Bipolar disorder, also known as manic depressive illness, is a mental disorder characterized by extreme unusual shifts in energy, mood, and activity levels, impacting the ability to carry out day-to-day tasks. Although it is not a neurodegenerative disease like other previous topics discussed, bipolar disorder is neuroprogressive. Tissue damage and structural changes occur in areas involved in mood regulation increase the risk of recurrence of episodes and reduce the effectiveness of treatment. Several factors have been identified to contribute to the neuroprogression in BPD. First, let’s break down the symptoms and diagnosis of this disorder.
Symptoms
Bipolar disorder is characterized by extreme manic and depressive mood episodes. Cycles between manic and depressive episodes vary in frequency and severity from one individual to another.
Manic episode symptoms: mood changes consisting of a long period of feeling overly happy or outgoing mood or extreme irritability (hypomania), talking very fast, jumping from one idea to another, racing thoughts, easily distracted, increase in activities such as taking on a variety of new projects all at once, overly restless, sleeping little, unrealistic belief in one’s ability, impulsive behavior, engaging in pleasurable, high-risk behaviors
Depression episode symptoms: extended period of feeling sad or hopeless, loss of interest in previously enjoyed activities, including sex, problems in concentration, memory, and decision-making, restless/irritable, changes in eating, sleeping, or other habits, thoughts of death or suicide, including suicide attempts
Diagnosis
The onset of bipolar disorder occurs due to genetic influences, stress, and other factors such as substance abuse. Someone with a bipolar family member is at an increased risk for developing the disorder, but onset is not guaranteed. Bipolar disorder usually develops in early adulthood, with half of all cases starting before age 25. Bipolar disorder worsens if left undiagnosed and untreated. Unfortunately, bipolar disorder is often misdiagnosed as ADHD or major depression due to similar symptoms, and by the time it is properly diagnosed, manic and depressive cycles are much more severe and difficult to treat. Here is a brief overview of the different bipolar diagnoses according to the DSM (Diagnostic and Statistical Manual of Mental Disorders):
Bipolar I: manic or mixed episodes persisting for at least 7 days or severe manic symptoms that require hospitalization, depressive episodes also occur, persisting for at least 2 weeks
Bipolar II: pattern of hypomania episodes and depressive episodes, but no full-blown manic episodes as observed in Bipolar I
Bipolar Disorder Not Otherwise Specified (BP-NOS): symptoms of illness exist and are out of the person’s normal behavior but do not fit criteria for Bipolar I or II
Cyclothymia: mild form of BPD, episodes of hypomania and mild depression present for at least 2 years, symptoms do not meet requirements for any type of BPD
Rapid-cycling: 4 or more episodes of mania, hypomania, mixed states, or depression within one year, more common for those with first bipolar episode onset at a younger age
Neuroprogression of Bipolar Disorder
The underlying mechanisms behind the progression of the disease remain largely a mystery. However, recent findings have identified structural changes and factors involved in the neuropathology. Grey matter loss in the anterior cingulate cortex of the brain has been observed in those with Bipolar disorder, particularly the anterior limbic regions. These areas of the brain are associated with cognitive functions including executive control, emotional processing, reward anticipation, and decision-making.
Recent research has identified inflammation and oxidative stress as factors involved in the neuropathology of BPD. These factors are also present in neurodegenerative diseases such as Alzheimer’s disease. Excess levels of dopamine, a neurotransmitter involved in reward behavior, and glutamate, an excitatory transmitter, are present in BPD brains. Excess levels of dopamine and glutamate lead to an increase of calcium in the cell, causing oxidative stress, which damages neurons.
Increased levels of cytokines, pro-inflammatory molecules involved in immune responses, have also been observed in those with BPD. When the brain becomes inflamed, it activates cytokines, which increase the number of oxidative species in the brain. Oxidative species damage the cell and eventually lead to cell death. Although increased cytokine levels have been identified, their exact link between the inflammation process and bipolar disorder is still unknown.
Treatment
Bipolar disorder is treated with a variety of medications, usually a combination of mood stabilizers and antidepressants. The most effective mood stabilizer is Lithium, which helps control manic symptoms. Though not much is known as to why Lithium is so effective, it has been suggested to protect against inflammation and oxidative stress. Antidepressants are used to treat the depressive symptoms of BPD, but unfortunately can increase the risk of developing rapid-cycling symptoms. This is why they are often required to be given in conjunction with mood stabilizers like Lithium. Finding the appropriate dosage of both mood stabilizers and antidepressants to treat bipolar disorder is a difficult and painstaking process, often requiring many adjustments to medication and dosages before finding one that best controls the cycles. More research is needed to further investigate the role of inflammation and oxidative stress in the pathology of Bipolar Disorder. With a better understanding of the underlying mechanisms of bipolar disorder, we can create more effective treatment plans and stop the vicious cycles for good.
