Avances en enfoques multidisciplinarios y en diversas especies para el examen de la neurobiología de los trastornos psiquiátricos

Kas, Martien; Krishnan, Vaishnav; Gould, Todd D.; Collier, David; Olivier, Berend; Lesch, Klaus‐Peter; Domenici, Enrico; Fuchs, Eberhard; Gross, Cornelius; Ċastrén, Eero

doi:10.1016/j.psiq.2012.03.001

Cited by 1 publication

(1 citation statement)

References 152 publications

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“…Nonetheless, the present results suggest interesting avenues 419 of investigation on the relationship between genetics and the pathophysiology and pharmacology of 420 PD. First, the observation of cross-species associations between genes discovered in the GWAS 421 metanalysis and neurobehavioral traits of fear prompts the idea of conservation across species of 422 specific endophenotypes (de Mooij-van Malsen et al, 2011;Kas et al, 2012), such as alterations in 423 fear conditioning (Battaglia and Ogliari, 2005;Bouton et al, 2001). Second, and perhaps a more 424 interesting point, is the observation that these endophenotypes are not only related to the expression 425 14/23 levels of risk genes in regions such as prefrontal cortex, amygdala, and hypothalamus, but also that 426 these genes are more expressed in myelinating oligodendrocytes and microglia than neurons and 427 astrocytes, the brain cells which are more studied and usually highly associated with psychiatric 428 disorders in GWAS ontology studies (Lotan et al, 2014;Wray et al, 2018).…”

Section: Consequences For the Pathophysiology And Pharmacology Of Pd 417mentioning

confidence: 99%

Metanalysis of genome-wide association studies for panic disorder suggest pathways and mechanisms of pathogenesis

Silva

Rocha

Souza

et al. 2018

Preprint

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20Panic disorder (PD) is characterized by abrupt surges of intense fear and distress. There is evidence 21 for a genetic component in this disorder. We ran a meta-analysis of genome-wide association studies 22 of patients with PD, and found 25 single-nucleotide polymorphisms that were associated with the 23 disorder. Causal gene prediction based on these polymorphisms uncovered 20 hits. Exploratory 24 analyses suggested that these genes formed interactor networks, which was enriched in signaling 25 pathways associated with immune and inflammatory responses, as well as growth factors and other 26 developmental mediators. A subset of genes is enriched in limbic regions of the human brain and in 27 microglia and myelinating oligodendrocytes of mice. While these genes were not associated with 28 relevant neurobehavioral phenotypes in mutant mice, expression levels of several causal genes in 29 the amygdala, prefrontal cortex, hippocampus,, hypothalamus, and adrenal gland of recombinant 30 mouse strains was associated with endophenotypes of fear conditioning. Drug repositioning 31 prediction was unsuccessful, but this does not discard these genes and pathways as targets for 32 investigational drugs. In general, ASB3, EIF2S2, RASGRF2, and TRMT2B (and its coded proteins) 33 emerged as interesting targets for mechanistic research on PD. These exploratory findings point 34 towards hypotheses of pathogenesis and neuropharmacology that need to be further investigated. 35

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Section: Consequences For the Pathophysiology And Pharmacology Of Pd 417mentioning

confidence: 99%

Metanalysis of genome-wide association studies for panic disorder suggest pathways and mechanisms of pathogenesis

Silva

Rocha

Souza

et al. 2018

Preprint

View full text Add to dashboard Cite

show abstract

Avances en enfoques multidisciplinarios y en diversas especies para el examen de la neurobiología de los trastornos psiquiátricos

Cited by 1 publication

References 152 publications

Metanalysis of genome-wide association studies for panic disorder suggest pathways and mechanisms of pathogenesis

Metanalysis of genome-wide association studies for panic disorder suggest pathways and mechanisms of pathogenesis

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