Comment on the publication Microglial Activity in People at Ultra High Risk of Psychosis and in Schizophrenia: An [11C]PBR28 PET Brain Imaging Study, with reference to the publication NEUROIMMUNE MECHANISMS IN FETAL ALCOHOL SPECTRUM DISORDER

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Microglial Activity in People at Ultra High
Risk of Psychosis and in Schizophrenia: An
[11
C]PBR28 PET Brain Imaging Study
Peter S. Bloomfield, M.Sc., Sudhakar Selvaraj, M.D., Ph.D., Mattia
Veronese, Ph.D., Gaia Rizzo, Ph.D., Alessandra Bertoldo, Ph.D., David
R. Owen, M.D., Ph.D., Michael A.P. Bloomfield, M.D., Ilaria Bonoldi,
M.D., Nicola Kalk, M.D., Federico Turkheimer, Ph.D., Philip McGuire,
M.D., Ph.D., Vincenzo de Paola, Ph.D., Oliver D. Howes, M.D.Ph.D.
Received: October 29, 2014
Accepted: July 02, 2015
http://dx.doi.org/10.1176/appi.ajp.2015.14101358
• Abstract Full Text References Supplementary Materials PDF
Abstract
Objective:
The purpose of this study was to determine whether microglial activity,
measured using translocator-protein positron emission tomography
(PET) imaging, is increased in unmedicated persons presenting with
subclinical symptoms indicating that they are at ultra high risk of
psychosis and to determine whether microglial activity is elevated in
schizophrenia after controlling for a translocator-specific genetic
polymorphism.

2. The authors used the second-generation radioligand [11
C]PBR28 and
PET to image microglial activity in the brains of participants at ultra
high risk for psychosis. Participants were recruited from early
intervention centers. The authors also imaged a cohort of patients with
schizophrenia and matched healthy subjects for comparison. In total,
56 individuals completed the study. At screening, participants were
genotyped to account for the rs6971 polymorphism in the gene
encoding the 18Kd translocator protein. The main outcome measure
was total gray matter [11
C]PBR28 binding ratio, representing microglial
activity.
Results:
[11
C]PBR28 binding ratio in gray matter was elevated in ultra-high-risk
participants compared with matched comparison subjects (Cohen’s d
>1.2) and was positively correlated with symptom severity (r=0.730).
Patients with schizophrenia also demonstrated elevated microglial
activity relative to matched comparison subjects (Cohen’s d >1.7).
Conclusions:
Microglial activity is elevated in patients with schizophrenia and in
persons with subclinical symptoms who are at ultra high risk of
psychosis and is related to at-risk symptom severity. These findings
suggest that neuroinflammation is linked to the risk of psychosis and
related disorders, as well as the expression of subclinical symptoms.

3. Comment on the above publication
Alcohol, prenatal, and postnatal, interferes with the normal development and
function of microglia.
95% of individuals diagnosed FASD will subsequently receive diagnoses from the
DSM, including schizophrenia.
The following is from
Dev Neurobiol. 2012 Oct; 72(10): 1302–1316.
Published online 2012 Sep 1. doi: 10.1002/dneu.22035
PMCID: PMC3435481
NIHMSID: NIHMS393307
NEUROIMMUNE MECHANISMS IN FETAL ALCOHOL SPECTRUM
DISORDER
Cynthia J. M. Kane, Kevin D. Phelan, and Paul D. Drew
CONCLUSION
FASD have a devastating effect on society and on the individual. Human imaging
studies have revealed the presence of structural changes that occur throughout the
CNS as well as neuropsychological and behavioral changes that contribute to the
clinical diagnosis of FASD. Future studies will undoubtedly elaborate on the
correlation between specific neuropathological changes in the brain and behavioral
alterations. Animal models have been instrumental in defining the relationship
between temporal exposure to alcohol during early stages of development and the
sequelae of events that follow as the animal ages. The neuroimmune system is
emerging as central player in alcohol pathology although the extent of our
knowledge is still in its infancy. Microglia appear to be one of the most important
players in this regard. These cells normally function in maintaining homeostasis
within the CNS, however, if chronically activated they can cause damage to
resident cells and tissues. The microglial response to alcohol is complex and
involves the TLR signaling pathway. A more complete understanding of the
signaling pathways involved in alcohol modulation of neuroimmune mechanisms
in the CNS as well as the role of these molecules in modulating addiction to
alcohol must be a focus of future research studies.
Barry Stanley
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