How Does Bipolar Disorder Affect The Brain?

Bipolar disorder affects over two million Americans, and those with the condition often experience periods of sadness and hyperactivity. But what causes these mood changes? Why do those with bipolar disorder have such intense mood swings and emotional highs and lows? And what's happening inside of the brain to cause these emotional rollercoasters?

Here's what current research says about bipolar disorders and the brain.

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What is bipolar disorder?

Bipolar disorder is a physical and emotional brain disorder characterized by mood swings between mania (extreme happiness or irritability) and depression (extreme mental lows and sadness). While most people experience mood swings between mania and depression to a small extent, those with bipolar disorder often go days, weeks, or even months in one mood. When that mood changes, it can cause people to change their daily habits, distance themselves from friends and family, and act in irrational or unfamiliar ways.

Treatment for bipolar disorder typically involves medication combined with therapy. Various mood-stabilizing medications can help minimize or even prevent bipolar mood swings.

Types of bipolar disorder

The term "bipolar disorder" actually refers to a category of brain disorders. The Diagnostic and Statistical Manual of Mental Disorders (DSM)-5, which is the basis on which all mental health conditions are diagnosed, includes four distinct types of bipolar disorder. Each type of bipolar disorder is caused by unique factors. These include:

  • Bipolar 1 disorder

  • Bipolar 2 disorder

  • Cyclothymic disorder

  • Not Otherwise Specified (NOS) or mixed disorder

Bipolar 1 and Bipolar 2 disorder differ in the severity of mania. Bipolar 1 disorder involves episodes of mania. These episodes of extreme energy (both mentally and physically) are often severe and can even lead to hospitalization. Bipolar 2 disorder involves episodes of hypomania. These episodes are less intense than mania — but they can still negatively impact your life.

Cyclothymic disorder is similar to Bipolar 1 and Bipolar 2 disorders, but the episodes of depression and mania are much less severe. Those with cyclothymia disorder often shift between periods of feeling happy and excitable to periods of feeling down and sad.

Some bipolar disorders do not fit into any of the categories above. They may have features of multiple types of bipolar disorder, or they may simply not yet have a well-defined category. For example, some researchers recently proposed¹ that bipolar disorders stemming from recent childbirths (i.e., "first-onset postpartum psychosis" disorders) be considered a unique type of bipolar disorder. People with unspecified or mixed disorders still benefit from the same therapy and medications as other types of bipolar disorders.

Parts of the brain impacted by bipolar disorder

The exact cause of bipolar disorder is unknown. However, most experts agree that bipolar disorder involves both environmental and physical factors. While whole-brain research is still in its infancy, many studies have already shown that bipolar disorder physically impacts many different areas of the brain. Multiple recent large-scale neuroimaging projects have demystified some of the core areas of the brain responsible for bipolar disorder.

Gray matter

The human brain has two types of tissue: gray matter and white matter. Gray matter is responsible for the majority of mental processing, while white matter is responsible for communication between regions of the brain with gray matter. Large MRI-based studies² in people with bipolar disorder have shown a thinning of gray matter in different areas of the brain.

The two areas most commonly affected by this gray matter thinning are the frontal and temporal regions. Both of these regions are functionally involved in emotional processing, decision making, motivation, inhibition, and motor skills. Research shows that people with reduced gray matter volume in these areas may experience symptoms such as:

  • An inability to focus

  • Difficulties regulating reflexes

  • Decreased decision-making abilities and impulse control

  • Problems with motor skills (e.g., writing, driving, running, etc.)

Interestingly, studies in adolescents and children show similar structural changes in the brain to those of adults. In one recent study³, MRI images for 8,634 adolescents (nine to 11 years old) in the United States were analyzed and compared to adults. Researchers found that the "cortical and subcortical volume" (i.e., gray matter) of children with bipolar disorder was reduced. In fact, the imaging findings of adolescents with bipolar disorder nearly mimicked those of adults. This suggests that brain abnormalities associated with bipolar disorder may develop early in a person's life.

Hippocampus

For years, scientists have known that the hippocampus — an area of the brain heavily involved in learning, memory, and emotion — is smaller in those with the brain disorder, schizophrenia.

Recent research has suggested similar findings in people with bipolar disorder. According to a study⁴ by researchers at The University of Texas Health Science Center in Houston, Texas, hippocampal volumes are reduced in those with bipolar and other mood disorders. In fact, increased shrinkage in areas of the hippocampus directly correlated with the number of manic episodes a person had.

A major review⁵ of neuroscience research in Nature even suggests that new mood disorder treatments should directly target the hippocampus, since it's thought to contain the majority of brain circuitry that regulates mood and emotion.

People with reduced volume in the hippocampus may experience symptoms such as:

  • Mood swings

  • Lack of impulse control

  • Difficulty learning

  • Short-term memory problems

  • Long-term memory problems

Chemical imbalances

The brain is filled with chemicals called neurotransmitters that influence mood, help cells communicate, and regulate heart rate. Research suggests imbalances in these transmitters may play a role in bipolar disorders. In particular, three neurotransmitters are thought to play a role in anxiety, depression, and mood disorders: noradrenaline, serotonin, and dopamine. All three of these neurotransmitters are actually unique. They all induce both mental and physical responses, and all three act as both neurotransmitters and hormones.

For example, noradrenaline — a neurotransmitter responsible for alertness, memory, attention, and anxiety — has direct links⁶ to bipolar disorders. When levels of noradrenaline in the brain are too high, people can experience manic episodes. When levels are too low, they can experience depression.

Certain bipolar medications called serotonin-norepinephrine reuptake inhibitors (SNRIs) help regulate levels of noradrenaline in the brain. These medications have proven highly effective for certain people with bipolar disorders.

Serotonin — a neurotransmitter responsible for overall mood stabilization — also plays a direct role in bipolar disorders. Low levels of serotonin are strongly correlated⁷ with major depressive episodes. Medications called selective serotonin reuptake inhibitors (SSRI) are often used to treat bipolar disorder by helping regulate serotonin levels throughout the body and brain.

Dopamine plays a direct role in both serotonin and noradrenaline regulations. But some researchers hypothesize⁸ that dysregulation of dopamine receptors may play an independent role in depressive and manic episodes in those with bipolar disorder.

Mitochondrial disorders

Bipolar research is constantly evolving. A relatively new theory⁹ on bipolar disorder involves mitochondrial dysfunction. Mitochondria — the powerhouses of human cells — play an important role in the survival and death of neurotransmitter hormones and brain matter. Genetic issues with mitochondrial function may promote excessive oxidative stress, inflammation, and hippocampal shrinkage.

Is bipolar disorder genetic?

Researchers are still working diligently to uncover the exact genes responsible for bipolar disorder. However, one thing is clear; bipolar disorder can be genetic. In fact, up to 90 percent¹⁰ of those with bipolar disorder have a close relative with the condition and/or depression. Those with parents or siblings with bipolar disorder are four to six times¹¹ more likely to get bipolar disorder during their lives.

Twin studies have also shown genetic links. If one twin has bipolar disorder, the other has a 70 percent¹¹ chance of developing it at some point during their life. However, there's still a 30 percent chance that one twin will never develop bipolar disorder. In other words, bipolar disorder isn't purely genetic. Environmental factors play a role.

Are you born with bipolar disorder?

Despite bipolar disorder being genetic in some cases, most people don't experience bipolar disorder until they're in the second or third decade¹² of their lives. Adolescents and children can also develop bipolar disorder, but this is rare.

Most people with bipolar disorder are born with a genetic predisposition. But not everyone with a genetic predisposition to bipolar disorder will develop it during their lifetime. Certain physical or environmental triggers are thought to cause the onset of bipolar disorder in those born with a genetic predisposition.

Known triggers include:

  • Periods of extreme stress

  • Traumatic life events (e.g., death of a loved one, loss of a pet, academic pressures, etc.)

  • Alcohol or drug abuse

Does bipolar disorder damage the brain?

Most research agrees: people with bipolar disorder have brains that are physically different from those without mood disorders. However, no one knows if bipolar disorder itself damages the brain. Those with bipolar disorder may be born with genetic abnormalities that cause physical changes to the brain: these physical changes may lead to bipolar disorders.

Luckily, these physical changes can be managed with medication. Certain medications can help regulate hormone imbalances, restore the brain’s gray matter, and reduce shrinkage to the hippocampus. People with bipolar disorder should discuss medications and therapy with their doctors. While bipolar disorder is a lifelong disorder, it can be well-managed in today's medical ecosystem.

The lowdown

Bipolar disorder is a mood disorder characterized by alternating episodes of mania and depression. Current research suggests those with bipolar disorder have physical differences in their brains compared to the general population. However, modern medications can help manage these physical and structural changes. Bipolar disorder is highly treatable, and new and improved therapeutic and medical advancements are being made each year.

Have you considered clinical trials for Bipolar disorder?

We make it easy for you to participate in a clinical trial for Bipolar disorder, and get access to the latest treatments not yet widely available - and be a part of finding a cure.

Joining community groups and exercise programs for my condition made me feel empowered – but I want to be part of finding a cure.
Peter, 64

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