Molecular characterization of bipolar disorder by comparing gene expression profiles of postmortem brains of major mental disorders

Iwamoto, Kazuya; Kakiuchi, Chihiro; Bundo, Miki; Ikeda, Kazuhiko; Kato, Takeshi

doi:10.1038/sj.mp.4001437

Cited by 310 publications

(258 citation statements)

References 42 publications

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“…This level of fold-change threshold was selected because it was well above the technical reproducibility of the Affymetrix platform, and it has also been used by others to identify differentially expressed genes in BD1. 33 A gene was determined to have altered expression in BD1 if it showed a X1.3-fold expression difference, in the same direction, in all three twin pairs. At a fold-change cutoff of 1.3, there were 269 genes differentially expressed in all three discordant twin pairs (see Supplementary Table 2).…”

Section: Resultsmentioning

confidence: 99%

“…Previous microarray studies using post-mortem brains from BD1 patients have found differential expression of genes related to apoptosis and neuroprotection; 35,36 neurotransmission and energy metabolism; 37 mitochondrial function; 37,38 receptor/transport, stress response, molecular chaperones and transcription factors; 33 signal transduction; 33,35 myelination and oligodendrocyte function 39 and ubiquitin cycle and synaptic-related genes. 40 Microarray studies assessing white blood cell-derived gene expression levels in BD1 have found, among many different processes, aberrations in RNA binding and ribosomal function, 6 as well as the ER stress response.…”

Section: Discussionmentioning

confidence: 99%

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Expression profiling in monozygotic twins discordant for bipolar disorder reveals dysregulation of the WNT signalling pathway

et al. 2007

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To identify genes dysregulated in bipolar disorder (BD1), we carried out global gene expression profiling using whole-genome microarrays. To minimize genetic variation in gene expression levels between cases and controls, we compared expression profiles in lymphoblastoid cell lines from monozygotic twin pairs discordant for the disease. We identified 82 genes that were differentially expressed by X1.3-fold in three BD1 cases compared to their co-twins, and which were statistically (Pp0.05) differentially expressed between the groups of BD1 cases and controls. Using quantitative reverse transcriptasepolymerase chain reaction, we confirmed the differential expression of some of these genes, including: KCNK1, MAL, PFN2, TCF7, PGK1 and PI4KCB, in at least two of the twin pairs. In contrast to the findings of a previous study by Kakiuchi and colleagues with similar discordant BD1 twin design, our data do not support the dysregulation of XBP1 and HSPA5. From pathway and gene ontology analysis, we identified upregulation of the WNT signalling pathway and the biological process of apoptosis. The differentially regulated genes and pathways identified in this study may provide insights into the biology of BD1.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Expression profiling in monozygotic twins discordant for bipolar disorder reveals dysregulation of the WNT signalling pathway

et al. 2007

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“…36,37,58,59 Few studies have explored global expression changes between groups of suicides and psychiatrically normal controls, some have however focused on a particular psychiatric diagnosis, such as bipolar disorder or schizophrenia, and included within these groups subjects that died by suicide. [60][61][62][63][64][65][66][67] Sibille et al 51 recently compared expression patterns in BA9 and BA47 of depressed suicides versus psychiatrically normal controls matched on the basis of sex, age, DAVID genes correspond to the total number of unique DAVID annotated genes. The percentage represents the number of differentially expressed genes belonging to a given category over the total number of DAVID annotated genes.…”

Section: Discussionmentioning

confidence: 99%

“…The combination of the ANOVA and subsequent t-tests is commonly referred to as Fisher protected least significant difference (LSD) test. In the case of gene expression studies of complex traits such as psychiatric disorders, it has been suggested to use less stringent criteria in the initial analysis stages, 76 and the use of only t-tests or Fisher protected LSD test has been commonly accepted in psychiatric brain expression studies 50,64,65 as well as in other research areas. 77 Multiplicity is always a concern when performing microarray analysis and many correction procedures have been developed to address it such as the Bonferroni-method or false discovery rate-based methods.…”

Section: Discussionmentioning

confidence: 99%

“…For instance, many researchers have found not genes but families of genes or pathways as being implicated in psychiatric disorders in the past. 62,64,65,76,[80][81][82][83][84][85] One additional consideration for this research was the distinction between depressed and non-depressed suicides, permitting the evaluation of depression-specific effects on gene expression separately from suicide-specific effects.…”

Section: Discussionmentioning

confidence: 99%

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Patterns of gene expression in the limbic system of suicides with and without major depression

et al. 2007

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The limbic system has consistently been associated with the control of emotions and with mood disorders. The goal of this study was to identify new molecular targets associated with suicide and with major depression using oligonucleotide microarrays in the limbic system (amygdala, hippocampus, anterior cingulate gryus (BA24) and posterior cingulate gyrus (BA29)). A total of 39 subjects were included in this study. They were all male subjects and comprised 26 suicides (depressed suicides = 18, non depressed suicides = 8) and 13 matched controls. Brain gene expression analysis was carried out on human brain samples using the Affymetrix HG U133 chip set. Differential expression in each of the limbic regions showed group-specific patterns of expression, supporting particular neurobiological mechanisms implicated in suicide and depression. Confirmation of genes selected based on their significance and the interest of their function with reverse transcriptase-polymerase chain reaction showed consistently correlated signals with the results obtained in the microarray analysis. Gene ontology analysis with differentially expressed genes revealed an overrepresentation of transcription and metabolism-related genes in the hippocampus and amygdala, whereas differentially expressed genes in BA24 and BA29 were more generally related to RNA-binding, regulation of enzymatic activity and protein metabolism. Limbic expression patterns were most extensively altered in the hippocampus, where processes related to major depression were associated with altered expression of factors involved with transcription and cellular metabolism. Additionally, our results confirm previous evidence pointing to global alteration of gabaergic neurotransmission in suicide and major depression, offering new avenues in the study and possibly treatment of such complex disorders. Overall, these data suggest that specific patterns of expression in the limbic system contribute to the etiology of depression and suicidal behaviors and highlight the role of the hippocampus in major depression.

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Mitochondrial Complex I Activity and Oxidative Damage to Mitochondrial Proteins in the Prefrontal Cortex of Patients With Bipolar Disorder

Andreazza

Shao²,

Wang³

et al. 2010

Arch Gen Psychiatry

398

249

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Molecular characterization of bipolar disorder by comparing gene expression profiles of postmortem brains of major mental disorders

Cited by 310 publications

References 42 publications

Expression profiling in monozygotic twins discordant for bipolar disorder reveals dysregulation of the WNT signalling pathway

Expression profiling in monozygotic twins discordant for bipolar disorder reveals dysregulation of the WNT signalling pathway

Patterns of gene expression in the limbic system of suicides with and without major depression

Mitochondrial Complex I Activity and Oxidative Damage to Mitochondrial Proteins in the Prefrontal Cortex of Patients With Bipolar Disorder

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