Evidence of reward system dysfunction in youth at clinical high-risk for psychosis from two event-related fMRI paradigms

Millman, Zachary B.; Gallagher, Keith; Demro, Caroline; Schiffman, Jason; Reeves, Gloria; Gold, James M.; Rouhakhtar, Pamela Rakhshan; Fitzgerald, Jessica; Andorko, Nicole D.; Redman, Samantha; Boyer, Robert; Rowland, Laura M.; Waltz, James A.

doi:10.1016/j.schres.2019.03.017

Cited by 27 publications

(36 citation statements)

References 40 publications

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“…In line with previous studies in unmedicated patients 26–28 (but see Ermakova et al 29 ) as well as in youth at risk for psychosis, 30 patients were impaired in reversal learning on the behavioral level and displayed reduced coding of reward prediction error in the ventral striatum compared to controls. The prediction error signal serves as a crucial teaching signal in order to optimally learn from interacting with a dynamic environment.…”

Section: Discussionsupporting

confidence: 91%

“…The proposedly chaotic nature of prediction error signaling may reduce signal-to-noise ratio, and thus, prediction errors to actually relevant events may stand out less causing devaluation of relevant outcomes, which may reduce motivation and increase motivational negative symptoms. 16 Human imaging studies reported striatal BOLD prediction error signaling to be decreased in schizophrenia patients receiving no antipsychotic medication 26–28 (but see Ermakova et al 29 ) and in youth at clinical high-risk for psychosis, 30 whereas findings in medicated patients are more heterogeneous. 31–36 Further brain regions, such as midbrain or DLPFC also showed reduced prediction error coding in patients with schizophrenia.…”

Section: Introductionmentioning

confidence: 99%

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Striatal Dopamine and Reward Prediction Error Signaling in Unmedicated Schizophrenia Patients

Katthagen

Kaminski

Heinz

et al. 2020

Schizophrenia Bulletin

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Increased striatal dopamine synthesis capacity has consistently been reported in patients with schizophrenia. However, the mechanism translating this into behavior and symptoms remains unclear. It has been proposed that heightened striatal dopamine may blunt dopaminergic reward prediction error signaling during reinforcement learning. In this study, we investigated striatal dopamine synthesis capacity, reward prediction errors, and their association in unmedicated schizophrenia patients (n = 19) and healthy controls (n = 23). They took part in FDOPA-PET and underwent functional magnetic resonance imaging (fMRI) scanning, where they performed a reversal-learning paradigm. The groups were compared regarding dopamine synthesis capacity (Kicer), fMRI neural prediction error signals, and the correlation of both. Patients did not differ from controls with respect to striatal Kicer. Taking into account, comorbid alcohol abuse revealed that patients without such abuse showed elevated Kicer in the associative striatum, while those with abuse did not differ from controls. Comparing all patients to controls, patients performed worse during reversal learning and displayed reduced prediction error signaling in the ventral striatum. In controls, Kicer in the limbic striatum correlated with higher reward prediction error signaling, while there was no significant association in patients. Kicer in the associative striatum correlated with higher positive symptoms and blunted reward prediction error signaling was associated with negative symptoms. Our results suggest a dissociation between striatal subregions and symptom domains, with elevated dopamine synthesis capacity in the associative striatum contributing to positive symptoms while blunted prediction error signaling in the ventral striatum related to negative symptoms.

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Section: Discussionsupporting

confidence: 91%

Section: Introductionmentioning

confidence: 99%

Striatal Dopamine and Reward Prediction Error Signaling in Unmedicated Schizophrenia Patients

Katthagen

Kaminski

Heinz

et al. 2020

Schizophrenia Bulletin

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“…Socio-demographic factors have also been associated with negative symptoms (e.g., male sex, lower income, summer birth) (37). Several of these factors have been associated with negative symptoms not only during the chronic phase of illness, but also in the prodromal phase, suggesting that they may be involved with the emergence of negative symptoms and risk for conversion to overt illness (38)(39)(40)(41)(42). Using Bronfenbrenner's terminology, these biological and psychological person-level factors would determine an individual's demand, resource, and force characteristics and may influence the quality or quantity of their microsystems.…”

Section: Person-level Factorsmentioning

confidence: 99%

A Bioecosystem Theory of Negative Symptoms in Schizophrenia

Strauss

2021

Front. Psychiatry

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Objective: Negative symptoms are a core feature of schizophrenia that has been linked to numerous poor clinical outcomes. Although person-level mechanisms have been identified for negative symptoms, psychosocial and pharmacological treatments targeting these mechanisms have been ineffective. The current theoretical paper proposes that limited treatment progress may result in part from a failure to identify and target environmental processes that cause and maintain negative symptoms.Methods: A novel theoretical model is outlined, called the bioecosystem theory of negative symptoms, that offers a conceptual framework for studying interactions among environmental systems and person-related biological and psychosocial factors.Results: Relying on Bronfenbrenner's developmental theory as an organizing framework, four interactive environmental systems are proposed to be critical for the genesis and maintenance of negative symptoms: (1) Microsystem: the immediate environment; (2) Mesosystem: the interactions among microsystems; (3) Exosystem: indirect environments that influence the individual through the microsystems; (4) Macrosystem: socio-cultural factors. The environmental factors within these systems are proposed to function as a network and have dynamic within-system interactions, as well as cross-system interactions that change over time and across phases of illness.Conclusions: Environmental contributions to negative symptoms have received minimal empirical attention, despite their potential to explain variance in negative symptom severity. The bioecosystem model of negative symptoms introduced here offers a novel conceptual framework for exploring environmental contributions to negative symptoms and their interaction with person-level biological and psychological factors. This theory may facilitate new avenues for identifying environmental treatment targets and novel systems-level interventions.

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“…In psychotic disorders, there is evidence of a blunted responses to reward feedback [22,43] and blunted striatal activation to prediction errors [44,45], including in unmedicated samples [46,47]. However, the results for prediction errors in ultra-high-risk groups are mixed, with some evidence of increased striatal prediction error processing [42], although other research finds blunted striatal prediction error signals [48] or no significant evidence of striatal impairment [19], indicating that perhaps the degree of striatum-related reinforcement learning impairments depends on the degree of current dopaminergic dysfunction [19]. Furthermore, these previous studies did not specifically examine striatal activation for reward versus punishment on a RLT, as we did in the current study.…”

Section: Discussionmentioning

confidence: 99%

Striatum-related functional activation during reward- versus punishment-based learning in psychosis risk

Karcher

Hua

Kerns

2019

Neuropsychopharmacol.

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Psychosis is strongly related to increased striatal dopamine. However, the neural consequences of increased striatal dopamine in psychosis risk are still not fully understood. Consistent with an increase in striatal dopamine, in previous research, psychosis risk has been associated with neural EEG evidence of a greater response to unexpected reward than unexpected punishment feedback on a reversal-learning task. However, previous research has not directly examined whether psychosis risk is associated with altered striatal activation when receiving unexpected feedback on this task. There were two groups of participants: an antipsychotic medication-naive psychosis risk group (n = 21) who had both (a) extreme levels of self-reported psychotic-like beliefs and experiences and (b) interview-rated current-attenuated psychotic symptoms; and a comparison group (n = 20) who had average levels of self-reported psychotic-like beliefs and experiences. Participants completed a reversal-leaning task during fMRI scanning. As expected, in both ROI and whole-brain analyses, the psychosis risk group exhibited greater striatal activation (for whole-brain analyses, the peak was located in the right caudate) to unexpected reward than unexpected punishment feedback relative to the comparison group. These results indicate that psychosis risk is associated with a relatively increased neural sensitivity to unexpected reward than unexpected punishment outcomes and appears consistent with increased striatal dopamine. The results may help us better understand and detect striatal dysfunction in psychosis risk.

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Evidence of reward system dysfunction in youth at clinical high-risk for psychosis from two event-related fMRI paradigms

Cited by 27 publications

References 40 publications

Striatal Dopamine and Reward Prediction Error Signaling in Unmedicated Schizophrenia Patients

Striatal Dopamine and Reward Prediction Error Signaling in Unmedicated Schizophrenia Patients

A Bioecosystem Theory of Negative Symptoms in Schizophrenia

Striatum-related functional activation during reward- versus punishment-based learning in psychosis risk

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