Neurobiology of stress and vulnerability to psychopathology
Coordinator: Dr. Antonio Armario
1) Understanding brain processing of stressors and the usefulness of different biological markers of neuronal activation.
2) Describing processes and mechanisms involved in adaptation to chronic stress.
3) Understanding the impact of stress in psychopathology and the underlying neurobiological mechanisms.
1) To identify brain areas and neuronal phenotypes activated by exposure to emotional and pharmacological (i.e. addictive drugs) stressors. We use expression of immediate early genes (IEGs) such as c-fos and arc and epigenetic changes (i.e. histone phosphorylation and acetylation). Our hypothesis is that epigenetic changes are more restricted that expression of IEGs and can help identifying critical brain areas and neurons. With these tools we are exploring how simultaneous exposure to two stressors or to stressors and addictive drugs interact in the brain.
2. After repeated exposure to a wide range of predominantly emotional stressors, there is a reduction of the response to the same (homotypic) stressor that is observed at physiological (i.e. hypothalamic-pituitary-adrenal hormones) and behavioural levels. Adaptation is also observed in brain expression of IEGs. Our main purposes are to identify cognitive/emotional processes involved in adaptation as well as the brain areas and neurochemical mechanisms involved. One of our main hypotheses is that adaptation to repeated stress is not a simple habituation process, as usually assumed, but a complex brain process that may involve cognitive aspects and associative signals. A second one is that adaptation to stress is so difficult to block pharmacologically or by brain lesions because it likely involves several different brain pathways and neurochemical processes acting in a parallel and redundant way.
3. It has been known for decades that exposure to stress in humans is involved in the development of psychopathologies including anxiety, depression and drug addiction. More recently, it has been demonstrated that a single exposure to certain severe stressors can result in long-lasting neuroendocrine, cognitive and emotional changes, reminiscent of post-traumatic stress disorder (PTSD). Our purpose is to characterize the characteristics of stressors that determine their psychopathological impact, as well as the biological basis of individual differences in resilience or vulnerability to the consequences of stress. In this regard, one of our main focuses is the activation of the HPA axis and its key brain regulator, the corticotropin-releasing factor/hormone (CRF o CRH), which has been demonstrated to constitute a critical biological link between stress and psychopathology. In addition, we have obtained evidence that activation of BNDF-trkB pathways in critical areas such as the hippocampal formation and the amygdala may also be important to limit the negative consequences of severe stressors.
1) Evaluación de la eficacia de inhibidores epigenéticos en modelos experimentales de patologías humana. RETOS Colaboracion 2015. Ministerio de Economia y Competitividad (REF. RTC-2015-3898-1)
· Corominas-Roso M, Armario A, Palomar G, Corrales M, Carrasco J, Richarte V, Ferrer R, Casas M, Ramos-Quiroga JA. IL-6 and TNF-?in unmedicated adults with ADHD: Relationship to cortisol awakening response. Psychoneuroendocrinology. 2017 May;79:67-73. PMID: 28262601
· Marín-Blasco I, Muñoz-Abellán C, Andero R, Nadal R, Armario A. Neuronal Activation After Prolonged Immobilization: Do the Same or Different Neurons Respond to a Novel Stressor? Cereb Cortex. 2017 Feb 16:1-12. PMID: 28203747
· Sanchís-Ollé M, Ortega-Sánchez JA, Belda X, Gagliano H, Nadal R, Armario A. Lithium-induced malaise does not interfere with adaptation of the hypothalamic-pituitary-adrenal axis to stress. Prog Neuropsychopharmacol Biol Psychiatry. 2017 Apr 3;75:77-83.
· Galatzer-Levy IR, Andero R, Sawamura T, Jovanovic T, Papini S, Ressler KJ, Norrholm SD. A cross species study of heterogeneity in fear extinction learning in relation to FKBP5 variation and expression: Implications for the acute treatment of posttraumatic stress disorder. Neuropharmacology. 2017 Apr;116:188-195.
Visit also: Neurobiology of Stress and Addiction's
Ref: SGR 2017-457