Lower Locus Coeruleus MRI intensity in patients with late-life major depression

Andrés Guinea-Izquierdo; Mónica Giménez; Ignacio Martínez-Zalacaín; Inés Del Cerro; Pol Canal-Noguer; Gerard Blasco; Jordi Gascón; Ramon Reñé; Inmaculada Rico; Angels Camins; Carlos Aguilera; Mikel Urretavizcaya; Isidre Ferrer; José Manuel Menchón; Virginia Soria; Carles Soriano-Mas

doi:10.7717/peerj.10828

Lower Locus Coeruleus MRI intensity in patients with late-life major depression

PeerJ. 2021 Feb 16:9:e10828. doi: 10.7717/peerj.10828. eCollection 2021.

Authors

Andrés Guinea-Izquierdo^#^{1

2}, Mónica Giménez^#², Ignacio Martínez-Zalacaín^{1

2}, Inés Del Cerro^{1

2

3}, Pol Canal-Noguer^{4

5

6}, Gerard Blasco⁷, Jordi Gascón⁸, Ramon Reñé⁸, Inmaculada Rico⁸, Angels Camins⁷, Carlos Aguilera⁷, Mikel Urretavizcaya^{1

2

3}, Isidre Ferrer^{9

10

11}, José Manuel Menchón^{1

2

3}, Virginia Soria^{1

2

3}, Carles Soriano-Mas^{2

3

12}

Affiliations

¹ Department of Clinical Sciences/School of Medicine, University of Barcelona, Barcelona, Spain.
² Department of Psychiatry/Bellvitge University Hospital, Bellvitge Biomedical Research Institute (IDIBELL), Hospitalet de Llobregat (Barcelona), Spain.
³ Network Center for Biomedical Research on Mental Health (CIBERSAM), Madrid, Spain.
⁴ B2SLab/Departament d'Enginyeria de Sistemes, Automàtica i Informàtica Industrial, Universitat Politècnica de Catalunya, Barcelona, Spain.
⁵ Networking Biomedical Research Centre in the subject area of Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Madrid, Spain.
⁶ Institut de Recerca Pediàtrica, Hospital Sant Joan de Déu, Esplugues de Llobregat (Barcelona), Spain.
⁷ Imaging Diagnostic Institute (IDI), Bellvitge University Hospital, Hospitalet de Llobregat (Barcelona), Spain.
⁸ Dementia Diagnostic and Treatment Unit/Department of Neurology, Bellvitge University Hospital, Hospitalet de Llobregat (Barcelona), Spain.
⁹ Department of Pathology and Experimental Therapeutics/Institute of Neurosciences, University of Barcelona, Hospitalet de Llobregat (Barcelona), Spain.
¹⁰ Department of Pathologic Anatomy/Bellvitge University Hospital, Bellvitge Biomedical Research Institute-IDIBELL, Hospitalet de Llobregat (Barcelona), Spain.
¹¹ Network Center for Biomedical Research on Neurodegenerative diseases (CIBERNED), Madrid, Spain.
¹² Department of Psychobiology and Methodology in Health Sciences, Universitat Autònoma de Barcelona, Bellaterra (Barcelona), Spain.

^# Contributed equally.

Abstract

Background: The locus coeruleus (LC) is the major noradrenergic source in the central nervous system. Structural alterations in the LC contribute to the pathophysiology of different neuropsychiatric disorders, which may increase to a variable extent the likelihood of developing neurodegenerative conditions. The characterization of such alterations may therefore help to predict progression to neurodegenerative disorders. Despite the LC cannot be visualized with conventional magnetic resonance imaging (MRI), specific MRI sequences have been developed to infer its structural integrity.

Methods: We quantified LC signal Contrast Ratios (LCCRs) in late-life major depressive disorder (MDD) (n = 37, 9 with comorbid aMCI), amnestic Mild Cognitive Impairment (aMCI) (n = 21, without comorbid MDD), and healthy controls (HCs) (n = 31), and also assessed the putative modulatory effects of comorbidities and other clinical variables.

Results: LCCRs were lower in MDD compared to aMCI and HCs. While no effects of aMCI comorbidity were observed, lower LCCRs were specifically observed in patients taking serotonin/norepinephrine reuptake inhibitors (SNRIs).

Conclusion: Our results do not support the hypothesis that lower LCCRs characterize the different clinical groups that may eventually develop a neurodegenerative disorder. Conversely, our results were specifically observed in patients with late-life MDD taking SNRIs. Further research with larger samples is warranted to ascertain whether medication or particular clinical features of patients taking SNRIs are associated with changes in LC neurons.

Keywords: Amnestic mild cognitive impairment; Locus coeruleus; Magnetic resonance imaging; Major depressive disorder; Neuromelanin; Serotonin/norepinephrine reuptake inhibitors.

Grants and funding

This study was supported by the Agency for Management of University and Research Grants of the Catalan Government (2017SGR1247), the Carlos III Health Institute, Spain (Grant PIE14/00034) and FEDER Funds/European Regional Development Fund (ERDF) (‘A way to build Europe’). Andrés Guinea-Izquierdo was supported by a FPU14/04822 grant. Ignacio Martínez-Zalacaín is supported by a P-FIS grant (FI17/00294) from the Carlos III Health Institute (Spain). Inés del Cerro is supported by CIBERSAM and previously by a PhD FI Grant from AGAUR-Catalan Government (2016FI_B 00712), grant co-funded by the European Social Fund (ESF) “ESF, Investing in your future”. Isidre Ferrer is supported by CIBERNED and CS-M was supported by a Miguel Servet contract from the Carlos III Health Institute (CPII16/00048). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.