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 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 Neural correlates of aberrant emotional salience predict psychotic symptoms and global functioning in high-risk and first-episode psychosis

2015 ◽  
Vol 10 (10) ◽  
pp. 1429-1436 ◽  
Author(s):  
Gemma Modinos ◽  
Huai-Hsuan Tseng ◽  
Irina Falkenberg ◽  
Carly Samson ◽  
Philip McGuire ◽  
...  
Keyword(s):  
High Risk ◽  
Neural Correlates ◽  
First Episode Psychosis ◽  
Psychotic Symptoms ◽  
First Episode ◽  
Global Functioning ◽  
Episode Psychosis ◽  
Emotional Salience

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 Treatment response after 6 and 26 weeks is related to baseline glutamate and GABA levels in antipsychotic-naïve patients with psychosis

2019 ◽  
Vol 50 (13) ◽  
pp. 2182-2193 ◽  
Author(s):  
Kirsten B. Bojesen ◽  
Bjørn H. Ebdrup ◽  
Kasper Jessen ◽  
Anne Sigvard ◽  
Karen Tangmose ◽  
...  
Keyword(s):  
Psychotic Disorders ◽  
Poor Response ◽  
First Episode Psychosis ◽  
Anterior Cingulate ◽  
First Episode ◽  
Antipsychotic Treatment ◽  
Resonance Spectroscopy ◽  
Reference Levels ◽  
Clinical Prognosis ◽  
Episode Psychosis

AbstractBackgroundPoor response to dopaminergic antipsychotics constitutes a major challenge in the treatment of psychotic disorders and markers for non-response during first-episode are warranted. Previous studies have found increased levels of glutamate and γ-aminobutyric acid (GABA) in non-responding first-episode patients compared to responders, but it is unknown if non-responders can be identified using reference levels from healthy controls (HCs).MethodsThirty-nine antipsychotic-naïve patients with first-episode psychosis and 36 matched HCs underwent repeated assessments with the Positive and Negative Syndrome Scale and 3T magnetic resonance spectroscopy. Glutamate scaled to total creatine (/Cr) was measured in the anterior cingulate cortex (ACC) and left thalamus, and levels of GABA/Cr were measured in ACC. After 6 weeks, we re-examined 32 patients on aripiprazole monotherapy and 35 HCs, and after 26 weeks we re-examined 30 patients on naturalistic antipsychotic treatment and 32 HCs. The Andreasen criteria defined non-response.ResultsBefore treatment, thalamic glutamate/Cr was higher in the whole group of patients but levels normalized after treatment. ACC levels of glutamate/Cr and GABA/Cr were lower at all assessments and unaffected by treatment. When compared with HCs, non-responders at week 6 (19 patients) and week 26 (16 patients) had higher baseline glutamate/Cr in the thalamus. Moreover, non-responders at 26 weeks had lower baseline GABA/Cr in ACC. Baseline levels in responders and HCs did not differ.ConclusionGlutamatergic and GABAergic abnormalities in antipsychotic-naïve patients appear driven by non-responders to antipsychotic treatment. If replicated, normative reference levels for glutamate and GABA may aid estimation of clinical prognosis in first-episode psychosis patients.

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.

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 Longitudinal changes in brain metabolites in healthy subjects and patients with first episode psychosis (FEP): a 7-Tesla MRS study

2020 ◽  
Author(s):  
Min Wang ◽  
Peter B. Barker ◽  
Nicola Cascella ◽  
Jennifer M. Coughlin ◽  
Gerald Nestadt ◽  
...  
Keyword(s):  
Young Adulthood ◽  
Brain Regions ◽  
First Episode Psychosis ◽  
Anterior Cingulate ◽  
7 Tesla ◽  
First Episode ◽  
Resonance Spectroscopy ◽  
Invasive Approach ◽  
Longitudinal Changes ◽  
Episode Psychosis

AbstractObjective7 Tesla (T) longitudinal magnetic resonance spectroscopy (MRS) offers a precise measurment of metabolic levels in human brain via a non-invasive approach. Studying longitudinal changes in neurometabolites could help identify trait and state markers for diseases and understand inconsistent findings from different researchers due to differences in the age of study participants and duration of illness. This study is the first to report novel longitudinal patterns in young adulthood from both physiological and pathological viewpoints using 7T MRS.MethodsUtilizing a four-year longitudinal cohort with 38 first episode psychosis (FEP) patients (onset within 2 years) and 48 healthy controls (HC), the authors examined the annual percentage changes of 9 neurometabolites in 5 brain regions.ResultsBoth FEP patients and HC subjects were found to have significant longitudinal reductions in glutamate (Glu) in the anterior cingulate cortex (ACC). Only FEP patients were found to have a significant decrease over time in γ-aminobutyric acid (GABA), N-acetyl aspartate (NAA), myo-inositol (mI), and total choline (tCho: phosphocholine plus glycerophosphocholine) in the ACC. Uniquely, glutathione (GSH) was found to have a near zero annual percentage change in both FEP patients and HC subjects in all 5 brain regions over a four-year timespan in young adulthood.ConclusionsGSH could be a trait marker for diagnostic applications at least in young adulthood. Glu, GABA, NAA, mI, and tCho in the ACC are associated with the patient’s status and could be state markers for mechanistic studies of psychotic disorders, including those for progressive pathological changes and medication effects in young adulthood.

iMAgery focused psychological therapy for persecutory delusions in PSychosis (iMAPS): a multiple baseline experimental case series

2020 ◽  
Vol 48 (5) ◽  
pp. 530-545
Author(s):  
Christopher D.J. Taylor ◽  
Penny E. Bee ◽  
James Kelly ◽  
Richard Emsley ◽  
Gillian Haddock
Keyword(s):  
Case Series ◽  
First Episode Psychosis ◽  
Psychological Therapy ◽  
Multiple Baseline ◽  
Psychotic Symptoms ◽  
First Episode ◽  
Multiple Baseline Design ◽  
Persecutory Delusions ◽  
Baseline Design ◽  
Episode Psychosis

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.

scholarly journals Cannabis use and first-episode psychosis: relationship with manic and psychotic symptoms, and with age at presentation

2013 ◽  
Vol 44 (3) ◽  
pp. 499-506 ◽  
Author(s):  
J. M. Stone ◽  
H. L. Fisher ◽  
B. Major ◽  
B. Chisholm ◽  
J. Woolley ◽  
...  
Keyword(s):  
Longitudinal Design ◽  
First Episode Psychosis ◽  
Cannabis Use ◽  
Daily Functioning ◽  
Psychotic Symptoms ◽  
First Episode ◽  
Time Points ◽  
Manic Symptoms ◽  
Episode Psychosis ◽  
Early Intervention In Psychosis

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.

scholarly journals Dilemmas in the treatment of early-onset first-episode psychosis

2018 ◽  
Vol 8 (8) ◽  
pp. 231-239 ◽  
Author(s):  
Daniel Hayes ◽  
Marinos Kyriakopoulos
Keyword(s):  
Young People ◽  
Early Onset ◽  
Clinical Decision Making ◽  
Clinical Decision ◽  
First Episode Psychosis ◽  
Psychotic Symptoms ◽  
First Episode ◽  
Close Monitoring ◽  
Optimal Outcomes ◽  
Episode Psychosis

Early-onset first-episode psychosis (EOP) is a severe mental disorder that can pose a number of challenges to clinicians, young people and their families. Its assessment and differentiation from other neurodevelopmental and mental health conditions may at times be difficult, its treatment may not always lead to optimal outcomes and can be associated with significant side effects, and its long-term course and prognosis seem to be less favourable compared with the adult-onset disorder. In this paper, we discuss some dilemmas associated with the evaluation and management of EOP and propose approaches that can be used in the clinical decision-making process. A detailed and well-informed assessment of psychotic symptoms and comorbidities, a systematic approach to treatment with minimum possible medication doses and close monitoring of its effectiveness and adverse effects, and multidimensional interventions taking into consideration risks and expectations associated with EOP, are paramount in the achievement of the most favourable outcomes for affected children and young people.

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