Bipolar disorder (BD) is a mental disorder known for its manic and depressive episodes. Unlike our previous topics, it is not neurodegenerative, but it is neuroprogressive. When I think about BD, I think of massive mood swings from the highest of highs and the lowest of lows. I think of chemicals imbalances in the areas of the brain that control mood. I don’t think of structural changes occurring in the brain that mark this as a neurological disorder. Even more than that, I don’t picture a brain that shares dysfunctional pathways with all of our other neurodegenerative disorders such as inflammation, excitotoxity, and oxidative stress. Bipolar disorder can be extremely hard to diagnose even with the new DSMV guidelines. The median age for BD is 25, a time when people are finishing school or entering the job force – in general, a very high stress times. It is not hard to imagine stress causing individuals to enter into a depressive or manic state depending on their coping mechanisms. It may take years to accurately diagnose. Especially in teenagers, who are commonly misdiagnosed with other psychological disorders such as ADD/ADHD and depression.
The neuroprogressive aspect of the BD makes it vital to try to accurately diagnose the disorder in the earliest stages. Brains with the disorder exhibit a loss in grey matter in the anterior limbic region responsible for executive control and emotional reasoning. However, the highest amount of grey matter loss occurs in the anterior cingulate cortex (ACC), which controls emotional responses and other cognitive functions. An individual with BD has the world working against them in manner ways. First of all, there needs to be a special combination of genetic factors, stressors, and aggravating factors, such a substance abuse, which illicit the disorder. The sum of all these factors manifests in manic and depressive episodes characteristic of the disease. As the time between episodes decreases, the severity of each one increases while the responsiveness to therapies decreases. Ultimately, BD leads to issues with cognition and mood modulation. Inflammation, oxidative stress and neurotrophic factors were focused on in this week’s paper. What makes certain brain mechanisms go awry? The paper suggests that is a lack of compensatory mechanisms within a BD patient.
There is no one drug therapy for BD, so patients end up taking a cocktail of medications that target both the mania and depression. One treatment seems to target many of the pathways suggested in the paper that contribute to BD pathology. Lithium has shown to decrease reactive oxidative species (ROS), increase BDNF – a protein which functions in cell growth, differentiation, survival – and inhibits proteins involved in the apoptotic pathway such as GSKα and caspase. In addition, lithium treatments increase mitochondrial expression of complex I, decreasing mitochondrial dysfunction and contribution to oxidative stress, and restores cytokine levels therefore decreasing inflammation. Aspirin is also used to decrease inflammation and ROS, and acts as an antidepressant.
As this week’s paper shows, there is a lot more happening in the brain of a patient with BD that what we see. Bipolar leads to increased mood and cognitive impairment because of the snowball effect of increased episodes in areas of the brain involved in mood regulation and higher order thinking. Treatments need to target the specific pathways that run awry. It is usually hard to target one pathway or one area of the brain for treatment. Remarkably, lithium seems to target a combination of pathways. As a society, we have a stigma around psychological disorders which puts anyone with one in a negative light. This stems from an ignorance of what is happening to people with such disorders. Bipolar disorder, as discussed, has so much more happening in the brain than chemical imbalances. I hope that people may do more research on BD and other psychological disorders so we can show more empathy and less judgment towards those with diagnoses of depression or BD.
Understanding the Highs and Lows of Bipolar Disorder
