PMID- 28762055
OWN - NLM
STAT- MEDLINE
DCOM- 20180723
LR  - 20181113
IS  - 1432-1106 (Electronic)
IS  - 0014-4819 (Linking)
VI  - 235
IP  - 10
DP  - 2017 Oct
TI  - Gulf War illness (GWI) as a neuroimmune disease.
PG  - 3217-3225
LID - 10.1007/s00221-017-5050-0 [doi]
AB  - Gulf War illness (GWI) is a chronic disease characterized by the involvement of 
      several organs, including the brain (Christova et al., Exp Brain Res doi: 
      10.1007/s00221-017-5010-8 , 2017). In a previous study (Georgopoulos et al., J 
      Neural Eng 4:349-355, 2015), we identified six protective alleles from Class II 
      human leukocyte antigen (HLA) genes, and more recently, we investigated the brain 
      correlates of this protection (James et al., EBioMedicine 13:72-79, 2016). Those 
      and other studies (Israeli, Lupus, 21:190-194, 2012) suggested an involvement of 
      the immune system in GWI. In a recent study (Engdahl et al., EBioMedicine doi: 
      10.1016/j.ebiom.2016.08.030 , 2016), we showed that the brain pattern of 
      synchronous neural interactions (SNI; Georgopoulos et al., J Neural Eng 
      4:349-355, 2007) in GWI is distinctly different from that in healthy controls. 
      Here we focused on the SNI itself, as a basic measure of neural communication 
      (irrespective of specific connections) and compared it between GWI and seven 
      other diseases that cover a broad spectrum of etiology and pathophysiology. 
      Specifically, we sought to determine which, if any, of those diseases might 
      resemble GWI SNI, overall and within the HLA protective domain, and thus gain 
      further knowledge regarding the nature of GWI brain abnormality. We studied a 
      total of 962 participants from a healthy control population (N = 583) and eight 
      different diseases, including GWI (N = 40), schizophrenia (SZ; N = 21), 
      Alzheimer's disease (AD; N = 66), posttraumatic stress disorder (PTSD; N = 159), 
      major depressive disorder (MDD; N = 10), relapsing-remitting multiple sclerosis 
      (RRMS; N = 43), Sjogren's syndrome (SS; N = 32), and rheumatoid arthritis (RA; 
      N = 8). They all underwent a resting-state magnetoencephalographic (MEG) scan to 
      calculate SNIs. Data were analyzed using analysis of covariance (ANCOVA) with 
      disease as fixed factor, and sex and age as covariates. We found that GWI SNIs 
      differed significantly from control SZ, AD, PTSD and MDD but not from RRMS, SS 
      and RA. In addition, we compared GWI to RRMS, SS and RA with respect to SNIs of 
      MEG sensor pairs that were related to the HLA alleles protective for GWI (James 
      et al., EBioMedicine 13:72-79, 2016). We found that GWI SNIs did not differ 
      significantly from any of these three diseases but they did so from control SZ, 
      AD, PTSD and MDD. These findings indicate that (a) GWI brain synchronicity does 
      not differ significantly from that of known immune-related diseases (RRMS, SS, 
      RA), and (b) that this SNI similarity is present within the HLA-related SNIs. In 
      contrast, GWI SNIs differed significantly from those of the other diseases. We 
      conclude that altered brain communication in GWI likely reflects immune-related 
      processes, as postulated previously (James et al., EBioMedicine 13:72-79, 2016). 
      By extension, these findings also indicate that functional brain abnormalities in 
      RRMS, SS and RA might be, in part, due to lack of protective HLA alleles as 
      documented for GWI (Georgopoulos et al., EBioMedicine 3:79-85, 2015).
FAU - Georgopoulos, Apostolos P
AU  - Georgopoulos AP
AD  - Brain Sciences Center (11B), Minneapolis Veterans Affairs Health Care System, One 
      Veterans Drive, Minneapolis, MN, 55417, USA. omega@umn.edu.
AD  - Department of Neuroscience, University of Minnesota Medical School, Minneapolis, 
      MN, 55455, USA. omega@umn.edu.
AD  - Center for Cognitive Sciences, University of Minnesota, Minneapolis, MN, 55455, 
      USA. omega@umn.edu.
AD  - Department of Psychiatry, University of Minnesota Medical School, Minneapolis, 
      MN, 55455, USA. omega@umn.edu.
AD  - Department of Neurology, University of Minnesota Medical School, Minneapolis, MN, 
      55455, USA. omega@umn.edu.
FAU - James, Lisa M
AU  - James LM
AD  - Brain Sciences Center (11B), Minneapolis Veterans Affairs Health Care System, One 
      Veterans Drive, Minneapolis, MN, 55417, USA.
AD  - Department of Neuroscience, University of Minnesota Medical School, Minneapolis, 
      MN, 55455, USA.
AD  - Center for Cognitive Sciences, University of Minnesota, Minneapolis, MN, 55455, 
      USA.
AD  - Department of Psychiatry, University of Minnesota Medical School, Minneapolis, 
      MN, 55455, USA.
FAU - Carpenter, Adam F
AU  - Carpenter AF
AD  - Brain Sciences Center (11B), Minneapolis Veterans Affairs Health Care System, One 
      Veterans Drive, Minneapolis, MN, 55417, USA.
AD  - Department of Neurology, University of Minnesota Medical School, Minneapolis, MN, 
      55455, USA.
FAU - Engdahl, Brian E
AU  - Engdahl BE
AD  - Brain Sciences Center (11B), Minneapolis Veterans Affairs Health Care System, One 
      Veterans Drive, Minneapolis, MN, 55417, USA.
AD  - Department of Neuroscience, University of Minnesota Medical School, Minneapolis, 
      MN, 55455, USA.
AD  - Center for Cognitive Sciences, University of Minnesota, Minneapolis, MN, 55455, 
      USA.
AD  - Department of Psychology, University of Minnesota, Minneapolis, USA.
FAU - Leuthold, Arthur C
AU  - Leuthold AC
AD  - Brain Sciences Center (11B), Minneapolis Veterans Affairs Health Care System, One 
      Veterans Drive, Minneapolis, MN, 55417, USA.
AD  - Department of Neuroscience, University of Minnesota Medical School, Minneapolis, 
      MN, 55455, USA.
FAU - Lewis, Scott M
AU  - Lewis SM
AD  - Brain Sciences Center (11B), Minneapolis Veterans Affairs Health Care System, One 
      Veterans Drive, Minneapolis, MN, 55417, USA.
AD  - Department of Neurology, University of Minnesota Medical School, Minneapolis, MN, 
      55455, USA.
LA  - eng
GR  - Service Directed Grant/U.S. Department of Veterans Affairs/International
GR  - W81XWH-15-1-0520/U.S. Department of Defense/International
PT  - Comparative Study
PT  - Journal Article
DEP - 20170731
PL  - Germany
TA  - Exp Brain Res
JT  - Experimental brain research
JID - 0043312
RN  - 0 (Histocompatibility Antigens Class II)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Alzheimer Disease/genetics/physiopathology
MH  - Arthritis, Rheumatoid/genetics/physiopathology
MH  - Autoimmune Diseases/genetics/*physiopathology
MH  - Brain/*physiopathology
MH  - Brain Diseases/genetics/*physiopathology
MH  - Depressive Disorder, Major/genetics/physiopathology
MH  - Electroencephalography Phase Synchronization/*physiology
MH  - Female
MH  - Histocompatibility Antigens Class II/*genetics
MH  - Humans
MH  - Magnetoencephalography/*methods
MH  - Male
MH  - Mental Disorders/genetics/*physiopathology
MH  - Middle Aged
MH  - Multiple Sclerosis, Relapsing-Remitting/genetics/physiopathology
MH  - Persian Gulf Syndrome/classification/genetics/*physiopathology
MH  - Schizophrenia/genetics/physiopathology
MH  - Stress Disorders, Post-Traumatic/genetics/physiopathology
OTO - NOTNLM
OT  - Alzheimer's disease
OT  - Gulf War illness (GWI)
OT  - Human leukocyte antigen (HLA)
OT  - Magnetoencephalography
OT  - Major depressive disorder
OT  - Posttraumatic stress disorder
OT  - Relapsing-remitting multiple sclerosis
OT  - Rheumatoid arthritis
OT  - Schizophrenia
OT  - Sjogren's syndrome
OT  - Veterans
EDAT- 2017/08/02 06:00
MHDA- 2018/07/24 06:00
CRDT- 2017/08/02 06:00
PHST- 2017/02/11 00:00 [received]
PHST- 2017/07/26 00:00 [accepted]
PHST- 2017/08/02 06:00 [pubmed]
PHST- 2018/07/24 06:00 [medline]
PHST- 2017/08/02 06:00 [entrez]
AID - 10.1007/s00221-017-5050-0 [pii]
AID - 10.1007/s00221-017-5050-0 [doi]
PST - ppublish
SO  - Exp Brain Res. 2017 Oct;235(10):3217-3225. doi: 10.1007/s00221-017-5050-0. Epub 
      2017 Jul 31.