Counting on Lucile Capuron!

“The impact of research on society is what is most important for us.” These words from Lucile Capuron, said with the strength and conviction she embodies, say it all: her connection to INRA, her sense of teamwork and relationships with patients, everything that has driven her for so many years.

When she was in school, she had a penchant for philosophy and maths, but science was also high on her list of favourite subjects. However, human behaviour fascinated her more than anything, making the decision of what to study at university – neurosciences – quite easy.

Instead of nurturing vague ideas people often have of psychology, Lucile focused on experimental and health psychology and did several internships at biology laboratories. She eventually joined the Integrative Neurobiology Laboratory, where she completed her doctoral thesis under the direction of Robert Dantzer, who was an INRA research director at the time.

When depression and inflammation come together

Lucile found herself at the crossroads of psychology, biomedical science, psychoneuroimmunology and neurosciences, and began exploring why patients with cancer treated with cytokine-based immunotherapy developed serious depression. Her work shed light on the type, characteristics and dynamics of the psychotropic effects that emerge with these treatments. It also opened the door to numerous opportunities which led Lucile to the United States, where she stayed for six years. While there, she furthered her training in biological psychiatry while implementing an in-depth programme to study the physiopathological mechanisms underlying the appearance of neuropsychiatric changes in inflammatory conditions.

In 2005, and while never quite letting go of her foothold in the States, she returned to her first love. She was hired at INRA as a research scientist, where she joined the Nutrition and Integrative Neurobiology Unit (INRA, University of Bordeaux) at INRA’s Nouvelle-Aquitaine–Bordeaux centre, which does research on the impact of nutrition on brain function. Her work focused on developing clinical research on people, while her colleagues studied animals. With her team, she continued exploring the many complex leads on the mechanisms of depression, a very common disease that is becoming the leading debilitating disorder in the world and for which one-third of patients do not respond to treatment.

Down about depression

Understanding how nutrition affects mental health

Lucile and her teams have found that systemic inflammation, of which cytokines are a key marker, is a major risk factor in depression. They have also produced clinical results showing that patients with immune diseases or with inflammatory components (cancer, autoimmune diseases, cardiovascular disease, chronic diseases, metabolic disorders, etc.) suffer from depression more than the general population (15% to 60% versus 5% to 10%). Furthermore, they have been able to identify the role of underlying chronic inflammation, which is typical in obesity, in the physiopathology of neuropsychiatric issues in obese patients.

More recently, they have shown that inflammation, whether chronic or systemic, affects the metabolism of serotonin and dopamine, two neurotransmitters that are essential for proper brain function and mood in people. Inflammation also produces neurotoxic processes and impacts network function. This is how it contributes to the development of symptoms of depression.

Future plans

Any free time that Lucile has, she spends with her children. If there were more hours in the day, she says she would love to do a bit more sport or go out more.

I want us to succeed

Lucile is known over the world for her research on the link between inflammation and neuropsychiatric symptoms. She is as determined as ever to continue her research because there is “so much to do”. Her goal? Better understand the mechanisms involved in treatment-resistant depression and its clinical expression, identify the mechanisms of resistance to standard treatment and develop new preventive and therapeutic strategies. The common thread in her plans: bring nutrition and psychiatry closer together. This research is extremely important as so many patients – some of whom are in incredible psychological pain – write to her, almost as though to Santa Claus, to tell her how much hope they have in her.

Serotonin and dopamine, the paths to well-being

Sometimes called “happy hormones”, serotonin and dopamine are neurotransmitters – chemical substances that help the nervous system communicate. They are produced from the amino acids tryptophan and tyrosine, respectively.

Lucile Capuron decided to observe the activity of two enzymatic pathways, IDO and BH4, involved in breaking down these two amino acids in patients with treatment-resistant depression. Indoleamine-pyrrole 2,3-dioxygenase (IDO) is an enzyme that helps break down tryptophan. This enzyme, known to be caused by inflammation, also produces neurotoxic substances. Tetrahydrobiopterin (BH4) is an essential cofactor in the synthesis of dopamine and serotonin from tyrosine and tryptophan. Its production involves another enzyme, guanosine triphosphate cyclohydrolase I (GTPCHI), whose activity is modified under inflammatory conditions.

Find out more

Oriolo G., Huet L., Dexpert S., Beau C., Forestier D., Ledaguenel P., Magne E., Martin-Santos R., and Capuron L. 2019. History of major depression is associated with neuropsychiatric symptoms but not systemic inflammation in a cross-sectional study in obese patients. Brain, Behavior, and Immunity 76, 215-222.

Vancassel S., Capuron L., and Castanon N. Brain kynurenine and BH4 pathways: Relevance to the pathophysiology and treatment of inflammation-driven depressive symptoms. Frontiers in Neuroscience, 24 July 2018.

Delgado I., Huet L., Dexpert S., Beau C., Forestier D., Ledaguenel P., Aubert A., Sauvant J., Aouizerate B., Magne E., and Capuron L. 2018. Depressive symptoms in obesity: Relative contribution of low-grade inflammation and metabolic health. Psychoneuroendocrinology 91, 55-61. 

Huet L., Delgado I., Aouizerate B., Castanon N., and Capuron L. Obesity and depression: shared pathophysiology and translational implication. In: Quevedo J., Carvalho A.F., and Zarate C.A. (Eds). Neurobiology of Depression, Road to Novel Therapeutics, 2019, Elsevier, pp. 169-176.