Publications

Authors:

Marchetti, Luca; Lauria, Mario; Caberlotto, Laura; Musazzi, Laura; Popoli, Maurizio; Mathé, Aleksander A; Domenici, Enrico; Carboni, Lucia

Title:

Gene expression signature of antidepressant treatment response/non-response in Flinders Sensitive Line rats subjected to maternal separation

Year:

2020

Type of item:

Articolo in Rivista

Tipologia ANVUR:

Articolo su rivista

Language:

Inglese

Referee:

No

Name of journal:

International Journal of Neuropsychopharmacology

ISSN of journal:

0924-977X

N° Volume:

31

:

Cambridge University Press

Page numbers:

69-85

Keyword:

Bioinformatics; Escitalopram; Forced swim test; Gene expression; Major depressive disorder; Nortriptyline

Short description of contents:

Neurobiological underpinnings of treatment-resistant depression, a debilitating condition associated with significant functional impairment, have not been elucidated. Consequently, the aim of this study was to use animal models of response and resistance to antidepressant treatment, in an attempt to identify differences in associated transcriptional responses. Flinders Sensitive Line rats were subjected to maternal separation (MS) and chronically treated with Escitalopram or Nortriptyline. Antidepressants reduced immobility time in the forced swim test in non-MS rats, while lack of antidepressant behavioural response was observed in MS animals. We developed a novel bioinformatic algorithm that enabled identification of transcriptional signatures in hippocampus and pre-frontal cortex that discriminate vehicle-and antidepressant-treated subjects in both MS and non-MS rats. Functional annotation analysis showed that in antidepressant-responder rats the most enriched pathways included IQGAPs activation, toll-like receptor trafficking, energy metabolism, and regulation of endopeptidase activity. The analysis of interacting proteins implicated synaptic vesicles and neurotransmitter release, ubiquitin regulation, cytoskeleton organisation and carbohydrate metabolism. In contrast, in treatment-resistant MS rats, main expression changes were revealed in ribosomal proteins, inflammatory responses, transcriptional/epigenetic regulation, and small GTPases. Susceptibility signature shared Rtn1, Zdhhc5, Igsf6, and Sim1 genes with the latest depression GWAS meta-analysis, while antidepressant resistance signature shared Ctnnd1, Rbms3, Atp1a3, and Pla2r1 genes. In conclusion, this study demonstrated that distinct transcriptional signatures are associated with behavioural response or non-response to antidepressant treatment. The identification of genes involved in antidepressant response will increase the comprehension of the neurobiological underpinnings of treatment-resistant depression, thus contributing to identification of novel therapeutic targets.

Product ID:

115341

Handle IRIS:

11562/1021223

Last Modified:

November 30, 2022

Bibliographic citation:

Marchetti, Luca; Lauria, Mario; Caberlotto, Laura; Musazzi, Laura; Popoli, Maurizio; Mathé, Aleksander A; Domenici, Enrico; Carboni, Lucia, Gene expression signature of antidepressant treatment response/non-response in Flinders Sensitive Line rats subjected to maternal separation «International Journal of Neuropsychopharmacology» , vol. 31 , 2020 , pp. 69-85

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