title: Nicotine withdrawal alters neural responses to psychosocial stress.
abstract: Psychosocial stress is considered to be an important mechanism underlying smoking behavior and relapse. Thus, understanding the effects of acute nicotine withdrawal on responses to stress is important to intervene to prevent stress-induced relapse. The current study investigated the neural correlates of psychosocial stress during acute nicotine withdrawal in chronic smokers.
  
  
  
  Thirty-nine treatment-seeking smokers were randomized to one of two conditions (abstinent 24 h (n = 21) or smoking as usual (n = 18)). They were then exposed to the Montreal Imaging Stress Task (MIST), a psychosocial stress task consisting of difficult mental arithmetic problems while receiving negative performance feedback while undergoing functional magnetic resonance imaging (fMRI).
  
  
  
  Subjective measures of stress increased following the MIST, compared to baseline. Whole brain between-group analysis identified significant activation clusters in four regions for the stress induction minus control contrast: inferior frontal gyrus (IFG), anterior/para cingulate cortex (ACC), precuneus, and supramarginal gyrus (SMG). In all regions, the deprived group showed significantly greater activation compared to the non-deprived group. No significant correlations were found between subjective stress and BOLD signal activation (ps > 0.07).
  
  
  
  This study provides new evidence that brain regions previously shown to be predictive of relapse, such as the precuneus and IFG, display heightened neural responses to stress during nicotine deprivation. These data identify the brain regions that may be associated with withdrawal-related stress responses. Increased stress-related activation during nicotine withdrawal may identify those most vulnerable to relapse and represent a target for novel pharmacological intervention.
authors.affiliation: Center for Interdisciplinary Research on Nicotine Addiction, Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, 3535 Market St., Suite 4100, Philadelphia, PA, 19104, USA. rlashare@mail.med.upenn.edu.
authors.forename: Rebecca L
authors.initials: RL
authors.lastname: Ashare
authors.affiliation: Center for Interdisciplinary Research on Nicotine Addiction, Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, 3535 Market St., Suite 4100, Philadelphia, PA, 19104, USA.
authors.forename: Caryn
authors.initials: C
authors.lastname: Lerman
authors.affiliation: Center for Interdisciplinary Research on Nicotine Addiction, Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, 3535 Market St., Suite 4100, Philadelphia, PA, 19104, USA.
authors.forename: Wen
authors.initials: W
authors.lastname: Cao
authors.affiliation: Center for Interdisciplinary Research on Nicotine Addiction, Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, 3535 Market St., Suite 4100, Philadelphia, PA, 19104, USA.
authors.forename: Mary
authors.initials: M
authors.lastname: Falcone
authors.affiliation: Center for Interdisciplinary Research on Nicotine Addiction, Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, 3535 Market St., Suite 4100, Philadelphia, PA, 19104, USA.
authors.forename: Leah
authors.initials: L
authors.lastname: Bernardo
authors.affiliation: Brain Behavior Laboratory, Neuropsychiatry Department, Hospital of the University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Kosha
authors.initials: K
authors.lastname: Ruparel
authors.affiliation: Brain Behavior Laboratory, Neuropsychiatry Department, Hospital of the University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Ryan
authors.initials: R
authors.lastname: Hopson
authors.affiliation: Brain Behavior Laboratory, Neuropsychiatry Department, Hospital of the University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Ruben
authors.initials: R
authors.lastname: Gur
authors.affiliation: Departments of Psychology, Psychiatry, Neurology and Neurosurgery, Douglas Institute, McGill University, Montreal, Quebec, Canada.
authors.forename: Jens C
authors.initials: JC
authors.lastname: Pruessner
authors.affiliation: Center for Interdisciplinary Research on Nicotine Addiction, Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, 3535 Market St., Suite 4100, Philadelphia, PA, 19104, USA.
authors.forename: James
authors.initials: J
authors.lastname: Loughead
mesh_terms: D000328:Adult; D001921:Brain / Q000187:drug effects* / Q000503:physiopathology; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009538:Nicotine / Q000009:adverse effects*; D012907:Smoking / Q000523:psychology*; D016540:Smoking Cessation / Q000523:psychology*; D013315:Stress, Psychological / Q000209:etiology* / Q000517:prevention & control; D013375:Substance Withdrawal Syndrome / Q000523:psychology*
chemical_list: D009538:Nicotine
keywords: Imaging; Nicotine; Smoking; Stress; Withdrawal; fMRI