Bipolar disorder is a complex mental health condition marked by significant shifts in mood, energy, and the ability to function. Individuals experience distinct periods of elevated or irritable mood, known as mania or hypomania, alternating with episodes of profound depression. While precise causes are still under investigation, research uncovers the underlying biological mechanisms, or “pathophysiology,” that contribute to its development and diverse manifestations.
Neurotransmitter Dysregulation
Imbalances in brain chemicals, known as neurotransmitters, are thought to play a role in bipolar disorder. Dopamine, linked to reward and motivation, may show dysregulation. During manic episodes, excess dopamine activity contributes to elevated mood, increased energy, and racing thoughts. Conversely, reduced dopamine activity contributes to depressive states, leading to low motivation and anhedonia.
Serotonin influences mood, sleep, appetite, and impulse control. Lower levels or impaired signaling are often associated with depressive symptoms, such as persistent sadness and sleep disturbances. Maintaining stable serotonin levels is important for overall mood regulation.
Norepinephrine, also known as noradrenaline, is involved in alertness, energy, and the body’s stress response. Fluctuations in norepinephrine levels are implicated in both manic and depressive episodes. An increase in norepinephrine contributes to the heightened energy, agitation, and sleeplessness seen in mania, while a decrease leads to the fatigue and lack of concentration characteristic of depression.
Brain Structure and Functional Alterations
Differences in brain structure and activity are frequently observed in individuals with bipolar disorder. The prefrontal cortex, involved in decision-making, impulse control, and emotional regulation, often shows altered function. Reduced activity or volume in this region can impair emotional regulation and inhibit impulsive behaviors, contributing to mood dysregulation.
The amygdala, central to processing emotions like fear and anxiety, may exhibit hyperactivity. This heightened activity can lead to more intense emotional responses and difficulty managing stress, contributing to emotional volatility during mood episodes. These changes can make emotional processing more reactive.
The hippocampus, involved in memory and mood, can also show changes in volume. Alterations in hippocampal volume or function might affect memory consolidation and emotional processing. Communication pathways between these brain regions, known as neural connectivity, may also be altered. Disrupted communication can hinder the brain’s ability to coordinate emotional and cognitive responses effectively.
Genetic Predisposition and Cellular Processes
Bipolar disorder often runs in families, indicating a strong genetic influence. It is not typically caused by a single gene, but rather a polygenic disorder, meaning multiple genes interact with environmental factors to increase susceptibility. These genetic predispositions can influence various cellular processes within the brain.
Mitochondrial dysfunction is one such process. Mitochondria generate energy for cellular functions. Impaired mitochondrial function in brain cells can lead to reduced energy production, affecting neuronal health and contributing to mood dysregulation. This energy deficit can impact the brain’s ability to maintain stable neural activity.
Neuroplasticity, the brain’s capacity to adapt and change in response to experiences, can be disrupted. This includes reduced production of brain-derived neurotrophic factor (BDNF), a protein supporting neuron growth, survival, and differentiation. Lower BDNF levels can compromise neuronal health and impact the brain’s ability to form new connections, affecting mood regulation and cognitive function.
Genetic influences can also disrupt the body’s natural sleep-wake cycles, known as circadian rhythms. Individuals with bipolar disorder frequently experience severe disturbances in their circadian rhythms, such as insomnia during manic phases and hypersomnia during depressive episodes. These disruptions can trigger or exacerbate mood episodes.
Neuroinflammation and Oxidative Stress
Emerging research highlights the roles of neuroinflammation and oxidative stress within the brain as contributors to bipolar disorder. Neuroinflammation refers to an inflammatory response occurring within the brain, potentially involving immune cells like microglia. Chronic low-grade inflammation can damage neurons and disrupt neurotransmitter systems, contributing to neuronal vulnerability and impaired brain function.
Oxidative stress is another process characterized by an imbalance between harmful free radicals and protective antioxidants. This imbalance can lead to cellular damage, particularly in brain cells, which are highly susceptible to oxidative damage. Such damage can impair neuronal function and contribute to the progression of bipolar disorder symptoms. The brain’s high metabolic rate makes it particularly vulnerable to oxidative damage if antioxidant defenses are overwhelmed.
These two processes are often interconnected and can exacerbate each other. Inflammation can generate free radicals, increasing oxidative stress, while oxidative stress can trigger further inflammatory responses. This cycle contributes to neuronal vulnerability and dysfunction.