scholarly journals PET studies of the glial cell marker TSPO in psychosis patients - a meta-analysis using individual participant data

2017 ◽  
Author(s):  
Pontus Plavén-Sigray ◽  
Granville J. Matheson ◽  
Karin Collste ◽  
Abhishekh H. Ashok ◽  
Jennifer M. Coughlin ◽  
...  
Keyword(s):  
Immune Cells ◽  
Temporal Cortex ◽  
Strong Support ◽  
First Episode Psychosis ◽  
Translocator Protein ◽  
First Episode ◽  
Healthy Controls ◽  
Control Subjects ◽  
Episode Psychosis ◽  
Healthy Control

Background:Accumulating evidence suggests that the immune system may be an important target for new treatment approaches in schizophrenia. Positron emission tomography (PET) and radioligands binding to the translocator protein (TSPO), which is expressed in glial cells in brain including immune cells, represents a potential method for patient stratification and treatment monitoring. This study examined if patients with first episode psychosis and schizophrenia had altered TSPO levels as compared to healthy control subjects.Methods:PubMed was searched for studies comparing patients with psychosis to healthy controls using second-generation TSPO radioligands. The outcome measure was distribution volume (VT), an index of TSPO levels, in frontal cortex (FC), temporal cortex (TC) and hippocampus (HIP). Bayes factors (BF) were applied to examine the relative support for higher, lower or no-change of TSPO levels in patients as compared to healthy controls.Results:Five studies, with 75 patients with first-episode psychosis or schizophrenia and 77 healthy control subjects were included. BF showed strong support for lower patient VT relative to no-change (all BF>32) or relative to an increase (all BF>422) in all brain regions. From the posterior distributions, mean patient-control differences in standardized VT values were −0.48 for FC (95% credible interval (CredInt)=-0.88 to −0.09), −0.47 for TC (CredInt=−0.87 to −0.07) and −0.63 for HIP (CredInt=−1.00 to −0.25).Discussion:The observed reduction of TPSO in compared to control subjects in patients may correspond to altered function or lower density of brain immune cells. Future studies should focus on investigating the underlying biological mechanisms and their relevance for treatment.

scholarly journals T7. UPDATED INDIVIDUAL PARTICIPANT DATA META-ANALYSIS CONFIRMS LOWER LEVELS OF THE GLIAL MARKER TSPO IN PSYCHOSIS PATIENTS

2020 ◽  
Vol 46 (Supplement_1) ◽  
pp. S233-S233
Author(s):  
Pontus Plavén-Sigray ◽  
Granville Matheson ◽  
Jennifer Coughlin ◽  
Sina Hafizi ◽  
Heikki Laurikainen ◽  
...  
Keyword(s):  
Disease Duration ◽  
Meta Analysis ◽  
Strong Support ◽  
First Episode ◽  
Individual Participant Data ◽  
Control Subjects ◽  
Episode Psychosis ◽  
Individual Participant ◽  
Healthy Control ◽  
Glial Marker

Abstract Background Treatment targeting the immune system is a promising new approach in schizophrenia. In search for tools for stratification and treatment monitoring, much effort has been invested in the use of positron emission tomography (PET) and radioligands binding to a glial marker, the 18 kDa translocator protein (TSPO). We previously demonstrated lower TSPO in psychosis patients in an individual participant data (IPD) meta-analysis of studies using second generation TSPO radioligands (Plavén-Sigray et al., 2018). Subsequently, a summary-statistics meta-analysis, including one newly published study, showed no difference (Marques et al., 2019). Here, the aim was to repeat the IPD analysis including this new sample, and an additional unpublished dataset in first episode psychosis patients. The primary objective was to re-evaluate the hypotheses of 1) higher or 2) lower or 3) no difference in radioligand binding between patients and healthy control subjects. Secondary objectives were to assess the effects of antipsychotic medication on TSPO binding, as well as relationships between TSPO binding and disease duration and symptom measures. Methods Individual participant data were obtained from PET studies that 1) used a second generation TSPO radioligand, 2) reported distribution volume (VT) values in brain in patients with psychosis as compared to healthy controls, and 3) reported TSPO affinity type of all participants. The outcome measure was VT in frontal cortex (FC), temporal cortex (TC) and hippocampus (HIP). Bayes factors (BF) were applied to examine the relative support for higher, lower, or no-change of TSPO levels in patients compared to healthy controls. Results Individual participant data from seven studies were included, amounting to 99 patients with first-episode psychosis or schizophrenia and 109 healthy control subjects. In all regions investigated, BF showed moderate to strong support (BF > 5) for lower VT in patients as compared to no difference, and strong support (BF > 10) for lower VT compared to higher VT in patients. Mean patient-control differences in standardized VT values were -0.41 for FC (95%CI -0.67 to -0.15, p = 0.0022), -0.38 for TC (95%CI -0.64 to -0.12, p = 0.0048) and -0.53 for HIP (95% CI -0.79 to -0.27, p = 0.0001). The mean change in standardized VT due to medication was 0.10 for FC (CI95% -0.10 to 0.30, p = 0.615), -0.08 for TC (CI95% -0.32 to 0.48, p = 0.666) and 0.08 for HIP (CI95% -0.46 to 0.30, p = 0.682). No association was observed between VT and disease duration or symptom levels (all p > 0.526). Discussion In this updated IPD meta-analysis including two new datasets, we found moderate to strong support for lower TSPO in psychosis patients compared to control subjects. In vitro data has shown a lack of correspondence between TSPO and pro-inflammatory activation, also recently confirmed in a post-mortem study in schizophrenia. Hence, based on the present results no firm conclusions can be made regarding the pro- versus anti-inflammatory status of glial cells in psychosis patients. Additional work is needed to understand the biological relevance of the observed lower TSPO in patients.

Cognitive clusters in first-episode psychosis: Overlap with healthy controls and relationship to concurrent and prospective symptoms and functioning.

2017 ◽  
Vol 31 (7) ◽  
pp. 787-797 ◽  
Author(s):  
Jacqueline Uren ◽  
Susan M. Cotton ◽  
Eoin Killackey ◽  
Michael M. Saling ◽  
Kelly Allott
Keyword(s):  
First Episode Psychosis ◽  
First Episode ◽  
Healthy Controls ◽  
Episode Psychosis

scholarly journals Identifying Clinically and Functionally Distinct Groups Among Healthy Controls and First Episode Psychosis Patients by Clustering on EEG Patterns

2020 ◽  
Vol 11 ◽  
Author(s):  
Xiaodong Qu ◽  
Saran Liukasemsarn ◽  
Jingxuan Tu ◽  
Amy Higgins ◽  
Timothy J. Hickey ◽  
...  
Keyword(s):  
First Episode Psychosis ◽  
First Episode ◽  
Healthy Controls ◽  
Episode Psychosis

A-8 Developmental Cognitive Phenotypes in First-Episode Psychosis and Longitudinal Cognitive Change Following Antipsychotic Treatment

2021 ◽  
Vol 36 (6) ◽  
pp. 1030-1030
Author(s):  
Milena Y Gotra ◽  
Elmma Khalid ◽  
Madison M Dykins ◽  
Scot K Hill
Keyword(s):  
Cognitive Ability ◽  
Antipsychotic Medication ◽  
Cognitive Change ◽  
First Episode Psychosis ◽  
First Episode ◽  
Healthy Controls ◽  
Significant Group ◽  
Cognitive Improvement ◽  
Episode Psychosis ◽  
Chronic Psychosis

Abstract Objective The present study applied a developmentally based subgrouping procedure previously examined in chronic psychosis patients to a sample of first-episode psychosis (FEP) and examined change in cognition following treatment with antipsychotic medication. Method Medication naïve FEP patients (n = 119; age = 27.96; 63.9% male; 62.2% White, 32.8% Black, 5.0% Other) recruited during initial hospitalization were categorized into groups based on 1) estimated premorbid intellectual ability and 2) the discrepancy between predicted (modeled on 151 healthy controls) and current cognitive ability. Consistent with findings from chronic psychosis samples, groups were characterized as Preserved (n = 46; average premorbid, no discrepancy), Deteriorated (n = 44; average premorbid, significant discrepancy), and Compromised (n = 29, low premorbid and current cognitive ability). A mixed analysis of variance was used to examine change in a composite cognitive score derived from a comprehensive neuropsychological battery at baseline, 6 weeks, and 12 months. Results There was a significant group by time interaction [Figure 1; F(5.4142.4) = 2.81, p = 0.02] in which the Preserved group performed similar to healthy controls across all time points, the Compromised group demonstrated stable deficits after treatment, and the Deteriorated group diverged from the Compromised group at 6 weeks and 12 months. Discussion There is considerable cognitive heterogeneity in FEP at baseline and after initiation of antipsychotic medication. Findings of cognitive improvement in the Deteriorated group after treatment initiation suggests a differential response to antipsychotic medications that was not found in the Compromised or Preserved groups. Future work may benefit from examining medication and symptom severity as potential factors contributing to the unique change observed in the Deteriorated group.

scholarly journals S150. EMOTIONAL BEHAVIOUR IN HIGH-RISK AND FIRST-EPISODE PSYCHOSIS

2020 ◽  
Vol 46 (Supplement_1) ◽  
pp. S93-S93
Author(s):  
Irina Falkenberg ◽  
Huai-Hsuan Tseng ◽  
Gemma Modinos ◽  
Barbara Wild ◽  
Philip McGuire ◽  
...  
Keyword(s):  
High Risk ◽  
Emotion Recognition ◽  
Psychotic Disorders ◽  
First Episode Psychosis ◽  
First Episode ◽  
Healthy Controls ◽  
Emotional Faces ◽  
Facial Movements ◽  
Episode Psychosis ◽  
Ultra High Risk

Abstract Background Studies indicate that people with schizophrenia and first-episode psychosis experience deficits in their ability to accurately detect and display emotions through facial expressions, and that functioning and symptoms are associated with these deficits. This study aims to examine how emotion recognition and facial emotion expression are related to functioning and symptoms in a sample of individuals at ultra-high risk, first-episode psychosis and healthy controls. Methods During fMRI, we combined the presentation of emotional faces with the instruction to react with facial movements predetermined and assigned. 18 patients with first-episode psychosis (FEP), 18 individuals at ultra high risk of psychosis (UHR) and 22 healthy controls (HCs) were examined while viewing happy, sad, or neutral faces and were instructed to simultaneously move the corners of their mouths either (a). upwards or (b). downwards, or (c). to refrain from movement. The subjects’ facial movements were recorded with an MR-compatible video camera. Results Neurofunctional and behavioral response to emotional faces were measured. Analyses have only recently commenced and are ongoing. Full results of the clinical and functional impact of behavioral and neuroimaging results will be presented at the meeting. Discussion Increased knowledge about abnormalities in emotion recognition and behaviour as well as their neural correlates and their impact on clinical measures and functional outcome can inform the development of novel treatment approaches to improve social skills early in the course of schizophrenia and psychotic disorders.

scholarly journals Clinical utility of magnetic resonance imaging in first-episode psychosis

2017 ◽  
Vol 211 (4) ◽  
pp. 231-237 ◽  
Author(s):  
Irina Falkenberg ◽  
Stefania Benetti ◽  
Marie Raffin ◽  
Phillipe Wuyts ◽  
William Pettersson-Yeo ◽  
...  
Keyword(s):  
Magnetic Resonance Imaging ◽  
Magnetic Resonance ◽  
Clinical Sample ◽  
Great Majority ◽  
First Episode Psychosis ◽  
First Episode ◽  
Healthy Controls ◽  
Resonance Imaging ◽  
Episode Psychosis ◽  
Mri Scans

BackgroundThere is no consensus as to whether magnetic resonance imaging (MRI) should be used as part of the initial clinical evaluation of patients with first-episode psychosis (FEP).Aims(a) To assess the logistical feasibility of routine MRI; (b) to define the clinical significance of radiological abnormalities in patients with FEP.MethodRadiological reports from MRI scans of two FEP samples were reviewed; one comprised 108 patients and 98 healthy controls recruited to a research study and the other comprised 241 patients scanned at initial clinical presentation plus 66 healthy controls.ResultsIn the great majority of patients, MRI was logistically feasible. Radiological abnormalities were reported in 6% of the research sample and in 15% of the clinical sample (odds ratio (OR) = 3.1, 95% CI 1.26–7.57, χ2(1) = 6.63, P = 0.01). None of the findings necessitated a change in clinical management.ConclusionsRates of neuroradiological abnormalities in FEP are likely to be underestimated in research samples that often exclude patients with organic abnormalities. However, the majority of findings do not require intervention.

scholarly journals S166. EFFECTIVE CONNECTIVITY OF FRONTOSTRIATAL SYSTEMS IN FIRST-EPISODE PSYCHOSIS

2020 ◽  
Vol 46 (Supplement_1) ◽  
pp. S99-S100
Author(s):  
Kristina Sabaroedin ◽  
Adeel Razi ◽  
Kevin Aquino ◽  
Sidhant Chopra ◽  
Amy Finlay ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Nucleus Accumbens ◽  
Effective Connectivity ◽  
First Episode Psychosis ◽  
First Episode ◽  
Positive Symptoms ◽  
Healthy Controls ◽  
Top Down ◽  
Imaging Protocol ◽  
Episode Psychosis

Abstract Background Neuroimaging studies have found dysconnectivity of frontostriatal circuits across a broad spectrum of psychotic symptoms. However, it is unknown whether dysconnectivity within frontostriatal circuits originates from disrupted bottom-up or top-down control signaling within these systems. Here, we used dynamic causal modelling (DCM) to examine the effective connectivity of frontostriatal systems in first-episode psychosis (FEP). Methods A total of 55 FEP patients (26 males; mean [SD] age = 19.24 [2.89]) and 24 healthy controls (15 males; mean [SD] age = 21.83 [1.93]) underwent a resting-state functional magnetic resonance imaging protocol. Biologically plausible connections between eight left hemisphere regions encompassing the dorsal and ventral frontostriatal systems were modelled using spectral DCM. The regions comprise dorsolateral prefrontal cortex, ventromedial prefrontal cortex, anterior hippocampus, amygdala, dorsal caudate, nucleus accumbens, thalamus, and the midbrain. Effective connectivity between groups were assessed using a parametric Bayesian model. Associations between effective connectivity parameters and positive symptoms, measured by the Brief Psychiatric Rating Scale positive subscale, was assessed in the patient group in a separate Bayesian general linear model. Results DCM shows evidence for differences in effective connectivity between patients and healthy controls, namely in the bottom-down connections distributed in the frontostriatal system encompassing the hippocampus, amygdala, striatum, and midbrain. Compared to healthy controls, patients also demonstrated increased disinhibition of the midbrain. In patients, positive symptoms are associated with increased top-down connections to the midbrain. Outgoing connection from the midbrain to the nucleus accumbens is also increased in association with positive symptoms. Discussion Aberrant top-down connectivity in the frontostriatal system in patients is consistent with top-down dysregulation of dopamine function in FEP, as dopaminergic activity in the midbrain is proposed to be under the control of higher brain areas. In patients, increased self-inhibition of the midbrain, as well as symptom associations in both ingoing and outgoing connections of this region, are congruous with hyperactivity of the midbrain as proposed by the dopamine dysregulation hypothesis. Here, we demonstrate that mathematical models of brain imaging signals can be used to identify the key disruptions driving brain circuit dysfunction, identifying new targets for treatment.

Resting-state functional connectivity of the striatum predicts improvement in negative symptoms and general functioning in patients with first-episode psychosis: A 1-year naturalistic follow-up study

2019 ◽  
Vol 54 (5) ◽  
pp. 509-518 ◽  
Author(s):  
Sanghoon Oh ◽  
Minah Kim ◽  
Taekwan Kim ◽  
Tae Young Lee ◽  
Jun Soo Kwon
Keyword(s):  
Functional Connectivity ◽  
Anterior Cingulate Cortex ◽  
Negative Symptoms ◽  
Primary Motor Cortex ◽  
Cingulate Cortex ◽  
First Episode Psychosis ◽  
Anterior Cingulate ◽  
First Episode ◽  
Healthy Controls ◽  
Episode Psychosis

Objective: The persistent disease burden of psychotic disorders often comes from negative symptoms; however, prognostic biomarkers for negative symptoms have not been fully understood. This study investigated whether the altered functional connectivity of the striatum predicts improvement in negative symptoms and functioning after 1 year of usual treatment in patients with first-episode psychosis. Methods: Resting-state functional magnetic imaging was obtained from 40 first-episode psychosis patients and 40 age- and sex-matched healthy control subjects. Whole-brain functional connectivity maps were generated with subdivisions of the striatum as seed regions and compared between first-episode psychosis patients and healthy controls. In 22 patients with first-episode psychosis, follow-up assessments of negative symptom severity and general functional status were conducted after 1 year of usual treatment. Multiple regression analyses were performed to examine factors predictive of symptomatic or functional improvements over the 1-year period. Results: First-episode psychosis patients showed greater functional connectivity between the left dorsal caudate and left primary motor cortex, as well as between the left ventral rostral putamen and right temporal occipital fusiform cortex, than healthy controls. Lower functional connectivity between the right dorsal rostral putamen and anterior cingulate cortex was observed in the first-episode psychosis patients than in healthy controls. In multiple regression analyses, lower functional connectivity of the left dorsal caudate–left primary motor cortex/right dorsal rostral putamen–anterior cingulate cortex predicted improvement in negative symptoms. In addition, lower right dorsal rostral putamen–anterior cingulate cortex functional connectivity predicted improvement in general functioning. Conclusion: These results suggest that altered striatal functional connectivity can be a potent neurobiological marker in the prognosis prediction of first-episode psychosis. Furthermore, altered striatal functional connectivity may provide a potential target in developing treatments for negative symptoms.

scholarly journals 86. The Impact of Childhood Trauma on Brain Structure and Stress Response: Differences Between First-Episode Psychosis Patients and Healthy Controls

2017 ◽  
Vol 43 (suppl_1) ◽  
pp. S47-S48
Author(s):  
Simone Ciufolini ◽  
Valeria Mondelli ◽  
Matthew Kempton ◽  
Craig Morgan ◽  
Simone Reinders ◽  
...  
Keyword(s):  
Stress Response ◽  
Childhood Trauma ◽  
Brain Structure ◽  
First Episode Psychosis ◽  
First Episode ◽  
Healthy Controls ◽  
Episode Psychosis ◽  
The Impact
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