What Causes Depression?

Clinical depression is the world’s single leading cause of disability, ahead of heart disease and cancer.  It is a devastating illness that shatters lives. And yet science does not have a firm understanding of it or new ways to treat it. Conventional medications like Prozac (or other SSRIs) are over 35 years old and do not fully work for 50% of patients. 

The Hope for Depression Research Foundation (HDRF) is working to change that with advanced research. Many have heard that depression is caused by a “chemical imbalance” in the brain, something to do with a serotonin deficiency. This explanation is not inaccurate, but it is too simplistic to lead to new treatments.     

In fact, the most important underlying cause of depression lies elsewhere. It involves our stress response; when our brain’s fight or flight circuits get stuck in the “on” position for so long that it becomes toxic. Cells and circuits are thrown off balance, affecting sleep, memory, mood and behavior. 

“Depression affects a large swath of the brain,” said acclaimed brain scientist Dr. Huda Akil, Ph.D., who works with HDRF. “The entire biochemical and cellular balance of many brain areas is altered.”  

Conor Liston, M.D Ph.D., Helen S. Mayberg, M.D., Michael Meaney, Ph.D, René Hen, Ph.D., Elisabeth Binder, M.D Ph.D., Kafui Dzirasa, M.D Ph.D., Eric Nestler, M.D., Ph.D., Huda Akil, Ph.D., Jonathan Javitch, M.D., Ph.D.

Our stress response involves hundreds of molecules and hormones that influence the brain and change it. Some stress is good for us, but an extended or chronic stress response can leave what might be viewed as “scars” in the brain that initiate the pathology of depression. But how? And when? 

This is where the HDRF Depression Task Force comes in.  This team of nine world-acclaimed neuroscientists are from different universities but have joined forces in a historic effort under the auspices of the Hope for Depression Research Foundation.  

The Depression Task Force (DTF) is starting to discover more about these “scars” left by stress in the brain, and also the genetic variations that make some of us more vulnerable to stress than others. This is leading to new ideas for treatment; HDRF has one clinical trial underway currently at Columbia and Mount Sinai, and others in the pipeline.    

No other team has been able to achieve the Depression Task Force’s integrated approach. Their labs collaborate seamlessly and share unpublished data to accelerate discovery. Working together, the HDRF researchers can embrace the complexity of the brain, from genes to molecules to cells and entire circuit networks. They can also step back to see how risk pathways develop during the life course, from infancy to old age.  

“While we are working on understanding the genetics and brain biology of mood disorder and on finding better treatments,” said Dr. Akil, “the real goal is to prevent the illness and stem the epidemic of depression.”   

“Their leadership will influence the field for the next 50 years and beyond,” said Dr. Nestler, current Chair of the DTF and head of the Friedman Brain Institute at Mount Sinai.