Bipolar disorder: the story on HearLore

Bipolar disorder

In 1854, French physician Jules-Gabriel-François Baillarger presented a paper to the French Imperial Académie Nationale de Médecine describing a condition he called madness in double form, a biphasic mental illness causing recurrent oscillations between mania and melancholia. This was the first formal medical recognition of what we now know as bipolar disorder, yet for decades, the condition remained shrouded in confusion and misdiagnosis. Before the term manic depressive psychosis was coined by German psychiatrist Emil Kraepelin in the late 19th century, patients were often labeled as having dementia praecox, a term now known as schizophrenia, or simply as morally corrupt. The distinction between the two was not clear until Kraepelin observed that periods of acute illness, whether manic or depressive, were generally punctuated by relatively symptom-free intervals where the patient was able to function normally. This observation laid the groundwork for modern psychiatry, but the human cost of the earlier confusion was immense. Individuals suffering from these mood swings were frequently institutionalized without understanding the nature of their illness, and their families were left to navigate a landscape of fear and misunderstanding. The term manic depressive reaction appeared in the first version of the Diagnostic and Statistical Manual of Mental Disorders in 1952, influenced by the legacy of Adolf Meyer, but it was not until the 1970s that subtypes like bipolar II and rapid cycling were included, based on the pioneering work of David Dunner, Elliot Gershon, Frederick Goodwin, Ronald Fieve, and Joseph Fleiss. The journey from madness in double form to the nuanced spectrum of today has been long, marked by both scientific breakthroughs and persistent social stigma.

The Genetic And Environmental Storm

Genetic influences are believed to account for 73 to 93 percent of the risk of developing bipolar disorder, indicating a strong hereditary component that has puzzled researchers for decades. Twin studies have shown that the rate at which identical twins both have bipolar I disorder is around 40 percent, compared to about 5 percent in fraternal twins, suggesting that while genes play a massive role, they are not the sole determinant. The first genetic linkage finding for mania was in 1969, but subsequent studies have been inconsistent, pointing strongly to heterogeneity with different genes implicated in different families. Robust and replicable genome-wide significant associations have shown several common single-nucleotide polymorphisms are associated with bipolar disorder, including variants within the genes CACNA1C, ODZ4, and NCAN. In 2022, the AKAP11 gene was discovered as the first gene linked to bipolar disorder through the analysis of exomes from around 14,000 individuals. This gene's interaction with the GSK3B protein, a molecular target of lithium, points to a possible mechanism behind the medication's therapeutic effects. However, environmental factors are equally critical, with 30 to 50 percent of adults diagnosed with bipolar disorder reporting traumatic or abusive experiences in childhood. These early life events are associated with an earlier onset, a higher rate of suicide attempts, and more co-occurring disorders such as post-traumatic stress disorder. The interplay between genetic predisposition and environmental stressors creates a complex web of risk, where the threshold for mood changes becomes progressively lower until episodes eventually start and recur spontaneously, a phenomenon known as the kindling hypothesis. This model suggests that when people who are genetically predisposed toward bipolar disorder experience stressful events, the stress threshold at which mood changes occur becomes progressively lower, until the episodes eventually start and recur spontaneously.

Common questions

When was bipolar disorder first formally recognized by medical professionals?

French physician Jules-Gabriel-François Baillarger presented the first formal medical recognition of bipolar disorder to the French Imperial Académie Nationale de Médecine in 1854. He described the condition as madness in double form, a biphasic mental illness causing recurrent oscillations between mania and melancholia.

What percentage of bipolar disorder risk is attributed to genetic factors?

Genetic influences account for 73 to 93 percent of the risk of developing bipolar disorder, indicating a strong hereditary component. Twin studies show that the rate at which identical twins both have bipolar I disorder is around 40 percent, compared to about 5 percent in fraternal twins.

How does the suicide rate for people with bipolar disorder compare to the general population?

The annual average suicide rate in people with bipolar disorder is 0.4 to 1.4 percent, which is 30 to 60 times greater than that of the general population. An estimated 15 to 20 percent of those with bipolar disorder die by suicide, and approximately 30 to 60 percent attempt suicide during their lifetime.

Which medication is the only one approved by the FDA for treating mania in children with bipolar disorder?

What is the global prevalence of bipolar disorder among homeless individuals?

A 2024 meta-analysis and systematic review estimates that there is a global prevalence of approximately 8 percent of bipolar disorder amongst homeless individuals. In the United States, it was reported that in veterans with bipolar disorder, 55 percent reported being homeless at some point in their lives.

Who was the first public figure to openly discuss their bipolar disorder diagnosis in 2000?

Actress Carrie Fisher went public with her bipolar disorder diagnosis in 2000, becoming one of the most well-recognized advocates for people with bipolar disorder in the public eye. She fiercely advocated to eliminate the stigma surrounding mental illnesses and helped draw attention to the disorder's chronicity and relapsing nature.

The Silent Epidemic Of Suicide

The annual average suicide rate in people with bipolar disorder is 0.4 to 1.4 percent, which is 30 to 60 times greater than that of the general population, making it one of the most lethal mental health conditions. An estimated 15 to 20 percent of those with bipolar disorder die by suicide, and approximately 30 to 60 percent attempt suicide during their lifetime. Among those with the condition, 40 to 50 percent overall and 78 percent of adolescents engaged in self-harm, highlighting the desperate nature of the struggle. Individuals whose bipolar disorder begins with a depressive or mixed affective episode seem to have a poorer prognosis and an increased risk of suicide, with the lifetime risk of suicide being much higher in those with bipolar disorder. Risk factors for suicide attempts and death from suicide include older age, prior suicide attempts, a depressive or mixed index episode, a manic index episode with psychotic symptoms, hopelessness or psychomotor agitation present during the episodes, co-existing anxiety disorder, a first degree relative with a mood disorder or suicide, interpersonal conflicts, occupational problems, bereavement or social isolation. The number of deaths from suicide in bipolar disorder is between 18 and 25 times higher than would be expected in similarly aged people without bipolar disorder. Despite the high rates of suicide, the condition is often misunderstood, with many believing that the mood swings are simply a result of personality flaws or lack of discipline. The reality is that the biological and psychological mechanisms of the disorder create a perfect storm of vulnerability, where the very symptoms that define the condition, such as the impulsivity of mania and the hopelessness of depression, combine to create a lethal risk. The annual average suicide rate is 0.4 to 1.4 percent, which is 30 to 60 times greater than that of the general population, making it one of the most lethal mental health conditions.

The Brain's Stormy Circuitry

Brain imaging studies have revealed differences in the volume of various brain regions between patients with bipolar disorder and healthy control subjects, suggesting that the condition is rooted in the structure and function of the brain. A neurologic model for bipolar disorder proposes that the emotional circuitry of the brain can be divided into two main parts: the ventral system, which regulates emotional perception, and the dorsal system, which is responsible for emotional regulation. The model hypothesizes that bipolar disorder may occur when the ventral system is overactivated and the dorsal system is underactivated. Meta-analyses of structural MRI studies have shown that certain brain regions, such as the left rostral anterior cingulate cortex, fronto-insular cortex, ventral prefrontal cortex, and claustrum, are smaller in people with bipolar disorder, whereas other regions, such as the lateral ventricles, globus pallidus, subgenual anterior cingulate, and the amygdala, are larger. Functional MRI findings suggest that the ventricular prefrontal cortex regulates the limbic system, especially the amygdala, and in people with bipolar disorder, decreased ventricular prefrontal cortex activity allows for the dysregulated activity of the amygdala, which likely contributes to labile mood and poor emotional regulation. Manic and depressive episodes tend to be characterized by dysfunction in different regions of the ventricular prefrontal cortex, with manic episodes appearing to be associated with decreased activation of the right ventricular prefrontal cortex and depressive episodes associated with decreased activation of the left ventricular prefrontal cortex. These disruptions often occur during development linked with synaptic pruning dysfunction, and people with bipolar disorder who are in a euthymic mood state show decreased activity in the lingual gyrus compared to people without bipolar disorder. The biological mechanisms responsible for switching from a manic or hypomanic episode to a depressive episode, or vice versa, remain poorly understood, but the evidence points to a complex interplay of genetic, environmental, and neurological factors.

The Lithium And The Long Shadow

Lithium is the only medication approved by the FDA for treating mania in children and has the best overall evidence for reducing suicide, self-harm, and death in people with bipolar disorder. It is considered an effective treatment for acute manic episodes, preventing relapses, and bipolar depression, and is preferred for long-term mood stabilization. However, lithium treatment is also associated with adverse effects and has been shown to erode kidney and thyroid function over extended periods. Valproate has become a commonly prescribed treatment and effectively treats manic episodes, but it is teratogenic and should be avoided as a treatment in women of childbearing age. Carbamazepine is less effective in preventing relapse than lithium or valproate, but it effectively treats manic episodes, with some evidence it has greater benefit in rapid-cycling bipolar disorder, or those with more psychotic symptoms or more symptoms similar to that of schizoaffective disorder. Lamotrigine has some efficacy in treating depression, and this benefit is greatest in more severe depression, and may have a similar effectiveness to lithium for treating bipolar disorder, however, there is evidence to suggest that lamotrigine is less effective at preventing recurrent mania episodes. The effectiveness of topiramate is unknown, and the use of antidepressants in bipolar disorder is controversial, as they can be effective, but certain classes of antidepressants increase the risk of mania. Atypical antipsychotics are used for acute manic episodes or when mood stabilizers are ineffective or not tolerated, with long-acting injectables available for patients with adherence issues. Electroconvulsive therapy is effective in acute manic and depressive episodes, especially with psychosis or catatonia, and is also recommended for use in pregnant women with bipolar disorder. The choice of medications may differ depending on the bipolar disorder episode type or if the person is experiencing unipolar or bipolar depression, and other factors to consider when deciding on an appropriate treatment approach include if the person has any comorbidities, their response to previous therapies, adverse effects, and the desire of the person to be treated.

The Hidden Cost Of Homelessness

A 2024 meta-analysis and systematic review estimates that there is a global prevalence of approximately 8 percent of bipolar disorder amongst homeless individuals, which is several times higher than the population averages. In the United States, it was reported that in veterans with bipolar disorder, 55 percent reported being homeless at some point in their lives, and 12 percent had been homeless within the last four weeks. Homelessness was also highly associated with prior incarceration and co-occurring substance use, which highlights the cyclical relationship between social instability and mental illness. Individuals with bipolar disorder who are experiencing homelessness often have an early onset of illness, more frequent manic or depressive episodes, and poor adherence to medication, which can increase the likelihood of relapse and the loss of housing. Veterans and individuals who have been to correctional or psychiatric settings are especially at risk, and this highlights that the lack of post-discharge support contributes to the chronic cycles of instability. Social determinants like poverty, unemployment, and stigma also increase vulnerability to both bipolar disorder and homelessness. Once you are homeless, factors like stress, sleep deprivation, and exposure to unsafe environments are very prevalent and can worsen mood symptoms, making lasting recovery and reintegration even more difficult. Access to care is a significant barrier, as homeless patients were less likely to have insurance, the ability to maintain continuous care, and more likely to rely on emergency services in comparison to housed individuals. Disruptions in care contribute to poor participation in treatment plans, higher rates of psychiatric hospitalization, and worsened long-term outcomes. Individuals with bipolar disorder require consistent medication management and therapeutic monitoring, but unstable living conditions make meeting these needs quite difficult, unable to refill medications, attend appointments, or engage in therapy.

The Celebrity And The Stigma

In 2000, actress Carrie Fisher went public with her bipolar disorder diagnosis, becoming one of the most well-recognized advocates for people with bipolar disorder in the public eye and fiercely advocating to eliminate the stigma surrounding mental illnesses. Stephen Fried, who has written extensively on the topic, noted that Fisher helped to draw attention to the disorder's chronicity, relapsing nature, and that bipolar disorder relapses do not indicate a lack of discipline or moral shortcomings. Since being diagnosed at age 37, actor Stephen Fry has pushed to raise awareness of the condition, with his 2006 documentary Stephen Fry: The Secret Life of the Manic Depressive. In an effort to ease the social stigma associated with bipolar disorder, the orchestra conductor Ronald Braunstein cofounded the ME/2 Orchestra with his wife Caroline Whiddon in 2011. Braunstein was diagnosed with bipolar disorder in 1985 and his concerts with the ME/2 Orchestra were conceived in order to create a welcoming performance environment for his musical colleagues, while also raising public awareness about mental illness. Notable authors have written about bipolar disorder and many successful people have openly discussed their experience with it, including Kay Redfield Jamison, a clinical psychologist and professor of psychiatry at the Johns Hopkins University School of Medicine, who profiled her own bipolar disorder in her memoir An Unquiet Mind in 1995. Other celebrities who have publicly shared that they have bipolar disorder include Catherine Zeta-Jones, Mariah Carey, Kanye West, Jane Pauley, Demi Lovato, Selena Gomez, and Russell Brand. Media portrayals have also played a role, with dramatic works like Mr. Jones in 1993, The Mosquito Coast in 1986, and the play Death of a Salesman featuring Willy Loman, all presenting characters with traits suggestive of the diagnosis. These portrayals have been the subject of discussion by psychiatrists and film experts alike, highlighting the need for more accurate and nuanced representations of the condition in popular culture.

The Future Of The Spectrum

Bipolar disorder is the sixth leading cause of disability worldwide and has a lifetime prevalence of about 1 to 3 percent in the general population, but a reanalysis of data from the National Epidemiological Catchment Area survey in the United States suggested that 0.8 percent of the population experience a manic episode at least once and a further 0.5 percent have a hypomanic episode. Including sub-threshold diagnostic criteria, such as one or two symptoms over a short time-period, an additional 5.1 percent of the population, adding up to a total of 6.4 percent, were classified as having a bipolar spectrum disorder. A more recent analysis of data from a second US National Comorbidity Survey found that 1 percent met lifetime prevalence criteria for bipolar I, 1.1 percent for bipolar II, and 2.4 percent for subthreshold symptoms. Estimates vary about how many children and young adults have bipolar disorder, with these estimates ranging from 0.6 to 15 percent depending on differing settings, methods, and referral settings, raising suspicions of overdiagnosis. One meta-analysis of bipolar disorder in young people worldwide estimated that about 1.8 percent of people between the ages of seven and 21 have bipolar disorder. The incidence of bipolar disorder is similar in men and women as well as across different cultures and ethnic groups, but severity may differ widely across the globe. Disability-adjusted life year rates, for example, appear to be higher in developing countries, where medical coverage may be poorer and medication less available. Within the United States, Asian Americans have significantly lower rates than their African American and European American counterparts. The research on the prevalence of bipolar disorder in the homeless population is limited by the varying definitions of homelessness and challenges in keeping up with individuals on the move, and the variations in diagnostic methods across studies. As a result of this, current estimates of the prevalence of bipolar disorder in the homeless population may be underestimated. Expanding integrated models of care that combine psychiatric treatment with housing and social services has been suggested as a potential approach to improving long-term stability and reducing emergency service use. The future of bipolar disorder research lies in understanding the complex interplay of genetic, environmental, and neurological factors, and in developing more effective treatments that can address the full spectrum of the condition, from the most severe manic episodes to the subtle hypomanic states that often go undiagnosed.