Elsevier

Biological Psychiatry

Volume 55, Issue 3, 1 February 2004, Pages 225-233
Biological Psychiatry

Original article
Serotonin 5-HT1A, 5-HT1B, and 5-HT2A receptor mRNA expression in subjects with major depression, bipolar disorder, and schizophrenia

https://doi.org/10.1016/j.biopsych.2003.09.017Get rights and content

Abstract

Background

Alterations of serotonin neurotransmission are implicated in both mood disorders and schizophrenia. Specific serotonin-receptor-based abnormalities in these psychiatric illnesses have been intensively studied; however, it has been difficult to draw any conclusions because of a lack of consensus. These inconsistencies have most likely arisen from the unavailability of selective ligands.

Methods

Our study used in situ hybridization to quantify 5-HT1A, 5-HT1B, and 5-HT2A mRNA levels in the hippocampus (HC) and 5-HT1A and 5-HT2A mRNA levels in the dorsolateral prefrontal cortex (DLPFC) of subjects with a history of major depression disorder (MDD), bipolar disorder (BPD), schizophrenia, and a normal comparison group (15 subjects per group).

Results

In the DLPFC, there is a significant decrease in 5-HT1A mRNA of subjects with MDD and in 5-HT2A mRNA of subjects with BPD. Subjects with MDD have a significant decrease in 5-HT1A mRNA in the HC; subjects with BPD and schizophrenia had increased 5-HT1B mRNA levels and a significant decrease in 5-HT2A mRNA levels in the hippocampal formation.

Conclusions

Alterations in 5-HT1A, 5-HT1B, and 5-HT2A mRNA levels in the brains of subjects with both mood disorders and schizophrenia add further support for hypothesis of dysregulation of the serotonergic system in these psychiatric disorders.

Section snippets

Subjects

Sixty subjects from the Stanley Foundation Neuropathology Consortium were analyzed in this project. Postmortem brains comprised four groups of 15 subjects each, with diagnoses of schizophrenia, bipolar disorder, major depression disorder without psychotic features, and a normal comparison group. For a detailed description of subject selection, diagnostic methods, and tissue handling, see Torrey et al (2000).

Samples were matched for age (overall mean ± SEM: 45.4 ± 1.7), gender, ethnicity, side

5-HT1A mRNA

Densitometric analysis of the distribution of 5-HT1A mRNA in the human DLPFC shows a pattern of four bands (Figure 1A). In the control group, labeling was more intense in B1, lower in B2 (approximately half of B1) and B4 (approximately a quarter of B1), and the lowest was B3 (approximately a 10th of B1, Figure 2A).

In the HC, 5-HT1A mRNA was present in all the regions analyzed (CA1, CA2, CA4, and DG), with the highest levels in CA1, followed by CA2 and DG (with approximately half of CA1's

Distribution of 5-HT1A, 5-HT1B, and 5-HT2A in the dorsolateral prefrontal cortex and hippocampus

The expression pattern of each mRNA followed a different pattern of hybridization within the DLPFC and HC. In the DLPFC the “densitometric” patterns are referred to as bands to differentiate these patterns from the already characterized and well-described anatomic cortical layers. The bands might not correspond exactly with the number, extension, and distribution of the classical layers. As described subsequently, the results are consistent with previous descriptions, but we note that the bands

Acknowledgements

We acknowledge the support of Drs. James H Meador-Woodruff, Charles Neal Jr., Marco Cecchi, Mohamed Kabbaj, Mónica Beneyto Santonja, Inés Morano, Lucio Díaz-Flores Feo, Tomás González Hernández, and Elena Vigo Moreno. Postmortem brains were donated by the Stanley Medical Research Institute's Brain Collection, courtesy of Drs. Michael Knable, E. Fuller Torrey, Maree J. Webster, Serge Weis, and Robert H. Yolken.

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