Relationship between G1287A of the NET Gene Polymorphisms and Brain Volume in Major Depressive Disorder: A Voxel-Based MRI Study.

Issei Ueda,Yukunori Korogi,Reiji Yoshimura,Hikaru Hori,Keita Watanabe,Shingo Kakeda,Nakao Iwata,Satoru Ide,Asuka Katsuki,Taro Kishi,Jun Nakamura,Junji Moriya,Osamu Abe,Peter John Mckenna

doi:10.1371/journal.pone.0150712

Abstract

BackgroundEarlier studies implicated norepinephrine transporter (NET) gene (SLC6A2) polymorphisms in the etiology of major depressive disorder (MDD). Recently, two single nucleotide SLC6A2 polymorphisms, G1287A in exon 9 and T-182C in the promoter region, were found to be associated with MDD in different populations. We investigated the relationship between the brain volume and these two polymorphisms of the SLC6A2 in MDD patients.MethodsWe obtained 3D high-resolution T1-weighted images of 30 first-episode MDD patients and 48 age- and sex-matched healthy subjects (HS). All were divided into 4 groups based on polymorphism of either the G1287A or the T-182C genotype. VBM analysis examined the effects of diagnosis, genotype, and genotype-diagnosis interactions.ResultsDiagnosis effects on the brain morphology were found in the left superior temporal cortex. No significant genotype effects were found in the T-182C and the G1287A. A significant genotype (G1287A)–diagnosis interaction was found in the left dorsolateral prefrontal cortex. No significant genotype (T-182C)–diagnosis interaction effects were observed in any brain region.ConclusionsIn MDD patients there seems to be a relationship between the volume of the dorsolateral prefrontal cortex and polymorphism of the SLC6A2 G1287A gene.

Highlights

Norepinephrine (NE) is a monoamine neurotransmitter implicated in various behavioral and psychological functions including learning and memory, anxiety, arousal, and mood, as well as other disorders such as addiction, depression, and attention deficit/hyperactivity disorder [1, 2]
In major depressive disorder (MDD) patients there seems to be a relationship between the volume of the dorsolateral prefrontal cortex and polymorphism of the SLC6A2 G1287A gene
The norepinephrine transporter (NET), which is known as solute carrier family 6 member 2 (SLC6A2), is responsible for norepinephrine re-uptake by the presynaptic terminal, and is a target for tricyclic antidepressants, selective norepinephrine re-uptake inhibitors, and serotonin-NE re-uptake inhibitors used to treat major depressive disorder (MDD) [3, 4]

Summary

Introduction

Norepinephrine (NE) is a monoamine neurotransmitter implicated in various behavioral and psychological functions including learning and memory, anxiety, arousal, and mood, as well as other disorders such as addiction, depression, and attention deficit/hyperactivity disorder [1, 2]. Among the several known SLC6A2 polymorphisms, most studies on the etiology of MDD have focused on T-182C (rs2242446) in the 5’-flanking promoter region and G1287A (rs5569) in exon 9. Jonsson and colleagues reported that healthy subjects (HS) with the G/G genotype of the G1287A had higher cerebrospinal fluid concentration of the NE metabolite 3-methoxy-4-hydroxyphenylglycol (MPHG) compared to other genotypes [8] These single nucleotide polymorphisms (SNPs) were found to be associated with MDD [9, 10]. Earlier studies implicated norepinephrine transporter (NET) gene (SLC6A2) polymorphisms in the etiology of major depressive disorder (MDD). Two single nucleotide SLC6A2 polymorphisms, G1287A in exon 9 and T-182C in the promoter region, were found to be associated with MDD in different populations. We investigated the relationship between the brain volume and these two polymorphisms of the SLC6A2 in MDD patients

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