Brain Connectivity Abnormalities Predating the Onset of Psychosis Correlation With the Effect of Medication

Andre Schmidt; Renata Smieskova; Jacqueline Aston; Andor Simon; Paul Allen; Paulo Fusar-Poli; Philip McGuire; Anita Riecher-Roessler; Klaas Stephan; E. Klaas; Stefan Borgwandt

doi:10.1001/jamapsychiatry.2013.117

Brain Connectivity Abnormalities Predating the Onset of Psychosis Correlation With the Effect of Medication

Andre Schmidt, Renata Smieskova, Jacqueline Aston, Andor Simon, Paul Allen, Paulo Fusar-Poli, Philip McGuire, Anita Riecher-Roessler, Klaas Stephan, E. Klaas, Stefan Borgwandt

Research output: Contribution to journal › Article

Abstract

IMPORTANCE Brain imaging studies have identified robust changes in brain structure and function during the development of psychosis, but the contribution of abnormal brain connectivity to the onset of psychosis is unclear. Furthermore, antipsychotic treatment can modulate brain activity and functional connectivity during cognitive tasks.OBJECTIVES To investigate whether dysfunctional brain connectivity during working memory (WM) predates the onset of psychosis and whether connectivity parameters are related to antipsychotic treatment.DESIGN Dynamic causal modeling study of functional magnetic resonance imaging data.SETTING Participants were recruited from the specialized clinic for the early detection of psychosis at the Department of Psychiatry, University of Basel, Basel, Switzerland. PARTICIPANTS Seventeen participants with an at-risk mental state (mean [SD] age, 25.24 [6.3] years), 21 individuals with first-episode psychosis (mean [SD] age, 28.57 [7.2] years), and 20 healthy controls (mean [SD] age, 26.5 [4] years).MAIN OUTCOME AND MEASURE Functional magnetic resonance imaging data were recorded while participants performed an N-back WM task. Functional interactions among brain regions involved in WM, in particular between frontal and parietal brain regions, were characterized using dynamic causal modeling. Bayesian model selection was performed to evaluate the likelihood of alternative WM network architectures across groups, whereas bayesian model averaging was used to examine group differences in connection strengths.RESULTS We observed a progressive reduction in WM-induced modulation of connectivity from the middle frontal gyrus to the superior parietal lobule in the right hemisphere in healthy controls, at-risk mental state participants, and first-episode psychosis patients. Notably, the abnormal modulation of connectivity in first-episode psychosis patients was normalized by treatment with antipsychotics.CONCLUSIONS AND RELEVANCE Our findings suggest that the vulnerability to psychosis is associated with a progressive failure of functional integration of brain regions involved in WM processes, including visual encoding and rule updating, and that treatment with antipsychotics may have the potential to counteract this.

Original language	English
Pages (from-to)	903-912
Journal	JAMA PSYCHIATRY
Volume	70
Issue number	9
DOIs	https://doi.org/10.1001/jamapsychiatry.2013.117
Publication status	Published - 2013

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10.1001/jamapsychiatry.2013.117

http://dx.doi.org/10.1001/jamapsychiatry.2013.117

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@article{be3d73c48bc240ee8a82df75bc07044f,

title = "Brain Connectivity Abnormalities Predating the Onset of Psychosis Correlation With the Effect of Medication",

abstract = "IMPORTANCE Brain imaging studies have identified robust changes in brain structure and function during the development of psychosis, but the contribution of abnormal brain connectivity to the onset of psychosis is unclear. Furthermore, antipsychotic treatment can modulate brain activity and functional connectivity during cognitive tasks.OBJECTIVES To investigate whether dysfunctional brain connectivity during working memory (WM) predates the onset of psychosis and whether connectivity parameters are related to antipsychotic treatment.DESIGN Dynamic causal modeling study of functional magnetic resonance imaging data.SETTING Participants were recruited from the specialized clinic for the early detection of psychosis at the Department of Psychiatry, University of Basel, Basel, Switzerland. PARTICIPANTS Seventeen participants with an at-risk mental state (mean [SD] age, 25.24 [6.3] years), 21 individuals with first-episode psychosis (mean [SD] age, 28.57 [7.2] years), and 20 healthy controls (mean [SD] age, 26.5 [4] years).MAIN OUTCOME AND MEASURE Functional magnetic resonance imaging data were recorded while participants performed an N-back WM task. Functional interactions among brain regions involved in WM, in particular between frontal and parietal brain regions, were characterized using dynamic causal modeling. Bayesian model selection was performed to evaluate the likelihood of alternative WM network architectures across groups, whereas bayesian model averaging was used to examine group differences in connection strengths.RESULTS We observed a progressive reduction in WM-induced modulation of connectivity from the middle frontal gyrus to the superior parietal lobule in the right hemisphere in healthy controls, at-risk mental state participants, and first-episode psychosis patients. Notably, the abnormal modulation of connectivity in first-episode psychosis patients was normalized by treatment with antipsychotics.CONCLUSIONS AND RELEVANCE Our findings suggest that the vulnerability to psychosis is associated with a progressive failure of functional integration of brain regions involved in WM processes, including visual encoding and rule updating, and that treatment with antipsychotics may have the potential to counteract this.",

author = "Andre Schmidt and Renata Smieskova and Jacqueline Aston and Andor Simon and Paul Allen and Paulo Fusar-Poli and Philip McGuire and Anita Riecher-Roessler and Klaas Stephan and E. Klaas and Stefan Borgwandt",

year = "2013",

doi = "10.1001/jamapsychiatry.2013.117",

language = "English",

volume = "70",

pages = "903--912",

journal = "JAMA PSYCHIATRY",

issn = "2168-622X",

publisher = "American Medical Association",

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TY - JOUR

T1 - Brain Connectivity Abnormalities Predating the Onset of Psychosis Correlation With the Effect of Medication

AU - Schmidt, Andre

AU - Smieskova, Renata

AU - Aston, Jacqueline

AU - Simon, Andor

AU - Allen, Paul

AU - Fusar-Poli, Paulo

AU - McGuire, Philip

AU - Riecher-Roessler, Anita

AU - Stephan, Klaas

AU - Klaas, E.

AU - Borgwandt, Stefan

PY - 2013

Y1 - 2013

N2 - IMPORTANCE Brain imaging studies have identified robust changes in brain structure and function during the development of psychosis, but the contribution of abnormal brain connectivity to the onset of psychosis is unclear. Furthermore, antipsychotic treatment can modulate brain activity and functional connectivity during cognitive tasks.OBJECTIVES To investigate whether dysfunctional brain connectivity during working memory (WM) predates the onset of psychosis and whether connectivity parameters are related to antipsychotic treatment.DESIGN Dynamic causal modeling study of functional magnetic resonance imaging data.SETTING Participants were recruited from the specialized clinic for the early detection of psychosis at the Department of Psychiatry, University of Basel, Basel, Switzerland. PARTICIPANTS Seventeen participants with an at-risk mental state (mean [SD] age, 25.24 [6.3] years), 21 individuals with first-episode psychosis (mean [SD] age, 28.57 [7.2] years), and 20 healthy controls (mean [SD] age, 26.5 [4] years).MAIN OUTCOME AND MEASURE Functional magnetic resonance imaging data were recorded while participants performed an N-back WM task. Functional interactions among brain regions involved in WM, in particular between frontal and parietal brain regions, were characterized using dynamic causal modeling. Bayesian model selection was performed to evaluate the likelihood of alternative WM network architectures across groups, whereas bayesian model averaging was used to examine group differences in connection strengths.RESULTS We observed a progressive reduction in WM-induced modulation of connectivity from the middle frontal gyrus to the superior parietal lobule in the right hemisphere in healthy controls, at-risk mental state participants, and first-episode psychosis patients. Notably, the abnormal modulation of connectivity in first-episode psychosis patients was normalized by treatment with antipsychotics.CONCLUSIONS AND RELEVANCE Our findings suggest that the vulnerability to psychosis is associated with a progressive failure of functional integration of brain regions involved in WM processes, including visual encoding and rule updating, and that treatment with antipsychotics may have the potential to counteract this.

AB - IMPORTANCE Brain imaging studies have identified robust changes in brain structure and function during the development of psychosis, but the contribution of abnormal brain connectivity to the onset of psychosis is unclear. Furthermore, antipsychotic treatment can modulate brain activity and functional connectivity during cognitive tasks.OBJECTIVES To investigate whether dysfunctional brain connectivity during working memory (WM) predates the onset of psychosis and whether connectivity parameters are related to antipsychotic treatment.DESIGN Dynamic causal modeling study of functional magnetic resonance imaging data.SETTING Participants were recruited from the specialized clinic for the early detection of psychosis at the Department of Psychiatry, University of Basel, Basel, Switzerland. PARTICIPANTS Seventeen participants with an at-risk mental state (mean [SD] age, 25.24 [6.3] years), 21 individuals with first-episode psychosis (mean [SD] age, 28.57 [7.2] years), and 20 healthy controls (mean [SD] age, 26.5 [4] years).MAIN OUTCOME AND MEASURE Functional magnetic resonance imaging data were recorded while participants performed an N-back WM task. Functional interactions among brain regions involved in WM, in particular between frontal and parietal brain regions, were characterized using dynamic causal modeling. Bayesian model selection was performed to evaluate the likelihood of alternative WM network architectures across groups, whereas bayesian model averaging was used to examine group differences in connection strengths.RESULTS We observed a progressive reduction in WM-induced modulation of connectivity from the middle frontal gyrus to the superior parietal lobule in the right hemisphere in healthy controls, at-risk mental state participants, and first-episode psychosis patients. Notably, the abnormal modulation of connectivity in first-episode psychosis patients was normalized by treatment with antipsychotics.CONCLUSIONS AND RELEVANCE Our findings suggest that the vulnerability to psychosis is associated with a progressive failure of functional integration of brain regions involved in WM processes, including visual encoding and rule updating, and that treatment with antipsychotics may have the potential to counteract this.

U2 - 10.1001/jamapsychiatry.2013.117

DO - 10.1001/jamapsychiatry.2013.117

M3 - Article

SN - 2168-622X

VL - 70

SP - 903

EP - 912

JO - JAMA PSYCHIATRY

JF - JAMA PSYCHIATRY

IS - 9

ER -