title: Neurophysiological correlates of metabolic syndrome and cognitive impairment in schizophrenia: a structural equation modeling approach.
abstract: OBJECTIVE
  We aimed to investigate the brain functional substrate underlying relationships between metabolic syndrome (MetS) and cognitive impairment in schizophrenia.
  
  
  METHODS
  In this cross-sectional study, we collected socio-demographic, clinical, anthropometric, blood, and cognition data and performed brain 99mTc-ECD-SPECT imaging of cerebral blood flow in patients with schizophrenia. Patients were grouped according to the absence or presence of MetS. Whole-brain perfusion SPECTs were compared at voxel level between these two groups, and voxel-wise interregional correlation was performed to compare functional connectivity (voxel level significance of p<0.005, uncorrected; p<0.05 for the cluster, uncorrected; using SPM8). A structural equation model (SEM) was applied to examine the relationships between brain perfusion, connectivity between brain areas, and cognition.
  
  
  RESULTS
  Of the 55 patients, 17 had MetS. They performed significantly worse than patients without MetS on tests of executive functions (processing speed p=0.005 for TMT-A; and reactive flexibility p=0.014 for TMT-B), attention (D2 attention task p=0.007), and memory (California Verbal Learning Test p=0.039). In comparison to patients without MetS, those with MetS exhibited significant hypoperfusion within the left orbital prefrontal cortex and greater functional connectivity from this left frontal cluster within the left insula and middle/superior frontal gyrus. SEM confirmed the effect on executive functions of brain hypoperfusion and of increased connectivity, suggesting possible compensatory networks in patients with MetS.
  
  
  CONCLUSIONS
  Our study identifies the brain functional impact of MetS on cognition, with orbital prefrontal impairment and possible compensatory networks.
authors.affiliation: Aix-Marseille Univ, EA 3279 - Public Health, Chronic Diseases and Quality of Life - Research Unit, 13005 Marseille, France. Electronic address: laurent.boyer@ap-hm.fr.
authors.forename: Laurent
authors.initials: L
authors.lastname: Boyer
authors.affiliation: Department of Psychiatry, Sainte-Marguerite University Hospital, 13009 Marseille, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Testart
authors.affiliation: Aix-Marseille Univ, EA 3279 - Public Health, Chronic Diseases and Quality of Life - Research Unit, 13005 Marseille, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Michel
authors.affiliation: Department of Psychiatry, Sainte-Marguerite University Hospital, 13009 Marseille, France.
authors.forename: Raphaëlle
authors.initials: R
authors.lastname: Richieri
authors.affiliation: Department of Psychiatry, Sainte-Marguerite University Hospital, 13009 Marseille, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Faget-Agius
authors.affiliation: Department of Psychiatry, Sainte-Marguerite University Hospital, 13009 Marseille, France.
authors.forename: Violette
authors.initials: V
authors.lastname: Vanoye
authors.affiliation: Aix-Marseille Univ, EA 3279 - Public Health, Chronic Diseases and Quality of Life - Research Unit, 13005 Marseille, France.
authors.forename: Pascal
authors.initials: P
authors.lastname: Auquier
authors.affiliation: Aix-Marseille Univ, EA 3279 - Public Health, Chronic Diseases and Quality of Life - Research Unit, 13005 Marseille, France; Department of Psychiatry, Sainte-Marguerite University Hospital, 13009 Marseille, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Lancon
authors.affiliation: APHM, Hôpital de la Timone, Service Central de Biophysique et Médecine Nucléaire, 13005 Marseille, France; Aix-Marseille Univ, CERIMED 13005, Marseille, France; Aix-Marseille Univ, INT, 13005 Marseille, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Guedj
mesh_terms: D000328:Adult; D001921:Brain / Q000000981:diagnostic imaging / Q000503:physiopathology*; D002560:Cerebrovascular Circulation / Q000502:physiology; D003072:Cognition Disorders / Q000150:complications / Q000000981:diagnostic imaging / Q000503:physiopathology*; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D008297:Male; D024821:Metabolic Syndrome / Q000150:complications / Q000000981:diagnostic imaging / Q000503:physiopathology*; D008875:Middle Aged; D008962:Models, Theoretical; D009483:Neuropsychological Tests; D011877:Radionuclide Imaging; D012559:Schizophrenia / Q000150:complications / Q000000981:diagnostic imaging / Q000503:physiopathology*
keywords: Cerebral blood flow; Cognition; Metabolic syndrome; SPM; Schizophrenia; Single-photon emission computed tomography (SPECT); Structural equation modeling