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Blood and Brain Gene Expression in Major Psychiatric Disorders: A Search for Biomarkers

  • Gursharan Chana
  • Stephen J. Glatt
  • Ian P. Everall
  • Ming T. Tsuang
Chapter

Abstract

Microarray investigations in psychiatry have so far implicated a number of genes to be associated with major psychiatric disorders, in particular schizophrenia. In postmortem brain studies, alterations in the expression of transcripts encoding for oligodendrocyte functioning and myelination, mitochondrial-related genes, and energy metabolism, as well as synaptic structure and transmission, have been demonstrated. To a certain extent, these alterations reflect changes in associated mRNAs and proteins previously seen in neuropathological investigations of major psychiatric disorders and hence are of great interest. Assessing gene expression changes in the blood of patients with psychiatric disorders will aid in the characterization of their genetic profile. This, in turn, may eventually allow us to relate these findings to brain-related changes, and hence to potentially identify biomarkers for detection, intervention, and treatment. However, while microarray technology has opened the way for high-throughput gene expression analysis, a significant amount of methodological and technical variability still exists in their application. Therefore, it is necessary that a stringent approach be adopted by researchers in designing such experiments and precaution taken in the final analysis and interpretation of results. The aim of this chapter is to provide a balanced view of microarray investigations in the blood and brain in major psychiatric disorders by highlighting the strengths and weaknesses of such studies in identifying candidate genes. Strategies to overcome these weaknesses will be discussed in the context of advancing and improving future microarray investigations in psychiatry.

Keywords

Bipolar Disorder Gene Expression Change Gene Expression Study Laser Capture Microdissection Gene Chip 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Abbreviations:

ACHR

Acetylcholine receptor

AMPA1-2

2-Aminomethyl phenylacetic acid

Apo

Apolipoprotein

BDNF

Brain-derived neurotrophic factor

BTG1

B-cell translocation gene 1

CCK

Cholecystokinin

CD14

Cell differentiation 14

CNP

Cyclic nucleotide phosphodiesterase

dlPFC

Dorsolateral prefrontal cortex

DRD2

Dopamine receptor D2

EDGF

Epidermal-derived growth factor

ER

Endoplasmic reticulum

erbB2

Erythroblastic leukemia viral oncogene homolog 2

FGF

Fibroblast growth factor

GABA

Gamma-amino butyric acid

GAP-43

Growth associated protein-43

GAD67

Glutamate decarboxylase-67

GluR1-2

Glutamate receptor 1–2

GNA01

Guanine nucleotide binding protein alpha 1

GO

Gene ontology

GSK3A

Glycogen synthase kinase 3 alpha

HERC2

Heat domain and rcc1-like domain 2) Giα1 (g-protein inhibitory alpha1)

HLA-DRB1

Major histocompatibility complex DR beta 1

HER3

Heregulin-3

HML-2

Human macrophage lectin 2

HNRPA3

Heterogeneous nuclear ribonucleoprotein A3

IFITM1

Interferon-induced protein with tetratricopeptide repeats 1

HSPB1

Heat shock protein beta 1

Kir2.3

Potassium channel inward rectifying 2.3

LARS2

Leucyl-tRNA synthetase, mitochondrial

LCM

Laser capture microdissection

MAG

Myelin-associated glycoprotein

MAL

Myelin and lymphocyte protein

MARCKS

Myristolated alanine-rich C-kinase substrate

MBP

Myelin basic protein

MDD

Major depressive disorder

MDH1

Malate dehydrogenase 1

MM

Mismatch

MOBP

Myelin-oligodendrocyte basic protein

MOG

Myelin-oligodendrocytic protein

MRI

Magnetic resonance imaging

MT2A

Metallothionein 2A

Neurod1

Neurogenic differentiation 1

NMDA1

N-methyl-D-aspartate 1

NPY

Neuropeptide Y

NRG-1

Neuregulin-1

NSF

N-ethylmaleimide sensitive fusion protein

PDE4D

Phosphodiesterase 4D

PEA-15

Phosphoprotein enriched in astrocytes 15

PFC

Prefrontal cortex

PLP

Proteolipid protein

PM

Perfect match

PMI

Postmortem interval

PMP22

Peripheral myelin protein 22

qRT-PCR

Quantitative real time polymerase chain reaction

RGS4

Regulator of g-protein signalling-4

RMA

Robust multichip algorithm

S100

Calcium-binding protein A1

SELENBP1

Selenium binding protein-1

SERPINA3

Alpha-1-antichymotrypsin A3

SFRS1

Splicing factor, arginine/serine rich 1

SMDF

Sensory and motor neuron derived factor

SNP

Single nucleotide polymorphism

SOX10

SRY-related homeobox gene 10

SPR

Sepiaterin reductase

TGF-α

Transforming growth factor-alpha

TGF-β 1

Transforming growth factor beta 1

TRAF4

Tumor necrosis factor receptor associated factor 4

XBP1

X box binding protein 1

Notes

Acknowledgments

Thanks are due to Dr Sharon Doc Chandler for her assistance in revising this chapter.

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Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • Gursharan Chana
  • Stephen J. Glatt
  • Ian P. Everall
  • Ming T. Tsuang
    • 1
  1. 1.Center for Behavioral Genomics, Department of PsychiatryUniversity of CaliforniaSan Diego, La Jolla

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