Effect of polymorphisms of three genes mediating monoamine signalling on brain morphometry in schizophrenia and healthy subjects.
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.


CONCLUSIONS
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.
Multimodal Brain Image Analysis Laboratory (MBIAL), India.|Departments of Psychiatry, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, India.
Anupa A
AA
Vijayakumari
Multimodal Brain Image Analysis Laboratory (MBIAL), India.|Departments of Psychiatry, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, India.|Departments of Clinical Neuroscience, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, India.
John P
JP
John
Departments of Neurophysiology, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, India.
Harsha N
HN
Halahalli
Departments of Psychiatry, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, India.
Pradip
P
Paul
Multimodal Brain Image Analysis Laboratory (MBIAL), India.|Departments of Psychiatry, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, India.
Priyadarshini
P
Thirunavukkarasu
Departments of Psychiatry, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, India.
Meera
M
Purushottam
Departments of Psychiatry, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, India.
Sanjeev
S
Jain
5-Hydroxy tryptamine 2A; 5-Hydroxy tryptamine transporter linked polymorphic region; Catechol-O-methyl transferase; Gene polymorphism; Magnetic resonance imaging; Voxel-based morphometry