Decreased hippocampal 5-HT2A receptor binding in major depressive disorder: in vivo measurement with [18F]altanserin positron emission tomography

doi:10.1016/j.biopsych.2003.08.015

Biological Psychiatry

Volume 55, Issue 3, 1 February 2004, Pages 217-224

https://doi.org/10.1016/j.biopsych.2003.08.015 Get rights and content

Abstract

Background

Serotonin 5-HT_2A receptors play an important role in the regulation of many functions that are disturbed in patients with major depressive disorder. Postmortem and positron emission tomography studies have reported both increased and decreased 5-HT_2A receptor binding in different limbic and paralimbic regions.

Methods

We conducted a quantitative 5-HT_2A receptor binding study using positron emission tomography and [¹⁸F]altanserin of four regions hypothesized to have altered levels of 5-HT_2A receptors in major depressive disorder. Using a four-compartment model, the 5-HT_2A receptor distribution was estimated by calculating the regional [¹⁸F]altanserin k₃/k₄ ratio in which k₃ is the rate of binding to the receptor and k₄ is the rate of dissociation from the receptor. Forty-six antidepressant-free patients with major depressive disorder and 29 healthy control subjects were enrolled.

Results

5-HT_2A receptor binding in the hippocampus was reduced by 29% in depressed subjects (p = .004). In other regions, 5-HT_2A receptor binding was decreased (averaging 15%) but not significantly. Both groups had similar age-dependent decreases in 5-HT_2A receptors throughout all brain regions.

Conclusions

Altered serotoninergic function in the hippocampus is likely involved in the disturbances of mood regulation in major depressive disorder, although the specific role of the 5-HT_2A receptor changes is still unclear.

Section snippets

Participants

Forty-six patients, 16 male patients and 30 female patients (mean age 49.6 ± 15.6 years, range 20–85 years), meeting DSM-IV criteria for MDD were recruited to the outpatient psychiatry service from referrals from other psychiatrists and also from the community by advertisement. Inclusion criteria were a current untreated episode meeting criteria for MDD, right-handedness, and no other medical illness potentially affecting the central nervous system (CNS). Clinical assessment was conducted by a

Results

Clinical characteristics of the 46 depressed patients and 29 healthy subjects are presented in Table 1. Mean ages between the two groups were similar (49.6 vs. 45.8 years, respectively). Ranges of ages between the groups were also similar (depressed: 20–85 years; controls: 22–79 years). There was no significant difference in gender, age, or years of education between these clinical groups (Table 1). Excluding the six patients with LOD resulted in changing the mean MDD patient age to 46.4 years

Discussion

In the largest group of patients with MDD reported to date with in vivo PET imaging of 5-HT_2A receptors, we found a nearly 30% decrease of hippocampal [¹⁸F]altanserin binding in depressed patients compared with controls. No other region examined had a similar magnitude of difference, although all regions had a nonsignificant trend, averaging 15.4% less 5-HT_2A receptor binding in MDD.

Any finding of decreased hippocampal 5-HT_2A receptors in patients with MDD must be interpreted with caution

Acknowledgements

This work was supported by the National Institutes of Health (NIH) with Grants MH58444, MH54731, and RR00036. We thank Chester Mathis, Ph.D., for his valued advice and assistance in the radiosynthesis of [¹⁸F]altanserin; Lori Groh, Len Lich, Brigitte Mittler, and Pat Deppen for assistance with subject recruitment and scanning; Jon Christensen for assistance in data processing; William Morgenau and Dave Ficke for radioisotope production; Juanita Carl for assistance in metabolite analysis; and

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Original articleDecreased hippocampal 5-HT2A receptor binding in major depressive disorder: in vivo measurement with [18F]altanserin positron emission tomography

Abstract

Background

Methods

Results

Conclusions

Section snippets

Participants

Results

Discussion

Acknowledgements

Jpn J Pharmacol

Psychiatr Clin North Am

Biol Psychiatry

Magn Reson Imaging

Nucl Med Biol

Neuroimage

Biol Psychiatry

Trends Cogn Sci

Brain Res

Neuropharmacology

Psychiatry Res

Biol Psychiatry

Brain Res

Brain Res

Brain Res

Neuroimage

Neuroscience

Biol Psychiatry

J Chem Neuroanat

Psychiatry Res

Psychiatry Res

Psychiatry Res

Int J Rad Appl Instrum [A]

Trends Neurosci

Lancet

Nucl Med Biol

Behav Brain Res

Brain Res Bull

Biol Psychiatry

Alterations in monoamine receptors in the brain of suicide victims

J Clin Psychopharmacol

Serotonergic measures in the brains of suicide victims5-HT2 binding sites in the frontal cortex of suicide victims and control subjects

Am J Psychiatry

Brain morphometric abnormalities in geriatric depressionLong-term neurobiological effects of illness duration

Am J Psychiatry

Serotonin 5-HT2 receptor imaging in major depressionFocal changes in orbito-insular cortex

Br J Psychiatry

Hippocampal volume reduction in major depression

Am J Psychiatry

Architectonic subdivision of the orbital and medial prefrontal cortex in the macaque monkey

J Comp Neurol

Receptor sensitivity and the mechanism of action of antidepressant treatment. Implications for the etiology and therapy of depression

Arch Gen Psychiatry

Serotonin receptor subtypesImplications for psychopharmacology

Br J Psychiatry

Original article
Decreased hippocampal 5-HT_2A receptor binding in major depressive disorder: in vivo measurement with [¹⁸F]altanserin positron emission tomography