Abnormal Frontostriatal Interactions in People With Prodromal Signs of Psychosi: A Multimodal Imaging Study

Paolo Fusar-Poli; Oliver Howes; Paul Allen; Matthew Broome; Isabel Valli; Marie-Claude Asselin; Paul M. Grasby; Philip McGuire

Abnormal Frontostriatal Interactions in People With Prodromal Signs of Psychosi: A Multimodal Imaging Study

Paolo Fusar-Poli, Oliver Howes, Paul Allen, Matthew Broome, Isabel Valli, Marie-Claude Asselin, Paul M. Grasby, Philip McGuire

Research output: Contribution to journal › Article

Abstract

Context: Alterations in dopaminergic neurotransmission and function of the prefrontal cortex are thought to be central to the pathophysiology of schizophrenia, but the relationship between these factors in the development of psychosis is unclear.Objective: To investigate the relationship between striatal dopamine activity and prefrontal function in people at ultra high risk of psychosis.Design: Subjects were studied using functional magnetic resonance imaging while performing a working memory (N-back) task. Positron emission tomography with fluorine 18-labeled fluorodopa was used to investigate presynaptic striatal dopamine activity.Setting: Outpatient service for people with prodromal signs of psychosis.Patients and Other Participants: Thirty-four subjects participated in the study: 14 healthy volunteers and 20 subjects with an at-risk mental state (ARMS).Main Outcome Measures: Regional brain activation (blood oxygen level-dependent response), Ki for [(18)F] fluorodopa uptake, and objective ratings of psychopathology at the time of scanning.Results: In the associative part of the striatum, the Ki for [(18)F] fluorodopa was higher in the ARMS group than in the controls. During the N-back task, ARMS subjects displayed less activation in the right middle frontal gyrus, the medial frontal gyri, and the left superior parietal lobule than controls. The Ki for [(18)F] fluorodopa was positively correlated with activation in the right middle frontal gyrus in controls but negatively correlated with activation in this region in the ARMS group.Conclusions: In people with prodromal signs of psychosis, there are direct correlations between altered prefrontal cortical function and subcortical dopamine synthesis capacity, consistent with the notion that frontostriatal interactions play a critical role in the pathoetiology of schizophrenia.

Original language	English
Pages (from-to)	683-691
Journal	Archives of General Psychiatry
Volume	67
Issue number	7
Publication status	Published - 2010

Cite this

@article{a2c8dd13b1ec4fb89085f89ff9a9075f,

title = "Abnormal Frontostriatal Interactions in People With Prodromal Signs of Psychosi: A Multimodal Imaging Study",

abstract = "Context: Alterations in dopaminergic neurotransmission and function of the prefrontal cortex are thought to be central to the pathophysiology of schizophrenia, but the relationship between these factors in the development of psychosis is unclear.Objective: To investigate the relationship between striatal dopamine activity and prefrontal function in people at ultra high risk of psychosis.Design: Subjects were studied using functional magnetic resonance imaging while performing a working memory (N-back) task. Positron emission tomography with fluorine 18-labeled fluorodopa was used to investigate presynaptic striatal dopamine activity.Setting: Outpatient service for people with prodromal signs of psychosis.Patients and Other Participants: Thirty-four subjects participated in the study: 14 healthy volunteers and 20 subjects with an at-risk mental state (ARMS).Main Outcome Measures: Regional brain activation (blood oxygen level-dependent response), Ki for [(18)F] fluorodopa uptake, and objective ratings of psychopathology at the time of scanning.Results: In the associative part of the striatum, the Ki for [(18)F] fluorodopa was higher in the ARMS group than in the controls. During the N-back task, ARMS subjects displayed less activation in the right middle frontal gyrus, the medial frontal gyri, and the left superior parietal lobule than controls. The Ki for [(18)F] fluorodopa was positively correlated with activation in the right middle frontal gyrus in controls but negatively correlated with activation in this region in the ARMS group.Conclusions: In people with prodromal signs of psychosis, there are direct correlations between altered prefrontal cortical function and subcortical dopamine synthesis capacity, consistent with the notion that frontostriatal interactions play a critical role in the pathoetiology of schizophrenia.",

author = "Paolo Fusar-Poli and Oliver Howes and Paul Allen and Matthew Broome and Isabel Valli and Marie-Claude Asselin and Grasby, {Paul M.} and Philip McGuire",

year = "2010",

language = "English",

volume = "67",

pages = "683--691",

journal = "Archives of General Psychiatry",

issn = "0003-990X",

publisher = "American Medical Association",

number = "7",

}

TY - JOUR

T1 - Abnormal Frontostriatal Interactions in People With Prodromal Signs of Psychosi

T2 - A Multimodal Imaging Study

AU - Fusar-Poli, Paolo

AU - Howes, Oliver

AU - Allen, Paul

AU - Broome, Matthew

AU - Valli, Isabel

AU - Asselin, Marie-Claude

AU - Grasby, Paul M.

AU - McGuire, Philip

PY - 2010

Y1 - 2010

N2 - Context: Alterations in dopaminergic neurotransmission and function of the prefrontal cortex are thought to be central to the pathophysiology of schizophrenia, but the relationship between these factors in the development of psychosis is unclear.Objective: To investigate the relationship between striatal dopamine activity and prefrontal function in people at ultra high risk of psychosis.Design: Subjects were studied using functional magnetic resonance imaging while performing a working memory (N-back) task. Positron emission tomography with fluorine 18-labeled fluorodopa was used to investigate presynaptic striatal dopamine activity.Setting: Outpatient service for people with prodromal signs of psychosis.Patients and Other Participants: Thirty-four subjects participated in the study: 14 healthy volunteers and 20 subjects with an at-risk mental state (ARMS).Main Outcome Measures: Regional brain activation (blood oxygen level-dependent response), Ki for [(18)F] fluorodopa uptake, and objective ratings of psychopathology at the time of scanning.Results: In the associative part of the striatum, the Ki for [(18)F] fluorodopa was higher in the ARMS group than in the controls. During the N-back task, ARMS subjects displayed less activation in the right middle frontal gyrus, the medial frontal gyri, and the left superior parietal lobule than controls. The Ki for [(18)F] fluorodopa was positively correlated with activation in the right middle frontal gyrus in controls but negatively correlated with activation in this region in the ARMS group.Conclusions: In people with prodromal signs of psychosis, there are direct correlations between altered prefrontal cortical function and subcortical dopamine synthesis capacity, consistent with the notion that frontostriatal interactions play a critical role in the pathoetiology of schizophrenia.

AB - Context: Alterations in dopaminergic neurotransmission and function of the prefrontal cortex are thought to be central to the pathophysiology of schizophrenia, but the relationship between these factors in the development of psychosis is unclear.Objective: To investigate the relationship between striatal dopamine activity and prefrontal function in people at ultra high risk of psychosis.Design: Subjects were studied using functional magnetic resonance imaging while performing a working memory (N-back) task. Positron emission tomography with fluorine 18-labeled fluorodopa was used to investigate presynaptic striatal dopamine activity.Setting: Outpatient service for people with prodromal signs of psychosis.Patients and Other Participants: Thirty-four subjects participated in the study: 14 healthy volunteers and 20 subjects with an at-risk mental state (ARMS).Main Outcome Measures: Regional brain activation (blood oxygen level-dependent response), Ki for [(18)F] fluorodopa uptake, and objective ratings of psychopathology at the time of scanning.Results: In the associative part of the striatum, the Ki for [(18)F] fluorodopa was higher in the ARMS group than in the controls. During the N-back task, ARMS subjects displayed less activation in the right middle frontal gyrus, the medial frontal gyri, and the left superior parietal lobule than controls. The Ki for [(18)F] fluorodopa was positively correlated with activation in the right middle frontal gyrus in controls but negatively correlated with activation in this region in the ARMS group.Conclusions: In people with prodromal signs of psychosis, there are direct correlations between altered prefrontal cortical function and subcortical dopamine synthesis capacity, consistent with the notion that frontostriatal interactions play a critical role in the pathoetiology of schizophrenia.

M3 - Article

SN - 0003-990X

VL - 67

SP - 683

EP - 691

JO - Archives of General Psychiatry

JF - Archives of General Psychiatry

IS - 7

ER -