title: Altered threat and safety neural processing linked to persecutory delusions in schizophrenia: a two-task fMRI study.
abstract: Persecutory delusions are a clinically important symptom in schizophrenia associated with social avoidance and increased violence. Few studies have investigated the neurobiology of persecutory delusions, which is a prerequisite for developing novel treatments. The aim of this two-paradigm functional magnetic resonance imaging (fMRI) study is to characterize social "real world" and linguistic threat brain activations linked to persecutory delusions in schizophrenia (n=26) using instructed-fear/safety and emotional word paradigms. Instructed-fear/safety activations correlated to persecutory delusion severity demonstrated significant increased lateral orbitofrontal cortex and visual association cortex activations for the instructed-fear vs. safety and instructed-fear vs. baseline contrasts; decreased lateral orbitofrontal cortex and ventral occipital-temporal cortex activations were observed for the instructed-safety stimuli vs. baseline contrast. The salience network also showed divergent fear and safety cued activations correlated to persecutory delusions. Emotional word paradigm analyses showed positive correlations between persecutory delusion severity and left-lateralized linguistic and hippocampal-parahippocampal activations for the threat vs. neutral word contrast. Visual word form area activations correlated positively with persecutory delusions for both threat and neutral word vs. baseline contrasts. This study links persecutory delusions to enhanced neural processing of threatening stimuli and decreased processing of safety cues, and helps elucidate systems-level activations associated with persecutory delusions in schizophrenia.
authors.affiliation: Functional Neuroimaging Laboratory, Brigham and Women's Hospital, Harvard Medical School, Department of Psychiatry, 824 Boylston Street, Chestnut Hill, MA 02467, USA.
authors.forename: David L
authors.initials: DL
authors.lastname: Perez
authors.affiliation: Functional Neuroimaging Laboratory, Brigham and Women's Hospital, Harvard Medical School, Department of Psychiatry, 824 Boylston Street, Chestnut Hill, MA 02467, USA; Brigham and Women's Hospital, Department of Radiology, Harvard Medical School, Boston, MA, USA.
authors.forename: Hong
authors.initials: H
authors.lastname: Pan
authors.affiliation: Functional Neuroimaging Laboratory, Brigham and Women's Hospital, Harvard Medical School, Department of Psychiatry, 824 Boylston Street, Chestnut Hill, MA 02467, USA; Brigham and Women's Hospital, Department of Neurology, Boston, MA, USA.
authors.forename: Daniel S
authors.initials: DS
authors.lastname: Weisholtz
authors.affiliation: Memorial Sloan Kettering Cancer Center, Department of Psychiatry and Behavioral Sciences, New York, NY, USA.
authors.forename: James C
authors.initials: JC
authors.lastname: Root
authors.affiliation: University Medical Center Freiburg, Department of Neurology, Freiburg im Breisgau, Germany; University Medical Centre Mainz, Department of Psychiatry and Psychotherapy, Mainz, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Tuescher
authors.affiliation: Functional Neuroimaging Laboratory, Brigham and Women's Hospital, Harvard Medical School, Department of Psychiatry, 824 Boylston Street, Chestnut Hill, MA 02467, USA.
authors.forename: David B
authors.initials: DB
authors.lastname: Fischer
authors.affiliation: Langone Medical Center, New York University School of Medicine, New York, NY, USA.
authors.forename: Tracy
authors.initials: T
authors.lastname: Butler
authors.affiliation: Functional Neuroimaging Laboratory, Brigham and Women's Hospital, Harvard Medical School, Department of Psychiatry, 824 Boylston Street, Chestnut Hill, MA 02467, USA.
authors.forename: David R
authors.initials: DR
authors.lastname: Vago
authors.affiliation: Neuroscience Institute, Virginia Mason Medical Center, Seattle, WA, USA.
authors.forename: Nancy
authors.initials: N
authors.lastname: Isenberg
authors.affiliation: Functional Neuroimaging Laboratory, Brigham and Women's Hospital, Harvard Medical School, Department of Psychiatry, 824 Boylston Street, Chestnut Hill, MA 02467, USA.
authors.forename: Jane
authors.initials: J
authors.lastname: Epstein
authors.affiliation: Weill Cornell Medical Center, Department of Psychiatry, New York, NY, USA.
authors.forename: Yulia
authors.initials: Y
authors.lastname: Landa
authors.affiliation: New York State Psychiatric Institute, Columbia University, New York, NY, USA.
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Smith
authors.affiliation: Weill Cornell Medical Center, Department of Psychiatry, New York, NY, USA.
authors.forename: Adam J
authors.initials: AJ
authors.lastname: Savitz
authors.affiliation: Functional Neuroimaging Laboratory, Brigham and Women's Hospital, Harvard Medical School, Department of Psychiatry, 824 Boylston Street, Chestnut Hill, MA 02467, USA; Brigham and Women's Hospital, Department of Neurology, Boston, MA, USA.
authors.forename: David A
authors.initials: DA
authors.lastname: Silbersweig
authors.affiliation: Functional Neuroimaging Laboratory, Brigham and Women's Hospital, Harvard Medical School, Department of Psychiatry, 824 Boylston Street, Chestnut Hill, MA 02467, USA; Brigham and Women's Hospital, Department of Radiology, Harvard Medical School, Boston, MA, USA. Electronic address: estern3@partners.org.
authors.forename: Emily
authors.initials: E
authors.lastname: Stern
mesh_terms: D000328:Adult; D015331:Cohort Studies; D003702:Delusions / Q000175:diagnosis / Q000378:metabolism* / Q000523:psychology; D004644:Emotions / Q000502:physiology; D005239:Fear / Q000502:physiology* / Q000523:psychology; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D009415:Nerve Net / Q000378:metabolism*; D010775:Photic Stimulation / Q000379:methods; D011597:Psychomotor Performance / Q000502:physiology*; D012559:Schizophrenia / Q000175:diagnosis / Q000378:metabolism*; D012565:Schizophrenic Psychology; D055815:Young Adult
keywords: Delusion; Fear; Paranoid; Psychosis; Safety; fMRI