A new study published in The Lancet Psychiatry has found that levels of C-reactive protein, an inflammation marker, are increased in bipolar disorder – especially during phases of mania.
Bipolar disorder, formerly known as manic-depressive illness, is a mental health disorder characterized by recurrent cycles of depression and mania. During depressive periods, individuals with bipolar disorder are sad, lethargic, anxious, tired, irritable and angry; during manic periods, individuals are abnormally energized, talkative, distracted and have a decreased need for sleep. Bipolar disorder also has also been linked to other diseases, such as diabetes, obesity, and cardiovascular disease. This disorder affects about 2.6% of the American population over 18 years of age, with more than half of these patients having their first episode before they turn 20.
While the exact cause of bipolar disorder is unknown, factors such as biological differences (like changes in brain morphology), an imbalance in neurotransmitters, and inherited traits, have all been implicated in this mental disorder. Interestingly, inflammation has also been linked to a number of mental disorders, including bipolar disorder. Previous studies have found that concentrations of pro-inflammatory cytokines (substances released by immune cells as part of an immune response, attracting other cells to the site of injury) are increased in bipolar disorder. As well, it has been shown that individuals with inflammatory diseases have an increased risk of developing a future psychiatric event.
C-reactive protein is a substance that is produced by the liver and released into the bloodstream in response to inflammation (usually the result of an infection or injury). Tests that measure the levels of C-reactive protein in the blood are commonly done to detect the presence of inflammation and confirm the presence of an inflammatory-associated disease. Previous studies have linked high concentrations of C-reactive proteins to an increased risk of a first episode of depression, schizophrenia, and bipolar disorder; but it is not known to which periods of bipolar disorder (either mania or depression) high C-reactive protein levels are linked.
Following a meta-analysis and systemic review published in The Lancet Psychiatry, researchers are able to determine more specific levels of C-reactive protein in different stages of bipolar disorder. Researchers reviewed a number of databases and analyzed 27 studies with a total of 2161 patients with bipolar disorder and 81, 932 healthy controls, to determine the levels of C-reactive protein in manic and depressive stages. They found that during stages of depression and euthymia (a state of normality), the concentration of C-reactive protein was slightly higher in those with bipolar disorder than in those without the disease. As well, they determined that the concentration was highest during the stage of mania in bipolar disorder and that those that were not taking any medications had higher levels than those on medications. Interestingly, the degree of increase in this concentration was not related to the severity of symptoms. As expected, the levels of C-reactive protein decreased when the depressive or manic episode was resolved.
Increases of CRP in the body can be detrimental; high levels can increase the permeability of the blood-brain barrier – a barrier that is normally highly selective, separating the blood that circulates throughout the body from the extracellular fluid in the central nervous system. Increased permeability then allows CRP to enter the brain and directly influence it. CRP has been shown to induce reactivity in microglia and astrocytes (glial cells which are responsible for providing support for neurons of the nervous system), leading to the possibility of neuronal death.
The researchers of this review suggest that anti-inflammatory medications such as statins could be beneficial in treating bipolar disorder and other similar mental disorders, like depression and schizophrenia. However, data on obesity, smoking, and low vitamin D levels – 3 factors known to influence chronic inflammation – was not collected, which could have skewed the results. In summary, the results show that blood levels of CRP are increased in bipolar disease patients. Future studies should investigate whether these changes are the result or cause of bipolar disease.
Written By: Alexandra Lostun, BSc Hons