PMID- 27445670
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20160722
LR  - 20200930
IS  - 1662-4548 (Print)
IS  - 1662-453X (Electronic)
IS  - 1662-453X (Linking)
VI  - 10
DP  - 2016
TI  - 5-HT2A Gene Variants Moderate the Association between PTSD and Reduced Default 
      Mode Network Connectivity.
PG  - 299
LID - 10.3389/fnins.2016.00299 [doi]
LID - 299
AB  - The default mode network (DMN) has been used to study disruptions of functional 
      connectivity in a wide variety of psychiatric and neurological conditions, 
      including posttraumatic stress disorder (PTSD). Studies indicate that the 
      serotonin system exerts a modulatory influence on DMN connectivity; however, no 
      prior study has examined associations between serotonin receptor gene variants 
      and DMN connectivity in either clinical or healthy samples. We examined serotonin 
      receptor single nucleotide polymorphisms (SNPs), PTSD, and their interactions for 
      association with DMN connectivity in 134 White non-Hispanic veterans. We began by 
      analyzing candidate SNPs identified in prior meta-analyses of relevant 
      psychiatric traits and found that rs7997012 (an HTR2A SNP), implicated previously 
      in anti-depressant medication response in the Sequenced Treatment Alternatives 
      for Depression study (STAR(*)D; McMahon et al., 2006), interacted with PTSD to 
      predict reduced connectivity between the posterior cingulate cortex (PCC) and the 
      right medial prefrontal cortex and right middle temporal gyrus (MTG). rs130058 
      (HTR1B) was associated with connectivity between the PCC and right angular gyrus. 
      We then expanded our analysis to 99 HTR1B and HTR2A SNPs and found two HTR2A SNPs 
      (rs977003 and rs7322347) that significantly moderated the association between 
      PTSD severity and the PCC-right MTG component of the DMN after correcting for 
      multiple testing. Finally, to obtain a more precise localization of the most 
      significant SNP x PTSD interaction, we performed a whole cortex vertex-wise 
      analysis of the rs977003 effect. This analysis revealed the locus of the 
      pre-frontal effect to be in portions of the superior frontal gyrus, while the 
      temporal lobe effect was centered in the middle and inferior temporal gyri. These 
      findings point to the influence of HTR2A variants on DMN connectivity and advance 
      knowledge of the role of 5-HT2A receptors in the neurobiology of PTSD.
FAU - Miller, Mark W
AU  - Miller MW
AD  - Behavioral Science Division, National Center for PTSD, VA Boston Healthcare 
      SystemBoston, MA, USA; Department of Psychiatry, Boston University School of 
      MedicineBoston, MA, USA.
FAU - Sperbeck, Emily
AU  - Sperbeck E
AD  - Department of Psychiatry, Boston University School of Medicine Boston, MA, USA.
FAU - Robinson, Meghan E
AU  - Robinson ME
AD  - Neuroimaging Research for Veterans Center, VA Boston Healthcare SystemBoston, MA, 
      USA; Geriatric Research Educational and Clinical Center and Translational 
      Research Center for TBI and Stress Disorders, VA Boston Healthcare SystemBoston, 
      MA, USA; Department of Neurology, Boston University School of MedicineBoston, MA, 
      USA.
FAU - Sadeh, Naomi
AU  - Sadeh N
AD  - Behavioral Science Division, National Center for PTSD, VA Boston Healthcare 
      SystemBoston, MA, USA; Department of Psychiatry, Boston University School of 
      MedicineBoston, MA, USA.
FAU - Wolf, Erika J
AU  - Wolf EJ
AD  - Behavioral Science Division, National Center for PTSD, VA Boston Healthcare 
      SystemBoston, MA, USA; Department of Psychiatry, Boston University School of 
      MedicineBoston, MA, USA.
FAU - Hayes, Jasmeet P
AU  - Hayes JP
AD  - Behavioral Science Division, National Center for PTSD, VA Boston Healthcare 
      SystemBoston, MA, USA; Department of Psychiatry, Boston University School of 
      MedicineBoston, MA, USA.
FAU - Logue, Mark
AU  - Logue M
AD  - Behavioral Science Division, National Center for PTSD, VA Boston Healthcare 
      SystemBoston, MA, USA; Department of Psychiatry, Boston University School of 
      MedicineBoston, MA, USA; Biomedical Genetics, Boston University School of 
      MedicineBoston, MA, USA; Department of Biostatistics, Boston University School of 
      Public HealthBoston, MA, USA.
FAU - Schichman, Steven A
AU  - Schichman SA
AD  - Pharmacogenomics Analysis Laboratory, Research Service, Central Arkansas Veterans 
      Healthcare System Little Rock, AR, USA.
FAU - Stone, Angie
AU  - Stone A
AD  - Pharmacogenomics Analysis Laboratory, Research Service, Central Arkansas Veterans 
      Healthcare System Little Rock, AR, USA.
FAU - Milberg, William
AU  - Milberg W
AD  - Geriatric Research Educational and Clinical Center and Translational Research 
      Center for TBI and Stress Disorders, VA Boston Healthcare SystemBoston, MA, USA; 
      Department of Psychiatry, Harvard Medical SchoolBoston, MA, USA.
FAU - McGlinchey, Regina
AU  - McGlinchey R
AD  - Geriatric Research Educational and Clinical Center and Translational Research 
      Center for TBI and Stress Disorders, VA Boston Healthcare SystemBoston, MA, USA; 
      Department of Psychiatry, Harvard Medical SchoolBoston, MA, USA.
LA  - eng
GR  - R21 MH102834/MH/NIMH NIH HHS/United States
PT  - Journal Article
DEP - 20160628
PL  - Switzerland
TA  - Front Neurosci
JT  - Frontiers in neuroscience
JID - 101478481
PMC - PMC4923242
OTO - NOTNLM
OT  - HTR1B
OT  - HTR2A
OT  - default mode network
OT  - functional connectivity
OT  - posttraumatic stress disorder
OT  - serotonin receptor
EDAT- 2016/07/23 06:00
MHDA- 2016/07/23 06:01
PMCR- 2016/01/01
CRDT- 2016/07/23 06:00
PHST- 2016/03/07 00:00 [received]
PHST- 2016/06/13 00:00 [accepted]
PHST- 2016/07/23 06:00 [entrez]
PHST- 2016/07/23 06:00 [pubmed]
PHST- 2016/07/23 06:01 [medline]
PHST- 2016/01/01 00:00 [pmc-release]
AID - 10.3389/fnins.2016.00299 [doi]
PST - epublish
SO  - Front Neurosci. 2016 Jun 28;10:299. doi: 10.3389/fnins.2016.00299. eCollection 
      2016.