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. Author manuscript; available in PMC: 2016 Jul 28.
Published in final edited form as: Biol Psychiatry. 2013 Oct 18;75(12):920–928. doi: 10.1016/j.biopsych.2013.09.035

Table 1.

Similarities and/or Differences between Peripheral Sample and CNS Samples

Sampling References


Disease Periphery CNS From Same
Individuals
Research
Design/Focus
Experimental Method Findings Similarities between CNS
and Periphery
Year, Journal PMID
Genomics
  BPD LCLs Postmortem brain
  (DLPFC)
No An unbiased
  genome-wide
DNA microarray Differential expressions of
  PDLIM5 and HSPF1 both in
  blood and brain of BPD
Two genes, out of 10
  genes identified in
  postmortem, were
  replicated in LCLs
2004, Mol
  Psychiatry
14743183
  SZ Blood Postmortem brain
  (DLPFC)
No An unbiased
  genome-wide
DNA microarray Upregulation of SELENBP1
  both in blood and brain of
  SZ
Six genes, out of 177
  genes identified in
  postmortem, were
  replicated in blood
2005, Proc Natl
  Acad Sci U S A
16223876
  Control Blood Postmortem brain
  (Multiple
  regions)
No An unbiased
  genome-wide
DNA microarray (1) Similarity of some signaling
  between blood/PFC
(2) Half of SZ genes expressed
  both in blood/PFC
Some signaling were
  similar
2006, Am J Med
  Genet B
  Neuropsychiatr
  Genet
16526044
  SZ/Control Lymphocyte Postmortem brain
  (PFC)
No HTR2A RT-PCR Disease associated SNP 102C
  is expressed lower than
  102T in brains
Lymphocyte: monoallelic,
  brain: biallelic
  expression
2006, Biol
  Psychiatry
17069769
  Control Blood Meta-analysis data No An unbiased
  genome-wide
DNA microarray Weak correlations between
  mean expression between
  brain and blood
Only some signaling were
  similar
2010, BMC
  Genomics
20961428
  Control Postmortem
  blood
Postmortem brain
  (cerebellum)
Yes An unbiased
  genome-wide
DNA microarray 22% of total transcriptome
  expressed in both
  cerebellum and blood with
  high correlation
  (γ = .98).
20% genes were
  expressed at similar
  level between blood
  and brain
2010, Am J Med
  Genet B
  Neuropsychiatr
  Genet
20127885
  SZ Blood
  (discordant
  MZ twins)
Postmortem brain No An unbiased
  methylome-
  wide
Methylation microarray Hypomethylation of
  ST6GALNAC1 both in blood
  and brain of SZ
Brain DNA methylation
  were higher (~85%)
  than the blood (~40%)
2011, Hum Mol
  Genet
21908516
  BPD LCLs Postmortem brain
  (PFC)
No An unbiased
  promoter-wide
Promoter tiling array
  and pyrosequencing
Hypermethylation of SLC6A4
  both in blood and brain of
  BPD
2011, Transl
  Psychiatry
22832526
  BPD Blood and
  sperm
Postmortem brain No HCG9 Bisulfite sequence Hypomethylation of HCG9 in
  all tissues of BPD
HCG9 methylation profiles
  were similar across
  tissues
2012, Mol
  Psychiatry
21647149
  Control Blood (before
  death)
Postmortem brain
  (multiple
  regions)
Yes An unbiased
  methylome-
  wide
Methylated DNA
  immunoprecipitation
Highly distinct patterns of
  DNA methylation between
  CNS and blood
Methylation was generally
  tissue-specific, while
  that of CpG-rich
  promoter is largely
  similar
2012, Genome Biol 22703893
  SZ/Control Blood Postmortem brain No An unbiased
  methylome-
  wide
Methylation microarray Methylation levels were less
  variable than gene
  expression
Moderate similarity of age-
  related CpG
  methylation (γ = .33)
2012, Genome
  Biol
23034122
Proteomics/Metabolics
  Control
  (SIDS)
Blood Cortex, retina Yes Fatty acid
  composition
Gas chromatography Breast-fed infants had a
  higher DHA% both in brain
  and RBC
Similar DHA% between
  brain/RBC (γ = .33)
1994, Am J Clin
  Nutr
7913291
  SZ/BPD/
    Control
RBC Postmortem brain
  (DLPFC)
No Lipid composition Mass spectrometry Alterations in the free fatty
  acids and ceramide both in
  blood and brain of SZ and
  BPD group
Closely correlated but
  quantitatively different
  between brain and RBC
2008, J Proteome
  Res
18778095
  SZ RBC, serum,
  and liver
Postmortem brain,
  CSF
Partially
Yes
Proteomic
  profiling
Mass spectroscopy and
  2D-DIGE
Downregulation of ApoA1 in
  all 5 tissues of SZ
No correlation of CSF and
  serum apoA1 levels
  from the same subjects
2008, Mol
  Psychiatry
17938634
  SZ Serum Postmortem brain
  (BA 10)
No Proteomic/
  metabolic
  profiling
Multiplex immunoassay
  panel (187 molecules)
21 analytes were altered in SZ
  postmortem brain
5 analytes showed same
  directional change both
  tissues
2012, PLoS One 23118852
Functional Cellular Assay
  SZ Skin fibroblast Multiple regions Yes Comparison of
  tyrosine kinetics
▪ Uptake of tyrosine
  (fibroblast)
▪ Tyrosine transport
  across
  BBB (PET)
Utilization of tyrosine was
  lower in the SZ (PET), and
  tyrosine transport was
  decreased in the fibroblast
Similar tyrosine kinetics
  between tissues
1991, J Nucl Med;
1994, Schizophr Res
1941137
7841139
  MDD Platelet CSF Yes Comparison of
  5-HT indexes
▪ 5-HT index (platelet)
▪ 5-HT (CSF)
No correlation between
  platelet and CSF for 5-HT
  indexes
No support for the use of
  platelet for CSF 5-HT
  monitoring
1992, Arch Gen
  Psychiatry
1376106
  SZ (first
    episode,
    drug
    naïve)
RBC Living brain Yes Comparison of
  lipid
  metabolism
▪ Fatty acids (RBC)
▪ 31P-MRS (brain)
A parallel decrease in RBC
  phospholipid fatty acids
  and phospholipid
  metabolism in the PFC of
  SZ individuals
Similarity between RBC
  and PFC lipid
  metabolism (γ= .56)
2002, Biol
  Psychiatry
12372654
  Control Plasma mPFC Yes Monitoring the
  brain Glu by
  plasma
▪ HPLC (plasma)
▪ 1H-MRS (brain)
No correlation between
  plasma and mPFC for Glu
  and Glx (Glu + Gln)
  concentration
No support for the use of
  blood for CNS Glu
  monitoring
2006, J Psychiatry
  Neurosci
17136218
  SZ Platelet Living brain Yes Platelet as a
  predictor of CNS
  function
▪ Mitochondrial
  complex I
  (platelet)
▪ FDG-PET (brain)
Complex I activity in platelet
  was correlated with PANSS
  and cerebral glucose
  metabolism
Similarity between
  peripheral and cerebral
  energy metabolism
2007, Prog
  Neuropsycho Biol
  Psychiatry
17329000
  MDD/BPD Plasma Living brain Yes Monitoring the
  brain PUFAs
  level by plasma
▪ PUFA (plasma)
▪ FDG-PET (brain)
Temporoparietal glucose
  usage correlated positively
  with both DHA% and AA%
Similar PUFA ratio
  between plasma and
  cortex
  (γ = .77)
2009,Prostaglandins
  Leukot Essent
  Fatty Acids
19128951

2D-DIGE, two-dimensional difference gel electrophoresis; 5-HT, serotonin; AA, arachidonic acid; BA, Brodmann area; BBB, blood-brain barrier; BPD, bipolar disorder; CNS, central nervous system; CSF, cerebrospinal fluid; DHA, docosahexaenoic acid; DLPFC, dorsolateral prefrontal cortex; FDG, fluorodeoxyglucose; Gln, glutamine; Glu, glutamate; Glx, glutamate + glutamine; HPLC, high-pressure liquid chromatography; LCLs, lymphoblastoid cell lines; mPFC, medial prefrontal cortex; MDD, major depressive disorder; MRS, magnetic resonance spectroscopy; MZ, monozygotic; PANSS, Positive and Negative Syndrome Scale; PBMC, peripheral blood mononuclear cell; PET, positron emission tomography; PFC, prefrontal cortex; PMID, PubMed identifier; PUFA, polyunsaturated fatty acids; RBC, red blood cells; RT-PCR, reverse transcriptase polymerase chain reaction; SIDS, sudden infant death syndrome; SZ, schizophrenia.