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Bipolar disorder, previously known as manic depression, is a
mental disorder A mental disorder, also referred to as a mental illness or psychiatric disorder, is a behavioral or mental pattern that causes significant distress or impairment of personal functioning. Such features may be persistent, relapsing and remitti ...
characterized by periods of depression and periods of abnormally elevated mood that last from days to weeks each. If the elevated mood is severe or associated with
psychosis Psychosis is a condition of the mind that results in difficulties determining what is real and what is not real. Symptoms may include delusions and hallucinations, among other features. Additional symptoms are incoherent speech and behavi ...
, it is called
mania Mania, also known as manic syndrome, is a mental and behavioral disorder defined as a state of abnormally elevated arousal, affect, and energy level, or "a state of heightened overall activation with enhanced affective expression together wi ...
; if it is less severe, it is called
hypomania Hypomania (literally "under mania" or "less than mania") is a mental and behavioural disorder, characterised essentially by an apparently non-contextual elevation of mood (euphoria) that contributes to persistently disinhibited behaviour. Th ...
. 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 also a reduced need for sleep during manic phases. During periods of depression, the individual may experience crying and have a negative outlook on life and poor eye contact with others. The risk of
suicide Suicide is the act of intentionally causing one's own death. Mental disorders (including depression, bipolar disorder, schizophrenia, personality disorders, anxiety disorders), physical disorders (such as chronic fatigue syndrome), and ...
is high; over a period of 20 years, 6% of those with bipolar disorder died by suicide, while 30–40% engaged in
self-harm Self-harm is intentional behavior that is considered harmful to oneself. This is most commonly regarded as direct injury of one's own skin tissues usually without a suicidal intention. Other terms such as cutting, self-injury and self-mutilati ...
. Other mental health issues, such as
anxiety disorder Anxiety disorders are a cluster of mental disorders characterized by significant and uncontrollable feelings of anxiety and fear such that a person's social, occupational, and personal function are significantly impaired. Anxiety may cause phy ...
s and
substance use disorder Substance use disorder (SUD) is the persistent use of drugs (including alcohol) despite substantial harm and adverse consequences as a result of their use. Substance use disorders are characterized by an array of mental/emotional, physical, and ...
s, are commonly associated with bipolar disorder. While the causes of this
mood disorder A mood disorder, also known as an affective disorder, is any of a group of conditions of mental and behavioral disorder where a disturbance in the person's mood is the main underlying feature. The classification is in the '' Diagnostic and St ...
are not clearly understood, both genetic and
environmental A biophysical environment is a biotic and abiotic surrounding of an organism or population, and consequently includes the factors that have an influence in their survival, development, and evolution. A biophysical environment can vary in scal ...
factors are thought to play a role. Many genes, each with small effects, may contribute to the development of the disorder. Genetic factors account for about 70–90% of the risk of developing bipolar disorder. Environmental risk factors include a history of
childhood abuse Child abuse (also called child endangerment or child maltreatment) is physical, sexual, and/or psychological maltreatment or neglect of a child or children, especially by a parent or a caregiver. Child abuse may include any act or failure to a ...
and long-term
stress Stress may refer to: Science and medicine * Stress (biology), an organism's response to a stressor such as an environmental condition * Stress (linguistics), relative emphasis or prominence given to a syllable in a word, or to a word in a phrase ...
. The condition is classified as
bipolar I disorder Bipolar I disorder (BD-I; pronounced "type one bipolar disorder") is a type of bipolar spectrum disorder characterized by the occurrence of at least one manic episode, with or without mixed or psychotic features. Most people also, at other ti ...
if there has been at least one manic episode, with or without depressive episodes, and as
bipolar II disorder Bipolar II disorder (BP-II) is a mood disorder on the bipolar spectrum, characterized by at least one episode of hypomania and at least one episode of major depression. Diagnosis for BP-II requires that the individual must never have experien ...
if there has been at least one hypomanic episode (but no full manic episodes) and one major depressive episode. It is classified as
Cyclothymia Cyclothymia ( ), also known as cyclothymic disorder, psychothemia/psychothymia, bipolar III, affective personality disorder and cyclothymic personality disorder, is a mental and behavioural disorder that involves numerous periods of symptoms of ...
if there are hypomanic episodes with periods of depression that do not meet the criteria for major depressive episodes. If these symptoms are due to drugs or medical problems, they are not diagnosed as bipolar disorder. Other conditions that have overlapping symptoms with bipolar disorder include
attention deficit hyperactivity disorder Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterised by excessive amounts of inattention, hyperactivity, and impulsivity that are pervasive, impairing in multiple contexts, and otherwise age-inap ...
,
personality disorder Personality disorders (PD) are a class of mental disorders characterized by enduring maladaptive patterns of behavior, cognition, and inner experience, exhibited across many contexts and deviating from those accepted by the individual's cultu ...
s,
schizophrenia Schizophrenia is a mental disorder characterized by continuous or relapsing episodes of psychosis. Major symptoms include hallucinations (typically hearing voices), delusions, and disorganized thinking. Other symptoms include social w ...
, and
substance use disorder Substance use disorder (SUD) is the persistent use of drugs (including alcohol) despite substantial harm and adverse consequences as a result of their use. Substance use disorders are characterized by an array of mental/emotional, physical, and ...
as well as many other medical conditions.
Medical test A medical test is a medical procedure performed to detect, diagnose, or monitor diseases, disease processes, susceptibility, or to determine a course of treatment. Medical tests such as, physical and visual exams, diagnostic imaging, genetic ...
ing is not required for a
diagnosis Diagnosis is the identification of the nature and cause of a certain phenomenon. Diagnosis is used in many different disciplines, with variations in the use of logic, analytics, and experience, to determine "cause and effect". In systems engin ...
, though
blood tests A blood test is a laboratory analysis performed on a blood sample that is usually extracted from a vein in the arm using a hypodermic needle, or via fingerprick. Multiple tests for specific blood components, such as a glucose test or a choles ...
or
medical imaging Medical imaging is the technique and process of imaging the interior of a body for clinical analysis and medical intervention, as well as visual representation of the function of some organs or tissues (physiology). Medical imaging seeks to re ...
can rule out other problems.
Mood stabilizer A mood stabilizer is a psychiatric medication used to treat mood disorders characterized by intense and sustained mood shifts, such as bipolar disorder and the bipolar type of schizoaffective disorder. Uses Mood stabilizers are best known for ...
s—
lithium Lithium (from el, λίθος, lithos, lit=stone) is a chemical element with the symbol Li and atomic number 3. It is a soft, silvery-white alkali metal. Under standard conditions, it is the least dense metal and the least dense soli ...
and certain
anticonvulsant Anticonvulsants (also known as antiepileptic drugs or recently as antiseizure drugs) are a diverse group of pharmacological agents used in the treatment of epileptic seizures. Anticonvulsants are also increasingly being used in the treatment of ...
s such as valproate and
carbamazepine Carbamazepine (CBZ), sold under the trade name Tegretol among others, is an anticonvulsant medication used primarily in the treatment of epilepsy and neuropathic pain. It is used as an adjunctive treatment in schizophrenia along with other m ...
as well as atypical antipsychotics such as aripiprazole—are the mainstay of long-term pharmacologic relapse prevention.
Antipsychotic Antipsychotics, also known as neuroleptics, are a class of psychotropic medication primarily used to manage psychosis (including delusions, hallucinations, paranoia or disordered thought), principally in schizophrenia but also in a range of ...
s 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 Psychotherapy (also psychological therapy, talk therapy, or talking therapy) is the use of psychological methods, particularly when based on regular personal interaction, to help a person change behavior, increase happiness, and overcome pro ...
improves the course of this disorder. The use of antidepressants in depressive episodes is controversial: they can be effective but have been implicated in triggering manic episodes. The treatment of depressive episodes, therefore, is often difficult.
Electroconvulsive therapy Electroconvulsive therapy (ECT) is a psychiatric treatment where a generalized seizure (without muscular convulsions) is electrically induced to manage refractory mental disorders.Rudorfer, MV, Henry, ME, Sackeim, HA (2003)"Electroconvulsive th ...
(ECT) is effective in acute manic and depressive episodes, especially with psychosis or
catatonia Catatonia is a complex neuropsychiatric behavioral syndrome that is characterized by abnormal movements, immobility, abnormal behaviors, and withdrawal. The onset of catatonia can be acute or subtle and symptoms can wax, wane, or change during ...
. Admission to a
psychiatric hospital Psychiatric hospitals, also known as mental health hospitals, behavioral health hospitals, are hospitals or wards specializing in the treatment of severe mental disorders, such as schizophrenia, bipolar disorder, eating disorders, dissociat ...
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 1% 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 Coronary artery disease (CAD), also called coronary heart disease (CHD), ischemic heart disease (IHD), myocardial ischemia, or simply heart disease, involves the reduction of blood flow to the heart muscle due to build-up of atherosclerotic pl ...
in people with bipolar disorder is twice that of the general population.


Signs and symptoms

Late adolescence and early adulthood are peak years for the onset of bipolar disorder. The condition is characterized by intermittent episodes of
mania Mania, also known as manic syndrome, is a mental and behavioral disorder defined as a state of abnormally elevated arousal, affect, and energy level, or "a state of heightened overall activation with enhanced affective expression together wi ...
and/or depression, with an absence of symptoms in between. During these episodes, people with bipolar disorder exhibit disruptions in normal mood, psychomotor activity (the level of physical activity that is influenced by mood)—e.g. constant fidgeting during mania or slowed movements during depression—
circadian rhythm A circadian rhythm (), or circadian cycle, is a natural, internal process that regulates the sleep–wake cycle and repeats roughly every 24 hours. It can refer to any process that originates within an organism (i.e., endogenous) and responds to ...
and cognition. Mania can present with varying levels of mood disturbance, ranging from
euphoria Euphoria ( ) is the experience (or affect) of pleasure or excitement and intense feelings of well-being and happiness. Certain natural rewards and social activities, such as aerobic exercise, laughter, listening to or making music and d ...
, which is associated with "classic mania", to dysphoria and
irritability Irritability (also called as crankiness) is the excitatory ability that living organisms have to respond to changes in their environment. The term is used for both the physiological reaction to stimuli and for the pathological, abnormal or excessi ...
. Psychotic symptoms such as delusions or hallucinations may occur in both manic and depressive episodes; their content and nature are consistent with the person's prevailing mood. According to the
DSM-5 The ''Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition'' (DSM-5), is the 2013 update to the '' Diagnostic and Statistical Manual of Mental Disorders'', the taxonomic and diagnostic tool published by the American Psychiatri ...
criteria, mania is distinguished from
hypomania Hypomania (literally "under mania" or "less than mania") is a mental and behavioural disorder, characterised essentially by an apparently non-contextual elevation of mood (euphoria) that contributes to persistently disinhibited behaviour. Th ...
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.


Manic episodes

Also known as a manic episode, mania is a distinct period of at least one week of elevated or irritable mood, which can range from euphoria to
delirium Delirium (also known as acute confusional state) is an organically caused decline from a previous baseline of mental function that develops over a short period of time, typically hours to days. Delirium is a syndrome encompassing disturbances ...
. The core symptom of mania involves an increase in energy of psychomotor activity. Mania can also present with increased self-esteem or grandiosity,
racing thoughts Racing thoughts refers to the rapid thought patterns that often occur in manic, hypomanic, or mixed episodes. While racing thoughts are most commonly described in people with bipolar disorder and sleep apnea, they are also common with anxiety dis ...
,
pressured speech Pressure of speech or pressured speech is a tendency to speak rapidly and frenziedly. Pressured speech is motivated by an urgency that may not be apparent to the listener. The speech produced is difficult to interpret. Such speech may be too fas ...
that is difficult to interrupt, decreased need for sleep, disinhibited social behavior, increased goal-oriented activities and impaired judgement, which can lead to exhibition of behaviors characterized as impulsive or high-risk, such as hypersexuality or excessive spending. To fit the definition of a manic episode, these behaviors must impair the individual's ability to socialize or work. If untreated, a manic episode usually lasts three to six months. In severe manic episodes, a person can experience psychotic symptoms, where thought content is affected along with mood. They may feel unstoppable, 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 Psychiatric hospitals, also known as mental health hospitals, behavioral health hospitals, are hospitals or wards specializing in the treatment of severe mental disorders, such as schizophrenia, bipolar disorder, eating disorders, dissociat ...
. 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 disturbance. Manic individuals often have a history of
substance use disorder Substance use disorder (SUD) is the persistent use of drugs (including alcohol) despite substantial harm and adverse consequences as a result of their use. Substance use disorders are characterized by an array of mental/emotional, physical, and ...
developed over years as a form of "self-medication".


Hypomanic episodes

Hypomania Hypomania (literally "under mania" or "less than mania") is a mental and behavioural disorder, characterised essentially by an apparently non-contextual elevation of mood (euphoria) that contributes to persistently disinhibited behaviour. Th ...
is the milder form of mania, defined as at least four days of the same criteria as mania, but which does not cause a significant decrease in the individual's ability to socialize or work, lacks psychotic features such as
delusions A delusion is a false fixed belief that is not amenable to change in light of conflicting evidence. As a pathology, it is distinct from a belief based on false or incomplete information, confabulation, dogma, illusion, hallucination, or som ...
or
hallucinations A hallucination is a perception in the absence of an external stimulus that has the qualities of a real perception. Hallucinations are vivid, substantial, and are perceived to be located in external objective space. Hallucination is a combinati ...
, and does not require psychiatric hospitalization. Overall functioning may actually increase during episodes of hypomania and is thought to serve as a defense mechanism against depression by some. Hypomanic episodes rarely progress to full-blown manic episodes. Some people who experience hypomania show increased creativity, while others are irritable or demonstrate poor judgment. 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 mood swings, 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. Most commonly, symptoms continue for time periods from a few weeks to a few months.


Depressive episodes

Symptoms of the depressive phase of bipolar disorder include persistent feelings of
sadness Sadness is an emotional pain associated with, or characterized by, feelings of disadvantage, loss, despair, grief, helplessness, disappointment and sorrow. An individual experiencing sadness may become quiet or lethargic, and withdraw them ...
, irritability or anger, loss of interest in previously enjoyed activities, excessive or inappropriate guilt,
hopelessness Depression is a mental state of low mood and aversion to activity, which affects more than 280 million people of all ages (about 3.5% of the global population). Classified medically as a mental and behavioral disorder, the experience of ...
, sleeping too much or not enough, changes in appetite and/or weight,
fatigue Fatigue describes a state of tiredness that does not resolve with rest or sleep. In general usage, fatigue is synonymous with extreme tiredness or exhaustion that normally follows prolonged physical or mental activity. When it does not resolve ...
, problems concentrating, self-loathing or feelings of worthlessness, and thoughts of death or
suicide Suicide is the act of intentionally causing one's own death. Mental disorders (including depression, bipolar disorder, schizophrenia, personality disorders, anxiety disorders), physical disorders (such as chronic fatigue syndrome), and ...
. Although the DSM-5 criteria for diagnosing unipolar and bipolar episodes are the same, some clinical features are more common in the latter, including increased sleep, sudden onset and resolution of symptoms, significant weight gain or loss, and severe episodes after childbirth. 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 A medical error is a preventable adverse effect of care ("iatrogenesis"), whether or not it is evident or harmful to the patient. This might include an inaccurate or incomplete diagnosis or treatment of a disease, injury, syndrome, behavior, i ...
as having major depression and incorrectly treated with prescribed antidepressants.


Mixed affective episodes

In bipolar disorder, a mixed state is an episode during which symptoms of both mania and depression occur simultaneously. Individuals experiencing a mixed state may have manic symptoms such as grandiose thoughts while simultaneously experiencing depressive symptoms such as excessive guilt or feeling suicidal. They are considered to have a higher risk for suicidal behavior as depressive emotions such as hopelessness are often paired with
mood swings A mood swing is an extreme or sudden change of mood. Such changes can play a positive part in promoting problem solving and in producing flexible forward planning, or be disruptive. When mood swings are severe, they may be categorized as par ...
or difficulties with impulse control.
Anxiety disorder Anxiety disorders are a cluster of mental disorders characterized by significant and uncontrollable feelings of anxiety and fear such that a person's social, occupational, and personal function are significantly impaired. Anxiety may cause phy ...
s occur more frequently as a comorbidity in mixed bipolar episodes than in non-mixed bipolar depression or mania. Substance (including
alcohol Alcohol most commonly refers to: * Alcohol (chemistry), an organic compound in which a hydroxyl group is bound to a carbon atom * Alcohol (drug), an intoxicant found in alcoholic drinks Alcohol may also refer to: Chemicals * Ethanol, one of sev ...
) use also follows this trend, thereby appearing to depict bipolar symptoms as no more than a consequence of substance use.


Comorbid conditions

People with bipolar disorder often have other co-existing psychiatric conditions such as
anxiety Anxiety is an emotion which is characterized by an unpleasant state of inner turmoil and includes feelings of dread over anticipated events. Anxiety is different than fear in that the former is defined as the anticipation of a future threat wh ...
(present in about 71% of people with bipolar disorder), substance abuse (56%),
personality disorders Personality disorders (PD) are a class of mental disorders characterized by enduring maladaptive patterns of behavior, cognition, and inner experience, exhibited across many contexts and deviating from those accepted by the individual's cultur ...
(36%) and attention deficit hyperactivity disorder (10–20%) which can add to the burden of illness and worsen the prognosis. Certain medical conditions are also more common in people with bipolar disorder as compared to the general population. This includes increased rates of
metabolic syndrome Metabolic syndrome is a clustering of at least three of the following five medical conditions: abdominal obesity, high blood pressure, high blood sugar, high serum triglycerides, and low serum high-density lipoprotein (HDL). Metabolic syndro ...
(present in 37% of people with bipolar disorder),
migraine headaches Migraine (, ) is a common neurological disorder characterized by recurrent headaches. Typically, the associated headache affects one side of the head, is pulsating in nature, may be moderate to severe in intensity, and could last from a few hou ...
(35%),
obesity Obesity is a medical condition, sometimes considered a disease, in which excess body fat has accumulated to such an extent that it may negatively affect health. People are classified as obese when their body mass index (BMI)—a person's ...
(21%) and
type 2 diabetes Type 2 diabetes, formerly known as adult-onset diabetes, is a form of diabetes mellitus that is characterized by high blood sugar, insulin resistance, and relative lack of insulin. Common symptoms include increased thirst, frequent urinatio ...
(14%). This contributes to a risk of death that is two times higher in those with bipolar disorder as compared to the general population.
Substance use disorder Substance use disorder (SUD) is the persistent use of drugs (including alcohol) despite substantial harm and adverse consequences as a result of their use. Substance use disorders are characterized by an array of mental/emotional, physical, and ...
is a common comorbidity in bipolar disorder; the subject has been widely reviewed.


Causes

The causes of bipolar disorder likely vary between individuals and the exact mechanism underlying the disorder remains unclear. Genetic influences are believed to account for 73–93% of the risk of developing the disorder indicating a strong hereditary component. The overall
heritability Heritability is a statistic used in the fields of breeding and genetics that estimates the degree of ''variation'' in a phenotypic trait in a population that is due to genetic variation between individuals in that population. The concept of her ...
of the
bipolar spectrum Bipolar disorder, previously known as manic depression, is a mental disorder characterized by periods of depression and periods of abnormally elevated mood that last from days to weeks each. If the elevated mood is severe or associated with ...
has been estimated at 0.71. Twin studies have been limited by relatively small sample sizes but have indicated a substantial genetic contribution, as well as environmental influence. For bipolar I disorder, the rate at which
identical twin Twins are two offspring produced by the same pregnancy.MedicineNet > Definition of TwinLast Editorial Review: 19 June 2000 Twins can be either ''monozygotic'' ('identical'), meaning that they develop from one zygote, which splits and forms two ...
s (same genes) will both have bipolar I disorder (concordance) is around 40%, compared to about 5% in
fraternal twins Twins are two offspring produced by the same pregnancy.MedicineNet > Definition of TwinLast Editorial Review: 19 June 2000 Twins can be either ''monozygotic'' ('identical'), meaning that they develop from one zygote, which splits and forms two em ...
. A combination of bipolar I, II, and
cyclothymia Cyclothymia ( ), also known as cyclothymic disorder, psychothemia/psychothymia, bipolar III, affective personality disorder and cyclothymic personality disorder, is a mental and behavioural disorder that involves numerous periods of symptoms of ...
similarly produced rates of 42% and 11% (identical and fraternal twins, respectively). The rates of bipolar II combinations without bipolar I are lowerbipolar II at 23 and 17%, and bipolar II combining with cyclothymia at 33 and 14%which may reflect relatively higher genetic heterogeneity. 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.


Genetic

Behavioral genetic studies have suggested that many
chromosomal A chromosome is a long DNA molecule with part or all of the genetic material of an organism. In most chromosomes the very long thin DNA fibers are coated with packaging proteins; in eukaryotic cells the most important of these proteins ar ...
regions and candidate genes are related to bipolar disorder susceptibility with each gene exerting a mild to moderate effect. The risk of bipolar disorder is nearly ten-fold higher in
first-degree relatives A first-degree relative (FDR) is a person's parent (father or mother), full sibling (brother or sister) or child. It constitutes a category of family members that largely overlaps with the term nuclear family, but without spouses. If the persons ...
of those with bipolar disorder than in the general population; similarly, the risk of major depressive disorder is three times higher in relatives of those with bipolar disorder than in the general population. Although the first
genetic linkage Genetic linkage is the tendency of DNA sequences that are close together on a chromosome to be inherited together during the meiosis phase of sexual reproduction. Two genetic markers that are physically near to each other are unlikely to be sep ...
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 polymorphism In genetics, a single-nucleotide polymorphism (SNP ; plural SNPs ) is a germline substitution of a single nucleotide at a specific position in the genome. Although certain definitions require the substitution to be present in a sufficiently ...
s (SNPs) are associated with bipolar disorder, including variants within the genes ''
CACNA1C Calcium channel, voltage-dependent, L type, alpha 1C subunit (also known as Cav1.2) is a protein that in humans is encoded by the ''CACNA1C'' gene. Cav1.2 is a subunit of L-type voltage-dependent calcium channel. Structure and function This ...
'', '' 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 A meta-analysis is a statistical analysis that combines the results of multiple scientific studies. Meta-analyses can be performed when there are multiple scientific studies addressing the same question, with each individual study reporting m ...
, but this association disappeared after correction for multiple testing. On the other hand, two polymorphisms in ''
TPH2 Tryptophan hydroxylase 2 (TPH2) is an isozyme of tryptophan hydroxylase found in vertebrates. In humans, TPH2 is primarily expressed in the serotonergic neurons of the brain, with the highest expression in the raphe nucleus of the midbrain. Until ...
'' 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 The adrenergic receptors or adrenoceptors are a class of G protein-coupled receptors that are targets of many catecholamines like norepinephrine (noradrenaline) and epinephrine (adrenaline) produced by the body, but also many medications like bet ...
signaling,
Phospholipase C Phospholipase C (PLC) is a class of membrane-associated enzymes that cleave phospholipids just before the phosphate group (see figure). It is most commonly taken to be synonymous with the human forms of this enzyme, which play an important role ...
signaling,
glutamate Glutamic acid (symbol Glu or E; the ionic form is known as glutamate) is an α-amino acid that is used by almost all living beings in the biosynthesis of proteins. It is a non-essential nutrient for humans, meaning that the human body can synt ...
receptor signaling, cardiac hypertrophy signaling, Wnt signaling, Notch signaling, and
endothelin 1 Endothelin 1 (ET-1), also known as preproendothelin-1 (PPET1), is a potent vasoconstrictor peptide produced by vascular endothelial cells. The protein encoded by this gene ''EDN1'' is proteolytically processed to release endothelin 1. Endothe ...
signaling. Of the 16 genes identified in these pathways, three were found to be dysregulated in the
dorsolateral prefrontal cortex The dorsolateral prefrontal cortex (DLPFC or DL-PFC) is an area in the prefrontal cortex of the primate brain. It is one of the most recently derived parts of the human brain. It undergoes a prolonged period of maturation which lasts until adult ...
portion of the brain in post-mortem studies: ''
CACNA1C Calcium channel, voltage-dependent, L type, alpha 1C subunit (also known as Cav1.2) is a protein that in humans is encoded by the ''CACNA1C'' gene. Cav1.2 is a subunit of L-type voltage-dependent calcium channel. Structure and function This ...
'', ''
GNG2 Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 is a protein that in humans is encoded by the ''GNG2'' gene. Heterotrimeric G proteins G proteins, also known as guanine nucleotide-binding proteins, are a family of prote ...
'', and '' ITPR2''. Bipolar disorder is associated with reduced expression of specific
DNA repair DNA repair is a collection of processes by which a cell identifies and corrects damage to the DNA molecules that encode its genome. In human cells, both normal metabolic activities and environmental factors such as radiation can cause DNA d ...
enzymes and increased levels of oxidative DNA damages.


Environmental

Psychosocial The psychosocial approach looks at individuals in the context of the combined influence that psychological factors and the surrounding social environment have on their physical and mental wellness and their ability to function. This approach is ...
factors play a significant role in the development and course of bipolar disorder, and individual psychosocial variables may interact with genetic dispositions. Recent life events and interpersonal relationships likely contribute to the onset and recurrence of bipolar mood episodes, just as they do for unipolar depression. In surveys, 30–50% of adults diagnosed with bipolar disorder report traumatic/abusive experiences in childhood, which is associated with earlier onset, a higher rate of suicide attempts, and more co-occurring disorders such as
post-traumatic stress disorder Post-traumatic stress disorder (PTSD) is a mental and behavioral disorder that can develop because of exposure to a traumatic event, such as sexual assault, warfare, traffic collisions, child abuse, domestic violence, or other threats o ...
. The number of reported stressful events in childhood is higher in those with an adult diagnosis of bipolar spectrum disorder than in those without, particularly events stemming from a harsh environment rather than from the child's own behavior. Acutely, mania can be induced by
sleep deprivation Sleep deprivation, also known as sleep insufficiency or sleeplessness, is the condition of not having adequate duration and/or quality of sleep to support decent alertness, performance, and health. It can be either chronic or acute and may vary ...
in around 30% of people with bipolar disorder.


Neurological

Less commonly, bipolar disorder or a bipolar-like disorder may occur as a result of or in association with a neurological condition or injury including
stroke A stroke is a disease, medical condition in which poor cerebral circulation, blood flow to the brain causes cell death. There are two main types of stroke: brain ischemia, ischemic, due to lack of blood flow, and intracranial hemorrhage, hemorr ...
,
traumatic brain injury A traumatic brain injury (TBI), also known as an intracranial injury, is an injury to the brain caused by an external force. TBI can be classified based on severity (ranging from mild traumatic brain injury TBI/concussionto severe traumatic br ...
, HIV infection,
multiple sclerosis Multiple (cerebral) sclerosis (MS), also known as encephalomyelitis disseminata or disseminated sclerosis, is the most common demyelinating disease, in which the insulating covers of nerve cells in the brain and spinal cord are damaged. This ...
,
porphyria Porphyria is a group of liver disorders in which substances called porphyrins build up in the body, negatively affecting the skin or nervous system. The types that affect the nervous system are also known as acute porphyria, as symptoms are ...
, and rarely
temporal lobe epilepsy Temporal lobe epilepsy (TLE) is a chronic disorder of the nervous system which is characterized by recurrent, unprovoked focal seizures that originate in the temporal lobe of the brain and last about one or two minutes. TLE is the most common ...
.


Proposed mechanisms

The precise mechanisms that cause bipolar disorder are not well understood. Bipolar disorder is thought to be associated with abnormalities in the structure and function of certain brain areas responsible for cognitive tasks and the processing of emotions. A neurologic model for bipolar disorder proposes that the emotional circuitry of the brain can be divided into two main parts. The ventral system (regulates emotional perception) includes brain structures such as the
amygdala The amygdala (; plural: amygdalae or amygdalas; also '; Latin from Greek, , ', 'almond', 'tonsil') is one of two almond-shaped clusters of nuclei located deep and medially within the temporal lobes of the brain's cerebrum in complex ver ...
, insula, ventral
striatum The striatum, or corpus striatum (also called the striate nucleus), is a nucleus (a cluster of neurons) in the subcortical basal ganglia of the forebrain. The striatum is a critical component of the motor and reward systems; receives gluta ...
, ventral
anterior cingulate cortex In the human brain, the anterior cingulate cortex (ACC) is the frontal part of the cingulate cortex that resembles a "collar" surrounding the frontal part of the corpus callosum. It consists of Brodmann areas 24, 32, and 33. It is involve ...
, and the
prefrontal cortex In mammalian brain anatomy, the prefrontal cortex (PFC) covers the front part of the frontal lobe of the cerebral cortex. The PFC contains the Brodmann areas BA8, BA9, BA10, BA11, BA12, BA13, BA14, BA24, BA25, BA32, BA44, BA45, BA ...
. The dorsal system (responsible for emotional regulation) includes the
hippocampus The hippocampus (via Latin from Greek , 'seahorse') is a major component of the brain of humans and other vertebrates. Humans and other mammals have two hippocampi, one in each side of the brain. The hippocampus is part of the limbic syste ...
, dorsal anterior cingulate cortex, and other parts of the prefrontal cortex. The model hypothesizes that bipolar disorder may occur when the ventral system is overactivated and the dorsal system is underactivated. Other models suggest the ability to regulate emotions is disrupted in people with bipolar disorder and that dysfunction of the ventricular prefrontal cortex (vPFC) is crucial to this disruption.
Meta-analyses A meta-analysis is a statistical analysis that combines the results of multiple scientific studies. Meta-analyses can be performed when there are multiple scientific studies addressing the same question, with each individual study reporting m ...
of structural MRI studies have shown that certain brain regions (e.g., the left rostral
anterior cingulate cortex In the human brain, the anterior cingulate cortex (ACC) is the frontal part of the cingulate cortex that resembles a "collar" surrounding the frontal part of the corpus callosum. It consists of Brodmann areas 24, 32, and 33. It is involve ...
, fronto-insular cortex, ventral prefrontal cortex, and
claustrum The claustrum (Latin, meaning "to close" or "to shut") is a thin, bilateral collection of neurons and supporting glial cells, that connects to cortical (e.g., the pre-frontal cortex) and subcortical regions (e.g., the thalamus) of the brain. It ...
) are smaller in people with bipolar disorder, whereas other regions are larger ( lateral ventricles,
globus pallidus The globus pallidus (GP), also known as paleostriatum or dorsal pallidum, is a subcortical structure of the brain. It consists of two adjacent segments, one external, known in rodents simply as the globus pallidus, and one internal, known in rode ...
, subgenual anterior cingulate, and the amygdala). Additionally, these meta-analyses found that people with bipolar disorder have higher rates of deep
white matter White matter refers to areas of the central nervous system (CNS) that are mainly made up of myelinated axons, also called tracts. Long thought to be passive tissue, white matter affects learning and brain functions, modulating the distribu ...
hyperintensities. Functional MRI findings suggest that the vPFC regulates the
limbic system The limbic system, also known as the paleomammalian cortex, is a set of brain structures located on both sides of the thalamus, immediately beneath the medial temporal lobe of the cerebrum primarily in the forebrain.Schacter, Daniel L. 2012. ''P ...
, especially the amygdala. In people with bipolar disorder, decreased vPFC 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 vPFC activity to the levels in non-manic people, suggesting that vPFC 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 vPFC. Manic episodes appear to be associated with decreased activation of the right vPFC whereas depressive episodes are associated with decreased activation of the left vPFC. 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 The lingual gyrus, also known as the ''medial'' occipitotemporal gyrus, is a brain structure that is linked to processing vision, especially related to letters. It is thought to also play a role in analysis of logical conditions (i.e., logical ord ...
compared to people without bipolar disorder. In contrast, they demonstrate decreased activity in the inferior
frontal cortex The frontal lobe is the largest of the four major lobes of the brain in mammals, and is located at the front of each cerebral hemisphere (in front of the parietal lobe and the temporal lobe). It is parted from the parietal lobe by a groove be ...
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. 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 A mitochondrion (; ) is an organelle found in the cells of most Eukaryotes, such as animals, plants and fungi. Mitochondria have a double membrane structure and use aerobic respiration to generate adenosine triphosphate (ATP), which is used ...
and a sodium
ATPase ATPases (, Adenosine 5'-TriPhosphatase, adenylpyrophosphatase, ATP monophosphatase, triphosphatase, SV40 T-antigen, ATP hydrolase, complex V (mitochondrial electron transport), (Ca2+ + Mg2+)-ATPase, HCO3−-ATPase, adenosine triphosphatase) are ...
pump A pump is a device that moves fluids (liquids or gases), or sometimes slurries, by mechanical action, typically converted from electrical energy into hydraulic energy. Pumps can be classified into three major groups according to the method they ...
.
Circadian rhythm A circadian rhythm (), or circadian cycle, is a natural, internal process that regulates the sleep–wake cycle and repeats roughly every 24 hours. It can refer to any process that originates within an organism (i.e., endogenous) and responds to ...
s and regulation of the hormone
melatonin Melatonin is a natural product found in plants and animals. It is primarily known in animals as a hormone released by the pineal gland in the brain at night, and has long been associated with control of the sleep–wake cycle. In vertebrat ...
also seem to be altered.
Dopamine Dopamine (DA, a contraction of 3,4-dihydroxyphenethylamine) is a neuromodulatory molecule that plays several important roles in cells. It is an organic chemical of the catecholamine and phenethylamine families. Dopamine constitutes about 80% o ...
, a
neurotransmitter A neurotransmitter is a signaling molecule secreted by a neuron to affect another cell across a synapse. The cell receiving the signal, any main body part or target cell, may be another neuron, but could also be a gland or muscle cell. Neu ...
responsible for mood cycling, has increased transmission during the manic phase. The dopamine hypothesis states that the increase in dopamine results in secondary
homeostatic In biology, homeostasis (British also homoeostasis) (/hɒmɪə(ʊ)ˈsteɪsɪs/) is the state of steady internal, physical, and chemical conditions maintained by living systems. This is the condition of optimal functioning for the organism an ...
downregulation In the biological context of organisms' production of gene products, downregulation is the process by which a cell decreases the quantity of a cellular component, such as RNA or protein, in response to an external stimulus. The complementary pr ...
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 Glutamic acid (symbol Glu or E; the ionic form is known as glutamate) is an α-amino acid that is used by almost all living beings in the biosynthesis of proteins. It is a non-essential nutrient for humans, meaning that the human body can synt ...
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 Inositol, or more precisely ''myo''-inositol, is a carbocyclic sugar that is abundant in the brain and other mammalian tissues; it mediates cell signal transduction in response to a variety of hormones, neurotransmitters, and growth factors and ...
levels, inhibition of cAMP signaling, 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 Serotonin () or 5-hydroxytryptamine (5-HT) is a monoamine neurotransmitter. Its biological function is complex and multifaceted, modulating mood, cognition, reward, learning, memory, and numerous physiological processes such as vomiting and va ...
, are present in the
cerebrospinal fluid Cerebrospinal fluid (CSF) is a clear, colorless body fluid found within the tissue that surrounds the brain and spinal cord of all vertebrates. CSF is produced by specialised ependymal cells in the choroid plexus of the ventricles of the ...
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 Dopamine (DA, a contraction of 3,4-dihydroxyphenethylamine) is a neuromodulatory molecule that plays several important roles in cells. It is an organic chemical of the catecholamine and phenethylamine families. Dopamine constitutes about 80% o ...
agonists to stimulate mania in people with bipolar disorder. Decreased sensitivity of regulatory α2
adrenergic receptor The adrenergic receptors or adrenoceptors are a class of G protein-coupled receptors that are targets of many catecholamines like norepinephrine (noradrenaline) and epinephrine (adrenaline) produced by the body, but also many medications like bet ...
s as well as increased cell counts in the
locus coeruleus The locus coeruleus () (LC), also spelled locus caeruleus or locus ceruleus, is a nucleus in the pons of the brainstem involved with physiological responses to stress and panic. It is a part of the reticular activating system. The locus coer ...
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 -Tyrosine or tyrosine (symbol Tyr or Y) or 4-hydroxyphenylalanine is one of the 20 standard amino acids that are used by cells to synthesize proteins. It is a non-essential amino acid with a polar side group. The word "tyrosine" is from the G ...
depletion was found to reduce the effects of
methamphetamine Methamphetamine (contracted from ) is a potent central nervous system (CNS) stimulant that is mainly used as a recreational drug and less commonly as a second-line treatment for attention deficit hyperactivity disorder and obesity. Methamp ...
in people with bipolar disorder as well as symptoms of mania, implicating dopamine in mania.
VMAT2 The solute carrier family 18 member 2 (SLC18A2) also known as vesicular monoamine transporter 2 (VMAT2) is a protein that in humans is encoded by the ''SLC18A2'' gene. SLC18A2 is an integral membrane protein that transports monoamines—partic ...
binding was found to be increased in one study of people with bipolar mania.


Diagnosis

Bipolar disorder is commonly diagnosed during adolescence or early adulthood, but onset can occur throughout life. Its diagnosis is based on the self-reported experiences of the individual, abnormal behavior reported by family members, friends or co-workers, observable signs of illness as assessed by a clinician, and ideally a medical work-up to rule out other causes. Caregiver-scored rating scales, specifically from the mother, have shown to be more accurate than teacher and youth-scored reports in identifying youths with bipolar disorder. Assessment is usually done on an outpatient basis; admission to an inpatient facility is considered if there is a risk to oneself or others. The most widely used criteria for diagnosing bipolar disorder are from the
American Psychiatric Association The American Psychiatric Association (APA) is the main professional organization of psychiatrists and trainee psychiatrists in the United States, and the largest psychiatric organization in the world. It has more than 37,000 members are invo ...
's (APA) ''Diagnostic and Statistical Manual of Mental Disorders'', Fifth Edition (DSM-5) and the
World Health Organization The World Health Organization (WHO) is a specialized agency of the United Nations responsible for international public health. The WHO Constitution states its main objective as "the attainment by all peoples of the highest possible level o ...
'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 The ''Diagnostic and Statistical Manual of Mental Disorders'' (DSM; latest edition: DSM-5-TR, published in March 2022) is a publication by the American Psychiatric Association (APA) for the classification of mental disorders using a common langua ...
. This work has influenced the upcoming eleventh revision of the ICD, which includes the various diagnoses within the bipolar spectrum of the DSM-V. Several rating scales 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 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.


Differential diagnosis

Bipolar disorder is classified by the
International Classification of Diseases The International Classification of Diseases (ICD) is a globally used diagnostic tool for epidemiology, health management and clinical purposes. The ICD is maintained by the World Health Organization (WHO), which is the directing and coordinating ...
as a mental and behavioural
disorder Disorder may refer to randomness, non-order, or no intelligible pattern. Disorder may also refer to: Healthcare * Disorder (medicine), a functional abnormality or disturbance * Mental disorder or psychological disorder, a psychological pattern ...
. Mental disorders that can have symptoms similar to those seen in bipolar disorder include
schizophrenia Schizophrenia is a mental disorder characterized by continuous or relapsing episodes of psychosis. Major symptoms include hallucinations (typically hearing voices), delusions, and disorganized thinking. Other symptoms include social w ...
, major depressive disorder, attention deficit hyperactivity disorder (ADHD), and certain personality disorders, such as
borderline personality disorder Borderline personality disorder (BPD), also known as emotionally unstable personality disorder (EUPD), is a personality disorder characterized by a long-term pattern of unstable interpersonal relationships, distorted sense of self, and strong ...
. A key difference between bipolar disorder and borderline personality disorder is the nature of the mood swings; in contrast to the sustained changes to mood over days to weeks or longer, those of the latter condition (more accurately called emotional dysregulation) are sudden and often short-lived, and secondary to social stressors. 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 Multiple (cerebral) sclerosis (MS), also known as encephalomyelitis disseminata or disseminated sclerosis, is the most common demyelinating disease, in which the insulating covers of nerve cells in the brain and spinal cord are damaged. This ...
, complex partial seizures,
stroke A stroke is a disease, medical condition in which poor cerebral circulation, blood flow to the brain causes cell death. There are two main types of stroke: brain ischemia, ischemic, due to lack of blood flow, and intracranial hemorrhage, hemorr ...
s, brain tumors, Wilson's disease,
traumatic brain injury A traumatic brain injury (TBI), also known as an intracranial injury, is an injury to the brain caused by an external force. TBI can be classified based on severity (ranging from mild traumatic brain injury TBI/concussionto severe traumatic br ...
,
Huntington's disease Huntington's disease (HD), also known as Huntington's chorea, is a neurodegenerative disease that is mostly inherited. The earliest symptoms are often subtle problems with mood or mental abilities. A general lack of coordination and an uns ...
, and complex
migraine Migraine (, ) is a common neurological disorder characterized by recurrent headaches. Typically, the associated headache affects one side of the head, is pulsating in nature, may be moderate to severe in intensity, and could last from a few hou ...
s can mimic features of bipolar disorder. An EEG may be used to exclude
neurological disorder A neurological disorder is any disorder of the nervous system. Structural, biochemical or electrical abnormalities in the brain, spinal cord or other nerves can result in a range of symptoms. Examples of symptoms include paralysis, muscle weakn ...
s such as
epilepsy Epilepsy is a group of non-communicable neurological disorders characterized by recurrent epileptic seizures. Epileptic seizures can vary from brief and nearly undetectable periods to long periods of vigorous shaking due to abnormal electrica ...
, and a CT scan or MRI of the head may be used to exclude brain lesions. Additionally, disorders of the
endocrine system The endocrine system is a messenger system comprising feedback loops of the hormones released by internal glands of an organism directly into the circulatory system, regulating distant target organs. In vertebrates, the hypothalamus is th ...
such as
hypothyroidism Hypothyroidism (also called ''underactive thyroid'', ''low thyroid'' or ''hypothyreosis'') is a disorder of the endocrine system in which the thyroid gland does not produce enough thyroid hormone. It can cause a number of symptoms, such as ...
,
hyperthyroidism Hyperthyroidism is the condition that occurs due to excessive production of thyroid hormones by the thyroid gland. Thyrotoxicosis is the condition that occurs due to excessive thyroid hormone of any cause and therefore includes hyperthyroidis ...
, and
Cushing's disease Cushing's disease is one cause of Cushing's syndrome characterised by increased secretion of adrenocorticotropic hormone (ACTH) from the anterior pituitary (secondary hypercortisolism). This is most often as a result of a pituitary adenoma (spe ...
are in the differential as is the
connective tissue disease A connective tissue disease (collagenosis) is any disease that has the connective tissues of the body as a target of pathology. Connective tissue is any type of biological tissue with an extensive extracellular matrix that supports, binds togeth ...
systemic lupus erythematosus Lupus, technically known as systemic lupus erythematosus (SLE), is an autoimmune disease in which the body's immune system mistakenly attacks healthy tissue in many parts of the body. Symptoms vary among people and may be mild to severe. Commo ...
. Infectious causes of mania that may appear similar to bipolar mania include
herpes encephalitis Herpesviral encephalitis, or herpes simplex encephalitis (HSE), is encephalitis due to herpes simplex virus. It is estimated to affect at least 1 in 500,000 individuals per year, and some studies suggest an incidence rate of 5.9 cases per 100,000 ...
, HIV,
influenza Influenza, commonly known as "the flu", is an infectious disease caused by influenza viruses. Symptoms range from mild to severe and often include fever, runny nose, sore throat, muscle pain, headache, coughing, and fatigue. These symptom ...
, or neurosyphilis. Certain vitamin deficiencies such as pellagra (
niacin Niacin, also known as nicotinic acid, is an organic compound and a form of vitamin B3, an essential human nutrient. It can be manufactured by plants and animals from the amino acid tryptophan. Niacin is obtained in the diet from a variet ...
deficiency),
Vitamin B12 deficiency Vitamin B12 deficiency, also known as cobalamin deficiency, is the medical condition in which the blood and tissue have a lower than normal level of vitamin B12. Symptoms can vary from none to severe. Mild deficiency may have few or absent symp ...
,
folate deficiency Folate deficiency, also known as vitamin B9 deficiency, is a low level of folate and derivatives in the body. Signs of folate deficiency are often subtle. A low number of red blood cells (anemia) is a late finding in folate deficiency and folat ...
, and Wernicke Korsakoff syndrome ( thiamine deficiency) can also lead to mania. Common medications that can cause manic symptoms include antidepressants,
prednisone Prednisone is a glucocorticoid medication mostly used to suppress the immune system and decrease inflammation in conditions such as asthma, COPD, and rheumatologic diseases. It is also used to treat high blood calcium due to cancer and ad ...
,
Parkinson's disease Parkinson's disease (PD), or simply Parkinson's, is a long-term degenerative disorder of the central nervous system that mainly affects the motor system. The symptoms usually emerge slowly, and as the disease worsens, non-motor symptoms beco ...
medications,
thyroid hormone File:Thyroid_system.svg, upright=1.5, The thyroid system of the thyroid hormones T3 and T4 rect 376 268 820 433 Thyroid-stimulating hormone rect 411 200 849 266 Thyrotropin-releasing hormone rect 297 168 502 200 Hypothalamus rect 66 216 386 25 ...
, stimulants (including
cocaine Cocaine (from , from , ultimately from Quechua: ''kúka'') is a central nervous system (CNS) stimulant mainly used recreationally for its euphoric effects. It is primarily obtained from the leaves of two Coca species native to South Am ...
and methamphetamine), and certain
antibiotic An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting bacterial infections, and antibiotic medications are widely used in the treatment and prevention ...
s.


Bipolar spectrum

Bipolar spectrum disorders include: bipolar I disorder, bipolar II disorder, cyclothymic disorder and cases where subthreshold symptoms are found to cause clinically significant impairment or distress. These disorders involve major depressive episodes that alternate with manic or hypomanic episodes, or with mixed episodes that feature symptoms of both mood states. The concept of the bipolar
spectrum A spectrum (plural ''spectra'' or ''spectrums'') is a condition that is not limited to a specific set of values but can vary, without gaps, across a continuum. The word was first used scientifically in optics to describe the rainbow of colors ...
is similar to that of
Emil Kraepelin Emil Wilhelm Georg Magnus Kraepelin (; ; 15 February 1856 – 7 October 1926) was a German psychiatrist. H. J. Eysenck's ''Encyclopedia of Psychology'' identifies him as the founder of modern scientific psychiatry, psychopharmacology and psych ...
's original concept of manic depressive illness. Bipolar II disorder was established as a diagnosis in 1994 within DSM IV; though debate continues over whether it is a distinct entity, part of a spectrum, or exists at all.


Criteria and subtypes

The DSM and the ICD characterize bipolar disorder as a spectrum of disorders occurring on a continuum. The DSM-5 and ICD-11 lists three specific subtypes: *
Bipolar I disorder Bipolar I disorder (BD-I; pronounced "type one bipolar disorder") is a type of bipolar spectrum disorder characterized by the occurrence of at least one manic episode, with or without mixed or psychotic features. Most people also, at other ti ...
: At least one manic episode is necessary to make the diagnosis; depressive episodes are common in the vast majority of cases with bipolar disorder I, but are unnecessary for the diagnosis. Specifiers such as "mild, moderate, moderate-severe, severe" and "with psychotic features" should be added as applicable to indicate the presentation and course of the disorder. *
Bipolar II disorder Bipolar II disorder (BP-II) is a mood disorder on the bipolar spectrum, characterized by at least one episode of hypomania and at least one episode of major depression. Diagnosis for BP-II requires that the individual must never have experien ...
: No manic episodes and one or more hypomanic episodes and one or more major depressive episodes. Hypomanic episodes do not go to the full extremes of mania (''i.e.'', do not usually cause severe social or occupational impairment, and are without psychosis), and this can make bipolar II more difficult to diagnose, since the hypomanic episodes may simply appear as periods of successful high productivity and are reported less frequently than a distressing, crippling depression. *
Cyclothymia Cyclothymia ( ), also known as cyclothymic disorder, psychothemia/psychothymia, bipolar III, affective personality disorder and cyclothymic personality disorder, is a mental and behavioural disorder that involves numerous periods of symptoms of ...
: A history of hypomanic episodes with periods of depression that do not meet criteria for major depressive episodes. 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.


Rapid cycling

Most people who meet criteria for bipolar disorder experience a number of episodes, on average 0.4 to 0.7 per year, lasting three to six months. ''Rapid cycling'', however, is a course specifier that may be applied to any bipolar subtype. It is defined as having four or more mood disturbance episodes within a one-year span. Rapid cycling is usually temporary but is common amongst people with bipolar disorder and affects between 25.8 and 45.3% of them at some point in their life. These episodes are separated from each other by a remission (partial or full) for at least two months or a switch in mood polarity (i.e., from a depressive episode to a manic episode or vice versa). The definition of rapid cycling most frequently cited in the literature (including the DSM-V and ICD-11) is that of Dunner and Fieve: at least four major depressive, manic, hypomanic or mixed episodes during a 12-month period. The literature examining the pharmacological treatment of rapid cycling is sparse and there is no clear consensus with respect to its optimal pharmacological management. People with the rapid cycling or ultradian subtypes of bipolar disorder tend to be more difficult to treat and less responsive to medications than other people with bipolar disorder.


Coexisting psychiatric conditions

The diagnosis of bipolar disorder can be complicated by coexisting (
comorbid In medicine, comorbidity - from Latin morbus ("sickness"), co ("together"), -ity (as if - several sicknesses together) - is the presence of one or more additional conditions often co-occurring (that is, concomitant or concurrent) with a primary ...
) psychiatric conditions including
obsessive–compulsive disorder Obsessive–compulsive disorder (OCD) is a mental and behavioral disorder in which an individual has intrusive thoughts and/or feels the need to perform certain routines repeatedly to the extent where it induces distress or impairs general ...
, substance-use disorder,
eating disorder An eating disorder is a mental disorder defined by abnormal eating behaviors that negatively affect a person's physical or mental health. Only one eating disorder can be diagnosed at a given time. Types of eating disorders include binge eating d ...
s,
attention deficit hyperactivity disorder Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterised by excessive amounts of inattention, hyperactivity, and impulsivity that are pervasive, impairing in multiple contexts, and otherwise age-inap ...
, social phobia,
premenstrual syndrome Premenstrual syndrome (PMS) refers to emotional and physical symptoms that regularly occur in the one to two weeks before the start of each menstrual period. Symptoms resolve around the time menstrual bleeding begins. Different women experien ...
(including
premenstrual dysphoric disorder Premenstrual dysphoric disorder (PMDD) is a mood disorder characterized by emotional, cognitive, and physical symptoms that cause significant distress or impairment in menstruating women during the luteal phase of the menstrual cycle. The symptom ...
), or
panic disorder Panic disorder is a mental and behavioral disorder, specifically an anxiety disorder characterized by reoccurring unexpected panic attacks. Panic attacks are sudden periods of intense fear that may include palpitations, sweating, shaking, short ...
. A thorough longitudinal analysis of symptoms and episodes, assisted if possible by discussions with friends and family members, is crucial to establishing a treatment plan where these comorbidities exist. Children of parents with bipolar disorder more frequently have other mental health problems.


Children

In the 1920s, Kraepelin noted that manic episodes are rare before puberty. In general, bipolar disorder in children was not recognized in the first half of the twentieth century. This issue diminished with an increased following of the DSM criteria in the last part of the twentieth century. The diagnosis of childhood bipolar disorder, while formerly controversial, has gained greater acceptance among childhood and adolescent psychiatrists. American children and adolescents diagnosed with bipolar disorder in
community hospital A community hospital can be purely a nominal designation or have a more specific meaning. When specific, it refers to a hospital that is accessible to the general public, and provides a general or specific medical care which is usually short-term, ...
s increased 4-fold reaching rates of up to 40% in 10 years around the beginning of the 21st century, while in outpatient clinics it doubled reaching 6%. Studies using DSM criteria show that up to 1% of youth may have bipolar disorder. The DSM-5 has established a diagnosis— disruptive mood dysregulation disorder—that covers children with long-term, persistent irritability that had at times been misdiagnosed as having bipolar disorder, distinct from irritability in bipolar disorder that is restricted to discrete mood episodes.


Elderly

Bipolar disorder is uncommon in older patients, with a measured lifetime prevalence of 1% in over 60s and a 12-month prevalence of 0.10.5% in people over 65. Despite this, it is overrepresented in psychiatric admissions, making up 48% of inpatient admission to aged care psychiatry units, and the incidence of mood disorders is increasing overall with the aging population. Depressive episodes more commonly present with sleep disturbance, fatigue, hopelessness about the future, slowed thinking, and poor concentration and memory; the last three symptoms are seen in what is known as pseudodementia. Clinical features also differ between those with late-onset bipolar disorder and those who developed it early in life; the former group present with milder manic episodes, more prominent cognitive changes and have a background of worse psychosocial functioning, while the latter present more commonly with mixed affective episodes, and have a stronger family history of illness. Older people with bipolar disorder experience cognitive changes, particularly in executive functions such as abstract thinking and switching cognitive sets, as well as concentrating for long periods and decision-making.


Prevention

Attempts at prevention of bipolar disorder have focused on stress (such as childhood adversity or highly conflictual families) which, although not a diagnostically specific causal agent for bipolar, does place genetically and biologically vulnerable individuals at risk for a more severe course of illness. Longitudinal studies have indicated that full-blown manic stages are often preceded by a variety of prodromal clinical features, providing support for the occurrence of an at-risk state of the disorder when an early intervention might prevent its further development and/or improve its outcome.


Management

The aim of management is to treat acute episodes safely with medication and work with the patient in long-term maintenance to prevent further episodes and optimise function using a combination of pharmacological and
psychotherapeutic Psychotherapy (also psychological therapy, talk therapy, or talking therapy) is the use of psychological methods, particularly when based on regular personal interaction, to help a person change behavior, increase happiness, and overcome prob ...
techniques. Hospitalization may be required especially with the manic episodes present in bipolar I. This can be voluntary or (local legislation permitting) involuntary. Long-term inpatient stays are now less common due to
deinstitutionalization Deinstitutionalisation (or deinstitutionalization) is the process of replacing long-stay psychiatric hospitals with less isolated community mental health services for those diagnosed with a mental disorder or developmental disability. In the la ...
, although these can still occur. Following (or in lieu of) a hospital admission, support services available can include
drop-in center A drop-in center is a service agency for either the mentally ill, homeless people, teenagers, and other communities that offers a place where people can go to obtain food and other services. A mental health drop-in center can provide a friendly en ...
s, visits from members of a
community mental health team Center for Mental Health Services''(CMHS), also known as community mental health teams (CMHT) in the United Kingdom, support or treat people with mental disorders (mental illness or mental health difficulties) in a domiciliary setting, instead o ...
or an
Assertive Community Treatment Assertive community treatment (ACT) is an intensive and highly integrated approach for community mental health service delivery. ACT teams serve individuals that have been diagnosed with serious and persistent forms of mental illness, predominantly ...
team,
supported employment Supported employment refers to service provisions wherein people with disabilities, including intellectual disabilities, mental health, and traumatic brain injury, among others, are assisted with obtaining and maintaining employment. Supported e ...
, patient-led support groups, and intensive outpatient programs. These are sometimes referred to as partial-inpatient programs.


Psychosocial

Psychotherapy Psychotherapy (also psychological therapy, talk therapy, or talking therapy) is the use of psychological methods, particularly when based on regular personal interaction, to help a person change behavior, increase happiness, and overcome pro ...
aims to assist a person with bipolar disorder in accepting and understanding their diagnosis, coping with various types of stress, improving their interpersonal relationships, and recognizing prodromal symptoms before full-blown recurrence.
Cognitive behavioral therapy Cognitive behavioral therapy (CBT) is a psycho-social intervention that aims to reduce symptoms of various mental health conditions, primarily depression and anxiety disorders. CBT focuses on challenging and changing cognitive distortions (suc ...
, family-focused therapy, and psychoeducation have the most evidence for efficacy in regard to relapse prevention, while interpersonal and social rhythm therapy and cognitive-behavioral therapy appear the most effective in regard to residual depressive symptoms. Most studies have been based only on bipolar I, however, and treatment during the acute phase can be a particular challenge. Some clinicians emphasize the need to talk with individuals experiencing mania, to develop a
therapeutic alliance A therapeutic alliance, or working alliance, is a partnership between a patient and his or her therapist that allows them to achieve goals through agreed-upon tasks. The concept of therapeutic alliance dates back to Sigmund Freud. Over the cour ...
in support of recovery.


Medication

Medications are often prescribed to help improve symptoms of bipolar disorder. Medications approved for treating bipolar disorder including mood stabilizers, antipsychotics, and antidepressants. Sometimes a combination of medications may also be suggested. The choice of medications may differ depending on the bipolar disorder episode type or if the person is experiencing unipolar or bipolar depression. Other factors to consider when deciding on an appropriate treatment approach includes if the person has any comorbidities, their response to previous therapies, adverse effects, and the desire of the person to be treated.


Mood stabilizers

Lithium and the
anticonvulsant Anticonvulsants (also known as antiepileptic drugs or recently as antiseizure drugs) are a diverse group of pharmacological agents used in the treatment of epileptic seizures. Anticonvulsants are also increasingly being used in the treatment of ...
s
carbamazepine Carbamazepine (CBZ), sold under the trade name Tegretol among others, is an anticonvulsant medication used primarily in the treatment of epilepsy and neuropathic pain. It is used as an adjunctive treatment in schizophrenia along with other m ...
,
lamotrigine Lamotrigine, sold under the brand name Lamictal among others, is a medication used to treat epilepsy and stabilize mood in bipolar disorder. For epilepsy, this includes focal seizures, tonic-clonic seizures, and seizures in Lennox-Gastaut sy ...
, and valproic acid are classed as mood stabilizers due to their effect on the mood states in bipolar disorder. Lithium has the best overall evidence and is considered an effective treatment for acute manic episodes, preventing relapses, and bipolar depression. Lithium reduces the risk of suicide, self-harm, and death in people with bipolar disorder. Lithium is preferred for long-term mood stabilization. Lithium treatment is also associated with adverse effects and it has been shown to erode kidney and thyroid function over extended periods. Valproate has become a commonly prescribed treatment and effectively treats manic episodes. Carbamazepine is less effective in preventing relapse than lithium or valproate. Lamotrigine has some efficacy in treating depression, and this benefit is greatest in more severe depression. It has also been shown to have some benefit in preventing bipolar disorder relapses, though there are concerns about the studies done, and is of no benefit in rapid cycling subtype of bipolar disorder. 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. The effectiveness of
topiramate Topiramate, sold under the brand name Topamax among others, is a carbonic anhydrase inhibitor medication used to treat epilepsy and prevent migraines. It has also been used in alcohol dependence. For epilepsy this includes treatment for genera ...
is unknown. Carbamazepine 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 Schizoaffective disorder (SZA, SZD or SAD) is a mental disorder characterized by abnormal thought processes and an unstable mood. This diagnosis is made when the person has symptoms of both schizophrenia (usually psychosis) and a mood disorder: ...
. Mood stabilizers are used for long-term maintenance but have not demonstrated the ability to quickly treat acute bipolar depression.


Antipsychotics

Antipsychotic Antipsychotics, also known as neuroleptics, are a class of psychotropic medication primarily used to manage psychosis (including delusions, hallucinations, paranoia or disordered thought), principally in schizophrenia but also in a range of ...
medications are effective for short-term treatment of bipolar manic episodes and appear to be superior to lithium and anticonvulsants for this purpose. Atypical antipsychotics are also indicated for bipolar depression refractory to treatment with mood stabilizers.
Olanzapine Olanzapine (sold under the trade name Zyprexa among others) is an atypical antipsychotic primarily used to treat schizophrenia and bipolar disorder. For schizophrenia, it can be used for both new-onset disease and long-term maintenance. It is t ...
is effective in preventing relapses, although the supporting evidence is weaker than the evidence for lithium. A 2006 review found that haloperidol was an effective treatment for acute mania, limited data supported no difference in overall efficacy between haloperidol,
olanzapine Olanzapine (sold under the trade name Zyprexa among others) is an atypical antipsychotic primarily used to treat schizophrenia and bipolar disorder. For schizophrenia, it can be used for both new-onset disease and long-term maintenance. It is t ...
or risperidone, and that it could be less effective than aripiprazole.


Antidepressants

Antidepressants are not recommended for use alone in the treatment of bipolar disorder and do not provide any benefit over mood stabilizers. Atypical antipsychotic medications (e.g., aripiprazole) are preferred over antidepressants to augment the effects of mood stabilizers due to the lack of efficacy of antidepressants in bipolar disorder. Treatment of bipolar disorder using antidepressants carries a risk of affective switches; where a person switches from depression to manic or hypomanic phases. The risk of affective switches is higher in bipolar I depression; antidepressants are generally avoided in bipolar I disorder or only used with mood stabilizers when they are deemed necessary. There is also a risk of accelerating cycling between phases when antidepressants are used in bipolar disorder.


Combined treatment approaches

Antipsychotic Antipsychotics, also known as neuroleptics, are a class of psychotropic medication primarily used to manage psychosis (including delusions, hallucinations, paranoia or disordered thought), principally in schizophrenia but also in a range of ...
s and mood stabilizers used together are quicker and more effective at treating mania than either class of drug used alone. Some analyses indicate antipsychotics alone are also more effective at treating acute mania. A first-line treatment for depression in bipolar disorder is a combination of olanzapine and fluoxetine.


Other drugs

Short courses of
benzodiazepines Benzodiazepines (BZD, BDZ, BZs), sometimes called "benzos", are a class of depressant drugs whose core chemical structure is the fusion of a benzene ring and a diazepine ring. They are prescribed to treat conditions such as anxiety disorders, ...
are used in addition to other medications for calming effect until mood stabilizing become effective.
Electroconvulsive therapy Electroconvulsive therapy (ECT) is a psychiatric treatment where a generalized seizure (without muscular convulsions) is electrically induced to manage refractory mental disorders.Rudorfer, MV, Henry, ME, Sackeim, HA (2003)"Electroconvulsive th ...
(ECT) is an effective form of treatment for acute mood disturbances in those with bipolar disorder, especially when psychotic or
catatonic Catatonia is a complex neuropsychiatric behavioral syndrome that is characterized by abnormal movements, immobility, abnormal behaviors, and withdrawal. The onset of catatonia can be acute or subtle and symptoms can wax, wane, or change during ...
features are displayed. ECT is also recommended for use in pregnant women with bipolar disorder. It is unclear if
ketamine Ketamine is a dissociative anesthetic used medically for induction and maintenance of anesthesia. It is also used as a recreational drug. It is one of the safest anesthetics, as, in contrast with opiates, ether, and propofol, it suppress ...
(a common general dissociative anesthetic used in surgery) is useful in bipolar disorder. Gabapentin and pregabalin are not proven to be effective for treating bipolar disorder.


Children

Treating bipolar disorder in children involves medication and psychotherapy. The literature and research on the effects of psychosocial therapy on bipolar spectrum disorders are scarce, making it difficult to determine the efficacy of various therapies.
Mood stabilizer A mood stabilizer is a psychiatric medication used to treat mood disorders characterized by intense and sustained mood shifts, such as bipolar disorder and the bipolar type of schizoaffective disorder. Uses Mood stabilizers are best known for ...
s and atypical antipsychotics are commonly prescribed. Among the former,
lithium Lithium (from el, λίθος, lithos, lit=stone) is a chemical element with the symbol Li and atomic number 3. It is a soft, silvery-white alkali metal. Under standard conditions, it is the least dense metal and the least dense soli ...
is the only compound approved by the FDA for children. Psychological treatment combines normally education on the disease,
group therapy Group psychotherapy or group therapy is a form of psychotherapy in which one or more therapists treat a small group of clients together as a group. The term can legitimately refer to any form of psychotherapy when delivered in a group format, i ...
, and
cognitive behavioral therapy Cognitive behavioral therapy (CBT) is a psycho-social intervention that aims to reduce symptoms of various mental health conditions, primarily depression and anxiety disorders. CBT focuses on challenging and changing cognitive distortions (suc ...
. Long-term medication is often needed.


Resistance to treatment

The occurrence of poor response to treatment in has given support to the concept of resistance to treatment in bipolar disorder. Guidelines to the definition of such treatment resistance and evidence-based options for its management were reviewed in 2020.


Prognosis

A lifelong condition with periods of partial or full recovery in between recurrent episodes of relapse, bipolar disorder is considered to be a major health problem worldwide because of the increased rates of disability and premature mortality. It is also associated with co-occurring psychiatric and medical problems, higher rates of death from natural causes (e.g.,
cardiovascular disease Cardiovascular disease (CVD) is a class of diseases that involve the heart or blood vessels. CVD includes coronary artery diseases (CAD) such as angina and myocardial infarction (commonly known as a heart attack). Other CVDs include stroke, hea ...
), and high rates of initial under- or misdiagnosis, causing a delay in appropriate treatment and contributing to poorer prognoses. When compared to the general population, people with bipolar disorder also have higher rates of other serious medical comorbidities including
diabetes mellitus Diabetes, also known as diabetes mellitus, is a group of metabolic disorders characterized by a high blood sugar level ( hyperglycemia) over a prolonged period of time. Symptoms often include frequent urination, increased thirst and increased ...
, respiratory diseases, HIV, and
Hepatitis C Hepatitis C is an infectious disease caused by the hepatitis C virus (HCV) that primarily affects the liver; it is a type of viral hepatitis. During the initial infection people often have mild or no symptoms. Occasionally a fever, dark urine, ...
virus infection. After a diagnosis is made, it remains difficult to achieve complete remission of all symptoms with the currently available psychiatric medications and symptoms often become progressively more severe over time. 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 Self-harm is intentional behavior that is considered harmful to oneself. This is most commonly regarded as direct injury of one's own skin tissues usually without a suicidal intention. Other terms such as cutting, self-injury and self-mutilati ...
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.


Functioning

Changes in
cognitive Cognition refers to "the mental action or process of acquiring knowledge and understanding through thought, experience, and the senses". It encompasses all aspects of intellectual functions and processes such as: perception, attention, thought ...
processes and abilities are seen in mood disorders, with those of bipolar disorder being greater than those in major depressive disorder. These include reduced
attention Attention is the behavioral and cognitive process of selectively concentrating on a discrete aspect of information, whether considered subjective or objective, while ignoring other perceivable information. William James (1890) wrote that "Att ...
al and
executive Executive ( exe., exec., execu.) may refer to: Role or title * Executive, a senior management role in an organization ** Chief executive officer (CEO), one of the highest-ranking corporate officers (executives) or administrators ** Executive di ...
capabilities and impaired
memory Memory is the faculty of the mind by which data or information is encoded, stored, and retrieved when needed. It is the retention of information over time for the purpose of influencing future action. If past events could not be remember ...
. People with bipolar disorder often experience a decline in cognitive functioning during (or possibly before) their first episode, after which a certain degree of cognitive dysfunction typically becomes permanent, with more severe impairment during acute phases and moderate impairment during periods of remission. As a result, two-thirds of people with BD continue to experience impaired psychosocial functioning in between episodes even when their mood symptoms are in full remission. A similar pattern is seen in both BD-I and BD-II, but people with BD-II experience a lesser degree of impairment. 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.


Recovery and recurrence

A naturalistic study in 2003 by Tohen and coworkers from the first admission for mania or mixed episode (representing the hospitalized and therefore most severe cases) found that 50% achieved syndromal recovery (no longer meeting criteria for the diagnosis) within six weeks and 98% within two years. Within two years, 72% achieved symptomatic recovery (no symptoms at all) and 43% achieved functional recovery (regaining of prior occupational and residential status). However, 40% went on to experience a new episode of mania or depression within 2 years of syndromal recovery, and 19% switched phases without recovery. 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 Coping refers to conscious strategies used to reduce unpleasant emotions. Coping strategies can be cognitions or behaviours and can be individual or social. Theories of coping Hundreds of coping strategies have been proposed in an attempt to ...
when noticing such symptoms with encouraging results.


Suicide

Bipolar disorder can cause suicidal ideation that leads to
suicide Suicide is the act of intentionally causing one's own death. Mental disorders (including depression, bipolar disorder, schizophrenia, personality disorders, anxiety disorders), physical disorders (such as chronic fatigue syndrome), and ...
attempts. Individuals whose bipolar disorder begins with a depressive or mixed affective episode seem to have a poorer prognosis and an increased risk of suicide. One out of two people with bipolar disorder attempt suicide at least once during their lifetime and many attempts are successfully completed. The annual average suicide rate is 0.4%, which is 10–20 times that of the general population. The number of deaths from
suicide Suicide is the act of intentionally causing one's own death. Mental disorders (including depression, bipolar disorder, schizophrenia, personality disorders, anxiety disorders), physical disorders (such as chronic fatigue syndrome), and ...
in bipolar disorder is between 18 and 25 times higher than would be expected in similarly aged people without bipolar disorder. The lifetime risk of suicide has been estimated to be as high as 20% in those with bipolar disorder. 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.


Epidemiology

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 The World Health Organization (WHO) is a specialized agency of the United Nations responsible for international public health. The WHO Constitution states its main objective as "the attainment by all peoples of the highest possible level o ...
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 American Asian Americans are Americans of Asian ancestry (including naturalized Americans who are immigrants from specific regions in Asia and descendants of such immigrants). Although this term had historically been used for all the indigenous peopl ...
s have significantly lower rates than their
African American African Americans (also referred to as Black Americans and Afro-Americans) are an ethnic group consisting of Americans with partial or total ancestry from sub-Saharan Africa. The term "African American" generally denotes descendants of ens ...
and
European American European Americans (also referred to as Euro-Americans) are Americans of European ancestry. This term includes people who are descended from the first European settlers in the United States as well as people who are descended from more recent Eu ...
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.


History

In the early 1800s, French psychiatrist
Jean-Étienne Dominique Esquirol Jean-Étienne Dominique Esquirol (3 February 1772 – 12 December 1840) was a French psychiatrist. Early life and education Born and raised in Toulouse, Esquirol completed his education at Montpellier. He came to Paris in 1799 where he worke ...
's lypemania, one of his affective monomanias, was the first elaboration on what was to become modern depression. The basis of the current conceptualization of bipolar illness can be traced back to the 1850s. In 1850,
Jean-Pierre Falret Jean-Pierre Falret (; 26 April 1794 – 28 October 1870) was a French psychiatrist. He was born and died in Marcilhac-sur-Célé.
described "circular insanity" (la folie circulaire, ); the lecture was summarized in 1851 in the "Gazette des hôpitaux" ("Hospital Gazette"). Three years later, in 1854, Jules-Gabriel-François Baillarger (1809–1890) described to the French Imperial
Académie Nationale de Médecine Situated at 16 Rue Bonaparte in the 6th arrondissement of Paris, the Académie nationale de médecine (National Academy of Medicine) was created in 1820 by King Louis XVIII at the urging of baron Antoine Portal. At its inception, the instituti ...
a biphasic mental illness causing recurrent oscillations between mania and melancholia, which he termed ''folie à double forme'' (, "madness in double form"). Baillarger's original paper, "De la folie à double forme," appeared in the medical journal '' Annales médico-psychologiques'' (''Medico-psychological annals'') in 1854. These concepts were developed by the German psychiatrist
Emil Kraepelin Emil Wilhelm Georg Magnus Kraepelin (; ; 15 February 1856 – 7 October 1926) was a German psychiatrist. H. J. Eysenck's ''Encyclopedia of Psychology'' identifies him as the founder of modern scientific psychiatry, psychopharmacology and psych ...
(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 Karl Kleist (born 31 January 1879 in Mulhouse, Alsace, died 26 December 1960) was a German neurologist and psychiatrist who made notable advances in descriptive psychopathology and neuropsychology. Kleist coined the terms unipolar (‘einpolig’) ...
'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.David L. Dunner interviewed by Thomas A. Ban
for the ANCP, Waikoloa, Hawaii, December 13, 2001


Society and culture


Cost

The
United States The United States of America (U.S.A. or USA), commonly known as the United States (U.S. or US) or America, is a country Continental United States, primarily located in North America. It consists of 50 U.S. state, states, a Washington, D.C., ...
spent approximately $202.1 billion on people diagnosed with bipolar I disorder (excluding other subtypes of bipolar disorder and undiagnosed people) in 2015. One analysis estimated that the
United Kingdom The United Kingdom of Great Britain and Northern Ireland, commonly known as the United Kingdom (UK) or Britain, is a country in Europe, off the north-western coast of the continental mainland. It comprises England, Scotland, Wales and ...
spent approximately £5.2 billion on the disorder in 2007. In addition to the economic costs, bipolar disorder is a leading cause of disability and lost productivity worldwide. People with bipolar disorder are generally more disabled, have a lower level of functioning, longer duration of illness, and increased rates of work absenteeism and decreased productivity when compared to people experiencing other mental health disorders. The decrease in the productivity seen in those who care for people with bipolar disorder also significantly contributes to these costs.


Advocacy

There are widespread issues with
social stigma Social stigma is the disapproval of, or discrimination against, an individual or group based on perceived characteristics that serve to distinguish them from other members of a society. Social stigmas are commonly related to culture, gender, ra ...
, stereotypes, and prejudice against individuals with a diagnosis of bipolar disorder. In 2000, actress Carrie Fisher went public with her bipolar disorder diagnosis. She became one of the most well-recognized advocates for people with bipolar disorder in the public eye and fiercely advocated to eliminate the stigma surrounding mental illnesses, including bipolar disorder. 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 Stephen John Fry (born 24 August 1957) is an English actor, broadcaster, comedian, director and writer. He first came to prominence in the 1980s as one half of the comic double act Fry and Laurie, alongside Hugh Laurie, with the two starring ...
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 cases

Numerous authors have written about bipolar disorder and many successful people have openly discussed their experience with it.
Kay Redfield Jamison Kay Redfield Jamison (born June 22, 1946) is an American clinical psychologist and writer. Her work has centered on bipolar disorder, which she has had since her early adulthood. She holds the post of the Dalio Professor in Mood Disorders and Psy ...
, a clinical psychologist and professor of psychiatry at the Johns Hopkins University School of Medicine, profiled her own bipolar disorder in her memoir '' An Unquiet Mind'' (1995). Several celebrities have also publicly shared that they have bipolar disorder; in addition to Carrie Fisher and
Stephen Fry Stephen John Fry (born 24 August 1957) is an English actor, broadcaster, comedian, director and writer. He first came to prominence in the 1980s as one half of the comic double act Fry and Laurie, alongside Hugh Laurie, with the two starring ...
these include
Catherine Zeta-Jones Catherine Zeta-Jones (; born 25 September 1969) is a Welsh actress. Known for her versatility, she is the recipient of various accolades, including an Academy Award, a British Academy Film Award, and a Tony Award. In 2010, she was appointed ...
,
Mariah Carey Mariah Carey (; born March 27, 1969) is an American singer, songwriter, actress, and record producer. Referred to as the " Songbird Supreme", she is noted for her five-octave vocal range, melismatic singing style and signature use of the w ...
,
Kanye West Ye ( ; born Kanye Omari West ; June 8, 1977) is an American rapper, singer, songwriter, record producer, and fashion designer. Born in Atlanta and raised in Chicago, West gained recognition as a producer for Roc-A-Fella Records in the ea ...
,
Jane Pauley Margaret Jane Pauley (born October 31, 1950) is an American television host, and author, active in news reporting since 1972. Pauley first became widely known as Barbara Walters's successor on the NBC morning show ''Today'', beginning at the ag ...
,
Demi Lovato Demetria Devonne Lovato ( ; born August 20, 1992), known as Demi Lovato, is an American singer, songwriter, and actress. After appearing on the children's television series '' Barney & Friends'' (2002–2004), Lovato rose to prominence for p ...
,
Selena Gomez Selena Marie Gomez ( ; born July 22, 1992) is an American singer, actress and producer. Gomez began her acting career on the children's television series ''Barney & Friends'' (2002–2004). As a teenager, she rose to prominence for starring a ...
, and
Russell Brand Russell Edward Brand (born 4 June 1975) is an English comedian and actor known for his flamboyant, loquacious style and manner. Brand has received three British Comedy Awards: Best Newcomer (2006), Best Live Stand-Up (2008), and the award for ...
.


Media portrayals

Several dramatic works have portrayed characters with traits suggestive of the diagnosis which have been the subject of discussion by psychiatrists and film experts alike. In '' Mr. Jones'' (1993), (
Richard Gere Richard Tiffany Gere ( ; born August 31, 1949) is an American actor. He began in films in the 1970s, playing a supporting role in '' Looking for Mr. Goodbar'' (1977) and a starring role in ''Days of Heaven'' (1978). He came to prominence with ...
) 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 Harrison Ford (born July 13, 1942) is an American actor. His films have grossed more than $5.4billion in North America and more than $9.3billion worldwide, making him the seventh-highest-grossing actor in North America. He is the recipient o ...
) displays some features including recklessness, grandiosity, increased goal-directed activity and mood lability, as well as some
paranoia Paranoia is an instinct or thought process that is believed to be heavily influenced by anxiety or fear, often to the point of delusion and irrationality. Paranoid thinking typically includes persecutory beliefs, or beliefs of conspiracy c ...
. Psychiatrists have suggested that
Willy Loman William "Willy" Loman is a fictional character and the protagonist of Arthur Miller's play ''Death of a Salesman'', which debuted on Broadway with Lee J. Cobb playing Loman at the Morosco Theatre on February 10, 1949. Loman is a 63-year-old t ...
, the main character in
Arthur Miller Arthur Asher Miller (October 17, 1915 – February 10, 2005) was an American playwright, essayist and screenwriter in the 20th-century American theater. Among his most popular plays are ''All My Sons'' (1947), '' Death of a Salesman'' (1 ...
's classic play ''
Death of a Salesman ''Death of a Salesman'' is a 1949 stage play written by American playwright Arthur Miller. The play premiered on Broadway in February 1949, running for 742 performances. It is a two-act tragedy set in late 1940s Brooklyn told through a montage ...
'', 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 ''EastEnders'' is a Television in the United Kingdom, British soap opera created by Julia Smith (producer), Julia Smith and Tony Holland which has been broadcast on BBC One since February 1985. Set in the fictional borough of Walford in the Ea ...
, has been diagnosed with the disorder. The storyline was developed as part of the BBC's Headroom campaign. The
Channel 4 Channel 4 is a British free-to-air public broadcast television network operated by the state-owned Channel Four Television Corporation. It began its transmission on 2 November 1982 and was established to provide a fourth television service ...
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 A political thriller is a thriller that is set against the backdrop of a political power struggle, high stakes and suspense is the core of the story. The genre often forces the audiences to consider and understand the importance of politics. The st ...
drama ''
Homeland A homeland is a place where a cultural, national, or racial identity has formed. The definition can also mean simply one's country of birth. When used as a proper noun, the Homeland, as well as its equivalents in other languages, often has ethn ...
'' protagonist
Carrie Mathison Carrie Anne Mathison, played by actress Claire Danes, is a fictional character and the protagonist of the American television drama/thriller series ''Homeland'' on Showtime, created by Alex Gansa and Howard Gordon. Carrie is a CIA officer who, ...
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 Dave may refer to: Film, television, and theater * ''Dave'' (film), a 1993 film starring Kevin Kline and Sigourney Weaver * ''Dave'' (musical), a 2018 stage musical adaptation of the film * Dave (TV channel), a digital television channel in the ...
'', the eponymous main character, played by
Lil Dicky David Andrew Burd (born March 15, 1988), better known by his stage name Lil Dicky, is an American rapper, comedian, and actor. He came to prominence with the release of the music video for his song "Ex-Boyfriend" in 2013, which became popular w ...
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.


Creativity

A link between mental illness and professional success or creativity has been suggested, including in accounts by
Socrates Socrates (; ; –399 BC) was a Greek philosopher from Athens who is credited as the founder of Western philosophy and among the first moral philosophers of the ethical tradition of thought. An enigmatic figure, Socrates authored no t ...
,
Seneca the Younger Lucius Annaeus Seneca the Younger (; 65 AD), usually known mononymously as Seneca, was a Stoic philosopher of Ancient Rome, a statesman, dramatist, and, in one work, satirist, from the post-Augustan age of Latin literature. Seneca was born ...
, and
Cesare Lombroso Cesare Lombroso (, also ; ; born Ezechia Marco Lombroso; 6 November 1835 – 19 October 1909) was an Italian criminologist, phrenologist, physician, and founder of the Italian School of Positivist Criminology. Lombroso rejected the establi ...
. Despite prominence in popular culture, the link between creativity and bipolar has not been rigorously studied. This area of study also is likely affected by
confirmation bias Confirmation bias is the tendency to search for, interpret, favor, and recall information in a way that confirms or supports one's prior beliefs or values. People display this bias when they select information that supports their views, ignoring ...
. Some evidence suggests that some heritable component of bipolar disorder overlaps with heritable components of creativity. Probands of people with bipolar disorder are more likely to be professionally successful, as well as to demonstrate temperamental traits similar to bipolar disorder. Furthermore, while studies of the frequency of bipolar disorder in creative population samples have been conflicting, full-blown bipolar disorder in creative samples is rare.


Research

Research directions for bipolar disorder in children include optimizing treatments, increasing the knowledge of the genetic and neurobiological basis of the pediatric disorder and improving diagnostic criteria. Some treatment research suggests that
psychosocial The psychosocial approach looks at individuals in the context of the combined influence that psychological factors and the surrounding social environment have on their physical and mental wellness and their ability to function. This approach is ...
interventions that involve the family, psychoeducation, and skills building (through therapies such as CBT, DBT, and IPSRT) can benefit in addition to pharmocotherapy.


See also

* List of people with bipolar disorder *
Outline of bipolar disorder The following outline is provided as an overview of and topical guide to bipolar disorder: Bipolar disorder – mental disorder with periods of depression and periods of elevated mood. The elevated mood is significant and is known as mania or ...
*
Bipolar I disorder Bipolar I disorder (BD-I; pronounced "type one bipolar disorder") is a type of bipolar spectrum disorder characterized by the occurrence of at least one manic episode, with or without mixed or psychotic features. Most people also, at other ti ...
*
Bipolar II disorder Bipolar II disorder (BP-II) is a mood disorder on the bipolar spectrum, characterized by at least one episode of hypomania and at least one episode of major depression. Diagnosis for BP-II requires that the individual must never have experien ...
* Bipolar NOS *
Cyclothymia Cyclothymia ( ), also known as cyclothymic disorder, psychothemia/psychothymia, bipolar III, affective personality disorder and cyclothymic personality disorder, is a mental and behavioural disorder that involves numerous periods of symptoms of ...
* Bipolar disorders research *
Borderline personality disorder Borderline personality disorder (BPD), also known as emotionally unstable personality disorder (EUPD), is a personality disorder characterized by a long-term pattern of unstable interpersonal relationships, distorted sense of self, and strong ...
* Emotional dysregulation *
Mood (psychology) In psychology, a mood is an affective state. In contrast to emotions or feelings, moods are less specific, less intense and less likely to be provoked or instantiated by a particular stimulus or event. Moods are typically described as having e ...
* Mood swing * Ultradian bipolar disorder *
International Society for Bipolar Disorders The International Society for Bipolar Disorders (ISBD) is a nonprofit organization based in Pittsburgh, Pennsylvania, where it was founded June 17, 1999. The society focuses on research and education in bipolar disorders. The society has a members ...


Explanatory notes


Citations


Cited texts

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Further reading

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External links

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