scholarly journals On the relationship of first-episode psychosis to the amphetamine-sensitized state: a dopamine D2/3 receptor agonist radioligand study

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Ana Weidenauer ◽  
Martin Bauer ◽  
Ulrich Sauerzopf ◽  
Lucie Bartova ◽  
Lukas Nics ◽  
...  
Keyword(s):  
Healthy Volunteers ◽  
Receptor Agonist ◽  
Dopamine Release ◽  
First Episode Psychosis ◽  
First Episode ◽  
Single Pair ◽  
Dopamine System ◽  
Prefrontal Cortical ◽  
Positron Emission ◽  
Episode Psychosis

AbstractSchizophrenia is characterized by increased behavioral and neurochemical responses to dopamine-releasing drugs. This prompted the hypothesis of psychosis as a state of “endogenous” sensitization of the dopamine system although the exact basis of dopaminergic disturbances and the possible role of prefrontal cortical regulation have remained uncertain. To show that patients with first-episode psychosis release more dopamine upon amphetamine-stimulation than healthy volunteers, and to reveal for the first time that prospective sensitization induced by repeated amphetamine exposure increases dopamine-release in stimulant-naïve healthy volunteers to levels observed in patients, we collected data on amphetamine-induced dopamine release using the dopamine D2/3 receptor agonist radioligand [11C]-(+)-PHNO and positron emission tomography. Healthy volunteers (n = 28, 14 female) underwent a baseline and then a post-amphetamine scan before and after a mildly sensitizing regimen of repeated oral amphetamine. Unmedicated patients with first-episode psychosis (n = 21; 6 female) underwent a single pair of baseline and then post-amphetamine scans. Furthermore, T1 weighted magnetic resonance imaging of the prefrontal cortex was performed. Patients with first-episode psychosis showed larger release of dopamine compared to healthy volunteers. After sensitization of healthy volunteers their dopamine release was significantly amplified and no longer different from that seen in patients. Healthy volunteers showed a negative correlation between prefrontal cortical volume and dopamine release. There was no such relationship after sensitization or in patients. Our data in patients with untreated first-episode psychosis confirm the “endogenous sensitization” hypothesis and support the notion of impaired prefrontal control of the dopamine system in schizophrenia.

scholarly journals O8.4. CORTICAL DOPAMINE RELEASE IN RESPONSE TO A COGNITIVE CHALLENGE: PRELIMINARY RESULTS IN FIRST EPISODE PSYCHOSIS AND CLINICAL HIGH RISK

2019 ◽  
Vol 45 (Supplement_2) ◽  
pp. S184-S184
Author(s):  
Abanti Tagore ◽  
Naren Rao ◽  
Christin Schifani ◽  
Huai-Hsuan Tseng ◽  
Pablo Rusjan ◽  
...  
Keyword(s):  
High Risk ◽  
Dopamine Release ◽  
First Episode Psychosis ◽  
First Episode ◽  
Clinical High Risk ◽  
Preliminary Results ◽  
Episode Psychosis ◽  
Cognitive Challenge

scholarly journals No association between cortical dopamine D2 receptor availability and cognition in antipsychotic-naive first-episode psychosis

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Maria Lee ◽  
Helena Fatouros-Bergman ◽  
Pontus Plavén-Sigray ◽  
Pauliina Ikonen Victorsson ◽  
Carl M. Sellgren ◽  
...  
Keyword(s):  
Dopamine D2 Receptor ◽  
D2 Receptor ◽  
Brain Regions ◽  
First Episode Psychosis ◽  
First Episode ◽  
Dopamine D2 ◽  
Clinical Observations ◽  
Positron Emission ◽  
Episode Psychosis ◽  
Dorsolateral Prefrontal

AbstractCognitive impairment is an important predictor of disability in schizophrenia. Dopamine neurotransmission in cortical brain regions has been suggested to be of importance for higher-order cognitive processes. The aim of this study was to examine the relationship between extrastriatal dopamine D2-R availability and cognitive function, using positron emission tomography and the high-affinity D2-R radioligand [11C]FLB 457, in an antipsychotic-naive sample of 18 first-episode psychosis patients and 16 control subjects. We observed no significant associations between D2-R binding in the dorsolateral prefrontal cortex or hippocampus (β = 0.013–0.074, partial r = −0.037–0.273, p = 0.131–0.841). Instead, using Bayesian statistics, we found moderate support for the null hypothesis of no relationship (BFH0:H1 = 3.3–8.2). Theoretically, our findings may suggest a lack of detrimental effects of D2-R antagonist drugs on cognition in schizophrenia patients, in line with clinical observations.

scholarly journals Expression and Functionality Study of 9 Toll-Like Receptors in 33 Drug-Naïve Non-Affective First Episode Psychosis Individuals: A 3-Month Study

2020 ◽  
Vol 21 (17) ◽  
pp. 6106
Author(s):  
Maria Juncal-Ruiz ◽  
Laura Riesco-Davila ◽  
Javier Vazquez-Bourgon ◽  
Victor Ortiz-Garcia de la Foz ◽  
Jacqueline Mayoral-Van Son ◽  
...  
Keyword(s):  
Healthy Volunteers ◽  
Mononuclear Cells ◽  
First Episode Psychosis ◽  
First Episode ◽  
Antipsychotic Treatment ◽  
Toll Like Receptors ◽  
Peripheral Blood Mononuclear ◽  
Episode Psychosis ◽  
Tnf Α ◽  
Drug Naïve

Toll-like receptors (TLRs) are a pivotal component of the innate immune system that seem to have a role in the pathogenesis of psychosis. The purpose of this work was to compare the expression and functionality of 9 TLRs in three peripheral blood mononuclear cells (PBMCs) (monocytes, B cells, and T cells) between 33 drug-naïve first-episode psychosis (FEP) individuals and 26 healthy volunteers, at baseline and after 3-month of antipsychotic treatment. The expression of TLRs 1–9 were assessed by flow cytometry. For the assessment of the TLR functionality, cells collected in sodium heparin tubes were polyclonally stimulated for 18 h, with different agonists for human TLR1–9. The results of our study highlight the role that TLR5 and TLR8 might play in the pathophysiology of psychosis. We found a lower expression of these receptors in FEP individuals, regarding healthy volunteers at baseline and after 3-month of treatment on the three PBMCs subsets. Most TLRs showed a lower functionality (especially reduced intracellular levels of TNF-α) in patients than in healthy volunteers. These results, together with previous evidence, suggest that individuals with psychosis might show a pattern of TLR expression that differs from that of healthy volunteers, which could vary according to the intensity of immune/inflammatory response.

scholarly journals M7. LOWER THALAMIC DOPAMINE D2-RECEPTOR BINDING IN DRUG-NAIVE PATIENTS WITH PSYCHOSIS – A REPLICATION STUDY USING POSITRON EMISSION TOMOGRAPHY

2020 ◽  
Vol 46 (Supplement_1) ◽  
pp. S135-S136
Author(s):  
Pauliina Victorsson ◽  
Pontus Plavén-Sigray ◽  
Granville Matheson ◽  
Alexander Santillo ◽  
Maria Lee ◽  
...  
Keyword(s):  
High Resolution ◽  
Bayes Factor ◽  
Dopamine D2 Receptor ◽  
D2 Receptor ◽  
First Episode Psychosis ◽  
First Episode ◽  
Cohen’S D ◽  
Positron Emission ◽  
Episode Psychosis ◽  
Cohen's D

Abstract Background The dopamine system is a central focus of research on the pathophysiology and treatment of schizophrenia. With regard to the dopamine D2-receptor (D2-R), Positron Emission Tomography (PET) studies have shown a small increase in striatal receptor availability. In contrast, a more recent line of research has demonstrated lower levels of D2-R (Cohen’s D = -0.32) in the thalamus, a region of key interest for the pathophysiology of schizophrenia. However, some studies included patients previously on antipsychotic medication, or were performed using radioligands with suboptimal affinity for the much lower D2-R density in thalamus compared to striatum. In addition, the resolution of previous PET systems has not allowed for a more detailed analysis of functional thalamic subregions. Here we examined a fully antipsychotic-naïve sample of first-episode psychosis patients using the high-affinity D2-R radioligand [11C]FLB457 and high-resolution PET. The aim was to a) replicate previous findings of lower D2-R in thalamus in patients and b) specifically examine patient-control differences in thalamic subregions based on their cortical connectivity. Methods Nineteen antipsychotic-naïve first episode psychosis patients (mean age = 29.3; sd = 6.3, 11 males) and 19 age- and sex matched healthy comparison subjects were included in the analysis. PET measurements were obtained using a High Resolution Research Tomograph (HRRT). A ROI for whole thalamus was defined using the FSL Harvard Oxford Subcortical Atlas, whereas ROIs for thalamic subregions were based on the Oxford Thalamic Connectivity Atlas. Binding potential (BPND) was calculated using the Logan graphical analysis with cerebellum as reference region. The statistical analyses, which were all pre-registered, were performed using frequentist and Bayesian paired-samples t-tests. Results The frequentist paired t-test showed that patients had significantly lower binding than control subjects in whole thalamus (Cohen’s D = -0.479, p = 0.026). Bayes factor from the Bayesian paired t-test indicated that there was approximately 5 times more support for the hypothesis of lower BPND in patients, compared to the null hypothesis of no difference. Among subregions, the ROI corresponding to prefrontal thalamic connectivity showed the largest effect (Cohen’s D = -0.527, p = 0.017), and Bayes factor indicated that there was 6 times more support for lower BPND in patients compared to no difference. Discussion Using high resolution PET and a high affinity D2-R radioligand in antipsychotic-naïve first-episode psychosis patients, this study replicates the previously reported meta-analytical effect size of lower thalamic receptor availability in patients. The strongest effect was observed in the subregion dominated by connections to prefrontal cortex. The findings may reflect a dysregulation of the thalamic dopamine system in schizophrenia, which in turn could underlie aberrant functional connectivity in key fronto-thalamic circuits.

scholarly journals An In Vivo MRI Study of Prefrontal Cortical Complexity in First-Episode Psychosis

2005 ◽  
Vol 162 (1) ◽  
pp. 65-70 ◽  
Author(s):  
Laura C. Wiegand ◽  
Simon K. Warfield ◽  
James J. Levitt ◽  
Yoshio Hirayasu ◽  
Dean F. Salisbury ◽  
...  
Keyword(s):  
First Episode Psychosis ◽  
First Episode ◽  
Prefrontal Cortical ◽  
Episode Psychosis ◽  
Mri Study

scholarly journals Effective Connectivity and Dopaminergic Function of Fronto-Striato-Thalamic Circuitry in First-Episode Psychosis, Established Schizophrenia, and Healthy Controls

2021 ◽  
Author(s):  
Kristina Sabaroedin ◽  
Adeel Razi ◽  
Sidhant Chopra ◽  
Nancy Tran ◽  
Andrii Pozaruk ◽  
...  
Keyword(s):  
Symptom Severity ◽  
Effective Connectivity ◽  
First Episode Psychosis ◽  
Striatal Dopamine ◽  
Positive Symptom ◽  
Dopamine Synthesis ◽  
First Episode ◽  
Positron Emission ◽  
Episode Psychosis ◽  
Patient Groups

Dysfunction of fronto-striato-thalamic (FST) circuits is thought to contribute to dopaminergic dysfunction and symptom onset in psychosis, but it remains unclear whether this dysfunction is driven by aberrant bottom-up subcortical signaling or impaired top-down cortical regulation. Here, we used spectral dynamic causal modelling (DCM) of resting-state functional magnetic resonance imaging (fMRI) to characterize the effective connectivity of dorsal and ventral FST circuits in a sample of 46 antipsychotic-naive first-episode psychosis (FEP) patients and 23 controls and an independent sample of 36 patients with established schizophrenia (SCZ) patients and 100 controls. We found that midbrain and thalamic connectivity were implicated across both patient groups. Dysconnectivity in FEP patients was mainly restricted to the subcortex, with positive symptom severity being associated with midbrain connectivity. Dysconnectivity between the cortex and subcortical systems was only apparent in SCZ patients. In another independent sample of 33 healthy individuals who underwent concurrent fMRI and [18F]DOPA positron emission tomography, we found that striatal dopamine synthesis capacity was associated with the effective connectivity of nigrostriatal and striatothalamic pathways, implicating similar circuits as those associated with psychotic symptom severity in patients. Our findings thus indicate that subcortical dysconnectivity is salient in the early stages of psychosis, that cortical dysfunction may emerge later in the illness, and that nigrostriatal and striatothalamic signaling are closely related to striatal dopamine synthesis capacity, which is a robust risk marker for psychosis.

scholarly journals Hypofrontality in men with first-episode psychosis

2005 ◽  
Vol 186 (3) ◽  
pp. 203-208 ◽  
Author(s):  
V. Molina ◽  
J. Sanz ◽  
S. Reig ◽  
R. Martínez ◽  
F. Sarramea ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
First Episode Psychosis ◽  
First Episode ◽  
Psychotic Episode ◽  
Attention Task ◽  
Positron Emission ◽  
Episode Psychosis ◽  
Dorsolateral Prefrontal ◽  
Prefrontal Region ◽  
And Control

BackgroundDecreased metabolic activity in the prefrontal cortex during cognitive activation is a recurrent finding and a likely functional marker of schizophrenia.AimsTo investigate the occurrence of hypofrontality in patients with first-episode psychosis, with or without evolution to schizophrenia.MethodWe used fluorodeoxyglucose positron emission tomography during the performance of an attention task and magnetic resonance imaging to study the dorsolateral prefrontal region in 13 men with a first episode of psychosis. Data from patients who progressed to schizophrenia were compared with those of patients who did not meet criteria for this diagnosis after 2 years.ResultsPatients who developed schizophrenia demonstrated a significant hypofrontality in the dorsolateral prefrontal cortex in comparison with the non-schizophrenia and control groups.ConclusionsOur results suggest that hypofrontality could be a marker of schizophrenia at the time of the first psychotic episode, in agreement with neurodevelopmental theories of schizophrenia.

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