Post-mortem molecular profiling of three psychiatric disorders

Ramaker, Ryne C.; Bowling, Kevin M.; Lasseigne, Brittany N.; Hagenauer, Megan Hastings; Hardigan, Andrew A.; Davis, Nick; Gertz, Jason; Cartagena, Preston; Walsh, David; Vawter, Marquis P.; Schatzberg, Alan F.; Barchas, Jack D.; Watson, S.J.; Bunney, Blynn G.; Akil, Huda; Bunney, William E.; Li, Jun Z.; Cooper, Sara J.; Myers, R

doi:10.1101/061416

Cited by 13 publications

(23 citation statements)

References 58 publications

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“…Showing regionally specific changes in cortical gene expression agrees with previous studies in MD (Choudary et al, 2005; Evans and Heather, 2016; Klempan et al, 2009; Labonte et al, 2017; Ramaker et al, 2017; Sequeira et al, 2007; Sequeira et al, 2009) and BD (Evans et al, 2004; Ramaker et al, 2017). Given these data, it can be concluded that unique changes in gene expression within many cortical regions are probably contributing to the region-specific changes in cortical dysfunction known to occur in MD and BD (Drevets et al, 2008).…”

Section: Discussionsupporting

confidence: 90%

“…Another study found that changes in gene expression in the anterior cingulate from subjects with BD would have a much more focussed impact because of changes in expression of G protein–coupled receptors and their regulatory pathways (Cruceanu et al, 2015). In a study using tissue from subjects with MD, BD and Sz, it was suggested that there was evidence for lower expression of neuron-specific genes and higher expression of astrocytic genes in the anterior cingulate cortex from subjects with BD and schizophrenia (Ramaker et al, 2017). This study was somewhat unusual as it found no significant changes in gene expression in the dorsolateral prefrontal cortex from subjects with BD and schizophrenia and found no significant changes in gene expression in any CNS region from subjects with MD.…”

Section: Introductionmentioning

confidence: 99%

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Changed cortical risk gene expression in major depression and shared changes in cortical gene expression between major depression and bipolar disorders

Scarr

Udawela

Dean

2019

Aust N Z J Psychiatry

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Background: Mood disorders likely occur in someone with a genetic predisposition who encounters a deleterious environmental factor leading to dysregulated physiological processes due to genetic mutations and epigenetic mechanisms altering gene expression. To gain data to support this hypothesis, we measured levels of gene expression in three cortical regions known to be affected by the pathophysiologies of major depression and bipolar disorders. Methods: Levels of RNA were measured using the Affymetrix™ Human Exon 1.0 ST Array in Brodmann’s areas 9, 10 and 33 (left hemisphere) from individuals with major depression, bipolar disorder and age- and sex-matched controls with changed expression taken as a fold change in RNA ⩾1.2 at p < 0.01. Data were analysed using JMP® genomics 6.0 and the probable biological consequences of changes in gene expression determined using Core and Pathway Designer Analyses in Ingenuity Pathway Analysis. Results: There were altered levels of RNA in Brodmann’s area 9 (major depression = 424; bipolar disorder = 331), Brodmann’s area 10 (major depression = 52; bipolar disorder = 24) and Brodmann’s area 33 (major depression = 59 genes; bipolar disorder = 38 genes) in mood disorders. No gene was differentially expressed in all three regions in either disorder. There was a high correlation between fold changes in levels of RNA from 112 genes in Brodmann’s area 9 from major depression and bipolar disorder ( r2 = 0.91, p < 0.001). Levels of RNA for four risk genes for major depression were lower in Brodmann’s area 9 in that disorder. Conclusion: Our data argue that there are complex regional-specific changes in cortical gene expression in major depression and bipolar disorder that includes the expression of some risk genes for major depression in those with that disorder. It could be hypothesised that the common changes in gene expression in major depression and bipolar disorder are involved in the genesis of symptoms common to both disorders.

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Section: Discussionsupporting

confidence: 90%

Section: Introductionmentioning

confidence: 99%

Changed cortical risk gene expression in major depression and shared changes in cortical gene expression between major depression and bipolar disorders

Scarr

Udawela

Dean

2019

Aust N Z J Psychiatry

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“…The cases in each dataset were diagnosed with MDD through psychological autopsies that included interviews with family or individuals best-acquainted with the deceased. More information is outlined in the respective studies 13,20,21 .…”

Section: Mdd Transcriptomic Studiesmentioning

confidence: 99%

“…Samples from the anterior cingulate cortex, dorsolateral prefrontal cortex and the nucleus accumbens were profiled by Ramaker et al using RNA sequencing. We used data from the controls and those with MDD for a total of 48 subjects 21 . We re-processed the metadata and raw count files obtained from GSE80655 using the BioJupies R package referencing the methods in their paper 22 .…”

Section: Ramaker Et Al Transcriptomic Analysesmentioning

confidence: 99%

Differential and spatial expression meta-analysis of genes identified in genome-wide association studies of depression

Howard

Sibille

et al. 2021

Transl Psychiatry

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Major depressive disorder (MDD) is the most prevalent psychiatric disorder worldwide and affects individuals of all ages. It causes significant psychosocial impairments and is a major cause of disability. A recent consortium study identified 102 genetic variants and 269 genes associated with depression. To provide targets for future depression research, we prioritized these recently identified genes using expression data. We examined the differential expression of these genes in three studies that profiled gene expression of MDD cases and controls across multiple brain regions. In addition, we integrated anatomical expression information to determine which brain regions and transcriptomic cell types highly express the candidate genes. We highlight 12 of the 269 genes with the most consistent differential expression: MANEA, UBE2M, CKB, ITPR3, SPRY2, SAMD5, TMEM106B, ZC3H7B, LST1, ASXL3, ZNF184 and HSPA1A. The majority of these top genes were found to have sex-specific differential expression. We place greater emphasis on ZNF184 as it is the top gene in a more conservative analysis of the 269. Specifically, the differential expression of ZNF184 was strongest in subcortical regions in males and females. Anatomically, our results suggest the importance of the dorsal lateral geniculate nucleus, cholinergic, monoaminergic and enteric neurons. These findings provide a guide for targeted experiments to advance our understanding of the genetic underpinnings of depression.

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“…For SZ and ASD, transcriptomic analysis developed as a valuable tool for the discrimination of disease phenotypes and a deeper understanding of disease‐related genes and molecular pathways 23,24 . However, transcriptome profiling of patients and iPSC‐derived neuronal models is biased through the genetic heterogeneity of different individuals.…”

Section: Transcriptome Analysismentioning

confidence: 99%

The potential of induced pluripotent stem cells for discriminating neurodevelopmental disorders

Stock

Jeckel

Kraushaar

et al. 2020

Stem Cells Translational Medicine

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Studying human disease-specific processes and mechanisms in vitro is limited by a lack of valid human test systems. Induced pluripotent stem cells (iPSCs) evolve as an important and promising tool to better understand the molecular pathology of neurodevelopmental disorders. Patient-derived iPSCs enable analysis of unique disease mechanisms and may also serve for preclinical drug development. Here, we review the current knowledge on iPSC models for schizophrenia and autism spectrum disorders with emphasis on the discrimination between them. It appears that transcriptomic analyses and functional read-outs are the most promising approaches to uncover specific disease mechanisms in vitro.

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Post-mortem molecular profiling of three psychiatric disorders

Cited by 13 publications

References 58 publications

Changed cortical risk gene expression in major depression and shared changes in cortical gene expression between major depression and bipolar disorders

Changed cortical risk gene expression in major depression and shared changes in cortical gene expression between major depression and bipolar disorders

Differential and spatial expression meta-analysis of genes identified in genome-wide association studies of depression

The potential of induced pluripotent stem cells for discriminating neurodevelopmental disorders

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