Bipolar Disorder (Mühleisen, 2014) – Is bipolar genetic?

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Nebula Genomics DNA report for bipolar disorder

Is bipolar genetic? We created a DNA report based on a study that attempted to answer this question. Below you can see a SAMPLE DNA report. To get your personalized DNA report, purchase our Whole Genome Sequencing!

A sample report on bipolar disorder from Nebula Genomics
A sample report on bipolar disorder genetic variants from Nebula Genomics

Additional Information

What is bipolar disorder? (Part 1 of Is bipolar genetic?)

Bipolar disorder is the established short name for bipolar affective disorder (BAS). It is a mental illness that belongs to mood disorders (affect disorders). Previous names for this condition were manic-depressive illness or manic depression.

The disorder is manifested by extreme, bipolar opposite mood swings, drive, and activity levels. These swings occur in phases and extend far beyond normal levels. Those affected oscillate back and forth between depression and mania without being able to control these changes voluntarily. Symptoms usually become apparent gradually. 

Depressive episodes are characterized by above-average depressed mood and decreased drive. A manic episode is characterized by increased drive and restlessness, often accompanied by inadequately exuberant or irritable mood. In the process, the ability to examine reality is sometimes severely impaired.

Depending on the course of the disease, there may be more or less long periods between the acute episodes in which the affected person has no symptoms at all. Bipolar disorder occurs in a wide variety of degrees of severity. Individuals may appear as a charismatic personality during the manic episode. However, possible negative social consequences of the disorder for the individual can be very severe.

Forms (Part 2 of Is bipolar genetic?)

There are three types of bipolar disorders. While they are all characterized by drastic swings in mood, they are distinguished by the severity of the disease. 

Bipolar I disorder: the patient experiences manic episodes lasting at least 7 days or manic symptoms that are so severe that the person needs immediate hospital care. Usually, major depressive episodes occur as well, typically lasting at least 2 weeks. Having depressive symptoms and manic symptoms at the same time are also possible.

Bipolar II disorder: the patient has a pattern of depressive episodes and hypomanic episodes, but not the full-blown manic episodes that are typical of Bipolar I Disorder.

Cyclothymic Disorder: the patient has periods of hypomanic symptoms as well as periods of depressive symptoms and they must last for at least 2 years. However, the symptoms do not meet the diagnostic requirements for a hypomanic episode and a depressive episode.

Other Specified and Unspecified Bipolar and Related Disorders: the patient has bipolar symptoms that do not fit into the other categories

A graphical representation of mood shifts
Bipolar mood shifts. Osmosis. Attribution-Share Alike 4.0 International.

Epidemiology (Part 3 of Is bipolar genetic?)

Based on diagnostic interview data from National Comorbidity Survey Replication (NCS-R), an estimated 2.8% of U.S. adults had bipolar disorder between 2001 – 2003. Prevalence was nearly identical between males and females.

Bipolar disorder in children often goes undiagnosed because of its similarity to other conditions, such as ADHD.

Characteristics and Symptoms (Part 4 of Is bipolar genetic?)

Symptoms and severity of bipolar disorder differ among individuals. Patients often suffer distinct episodes of mania and depression. However, sometimes people will go for years without symptoms. On the other hand, a patient can seemingly experience both symptoms simultaneously or in rapid succession. 

Mania or hypomania: Mania is characterized by an elevated mood. Hypomania is a milder form of this effect. Although initial mood elevation may appear good, patients may find that they quickly become more irritable, their behavior more unpredictable and their judgment more impaired. Reckless behavior is often associated with a manic episode. To be diagnosed with bipolar disorder, a person must have experienced at least one manic episode. 

Depression: In patients with bipolar disorder, the depressive state is often very debilitating and can be classified as major depression. Sleep is generally affected (sleeping too much or not sleeping enough). They may become obsessed with feelings associated with clinical depression including feelings of loss, personal failure, guilt or helplessness. These symptoms can be heightened due to life events such as a death in the family. To be diagnosed, the depression symptoms must last every day for a period of at least two weeks.

Feelings of suicide may occur in either the manic or depressive episodes of this condition. It’s important that if you are feeling suicidal, you contact 911 or a national helpline immediately. 

Symptoms may also include psychosis, such as hallucinations or delusions. 

Several conditions tend to co-exist with bipolar disorder. These other mental health disorders can assperate bipolar symptoms and often lead to a misdiagnosis.

  • Psychosis. Sometimes people who have severe episodes of mania or depression also have psychotic symptoms, such as hallucinations or delusions. The psychotic symptoms tend to match the person’s extreme mood
  • Anxiety Disorders Deficit/Hyperactivity Disorder (ADHD)
  • Misuse of Drugs or Alcohol
  • Eating Disorders
A pictorial representation of mental illnesses
The symptoms of bipolar disorder are similar to those of other mental illnesses. Paget Michael Creelman. Attribution-Share Alike 4.0 International.

Causes (Part 5 of Is bipolar genetic?)

Research suggests that a combination of genetic factors and environmental triggers, such as a stressful event, ultimately play a role in the onset of bipolar disorder.

Is bipolar disorder genetic?

A review of twin studies published in 2013 suggests that the disorder can run in families and the the heritability of an increased risk of bipolar disorder is estimated at over 80%. The risk of developing the condition is nearly ten-fold higher when a first-degree family member has the condition than in the general population.

A 2015 review suggested that, to date, a large number of genetic alterations had been identified in developing bipolar disorder. However, each genetic component only contributes very slightly to an increased risk factor. This means that many small genetic variants taken together likely influence a greater predisposition to the disease but no single gene can be identified as a cause. 

Genome-wide associations studies conducted in 2013 and 2014 showed several common single-nucleotide polymorphisms (SNPs) are associated with bipolar disorder, including variants within the genes CACNA1C, ODZ4, and NCAN. None of these associations could confirm a large causal effect, helping to confirm the belief that increased risk of disease results from a combination of genetic and environmental factors. 

Out of these genes, CACNA1C is the most widely studied variant in relation to bipolar disorder. It codes for the subunit of a voltage-dependent calcium channel that mediates the influx of calcium ions upon membrane polarization. Mutations in the gene have been associated with a disruption in brain connectivity in patients with bipolar disorder and has also been linked to schizophrenia

More recently, in 2016, two additional polymorphisms in TPH2 were also associated with the condition. 

Additional genome wide association studies are being conducted to search for more links between specific genes and bipolar disorder. 

Non-genetic risk factors (Part 7 of Is bipolar genetic?)

Brain physiology

Using neuroimaging, changes in the brain of a person with bipolar disorder include decreased gray matter volume in the prefrontal and temporal cortex, hippocampus (memory functions), and amygdala (emotion responses), as well as decreases in the volume and function of white matter, which connects prefrontal and subcortical (such as amygdala and hippocampus) regions. 

Various sections of the brain affected by bipolar disorder
Bipolar disorder affects multiple areas of the brain. Maletic V, Raison C. Attribution 4.0 International. 

Brain chemistry

Disorders of neurochemical signal transduction mainly affect four of the most important neurotransmitters: the three monoamines norepinephrine, dopamine, and serotonin, and especially glutamate. Additional variations within neurons in the secondary messengers play a crucial role and are necessary components of the theories of development and progression in bipolar disorder.

Environmental factors

Environmental influences and personality traits also play a decisive role. Critical life events, such as trauma or psychosocial stress, are thought to trigger the illness although individual mechanisms are not understood.  

Weakening of self-esteem, an irregular day/night rhythm, or alcohol and other drug abuse are also discussed as triggering factors. 

Diagnosis (Part 8 of Is bipolar genetic?)

Bipolar disorder is typically diagnosed in late adolescence or early adulthood. 

According to the National Institute of Mental Health, bipolar disorder is diagnosed through:

  • Complete a full physical exam, including a family history and medically reviewed health history
  • Order medical testing to rule out other illnesses
  • Refer the person for an evaluation by a psychiatrist. The mental health professional may use criteria for bipolar and related disorders in the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), published by the American Psychiatric Association to confirm diagnosis

Some people have bipolar disorder for years before it is diagnosed. This may be because:

  • Bipolar disorder has symptoms in common with several other mental health disorders and can be easily misdiagnosed
  • Family and friends may notice the symptoms, but not realize that the symptoms are part of a more significant problem
  • People with bipolar disorder often have other health conditions, which can make it hard to diagnose bipolar disorder

Treatment (Part 9 of Is bipolar genetic?)

Although the symptoms may vary over time, bipolar disorder usually requires lifelong treatment targeted at mediating symptoms. Following a prescribed treatment plan can help people manage their symptoms and improve their quality of life.

According to Mayo Clinic, treating bipolar disorder may include:

Medications and programs

Medications. These are often the first prescribed treatment and may include mood stabilizers, antipsychotics, antidepressants, antidepressant-antipsychotic, or anti-anxiety medications. Finding the right medication for an individual takes time and is often a process of trial and error.  

Continued treatment. This condition requires lifelong treatment with medications, even during periods when you feel better. People who skip maintenance treatment are at high risk of a relapse of symptoms or having minor mood changes turn into full-blown mania or depression

Day treatment programs. Programs that provide support and counseling, including talk therapy

Substance abuse treatment

Hospitalization. Your doctor may recommend hospitalization if you’re behaving dangerously, you feel suicidal or you become detached from reality (psychotic)

Psychotherapy

Psychotherapy is a vital part of treatment. It can be conducted as an individual or in a support group or family group. Psychotherapy options include interpersonal and social rhythm therapy (IPSRT), cognitive behavioral therapy (CBT), psychoeducation, or family-focused therapy. 

Treatment for bipolar disorder may also include electroconvulsive therapy (ECT) for some patients. In this approach, electrical currents are passed through the brain, intentionally triggering a brief seizure. The procedure seems to cause changes in brain chemistry that can alleviate symptoms. ECT is sometimes recommended to certain patients who find that medications are not effective or who can’t take traditional antidepressants.  

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