Clin Psychopharmacol Neurosci.  2015 Apr;13(1):68-82. 10.9758/cpn.2015.13.1.68.

Effect of Polymorphisms of Three Genes Mediating Monoamine Signalling on Brain Morphometry in Schizophrenia and Healthy Subjects

• Vijayakumari AA
• John JP
• Halahalli
• Paul P
• Thirunavukkarasu P
• Purushottam M
• Jain S

• KMID: 2171067
• DOI: http://doi.org/10.9758/cpn.2015.13.1.68

Abstract

OBJECTIVE
We examined the effect of risk alleles of polymorphisms of three schizophrenia risk genes that mediate monoamine signalling in the brain on regional brain volumes of schizophrenia and healthy control subjects. The risk alleles and the gene polymorphisms studied were: Val allele of catechol o-methyltransferase (COMT) rs4680 polymorphism; short allele of 5-hydroxy tryptamine transporter linked polymorphic region (5HTTLPR) polymorphism; and T allele of 5-hydroxy tryptamine 2A (5HT2A) rs6314 polymorphism.
METHODS
The study was carried out on patients with recent onset schizophrenia (n=41) recruited from the outpatient department of National Institute of Mental Health and Neurosciences, Bangalore, India and healthy control subjects (n=39), belonging to South Indian Dravidian ethnicity. Individual and additive effects of risk alleles of the above gene polymorphisms on brain morphometry were explored using voxel-based morphometry.
RESULTS
Irrespective of phenotypes, individuals with the risk allele T of the rs6314 polymorphism of 5HT2A gene showed greater (at cluster-extent equivalent to family wise error-correction [FWEc] p<0.05) regional brain volumes in the left inferior temporal and left inferior occipital gyri. Those with the risk alleles of the other two polymorphisms showed a trend (at p<0.001, uncorrected) towards lower regional brain volumes. A trend (at p<0.001, uncorrected) towards additive effects of the above 3 risk alleles (subjects with 2 or 3 risk alleles vs. those with 1 or no risk alleles) on brain morphology was also noted.
CONCLUSION
The findings of the present study have implications in understanding the role of individual and additive effects of genetic variants in mediating regional brain morphometry in health and disease.

Keyword

Magnetic resonance imaging; Gene polymorphism; Catechol-O-methyl transferase; 5-Hydroxy tryptamine 2A; 5-Hydroxy tryptamine transporter linked polymorphic region; Voxel-based morphometry

MeSH Terms

Alleles
Brain*
Catechol O-Methyltransferase
Humans
India
Magnetic Resonance Imaging
National Institute of Mental Health (U.S.)
Negotiating*
Neurosciences
Outpatients
Phenotype
Schizophrenia*
Catechol O-Methyltransferase