title: Antipsychotic dose and diminished neural modulation: a multi-site fMRI study.
abstract: BACKGROUND
  The effect of antipsychotics on the blood oxygen level dependent signal in schizophrenia is poorly understood. The purpose of the present investigation is to examine the effect of antipsychotic medication on independent neural networks during a motor task in a large, multi-site functional magnetic resonance imaging investigation.
  
  
  METHODS
  Seventy-nine medicated patients with schizophrenia and 114 comparison subjects from the Mind Clinical Imaging Consortium database completed a paced, auditory motor task during functional magnetic resonance imaging (fMRI). Independent component analysis identified temporally cohesive but spatially distributed neural networks. The independent component analysis time course was regressed with a model time course of the experimental design. The resulting beta weights were evaluated for group comparisons and correlations with chlorpromazine equivalents.
  
  
  RESULTS
  Group differences between patients and comparison subjects were evident in the cortical and subcortical motor networks, default mode networks, and attentional networks. The chlorpromazine equivalents correlated with the unimotor/bitemporal (rho=-0.32, P=0.0039), motor/caudate (rho=-0.22, P=0.046), posterior default mode (rho=0.26, P=0.020), and anterior default mode networks (rho=0.24, P=0.03). Patients on typical antipsychotics also had less positive modulation of the motor/caudate network relative to patients on atypical antipsychotics (t(77)=2.01, P=0.048).
  
  
  CONCLUSIONS
  The results suggest that antipsychotic dose diminishes neural activation in motor (cortical and subcortical) and default mode networks in patients with schizophrenia. The higher potency, typical antipsychotics also diminish positive modulation in subcortical motor networks. Antipsychotics may be a potential confound limiting interpretation of fMRI studies on the disease process in medicated patients with schizophrenia.
authors.affiliation: Dept. of Psychiatry, University of New Mexico, Albuquerque, New Mexico 87131, United States. cabbott@salud.unm.edu
authors.forename: C
authors.initials: C
authors.lastname: Abbott
authors.forename: M
authors.initials: M
authors.lastname: Juárez
authors.forename: T
authors.initials: T
authors.lastname: White
authors.forename: R L
authors.initials: RL
authors.lastname: Gollub
authors.forename: G D
authors.initials: GD
authors.lastname: Pearlson
authors.forename: J
authors.initials: J
authors.lastname: Bustillo
authors.forename: J
authors.initials: J
authors.lastname: Lauriello
authors.forename: B
authors.initials: B
authors.lastname: Ho
authors.forename: H J
authors.initials: HJ
authors.lastname: Bockholt
authors.forename: V P
authors.initials: VP
authors.lastname: Clark
authors.forename: V
authors.initials: V
authors.lastname: Magnotta
authors.forename: V D
authors.initials: VD
authors.lastname: Calhoun
mesh_terms: D000161:Acoustic Stimulation; D000328:Adult; D014150:Antipsychotic Agents / Q000145:classification / Q000627:therapeutic use*; D001921:Brain / Q000187:drug effects* / Q000503:physiopathology; D002540:Cerebral Cortex / Q000187:drug effects / Q000503:physiopathology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009044:Motor Cortex / Q000187:drug effects*; D011569:Psychiatric Status Rating Scales; D012559:Schizophrenia / Q000188:drug therapy / Q000503:physiopathology*; D055815:Young Adult
chemical_list: D014150:Antipsychotic Agents