PMID- 22747567
OWN - NLM
STAT- MEDLINE
DCOM- 20130401
LR  - 20220311
IS  - 1471-2431 (Electronic)
IS  - 1471-2431 (Linking)
VI  - 12
DP  - 2012 Jul 2
TI  - Perinatal stress, brain inflammation and risk of autism-review and proposal.
PG  - 89
LID - 10.1186/1471-2431-12-89 [doi]
AB  - BACKGROUND: Autism Spectrum Disorders (ASD) are neurodevelopmental disorders 
      characterized by varying deficits in social interactions, communication, and 
      learning, as well as stereotypic behaviors. Despite the significant increase in 
      ASD, there are few if any clues for its pathogenesis, hampering early detection 
      or treatment. Premature babies are also more vulnerable to infections and 
      inflammation leading to neurodevelopmental problems and higher risk of developing 
      ASD. Many autism "susceptibility" genes have been identified, but "environmental" 
      factors appear to play a significant role. Increasing evidence suggests that 
      there are different ASD endophenotypes. DISCUSSION: We review relevant literature 
      suggesting in utero inflammation can lead to preterm labor, while insufficient 
      development of the gut-blood-brain barriers could permit exposure to potential 
      neurotoxins. This risk apparently may increase in parents with "allergic" or 
      autoimmune problems during gestation, or if they had been exposed to stressors. 
      The presence of circulating auto-antibodies against fetal brain proteins in 
      mothers is associated with higher risk of autism and suggests disruption of the 
      blood-brain-barrier (BBB). A number of papers have reported increased brain 
      expression or cerebrospinal fluid (CSF) levels of pro-inflammatory cytokines, 
      especially TNF, which is preformed in mast cells. Recent evidence also indicates 
      increased serum levels of the pro-inflammatory mast cell trigger neurotensin 
      (NT), and of extracellular mitochondrial DNA (mtDNA), which is immunogenic. Gene 
      mutations of phosphatase and tensin homolog (PTEN), the negative regulator of the 
      mammalian target of rapamycin (mTOR), have been linked to higher risk of autism, 
      but also to increased proliferation and function of mast cells. SUMMARY: 
      Premature birth and susceptibility genes may make infants more vulnerable to 
      allergic, environmental, infectious, or stress-related triggers that could 
      stimulate mast cell release of pro-inflammatory and neurotoxic molecules, thus 
      contributing to brain inflammation and ASD pathogenesis, at least in an 
      endophenotype of ASD patients.
FAU - Angelidou, Asimenia
AU  - Angelidou A
AD  - Molecular Immunopharmacology and Drug Discovery Laboratory, Department of 
      Molecular Physiology and Pharmacology, Tufts University School of Medicine and 
      Tufts Medical Center, Boston, MA 02111, USA.
FAU - Asadi, Shahrzad
AU  - Asadi S
FAU - Alysandratos, Konstantinos-Dionysios
AU  - Alysandratos KD
FAU - Karagkouni, Anna
AU  - Karagkouni A
FAU - Kourembanas, Stella
AU  - Kourembanas S
FAU - Theoharides, Theoharis C
AU  - Theoharides TC
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20120702
PL  - England
TA  - BMC Pediatr
JT  - BMC pediatrics
JID - 100967804
SB  - IM
MH  - Autistic Disorder/*etiology
MH  - Encephalitis/*complications
MH  - Female
MH  - *Fetal Diseases
MH  - Humans
MH  - Infant, Newborn
MH  - Pregnancy
MH  - *Premature Birth
MH  - Risk Factors
MH  - *Stress, Physiological
PMC - PMC3496584
EDAT- 2012/07/04 06:00
MHDA- 2013/04/02 06:00
PMCR- 2012/07/02
CRDT- 2012/07/04 06:00
PHST- 2011/07/13 00:00 [received]
PHST- 2012/05/28 00:00 [accepted]
PHST- 2012/07/04 06:00 [entrez]
PHST- 2012/07/04 06:00 [pubmed]
PHST- 2013/04/02 06:00 [medline]
PHST- 2012/07/02 00:00 [pmc-release]
AID - 1471-2431-12-89 [pii]
AID - 10.1186/1471-2431-12-89 [doi]
PST - epublish
SO  - BMC Pediatr. 2012 Jul 2;12:89. doi: 10.1186/1471-2431-12-89.