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Bipolar disorder ( BD), previously known as manic depression, is a mental disorder characterized by periods of depression and periods of abnormally elevated mood that each last from days to weeks, and in some cases months. If the elevated mood is severe or associated with psychosis, it is called mania; if it is less severe and does not significantly affect functioning, it is called hypomania. During mania, an individual behaves or feels abnormally energetic, happy, or irritable, and they often make impulsive decisions with little regard for the consequences. There is usually, but not always, a reduced need for sleep during manic phases.Note: Sleep disturbances are usually present during all phases of the disease. For details on the mechanisms behind them, see: Harvey, A. G., Talbot, L. S., & Gershon, A. (2009). "Sleep disturbance in bipolar disorder across the lifespan".
and Gold, A., & Sylvia, L. (2016). "The role of sleep in bipolar disorder". Nature and Science of Sleep
/ref> During periods of depression, the individual may experience crying, have a negative outlook on life, and demonstrate poor eye contact with others. The risk of suicide is high. Over a period of 20 years, 6% of those with bipolar disorder died by suicide, with about one-third Suicide attempt in their lifetime. Among those with the disorder, 40–50% overall and 78% of adolescents engaged in self-harm. Other mental health issues, such as and substance use disorders, are commonly associated with bipolar disorder. The global prevalence of bipolar disorder is estimated to be between 1–5% of the world's population.
While the causes of this mood disorder are not clearly understood, both Genetics and environmental factors are thought to play a role. Heritability may account for up to 70–90% of the risk of developing bipolar disorder.
, particularly lithium, and certain , such as lamotrigine and valproate, as well as atypical antipsychotics, including quetiapine, olanzapine, and aripiprazole are the mainstay of long-term pharmacologic relapse prevention. are additionally given during acute manic episodes as well as in cases where mood stabilizers are poorly tolerated or ineffective. In patients where compliance is of concern, long-acting injectable formulations are available. There is some evidence that psychotherapy improves the course of this disorder. The use of antidepressants in depressive episodes is controversial: they can be effective but certain classes of antidepressants increase the risk of mania. The treatment of depressive episodes, therefore, is often difficult. Electroconvulsive therapy (ECT) is effective in acute manic and depressive episodes, especially with psychosis or catatonia. Admission to a psychiatric hospital may be required if a person is a risk to themselves or others; involuntary treatment is sometimes necessary if the affected person refuses treatment.
Bipolar disorder occurs in approximately 2% of the global population. In the United States, about 3% are estimated to be affected at some point in their life; rates appear to be similar in females and males. Symptoms most commonly begin between the ages of 20 and 25 years old; an earlier onset in life is associated with a worse prognosis. Interest in functioning in the assessment of patients with bipolar disorder is growing, with an emphasis on specific domains such as work, education, social life, family, and cognition. Around one-quarter to one-third of people with bipolar disorder have financial, social or work-related problems due to the illness. Bipolar disorder is among the top 20 causes of disability worldwide and leads to substantial costs for society. Due to lifestyle choices and the side effects of medications, the risk of death from natural causes such as coronary heart disease in people with bipolar disorder is twice that of the general population.
According to the DSM-5 criteria, mania is distinguished from hypomania by the duration: hypomania is present if elevated mood symptoms persist for at least four consecutive days, while mania is present if such symptoms persist for more than a week. Unlike mania, hypomania is not always associated with impaired functioning. The biological mechanisms responsible for switching from a manic or hypomanic episode to a depressive episode, or vice versa, remain poorly understood.
In severe manic episodes, a person can experience psychosis symptoms, where thought content is affected along with mood. They may feel unstoppable, persecuted, or as if they have a special relationship with God, a great mission to accomplish, or other grandiose or delusional ideas. This may lead to violent behavior and, sometimes, hospitalization in an inpatient psychiatric hospital. The severity of manic symptoms can be measured by rating scales such as the Young Mania Rating Scale, though questions remain about the reliability of these scales.
The onset of a manic or depressive episode is often foreshadowed by Sleep disorder. Manic individuals often have a history of substance use disorder developed over years as a form of "self-medication".
Hypomania may feel good to some individuals who experience it, though most people who experience hypomania state that the stress of the experience is very painful. People with bipolar disorder who experience hypomania tend to forget the effects of their actions on those around them. Even when family and friends recognize , the individual will often deny that anything is wrong. If not accompanied by depressive episodes, hypomanic episodes are often not deemed problematic unless the mood changes are uncontrollable or volatile. In individuals with Bipolar II disorder, depressive symptoms typically overlap with hypomania symptoms. These individuals may not be able to identify these specific symptoms as hypomania, rather they view them as typical depression with slight alterations in mood.
The earlier the age of onset, the more likely the first few episodes are to be depressive. For most people with bipolar types 1 and 2, the depressive episodes are much longer than the manic or hypomanic episodes. Since a diagnosis of bipolar disorder requires a manic or hypomanic episode, many affected individuals are initially misdiagnosed as having major depression and treated with prescribed antidepressants.
Substance use disorder is a common comorbidity in bipolar disorder; the subject has been widely reviewed.
The cause of bipolar disorders overlaps with major depressive disorder. When defining concordance as the co-twins having either bipolar disorder or major depression, then the concordance rate rises to 67% in identical twins and 19% in fraternal twins. The relatively low concordance between fraternal twins brought up together suggests that shared family environmental effects are limited, although the ability to detect them has been limited by small sample sizes.
Although the first genetic linkage finding for mania was in 1969, linkage studies have been inconsistent. Findings point strongly to heterogeneity, with different genes implicated in different families. Robust and replicable genome-wide significant associations showed several common single-nucleotide polymorphisms (SNPs) are associated with bipolar disorder, including variants within the genes CACNA1C, ODZ4, and NCAN. The largest and most recent genome-wide association study failed to find any locus that exerts a large effect, reinforcing the idea that no single gene is responsible for bipolar disorder in most cases. Polymorphisms in BDNF, DRD4, DAO, and TPH1 have been frequently associated with bipolar disorder and were initially associated in a meta-analysis, but this association disappeared after correction for multiple testing. On the other hand, two polymorphisms in TPH2 were identified as being associated with bipolar disorder.
Due to the inconsistent findings in a genome-wide association study, multiple studies have undertaken the approach of analyzing SNPs in biological pathways. Signaling pathways traditionally associated with bipolar disorder that have been supported by these studies include corticotropin-releasing hormone signaling, cardiac β-adrenergic signaling, phospholipase C signaling, glutamate receptor signaling, cardiac hypertrophy signaling, Wnt signaling, Notch signaling, and endothelin 1 signaling. Of the 16 genes identified in these pathways, three were found to be dysregulated in the dorsolateral prefrontal cortex portion of the brain in post-mortem studies: CACNA1C, GNG2, and ITPR2.
Bipolar disorder is associated with reduced expression of specific DNA repair enzymes and increased levels of oxidative DNA damages. The AKAP11 gene was recently discovered as the first gene linked to bipolar disorder. The exomes of around 14,000 individuals with bipolar disorder were analysed and compared to those without the condition. The findings were combined with data from another study in the Schizophrenia Exome Sequencing Meta-Analysis (SCHEMA), examining the genome sequences of 24,000 people alongside the original 14,000 bipolar disorder cases. This study identified genetic variants, including the AKAP11 gene, associated with an increased risk of bipolar disorder. The AKAP11 gene's interaction with the GSK3B protein, a molecular target of lithium, points to a possible mechanism behind the medication's therapeutic effects.
Meta-analysis of structural MRI studies have shown that certain brain regions (e.g., the left rostral anterior cingulate cortex, insular cortex, ventral prefrontal cortex, and claustrum) are smaller in people with bipolar disorder, whereas other regions are larger (lateral ventricles, globus pallidus, subgenual anterior cingulate, and the amygdala). Additionally, these meta-analyses found that people with bipolar disorder have higher rates of deep white matter hyperintensities.
Functional MRI findings suggest that the ventricular prefrontal cortex regulates the limbic system, especially the amygdala. 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. Consistent with this, pharmacological treatment of mania returns ventricular prefrontal cortex activity to the levels in non-manic people, suggesting that ventricular prefrontal cortex activity is an indicator of mood state. However, while pharmacological treatment of mania reduces amygdala hyperactivity, it remains more active than the amygdala of those without bipolar disorder, suggesting amygdala activity may be a marker of the disorder rather than the current mood state. Manic and depressive episodes tend to be characterized by dysfunction in different regions of the ventricular prefrontal cortex. Manic episodes appear to be associated with decreased activation of the right ventricular prefrontal cortex whereas depressive episodes are associated with decreased activation of the left ventricular prefrontal cortex. These disruptions often occur during development linked with synaptic pruning dysfunction.
People with bipolar disorder who are in a euthymic mood state show decreased activity in the lingual gyrus compared to people without bipolar disorder. In contrast, they demonstrate decreased activity in the inferior frontal cortex during manic episodes compared to people without the disorder. Similar studies examining the differences in brain activity between people with bipolar disorder and those without did not find a consistent area in the brain that was more or less active when comparing these two groups. People with bipolar have increased activation of left hemisphere ventral limbic areaswhich mediate emotional experiences and generation of emotional responsesand decreased activation of right hemisphere cortical structures related to cognitionstructures associated with the regulation of emotions. However, further research is needed to consolidate neuroimaging findings, which are often heterogeneous and not consistently reported according to a common standard.
Neuroscientists have proposed additional models to try to explain the cause of bipolar disorder. One proposed model for bipolar disorder suggests that hypersensitivity of reward circuits consisting of frontostriatal circuits causes mania, and decreased sensitivity of these circuits causes depression. According to the "kindling" hypothesis, 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. There is evidence supporting an association between early-life stress and dysfunction of the hypothalamic-pituitary-adrenal axis leading to its overactivation, which may play a role in the pathogenesis of bipolar disorder. Other brain components that have been proposed to play a role in bipolar disorder are the mitochondria and a sodium ATPase pump. and regulation of the hormone melatonin also seem to be altered.
Dopamine, a neurotransmitter responsible for mood cycling, has increased transmission during the manic phase. The dopamine hypothesis states that the increase in dopamine results in secondary Homeostasis downregulation of key system elements and receptors such as lower sensitivity of dopaminergic receptors. This results in decreased dopamine transmission characteristic of the depressive phase. The depressive phase ends with homeostatic upregulation potentially restarting the cycle over again. Glutamate is significantly increased within the left dorsolateral prefrontal cortex during the manic phase of bipolar disorder, and returns to normal levels once the phase is over.
Medications used to treat bipolar may exert their effect by modulating intracellular signaling, such as through depleting myo-inositol levels, inhibition of Cyclic AMP, and through altering subunits of the dopamine-associated G-protein. Consistent with this, elevated levels of Gαi, Gαs, and Gαq/11 have been reported in brain and blood samples, along with increased protein kinase A (PKA) expression and sensitivity;
typically, PKA activates as part of the intracellular signalling cascade downstream from the detachment of Gαs subunit from the G protein complex.Decreased levels of 5-hydroxyindoleacetic acid, a byproduct of serotonin, are present in the cerebrospinal fluid of persons with bipolar disorder during both the depressed and manic phases. Increased dopaminergic activity has been hypothesized in manic states due to the ability of dopamine agonists to stimulate mania in people with bipolar disorder. Decreased sensitivity of regulatory α2 adrenergic receptors as well as increased cell counts in the locus coeruleus indicated increased noradrenergic activity in manic people. Low plasma GABA levels on both sides of the mood spectrum have been found. One review found no difference in monoamine levels, but found abnormal norepinephrine turnover in people with bipolar disorder. Tyrosine depletion was found to reduce the effects of methamphetamine in people with bipolar disorder as well as symptoms of mania, implicating dopamine in mania. VMAT2 binding was found to be increased in one study of people with bipolar mania.
The most widely used criteria for diagnosing bipolar disorder are from the American Psychiatric Association's (APA) Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) and the World Health Organization's (WHO) International Statistical Classification of Diseases and Related Health Problems, 10th Edition (ICD-10). The ICD-10 criteria are used more often in clinical settings outside of the U.S. while the DSM criteria are used within the U.S. and are the prevailing criteria used internationally in research studies. The DSM-5, published in 2013, includes further and more accurate specifiers compared to its predecessor, the DSM-IV-TR.
Several for the screening and evaluation of bipolar disorder exist, including the Bipolar Spectrum Diagnostic Scale, Mood Disorder Questionnaire, the General Behavior Inventory and the Hypomania Checklist. The use of evaluation scales cannot substitute for a full clinical interview, but they serve to systematize the recollection of symptoms. On the other hand, instruments for screening bipolar disorder tend to have lower sensitivity.
Although there are no biological tests that are diagnostic of bipolar disorder, blood tests and/or imaging are carried out to investigate whether medical illnesses with clinical presentations similar to that of bipolar disorder are present before making a definitive diagnosis. Neurologic diseases such as multiple sclerosis, complex , strokes, brain tumors, Wilson's disease, traumatic brain injury, Huntington's disease, and complex can mimic features of bipolar disorder. An EEG may be used to exclude neurological disorders such as epilepsy, and a CT scan or MRI of the head may be used to exclude brain lesions. Additionally, disorders of the endocrine system such as hypothyroidism, hyperthyroidism, and Cushing's disease are in the differential as is the connective tissue disease systemic lupus erythematosus. Infectious causes of mania that may appear similar to bipolar mania include herpes encephalitis, HIV, influenza, or neurosyphilis. Certain vitamin deficiencies such as pellagra (niacin deficiency), vitamin B12 deficiency, folate deficiency, and Wernicke–Korsakoff syndrome (thiamine deficiency) can also lead to mania. Common medications that can cause manic symptoms include antidepressants, prednisone, Parkinson's disease medications, Levothyroxine, stimulants (including cocaine and methamphetamine), and certain .
When relevant, specifiers for peripartum onset and with rapid cycling should be used with any subtype. Individuals who have subthreshold symptoms that cause clinically significant distress or impairment, but do not meet full criteria for one of the three subtypes may be diagnosed with other specified or unspecified bipolar disorder. Other specified bipolar disorder is used when a clinician chooses to explain why the full criteria were not met (e.g., hypomania without a prior major depressive episode). If the condition is thought to have a non-psychiatric medical cause, the diagnosis of bipolar and related disorder due to another medical condition is made, while substance/medication-induced bipolar and related disorder is used if a medication is thought to have triggered the condition.
Valproate and carbamazepine are teratogenic and should be avoided as a treatment in women of childbearing age, but discontinuation of these medications during pregnancy is associated with a high risk of relapse. Lithium is also tetratogenic in the first trimester, though it can be acceptable during this period after careful weighing of benefits and risks.
The effectiveness of topiramate is unknown.
Mood stabilizers are used for long-term maintenance but have not demonstrated the ability to quickly treat acute bipolar depression.
Whether modern antidepressants cause mania or cycle acceleration in bipolar disorder is highly controversial, as is whether antidepressants provide any benefit over mood stabilizers alone.
Compliance with medications is one of the most significant factors that can decrease the rate and severity of relapse and have a positive impact on overall prognosis. However, the types of medications used in treating BD commonly cause side effects and more than 75% of individuals with BD inconsistently take their medications for various reasons. Of the various types of the disorder, rapid cycling (four or more episodes in one year) is associated with the worst prognosis due to higher rates of self-harm and suicide. Individuals diagnosed with bipolar who have a family history of bipolar disorder are at a greater risk for more frequent manic/hypomanic episodes. Early onset and psychotic features are also associated with worse outcomes, as well as subtypes that are nonresponsive to lithium.
Early recognition and intervention also improve prognosis as the symptoms in earlier stages are less severe and more responsive to treatment. Onset after adolescence is connected to better prognoses for both genders, and being male is a protective factor against higher levels of depression. For women, better social functioning before developing bipolar disorder and being a parent are protective towards suicide attempts.
When bipolar disorder occurs in children, it severely and adversely affects their psychosocial development. Children and adolescents with bipolar disorder have higher rates of significant difficulties with substance use disorders, psychosis, academic difficulties, behavioral problems, social difficulties, and legal problems. Cognitive deficits typically increase over the course of the illness. Higher degrees of impairment correlate with the number of previous manic episodes and hospitalizations, and with the presence of psychotic symptoms. Early intervention can slow the progression of cognitive impairment, while treatment at later stages can help reduce distress and negative consequences related to cognitive dysfunction.
Despite the overly ambitious goals that are frequently part of manic episodes, symptoms of mania undermine the ability to achieve these goals and often interfere with an individual's social and occupational functioning. One-third of people with BD remain unemployed for one year following a hospitalization for mania. Depressive symptoms during and between episodes, which occur much more frequently for most people than hypomanic or manic symptoms over the course of illness, are associated with lower functional recovery in between episodes, including unemployment or underemployment for both BD-I and BD-II. However, the course of illness (duration, age of onset, number of hospitalizations, and the presence or not of rapid cycling) and cognitive performance are the best predictors of employment outcomes in individuals with bipolar disorder, followed by symptoms of depression and years of education.
Symptoms preceding a relapse (prodromal), especially those related to mania, can be reliably identified by people with bipolar disorder. There have been intents to teach patients coping strategies when noticing such symptoms with encouraging results.
Risk factors for suicide attempts and death from suicide in people with bipolar disorder include older age, prior suicide attempts, a depressive or mixed index episode (first 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.
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Bipolar disorder is the sixth leading cause of disability worldwide and has a lifetime prevalence of about 1 to 3% in the general population. However, a reanalysis of data from the National Epidemiological Catchment Area survey in the United States suggested that 0.8% of the population experience a manic episode at least once (the diagnostic threshold for bipolar I) and a further 0.5% have a hypomanic episode (the diagnostic threshold for bipolar II or cyclothymia). Including sub-threshold diagnostic criteria, such as one or two symptoms over a short time-period, an additional 5.1% of the population, adding up to a total of 6.4%, were classified as having a bipolar spectrum disorder. A more recent analysis of data from a second US National Comorbidity Survey found that 1% met lifetime prevalence criteria for bipolar I, 1.1% for bipolar II, and 2.4% for subthreshold symptoms. Estimates vary about how many children and young adults have bipolar disorder. These estimates range from 0.6 to 15% 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% of people between the ages of seven and 21 have bipolar disorder. Similar to adults, bipolar disorder in children and adolescents is thought to occur at a similar frequency in boys and girls.
There are conceptual and methodological limitations and variations in the findings. Prevalence studies of bipolar disorder are typically carried out by lay interviewers who follow fully structured/fixed interview schemes; responses to single items from such interviews may have limited validity. In addition, diagnoses (and therefore estimates of prevalence) vary depending on whether a categorical or spectrum approach is used. This consideration has led to concerns about the potential for both underdiagnosis and overdiagnosis.
The incidence of bipolar disorder is similar in men and women as well as across different cultures and ethnic groups. A 2000 study by the World Health Organization found that prevalence and incidence of bipolar disorder are very similar across the world. Age-standardized prevalence per 100,000 ranged from 421.0 in South Asia to 481.7 in Africa and Europe for men and from 450.3 in Africa and Europe to 491.6 in Oceania for women. However, 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.
In 2017, the Global Burden of Disease Study estimated there were 4.5 million new cases and a total of 45.5 million cases globally.
These concepts were developed by the German psychiatrist Emil Kraepelin (1856–1926), who, using Kahlbaum's concept of cyclothymia, categorized and studied the natural course of untreated bipolar patients. He coined the term manic depressive psychosis, after noting that periods of acute illness, manic or depressive, were generally punctuated by relatively symptom-free intervals where the patient was able to function normally.
The term "manic–depressive reaction" appeared in the first version of the DSM in 1952, influenced by the legacy of Adolf Meyer. Subtyping into "unipolar" depressive disorders and bipolar disorders has its origin in Karl Kleist's concept – since 1911 – of unipolar and bipolar affective disorders, which was used by Karl Leonhard in 1957 to differentiate between unipolar and bipolar disorder in depression. These subtypes have been regarded as separate conditions since publication of the DSM-III. The subtypes bipolar II and rapid cycling have been included since the DSM-IV, based on work from the 1970s by David Dunner, Elliot Gershon, Frederick Goodwin, Ronald Fieve, and Joseph Fleiss. Bipolar Depression: Molecular Neurobiology, Clinical Diagnosis and Pharmacotherapy Carlos A. Zarate Jr., Husseini K. Manji, Springer Science & Business Media, April 16, 2009 David L. Dunner interviewed by Thomas A. Ban for the ANCP, Waikoloa, Hawaii, December 13, 2001
In Mr. Jones (1993), (Richard Gere) swings from a manic episode into a depressive phase and back again, spending time in a psychiatric hospital and displaying many of the features of the syndrome. In The Mosquito Coast (1986), Allie Fox (Harrison Ford) displays some features including recklessness, grandiosity, increased goal-directed activity and mood lability, as well as some paranoia. Psychiatrists have suggested that Willy Loman, the main character in Arthur Miller's classic play Death of a Salesman, has bipolar disorder.
The 2009 drama 90210 featured a character, Silver, who was diagnosed with bipolar disorder. Stacey Slater, a character from the BBC soap EastEnders, has been diagnosed with the disorder. The storyline was developed as part of the BBC's Headroom campaign. The Channel 4 soap Brookside had earlier featured a story about bipolar disorder when the character Jimmy Corkhill was diagnosed with the condition. 2011 Showtime's political thriller drama Homeland protagonist Carrie Mathison has bipolar disorder, which she has kept secret since her school days. The 2014 ABC medical drama, Black Box, featured a world-renowned neuroscientist with bipolar disorder. In the TV series Dave, the eponymous main character, played by Lil Dicky as a fictionalized version of himself, is an aspiring rapper. Lil Dicky's real-life hype man GaTa also plays himself. In one episode, after being off his medication and having an episode, GaTa tearfully confesses to having bipolar disorder. GaTa has bipolar disorder in real life but, like his character in the show, he is able to manage it with medication.
Since 2024, Nicola Coughlan, has co-starred alongside Lydia West, in the British Channel 4 dark television comedy-drama Big Mood. Coughlan portrays the leading role of Maggie who was diagnosed with bipolar disorder. In a series about two best friends navigating friendship amidst a mental health crisis.
/ref>Harvey, A. G., Talbot, L. S., & Gershon, A. (2009). "Sleep disturbance in bipolar disorder across the lifespan".
( preview)Gold, A., & Sylvia, L. (2016). "The role of sleep in bipolar disorder". Nature and Science of Sleep
/ref>Tonon, A. C., Nexha, A., Mendonça da Silva, M., Gomes, F. A., Hidalgo, M. P., & Frey, B. N. (2024). "Sleep and circadian disruption in bipolar disorders: From psychopathology to digital phenotyping in clinical practice". Psychiatry and Clinical Neurosciences
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