Pánico en los genes

A neuropeptide S receptor variant associated with overinterpretation of fear reactions: a potential neurogenetic basis for catastrophizing




K A Raczka, N Gartmann, M-L Mechias, A Reif, C Büchel, J Deckert and R Kalisch

Libro de neuroanatomía a plumilla.

Los datos del presente trabajo publicado en "Nature" desentrañan el origen genético de las reacciones de pánico exageradas. Poco a poco los neurocientíficos correlacionan estructuras anatómicas del cerebro con sus funciones. Aquí se asocia una variante del receptor (estructura en la membrana celular) para el neuropéptido S (sustancia química producida en el cerebro) con las reacciones de miedo extremo. Se identifica el sustrato
 genético tanto como la neuroestructura anatómicamente implicada. Poniendo un poco de ciencia ficción al asunto, ¿se imaginan que se "usen" dichos resultados para "clasificar" a la gente por su capacidad de desarrollar reacciones de pánico?.

Abstract
Neuropeptide S (NPS) is a recently discovered G protein-coupled receptor ligand that modulates fear-like behaviors in rodents (datos en roedores). A frequent A>T single-nucleotide polymorphism in the human NPS receptor gene NPSR1 confers a 10-fold higher efficacy of NPS signaling in vitro and has been linked with panic disorder (PD). We here report data from a classical fear-conditioning paradigm in healthy normal volunteers, in which carriers of the NPSR1 T allele evaluated their fear reactions to conditioned stimuli (CSs) (estímulo condicionado) as more pronounced than AA homozygous participants, although they did not show elevated peripheral-physiological conditioned responses (skin conductance responses—SCRs). T carriers also exhibited stronger CS-evoked brain activity in the rostral dorsomedial prefrontal cortex (dmPFC), an area that supports the explicit, conscious appraisal of threat stimuli. By contrast, more caudally situated mid-dmPFC, which has previously been associated with the generation of SCRs, showed no elevated response. Moreover, rostral dmPFC activation was correlated with participants’ fear evaluations, further strengthening the link of this activation to increased individual fear appraisal.

Our data suggest a genetic and neuroanatomical substrate for catastrophizing overinterpretations of fear reactions and provide a mechanistic explanation for the association between the NPSR1 T allele and PD.
(base genética)