On the World Day of Depression we present the trajectory of the research group “Molecular Neuropsychopharmacology” led by Juan Carlos Leza from the Complutense University of Madrid

Who are we?

The research group “Molecular Neuropsychopharmacology” of the Department of Pharmacology and Toxicology of the Faculty of Medicine of the UCM has among its main scientific objectives the basic and translational research of neuropsychiatric pathologies, in order to find new therapeutic targets or biological markers of the same, as well as the identification and development of pharmacological tools to improve the quality of the treatments. The group is part of regional, national and supranational research Consortiums in Neuroscience and Mental Health.

https://www.ucm.es/farmatox/neuropsicofarmacologia-molecular

https://www.cibersam.es/grupos/grupo-de-investigacion?id=14261

What is the line / s lines of investigation that the group follows?

After extensive experience in the identification of intracellular and intercellular mechanisms of neuroinflammation and systemic immune dysregulation in experimental models of interest and in biological samples from patients with depression, in recent years our objectives have focused on the study of the possible origin and the consequences of inflammatory signaling. Specifically, the role that changes in the intestinal microbiota in patients with depression may have in the clinical picture of the disease and in its response to drugs. Also in the mechanisms by which inflammatory signals can be used to penetrate the brain and the possibilities of pharmacological modulation.

Latest published works

• Caso JR, MacDowell KS, González-Pinto A, García S, de Diego-Adeliño J, Carceller-Sindreu M, Sarramea F, Caballero-Villarraso J, Gracia-García P, De la Cámara C, Agüera L, Gómez-Lus ML, Alba C, Rodríguez JM, Leza JC. Gut microbiota, innate immune pathways, and inflammatory control mechanisms in patients with major depressive disorder. Transl Psychiatry. 2021 c 21;11(1):645. doi: 10.1038/s41398-021-01755-3.
• Fernández-Sevillano J, González-Ortega I, MacDowell K, Zorrilla I, López MP, Courtet P, Gabilondo A, Martínez-Cengotitabengoa M, Leza JC, Sáiz P, González-Pinto A. Inflammation biomarkers in suicide attempts and their relation to abuse, global functioning and cognition. World J Biol Psychiatry. 2021 3:1-11. doi: 10.1080/15622975.2021.1988703.
• De Picker LJ, Dias MC, Benros ME, Vai B, Branchi I, Benedetti F, Borsini A, Leza JC, Kärkkäinen H, Männikkö M, Pariante CM, Güngör ES, Szczegielniak A, Tamouza R, van der Markt A, Fusar-Poli P, Beezhold J, Leboyer M. Severe mental illness and European COVID-19 vaccination strategies. Lancet Psychiatry. 2021 May;8(5):356-359. doi: 10.1016/S2215-0366(21)00046-8. Erratum in: Lancet Psychiatry. 2021 Apr;8(4):e12.;
• Ayesa-Arriola R, López-Díaz Á, Ruiz-Veguilla M, Leza JC, Saura LF, Crespo- Facorro B. COVID-19 as a unique opportunity to unravel the link between prenatal maternal infection, brain development and neuropsychiatric disorders in offspring. Rev Psiquiatr Salud Ment (Engl Ed). 2021 Jan-Mar;14(1):1-3. English, Spanish. doi: 10.1016/j.rpsm.2020.12.003.
• Martínez M, Martín-Hernández D, Virto L, MacDowell KS, Montero E, González- Bris Á, Marín MJ, Ambrosio N, Herrera D, Leza JC, Sanz M, García-Bueno B, Figuero E. Periodontal diseases and depression: A pre-clinical in vivo study. J Clin Periodontol. 2021 ;48(4):503-527. doi: 10.1111/jcpe.13420..
• Rodríguez-Quiroga A, MacDowell KS, Leza JC, Carrasco JL, Díaz-Marsá M. Childhood trauma determines different clinical and biological manifestations in patients with eating disorders. Eat Weight Disord. 2021, 26(3):847-857. doi: 10.1007/s40519-020-00922-7.
• -De Picker LJ, Yolken R, Benedetti F, Borsini A, Branchi I, Fusar-Poli P, Carlos Leza J, Pariante C, Pollak T, Tamouza R, Vai B, Vernon AC, Benros ME, Leboyer M; ECNP Immuno-NeuroPsychiatry TWG. Viewpoint | European COVID-19 exit strategy for people with severe mental disorders: Too little, but not yet too late. Brain Behav Immun. 2021;94:15-17. doi: 10.1016/j.bbi.2021.01.008.
• MacDowell KS, Martín-Hernández D, Ulecia-Morón C, Bris ÁG, Madrigal JLM, García-Bueno B, Caso JR. Paliperidone attenuates chronic stress-induced changes in the expression of inflammasomes-related protein in the frontal cortex of male rats. Int Immunopharmacol. 2021;90:107217. doi: 10.1016/j.intimp.2020.107217.
• Florensa-Zanuy E, Garro-Martínez E, Adell A, Castro E, Díaz Á, Pazos Á, Mac-Dowell KS, Martín-Hernández D, Pilar-Cuéllar F. Cannabidiol antidepressant-like effect in the lipopolysaccharide model in mice: Modulation of inflammatory pathways. Biochem Pharmacol. 2021;185:114433. doi: 10.1016/j.bcp.2021.114433
• Bioque M, Mac-Dowell KS, Font C, Meseguer A, Macau E, Garcia-Orellana M, Valentí M, Leza JC, Bernardo M. Acute effects of a session of electroconvulsive therapy on brain-derived neurotrophic factor plasma levels. Rev Psiquiatr Salud Ment (Engl Ed). 2020 :S1888-9891(20)30069-0. English, Spanish. doi: 10.1016/j.rpsm.2020.05.011.
• Sayd A, Vargas-Caraveo A, Perea-Romero I, Robledo-Montaña J, Caso JR, Madrigal JLM, Leza JC, Orio L, Garcia-Bueno B. Depletion of brain perivascular macrophages regulates acute restraint stress-induced neuroinflammation and oxidative/nitrosative stress in rat frontal cortex. Eur Neuropsychopharmacol. 2020;34:50-64. doi: 10.1016/j.euroneuro.2020.03.004.
• Vargas-Caraveo A, Sayd A, Robledo-Montaña J, Caso JR, Madrigal JLM, García- Bueno B, Leza JC. Toll-like receptor 4 agonist and antagonist lipopolysaccharides modify innate immune response in rat brain circumventricular organs. J Neuroinflammation. 2020 6;17(1):6. doi: 10.1186/s12974-019-1690-2..
• Bioque M, Mac-Dowell KS, Meseguer A, Macau E, Valero R, Vieta E, Leza JC, Bernardo M. Effects of electroconvulsive therapy in the systemic inflammatory balance of patients with severe mental disorder. Psychiatry Clin Neurosci. 2019;73(10):628-635. doi: 10.1111/pcn.12906..
• Martín-Hernández D, Pereira MP, Tendilla-Beltrán H, Madrigal JLM, García- Bueno B, Leza JC, Caso JR. Modulation of Monoaminergic Systems by Antidepressants in the Frontal Cortex of Rats After Chronic Mild Stress Exposure. Mol Neurobiol. 2019 Nov;56(11):7522-7533. doi: 10.1007/s12035-019-1619-x. Epub 2019 May 3. PMID: 31054078.
• Martín-Hernández D, Tendilla-Beltrán H, Madrigal JLM, García-Bueno B, Leza JC, Caso JR. Chronic Mild Stress Alters Kynurenine Pathways Changing the Glutamate Neurotransmission in Frontal Cortex of Rats. Mol Neurobiol. 2019 ;56(1):490-501. doi: 10.1007/s12035-018-1096-7.
• Oriolo G, Blanco-Hinojo L, Navines R, Mariño Z, Martín-Hernández D, Cavero M, Gimenez D, Caso J, Capuron L, Forns X, Pujol J, Sola R, Martin-Santos R. Association of chronic inflammation and perceived stress with abnormal functional connectivity in brain areas involved with interoception in hepatitis C patients. Brain Behav Immun. 2019;80:204-218. doi: 10.1016/j.bbi.2019.03.008.