Inflammation, stress and heart disease
Livia Carvalho has been concentrating in the role of biological mediators of stress, like hormones and inflammation, in the development of depression in patients with cardiovascular disease. Depression in patient with heart disease increases the risk for cardiac morbidity and mortality. Indeed, depression is more prevalent in patients with heart disease than in the general population. Increasing evidence suggest that depressed patients and patients with heart disease have some shared vulnerabilities in common like emotional stress and inflammation. The mechanisms underlying the increased incidence of depression in patients with heart disease are, however, yet to be understood, despite the severe consequences for these patients’ health. Data of 800 people with heart disease is being collected in a four year follow-up study.
Extended (endo) phenotyping will include functional and molecular biomarkers, neuropsychological traits, endocrine and immune system functioning. In addition, depression is studied in elderly subjects, who also have extensive phenotypic data with respect to depression and DNA. With this work, one aims to generate more insight into the origins of depression. If hormones and inflammation are linked to depression, it is possible that the efficacy of antidepressants are partially attributable to suppression of inflammation. She has been using human clinical population to understand how antidepressants by modulating stress sensitivity may counteract stress hyperactivity and correct the inflammatory state, leading to improvement of depressive symptoms. blood gene expression profiles of depressed patients, controls will be generated providing new biomarkers and pathways for in depth analysis. In addition, a strong collaboration among several groups in the area of depression research allows for follow-up studies focusing on the contribution of polymorphisms, using cellular screening in vitro, and in human (patient) groups with specific endophenotypes.
The integration of the various technological platforms therefore combines the various approaches towards a systems biology approach. Recently, Livia Carvalho in a study conducted in collaboration with the SLAM Affective Disorder Unit, found that response to antidepressant treatment in moderately severe treatment-resistant depressed patients is associated with milder increase levels in the blood of substances produced by the inflammatory cells and greatly affect brain function, the so called cytokines. This substance is normally elevated in situations of danger and stress. The level of these substances, before starting the treatment with the antidepressant, were much higher in the blood of those patients who would not respond to antidepressant treatment in relation to those who would respond to treatment in the future. Additionally, in the patients who never respond to antidepressants the inflammatory cells do not respond to an antidepressant when it is added to the blood in a laboratory experiment. Whereas, in patients who do respond to antidepressants the inflammatory cells work just fine. This may be the first step into the development of a “blood test” to understand which patient may respond to which antidepressant, akin to the tests of “sensitivity” used for choosing the right antibiotic. This work is currently funded by the NARSAD and ECNP Young Investigator Awards to Livia Carvalho, the Biomedical Research Centre and the European Union Framework 7.