title: Nicotine enhances but does not normalize visual sustained attention and the associated brain network in schizophrenia.
abstract: Sustained attention abnormality in schizophrenia is usually refractory to available treatment. Nicotine can transiently improve sustained attention in schizophrenia patients, although its neural mechanisms are unknown. Understanding the neural basis of this effect may lead to new treatment strategies for this cognitive deficit. Twenty schizophrenia patients and 24 healthy comparison smokers participated in a double-blind, placebo-controlled, crossover, randomized functional magnetic resonance imaging study comparing nicotine vs placebo patch on sustained attention, using the rapid visual information-processing task. Schizophrenia patients had impaired visual sustained attention accuracy and processing speed (all P's <.001) and showed significantly reduced activation in the frontal-parietal-cingulate-thalamic attention network compared with healthy comparison subjects. Nicotine administration enhanced accuracy and processing speed compared with placebo (all P's ≤.006), with no drug × diagnosis interactions. However, schizophrenia patients' task performance remained impaired during the nicotine condition, even when compared with healthy comparison subjects in the placebo condition (all P's ≤.01). Nicotine exerted no significant reversal of the impaired attention network associated with schizophrenia. Activations in brain regions associated with nicotine-induced behavioral improvement were not significantly different between patients and comparison subjects. Thus, nicotine transiently enhanced sustained attention similarly in schizophrenia patients and in healthy comparison smokers. The neural mechanisms for this nicotinic effect in schizophrenia appear similar to those for healthy comparison subjects. However, nicotine, at least in a single sustained dose, does not normalize impaired sustained attention and its associated brain network in schizophrenia. These findings provide guidance for developing new treatment strategies for the sustained attention deficit in schizophrenia.
authors.affiliation: Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, USA. ehong@mprc.umaryland.edu
authors.forename: L Elliot
authors.initials: LE
authors.lastname: Hong
authors.forename: Matthew
authors.initials: M
authors.lastname: Schroeder
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Ross
authors.forename: Brittany
authors.initials: B
authors.lastname: Buchholz
authors.forename: Betty Jo
authors.initials: BJ
authors.lastname: Salmeron
authors.forename: Ikwunga
authors.initials: I
authors.lastname: Wonodi
authors.forename: Gunvant K
authors.initials: GK
authors.lastname: Thaker
authors.forename: Elliot A
authors.initials: EA
authors.lastname: Stein
mesh_terms: D000279:Administration, Cutaneous; D000328:Adult; D001288:Attention / Q000187:drug effects*; D001921:Brain / Q000187:drug effects* / Q000503:physiopathology; D001931:Brain Mapping; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009415:Nerve Net / Q000187:drug effects* / Q000503:physiopathology; D009538:Nicotine / Q000009:adverse effects / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D010364:Pattern Recognition, Visual / Q000187:drug effects*; D011597:Psychomotor Performance / Q000187:drug effects*; D011930:Reaction Time / Q000187:drug effects; D012559:Schizophrenia / Q000503:physiopathology*; D012907:Smoking / Q000503:physiopathology
chemical_list: D018722:Nicotinic Agonists; D009538:Nicotine