Ceramides and Clinical Depression: How They're Linked
Mental Illness Awareness Week (MIAW) is observed every year in the first full week of October. This week is used to spread awareness about important mental illness topics and help fight the negative stigmas associated with talking about mental illness. Mental illness affects nearly everyone in some way. Either we are personally living with a mental health condition, or we know someone that is. So, let’s all take some time to check in with our loved ones, talk with each other about our mental health, and focus on working together to raise awareness and fight the stigma. Visit the National Alliance on Mental Illness’s website to get more information and resources!
Why Lipid Research is Important for Mental Health
To better understand mental illness, we also need a better understanding of the brain’s chemistry and chemical composition. The brain is made up of many different chemicals with the total mass of these chemicals weighing in at an average of 3 pounds for an adult. Lipids, or fats, make up about 60% of the brain mass. The other 40% is a combination of water, proteins, carbohydrates, and salts. Since lipids are the major component of brain mass, it makes sense to investigate them with regards to mental illnesses (hopkinsmedicine.org).
Ceramides and clinical depression: how are they linked?
Recently, a particular class of lipids were linked to a common mood disorder called major depressive disorder (MDD), also commonly called clinical depression. MDD is more than a bout of the blues, and someone suffering from MDD typically can not simply “snap out” of it. MDD is characterized by a depressed mood, loss of appetite, fear, feelings of worthlessness, insomnia, and inability to concentrate. But aside from the symptoms that people commonly associate with depression, there are also many somatic symptoms such as increased risk of cardiovascular disease, increased concentration of inflammatory cytokines, and dyslipoproteinemia. How are all these symptoms linked to one pathogenesis? How can we explain the peripheral symptoms and their link to the central nervous system? Research published in the Journal of Biological Chemistry (Schumacher, et. al., 2022) attempted to answer these questions and others.
The study provides several novel insights into MDD pathogenesis and ultimately proposes a novel concept of pathogenesis, as well as novel treatment options. The first key finding was that ceramide levels were elevated in the blood plasma of mice with MDD symptoms caused by stress. Even more importantly, human patients suffering from MDD also had elevated levels of ceramides in the blood. To test whether blood levels of ceramides could directly induce MDD symptoms, the researchers injected blood from mice or patients with MDD into untreated mice. This injection alone was able to induce behavioral changes indicative of MDD. They went a step further and administered anti-ceramide antibodies to mice suffering from MDD and observed the prevention of MDD-like behavior.
They also tested the administration of ceramidase, phospholipase D, and phosphatidic acid as potential MDD reversing treatments. Each of these treatments were able to reverse the symptoms of MDD within 24 hours. Additionally, each of these treatments also proved to prevent a relapse of MDD-like behavior for at least four days, even with continuous exposure to stress.
One of the other major questions going into this study was, “How are the peripheral symptoms observed in MDD linked to the central nervous system?” Well, they may have provided an answer to this question as well. Increased levels of ceramides could also explain the peripheral symptoms observed in MDD patients, as ceramides are known to promote cardiovascular disease and exert a proinflammatory effect.
As you can see, paying extra attention to lipids in the brain proved to give major insight into MDD pathology and even its treatment. Lipids are a major component of the brain and as the brain’s lipid composition is further evaluated, it is likely that mental illness pathologies will become more and more clear, paving the way for safer, better treatments and healthier minds.