PMID- 35153877
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230303
IS  - 1664-0640 (Print)
IS  - 1664-0640 (Electronic)
IS  - 1664-0640 (Linking)
VI  - 13
DP  - 2022
TI  - Evidence for Schizophrenia-Specific Pathophysiology of Nicotine Dependence.
PG  - 804055
LID - 10.3389/fpsyt.2022.804055 [doi]
LID - 804055
AB  - Tobacco use is the top preventable cause of early mortality in schizophrenia. 
      Over 60% of people with schizophrenia smoke, three times the general prevalence. 
      The biological basis of this increased risk is not understood, and existing 
      interventions do not target schizophrenia-specific pathology. We therefore used a 
      connectome-wide analysis to identify schizophrenia-specific circuits of nicotine 
      addiction. We reanalyzed data from two studies: In Cohort 1, 35 smokers (18 
      schizophrenia, 17 control) underwent resting-state fMRI and clinical 
      characterization. A multivariate pattern analysis of whole-connectome data was 
      used to identify the strongest links between cigarette use and functional 
      connectivity. In Cohort 2, 12 schizophrenia participants and 12 controls were 
      enrolled in a randomized, controlled crossover study of nicotine patch with 
      resting-state fMRI. We correlated change in network functional connectivity with 
      nicotine dose. In Cohort 1, the strongest (p < 0.001) correlate between 
      connectivity and cigarette use was driven by individual variation in default mode 
      network (DMN) topography. In individuals with greater daily cigarette 
      consumption, we observed a pathological expansion of the DMN territory into the 
      identified parieto-occipital region, while in individuals with lower daily 
      cigarette consumption, this region was external to the DMN. This effect was 
      entirely driven by schizophrenia participants. Given the relationship between DMN 
      topography and nicotine use we observed in Cohort 1, we sought to directly test 
      the impact of nicotine on this network using an independent second cohort. In 
      Cohort 2, nicotine reduced DMN connectivity in a dose-dependent manner (R = 
      -0.50; 95% CI -0.75 to -0.12, p < 0.05). In the placebo condition, schizophrenia 
      subjects had hyperconnectivity compared to controls (p < 0.05). Nicotine 
      administration normalized DMN hyperconnectivity in schizophrenia. We here provide 
      direct evidence that the biological basis of nicotine dependence is different in 
      schizophrenia and in non-schizophrenia populations. Our results suggest the high 
      prevalence of nicotine use in schizophrenia may be an attempt to correct a 
      network deficit known to interfere with cognition.
CI  - Copyright (c) 2022 Ward, Beermann, Nawaz, Halko, Janes, Moran and Brady.
FAU - Ward, Heather Burrell
AU  - Ward HB
AD  - Beth Israel Deaconess Medical Center, Boston, MA, United States.
AD  - Harvard Medical School, Boston, MA, United States.
FAU - Beermann, Adam
AU  - Beermann A
AD  - Beth Israel Deaconess Medical Center, Boston, MA, United States.
FAU - Nawaz, Uzma
AU  - Nawaz U
AD  - Beth Israel Deaconess Medical Center, Boston, MA, United States.
FAU - Halko, Mark A
AU  - Halko MA
AD  - Harvard Medical School, Boston, MA, United States.
AD  - McLean Hospital, Belmont, MA, United States.
FAU - Janes, Amy C
AU  - Janes AC
AD  - Harvard Medical School, Boston, MA, United States.
AD  - McLean Hospital, Belmont, MA, United States.
FAU - Moran, Lauren V
AU  - Moran LV
AD  - Harvard Medical School, Boston, MA, United States.
AD  - McLean Hospital, Belmont, MA, United States.
FAU - Brady, Roscoe O Jr
AU  - Brady RO Jr
AD  - Beth Israel Deaconess Medical Center, Boston, MA, United States.
AD  - Harvard Medical School, Boston, MA, United States.
AD  - McLean Hospital, Belmont, MA, United States.
LA  - eng
GR  - R01 MH126000/MH/NIMH NIH HHS/United States
GR  - R01 MH122427/MH/NIMH NIH HHS/United States
GR  - R01 MH116170/MH/NIMH NIH HHS/United States
GR  - R56 MH125995/MH/NIMH NIH HHS/United States
GR  - R01 MH111868/MH/NIMH NIH HHS/United States
PT  - Journal Article
DEP - 20220127
PL  - Switzerland
TA  - Front Psychiatry
JT  - Frontiers in psychiatry
JID - 101545006
PMC - PMC8829345
OTO - NOTNLM
OT  - default mode (DMN) subnetwork
OT  - nicotine dependence
OT  - psychosis
OT  - resting-state functional MRI
OT  - schizophrenia
OT  - tobacco
COIS- AJ is a consultant for Axial Biotherapeutics for activities unrelated to this 
      work. The remaining authors declare that the research was conducted in the 
      absence of any commercial or financial relationships that could be construed as a 
      potential conflict of interest.
EDAT- 2022/02/15 06:00
MHDA- 2022/02/15 06:01
PMCR- 2022/01/27
CRDT- 2022/02/14 05:29
PHST- 2021/10/28 00:00 [received]
PHST- 2022/01/03 00:00 [accepted]
PHST- 2022/02/14 05:29 [entrez]
PHST- 2022/02/15 06:00 [pubmed]
PHST- 2022/02/15 06:01 [medline]
PHST- 2022/01/27 00:00 [pmc-release]
AID - 10.3389/fpsyt.2022.804055 [doi]
PST - epublish
SO  - Front Psychiatry. 2022 Jan 27;13:804055. doi: 10.3389/fpsyt.2022.804055. 
      eCollection 2022.