Hostname: page-component-8448b6f56d-t5pn6 Total loading time: 0 Render date: 2024-04-19T11:08:52.176Z Has data issue: false hasContentIssue false

Hippocampal volume and serotonin transporter polymorphism in major depressive disorder

Published online by Cambridge University Press:  27 February 2013

Jamila Ahdidan
Affiliation:
Aarhus University Hospital, Risskov, Denmark
Leslie Foldager*
Affiliation:
Aarhus University Hospital, Risskov, Denmark Bioinformatics Research Centre, Aarhus University, Aarhus, Denmark
Raben Rosenberg
Affiliation:
Aarhus University Hospital, Risskov, Denmark
Anders Rodell
Affiliation:
Department of Nuclear Medicine & PET Centre, Aarhus University Hospital, Aarhus, Denmark Center of Functionally Integrative Neuroscience, Aarhus University, Aarhus, Denmark
Poul Videbech
Affiliation:
Aarhus University Hospital, Risskov, Denmark
Ole Mors
Affiliation:
Aarhus University Hospital, Risskov, Denmark
*
Leslie Foldager, Aarhus University Hospital, Skovagervej 2, DK8240 Risskov, Denmark. Tel: +45 7847 1119; Fax: +45 7847 1108; E-mail: leslie@birc.au.dk

Abstract

Objective

The main aim of the present study was to replicate a previous finding in major depressive disorder (MDD) of association between reduced hippocampal volume and the long variant of the di- and triallelic serotonin transporter polymorphism in SLC6A4 on chromosome 17q11.2. Secondarily, we also hypothesised that 5-HTTLPR may be a risk factor for MDD.

Methods

Quantitative magnetic resonance imaging (MRI) of the hippocampus was studied in 23 inpatients suffering from MDD and in 33 healthy controls. Normalised volumetric MRI data of hippocampus were assessed with adjustment for total brain volume and tensor-based morphometry was used to elucidate structural brain differences. A triallelic genetic marker resulting from two SLC6A4 promoter region polymorphisms, 5-HTTLPR and rs25531, was analysed for association with MDD and quantitative traits.

Results

Healthy controls had a smaller relative hippocampal volume (relative to brain size) but a larger total brain volume compared with patients with MDD. For patients compared with healthy controls, atrophy was found in the right temporal lobe and pons medulla. Allele and genotype frequencies were strikingly different from the previous study that we aimed to replicate, and no significant associations with the serotonin transporter polymorphism were found.

Conclusions

The present quantitative and morphometric MRI study was not able to replicate the previous finding of association between reduced hippocampal volume in depressed patients and the serotonin transporter polymorphism.

Type
Original Articles
Copyright
Copyright © Scandinavian College of Neuropsychopharmacology 2013 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

1.Sullivan, PF, Neale, MC, Kendler, KS. Genetic epidemiology of major depression: review and meta-analysis. Am J Psychiatry 2000;157:15521562.CrossRefGoogle ScholarPubMed
2.Owens, MJ, Nemeroff, CB. Role of serotonin in the pathophysiology of depression: focus on the serotonin transporter. Clin Chem 1994;40:288295.CrossRefGoogle ScholarPubMed
3.Cohen-Woods, S, Schosser, A, McGuffin, P. From age correction to genome-wide association. Acta Psychiatr Scand 2009;120:355362.CrossRefGoogle ScholarPubMed
4.Hu, XZ, Lipsky, RH, Zhu, Get al. Serotonin transporter promoter gain-of-function genotypes are linked to obsessive-compulsive disorder. Am J Hum Genet 2006;78:815826.CrossRefGoogle ScholarPubMed
5.Frodl, T, Moller, HJ, Meisenzahl, E. Neuroimaging genetics: new perspectives in research on major depression. Acta Psychiatr Scand 2008;118:363372.CrossRefGoogle ScholarPubMed
6.Frodl, T, Meisenzahl, EM, Zill, Pet al. Reduced hippocampal volumes associated with the long variant of the serotonin transporter polymorphism in major depression. Arch Gen Psychiatry 2004;61:177183.CrossRefGoogle Scholar
7.Frodl, T, Koutsouleris, N, Bottlender, Ret al. Reduced gray matter brain volumes are associated with variants of the serotonin transporter gene in major depression. Mol Psychiatry 2008;13:10931101.CrossRefGoogle ScholarPubMed
8.Frodl, T, Zill, P, Baghai, Tet al. Reduced hippocampal volumes associated with the long variant of the tri- and diallelic serotonin transporter polymorphism in major depression. Am J Med Genet B Neuropsychiatr Genet 2008;147B:10031007.CrossRefGoogle Scholar
9.Taylor, WD, Steffens, DC, Payne, MEet al. Influence of serotonin transporter promoter region polymorphisms on hippocampal volumes in late-life depression. Arch Gen Psychiatry 2005;62:537544.CrossRefGoogle ScholarPubMed
10.Hickie, IB, Naismith, SL, Ward, PBet al. Serotonin transporter gene status predicts caudate nucleus but not amygdala or hippocampal volumes in older persons with major depression. J Affect Disord 2007;98:137142.CrossRefGoogle ScholarPubMed
11.Selvaraj, S, Godlewska, BR, Norbury, Ret al. Decreased regional gray matter volume in S′ allele carriers of the 5-HTTLPR triallelic polymorphism. Mol Psychiatry 2011;16:471473.CrossRefGoogle Scholar
12.Ahdidan, J, Hviid, LB, Chakravarty, MMet al. Longitudinal MR study of brain structure and hippocampus volume in major depressive disorder. Acta Psychiatr Scand 2011;123:211219.CrossRefGoogle ScholarPubMed
13.Videbech, P, Ravnkilde, B, Pedersen, ARet al. The Danish PET/depression project: PET findings in patients with major depression. Psychol Med 2001;31:11471158.CrossRefGoogle ScholarPubMed
14.American Psychiatric Association. Diagnostic and statistical manual of mental disorders, 3rd edn, revised. Washington, DC: APA, 1987.Google Scholar
15.Bech, P, Kastrup, M, Rafaelsen, OJ. Mini-compendium of rating scales for states of anxiety depression mania schizophrenia with corresponding DSM-III syndromes. Acta Psychiatr Scand 1986;326(Suppl.):137.Google ScholarPubMed
16.Mors, O, Perto, GP, Mortensen, PB. The Danish Psychiatric Central Research Register. Scand J Public Health 2011;39(Suppl.):5457.CrossRefGoogle ScholarPubMed
17.Sled, JG, Zijdenbos, AP, Evans, AC. A nonparametric method for automatic correction of intensity nonuniformity in MRI data. IEEE Trans Med Imaging 1998;17:8797.CrossRefGoogle ScholarPubMed
18.Smith, SM. Fast robust automated brain extraction. Hum Brain Mapp 2002;17:143155.CrossRefGoogle ScholarPubMed
19.Mazziotta, JC, Toga, AW, Evans, A, Fox, P, Lancaster, J. A probabilistic atlas of the human brain: theory and rationale for its development. The International Consortium for Brain Mapping (ICBM). Neuroimage 1995;2:89101.CrossRefGoogle Scholar
20.Collins, DL, Neelin, P, Peters, TM, Evans, AC. Automatic 3D intersubject registration of MR volumetric data in standardized Talairach space. J Comput Assist Tomogr 1994;18:192205.CrossRefGoogle ScholarPubMed
21.Collins, L, Evans, AC. ANIMAL: Automatic nonlinear image matching and anatomical labeling. In: Brain warping. Toga AW, editor. Academic Press, San Diego. 1999;133–142.CrossRefGoogle Scholar
22.Robbins, S, Evans, AC, Collins, DL, Whitesides, S. Tuning and comparing spatial normalization methods. Med Image Anal 2004;8:311323.CrossRefGoogle ScholarPubMed
23.Taylor, JE, Worsley, KJ. Inference for magnitudes and delays of responses in the FIAC data using BRAINSTAT/FMRISTAT. Hum Brain Mapp 2006;27:434441.CrossRefGoogle ScholarPubMed
24.Risch, N, Herrell, R, Lehner, Tet al. Interaction between the serotonin transporter gene (5-HTTLPR), stressful life events, and risk of depression: a meta-analysis. JAMA 2009;301:24622471.CrossRefGoogle ScholarPubMed
25.Kunugi, H, Hattori, M, Kato, Tet al. Serotonin transporter gene polymorphisms: ethnic difference and possible association with bipolar affective disorder. Mol Psychiatry 1997;2:457462.CrossRefGoogle ScholarPubMed
26.Karg, K, Burmeister, M, Shedden, K, Sen, S. The serotonin transporter promoter variant (5-HTTLPR), stress, and depression meta-analysis revisited: evidence of genetic moderation. Arch Gen Psychiatry 2011;68:444454.CrossRefGoogle ScholarPubMed