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 ◽  
...  

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.

2018 ◽  
Vol 43 (8) ◽  
pp. 1691-1699 ◽  
Author(s):  
Anna O. Ermakova ◽  
Franziska Knolle ◽  
Azucena Justicia ◽  
Edward T. Bullmore ◽  
Peter B. Jones ◽  
...  

Author(s):  
J. Haarsma ◽  
P. C. Fletcher ◽  
J. D. Griffin ◽  
H. J. Taverne ◽  
H. Ziauddeen ◽  
...  

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.


2018 ◽  
Author(s):  
Franziska Knolle ◽  
Anna O Ermakova ◽  
Azucena Justicia ◽  
Paul C Fletcher ◽  
Nico Bunzeck ◽  
...  

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.


2021 ◽  
Vol 12 ◽  
Author(s):  
Giacomo Ciocca ◽  
Tommaso B. Jannini ◽  
Michele Ribolsi ◽  
Rodolfo Rossi ◽  
Cinzia Niolu ◽  
...  

A considerable body of literature reports that individuals with psychotic disorders often suffer from sexual dysfunctions (SDs), with these representing a major unmet need. Long-term antipsychotic drug treatment may be the main cause for SDs in psychotic patients, through a plethora of different mechanisms, including prolactin dyscrasia, histamine-mediated sedation, and serotonin-induced sexual demotivation. However, a few pieces of evidence treat sexuality in patients at risk or the onset of psychosis. For this purpose, we systematically reviewed literature of the last 10 years in order to investigate sexuality in ultra-high risk (UHR) for psychosis and first-episode psychosis (FEP). We included in our review 34 articles fitting our research criteria on SDs in UHR and FEP. Evidence of SDs in the transition from UHR to FEP emerges through the selected studies. In FEP, sexuality is affected by the severity of the psychotic symptoms and, in some cases, by the iatrogenic effects of psychopharmacological treatment. Further experimental and clinical studies should systematically investigate the role of sexual functioning in the transition from UHR to FEP and, consequently, clarify whether or not SDs could be considered a possible marker for the onset of psychosis in at-risk populations. Moreover, psychiatrists and clinical psychologists should take into consideration the role of sexual life in young people with prodromal mental symptoms or at the onset of psychosis. Focusing on a thorough sexual evaluation might be a major challenge that could break down barriers of mental health promotion among young people with schizophrenia-spectrum disorders and therefore achieve better clinical outcomes.


2001 ◽  
Vol 178 (5) ◽  
pp. 433-440 ◽  
Author(s):  
John Milton ◽  
Shazad Amin ◽  
Swaran P. Singh ◽  
Glynn Harrison ◽  
Peter Jones ◽  
...  

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.


2017 ◽  
Vol 182 ◽  
pp. 42-48 ◽  
Author(s):  
Regitze Sølling Wils ◽  
Ditte Resendal Gotfredsen ◽  
Carsten Hjorthøj ◽  
Stephen F. Austin ◽  
Nikolai Albert ◽  
...  

2020 ◽  
Author(s):  
Santosh Lamichhane ◽  
Alex M. Dickens ◽  
Partho Sen ◽  
Heikki Laurikainen ◽  
Jaana Suvisaari ◽  
...  

AbstractPatients with schizophrenia have a lower than average life span, largely due to the increased prevalence of cardiometabolic co-morbidities. Identification of individuals with psychotic disorders with a high risk of rapid weight gain, and the associated development of metabolic complications, is an unmet need as regards public health. Here, we applied mass spectrometry-based lipidomics in a prospective study comprising 48 controls (CTR), 44 first-episode psychosis (FEP) patients and 22 individuals at clinical-high-risk (CHR) for psychosis, from two study centers (Turku/Finland and London/UK). Baseline serum samples were analyzed by lipidomics, while body mass index (BMI) was assessed at baseline and after 12 months. We found that baseline triacylglycerols with low double bond counts and carbon numbers were positively associated with the change in BMI at follow-up. In addition, a molecular signature comprised of two triacylglycerols (TG(48:0) and TG(45:0)), was predictive of weight gain in individuals with a psychotic disorder, with an area under the receiver operating characteristic curve (AUROC) of 0.74 (95% CI: 0.60–0.85). When independently tested in the CHR group, this molecular signature predicted said weight change with AUROC = 0.73 (95% CI: 0.61–0.83). We conclude that molecular lipids may serve as a predictor of weight gain in psychotic disorders in at-risk individuals, and may thus provide a useful marker for identifying individuals who are most prone to developing cardiometabolic co-morbidities.


2020 ◽  
Vol 48 (5) ◽  
pp. 530-545
Author(s):  
Christopher D.J. Taylor ◽  
Penny E. Bee ◽  
James Kelly ◽  
Richard Emsley ◽  
Gillian Haddock

AbstractBackground:Many people with psychosis experience persecutory delusions and report negative schematic beliefs and intrusive mental images which may be maintaining factors for psychotic symptoms.Aims:This study examined the feasibility and acceptability of a new psychological therapy targeting schemas and images (iMAPS therapy).Method:The study used a randomised multiple baseline design. Participants with first episode psychosis were randomised using a multiple baseline design with 2–5 assessments. Six sessions of therapy, consisting of a combination of imagery techniques and imagery rescripting techniques, was used. In each session, participants completed a Mental Imagery in Psychosis Questionnaire (MIPQ) and imagery interview. Mood and delusional beliefs (PSYRATS) were also measured at each session.Results:Five participants with first episode psychosis completed the baseline visits and attended all therapy sessions. One participant declined the final assessment. Results demonstrated significant reductions in negative schematic beliefs, delusions, imagery distress and other measures of schema (YSQ, SMI). Although multiple baseline randomisation strengthens the study, it lacked a control arm and blind assessments.Conclusions:iMAPS appears a feasible and acceptable treatment for psychosis, and further evaluation is indicated.


2013 ◽  
Vol 44 (3) ◽  
pp. 499-506 ◽  
Author(s):  
J. M. Stone ◽  
H. L. Fisher ◽  
B. Major ◽  
B. Chisholm ◽  
J. Woolley ◽  
...  

BackgroundCannabis use has been reported to be associated with an earlier onset of symptoms in patients with first-episode psychosis, and a worse outcome in those who continue to take cannabis. In general, studies have concentrated on symptoms of psychosis rather than mania. In this study, using a longitudinal design in a large naturalistic cohort of patients with first-episode psychosis, we investigated the relationship between cannabis use, age of presentation to services, daily functioning, and positive, negative and manic symptoms.MethodClinical data on 502 patients with first-episode psychosis were collected using the MiData audit database from seven London-based Early Intervention in psychosis teams. Individuals were assessed at two time points – at entry to the service and after 1 year. On each occasion, the Positive and Negative Syndrome Scale, Young Mania Rating Scale and Global Assessment of Functioning Scale disability subscale were rated. At both time points, the use of cannabis and other drugs of abuse in the 6 months preceding each assessment was recorded.ResultsLevel of cannabis use was associated with a younger age at presentation, and manic symptoms and conceptual disorganization, but not with delusions, hallucinations, negative symptoms or daily functioning. Cannabis users who reduced or stopped their use following contact with services had the greatest improvement in symptoms at 1 year compared with continued users and non-users. Continued users remained more symptomatic than non-users at follow-up.ConclusionsEffective interventions for reducing cannabis use may yield significant health benefits for patients with first-episode psychosis.


2019 ◽  
Vol 215 (6) ◽  
pp. 726-729 ◽  
Author(s):  
Cristina Marta Del-Ben ◽  
Rosana Shuhama ◽  
Camila Marcelino Loureiro ◽  
Taciana Cristina Carvalho Ragazzi ◽  
Daniela Perocco Zanatta ◽  
...  

We estimated the incidence of first-episode psychosis over a 3-year period in a Brazilian catchment area comprising the region's main city, Ribeirão Preto (1 425 306 persons-years at risk), and 25 other municipalities with a total of 1 646 556 persons-years at risk. The incidence rates were estimated and adjusted by gender and age, using the direct standardisation method to the world population as reference. The incidence of psychosis was higher in the younger groups, men, and among Black and minority ethnic Brazilians. Psychosis incidence was lower in Ribeirão Preto (16.69/100 000 person-years at risk; 95% CI 15.68–17.70) compared with the average incidence in the remaining municipalities (21.25/100 000 person-years at risk; 95% CI 20.20–22.31), which have lower population density, suggesting a distinct role for urbanicity in the incidence of first-episode psychosis in low- and middle-income countries.


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