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Impact of monoamine-related gene polymorphisms on hippocampal volume in treatment-resistant depression

Published online by Cambridge University Press:  20 May 2015

Jennifer Lynne Phillips ,
Lisa Ann Batten ,
Philippe Tremblay ,
Fahad Aldosary ,
Lisheng Du  and
Pierre Blier
Jennifer Lynne Phillips*
Affiliation:
University of Ottawa Institute of Mental Health Research, Ottawa, Canada Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, Canada
Lisa Ann Batten
Affiliation:
University of Ottawa Institute of Mental Health Research, Ottawa, Canada
Philippe Tremblay
Affiliation:
University of Ottawa Institute of Mental Health Research, Ottawa, Canada
Fahad Aldosary
Affiliation:
University of Ottawa Institute of Mental Health Research, Ottawa, Canada
Lisheng Du
Affiliation:
University of Ottawa Institute of Mental Health Research, Ottawa, Canada
Pierre Blier
Affiliation:
University of Ottawa Institute of Mental Health Research, Ottawa, Canada Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, Canada
*
Jennifer L. Phillips, University of Ottawa Institute of Mental Health Research, Mood Disorders Research Unit, 1145 Carling Avenue, Ottawa, ON K1Z 7K4, Canada. Tel: +1 613 722 6521; Fax: +1 613 761 3610; E-mail: Jennifer.Phillips@theroyal.ca
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Abstract

Objective

In major depressive disorder (MDD), single nucleotide polymorphisms (SNPs) in monoaminergic genes may impact disease susceptibility, treatment response, and brain volume. The objective of this study was to examine the effect of such polymorphisms on hippocampal volume in patients with treatment-resistant MDD and healthy controls. Candidate gene risk alleles were hypothesised to be associated with reductions in hippocampal volume.

Methods

A total of 26 outpatients with treatment-resistant MDD and 27 matched healthy controls underwent magnetic resonance imaging and genotyping for six SNPs in monoaminergic genes [serotonin transporter (SLC6A4), norepinephrine transporter (SLC6A2), serotonin 1A and 2A receptors (HTR1A and HTR2A), catechol-O-methyltransferase (COMT), and brain-derived neurotrophic factor (BDNF)]. Hippocampal volume was estimated using an automated segmentation algorithm (FreeSurfer).

Results

Hippocampal volume did not differ between patients and controls. Within the entire study sample irrespective of diagnosis, C allele-carriers for both the NET−182 T/C [rs2242446] and 5-HT1A−1019C/G [rs6295] polymorphisms had smaller hippocampal volumes relative to other genotypes. For the 5-HTTLPR (rs25531) polymorphism, there was a significant diagnosis by genotype interaction effect on hippocampal volume. Among patients only, homozygosity for the 5-HTTLPR short (S) allele was associated with smaller hippocampal volume. There was no association between the 5-HT2A, COMT, and BDNF SNPs and hippocampal volume.

Conclusion

The results indicate that the volume of the hippocampus may be influenced by serotonin- and norepinephrine-related gene polymorphisms. The NET and 5-HT1A polymorphisms appear to have similar effects on hippocampal volume in patients and controls while the 5-HTTLPR polymorphism differentially affects hippocampal volume in the presence of depression.

Keywords

hippocampal volumemagnetic resonance imagingmajor depressive disordersingle nucleotide polymorphism
Type
Original Articles
Information
Acta Neuropsychiatrica , Volume 27 , Issue 6 , December 2015 , pp. 353 - 361
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Copyright
© Scandinavian College of Neuropsychopharmacology 2015 

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