title: Association of enhanced limbic response to threat with decreased cortical facial recognition memory response in schizophrenia.
abstract: OBJECTIVE
  Recognition memory of faces is impaired in patients with schizophrenia, as is the neural processing of threat-related signals, but how these deficits interact to produce symptoms is unclear. The authors used an affective face recognition paradigm to examine possible interactions between cognitive and affective neural systems in schizophrenia.
  
  
  METHODS
  Blood-oxygen-level-dependent response was examined by means of functional magnetic resonance imaging (3 Tesla) in healthy comparison subjects (N=21) and in patients with schizophrenia (N=12) or schizoaffective disorder, depressed type (N=4), during a two-choice recognition task that used images of human faces. Each target face, previously displayed with a threatening or nonthreatening affect, was displayed with neutral affect. Responses to successful recognition and responses to the effect of previously threatening versus nonthreatening affect were evaluated, and correlations with symptom severity (total Brief Psychiatric Rating Scale score) were examined. Functional connectivity analyses examined the relationship between activation in the amygdala and cortical regions involved in recognition memory.
  
  
  RESULTS
  Patients performed the task more slowly than healthy comparison subjects. Comparison subjects recruited the expected cortical regions to a greater degree than patients, and patients with more severe symptoms demonstrated proportionally less recruitment. Increased symptoms were also correlated with augmented amygdala and orbitofrontal cortex response to threatening faces. Comparison subjects exhibited a negative correlation between activity in the amygdala and cortical regions involved in cognition, while patients showed weakening of this relationship.
  
  
  CONCLUSIONS
  Increased symptoms were related to an enhanced threat response in limbic regions and a diminished recognition memory response in cortical regions, supporting a link between these two brain systems that are often examined in isolation. This finding suggests that abnormal processing of threat-related signals in the environment may exacerbate cognitive impairment in schizophrenia.
authors.affiliation: Department of Psychiatry, University of Pennsylvania, Philadelphia, PA 19104, USA. Ted.Satterthwaite@uphs.upenn.edu
authors.forename: Theodore D
authors.initials: TD
authors.lastname: Satterthwaite
authors.forename: Daniel H
authors.initials: DH
authors.lastname: Wolf
authors.forename: James
authors.initials: J
authors.lastname: Loughead
authors.forename: Kosha
authors.initials: K
authors.lastname: Ruparel
authors.forename: Jeffrey N
authors.initials: JN
authors.lastname: Valdez
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Siegel
authors.forename: Christian G
authors.initials: CG
authors.lastname: Kohler
authors.forename: Raquel E
authors.initials: RE
authors.lastname: Gur
authors.forename: Ruben C
authors.initials: RC
authors.lastname: Gur
mesh_terms: D000339:Affect; D014150:Antipsychotic Agents / Q000627:therapeutic use; D002540:Cerebral Cortex / Q000098:blood supply*; D002560:Cerebrovascular Circulation / Q000502:physiology; D002746:Chlorpromazine / Q000627:therapeutic use; D005149:Facial Expression; D007839:Functional Laterality / Q000502:physiology; D006801:Humans; D007600:Judgment; D008032:Limbic System / Q000098:blood supply*; D008279:Magnetic Resonance Imaging; D008568:Memory; D009415:Nerve Net / Q000503:physiopathology; D010296:Parietal Lobe / Q000503:physiopathology; D010468:Perceptual Disorders / Q000175:diagnosis*; D021641:Recognition, Psychology; D012559:Schizophrenia / Q000150:complications* / Q000188:drug therapy / Q000503:physiopathology*; D012720:Severity of Illness Index
chemical_list: D014150:Antipsychotic Agents; D002746:Chlorpromazine