Depression and anxiety: looking for answers everywhere

Since 2004, the Dutch study into depression and anxiety (NESDA) has been looking for answers to questions such as “What are the psychosocial, biological, and genetic-risk/predictive factors for depression and anxiety disorders?” The study involves a broad range of disciplines and research groups, including psychiatry, family medicine, psychology, neuroscience, endocrinology, and genetics. Data from NESDA has been used in hundreds of publications.

Smartphones

The large-scale and interdisciplinary approach of NESDA founder Brenda Penninx is unique across the world. With this approach, she maps out the origin, course, and consequences of depression. Her work is of great importance for demonstrating and understanding the link between depression and physical conditions, such as cardiovascular disease and diabetes. “NESDA offers a great infrastructure, which a lot of innovative initiatives can be based on. For example, we added a study in which we measure daily fluctuations in mood using smartphones. There are also sub-studies looking at the microbiome (editor’s note: the entirety of microbes in the digestive tract) and brain scans.”

Generations

In early 2004, the group of participants consisted of people between the ages of 18 and 65 with and without symptoms of depression or anxiety. “Now, a total of about 3,500 people are taking part in this study: in addition to the original participants, we are now looking at the brothers and sisters of participants as well and we are also working on including children of participants in the study. This helps us to better understand what determines vulnerability and resilience within generations and across generations.
With NESDA there is not just one specific research question, but a more general approach. “We are looking for answers associated with the question of how the course of depression and anxiety looks like and what determines this course,” says Penninx.
“The beauty of NESDA is that we have a great variety of participants. There are people with and without symptoms, both young and old. For example, we conduct research into depression in certain phases of life. Think of people who stop working, an event that can trigger depression. Because we conduct research over a longer period of time, we can map out the situation before, during, and after the event.”

We conduct research into depression in certain phases of life. Think of people who stop working, an event that can trigger depression. Because we conduct research over a longer period of time, we can map out the situation before, during, and after the event

Brenda Penninx

Professor in Psychiatric epidemiology

Different types of depression

It is difficult for Penninx to indicate which achievement is the most important; it is a matter of choosing from many. But there are plenty of important findings. “First, we clearly see the negative impact of depression and anxiety on general health and biological aging over a longer term of many years. Second, we helped to further decipher the genetic basis of depression and anxiety. We are increasingly seeing that vulnerability for depression and anxiety and vulnerability for certain other conditions, such as obesity, have the same genetic basis. Third, it has become clear that the clinical picture is very diverse. People can get the same diagnosis, but with varying symptoms and underlying pathophysiology.”

Anti-inflammatory drugs against depression

The NESDA finding that there are different types of depression is a big breakthrough in depression research. There is one with the more typical melancholic symptoms. “But we also see people with depression with more atypical symptoms, who also seem to have specific abnormalities in the immune and metabolic system. This subgroup of patients with depression has ‘immunometabolic’ characteristics, often manifesting in abnormal blood values for cholesterol, lipids, and inflammatory markers that indicate an overactive immune system.”
NESDA has shown that this subgroup — compared to other patients with depression — is more likely to suffer from too much sleep, fatigue, and a large appetite. All of this often leads to weight gain. These people seem to benefit less from antidepressants. “We are now conducting a trial to investigate whether anti-inflammatory drugs are effective in these people.” Penninx is involved in this research as a professor; the lead investigators are Femke Lamers and Yuri Milaneschi. “I think it is important and beautiful to see that junior researchers in my team are now already leading their own projects that build on NESDA findings.”

Children

The NESDA study is leading to other studies. For example, there is the MARIO study on depression and anxiety disorders in children of people with depression. “Depression and anxiety occur relatively early in life, and children with a family predisposition are twice to three times as likely to develop these disorders. We look at the biological children of NESDA participants between the ages of 10 and 25 and extensively observe and describe them over a period of several years as well. With all this data, we can discover which children are susceptible to developing a mental illness at a young age and what role genetics and environment play in this.”
The MARIO study is also used to support children and their parents with an e-health prevention program. The idea is that they can arm themselves against developing depression, anxiety disorders, or bipolar disorders. “We hope to make the children a little bit stronger against developing these diseases. Via an online platform the children and young people learn more about depression and anxiety disorders, they receive cognitive therapy, and there is a program in which positive coping (editor’s note: recognizing that there are also positive sides to the situation) is stimulated through interaction and games.”

Coronavirus and depression and anxiety

Although Penninx is involved in numerous studies, she hardly has any time to do data analyses. “I sometimes think it is a shame that I don’t have the time to play around with the data myself, but I also get quite a lot of satisfaction from reading along and guiding junior researchers. It is simply too busy to do everything.”
Sometimes, work is added unexpectedly. The EU and NWO have awarded grants to conduct research within NESDA into the consequences of the coronavirus pandemic for people from the NESDA cohort. The online surveys suggest that depression and anxiety during the pandemic are not much more severe in people who are already susceptible to depression and anxiety. On the other hand, the “healthy” control group experiences depression and anxiety more often because of the pandemic. It is also striking that feelings of loneliness seem to increase in all groups during the pandemic. “These findings are reliable, because — contrary to many polls you read about in the media — we have data for these emotions prior to the pandemic.”

Text: Ingrid Lutke Schipholt
Photography: Martijn Gijsbertsen