Genetic Vulnerability to Affective Psychopathology in Childhood: A Combined Voxel-Based Morphometry and Functional Magnetic Resonance Imaging Study

Research output: Contribution to journalArticlepeer-review


  • Andrea Mechelli
  • Stefania Tognin
  • Philip K. McGuire
  • Diana Prata
  • Giuseppe Sartori
  • Paolo Fusar-Poli
  • Ahmad R. Hariri
  • Essi Viding

External organisations

  • King’s College London
  • University of Padova
  • Forensic Mental Health Science Department
  • University of Pittsburgh
  • University College London


Background: The majority of affective psychopathology is rooted early in life and first emerges during childhood and adolescence. However, little is known about how genetic vulnerability affects brain structure and function in childhood since the vast majority of studies published so far have been conducted on adult participants. The present investigation examined for the first time the effects of catechol-O-methyltransferase (COMT) valine (val) 158 methionine (met) (val158met) polymorphism, which has been shown to moderate predisposition to negative mood and affective disorders, on brain structure and function in children. Methods: Voxel-based morphometry and functional magnetic resonance imaging were used to measure gray matter volume and emotional reactivity in 50 children aged between 10 and 12 years. We tested the hypothesis that met158 allele affects structural brain development and confers heightened reactivity within the affective frontolimbic circuit in children. Results: The met158 allele was positively associated with gray matter volume in the left hippocampal head where genotype accounted for 59% of interindividual variance. In addition, the met158 allele was positively associated with neuronal responses to fearful relative to neutral facial expressions in the right parahippocampal gyrus where genotype accounted for 14% of the interindividual variance. Conclusions: These results indicate that the met158 allele is associated with increased gray matter volume and heightened reactivity during emotional processing within the limbic system in children as young as 10 to 12 years of age. These findings are consistent with the notion that genetic factors affect brain function to moderate vulnerability to affective psychopathology from childhood.


Original languageEnglish
Pages (from-to)231-237
Number of pages7
JournalBiological Psychiatry
Issue number3
Publication statusPublished - 1 Aug 2009


  • Affective psychopathology, childhood, COMT, emotional processing, hippocampus

ASJC Scopus subject areas