Gene expression profiling of major depression and suicide in the prefrontal cortex of postmortem brains

Genome-wide gene expression analysis using DNA microarray has a great advantage to identify the genes or specific molecular cascades involved in mental diseases, including major depression and suicide. In the present study, we conducted DNA microarray analysis of major depression using postmortem prefrontal cortices. The gene expression patterns were compared between the controls and subjects with major depression. As a result, 99 genes were listed as the differentially expressed genes in major depression, of which several genes such as FGFR1, NCAM1, and CAMK2A were of interest. Gene ontology analysis suggested an overrepresentation of genes implicated in the downregulation or inhibition of cell proliferation. The present results may support the hypothesis that major depression is associated with impaired cellular proliferation and plasticity. Comparison between the controls and suicide victims with major depression, bipolar disorder, or schizophrenia was also conducted in the present study. Two genes, CAD and ATP1A3, were differentially expressed in the three comparisons in the same direction. Interestingly, these two genes were also included in the differentially expressed 99 genes in major depression. It may be worth investigating the genes in relation to suicide or major depression.

[1]  K. Yamakawa,et al.  Characterization of a highly conserved human homolog to the chicken neural cell surface protein Bravo/Nr-CAM that maps to chromosome band 7q31. , 1996, Genomics.

[2]  K. Iwamoto,et al.  Expression of ribosomal subunit genes increased coordinately with postmortem interval in human brain , 2006, Molecular Psychiatry.

[3]  R. Wyatt,et al.  The Na,K-ATPase hypothesis for bipolar illness , 1995, Biological Psychiatry.

[4]  C. Grothe,et al.  The high molecular weight fibroblast growth factor-2 isoforms (21,000mol. wt and 23,000mol. wt) mediate neurotrophic activity on rat embryonic mesencephalic dopaminergic neurons in vitro , 2000, Neuroscience.

[5]  Pat Levitt,et al.  Analysis of complex brain disorders with gene expression microarrays: schizophrenia as a disease of the synapse , 2001, Trends in Neurosciences.

[6]  R. Yolken,et al.  The Stanley Foundation brain collection and Neuropathology Consortium , 2000, Schizophrenia Research.

[7]  David Patterson,et al.  Mapping of the gene encoding the multifunctional protein carrying out the first three steps of pyrimidine biosynthesis to human chromosome 2 , 1989, Human Genetics.

[8]  R. Myers,et al.  Altered cortical glutamatergic and GABAergic signal transmission with glial involvement in depression , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[9]  Paul Pavlidis,et al.  Gene Expression Profiling of Depression and Suicide in Human Prefrontal Cortex , 2004, Neuropsychopharmacology.

[10]  J. Nacher,et al.  Chronic Fluoxetine Treatment Increases the Expression of PSA-NCAM in the Medial Prefrontal Cortex , 2007, Neuropsychopharmacology.

[11]  K. Iwamoto,et al.  Molecular characterization of bipolar disorder by comparing gene expression profiles of postmortem brains of major mental disorders , 2004, Molecular Psychiatry.

[12]  M. Popoli,et al.  Selective regulation of presynaptic Calcium/Calmodulin-Dependent protein kinase II by psychotropic drugs , 2003, Biological Psychiatry.

[13]  Huda Akil,et al.  Systematic changes in gene expression in postmortem human brains associated with tissue pH and terminal medical conditions. , 2004, Human molecular genetics.

[14]  Perry F. Renshaw,et al.  Antidepressant-like effects of uridine and omega-3 fatty acids are potentiated by combined treatment in rats , 2005, Biological Psychiatry.

[15]  Kazuo Yamada,et al.  DNA Methylation Status of SOX10 Correlates with Its Downregulation and Oligodendrocyte Dysfunction in Schizophrenia , 2005, The Journal of Neuroscience.

[16]  Fuad G. Gwadry,et al.  Implication of SSAT by gene expression and genetic variation in suicide and major depression. , 2006, Archives of general psychiatry.

[17]  E G Jones,et al.  Dysregulation of the fibroblast growth factor system in major depression. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[18]  Neural plasticity to stress and antidepressant treatment , 1999, Biological Psychiatry.

[19]  P. Kelly.  Calmodulin-dependent protein kinase II , 1991, Molecular Neurobiology.

[20]  K. Iwamoto,et al.  Gene Expression Profiling in Schizophrenia and Related Mental Disorders , 2006, The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry.

[21]  William B Dobyns,et al.  Mutations in the Na+/K+-ATPase α3 Gene ATP1A3 Are Associated with Rapid-Onset Dystonia Parkinsonism , 2004, Neuron.

[22]  C. Benkelfat,et al.  Patterns of gene expression in the limbic system of suicides with and without major depression , 2007, Molecular Psychiatry.

[23]  P. Sedgwick,et al.  Hippocampal FGF-2 and FGFR1 mRNA expression in major depression, schizophrenia and bipolar disorder , 2006, Brain Research Bulletin.

[24]  Kazuya Iwamoto,et al.  Altered expression of mitochondria-related genes in postmortem brains of patients with bipolar disorder or schizophrenia, as revealed by large-scale DNA microarray analysis. , 2005, Human molecular genetics.

[25]  C. Nemeroff.  The neurobiology of depression. , 1998, Scientific American.

[26]  Jens Frahm,et al.  Stress-induced changes in cerebral metabolites, hippocampal volume, and cell proliferation are prevented by antidepressant treatment with tianeptine , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[27]  C Waternaux,et al.  Toward a clinical model of suicidal behavior in psychiatric patients. , 1999, The American journal of psychiatry.

[28]  Huda Akil,et al.  Microarray technology: a review of new strategies to discover candidate vulnerability genes in psychiatric disorders. , 2003, The American journal of psychiatry.

[29]  C. Aston,et al.  Original Research Article , 2004 .

[30]  Huda Akil,et al.  Effect of agonal and postmortem factors on gene expression profile: quality control in microarray analyses of postmortem human brain , 2004, Biological Psychiatry.