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Thursday, January 23, 2025

Bipolar disorder

From Wikipedia, the free encyclopedia

https://en.wikipedia.org/wiki/Bipolar_disorder

Bipolar disorder
Other names	Bipolar affective disorder (BPAD), bipolar illness, manic depression, manic depressive disorder, manic–depressive illness (historical), manic–depressive psychosis, circular insanity (historical), bipolar disease

Bipolar disorder is characterized by episodes of mania or hypomania and depression.
Specialty	Psychiatry, clinical psychology
Symptoms	Periods of depression and elevated mood
Complications	Suicide, self-harm
Usual onset	25 years old
Types	Bipolar I disorder, bipolar II disorder, others
Causes	Environmental and genetic
Risk factors	Family history, childhood abuse, long-term stress
Differential diagnosis	Attention deficit hyperactivity disorder, autism, personality disorders, schizophrenia, substance use disorder
Treatment	Psychotherapy, medications
Medication	Lithium, antipsychotics, anticonvulsants
Frequency	1–3%

Bipolar disorder, previously known as manic depression, is a mental disorder characterized by periods of depression and periods of abnormally elevated mood that each last from days to weeks. If the elevated mood is severe or associated with psychosis, it is called mania; if it is less severe and does not significantly affect functioning, it is called hypomania. During mania, an individual behaves or feels abnormally energetic, happy, or irritable, and they often make impulsive decisions with little regard for the consequences. There is usually, but not always, a reduced need for sleep during manic phases. During periods of depression, the individual may experience crying, have a negative outlook on life, and demonstrate poor eye contact with others. The risk of suicide is high. Over a period of 20 years, 6% of those with bipolar disorder died by suicide. 40-50% overall and 78% of adolescents engaged in self-harm. Other mental health issues, such as anxiety disorders and substance use disorders, are commonly associated with bipolar disorder. The global prevalence of bipolar disorder is estimated to be between 1–5% of the world's population.

While the causes of this mood disorder are not clearly understood, both genetic and environmental factors are thought to play a role. Genetic factors may account for up to 70–90% of the risk of developing bipolar disorder. Many genes, each with small effects, may contribute to the development of the disorder. Environmental risk factors include a history of childhood abuse and long-term stress. The condition is classified as bipolar I disorder if there has been at least one manic episode, with or without depressive episodes, and as bipolar II disorder if there has been at least one hypomanic episode (but no full manic episodes) and one major depressive episode. It is classified as cyclothymia 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, personality disorders, schizophrenia, and substance use disorder as well as many other medical conditions. Medical testing is not required for a diagnosis, though blood tests or medical imaging can rule out other problems.

Mood stabilizers, particularly lithium, and certain anticonvulsants, such as lamotrigine, valproate, and carbamazepine, as well as atypical antipsychotics, including quetiapine, olanzapine, aripiprazole, and cariprazine, are the mainstay of long-term pharmacologic relapse prevention. Antipsychotics are additionally given during acute manic episodes as well as in cases where mood stabilizers are poorly tolerated or ineffective. In patients where compliance is of concern, long-acting injectable formulations are available. There is some evidence that psychotherapy improves the course of this disorder. The use of antidepressants in depressive episodes is controversial: they can be effective but certain classes of antidepressants increase the risk of mania. The treatment of depressive episodes, therefore, is often difficult. Electroconvulsive therapy (ECT) is effective in acute manic and depressive episodes, especially with psychosis or catatonia. Admission to a psychiatric hospital may be required if a person is a risk to themselves or others; involuntary treatment is sometimes necessary if the affected person refuses treatment.

Bipolar disorder occurs in approximately 2% of the global population. In the United States, about 3% are estimated to be affected at some point in their life; rates appear to be similar in females and males. Symptoms most commonly begin between the ages of 20 and 25 years old; an earlier onset in life is associated with a worse prognosis. Interest in functioning in the assessment of patients with bipolar disorder is growing, with an emphasis on specific domains such as work, education, social life, family, and cognition. Around one-quarter to one-third of people with bipolar disorder have financial, social or work-related problems due to the illness. Bipolar disorder is among the top 20 causes of disability worldwide and leads to substantial costs for society. Due to lifestyle choices and the side effects of medications, the risk of death from natural causes such as coronary heart disease in people with bipolar disorder is twice that of the general population.

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, commonly (but not in every patient) alternating with bouts of 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 and cognition. Mania can present with varying levels of mood disturbance, ranging from euphoria, which is associated with "classic mania", to dysphoria and irritability. 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. In some people with bipolar disorder, depressive symptoms predominate, and the episodes of mania are always the more subdued hypomania type.

According to the DSM-5 criteria, mania is distinguished from hypomania by the duration: hypomania is present if elevated mood symptoms persist for at least four consecutive days, while mania is present if such symptoms persist for more than a week. Unlike mania, hypomania is not always associated with impaired functioning. The biological mechanisms responsible for switching from a manic or hypomanic episode to a depressive episode, or vice versa, remain poorly understood.

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. 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, pressured speech 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, persecuted, or as if they have a special relationship with God, a great mission to accomplish, or other grandiose or delusional ideas. This may lead to violent behavior and, sometimes, hospitalization in an inpatient psychiatric hospital. The severity of manic symptoms can be measured by rating scales such as the Young Mania Rating Scale, though questions remain about the reliability of these scales.

The onset of a manic or depressive episode is often foreshadowed by sleep disturbance. Manic individuals often have a history of substance use disorder developed over years as a form of "self-medication".

Hypomanic episodes

Hypomania 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 or hallucinations, 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, irritability or anger, loss of interest in previously enjoyed activities, excessive or inappropriate guilt, hopelessness, sleeping too much or not enough, changes in appetite or weight, fatigue, problems concentrating, self-loathing or feelings of worthlessness, and thoughts of death or suicide. 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 as having major depression and 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 or difficulties with impulse control. Anxiety disorders occur more frequently as a comorbidity in mixed bipolar episodes than in non-mixed bipolar depression or mania. Substance (including alcohol) 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 (present in about 71% of people with bipolar disorder), substance abuse (56%), personality disorders (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 (present in 37% of people with bipolar disorder), migraine headaches (35%), obesity (21%) and type 2 diabetes (14%). This contributes to a risk of death that is two times higher in those with bipolar disorder as compared to the general population. Hypothyroidism is also common regardless of drug choice.

Substance use disorder 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 of the bipolar spectrum 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 twins (same genes) will both have bipolar I disorder (concordance) is around 40%, compared to about 5% in fraternal twins. A combination of bipolar I, II, and cyclothymia similarly produced rates of 42% and 11% (identical and fraternal twins, respectively). The rates of bipolar II combinations without bipolar I are lower—bipolar 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 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 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 finding for mania was in 1969, linkage studies have been inconsistent. Findings point strongly to heterogeneity, with different genes implicated in different families. Robust and replicable genome-wide significant associations showed several common single-nucleotide polymorphisms (SNPs) are associated with bipolar disorder, including variants within the genes CACNA1C, ODZ4, and NCAN. The largest and most recent genome-wide association study failed to find any locus that exerts a large effect, reinforcing the idea that no single gene is responsible for bipolar disorder in most cases. Polymorphisms in BDNF, DRD4, DAO, and TPH1 have been frequently associated with bipolar disorder and were initially associated in a meta-analysis, but this association disappeared after correction for multiple testing. On the other hand, two polymorphisms in TPH2 were identified as being associated with bipolar disorder.

Due to the inconsistent findings in a genome-wide association study, multiple studies have undertaken the approach of analyzing SNPs in biological pathways. Signaling pathways traditionally associated with bipolar disorder that have been supported by these studies include corticotropin-releasing hormone signaling, cardiac β-adrenergic signaling, phospholipase C signaling, glutamate receptor signaling, cardiac hypertrophy signaling, Wnt signaling, Notch signaling, and endothelin 1 signaling. Of the 16 genes identified in these pathways, three were found to be dysregulated in the dorsolateral prefrontal cortex portion of the brain in post-mortem studies: CACNA1C, GNG2, and ITPR2.

Bipolar disorder is associated with reduced expression of specific DNA repair enzymes and increased levels of oxidative DNA damages.

Environmental

Psychosocial 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. Subtypes of abuse, such as sexual and emotional abuse, also contribute to violent behaviors seen in patients with bipolar disorder. 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 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, traumatic brain injury, HIV infection, multiple sclerosis, porphyria, and rarely temporal lobe epilepsy.

Proposed mechanisms

3-D image of human brain emphasizing emotional regulation circuits — Brain imaging studies have revealed differences in the volume of various brain regions between patients with bipolar disorder and healthy control subjects.

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, insula, ventral striatum, ventral anterior cingulate cortex, and the prefrontal cortex. The dorsal system (responsible for emotional regulation) includes the hippocampus, 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 is crucial to this disruption.

Meta-analyses of structural MRI studies have shown that certain brain regions (e.g., the left rostral anterior cingulate cortex, fronto-insular cortex, ventral prefrontal cortex, and claustrum) are smaller in people with bipolar disorder, whereas other regions are larger (lateral ventricles, globus pallidus, subgenual anterior cingulate, and the amygdala). Additionally, these meta-analyses found that people with bipolar disorder have higher rates of deep white matter hyperintensities.

Functional MRI findings suggest that the ventricular prefrontal cortex regulates the limbic system, especially the amygdala. In people with bipolar disorder, decreased ventricular prefrontal cortex activity allows for the dysregulated activity of the amygdala, which likely contributes to labile mood and poor emotional regulation. Consistent with this, pharmacological treatment of mania returns ventricular prefrontal cortex activity to the levels in non-manic people, suggesting that ventricular prefrontal cortex activity is an indicator of mood state. However, while pharmacological treatment of mania reduces amygdala hyperactivity, it remains more active than the amygdala of those without bipolar disorder, suggesting amygdala activity may be a marker of the disorder rather than the current mood state. Manic and depressive episodes tend to be characterized by dysfunction in different regions of the ventricular prefrontal cortex. Manic episodes appear to be associated with decreased activation of the right ventricular prefrontal cortex whereas depressive episodes are associated with decreased activation of the left ventricular prefrontal cortex. These disruptions often occur during development linked with synaptic pruning dysfunction.

People with bipolar disorder who are in a euthymic mood state show decreased activity in the lingual gyrus compared to people without bipolar disorder. In contrast, they demonstrate decreased activity in the inferior frontal cortex during manic episodes compared to people without the disorder. Similar studies examining the differences in brain activity between people with bipolar disorder and those without did not find a consistent area in the brain that was more or less active when comparing these two groups. People with bipolar have increased activation of left hemisphere ventral limbic areas—which mediate emotional experiences and generation of emotional responses—and decreased activation of right hemisphere cortical structures related to cognition—structures associated with the regulation of emotions. However, further research is needed to consolidate neuroimaging findings, which are often heterogeneous and not consistently reported according to a common standard.

Neuroscientists have proposed additional models to try to explain the cause of bipolar disorder. One proposed model for bipolar disorder suggests that hypersensitivity of reward circuits consisting of frontostriatal circuits causes mania, and decreased sensitivity of these circuits causes depression. According to the "kindling" hypothesis, when people who are genetically predisposed toward bipolar disorder experience stressful events, the stress threshold at which mood changes occur becomes progressively lower, until the episodes eventually start (and recur) spontaneously. There is evidence supporting an association between early-life stress and dysfunction of the hypothalamic-pituitary-adrenal axis leading to its overactivation, which may play a role in the pathogenesis of bipolar disorder. Other brain components that have been proposed to play a role in bipolar disorder are the mitochondria and a sodium ATPase pump. Circadian rhythms and regulation of the hormone melatonin also seem to be altered.

Dopamine, a neurotransmitter responsible for mood cycling, has increased transmission during the manic phase. The dopamine hypothesis states that the increase in dopamine results in secondary homeostatic downregulation of key system elements and receptors such as lower sensitivity of dopaminergic receptors. This results in decreased dopamine transmission characteristic of the depressive phase. The depressive phase ends with homeostatic upregulation potentially restarting the cycle over again. Glutamate is significantly increased within the left dorsolateral prefrontal cortex during the manic phase of bipolar disorder, and returns to normal levels once the phase is over.

Medications used to treat bipolar may exert their effect by modulating intracellular signaling, such as through depleting myo-inositol levels, inhibition of cAMP signaling, and through altering subunits of the dopamine-associated G-protein. Consistent with this, elevated levels of G_αi, G_αs, and G_αq/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 G_αs subunit from the G protein complex.

Decreased levels of 5-hydroxyindoleacetic acid, a byproduct of serotonin, are present in the cerebrospinal fluid of persons with bipolar disorder during both the depressed and manic phases. Increased dopaminergic activity has been hypothesized in manic states due to the ability of dopamine agonists to stimulate mania in people with bipolar disorder. Decreased sensitivity of regulatory α₂ adrenergic receptors as well as increased cell counts in the locus coeruleus indicated increased noradrenergic activity in manic people. Low plasma GABA levels on both sides of the mood spectrum have been found. One review found no difference in monoamine levels, but found abnormal norepinephrine turnover in people with bipolar disorder. Tyrosine depletion was found to reduce the effects of methamphetamine in people with bipolar disorder as well as symptoms of mania, implicating dopamine in mania. VMAT2 binding was found to be increased in one study of people with bipolar mania.

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's (APA) Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) and the World Health Organization's (WHO) International Statistical Classification of Diseases and Related Health Problems, 10th Edition (ICD-10). The ICD-10 criteria are used more often in clinical settings outside of the U.S. while the DSM criteria are used within the U.S. and are the prevailing criteria used internationally in research studies. The DSM-5, published in 2013, includes further and more accurate specifiers compared to its predecessor, the DSM-IV-TR. This work has influenced the 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 as a mental and behavioural disorder. Mental disorders that can have symptoms similar to those seen in bipolar disorder include schizophrenia, major depressive disorder, attention deficit hyperactivity disorder (ADHD), and certain personality disorders, such as borderline personality disorder. 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, complex partial seizures, strokes, brain tumors, Wilson's disease, traumatic brain injury, Huntington's disease, and complex migraines can mimic features of bipolar disorder. An EEG may be used to exclude neurological disorders such as epilepsy, and a CT scan or MRI of the head may be used to exclude brain lesions. Additionally, disorders of the endocrine system such as hypothyroidism, hyperthyroidism, and Cushing's disease are in the differential as is the connective tissue disease systemic lupus erythematosus. Infectious causes of mania that may appear similar to bipolar mania include herpes encephalitis, HIV, influenza, or neurosyphilis. Certain vitamin deficiencies such as pellagra (niacin deficiency), vitamin B₁₂ deficiency, folate deficiency, and Wernicke–Korsakoff syndrome (thiamine deficiency) can also lead to mania. Common medications that can cause manic symptoms include antidepressants, prednisone, Parkinson's disease medications, thyroid hormone, stimulants (including cocaine and methamphetamine), and certain antibiotics.

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 is similar to that of Emil Kraepelin'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: 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: 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: 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 25.8–45.3% 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. "Ultra rapid" and "ultradian" have been applied to faster-cycling types of bipolar disorder. People with the rapid cycling or faster-cycling 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) psychiatric conditions including obsessive–compulsive disorder, substance-use disorder, eating disorders, attention deficit hyperactivity disorder, social phobia, premenstrual syndrome (including premenstrual dysphoric disorder), or panic disorder. 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 hospitals 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.

Adults

Bipolar on average, starts during adulthood. Bipolar 1, on average, starts at the age of 18 years old, and Bipolar 2 starts at age 22 years old on average. However, most delay seeking treatment for an average of 8 years after symptoms start. Bipolar is often misdiagnosed with other psychiatric disorders. There is no definitive association between race, ethnicity, or Socioeconomic status (SES). Adults with Bipolar report having a lower quality of life, even outside of a manic or depressive episode. Bipolar can put strain on marriage and other relationships, having a job, and everyday functioning. Bipolar is associated with having higher rates of unemployment. Most have trouble keeping a job, leading to trouble with healthcare access, leading to more decline in their mental health due to not receiving treatment such as medicine and therapy.

Elderly

Bipolar disorder is uncommon in older patients, with a measured lifetime prevalence of 1% in over 60s and a 12-month prevalence of 0.1–0.5% in people over 65. Despite this, it is overrepresented in psychiatric admissions, making up 4–8% 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 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, although these can still occur. Following (or in lieu of) a hospital admission, support services available can include drop-in centers, visits from members of a community mental health team or an Assertive Community Treatment team, supported employment, patient-led support groups, and intensive outpatient programs. These are sometimes referred to as partial-inpatient programs. Compared to the general population, people with bipolar disorder are less likely to frequently engage in physical exercise. Exercise may have physical and mental benefits for people with bipolar disorder, but there is a lack of research.

Psychosocial

Psychotherapy 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 (CBT), 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 in support of recovery.

Medication

Lithium is often used to treat bipolar disorder and has the best evidence for reducing suicide.

Medications are often prescribed to help improve symptoms of bipolar disorder. Medications approved for treating bipolar disorder including mood stabilizers, antipsychotics, and certain 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 anticonvulsants carbamazepine, lamotrigine, 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. Lamotrigine may have a similar effectiveness to lithium for treating bipolar disorder, however, there is evidence to suggest that lamotrigine is less effective at preventing recurrent mania episodes. Lamotrigine treatment has been shown to be safer compared to lithium treatment, with less adverse effects. 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 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.

Mood stabilizers are used for long-term maintenance but have not demonstrated the ability to quickly treat acute bipolar depression.

Antipsychotics

Antipsychotic 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 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 or risperidone, and that it could be less effective than aripiprazole.

Antidepressants

Antidepressant monotherapy is not recommended in the treatment of bipolar disorder and does 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 may carry a risk of affective switches where a person switches from depression to manic or hypomanic phases or mixed states. There may also be a risk of accelerating cycling between phases when antidepressants are used in bipolar disorder. 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.

Whether modern antidepressants cause mania or cycle acceleration in bipolar disorder is highly controversial, as is whether antidepressants provide any benefit over mood stabilizers alone.

Combined treatment approaches

Antipsychotics 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 are used in addition to other medications for calming effect until mood stabilizing become effective. Electroconvulsive therapy (ECT) is an effective form of treatment for acute mood disturbances in those with bipolar disorder, especially when psychotic or catatonic features are displayed. ECT is also recommended for use in pregnant women with bipolar disorder. It is unclear if ketamine (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 stabilizers and atypical antipsychotics are commonly prescribed. Among the former, lithium is the only compound approved by the FDA for children. Psychological treatment combines normally education on the disease, group therapy, and cognitive behavioral therapy. Long-term medication is often needed.

Resistance to treatment

The poor response from some bipolar patients to treatment has given evidence to the concept of treatment-resistant bipolar disorder. Guidelines to the definition of treatment-resistant bipolar disorder and evidence-based options for its management were reviewed in 2020.

Management of obesity

A large proportion (approximately 68%) of people who seek treatment for bipolar disorder are obese or overweight and managing obesity is important for reducing the risk of other health conditions that are associated with obesity. Management approaches include non-pharmacological, pharmacological, and surgical. Examples of non-pharmacological include dietary interventions, exercise, behavioral therapies, or combined approaches. Pharmacological approaches include weight-loss medications or changing medications already being prescribed. Some people with bipolar disorder who have obesity may also be eligible for bariatric surgery. The effectiveness of these various approaches to improving or managing obesity in people with bipolar disorder is not clear.

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), 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, respiratory diseases, HIV, and hepatitis C 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 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 processes and abilities are seen in mood disorders, with those of bipolar disorder being greater than those in major depressive disorder. These include reduced attentional and executive capabilities and impaired memory. 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 when noticing such symptoms with encouraging results.

Suicide

Bipolar disorder can cause suicidal ideation that leads to suicide 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%-1.4%, which is 30 to 60 times greater than that of the general population. The number of deaths from suicide in bipolar disorder is between 18 and 25 times higher than would be expected in similarly aged people without bipolar disorder. The lifetime risk of suicide is much higher in those with bipolar disorder, with an estimated 34% of people attempting suicide and 15–20% dying by suicide.

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 found that prevalence and incidence of bipolar disorder are very similar across the world. Age-standardized prevalence per 100,000 ranged from 421.0 in South Asia to 481.7 in Africa and Europe for men and from 450.3 in Africa and Europe to 491.6 in Oceania for women. However, severity may differ widely across the globe. Disability-adjusted life year rates, for example, appear to be higher in developing countries, where medical coverage may be poorer and medication less available. Within the United States, Asian Americans have significantly lower rates than their African American and European American counterparts. In 2017, the Global Burden of Disease Study estimated there were 4.5 million new cases and a total of 45.5 million cases globally.

History

In the early 1800s, French psychiatrist Jean-Étienne Dominique Esquirol'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 described "circular insanity" (la folie circulaire, French pronunciation: [la fɔli siʁ.ky.lɛʁ]); 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 a biphasic mental illness causing recurrent oscillations between mania and melancholia, which he termed la folie à double forme (French pronunciation: [la fɔli a dubl fɔʀm], "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 (1856–1926), who, using Kahlbaum's concept of cyclothymia, categorized and studied the natural course of untreated bipolar patients. He coined the term manic depressive psychosis, after noting that periods of acute illness, manic or depressive, were generally punctuated by relatively symptom-free intervals where the patient was able to function normally.

The term "manic–depressive reaction" appeared in the first version of the DSM in 1952, influenced by the legacy of Adolf Meyer. Subtyping into "unipolar" depressive disorders and bipolar disorders has its origin in Karl Kleist's concept – since 1911 – of unipolar and bipolar affective disorders, which was used by Karl Leonhard in 1957 to differentiate between unipolar and bipolar disorder in depression. These subtypes have been regarded as separate conditions since publication of the DSM-III. The subtypes bipolar II and rapid cycling have been included since the DSM-IV, based on work from the 1970s by David Dunner, Elliot Gershon, Frederick Goodwin, Ronald Fieve, and Joseph Fleiss.

Society and culture

Cost

The United States 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 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, 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 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, 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). It is likely that Grigory Potemkin, Russian statesman and alleged husband of Catherine the Great, suffered from some kind of bipolar disorder. Several celebrities have also publicly shared that they have bipolar disorder; in addition to Carrie Fisher and Stephen Fry these include Catherine Zeta-Jones, Mariah Carey, Kanye West, Jane Pauley, Demi Lovato, Selena Gomez, and Russell Brand.

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) swings from a manic episode into a depressive phase and back again, spending time in a psychiatric hospital and displaying many of the features of the syndrome. In The Mosquito Coast (1986), Allie Fox (Harrison Ford) displays some features including recklessness, grandiosity, increased goal-directed activity and mood lability, as well as some paranoia. Psychiatrists have suggested that Willy Loman, the main character in Arthur Miller's classic play Death of a Salesman, has bipolar disorder.

The 2009 drama 90210 featured a character, Silver, who was diagnosed with bipolar disorder. Stacey Slater, a character from the BBC soap EastEnders, has been diagnosed with the disorder. The storyline was developed as part of the BBC's Headroom campaign. The Channel 4 soap Brookside had earlier featured a story about bipolar disorder when the character Jimmy Corkhill was diagnosed with the condition. 2011 Showtime's political thriller drama Homeland protagonist Carrie Mathison has bipolar disorder, which she has kept secret since her school days. The 2014 ABC medical drama, Black Box, featured a world-renowned neuroscientist with bipolar disorder. In the TV series Dave, the eponymous main character, played by Lil Dicky as a fictionalized version of himself, is an aspiring rapper. Lil Dicky's real-life hype man GaTa also plays himself. In one episode, after being off his medication and having an episode, GaTa tearfully confesses to having bipolar disorder. GaTa has bipolar disorder in real life but, like his character in the show, he is able to manage it with medication.

Creativity

A link between mental illness and professional success or creativity has been suggested, including in accounts by Socrates, Seneca the Younger, and Cesare Lombroso. 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. 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 interventions that involve the family, psychoeducation, and skills building (through therapies such as CBT, DBT, and IPSRT) can benefit in addition to pharmacotherapy.

Wednesday, January 22, 2025

Steady state (biochemistry)

From Wikipedia, the free encyclopedia

https://en.wikipedia.org/wiki/Steady_state_(biochemistry)

In biochemistry, steady state refers to the maintenance of constant internal concentrations of molecules and ions in the cells and organs of living systems. Living organisms remain at a dynamic steady state where their internal composition at both cellular and gross levels are relatively constant, but different from equilibrium concentrations. A continuous flux of mass and energy results in the constant synthesis and breakdown of molecules via chemical reactions of biochemical pathways. Essentially, steady state can be thought of as homeostasis at a cellular level.

Maintenance of steady state

Metabolic regulation achieves a balance between the rate of input of a substrate and the rate that it is degraded or converted, and thus maintains steady state. The rate of metabolic flow, or flux, is variable and subject to metabolic demands. However, in a metabolic pathway, steady state is maintained by balancing the rate of substrate provided by a previous step and the rate that the substrate is converted into product, keeping substrate concentration relatively constant.

Thermodynamically speaking, living organisms are open systems, meaning that they constantly exchange matter and energy with their surroundings. A constant supply of energy is required for maintaining steady state, as maintaining a constant concentration of a molecule preserves internal order and thus is entropically unfavorable. When a cell dies and no longer utilizes energy, its internal composition will proceed toward equilibrium with its surroundings.

In some occurrences, it is necessary for cells to adjust their internal composition in order to reach a new steady state. Cell differentiation, for example, requires specific protein regulation that allows the differentiating cell to meet new metabolic requirements.

ATP

The concentration of ATP must be kept above equilibrium level so that the rates of ATP-dependent biochemical reactions meet metabolic demands. A decrease in ATP will result in a decreased saturation of enzymes that use ATP as substrate, and thus a decreased reaction rate. The concentration of ATP is also kept higher than that of AMP, and a decrease in the ATP/AMP ratio triggers AMPK to activate cellular processes that will return ATP and AMP concentrations to steady state.

In one step of the glycolysis pathway catalyzed by PFK-1, the equilibrium constant of reaction is approximately 1000, but the steady state concentration of products (fructose-1,6-bisphosphate and ADP) over reactants (fructose-6-phosphate and ATP) is only 0.1, indicating that the ratio of ATP to AMP remains in a steady state significantly above equilibrium concentration. Regulation of PFK-1 maintains ATP levels above equilibrium.

In the cytoplasm of hepatocytes, the steady state ratio of NADP⁺ to NADPH is approximately 0.1 while that of NAD⁺ to NADH is approximately 1000, favoring NADPH as the main reducing agent and NAD⁺ as the main oxidizing agent in chemical reactions.

Blood glucose

Blood glucose levels are maintained at a steady state concentration by balancing the rate of entry of glucose into the blood stream (i.e. by ingestion or released from cells) and the rate of glucose uptake by body tissues. Changes in the rate of input will be met with a change in consumption, and vice versa, so that blood glucose concentration is held at about 5 mM in humans. A change in blood glucose levels triggers the release of insulin or glucagon, which stimulates the liver to release glucose into the bloodstream or take up glucose from the bloodstream in order to return glucose levels to steady state. Pancreatic beta cells, for example, increase oxidative metabolism as a result of a rise in blood glucose concentration, triggering secretion of insulin. Glucose levels in the brain are also maintained at steady state, and glucose delivery to the brain relies on the balance between the flux of the blood brain barrier and uptake by brain cells. In teleosts, a drop of blood glucose levels below that of steady state decreases the intracellular-extracellular gradient in the bloodstream, limiting glucose metabolism in red blood cells.

Blood lactate

Blood lactate levels are also maintained at steady state. At rest or low levels of exercise, the rate of lactate production in muscle cells and consumption in muscle or blood cells allows lactate to remain in the body at a certain steady state concentration. If a higher level of exercise is sustained, however, blood lactose levels will increase before becoming constant, indicating that a new steady state of elevated concentration has been reached. Maximal lactate steady state (MLSS) refers to the maximum constant concentration of lactase reached during sustained high-activity.

Nitrogen-containing molecules

Metabolic regulation of nitrogen-containing molecules, such as amino acids, is also kept at steady state. The amino acid pool, which describes the level of amino acids in the body, is maintained at a relatively constant concentration by balancing the rate of input (i.e. from dietary protein ingestion, production of metabolic intermediates) and rate of depletion (i.e. from formation of body proteins, conversion to energy-storage molecules). Amino acid concentration in lymph node cells, for example, is kept at steady state with active transport as the primary source of entry, and diffusion as the source of efflux.

Ions

One main function of plasma and cell membranes is to maintain asymmetric concentrations of inorganic ions in order to maintain an ionic steady state different from electrochemical equilibrium. In other words, there is a differential distribution of ions on either side of the cell membrane - that is, the amount of ions on either side is not equal and therefore a charge separation exists. However, ions move across the cell membrane such that a constant resting membrane potential is achieved; this is ionic steady state. In the pump-leak model of cellular ion homeostasis, energy is utilized to actively transport ions against their electrochemical gradient. The maintenance of this steady state gradient, in turn, is used to do electrical and chemical work, when it is dissipated though the passive movement of ions across the membrane.

In cardiac muscle, ATP is used to actively transport sodium ions out of the cell through a membrane ATPase. Electrical excitation of the cell results in an influx of sodium ions into the cell, temporarily depolarizing the cell. To restore the steady state electrochemical gradient, ATPase removes sodium ions and restores potassium ions in the cell. When an elevated heart rate is sustained, causing more depolarizations, sodium levels in the cell increase until becoming constant, indicating that a new steady state has been reached.

Stability of the steady-state

Steady-states can be stable or unstable. A steady-state is unstable if a small perturbation in one or more of the concentrations results in the system diverging from its state. In contrast, if a steady-state is stable, any perturbation will relax back to the original steady state. Further details can be found on the page Stability theory.

Simple Example

The following provides a simple example for computing the steady-state give a simple mathematical model.

Consider the open chemical system composed of two reactions with rates $v_{1}$ and $v_{2} :$ :

$X_{o} \overset{v_{1}}{⟶} S_{1} \overset{v_{2}}{⟶} X_{1}$

We will assume that the chemical species $X_{o}$ and $X_{1}$ are fixed external species and $S_{1}$ is an internal chemical species that is allowed to change. The fixed boundaries is to ensure the system can reach a steady-state. If we assume simple irreversible mass-action kinetics, the differential equation describing the concentration of $S_{1}$ is given by:

$\frac{d S_{1}}{d t} = k_{1} X_{o} - k_{2} S_{1}$

To find the steady-state the differential equation is set to zero and the equation rearranged to solve for $S_{1}$

$S_{1} = \frac{k_{1} X_{o}}{k_{2}}$

This is the steady-state concentration of $S_{1}$ .

The stability of this system can be determined by making a perturbation $δ S_{1}$ in $S_{1}$ This can be expressed as:

$\frac{d (S_{1} + δ S_{1})}{d t} = k_{1} X_{o} - k_{2} (S_{1} + δ S_{1})$

Note that the $δ S_{1}$ will elicit a change in the rate of change. At steady-state $k_{1} X_{o} - k_{2} S_{1} = 0$ , therefore the rate of change of $S_{1}$ as a result of this perturbation is:

$\frac{d δ S_{1}}{d t} = - k_{2} δ S_{1}$

This shows that the perturbation, $δ S_{1}$ decays exponetially, hence the system is stable.

Great Red Spot

From Wikipedia, the free encyclopedia
https://en.wikipedia.org/wiki/Great_Red_Spot

The Great Red Spot is a persistent high-pressure region in the atmosphere of Jupiter, producing an anticyclonic storm that is the largest in the Solar System. It is the most recognizable feature on Jupiter, owing to its red-orange color whose origin is still unknown. Located 22 degrees south of Jupiter's equator, it produces wind-speeds up to 432 km/h (268 mph). It was first observed in September 1831, with 60 recorded observations between then and 1878, when continuous observations began. A similar spot was observed from 1665 to 1713; if this is the same storm, it has existed for at least 360 years, but a study from 2024 suggests this is not the case.

Observation history

First observations

The Great Red Spot may have existed before 1665, but it could be that the present spot was first seen only in 1830, and was well studied only after a prominent appearance in 1879. The storm that was seen in the 17th century may have been different from the storm that exists today. A long gap separates its period of current study after 1830 from its 17th century discovery. Whether the original spot dissipated and reformed, whether it faded, or if the observational record was simply poor is unknown.

The first sighting of the Great Red Spot is often credited to Robert Hooke, who described a spot on the planet in May 1664. However, it is likely that Hooke's spot was not only in another belt altogether (the North Equatorial Belt, as opposed to the current Great Red Spot's location in the South Equatorial Belt), but also that it was in the shadow of a transiting moon, most likely Callisto. Far more convincing is Giovanni Cassini's description of a "permanent spot" the following year. With fluctuations in visibility, Cassini's spot was observed from 1665 to 1713, but the 48-year observational gap makes the identity of the two spots inconclusive. The older spot's shorter observational history and slower motion than the modern spot makes it difficult to conclude that they are the same.

A minor mystery concerns a Jovian spot depicted in a 1711 canvas by Donato Creti, which is exhibited in the Vatican. Part of a series of panels in which different (magnified) heavenly bodies serve as backdrops for various Italian scenes, and all overseen by the astronomer Eustachio Manfredi for accuracy, Creti's painting is the first known depiction of the Great Red Spot as red (albeit raised to the Jovian northern hemisphere due to an optical inversion inherent to the era's telescopes). No Jovian feature was explicitly described in writing as red before the late 19th century.

The Great Red Spot has been observed since 5 September 1831. By 1879, over 60 observations had been recorded. Since it came into prominence in 1879, it has been under continuous observation.

A 2024 study of historical observations suggests that the "permanent spot" observed from 1665 to 1713 may not be the same as the modern Great Red Spot observed since 1831. It is suggested that the original spot disappeared, and later another spot formed, which is the one seen today.

Late 20th and 21st centuries

On 25 February 1979, when the Voyager 1 spacecraft was 9,200,000 km (5,700,000 mi) from Jupiter, it transmitted the first detailed image of the Great Red Spot. Cloud details as small as 160 km (100 mi) across were visible. The colorful, wavy cloud pattern seen to the left (west) of the Red Spot is a region of extraordinarily complex and variable wave motion.

In the 21st century, the major diameter of the Great Red Spot has been observed to be shrinking in size. At the start of 2004, its length was about half that of a century earlier, when it reached a size of 40,000 km (25,000 mi), about three times the diameter of Earth. At the present rate of reduction, it will become circular by 2040. It is not known how long the spot will last, or whether the change is a result of normal fluctuations. In 2019, the Great Red Spot began "flaking" at its edge, with fragments of the storm breaking off and dissipating. The shrinking and "flaking" fueled speculation from some astronomers that the Great Red Spot could dissipate within 20 years. However, other astronomers believe that the apparent size of the Great Red Spot reflects its cloud coverage and not the size of the actual, underlying vortex, and they also believe that the flaking events can be explained by interactions with other cyclones or anticyclones, including incomplete absorptions of smaller systems; if this is the case, this would mean that the Great Red Spot is not in danger of dissipating.

A smaller spot, designated Oval BA, which formed in March 2000 from the merging of three white ovals, has turned reddish in color. Astronomers have named it the Little Red Spot or Red Jr. As of 5 June 2006, the Great Red Spot and Oval BA appeared to be approaching convergence. The storms pass each other about every two years, but the passings of 2002 and 2004 were of little significance. Amy Simon-Miller, of the Goddard Space Flight Center, predicted the storms would have their closest passing on 4 July 2006. She worked with Imke de Pater and Phil Marcus of UC Berkeley as well as a team of professional astronomers beginning in April 2006 to study the storms using the Hubble Space Telescope; on 20 July 2006, the two storms were photographed passing each other by the Gemini Observatory without converging. In May 2008, a third storm turned red.

The Juno spacecraft, which entered into a polar orbit around Jupiter in 2016, flew over the Great Red Spot upon its close approach to Jupiter on 11 July 2017, taking several images of the storm from a distance of about 8,000 km (5,000 mi) above the surface. Over the duration of the Juno mission, the spacecraft continued to study the composition and evolution of Jupiter's atmosphere, especially its Great Red Spot.

The Great Red Spot should not be confused with the Great Dark Spot, a feature observed near the northern pole of Jupiter in 2000 with the Cassini–Huygens spacecraft. There is also a feature in the atmosphere of Neptune called the Great Dark Spot. The latter feature was imaged by Voyager 2 in 1989 and may have been an atmospheric hole rather than a storm. It was no longer present as of 1994, although a similar spot had appeared farther to the north.

Mechanical dynamics

Jupiter's Great Red Spot rotates counterclockwise, with a period of about 4.5 Earth days, or 11 Jovian days, as of 2008. Measuring 16,350 km (10,160 mi) in width as of 3 April 2017, the Great Red Spot is 1.3 times the diameter of Earth. The cloud-tops of this storm are about 8 km (5 mi) above the surrounding cloud-tops. The storm has continued to exist for centuries because there is no planetary surface (only a mantle of hydrogen) to provide friction; circulating gas eddies persist for a very long time in the atmosphere because there is nothing to oppose their angular momentum.

Infrared data has long indicated that the Great Red Spot is colder (and thus higher in altitude) than most of the other clouds on the planet. The upper atmosphere above the storm, however, has substantially higher temperatures than the rest of the planet. Acoustic (sound) waves rising from the turbulence of the storm below have been proposed as an explanation for the heating of this region. The acoustic waves travel vertically up to a height of 800 km (500 mi) above the storm where they break in the upper atmosphere, converting wave energy into heat. This creates a region of upper atmosphere that is 1,600 K (1,330 °C; 2,420 °F)—several hundred kelvins warmer than the rest of the planet at this altitude. The effect is described as like "crashing [...] ocean waves on a beach".

Careful tracking of atmospheric features revealed the Great Red Spot's counterclockwise circulation as far back as 1966, observations dramatically confirmed by the first time-lapse movies from the Voyager fly-bys. The spot is confined by a modest eastward jet stream to its south and a very strong westward one to its north. Though winds around the edge of the spot peak at about 432 km/h (268 mph), currents inside it seem stagnant, with little inflow or outflow. The rotation period of the spot has decreased with time, perhaps as a direct result of its steady reduction in size.

The Great Red Spot's latitude has been stable for the duration of good observational records, typically varying by about a degree. Its longitude, however, is subject to constant variation, including a 90-day longitudinal oscillation with an amplitude of ~1°. Because Jupiter does not rotate uniformly at all latitudes, astronomers have defined three different systems for defining longitude. System II is used for latitudes of more than 10 degrees and was originally based on the average rotational period of the Great Red Spot of 9h 55m 42s. Despite this, however, the spot has "lapped" the planet in System II at least 10 times since the early 19th century. Its drift rate has changed dramatically over the years and has been linked to the brightness of the South Equatorial Belt and the presence or absence of a South Tropical Disturbance.

Internal depth and structure

Jupiter's Great Red Spot (GRS) is an elliptical shaped anticyclone, occurring at 22 degrees below the equator, in Jupiter's southern hemisphere. The largest anticyclonic storm (~16,000 km) in our solar system, little is known about its internal depth and structure. Visible imaging and cloud-tracking from in-situ observation determined the velocity and vorticity of the GRS, which is located in a thin anticyclonic ring at 70–85% of the radius and is located along Jupiter's fastest westward moving jet stream. During NASA's 2016 Juno mission, gravity signature and thermal infrared data were obtained that offered insight into the structural dynamics and depth of the GRS. During July 2017, the Juno spacecraft conducted a second pass of the GRS to collect Microwave Radiometer (MWR) scans of the GRS to determine how far the GRS extended toward the surface of the condensed H₂O layer. These MWR scans suggested that the GRS vertical depth extended to about 240 km below cloud level, with an estimated drop in atmospheric pressure to 100 bar. Two methods of analysis that constrain the data collected were the mascon approach, which found a depth of ~290 km, and the Slepian approach showing wind extending to ~310 km. These methods, along with gravity signature MWR data, suggest that the GRS zonal winds still increase at a rate of 50% of the velocity of the viable cloud level, before the wind decay starts at lower levels. This rate of wind decay and gravity data suggest the depth of the GRS is between 200 and 500 km.

Galileo and Cassini's thermal infrared imaging and spectroscopy of the GRS were conducted during 1995–2008, in order to find evidence of thermal inhomogeneities within the internal structure vortex of the GRS. Previous thermal infrared temperature maps from the Voyager, Galileo, and Cassini missions suggested the GRS is a structure of an anticyclonic vortex with a cold core within a upwelling warmer annulus; this data shows a gradient in the temperature of the GRS. Better understanding of Jupiter's atmospheric temperature, aerosol particle opacity, and ammonia gas composition was provided by thermal-IR imaging: a direct correlation of the visible cloud layers reactions, thermal gradient and compositional mapping to observational data were collected over decades. During December 2000, high spatial resolution images from Galileo, of an atmospheric turbulent area to the northwest of the GRS, showed a thermal contrast between the warmest region of the anticyclone and regions to the east and west of the GRS.

The vertical temperature of the structure of the GRS is constrained between the 100–600 mbar range, with the vertical temperature of the GRS core at approximately 400 mbar of pressure^{[clarification needed]} being 1.0–1.5°K, much warmer than regions of the GRS to the east–west, and 3.0–3.5°K warmer than regions to the north–south of the structure's edge. This structure is consistent with the data collected by the VISIR (VLT Mid-Infrared Imager Spectrometer on the ESO Very Large Telescope) imaging obtained in 2006; this revealed that the GRS was physically present at a wide range of altitudes that occur within the atmospheric pressure range of 80–600 mbar, and confirms the thermal infrared mapping result. To develop a model of the internal structure of the GRS, the Cassini instrument Composite Infrared Spectrometer (CIRS) and ground based spatial imaging mapped the composition of the phosphine and ammonia aerosols (PH₃, NH₃) and para-hydroxybenzoic acid within the anticyclonic circulation of the GRS. The images that were collected from the CIRS and ground-based imaging trace the vertical motion in the Jovian atmosphere by PH₃ and NH₃ spectra.

The highest concentrations of PH₃ and NH₃ were found to the north of the GRS peripheral rotation. They aided in determining the southward jet movement and showed evidence of an increase in altitude of the column of aerosols with pressures ranging from 200–500 mbar. However, the NH₃ composition data shows that there is a major depletion of NH₃ below the visible cloud layer at the southern peripheral ring of the GRS; this lower opacity is relative to a narrow band of atmospheric subsidence. The low mid-IR aerosol opacity, along with the temperature gradients, the altitude difference, and the vertical movement of the zonal winds, are involved with the development and sustainability of the vorticity. The stronger atmospheric subsidence and compositional asymmetries of the GRS suggest that the structure exhibits a degree of tilt from the northern edge to the southern edge of the structure.The GRS depth and internal structure has been constantly changing over decades; however there is still no logical reason that it is 200–500 km in depth, but the jet streams that supply the force that powers the GRS vortex are well below the structure base.

Color and composition

It is not known what causes the Great Red Spot's reddish color. Hypotheses supported by laboratory experiments suppose that it may be caused by chemical products created from the solar ultraviolet irradiation of ammonium hydrosulfide and the organic compound acetylene, which produces a reddish material—likely complex organic compounds called tholins. The high altitude of the compounds may also contribute to the coloring.

The Great Red Spot varies greatly in hue, from almost brick-red to pale salmon or even white. The spot occasionally disappears, becoming evident only through the Red Spot Hollow, which is its location in the South Equatorial Belt (SEB). Its visibility is apparently coupled to the SEB; when the belt is bright white, the spot tends to be dark, and when it is dark, the spot is usually light. These periods when the spot is dark or light occur at irregular intervals; from 1947 to 1997, the spot was darkest in the periods 1961–1966, 1968–1975, 1989–1990, and 1992–1993.

Contingency (evolutionary biology)

From Wikipedia, the free encyclopedia
https://en.wikipedia.org/wiki/Contingency_(evolutionary_biology)

In evolutionary biology, contingency describes how the outcome of evolution may be affected by the history of a particular lineage.

Overview

Evolution is a historical process, and the outcomes of history can be sensitive to the details of the interactions and events that preceded them. Contingency was especially emphasized by Stephen Jay Gould, particularly in his 1989 book Wonderful Life. Gould used the thought experiment of rewinding the "tape of life" to the distant past, and argued that even small changes to history would result in evolutionary outcomes very different from our world. Gould's thought experiment has inspired real experiments in the lab and in the field, as well as study of living and extinct organisms as natural experiments.

These studies have found that repeatability in evolution is common, particularly in cases of similar founding populations, when defining repeatability broadly, and over the timescales observable in experiments. Convergent evolution has also been found to be unexpectedly widespread in nature, though it occurs more often among closely related taxa that share more genes and developmental biases, indicating that contingency and convergence may both play a role. Additionally, a trait may be convergent at a broader level of description while being divergent at a more detailed level, with an example being the differently structured wings of insects, pterosaurs, birds, and bats. Knowing how common convergence is also requires more research into how often a trait failed to evolve under the same selective pressures, as well as into traits that evolved only once among all known organisms.

Some examples of contingency affecting evolutionary outcomes have been identified. In the E. coli long-term evolution experiment, out of the 12 populations, only one evolved the highly beneficial trait of growing on citrate, which further experimental replays using frozen ancestral bacteria showed required particular 'potentiating' mutations to arise first. Woodpeckers and aye-ayes occupy the same ecological niche of locating and extracting beetle larvae from wood, but do so by very different means (beak and elongated finger respectively) due to their respective evolutionary histories, as birds lack fingers and primates lack beaks. The unique flora and fauna of isolated locations on Earth, such as New Zealand, as well as from extinct lineages such as the non-avian dinosaurs during the Mesozoic, are also examples of contingency in evolution resulting in different outcomes.

In Wonderful Life

Replaying the "tape of life"

The central question proposed by Wonderful Life is that if life initially proliferated into a greater variety of phyla than currently exist and were subsequently decimated by the stochastic grim reaper of extinction, what then can be said about the inevitability of human intelligence and superiority? Additionally, Gould asks what role historical contingencies play in the evolution of life on Earth. It is these central ideas which prompt Gould to propose a thought experiment called "replaying the tape of life." Its central essence is this: if we rewind the clock and replay the history of life on Earth numerous times, will we consistently see the same outcome that is the reality we experience today? The outcome of this thought experiment has two possible interpretations, elaborated by Gould,

"Suppose that ten of a hundred designs will survive and diversify. If the ten survivors are predictable by superiority of anatomy (Interpretation 1), then they will win each time – and Burgess eliminations do not challenge our comforting view of life. But if the ten survivors are protégés of Lady Luck or fortunate beneficiaries of odd historical contingencies (Interpretation 2), then each replay of the tape will yield a different set of survivors and a radically different history. And if you recall from high-school algebra how to calculate permutations and combinations, you will realize that the total number of combinations for 10 items from a pool of 100 yields more than 17 trillion potential outcomes." – Stephen Jay Gould

Gould's opinion, and the central argument of Wonderful Life, is that "any replay of the tape of life would lead evolution down a pathway radically different from the road actually taken." Additionally, Gould argues, no outcome can be predicated from the start, but the resulting pattern that emerges after replaying the tape of life would be just as interpretable and logical as our current situation.

Evolutionary iconography

In Wonderful Life, Stephen Jay Gould discusses the iconography of evolution in popular culture and the damaging effects of the march of progress on public understanding of the theory.

The march of progress, Gould argues, has led to the popular interpretation that the evolution of increased mental powers, ultimately culminating in the development of man's complex brain, is the natural outcome of evolution. Thus, the term "Evolution" is often conflated with a linear progression of life towards ever-increasing mental powers and a "comfortable view of human inevitability and superiority." Gould argues that the definition of Evolution to professional biologists is "adaptation to changing environments", not progress, and that the composition of life on the planet is rather a "copiously branching bush, continually pruned by the grim reaper of extinction, not a ladder of predictable progress." He discusses society's obsession with unsuccessful lineages as "textbook cases" of "evolution". To elaborate, we consistently seek out "a single line of advance from the true topology of copious branching. In this misguided effort, we are inevitably drawn to branches so near the brink of total annihilation that they retain only one surviving twig. We then view this twig as the acme of upward achievement, rather than the probable last grasp of a richer ancestry." Gould uses the evolution of the horse to illustrate this point, as the unbroken connection between Hyracotherium (formerly called Eohippus) and Equus provides an apparent linear path from simplicity to complexity. The only reason the evolution of horses has become the canonical representation of progressive evolution is because their bush has been extremely unsuccessful. Instead, Gould argues, we should look to bats, antelopes, and rodents as champions of mammalian evolution as they present us with "thousands of twigs on a vigorous bush" and are the true embodiments of evolutionarily successful groups.

The cone vs the pyramid

Gould argues that the conventional view of evolution, as illustrated by the cone of increasing diversity, is flawed. It is typically assumed that early life is restricted in form, and from this restriction of form follows diversification into the variety of animal life that currently exists. This cone can be visualized as an inverted Christmas tree, with a narrow base and numerous branches proliferating outward into the present day. Gould presents an alternative hypothesis, however, which states that the history of life is better described as "decimation followed by diversification within a few remaining stocks", represented as a pyramid with a wide base of anatomical disparity that becomes increasingly constrained by natural selection and extinction level events as time moves forward. This is evidenced by the fact that the fossils excavated from the Burgess Shale in British Columbia represent a paleo-ecosystem with much greater anatomical disparity than currently exists and that fewer phyla exist today compared to the Cambrian seas. Gould offers the view that life during the Cambrian explosion quickly proliferated into the diversity of forms seen today due to the availability of numerous ecological niches and was subsequently decimated by extinction level events throughout geological time. He also notes that the survival of groups following extinction events bears no relationship to traditional notions of Darwinian success in normal times. For example,

"Even if fishes hone their adaptations to peaks of aquatic perfection, they will all die if the pond dries up. But grubby old buster the lungfish, former laughing stock of the piscine priesthood, may pull through – and not because a bunion on his great-grandfather's fin warned his ancestors about an impending comet. Buster and his kin may prevail because a feature evolved long ago for a different use has fortuitously permitted survival during a sudden and unpredictable change in the rules. And if we are Buster's legacy, and the result of a thousand other similarly happy accidents, how can we possibly view our mentality as inevitable, or even probable?" – Stephen Jay Gould

Ultimately, Gould explains, both the false iconography of the march of progress and our allegiance to the cone of increasing diversity have led us astray in our thinking about trends in evolutionary biology.

Implications in the Origin of Life and Extraterrestrial Life Detection

The paper Alternative Pathways in Astrobiology: Reviewing and Synthesizing Contingency and Non-Biomolecular Origins of Terrestrial and Extraterrestrial Life extends Gould' contingency concept to the origins of lifeAbiogenesis, proposing that non-biomolecular chemistry may have played a significant role in the emergence of life on Earth. The authors argue that prebiotic environments likely contained a diverse array of non-biomolecular compounds that could have contributed to the formation of life. This challenges the traditional view that life must arise solely from biomolecules, such as proteins and nucleic acids, and suggests that life's origins may be more complex and varied.

The paper also addresses the "N = 1 problem," which refers to the limitation of basing all theories of life on a single example—life on Earth. This terrestrial bias could hinder the search for extraterrestrial life by assuming that alien life must conform to Earth-like biochemical frameworks. The authors propose a model that incorporates both deterministic and contingent processes, suggesting a spectrum of possibilities for how life could arise under different environmental conditions. This broader understanding of the origins of life, which includes both biomolecular and non-biomolecular pathways, has significant implications for astrobiology and the detection of extraterrestrial biosignatures.

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Thursday, January 23, 2025

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Wednesday, January 22, 2025

Steady state (biochemistry)

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Great Red Spot

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Internal depth and structure

Color and composition

Contingency (evolutionary biology)

Overview

In Wonderful Life

Replaying the "tape of life"

Evolutionary iconography

The cone vs the pyramid

Implications in the Origin of Life and Extraterrestrial Life Detection

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