scholarly journals Precision weighting of cortical unsigned prediction error signals benefits learning, is mediated by dopamine, and is impaired in psychosis

2020 ◽  
Author(s):  
J. Haarsma ◽  
P. C. Fletcher ◽  
J. D. Griffin ◽  
H. J. Taverne ◽  
H. Ziauddeen ◽  
...  
Keyword(s):  
Dopamine Receptor ◽  
Prediction Error ◽  
First Episode Psychosis ◽  
Psychotic Symptoms ◽  
First Episode ◽  
Dopamine Receptor Agonist ◽  
Prediction Errors ◽  
Healthy Controls ◽  
Episode Psychosis ◽  
Dopaminergic Modulation

Abstract Recent theories of cortical function construe the brain as performing hierarchical Bayesian inference. According to these theories, the precision of prediction errors plays a key role in learning and decision-making, is controlled by dopamine and contributes to the pathogenesis of psychosis. To test these hypotheses, we studied learning with variable outcome-precision in healthy individuals after dopaminergic modulation with a placebo, a dopamine receptor agonist bromocriptine or a dopamine receptor antagonist sulpiride (dopamine study n = 59) and in patients with early psychosis (psychosis study n = 74: 20 participants with first-episode psychosis, 30 healthy controls and 24 participants with at-risk mental state attenuated psychotic symptoms). Behavioural computational modelling indicated that precision weighting of prediction errors benefits learning in health and is impaired in psychosis. FMRI revealed coding of unsigned prediction errors, which signal surprise, relative to their precision in superior frontal cortex (replicated across studies, combined n = 133), which was perturbed by dopaminergic modulation, impaired in psychosis and associated with task performance and schizotypy (schizotypy correlation in 86 healthy volunteers). In contrast to our previous work, we did not observe significant precision-weighting of signed prediction errors, which signal valence, in the midbrain and ventral striatum in the healthy controls (or patients) in the psychosis study. We conclude that healthy people, but not patients with first-episode psychosis, take into account the precision of the environment when updating beliefs. Precision weighting of cortical prediction error signals is a key mechanism through which dopamine modulates inference and contributes to the pathogenesis of psychosis.

scholarly journals Abnormal reward prediction error signalling in antipsychotic naïve individuals with first episode psychosis or clinical risk for psychosis

2017 ◽  
Author(s):  
Anna O Ermakova ◽  
Franziska Knolle ◽  
Azucena Justicia ◽  
Edward T Bullmore ◽  
Peter B Jones ◽  
...  
Keyword(s):  
At Risk ◽  
Prediction Error ◽  
First Episode Psychosis ◽  
Psychotic Symptoms ◽  
First Episode ◽  
Prediction Errors ◽  
Reward Prediction Error ◽  
Reward Prediction ◽  
Episode Psychosis ◽  
Risk Patients

AbstractOngoing research suggests preliminary, though not entirely consistent, evidence of neural abnormalities in signalling prediction errors in schizophrenia. Supporting theories suggest mechanistic links between the disruption of these processes and the generation of psychotic symptoms. However, it is not known at what stage in psychosis these impairments in prediction error signalling develop. One major confound in prior studies is the use of medicated patients with strongly varying disease durations. Our study aims to investigate the involvement of the meso-cortico-striatal circuitry during reward prediction error signalling in the earliest stages of psychosis. We studied patients with first episode psychosis (FEP) and help-seeking individuals at risk for psychosis due to subthreshold prodromal psychotic symptoms. Patients with either FEP (n = 14), or at-risk for developing psychosis (n= 30), and healthy volunteers (n = 39) performed a reinforcement learning task during fMRI scanning. ANOVA revealed significant (p<0.05 family-wise error corrected) prediction error signalling differences between groups in the dopaminergic midbrain and right middle frontal gyrus (dorsolateral prefrontal cortex, DLPFC). Patients with FEP showed disrupted reward prediction error signalling compared to controls in both regions. At-risk patients showed intermediate activation in the midbrain that significantly differed from controls and from FEP patients, but DLPFC activation that did not differ from controls. Our study confirms that patients with FEP have abnormal meso-cortical signalling of reward prediction errors, whilst reward prediction error dysfunction in the at-risk patients appears to show a more nuanced pattern of activation with a degree of midbrain impairment but preserved cortical function.

scholarly journals S10. SCREENING FOR ANTI-NMDAR ANTIBODIES AMONGST PATIENTS WITH FIRST EPISODE PSYCHOSIS

2020 ◽  
Vol 46 (Supplement_1) ◽  
pp. S33-S34
Author(s):  
Levente Herman ◽  
János Réthelyi ◽  
Réka Zsigmond
Keyword(s):  
First Episode Psychosis ◽  
Psychotic Symptoms ◽  
First Episode ◽  
Antibody Activity ◽  
Specific Method ◽  
Healthy Controls ◽  
Serum Samples ◽  
Nmdar Encephalitis ◽  
Episode Psychosis ◽  
Significant Difference

Abstract Background Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is an autoimmune limbic encephalitis, where psychiatric symptoms are often dominant in the initial phase. These patients are usually treated in psychiatric wards, due to first episode psychosis (FEP). The antibodies responsible for the symptoms, can be identified from the patients’ sera. During the past decade multiple studies had been launched to investigate whether anti-NMDAR antibodies were present in the sera of patients, treated with the diagnosis of schizophrenia, although results have not confirmed this hypothesis. It is possible, however, that autoimmune antibodies, which are not yet known, play a role in FEP, similarly to anti-NMDAR antibodies, therefore there is a rationale behind screening for other antibodies among these patients. The aim of our study is to screen patients with FEP for anti-NMDAR antibodies. We also would like to check whether there are any other potentially pathogenic antibodies, which are not yet known, but could be responsible for psychotic symptoms. Methods So far 26 patients have been recruited with FEP (with symptoms of schizophrenia), the total number of healthy controls involved in the study is currently 21. All of the patients were treated at Semmelweis University, Department of Psychiatry. Patients with affective psychosis, drug-related psychotic disorder and patients with clear signs of encephalitis had been excluded from the study. The patients’ blood samples were centrifuged, after which serum was separated from whole blood. Serum samples were then tested with EUROIMMUN immune fluorescent assays for anti-NMDAR antibodies. A different, non-specific method was also used to test anti-brain antibody activity on monkey-cerebellum and rat-hippocampus to show possibly relevant (but not yet known) antibodies. All of the immunological laboratory investigations were done at Semmelweis University, Central Laboratory and immunfluorescent slides were evaluated by an expert in this field. Further differentiation of this non-specific activity was not part of our current study. All of the samples had been freezed on -80 degrees Celsius and are stored for possible further investigations in the future. IL-6 levels will be checked in the next phase of our study. Results None of the samples from the 26 patients, nor any of the samples collected from healthy controls contained anti-NMDAR antibodies. However it should be noted that during the period of the study 3 patients were diagnosed with anti-NMDAR encephalitis, but as it was described earlier these cases had not been included in our study, because we focused on patients with pure psychotic symptoms. 11 of the patients’ serum showed positive reaction of the neuroendothelium (6 strong, 5 moderate), whereas only 4 of the samples collected from healthy controls showed similar pattern (all of them showed moderate or mild activity). These results suggest that there is a significant difference between the groups, however we will need to increase our sample size to verify these findings. There were other non-specific reactions in both groups in low numbers. Discussion None of the serum samples of the 26 patients proved positive for anti-NMDAR antibodies, which is in agreement with previous studies in the literature. However, a higher proportion of samples form patients showed activity on the neuroendothelium of non-specific immune fluorescent assays compared to healthy controls. We plan to increase our samples sizes in the near future and check the serum samples for interleukins and cytokines.

scholarly journals Brain responses to different types of salience in antipsychotic naïve first episode psychosis: An fMRI study

2018 ◽  
Author(s):  
Franziska Knolle ◽  
Anna O Ermakova ◽  
Azucena Justicia ◽  
Paul C Fletcher ◽  
Nico Bunzeck ◽  
...  
Keyword(s):  
Negative Emotion ◽  
First Episode Psychosis ◽  
Anterior Cingulate ◽  
Psychotic Symptoms ◽  
First Episode ◽  
Prediction Errors ◽  
Fmri Study ◽  
Episode Psychosis ◽  
Emotional Salience ◽  
Cortical Regions

AbstractAbnormal salience processing has been suggested to contribute to the formation of positive psychotic symptoms in schizophrenia and related conditions. Previous research utilising reward learning or anticipation paradigms has demonstrated cortical and subcortical abnormalities in people with psychosis, specifically in the prefrontal cortex, the dopaminergic midbrain and the striatum. In these paradigms, reward prediction errors attribute motivational salience to stimuli. However, little is known about possible abnormalities across different forms of salience processing in psychosis patients, and whether any such abnormalities involve the dopaminergic midbrain. The aim of our study was, therefore, to investigate possible alterations in psychosis in neural activity in response to various forms of salience: novelty, negative emotion, targetness (task-driven salience) and rareness/deviance. We studied 14 antipsychotic naïve participants with first episode psychosis, and 37 healthy volunteers. During fMRI scanning, participants performed a visual oddball task containing these four forms of salience. Psychosis patients showed abnormally reduced signalling in the substantia nigra/ventral tegmental area (SN/VTA) for novelty, negative emotional salience and targetness; reduced striatal and occipital (lingual gyrus) signalling to novelty and negative emotional salience, reduced signalling in the amygdala, anterior cingulate cortex and parahippocamal gyrus to negative emotional salience, and reduced cerebellar signalling to novelty and negative emotional salience. Our results indicate alterations of several forms of salience processing in patients with psychosis in the midbrain SN/VTA, with additional subcortical and cortical regions also showing alterations in salience signalling, the exact pattern of alterations depending on the form of salience in question.

scholarly journals Divergent effects of first-generation and second-generation antipsychotics on cortical thickness in first-episode psychosis

2014 ◽  
Vol 45 (3) ◽  
pp. 515-527 ◽  
Author(s):  
B. R. E. Ansell ◽  
D. B. Dwyer ◽  
S. J. Wood ◽  
E. Bora ◽  
W. J. Brewer ◽  
...  
Keyword(s):  
Cortical Thickness ◽  
First Generation ◽  
Second Generation ◽  
Interaction Analysis ◽  
First Episode Psychosis ◽  
Psychotic Symptoms ◽  
First Episode ◽  
Healthy Controls ◽  
Episode Psychosis ◽  
Second Generation Antipsychotics

BackgroundWhether there are differential effects of first-generation antipsychotics (FGAs) and second-generation antipsychotics (SGAs) on the brain is currently debated. Although some studies report that FGAs reduce grey matter more than SGAs, others do not, and research to date is limited by a focus on schizophrenia spectrum disorders. To address this limitation, this study investigated the effects of medication in patients being treated for first-episode schizophrenia or affective psychoses.MethodCortical thickness was compared between 52 first-episode psychosis patients separated into diagnostic (i.e. schizophrenia or affective psychosis) and medication (i.e. FGA and SGA) subgroups. Patients in each group were also compared to age- and sex-matched healthy controls (n = 28). A whole-brain cortical thickness interaction analysis of medication and diagnosis was then performed. Correlations between cortical thickness with antipsychotic dose and psychotic symptoms were examined.ResultsThe effects of medication and diagnosis did not interact, suggesting independent effects. Compared with controls, diagnostic differences were found in frontal, parietal and temporal regions. Decreased thickness in FGA-treated versus SGA-treated groups was found in a large frontoparietal region (p < 0.001, corrected). Comparisons with healthy controls revealed decreased cortical thickness in the FGA group whereas the SGA group showed increases in addition to decreases. In FGA-treated patients cortical thinning was associated with higher negative symptoms whereas increased cortical thickness in the SGA-treated group was associated with lower positive symptoms.ConclusionsOur results suggest that FGA and SGA treatments have divergent effects on cortical thickness during the first episode of psychosis that are independent from changes due to illness.

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

scholarly journals Aggressive incidents in first-episode psychosis

2001 ◽  
Vol 178 (5) ◽  
pp. 433-440 ◽  
Author(s):  
John Milton ◽  
Shazad Amin ◽  
Swaran P. Singh ◽  
Glynn Harrison ◽  
Peter Jones ◽  
...  
Keyword(s):  
First Episode Psychosis ◽  
Psychotic Symptoms ◽  
First Episode ◽  
Psychotic Episode ◽  
Increased Risk ◽  
Episode Psychosis ◽  
Clinical Associations ◽  
Independent Effects ◽  
One Act ◽  
Service Contact

BackgroundRecent research has reported increased risk of aggressive incidents by individuals with psychotic illness.AimsTo examine acts of aggression in first-episode psychosis.MethodSubjects with a first-episode psychosis were ascertained from a defined catchment area (Nottingham, UK) and reassessed at 3 years (n=166) using clinical interview, informants, health care and forensic records.ResultsOf the subjects, 9.6% demonstrated at least one act of serious aggression (defined as weapon use, sexual assault or victim injury) during at least one psychotic episode and 23.5% demonstrated lesser acts of aggression (defined as all other acts of aggression). For all aggressive subjects (33.1%), unemployment (OR=3.6, 95%CI 1.6–8.0), comorbid substance misuse (OR=3.1, CI 1.1–8.8) and symptoms of overactivity at service contact (OR=6.9, CI 2.7–17.8) had independent effects on risk of aggression.ConclusionsWe confirmed some previously reported demographic and clinical associations with aggression in first-episode psychosis but no relationship with specific psychotic symptoms or diagnostic groups was observed.

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.

Antipsychotic medication and remission of psychotic symptoms 10 years after a first-episode psychosis

2017 ◽  
Vol 182 ◽  
pp. 42-48 ◽  
Author(s):  
Regitze Sølling Wils ◽  
Ditte Resendal Gotfredsen ◽  
Carsten Hjorthøj ◽  
Stephen F. Austin ◽  
Nikolai Albert ◽  
...  
Keyword(s):  
Antipsychotic Medication ◽  
First Episode Psychosis ◽  
Psychotic Symptoms ◽  
First Episode ◽  
Episode Psychosis

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.

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