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Relaciones causales entre TDAH, TEA y estructura cerebral: un estudio de aleatorización mendeliana

Yilu Zhao1, Yamin Zhang1, Tao Li1

  • 1Affiliated Mental Health Center and Hangzhou Seventh People's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China; Nanhu Brain-computer Interface Institute, Hangzhou, Zhejiang, China; MOE Frontier Science Center for Brain Science and Brain-machine Integration, Zhejiang University, Hangzhou, Zhejiang, China; State Key Laboratory of Brain-machine Intelligence, Zhejiang University, Hangzhou, Zhejiang, China.

Progress in neuro-psychopharmacology & biological psychiatry
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PubMed
Resumen

Este estudio revela diferencias específicas en la estructura cerebral relacionadas con el trastorno por déficit de atención con hiperactividad (TDAH) y el trastorno del espectro autista (TEA). Los hallazgos destacan el lóbulo frontal

Palabras clave:
TDAHTEAEstructura cerebralAleatorización mendeliana

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Área de la Ciencia:

  • Neurociencia
  • Genética
  • Psiquiatría

Sus antecedentes:

  • Los trastornos del neurodesarrollo (TND) como el TDAH y el TEA presentan importantes desafíos de salud global.
  • Se observan alteraciones en la estructura cerebral en los TND, pero las relaciones causales siguen sin estar claras.
  • Comprender las bases genéticas de las variaciones en la estructura cerebral es crucial para la investigación de los TND.

Objetivo del estudio:

  • Investigar los vínculos causales entre la estructura cerebral (materia gris y blanca) y el riesgo de TDAH y TEA.
  • Identificar regiones cerebrales específicas y vías de sustancia blanca implicadas en la fisiopatología de estos TND.
  • Explorar los posibles papeles mediadores de la función cerebral en la relación entre la estructura cerebral y los TND.

Principales métodos:

  • Se utilizó un análisis de aleatorización mendeliana (AM) de dos muestras.
  • Se emplearon los últimos hallazgos del estudio de asociación del genoma completo (GWAS) para la estructura cerebral y los TND.
  • Se realizaron análisis de mediación que incorporan datos de GWAS de resonancia magnética funcional (RMf).

Principales resultados:

  • El aumento del área de superficie del giro frontal superior (GFS) está relacionado causalmente con un mayor riesgo de TDAH.
  • Una mayor área de superficie del giro frontal orbital (GFO) se asocia con un menor riesgo de TEA.
  • Vías específicas de la sustancia blanca, incluido el fórnix fronto-occipital inferior (IFO) y la parte retro-lenticular de la cápsula interna (RLIC), muestran asociaciones causales con el TDAH y el TEA, respectivamente.
  • No se encontró evidencia de causalidad inversa (los TND que causan alteraciones cerebrales).
  • La actividad funcional cerebral media el vínculo entre los cambios estructurales cerebrales y el riesgo de TND.

Conclusiones:

  • El lóbulo frontal desempeña un papel crítico en la neurobiología del TDAH y el TEA.
  • Se implican causalmente vías específicas de la sustancia blanca en el desarrollo de estos TND.
  • Los hallazgos ofrecen nuevas perspectivas sobre la compleja interacción de la genética, la estructura cerebral, la función y los TND.