Human Fronto-Tectal and Fronto-Striatal-Tectal Pathways Activate Differently During Anti-Saccades

Almost all cortical areas in the vertebrate brain take part in recurrent connections through the subcortical basal ganglia (BG) nuclei, through parallel inhibitory and excitatory loops. It has been suggested that these circuits can modulate our reactions to external events such that appropriate reactions are chosen from many available options, thereby imposing volitional control over behavior. The saccade system is an excellent model system to study cortico-BG interactions. In this study two possible pathways were investigated that might regulate automaticity of eye movements in the human brain; the cortico-tectal pathway, running directly between the frontal eye fields (FEF) and superior colliculus (SC) and the cortico-striatal pathway from the FEF to the SC involving the caudate nucleus (CN) in the BG. In an event-related functional magnetic resonance imaging (fMRI) paradigm participants made pro- and anti-saccades. A diffusion tensor imaging (DTI) scan was made for reconstruction of white matter tracts between the FEF, CN and SC. DTI fiber tracts were used to divide both the left and right FEF into two sub-areas, projecting to either ipsilateral SC or CN. For each of these FEF zones an event-related fMRI timecourse was extracted. In general activity in the FEF was larger for anti-saccades. This increase in activity was lateralized with respect to anti-saccade direction in FEF zones connected to the SC but not for zones only connected to the CN. These findings suggest that activity along the contralateral FEF–SC projection is responsible for directly generating anti-saccades, whereas the pathway through the BG might merely have a gating function withholding or allowing a pro-saccade

Non-steroidal anti-inflammatory drugs and the risk of psychosis

The objective of the current research was to examine the relation between nonsteroidal anti-inflammatory drugs (NSAID) use and risk of psychosis. To this end we performed a longitudinal case-control study using prescription data from a Dutch health insurance company. Men aged 25 years or over and women aged 30 years or over were excluded to prevent inclusion of non-incident cases. This resulted in eighty-two cases and 359 randomly selected controls from the same population. The overall relative risk of incident antipsychotic use for NSAID users, adjusted for age and prescription frequency, was 0.80 (95% CI: 0.48-1.33). After stratification for gender the risk of psychosis was significantly lower (59%) in male NSAID users only. The relative risks for male and female subjects were 0.41 (95% CI: 0.17-0.97) and 1.31 (95% CI: 0.65-2.64), respectively. These results suggest that in men NSAIDs may lower the risk of psychosis. (c) 2006 Elsevier B.V. and ECNP. All rights reserved

Impaired Cerebellar Functional Connectivity in Schizophrenia Patients and Their Healthy Siblings

The long-standing notion of schizophrenia as a disorder of connectivity is supported by emerging evidence from recent neuroimaging studies, suggesting impairments of both structural and functional connectivity in schizophrenia. However, investigations are generally restricted to supratentorial brain regions, thereby excluding the cerebellum. As increasing evidence suggests that the cerebellum contributes to cognitive and affective processing, aberrant connectivity in schizophrenia may include cerebellar dysconnectivity. Moreover, as schizophrenia is highly heritable, unaffected family members of schizophrenia patients may exhibit similar connectivity profiles. The present study applies resting-state functional magnetic resonance imaging to determine cerebellar functional connectivity profiles, and the familial component of cerebellar connectivity profiles, in 62 schizophrenia patients and 67 siblings of schizophrenia patients. Compared to healthy control subjects, schizophrenia patients showed impaired functional connectivity between the cerebellum and several left-sided cerebral regions, including the hippocampus, thalamus, middle cingulate gyrus, triangular part of the inferior frontal gyrus, supplementary motor area, and lingual gyrus (all p < 0.0025, whole-brain significant). Importantly, siblings of schizophrenia patients showed several similarities to patients in cerebellar functional connectivity, suggesting that cerebellar dysconnectivity in schizophrenia might be related to familial factors. In conclusion, our findings suggest that dysconnectivity in schizophrenia involves the cerebellum and that this defect may be related to the risk to develop the illness

Système d’Information pour l’Analyse du Métabolisme Territorial (SINAMET)

Les études de métabolisme territorial, c'est-à-dire l'analyse des flux de matières et d'énergie mobilisés par le système socio-économique d'un territoire, permettent d'obtenir des informations pertinentes pour évaluer l'impact de nos sociétés sur l'environnement. Mais de telles études sont longues et complexes à réaliser : Les données à mobiliser et à traiter sont nombreuses et dispersées, et les résultats peuvent être difficilement appréhendables. La façon de visualiser les informations sur le métabolisme est ainsi un élément important des études, le but étant de correspondre aux différents besoins des acteurs territoriaux. Les techniques de traitement des données étant jusqu'à présent essentiellement manuelles, nous présentons un Système d'INformation pour l'Analyse du MEtabolisme Territorial (SINAMET) qui a pour objectif de faciliter l’automatisation des traitements de données afin de rendre les résultats des études plus accessibles. Le SINAMET s’adresse à plusieurs profils d’usagers, allant du simple néophyte curieux des résultats finaux, jusqu’à des utilisateurs plus familier du traitement de données, qui pourront facilement implémenter leurs méthodes de traitement grâce à des fonctionnalités génériques intégrées dans le système d’information en cours de développement. Le SINAMET se base sur une architecture logicielle structurée autour d'un noyau logiciel et pouvant être enrichit de modules dédiés aux opérations d’importations, de traitement ou d'exportation/visualisation des données. Le système d’information inclut également une base de données structurée selon une ontologie voulue simple mais fonctionnelle pour agréger un grand nombre de données sur le métabolisme. Les notions de Territoire, Acteur, Flux, Stock, Omes (Objet/Matière/Energie/Service) et Transformation sont établies comme base conceptuelle permettant de manipuler l'information. Ce paradigme est renforcé par l'utilisation d'un mapping objet-relationnel (ORM) permettant d'abstraire la gestion d'une base de données, au profit d’une approche orienté objet. Les futures contributions pourront ainsi se concentrer sur le développement d’algorithmes de traitement de données et enrichir ainsi les fonctionnalités du SINAMET. L'approche présentée a été partiellement concrétisée à travers un prototype, une version alpha 0.1, qui a fourni des premiers résultats que nous présentons. Les travaux doivent être cependant poursuivis pour rendre réellement opérationnelle la solution logicielle. Notamment, la création d'une communauté autour du projet semble un point nécessaire pour son développement. Les futurs avancements du projet seront communiqués à l’adresse : https://metabolisme-territorial.fr/wiki/index.php/Siname

Disrupted upregulation of salience network connectivity during acute stress in siblings of schizophrenia patients

BACKGROUND: An adaptive neural stress response is essential to adequately cope with a changing environment. It was previously argued that sympathetic/noradrenergic activity during acute stress increases salience network (SN) connectivity and reduces executive control network (ECN) connectivity in healthy controls, with opposing effects in the late aftermath of stress. Altered temporal dynamics of these networks in response to stress are thought to play a role in the development of psychopathology in vulnerable individuals. METHODS: We exposed male healthy controls (n = 40, mean age = 33.9) and unaffected siblings of schizophrenia patients (n = 39, mean age = 33.2) to the stress or control condition of the trier social stress test and subsequently investigated resting state functional connectivity of the SN and ECN directly after and 1.5 h after stress. RESULTS: Acute stress resulted in increased functional connectivity within the SN in healthy controls, but not in siblings (group × stress interaction pfwe < 0.05). In the late aftermath of stress, stress reduced functional connectivity within the SN in both groups. Moreover, we found increased functional connectivity between the ECN and the cerebellum in the aftermath of stress in both healthy controls and siblings of schizophrenia patients. CONCLUSIONS: The results show profound differences between siblings of schizophrenia patients and controls during acute stress. Siblings lacked the upregulation of neural resources necessary to quickly and adequately cope with a stressor. This points to a reduced dynamic range in the sympathetic response, and may constitute a vulnerability factor for the development of psychopathology in this at-risk group

Social behavior and autism traits in a sex chromosomal disorder:Klinefelter (47XXY) syndrome

Although Klinefelter syndrome (47,XXY) has been associated with psychosocial difficulties, knowledge of the social behavioral phenotype is limited. We examined specific social abilities and autism traits in Klinefelter syndrome. Scores of 31 XXY men on the Scale for Interpersonal Behavior and the Autism Spectrum Questionnaire were compared to 24 and 20 control men respectively. XXY men reported increased distress during social interactions and less engagement in specific social behaviors. In the XXY group, levels of autism traits were significantly higher across all dimensions of the autism phenotype. These findings call for a clinical investigation of vulnerability to autism in Klinefelter syndrome. Klinefelter syndrome might serve as a model for studying a role of the X chromosome in social behavioral dysfunction and autism-like behavior

Brain structure, IQ, and psychopathology in young offspring of patients with schizophrenia or bipolar disorder

BACKGROUND.: Studying offspring of schizophrenia (SZo) and bipolar disorder patients (BDo) provides important information on the putative neurodevelopmental trajectories underlying development toward severe mental illnesses. We compared intracranial volume (ICV), as a marker for neurodevelopment, and global and local brain measures between SZo or BDo and control offspring (Co) in relation to IQ and psychopathology. METHODS.: T1-weighted magnetic resonance imaging (MRI) brain scans were obtained from 146 participants (8-19 years; 40 SZo, 66 BDo, 40 Co). Linear mixed models were applied to compare ICV, global, and local brain measures between groups. To investigate the effect of ICV, IQ (four subtests Wechsler Intelligence Scale for Children/Wechsler Adult Intelligence Scale-III) or presence of psychopathology these variables were each added to the model. RESULTS.: SZo and BDo had significantly lower IQ and more often met criteria for a lifetime psychiatric disorder than Co. ICV was significantly smaller in SZo than in BDo (d = -0.56) and Co (d = -0.59), which was largely independent of IQ (respectively, d = -0.54 and d = -0.35). After ICV correction, the cortex was significantly thinner in SZo than in BDo (d = -0.42) and Co (d = -0.75) and lateral ventricles were larger in BDo than in Co (d = 0.55). Correction for IQ or lifetime psychiatric diagnosis did not change these findings. CONCLUSIONS.: Despite sharing a lower IQ and a higher prevalence of psychiatric disorders, brain abnormalities in BDo appear less pronounced (but are not absent) than in SZo. Lower ICV in SZo implies that familial risk for schizophrenia has a stronger association with stunted early brain development than familial risk for bipolar disorder

The role of depression in the prediction of a "late" remission in first-episode psychosis:An analysis of the OPTiMiSE study

Objective: The identification of predictors of psychosis remission could guide early clinical decision-making for treatment of first-episode schizophrenia (FES). Methods: We analyzed two non-independent subsamples of patients with FES ages 18-40 years from the OPTiMiSE study dataset to investigate the demographic and clinical factors that might help to differentiate "late" re-mitters (i.e., not in remission at week 2 or 4, but achieving remission within a 10-week follow-up period) from non-remitters within the same period. Results: Subsample 1 included 216 individuals (55 females, mean age 25.9 years) treated with amisulpride in an open-label design who were not in remission at week 2. Early symptomatic response between baseline and week 2 (odds ratio (OR)- 4.186, 95% confidence interval (CI)- 2.082-8.416, p < 0.001) and older age (OR- 1.081, 95% = CI 1.026-1.138, p- 0.003) were the only variables significantly associated with a higher probability of psychosis remission at week 4. Subsample 2 was composed of the 72 participants (19 females, mean age 25.1 years) who were not in remission at week 4 and completed a 6-week double-blind randomized trial comparing continuation of amisulpride with switch to olanzapine. Depression at baseline (as measured with the Calgary Depression Scale for Schizophrenia) was significantly associated with a nearly 3-fold lower likelihood of psychosis remission during the 10-week follow-up (hazard ratio = 2.865, 95% CI = 1.187-6.916, p = 0.019). Conclusion: Our results reinforce the importance of assessing depressive symptoms in people with FES and support the relevance of an early response (as early as 2 weeks) as a predictor of clinical outcome in this population. (C) 2021 Elsevier B.V. All rights reserved

The Community Assessment of Psychic Experiences:Optimal cut-off scores for detecting individuals with a psychotic disorder

OBJECTIVES: The need for a brief screening tool for psychosis is widely recognized. The Community Assessment of Psychic Experiences (CAPE) is a popular self‐report measure of psychosis, but a cut‐off score that can detect those most likely to fulfill diagnostic criteria for psychotic disorder is not established. METHODS: A case–control sample from the Genetic Risk and Outcome of Psychosis Project study (N = 1375, healthy individuals, n = 507, and individuals with a psychotic disorder, n = 868), was used to examine cut‐off scores of the CAPE with receiver operating curve analyses. We examined 27 possible cut‐off scores computed from a combination of scores from the frequency and distress scales of the various factors of the CAPE. RESULTS: The weighted severity positive symptom dimension was most optimal in detecting individuals with a psychotic disorder (>1.75 cut‐off; area under the curve = 0.88; sensitivity, 75%; specificity, 88%), which correctly identified 80% of the sample as cases or controls with a diagnostic odds ratio of 22.69. CONCLUSIONS: The CAPE can be used as a first screening tool to detect individuals who are likely to fulfill criteria for a psychotic disorder. The >1.75 cut‐off of the weighted severity positive symptom dimension provides a better prediction than all alternatives tested so far