Genetic vulnerability to affective psychopathology in childhood: a combined voxel-based morphometry and functional magnetic resonance imaging study.
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.
Mechelli
Andrea
A
Department of Psychology, Institute of Psychiatry, PO Box 67, Division of Psychological Medicine and Psychiatry, King's College London, 103 Denmark Hill, London SE5 8AF, United Kingdom. a.mechelli@iop.kcl.ac.uk
Tognin
Stefania
S
McGuire
Philip K
PK
Prata
Diana
D
Sartori
Giuseppe
G
Fusar-Poli
Paolo
P
De Brito
Stephane
S
Hariri
Ahmad R
AR
Viding
Essi
E
D000341:Affective Disorders, Psychotic / Q000235:genetics* / Q000473:pathology*; D001921:Brain / Q000098:blood supply* / Q000473:pathology*; D001931:Brain Mapping; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D002648:Child; D005838:Genotype; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000379:methods; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008715:Methionine / Q000235:genetics; D009483:Neuropsychological Tests; D010100:Oxygen / Q000097:blood; D010775:Photic Stimulation; D011110:Polymorphism, Genetic / Q000187:drug effects*; D011930:Reaction Time / Q000502:physiology; D018433:Twin Studies as Topic; D014633:Valine / Q000235:genetics
D008715:Methionine; D002394:Catechol O-Methyltransferase; D014633:Valine; D010100:Oxygen