, studies are currently limited by the heterogeneity of the patients included. Future research should include studies to validate biomarkers for the assessment of bipolar disorder and studies of large and well characterized samples of patients with bipolar disorder.

Day Care Hospitals represent efficient structures for the treatment of various psychatric disorders through a large variety of medical care. In the litterature, multiple terms are used to define the various models of Day Care Hospitals, according to their use, their orientation and their therapeutic programmes. Our aim in this study is to compare, through a search on "Medline", the various existing models of Day Care Hospitals in France and in Belgium. Thereafter, the "specific" model which exists at the Centre Hospitalier du Luxembourg will be described. Two main types of Day Care Hospitals are described in the litterature: the "classical" type, with mainly a support fuction, resides on the downstream side of hospitalisation and the "specific" type, with a care function for a short duration, resides on its upstream side. The model developed at the Centre Hospitalier du Luxembourg is upstream the hospital. From our study, it is concluded that, rather of being an inconvenience, the large number of existing Day Care Hospitals, which differ by various specificities, represent excellent complementary opportunities for the current care of mental diseases.