Bipolar Disorder

 

Bipolar disorder, also known as manic depression, is a mental disorder with periods of depression and periods of elevated mood. The elevated mood is significant and is known as mania or hypomania, depending on its severity, or whether symptoms of psychosis are present. During mania, an individual behaves or feels abnormally energetic, happy or irritable. Individuals often make poorly thought-out decisions with little regard to the consequences. The need for sleep is usually reduced during manic phases. During periods of depression there may be crying, a negative outlook on life, and poor eye contact with others. The risk of suicide among those with the illness is high at greater than 6 percent over 20 years, while self-harm occurs in 30–40 percent. Other mental health issues such as anxiety disorders and substance use disorder are commonly associated.

The causes are not clearly understood, but both environmental and genetic factors play a role. Many genes of small effect contribute to risk. Environmental factors include a history of childhood abuse, and long-term stress. The condition is divided into bipolar I disorder if there is at least one manic episode and bipolar II disorder if there are at least one hypomanic episode and one major depressive episode. In those with less severe symptoms of a prolonged duration the condition cyclothymic disorder may be diagnosed. If due to drugs or medical problems, it is classified separately. Other conditions that may present in a similar manner include attention deficit hyperactivity disorder, personality disorders, schizophrenia, and substance use disorder as well as a number of medical conditions. Medical testing is not required for a diagnosis, though blood tests or medical imaging can be done to rule out other problems.

Treatment commonly includes psychotherapy, as well as medications such as mood stabilizers and antipsychotics. Examples of mood stabilizers that are commonly used include lithium and various anticonvulsants. Treatment in hospital without a person's consent may be required if a person is at risk to themselves or others but refuses treatment. Severe behavioral problems may be managed with short term antipsychotics or benzodiazepines. In periods of mania, it is recommended that antidepressants be stopped. If antidepressants are used for periods of depression they should be used with a mood stabilizer. Electroconvulsive therapy (ECT) may be helpful for those who do not respond to other treatments. If treatments are stopped, it is recommended that this be done slowly. Many individuals have financial, social or work-related problems due to the illness. These difficulties occur a quarter to a third of the time on average. The risk of death from natural causes such as heart disease is twice that of the general population. This is due to poor lifestyle choices and the side effects from medications.

About 3 percent of people in the United States are estimated to have bipolar disorder at some point in their life. Lower rates of around 1 percent are found in other countries. The most common age at which symptoms begin is 25. Rates appear to be similar in females and males. The economic costs of the disorder have been estimated at $45 billion for the United States in 1991. A large proportion of this was related to a higher number of missed workdays, estimated at 50 per year. People with bipolar disorder often face problems with social stigma.

Signs and symptoms

Mania is the defining feature of bipolar disorder and can occur with different levels of severity. With milder levels of mania, known as hypomania, individuals are energetic, excitable, and may be highly productive. As hypomania worsens, individuals begin to exhibit erratic and impulsive behavior, often making poor decisions due to unrealistic ideas about the future, and sleep much reduced. At the extreme, manic individuals can experience distorted or delusional beliefs about the universe, hallucinate, and hear voices, to the point of psychosis. A depressive episode commonly follows an episode of mania. The biological mechanisms responsible for switching from a manic or hypomanic episode to a depressive episode, or vice versa, remain poorly understood.

Manic episodes

Mania is a distinct period of at least one week of elevated or irritable mood, which can range from euphoria to delirium, and those experiencing hypo- or mania may exhibit three or more of the following behaviors: speak in a rapid, uninterruptible manner, short attention span, racing thoughts, increased goal-oriented activities, agitation, or they may exhibit behaviors characterized as impulsive or high-risk, such as hypersexuality or excessive spending. To meet the definition for 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.

People with hypomania or mania may experience a decreased need of sleep; speak excessively in addition to speaking rapidly, and impaired judgment. Manic individuals often have a history of substance abuse developed over years as a form of "self-medication". At the more extreme, a person in a full-blown manic state can experience psychosis; a break with reality, a state in which thinking is affected along with mood. They may feel unstoppable, or as if they have been "chosen" and are on a "special mission" or have 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 their reliability.

The onset of a manic (or depressive) episode is often foreshadowed by sleep disturbances. Mood changes, psychomotor and appetite changes, and an increase in anxiety can also occur up to three weeks before a manic episode develops.

Hypomanic episodes

Hypomania is the milder form of mania, defined as at least four days of the same criteria as mania, but 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 persons who experience it, though most people who experience hypomania state that the stress of the experience is very painful. Bipolar people who go hypo, however, 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. What might be called a "hypomanic event", if not accompanied by depressive episodes, is often not deemed problematic, unless the mood changes are uncontrollable, volatile or mercurial. Most commonly, symptoms continue for a few weeks to a few months.

Depressive episodes

Depression

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 and/or weight, fatigue, problems concentrating, self-loathing or feelings of worthlessness, and thoughts of death or suicidal ideation. In severe cases, the individual may develop symptoms of psychosis, a condition also known as severe bipolar disorder with psychotic features. These symptoms include delusions and hallucinations. A major depressive episode persists for at least two weeks and may result in suicide if left untreated.

The earlier the age of onset, the more likely the first few episodes are to be depressive. Because a bipolar diagnosis requires a manic or hypomanic episode, many patients are initially diagnosed and treated as having major depression and then incorrectly prescribed antidepressants.

Mixed affective episodes

In bipolar disorder, mixed state is a condition 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. Mixed states are considered to be high-risk for suicidal behavior since depressive emotions such as hopelessness are often paired with mood swings or difficulties with impulse control. Anxiety disorder occurs more frequently as comorbidity in mixed bipolar episodes than in non-mixed bipolar depression or mania. Substance abuse (including alcohol) also follows this trend, thereby appearing to depict bipolar symptoms as no more than a consequence of substance abuse.

Associated features

Associated features are clinical phenomena that often accompany the disorder but are not part of the diagnostic criteria. In adults with the condition, bipolar disorder is often accompanied by changes in cognitive processes and abilities. These include reduced attentional and executive capabilities and impaired memory. How the individual processes the universe also depends on the phase of the disorder, with differential characteristics between the manic, hypomanic and depressive states. Some studies have found a significant association between bipolar disorder and creativity. Those with bipolar disorder may have difficulty in maintaining relationships. There are several common childhood precursors seen in children who later receive a diagnosis of bipolar disorder; these disorders include mood abnormalities, full major depressive episodes, and attention deficit hyperactivity disorder (ADHD).

Comorbid conditions

The diagnosis of bipolar disorder can be complicated by coexisting (comorbid) psychiatric conditions including the following: obsessive-compulsive disorder, substance abuse, eating disorders, attention deficit hyperactivity disorder, social phobia, premenstrual syndrome (including premenstrual dysphoric disorder), or panic disorder. A careful longitudinal analysis of symptoms and episodes enriched, if possible, by discussions with friends and family members, is crucial to establishing a treatment plan where these comorbidities exist.

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 60–80 percent 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 disorder type I, the (probandwise) concordance rates in modern studies have been consistently estimated at around 40 percent in identical twins (same genes), compared to about 5 percent in fraternal twins. A combination of bipolar I, II and cyclothymia produced concordance rates of 42 percent vs. 11 percent, with a relatively lower ratio for bipolar II that likely reflects heterogeneity. There is overlap with unipolar depression and if this is also counted in the co-twin the concordance with bipolar disorder rises to 67 percent in monozygotic twins and 19 percent in dizygotic. The relatively low concordance between dizygotic 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

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 affected with bipolar disorder when compared to the general population; similarly, the risk of major depressive disorder is three times higher in relatives of those with bipolar disorder when compared to the general population.

Although the first genetic linkage finding for mania was in 1969, the linkage studies have been inconsistent. The largest and most recent genome-wide association study failed to find any particular locus that exerts a large effect reinforcing the idea that no single gene is responsible for bipolar disorder in most cases.

Findings point strongly to heterogeneity, with different genes being implicated in different families. Robust and replicable genome-wide significant associations showed several common single nucleotide polymorphisms, including variants within the genes CACNA1C, ODZ4, and NCAN.

Advanced paternal age has been linked to a somewhat increased chance of bipolar disorder in offspring, consistent with a hypothesis of increased new genetic mutations.

Physiological

 Brain imaging studies have revealed differences in the volume of various brain regions between BD patients and healthy control subjects.

Abnormalities in the structure and/or function of certain brain circuits could underlie bipolar. Meta-analyses of structural MRI studies in bipolar disorder report an increase in the volume of the lateral ventricles, globus pallidus and increase in the rates of deep white matter hyper-intensities. Functional MRI findings suggest that abnormal modulation between ventral prefrontal and limbic regions, especially the amygdala, are likely contribute to poor emotional regulation and mood symptoms.

Euthymic bipolar people show decreased activity in the lingual gyrus, while people who are manic demonstrated decreased activity in the inferior frontal cortex, while no differences were found in people with depressed bipolar. People with bipolar have increased activation of left hemisphere ventral limbic areas and decreased activation of right hemisphere cortical structures related to cognition.

One proposed model for bipolar suggests that hyper-sensitivity of reward circuits consisting of fronto-striatal circuits causes mania and hyposensitivity of these circuits cause 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 (HPA axis) leading to its over activation, which may play a role in the pathogenesis of bipolar disorder.

Other brain components which have been proposed to play a role are the mitochondria and a sodium ATPase pump. Circadian rhythms and melatonin activity also seem to be altered.

Environmental

Environmental factors play a significant role in the development and course of bipolar disorder, and individual psychosocial variables may interact with genetic dispositions. It is probable that recent life events and interpersonal relationships contribute to the likelihood of onsets and recurrences of bipolar mood episodes, as they do for onsets and recurrences of unipolar depression. In surveys, 30–50 percent of adults diagnosed with bipolar disorder report traumatic/abusive experiences in childhood, which is associated on average with earlier onset, a higher rate of suicide attempts, and more co-occurring disorders such as PTSD. The number of reported stressful events in childhood is higher in those with an adult diagnosis of bipolar spectrum disorder compared to those without, particularly events stemming from a harsh environment rather than from the child's own behavior.

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. Such conditions and injuries include (but are not limited to) stroke, traumatic brain injury, HIV infection, multiple sclerosis, porphyria, and rarely temporal lobe epilepsy.

Neurochemical

Dopamine, a known neurotransmitter responsible for mood cycling, has been shown to have increased transmission during the manic phase. The dopamine hypothesis states that the increase in dopamine results in secondary homeostatic down regulation of key systems and receptors such as an increase in dopamine mediated G protein-coupled receptors. This results in decreased dopamine transmission characteristic of the depressive phase. The depressive phase ends with homeostatic up regulation 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. The increase in GABA is possibly caused by a disturbance in early development causing a disturbance of cell migration and the formation of normal lamination, the layering of brain structures commonly associated with the cerebral cortex.

Medications use 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 G coupled proteins.

Decreased levels of 5-HIAA in the CSF of bipolar patients during both depressed and manic phases. Increased dopaminergic activity has been hypothesized in manic states due to the ability of dopamine agonist to stimulant mania in bipolar patients. Decreased sensitivity of regulatory a2 adrenergic receptors as well as increased cell counts in the locus coeruleus indicated increased noradrenergic activity in manic patients. 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 bipolar patients. Tyrosine depletion was found to attenuate the effects of methamphetamine in bipolar patients as well as symptoms of mania, implicating dopamine in mania. VMAT2 binding was found to be increased in one study of bipolar manic patients.

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 pernicious course of illness. There has been debate regarding the causal relationship between usage of cannabis and bipolar disorder.

Diagnosis

Bipolar disorder is commonly diagnosed during adolescence or early adulthood, but onset can occur throughout the life cycle. The disorder can be difficult to distinguish from unipolar depression and the average delay in diagnosis is 5–10 years after symptoms begin. Diagnosis of bipolar disorder takes several factors into account and considers the self-reported experiences of the symptomatic individual, abnormal behavior reported by family members, friends or co-workers, observable signs of illness as assessed by a clinician, and often a medical work-up to rule-out medical causes. In diagnosis, caregiver-scored rating scales, specifically the mother, has been found to be more accurate than teacher and youth report in predicting 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 clinically within the U.S. and are the prevailing criteria used internationally in research studies. The DSM-5, published in 2013, included further and more accurate specifiers compared to its predecessor, the DSM-IV-TR. Semi structured interviews such as the Kiddie Schedule for Affective Disorders and Schizophrenia (KSADS) and the Structured Clinical Interview for DSM-IV (SCID) are used for diagnostic confirmation of bipolar disorder.

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

There are several other mental disorders with symptoms similar to those seen in bipolar disorder. These disorders include schizophrenia, major depressive disorder, attention deficit hyperactivity disorder (ADHD), and certain personality disorders, such as borderline personality disorder.

Although there are no biological tests that are diagnostic of bipolar disorder, blood tests and/or imaging may be carried out to exclude medical illnesses with clinical presentations similar to that of bipolar disorder such as hypothyroidism or hyperthyroidism, metabolic disturbance, a chronic disease, or an infection such as HIV or syphilis. A review of current and recent medications and drug use is considered to rule out these causes; common medications that can cause manic symptoms include antidepressants, prednisone, Parkinson's disease medications, thyroid hormone, stimulants (including cocaine and methamphetamine), and certain antibiotics. 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. Additional testing is especially indicated when age of first onset is mid to late life. Investigations are not generally repeated for a relapse unless there is a specific medical indication.

Bipolar spectrum

 Since Emil Kraepelin's distinction between bipolar disorder and schizophrenia in the 19th century, researchers have defined a spectrum of different types of bipolar disorder.

Bipolar spectrum disorders includes: 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.

Unipolar hypomania without accompanying depression has been noted in the medical literature. There is speculation as to whether this condition may occur with greater frequency in the general, untreated population; successful social function of these potentially high-achieving individuals may lead to being labeled as normal, rather than as individuals with substantial dysregulation.

Criteria and subtypes

The DSM and the ICD characterize bipolar disorder as a spectrum of disorders occurring on a continuum. The DSM-5 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 episode. 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 peri-partum 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 provide an explanation for why the full criteria were not met (e.g., hypomania without a prior major depressive episode).

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 of the above subtypes. It is defined as having four or more mood disturbance episodes within a one-year span and is found in a significant proportion of individuals with bipolar disorder. 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) is that of Dunner and Fieve: at least four major depressive, manic, hypomanic or mixed episodes are required to have occurred during a 12-month period. Ultra-rapid (days) and ultra-ultra-rapid or ultradian (within a day) cycling have also been described. The literature examining the pharmacological treatment of rapid cycling is sparse and there is no clear consensus with respect to its optimal pharmacological management.

Management

There are a number of pharmacological and psychotherapeutic techniques used to treat bipolar disorder. Individuals may use self-help and pursue recovery.

Hospitalization may be required especially with the manic episodes present in bipolar I. This can be voluntary or (if mental health legislation allows and varying state-to-state regulations in the USA) involuntary (called civil or involuntary commitment). 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 and patient-led support groups, intensive outpatient programs. These are sometimes referred to as partial-inpatient programs.

Psychosocial

Psychotherapy is aimed at alleviating core symptoms, recognizing episode triggers, reducing negative expressed emotion in relationships, recognizing prodromal symptoms before full-blown recurrence, and, practicing the factors that lead to maintenance of remission. Cognitive behavioral therapy, 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 carbonate is one of many treatments for bipolar disorder

A number of medications are used to treat bipolar disorder. The medication with the best evidence is lithium, which is effective in treating acute manic episodes and preventing relapses; lithium is also an effective treatment for bipolar depression. Lithium reduces the risk of suicide, self-harm, and death in people with bipolar disorder. It is unclear if ketamine is useful in bipolar as of 2015.

Four anticonvulsants are used in the treatment of bipolar disorder. Carbamazepine effectively treats manic episodes, with some evidence it has greater benefit in rapid-cycling bipolar disorder, or those with more psychotic symptoms or a more schizoaffective clinical picture. It is less effective in preventing relapse than lithium or valproate. Carbamazepine became a popular treatment option for bipolar in the late 1980s and early 1990s, but was displaced by sodium valproate in the 1990s. Since then, valproate has become a commonly prescribed treatment, and is effective in treating manic episodes. Lamotrigine has some efficacy in treating bipolar depression, and this benefit is greatest in more severe depression. It has also been shown to have some benefit in preventing further episodes, though there are concerns about the studies done, and is of no benefit in rapid cycling disorder. The effectiveness of topiramate is unknown. Depending on the severity of the case, anticonvulsants may be used in combination with lithium or on their own.

Antipsychotic medications are effective for short-term treatment of bipolar manic episodes and appear to be superior to lithium and anticonvulsants for this purpose. However, other medications such as lithium are preferred for long-term use. Olanzapine is effective in preventing relapses, although the evidence is not as solid as the evidence for lithium. Antidepressants have not been found to be of any benefit over that found with mood stabilizers.

Short courses of benzodiazepines may be used in addition to other medications until mood stabilizing become effective.

Alternative medicine

Several studies have suggested that omega 3 fatty acids may have beneficial effects on depressive symptoms, but not manic symptoms. However, only a few small studies of variable quality have been published and there is not enough evidence to draw any firm conclusions.

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 and high rates of initial under- or misdiagnosis, causing a delay in appropriate treatment interventions and contributing to poorer prognoses. After a diagnosis is made, it remains is 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 prior to developing bipolar disorder and being a parent are protective towards suicide attempts.

Functioning

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 in seen in both BD-I and BD-II, but people with BD-II experience a lesser degree of impairment. 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 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 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 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 from first admission for mania or mixed episode (representing the hospitalized and therefore most severe cases) found that 50 percent achieved syndromal recovery (no longer meeting criteria for the diagnosis) within six weeks and 98 percent within two years. Within two years, 72 percent achieved symptomatic recovery (no symptoms at all) and 43 percent achieved functional recovery (regaining of prior occupational and residential status). However, 40 percent went on to experience a new episode of mania or depression within 2 years of syndromal recovery, and 19 percent 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 suicidal 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 percent, which is 10–20 times that of the general population. The standardized mortality ratio from suicide in bipolar disorder is between 18 and 25. The lifetime risk of suicide has been estimated to be as high as 20 percent in those with bipolar disorder.

Epidemiology

Bipolar disorder is the sixth leading cause of disability worldwide and has a lifetime prevalence of about 3 percent in the general population. However, a reanalysis of data from the National Epidemiological Catchment Area survey in the United States suggested that 0.8 percent of the population experience a manic episode at least once (the diagnostic threshold for bipolar I) and a further 0.5 percent 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 percent of the population, adding up to a total of 6.4 percent, were classified as having a bipolar spectrum disorder. A more recent analysis of data from a second US National Comorbidity Survey found that 1 percent met lifetime prevalence criteria for bipolar I, 1.1 percent for bipolar II, and 2.4 percent for subthreshold symptoms.

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 suffer 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 under-diagnosis 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 and European American counterparts.

Late adolescence and early adulthood are peak years for the onset of bipolar disorder. One study also found that in 10 percent of bipolar cases, the onset of mania had happened after the patient had turned 50.

History

German psychiatrist Emil Kraepelin first distinguished between manic–depressive illness and "dementia praecox" (now known as schizophrenia) in the late 19th century.

Variations in moods and energy levels have been observed as part of the human experience since throughout history. The words "melancholia", an old word for depression, and "mania" originated in Ancient Greece. The word melancholia is derived from melas (μελας), meaning "black", and chole (χολη), meaning "bile" or "gall", indicative of the term's origins in pre-Hippocratic humoral theory. Within the humoral theories, mania was viewed as arising from an excess of yellow bile, or a mixture of black and yellow bile. The linguistic origins of mania, however, are not so clear-cut. Several etymologies were proposed by the Ancient Roman physician Caelius Aurelianus, including the Greek word ania, meaning "to produce great mental anguish", and manos, meaning "relaxed" or "loose", which would contextually approximate to an excessive relaxing of the mind or soul. There are at least five other candidates, and part of the confusion surrounding the exact etymology of the word mania is its varied usage in the pre-Hippocratic poetry and mythology.

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; on January 31, 1854, Jules Baillarger described to the French Imperial Académie Nationale de Médecine a biphasic mental illness causing recurrent oscillations between mania and depression, which he termed folie à double forme (dual-form insanity). Two weeks later, on February 14, 1854, Jean-Pierre Falret presented a description to the Academy on what was essentially the same disorder, and which he called folie circulaire (circular insanity).

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 was first proposed by German psychiatrists Karl Kleist and Karl Leonhard in the 1950s and they have 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

Singer Rosemary Clooney's public revelation of bipolar disorder in 1977 made her an early celebrity spokeswoman for mental illness.

There are widespread problems with social stigma, stereotypes, and prejudice against individuals with a diagnosis of bipolar disorder.

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). In his autobiography Manicdotes: There's Madness in His Method (2008) Chris Joseph describes his struggle between the creative dynamism which allowed the creation of his multimillion-pound advertising agency Hook Advertising, and the money-squandering dark despair of his bipolar illness.

Several dramatic works have portrayed characters with traits suggestive of the diagnosis that has been the subject of discussion by psychiatrists and film experts alike. A notable example is Mr. Jones (1993), in which Mr. Jones (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, suffers from bipolar disorder, though that specific term for the condition did not exist when the play was written.

TV specials, for example the BBC's Stephen Fry: The Secret Life of the Manic Depressive, MTV's True Life: I'm Bipolar, talk shows, and public radio shows, and the greater willingness of public figures to discuss their own bipolar disorder, have focused on psychiatric conditions, thereby, raising public awareness.

On April 7, 2009, the nighttime drama 90210 on the CW network aired a special episode where the character Silver 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 is bipolar, which she has kept secret since her school days. In April 2014, ABC premiered a medical drama, Black Box, in which the main character, a world-renowned neuroscientist, is bipolar.

Specific populations

Children

Lithium is the only medication approved by the FDA for treating mania in children.

In the 1920s, Emil 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.

While in adults the course of bipolar disorder is characterized by discrete episodes of depression and mania with no clear symptomatology between them, in children and adolescents very fast mood changes or even chronic symptoms are the norm. Pediatric bipolar disorder is commonly characterized by outbursts of anger, irritability and psychosis, rather than euphoric mania, which is more likely to be seen in adults. Early onset bipolar disorder is more likely to manifest as depression rather than mania or hypomania.

The diagnosis of childhood bipolar disorder is controversial, although it is not under discussion that the typical symptoms of bipolar disorder have negative consequences for minors suffering them. The debate is mainly centered on whether what is called bipolar disorder in children refers to the same disorder as when diagnosing adults, and the related question of whether the criteria for diagnosis for adults are useful and accurate when applied to children. Regarding diagnosis of children, some experts recommend following the DSM criteria. Others believe that these criteria do not correctly separate children with bipolar disorder from other problems such as ADHD and emphasize fast mood cycles. Still others argue that what accurately differentiates children with bipolar disorder is irritability. The practice parameters of the AACAP encourage the first strategy. American children and adolescents diagnosed with bipolar disorder in community hospitals increased 4-fold reaching rates of up to 40 percent in 10 years around the beginning of the 21st century, while in outpatient clinics it doubled reaching 6 percent. Studies using DSM criteria show that up to 1 percent of youth may have bipolar disorder.

Treatment involves medication and psychotherapy. Drug prescription usually consists in mood stabilizers and atypical antipsychotics. 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. Chronic medication is often needed.

Current 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 a pharmoco-therapy. Unfortunately, the literature and research on the effects of psycho-social therapy on BPSD is scarce, making it difficult to determine the efficacy of various therapies. The DSM-5 has proposed a new diagnosis which is considered to cover some presentations currently thought of as childhood-onset bipolar.

Elderly

There is a relative lack of knowledge about bipolar disorder in late life. There is evidence that it becomes less prevalent with age but nevertheless accounts for a similar percentage of psychiatric admissions; that older bipolar patients had first experienced symptoms at a later age; that later onset of mania is associated with more neurologic impairment; that substance abuse is considerably less common in older groups; and that there is probably a greater degree of variation in presentation and course, for instance individuals may develop new-onset mania associated with vascular changes, or become manic only after recurrent depressive episodes, or may have been diagnosed with bipolar disorder at an early age and still meet criteria. There is also some weak and not conclusive evidence that mania is less intense and there is a higher prevalence of mixed episodes, although there may be a reduced response to treatment. Overall, there are likely more similarities than differences from younger adults. In the elderly, recognition and treatment of bipolar disorder may be complicated by the presence of dementia or the side effects of medications being taken for other conditions.

Narcissistic Personality Disorder

 Narcissistic personality disorder (NPD) is a personality disorder with a long-term pattern of abnormal behavior characterized by exaggerated feelings of self-importance, excessive need for admiration, and a lack of empathy. Those affected often spend a lot of time thinking about achieving power or success, or on their appearance. They often take advantage of the people around them. The behavior typically begins by early adulthood and occurs across a variety of social situations.

The cause of narcissistic personality disorder is unknown. It is a personality disorder classified within cluster B by the Diagnostic and Statistical Manual of Mental Disorders (DSM). Diagnosis is made by a healthcare professional interviewing the person in question. The condition needs to be differentiated from mania and substance use disorder.

Treatments have not been well-studied. Therapy is often difficult as people with the disorder frequently do not consider themselves to have a problem. About one percent of people are believed to be affected at some point in their lives. It appears to occur more often in males than females and affects young people more than older people. The personality was first described in 1925 by Robert Waelder, and the term NPD came into use in 1968.

Signs and symptoms

People with narcissistic personality disorder (NPD) are characterized by persistent grandiosity, excessive need for admiration, and a personal disdain and lack of empathy for others. As such, the person with NPD usually displays arrogance and a distorted sense of superiority, and they seek to establish abusive power and control over others. Self-confidence (a strong sense of self) is different from narcissistic personality disorder; people with NPD typically value themselves over others to the extent that they openly disregard the feelings and wishes of others, and expect to be treated as superior, regardless of their actual status or achievements. Moreover, the person with narcissistic personality disorder usually exhibits a fragile ego (self-concept), intolerance of criticism, and a tendency to belittle others to validate their own superiority.

The DSM-5 indicates that persons with NPD usually display some or all of the following symptoms, typically without the commensurate qualities or accomplishments:

1.            Grandiosity with expectations of superior treatment from other people

2.            Fixated on fantasies of power, success, intelligence, attractiveness, etc.

3.            Self-perception of being unique, superior, and associated with high-status people and institutions

4.            Needing continual admiration from others

5.            Sense of entitlement to special treatment and to obedience from others

6.            Exploitative of others to achieve personal gain

7.            Unwilling to empathize with the feelings, wishes, and needs of other people

8.            Intensely envious of others and the belief those others are equally envious of them

9.            Pompous and arrogant demeanor

Narcissistic personality disorder usually develops in adolescence or early adulthood. It is not uncommon for children and adolescents to display traits similar to those of NPD, but such occurrences are usually transient and below the criteria for a diagnosis of NPD. True symptoms of NPD are pervasive, apparent in varied situations, and rigid, remaining consistent over time. The NPD symptoms must be sufficiently severe that they significantly impair the person's capabilities to develop meaningful human relationships. Generally, the symptoms of NPD also impair the person's psychological abilities to function, either at work, school or in important social settings. The DSM-5 indicates that the traits manifested by the person must substantially differ from cultural norms, to qualify as symptoms of NPD.

Associated features

People with NPD tend to exaggerate their skills, accomplishments, and their level of intimacy with people they consider high-status. This sense of superiority may cause them to monopolize conversations or to become impatient or disdainful when others talk about themselves. When their own ego is wounded by a real or perceived criticism, their anger can be disproportionate to the situation, but typically, their actions and responses are deliberate and calculated. Despite occasional flare-ups of insecurity, their self-image is primarily stable (i.e., overinflated).

To the extent that people are pathologically narcissistic, they can be controlling, blaming, self-absorbed, intolerant of others' views, unaware of others' needs and the effects of their behavior on others, and insist that others see them as they wish to be seen. Narcissistic individuals use various strategies to protect themselves at the expense of others. They tend to devalue, derogate, insult, and blame others, and they often respond to threatening feedback with anger and hostility. Since the fragile ego of individuals with NPD is hypersensitive to perceived criticism or defeat, they are prone to feelings of shame, humiliation, and worthlessness over minor or even imagined incidents. They usually mask these feelings from others with feigned humility or by isolating themselves socially, or they may react with outbursts of rage, defiance, or by seeking revenge. The merging of the "inflated self-concept" and the "actual self" is seen in the inherent grandiosity of narcissistic personality disorder. Also inherent in this process are the defense mechanisms of denial, idealization, and devaluation.

According to the DSM-5: "Many highly successful individuals display personality traits that might be considered narcissistic. Only when these traits are inflexible, maladaptive, and persisting and because significant functional impairment or subjective distress do they constitute narcissistic personality disorder." Due to the high functionality associated with narcissism, some people may not view it as an impairment in their lives. Although overconfidence tends to make individuals with NPD ambitious, it does not necessarily lead to success and high achievement professionally. These individuals may be unwilling to compete or may refuse to take any risks to avoid appearing like a failure. In addition, their inability to tolerate setbacks, disagreements, or criticism, along with their lack of empathy, make it difficult for such individuals to work cooperatively with others or to maintain long-term professional relationships with superiors and colleagues.

Causes

The causes of narcissistic personality disorder are unknown. Experts tend to apply a biopsychosocial model of causation, meaning that a combination of environmental, social, genetic, and neurobiological factors is likely to play a role in formulating a narcissistic personality.

Genetic

There is evidence that narcissistic personality disorder is heritable, and individuals are much more likely to develop NPD if they have a family history of the disorder. Studies on the occurrence of personality disorders in twins determined that there is a moderate to high heritability for narcissistic personality disorder.

However, the specific genes and gene interactions that contribute to its cause—and how they may influence the developmental and physiological processes underlying this condition—have yet to be determined.

Environment

Environmental and social factors are also thought to have a significant influence on the onset of NPD. In some people, pathological narcissism may develop from an impaired attachment to their primary caregivers, usually their parents. This can result in the child's perception of himself/herself as unimportant and unconnected to others. The child typically comes to believe they have some personality defect that makes them unvalued and unwanted. Overindulgent, permissive parenting as well as insensitive, over-controlling parenting are believed to be contributing factors.

According to Leonard Groopman and Arnold Cooper, the following have been identified by various researchers as possible factors that promote the development of NPD:

•             An oversensitive temperament (personality traits) at birth.

•             Excessive admiration that is never balanced with realistic feedback.

•             Excessive praise for good behaviors or excessive criticism for bad behaviors in childhood.

•             Overindulgence and overvaluation by parents, other family members, or peers.

•             Being praised for perceived exceptional looks or abilities by adults.

•             Severe emotional abuse in childhood.

•             Unpredictable or unreliable caregiving from parents.

•             Learning manipulative behaviors from parents or peers.

•             Valued by parents as a means to regulate their own self-esteem.

Cultural elements are believed to influence the prevalence of NPD as well since NPD traits are more common in modern societies than in traditional ones.

Pathophysiology

There is little research into the neurological underpinnings of narcissistic personality disorder. However, recent research has identified a structural abnormality in the brains of those with narcissistic personality disorder, specifically noting less volume of gray matter in the left anterior insula. Another study has associated the condition with reduced gray matter in the prefrontal cortex.

The brain regions identified in the above studies are associated with empathy, compassion, emotional regulation, and cognitive functioning. These findings suggest that narcissistic personality disorder is related to a compromised capacity for emotional empathy and emotional regulation.

Diagnosis

DSM-5

The formulation of narcissistic personality disorder in the American Psychiatric Association's (APA) Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision (DSM-IV-TR) was criticized for failing to describe the range and complexity of the disorder. Critics said it focuses overly on "the narcissistic individual's external, symptomatic, or social interpersonal patterns—at the expense of ... internal complexity and individual suffering", which they argued reduced its clinical utility.

The Personality and Personality Disorders Work Group originally proposed the elimination of NPD as a distinct disorder in DSM-5 as part of a major revamping of the diagnostic criteria for personality disorders, replacing a categorical with a dimensional approach based on the severity of dysfunctional personality trait domains. Some clinicians objected to this, characterizing the new diagnostic system as an "unwieldy conglomeration of disparate models that cannot happily coexist" and may have limited usefulness in clinical practice. The general move towards a dimensional (personality trait-based) view of Personality Disorders has been maintained despite the reintroduction of NPD.

ICD-10

The World Health Organization's (WHO) International Statistical Classification of Diseases and Related Health Problems, 10th Edition (ICD-10) lists narcissistic personality disorder under other specific personality disorders. It is a requirement of ICD-10 that a diagnosis of any specific personality disorder also satisfies a set of general personality disorder criteria.

Subtypes

While the DSM-5 regards narcissistic personality disorder as a homogeneous syndrome, there is evidence for variations in its expression. In a 2015 paper, two major presentations of narcissism are typically suggested, an "overt" or "grandiose" subtype, characterized by grandiosity, arrogance, and boldness, and a "covert" or "vulnerable" subtype characterized by defensiveness and hypersensitivity. Those with "narcissistic grandiosity" express behavior "through interpersonally exploitative acts, lack of empathy, intense envy, aggression, and exhibitionism." Psychiatrist Glen Gabbard described the subtype, which he referred to as the "oblivious" subtype as being grandiose, arrogant, and thick-skinned. The subtype of "narcissistic vulnerability" entails (on a conscious level) "helplessness, emptiness, low self-esteem, and shame, which can be expressed in the behavior as being socially avoidant in situations where their self-presentation is not possible so they withdraw, or the approval they need/expect is not being met." Gabbard described this subtype, which he referred to as the "hypervigilant" subtype as being easily hurt, oversensitive, and ashamed. In addition, a "high-functioning" presentation, where there is less impairment in the areas of life where those with a more severe expression of the disorder typically have difficulties in, is suggested.

Theodore Millon suggested five subtypes of narcissism. However, there are few pure variants of any subtype, and the subtypes are not recognized in the DSM or ICD.

Unprincipled narcissist including antisocial features. Deficient conscience; unscrupulous, amoral, disloyal, fraudulent, deceptive, arrogant, exploitive; a con artist and charlatan; dominating, contemptuous, vindictive.

Amorous narcissist including histrionic features. Sexually seductive, enticing, beguiling, tantalizing; glib and clever; disinclined to real intimacy; indulge hedonistic desires; bewitch and inveigles others; pathological lying and swindling. Tends to have many affairs, often with exotic partners.

Compensatory narcissists include negative and avoidant features.  Seeks to counteract or cancel out deep feelings of inferiority and lack of self-esteem; offsets deficits by creating illusions of being superior, exceptional, admirable, and noteworthy; self-worth results from self-enhancement.

Elitist narcissist. A variant of the pure pattern feels privileged and empowered by special childhood status and pseudo-achievements; the entitled façade bears little relation to reality; seeks a favored and good life; is upwardly mobile; and cultivates special status and advantages by association.

Normal narcissist. Absent of the traits of the other four                 Least severe and most interpersonally concerned and empathetic, still entitled and deficient in reciprocity; bold in environments, self-confident, competitive, seeks high targets, feels unique; talent in leadership positions; expecting of recognition from others.

Possible additional categories not cited by the current theory of Millon might include:

Fanatic narcissist including paranoid features. Grandiose delusions are irrational and flimsy; pretentious, expensive supercilious contempt and arrogance toward others; lost pride reestablished with extravagant claims and fantasies. Reclassified under paranoid personality disorder.

Hedonistic narcissist. A mix of Millon's initial four subtypes, Hedonistic and self-deceptive, avoidant of responsibility and blame, shifted onto others; idiosyncratic, often self-biographical, proud of minor quirks and achievements, conflict-averse and sensitive to rejection; procrastinative, self-undoing, avolitive, ruminantly introspective; the most prone to fantastic inner worlds which replace social life

Malignant narcissist.  Including antisocial, sadistic, and paranoid features. Fearless, guiltless, remorseless, calculating, ruthless, inhumane, callous, brutal, rancorous, aggressive, biting, merciless, vicious, cruel, spiteful; hateful and jealous; anticipates betrayal and seeks punishment; desires revenge; has been isolated, and is potentially suicidal or homicidal.

Will Titshaw also suggests three subtypes of narcissistic personality disorder which are not officially recognized in any editions of the DSM or the ICD.

Pure Narcissist.                 Mainly just NPD characteristics.                 Someone who has narcissistic features described in the DSM and ICD and lacks features from other personality disorders.

Attention Narcissist. Including histrionic (HPD) features.                They display the traditional NPD characteristics described in the ICD & DSM along with histrionic features because they think they are superior and therefore should have everyone's attention, and when they do not have everyone's attention they go out of their way to capture the attention of as many people as possible.

Beyond The Rules Narcissist. Including antisocial (ASPD) features. This type of narcissist thinks that because they are so superior to everyone they do not have to follow the rules like most people and therefore show behavior included in the ICD for dissocial personality disorder and behavior, included in the DSM for antisocial personality disorder.

Comorbidity

NPD has a high rate of comorbidity with other mental disorders. Individuals with NPD are prone to bouts of depression, often meeting the criteria for co-occurring depressive disorders. In addition, NPD is associated with bipolar disorder, anorexia, and substance use disorders, especially cocaine. As far as other personality disorders, NPD may be associated with histrionic, borderline, antisocial, and paranoid personality disorders.

Treatment

Narcissistic personality disorder is rarely the primary reason for people seeking mental health treatment. When people with NPD enter treatment, it is typically prompted by life difficulties or to seek relief from another disorder, such as major depressive disorder, substance use disorder, bipolar disorder, or eating disorders, or at the insistence of relatives and friends. This is partly because individuals with NPD generally have poor insight and fail to recognize their perception and behavior as inappropriate and problematic due to their very positive self-image.

Treatment for NPD is centered around psychotherapy. In the 1960s, Heinz Kohut and Otto Kernberg challenged the conventional wisdom of the time by outlining clinical strategies for using psychoanalytic psychotherapy with clients with NPD that they claimed were effective in treating the disorder. Contemporary treatment modalities commonly involve transference-focused, metacognitive, and schema-focused therapies. Some improvement might be observed through the treatment of symptoms related to comorbid disorders with psycho-pharmaceuticals, but as of 2016, according to Elsa Ronningstam, a psychologist at Harvard Medical School, "Alliance building and engaging the patient's sense of agency and reflective ability are essential for change in pathological narcissism."

Pattern change strategies performed over a long period are used to increase the ability of those with NPD to become more empathic in everyday relationships. To help modify their sense of entitlement and self-centeredness schema, the strategy is to help them identify how to utilize their unique talents and to help others for reasons other than their own personal gain. This is not so much to change their self-perception of their "entitlement" feeling but more to help them empathize with others. Another type of treatment would be temperament change. Psychoanalytic psychotherapy may be effective in treating NPD, but therapists must recognize the patient's traits and use caution in tearing down narcissistic defenses too quickly. Anger, rage, impulsivity, and impatience can be worked on with skill training. Therapy may not be effective because patients may receive feedback poorly and defensively. Anxiety disorders and somatoform disorders are prevalent, but the most common would be depression.

Group treatment has its benefits, as the effectiveness of receiving peer feedback rather than the clinicians may be more accepted, but group therapy can also contradict itself as the patient may show "demandingness, egocentrism, social isolation and withdrawal, and socially deviant behavior". Researchers originally thought group therapy among patients with NPD would fail because it was believed that group therapy required empathy which NPD patients lack. However, studies show group therapy does hold value for patients with NPD because it lets them explore boundaries, develop trust, increase self-awareness, and accept feedback. Relationship therapy stresses the importance of learning and applying four basic interpersonal skills: "...effective expression, empathy, discussion, and problem-solving/conflict resolution". Marital/relationship therapy is most beneficial when both partners participate.

No medications are indicated for treating NPD, but may be used to treat co-occurring mental conditions or symptoms that may be associated with it such as depression, anxiety, and impulsiveness if present.

Prognosis

The effectiveness of psychotherapeutic and pharmacological interventions in the treatment of narcissistic personality disorder has yet to be systematically and empirically investigated. Clinical practice guidelines for the disorder have not yet been created, and current treatment recommendations are largely based on theoretical psychodynamic models of NPD and the experiences of clinicians with afflicted individuals in clinical settings.

The presence of NPD in patients undergoing psychotherapy for the treatment of other mental disorders is associated with slower treatment progress and higher dropout rates.

Epidemiology

The lifetime prevalence of NPD is estimated at 1% in the general population and 2% to 16% in clinical populations. A 2010 systematic review found the prevalence of NPD to be between 0% to 6% in community samples. There is a small gender difference, with men having a slightly higher incidence than women.

According to a 2015 meta-analysis that looked at gender differences in NPD, there has recently been a debate about a perceived increase in the prevalence of NPD among younger generations and among women. However, the authors found that this was not reflected in the data and that the prevalence has remained relatively stable for both genders over the last 30 years (when data on the disorder were first collected).

History

The use of the term "narcissism" to describe excessive vanity and self-centeredness predates by many years the modern medical classification of narcissistic personality disorder. The condition was named after Narcissus, a mythological Greek youth who became infatuated with his own reflection in a lake. He did not realize at first that it was his own reflection, but when he did, he died out of grief for having fallen in love with someone who did not exist outside himself.

The term "narcissistic personality structure" was introduced by Kernberg in 1967 and "narcissistic personality disorder" was first proposed by Heinz Kohut in 1968.

Early Freudianism

Sigmund Freud commented, regarding the adult neurotic's sense of omnipotence, "This belief is a frank acknowledgment of a relic of the old megalomania of infancy". He similarly concluded: "We can detect an element of megalomania in most other forms of paranoic disorder. We are justified in assuming that this megalomania is essentially of an infantile nature and that, as development proceeds, it is sacrificed to social considerations".

Edmund Bergler also considered megalomania to be normal in the child, and for it to be reactivated in later life in gambling. Otto Fenichel states that, for those who react in later life to narcissistic hurt with denial, a similar regression to the megalomania of childhood is taking place.

Object relations

Whereas Freud saw megalomania as an obstacle to psychoanalysis, in the second half of the 20th century, object relations theory, both in the United States and among British Kleinians, set about revaluing megalomania as a defense mechanism that offered potential access for therapy. Such an approach is built on Heinz Kohut's view of narcissistic megalomania as an aspect of normal development, by contrast with Kernberg's consideration of such grandiosity as a pathological development distortion.

Society and culture

In popular culture, narcissistic personality disorder has been called megalomania.

Fiction

An article on the Victorian Web argues that Rosamond Vincy, in George Eliot's Middlemarch (1871–72), is a full-blown narcissist as defined by the DSM.

In the film To Die For, Nicole Kidman's character wants to appear on television at all costs, even if this involves murdering her husband. A psychiatric assessment of her character noted: "[she] was seen as a prototypical narcissistic person by the raters: on average, she satisfied 8 of 9 criteria for narcissistic personality disorder... had she been evaluated for personality disorders, she would receive a diagnosis of narcissistic personality disorder".

Other examples in popular fiction include television characters Adam Demamp (portrayed by Adam DeVine in Workaholics) and Dennis Reynolds (portrayed by Glenn Howerton in It's Always Sunny in Philadelphia).

Criticism

A Norwegian study concluded that narcissism should be conceived as personality dimensions pertinent to the whole range of PDs rather than as a distinct diagnostic category. Alarcón and Sarabia, in examining past literature on the disorder, concluded that narcissistic personality disorder "shows nosological inconsistency and that its consideration as a trait domain with needed further research would be strongly beneficial to the field".

Hepatitis E

 

Hepatitis E is a viral hepatitis (liver inflammation) caused by infection with a virus called hepatitis E virus. It is one of five known human hepatitis viruses: A, B, C, D, and E. HEV is a positive-sense single-stranded non-enveloped RNA icosahedral virus, HEV has a fecal-oral transmission route. Infection with this virus was first documented in 1955 during an outbreak in New Delhi, India. A preventative vaccine (HEV 239) is approved for use in China.

Although Hepatitis E often causes an acute and self-limiting infection (the virus usually resolves itself and the individual recovers) with low mortality rates in the western world, it bears a high risk of developing chronic hepatitis in immunocompromised patients with substantial mortality rates. Organ transplant recipients who receive immunosuppressive medication to prevent rejection are thought to be the main population at risk for chronic hepatitis E. Furthermore, in healthy individuals during the duration of the infection, the disease severely impairs a person’s ability to work, care for family members, and other daily activities. Hepatitis E occasionally develops into an acute, severe liver disease, and is fatal in about 2% of all cases. Clinically, it is comparable to hepatitis A, but in pregnant women the disease is more often severe and is associated with a clinical syndrome called fulminant liver failure. Pregnant women, especially those in the third trimester, suffer an elevated mortality rate from the disease of around 20%.

Hepatitis E newly affected about 28 million people in 2013.

Signs and symptoms

Acute infection

The incubation period of hepatitis E varies from 3 to 8 weeks. After a short prodromal phase symptoms lasting from days to weeks follow. They may include jaundice, fatigue and nausea. The symptomatic phase coincides with elevated hepatic aminotransferase levels.

Viral RNA becomes detectable in stool and blood serum during incubation period. Serum IgM and IgG antibodies against HEV appear just before onset of clinical symptoms. Recovery leads to virus clearance from the blood, while the virus may persist in stool for much longer. Recovery is also marked by disappearance of IgM antibodies and increase of levels of IgG antibodies.

Chronic infection

While usually an acute disease, in immunocompromised subjects—particularly in solid organ transplanted patients—hepatitis E may cause a chronic infection. Occasionally this may cause liver fibrosis and cirrhosis.

Virology

Classification

There is only one serotype of the virus and classification is based on the nucleotide sequences of the genome. Genotype 1 has been classified into five subtypes, genotype 2 into two subtypes and genotypes 3 and 4 have been into ten and seven subtypes respectively. Differences have been noted between the different genotypes. For genotype 1, the age at which incidence peaks is between 15 and 35 years and mortality is about 1%. Genotype 3 and 4—the most common in Japan—are more common in people older than 60 years and the mortality is between 5 and 10%.

Distribution

•             Genotype 1 has been isolated from tropical and several subtropical countries in Asia and Africa.

•             Genotype 2 has been isolated from Mexico, Nigeria, and Chad.

•             Genotype 3 has been isolated almost worldwide including Asia, Europe, Oceania, North and South America.

•             Genotype 4 appears to be limited.

Genotypes 1 and 2 are restricted to humans and often associated with large outbreaks and epidemics in developing countries with poor sanitation conditions. Genotypes 3 and 4 infect humans, pigs and other animal species and have been responsible for sporadic cases of hepatitis E in both developing and industrialized countries.

In the United Kingdom the Department for Environment, Food and Rural Affairs (DEFRA) said that the number of human hepatitis E cases increased by 39% between 2011 and 2012.

Transmission

 Hepatitis E Virus in Pork Liver Sausage

Hepatitis E is widespread in Southeast Asia, northern and central Africa, India, and Central America. It is spread mainly by the fecal-oral route due to fecal contamination of water supplies or food; person-to-person transmission is uncommon.

The incubation period following exposure to the hepatitis E virus ranges from three to eight weeks, with a mean of 40 days. Outbreaks of epidemic hepatitis E most commonly occur after heavy rainfalls and monsoons because of their disruption of water supplies. Major outbreaks have occurred in New Delhi, India (30,000 cases in 1955–1956), Burma (20,000 cases in 1976–1977), Kashmir, India (52,000 cases in 1978), Kanpur, India (79,000 cases in 1991), and China (100,000 cases between 1986 and 1988).

DEFRA said that there was evidence that the increase in hepatitis E in the UK was due to food-borne zoonoses, citing a study that found 10% of pork sausages on sale in the UK contained the virus. Some research suggests that food must reach a temperature of 70 °C for 20 minutes to eliminate the risk of infection. An investigation by the Animal Health and Veterinary Laboratories Agency found hepatitis E in 49% of pigs in Scotland.

Animal reservoir

Domestic animals have been reported as a reservoir for the hepatitis E virus, with some surveys showing infection rates exceeding 95% among domestic pigs. Replicative virus has been found in the small intestine, lymph nodes, colon and liver of experimentally infected pigs. Transmission after consumption of wild boar meat and uncooked deer meat has been reported as well. The rate of transmission to humans by this route and the public health importance of this are, however, still unclear.

A number of other small mammals have been identified as potential reservoirs: the lesser bandicoot rat (Bandicota bengalensis), the black rat (Rattus rattus brunneusculus) and the Asian house shrew (Suncus murinus). A new virus designated rat hepatitis E virus has been isolated.

A rabbit hepatitis E virus has been described, with a study published in 2014 showing that research rabbits from two different American vendors showed seroprevalences of 40% for Supplier A and 50% for Supplier B when testing for antibodies against hepatitis E virus (HEV). Supplier A was a conventional rabbit farm, and supplier B was a commercial vendor of specific pathogen free (SPF) research rabbits. The study remarks "HEV probably is widespread in research rabbits, but effects on research remain unknown." Laboratory animal care personnel, researchers, and support staff represent a new population at risk for HEV infection, and research facilities should be diligent in measures to prevention of this possibly zoonotic pathogen.

An avian virus has been described that is associated with hepatitis-splenomegaly syndrome in chickens. This virus is genetically and antigenically related to mammalian HEV, and probably represents a new genus in the family.

Genomics

Geldanamycin

The virus has since been classified into the genus Orthohepevirus, and has been reassigned into the Hepeviridae family. The virus itself is a small non-enveloped particle. The genome is approximately 7200 bases in length, is a polyadenylated single-strand RNA molecule that contains three discontinuous and partially overlapping open reading frames (ORFs) along with 5' and 3' cis-acting elements, which have important roles in HEV replication and transcription. ORF1 encodes a methyltransferase, protease, helicase and replicase; ORF2 encodes the capsid protein and ORF3 encodes a protein of undefined function. A three-dimensional, atomic-resolution structure of the capsid protein in the context of a virus-like particle has been described.

As of 2009 there are approximately 1,600 sequences of both human and animal isolates of HEV available in open-access sequence databases. Species of this genus infect humans, pigs, boars, deer, rats, rabbits and birds.

Virus life cycle

The life cycle of Hepatitis E virus is unknown; the capsid protein obtains viral entry by binding to a cellular receptor. ORF2 (c-terminal) moderates viral entry by binding to HSC70.

Geldanamycin blocks the transport of HEV239 capsid protein but not the binding/entry of the truncated capsid protein, which indicates that HSP90 plays an important part in HEV transport.

Prevention

Sanitation

Sanitation is the most important measure in prevention of hepatitis E; this consists of proper treatment and disposal of human waste, higher standards for public water supplies, improved personal hygiene procedures and sanitary food preparation. Thus, prevention strategies of this disease are similar to those of many others that plague developing nations.

Vaccines

A vaccine based on recombinant viral proteins was developed in the 1990s and tested in a high-risk population (in Nepal) in 2001. The vaccine appeared to be effective and safe, but development was stopped for lack of profitability, since hepatitis E is rare in developed countries. There is no licensed hepatitis E vaccine for use in the US.

Although other HEV vaccine trials have been successful, these vaccines have not yet been produced or made available to susceptible populations. The exception is China, after more than a year of scrutiny and inspection by China's State Food and Drug Administration (SFDA), a hepatitis E vaccine developed by Chinese scientists was available at the end of 2012. The vaccine—called HEV 239 by its developer Xiamen Innovax Biotech—was approved for prevention of hepatitis E in 2012 by the Chinese Ministry of Science and Technology, following a controlled trial on 100,000+ people each from Jiangsu Province where none of the vaccinated became infected during a 12-month period, compared to 15 in the group given placebo treatment. The first vaccine batches came out of Innovax' factory in late October 2012, and will be sold to Chinese distributors.

Treatment

 Ribavirin

In terms of treatment, ribavirin is not registered for Hepatitis E treatment, though there is off-label experience for treating chronic Hepatitis E with this compound. The use of low doses, of ribavirin over a three-month period has been associated with viral clearance in about two-thirds of chronic cases. Other possible treatments include pegylated interferon or a combination of ribavirin and pegylated interferon. In general, chronic HEV infection is associated with immunosuppressive therapies, but remarkably little is known about how different immune-suppressants affect HEV infection. In individuals with solid-organ transplantation viral clearance can be achieved by temporal reduction of the level of immunosuppression.

Epidemiology

The hepatitis E virus causes around 20 million infections a year. This result in around three million acute illnesses and as of 2010, 57,000 deaths annually. It is particularly dangerous for pregnant women, who can develop an acute form of the disease that is lethal in 30 percent of cases or more. The virus (HEV) is a major cause of illness and of death in the developing world and disproportionate cause of deaths among pregnant women. Hepatitis E is endemic in Central Asia, while Central America and the Middle East have reported outbreaks.

Recent outbreaks

In 2004, there were two outbreaks, both of them in sub-Saharan Africa. There was an outbreak in Chad in which there were several cases and fatalities. The second was in Sudan also with several fatalities. Increasingly, hepatitis E is being seen in developed nations, with reports in 2005 of 329 cases of hepatitis E virus infection in England and Wales. The disease is thought to be a zoonosis in that animals are thought to be the source. Both deer and swine have been implicated.

In October 2007, an epidemic of hepatitis E was suspected in Kitgum District of northern Uganda where no previous epidemics had been documented. This outbreak has progressed to become one of the largest hepatitis E outbreaks in the world. By June 2009, the epidemic had caused illness in 10,196 persons and 160 deaths. In 2011, a minor outbreak was reported in Tangail, a neighborhood of Dhaka, Bangladesh.

In July 2012, an outbreak was reported in South Sudanese refugee camps in Maban County near the Sudan border. South Sudan's Ministry of Health reported over 400 cases and 16 fatalities as of September 13, 2012. Progressing further, as of February 2, 2013, 88 have died due to the outbreak. The "Medical charity Medecins Sans Frontieres (MSF) said it had treated almost 4,000 patients."

In April 2014 there was an outbreak in Nepal, Biratnagar Municipality with over 6,000 locals infected and at least 9 dead.

History

The most recent common ancestor of Hepatitis E evolved between 536 and 1344 years ago. It diverged into two clades—an anthropotropic and an enzootic form—which subsequently evolved into genotypes 1 and 2 and genotypes 3 and 4 respectively. The divergence dates for the various genotypes are as follows: Genotypes 1/2 367–656 years ago; Genotypes 3/4 417–679 years ago. For the most recent common ancestor of the various viruses themselves: Genotype 1 between 87 and 199 years ago; Genotype 3 between 265 and 342 years ago; and Genotype 4 between 131 and 266 years ago. The anthropotropic strains (genotype 1 and 2) have evolved more recently than the others suggesting that this virus was originally a zooenosis.

The use of an avian strain confirmed the proposed topology of the genotypes 1–4 and suggested that the genus may have evolved 1.36 million years ago (range 0.23 million years ago to 2.6 million years ago).

Genotypes 1, 3 and 4 all increased their effective population sizes in the 20th century. The population size of genotype 1 increased noticeably in the last 30–35 years. Genotypes 3 and 4 population sizes began to increase in the late 19th century up to 1940–1945. Genotype 3 underwent a subsequent increase in population size until the 1960s. Since 1990 both genotypes' population sizes have been reduced back to levels last seen in the 19th century. The overall mutation rate for the genome has been estimated at ~1.4×10−3 substitutions/site/year.