Study Report
Reference
| Citation | Joeyen-Waldorf J, 2012 PubMed |
| Full Info | Joeyen-Waldorf J, Nikolova YS, Edgar N, Walsh C, Kota R, Lewis DA et al. Adenylate cyclase 7 is implicated in the biology of depression and modulation of affective neural circuitry. Biol Psychiatry 2012; 71(7): 627-632.
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Study
| Hypothesis or Background |
Evolutionarily conserved genes and their associated molecular pathways can serve as a translational bridge between human and mouse research, extending our understanding of biological pathways mediating individual differences in behavior and risk for psychopathology.
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| Sample Information | serotonin transporter knockout mouse;two large independent samples |
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| Method Detail | Comparative gene array analysis in the amygdala and cingulate cortex between the serotonin transporter knockout mouse, a genetic animal model replicating features of human depression, and existing brain transcriptome data from postmortem tissue derived from clinically depressed humans was conducted to identify genes with similar changes across species (i.e., conserved) that may help explain risk of depressive-like phenotypes. Human neuroimaging analysis was then used to investigate the impact of a common single-nucleotide polymorphism (rs1064448) in a gene with identified conserved human-mouse changes, adenylate cyclase 7 (ADCY7), on threat-associated amygdala reactivity in two large independent samples. |
| Method Keywords | microarray; magnetic resonance imaging (MRI); genotyping |
| Result | Comparative analysis identified genes with conserved transcript changes in amygdala (n = 29) and cingulate cortex (n = 19), both critically involved in the generation and regulation of emotion. Selected results were confirmed by real-time quantitative polymerase chain reaction, including upregulation in the amygdala of transcripts for ADCY7, a gene previously implicated in human depression and associated with altered emotional responsiveness in mouse models. Translating these results back to living healthy human subjects, we show that genetic variation (rs1064448) in ADCY7 biases threat-related amygdala reactivity. |
| Conclusions | This converging cross-species evidence implicates ADCY7 in the modulation of mood regulatory neural mechanisms and, possibly, risk for and pathophysiology of depression, together supporting a continuous dimensional approach to major depressive disorder and other affective disorders. |
Relationships reported by
Joeyen-Waldorf J, 2012
| Component A Approved Name (Name in Paper) |
Component A Type |
Component B Approved Name (Name in Paper) |
Component B Type |
Statistical Result |
Relationship Description |
Result Category (Positive/Negative)) |
|
Amygdala (amygdala)
|
brain morphology and function |
rs1064448 (rs1064448) |
SNP |
|
Comparative analysis identified genes with conserved transcript changes in amygdala (n = 29) and cingulate cortex (n = 19), both critically involved in the generation and regulation of emotion. Selected results were confirmed by real-time quantitative polymerase chain reaction, including upregulation in the amygdala of transcripts for ADCY7, a gene previously implicated in human depression and associated with altered emotional responsiveness in mouse models. Translating these results back to living healthy human subjects, we show that genetic variation (rs1064448) in ADCY7 biases threat-related amygdala reactivity. |
Positive
|
|
Amygdala (amygdala)
|
brain morphology and function |
ADCY7 (ADCY7) |
gene |
|
Comparative analysis identified genes with conserved transcript changes in amygdala (n = 29) and cingulate cortex (n = 19), both critically involved in the generation and regulation of emotion. Selected results were confirmed by real-time quantitative polymerase chain reaction, including upregulation in the amygdala of transcripts for ADCY7, a gene previously implicated in human depression and associated with altered emotional responsiveness in mouse models. Translating these results back to living healthy human subjects, we show that genetic variation (rs1064448) in ADCY7 biases threat-related amygdala reactivity. |
Positive
|
