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Aspects of Bipolar Disorder

The difference between Bipolar Disorder and Unipolar Disorder (generally called Clinical Depression) is that Bipolar Disorder involves periods of abnormally elevated mood in addition to depressed or level mood. The duration and intensity of mood states varies widely among people with the Bipolar diagnosis. Fluctuating from one mood state to the next is called 'cycling'. Mood swings can cause impairment or improved functioning depending on their direction (up or down) and severity (mild to severe). There can be changes in one's energy level, sleep pattern, activity level, social rhythms and cognitive functioning. Some people may have difficulty functioning during these times.


People with Bipolar Disorder are about 3 times as likely to commit suicide as those suffering from Major (Clinical) Depression (12% to 30%). Although many people with Bipolar Disorder, who attempt suicide never actually complete it, the annual average suicide rate in males and females with diagnosed Bipolar Disorder (0.4%) is 10 to more than 20 times that in the general population.


Individuals with Bipolar Disorder tend to become suicidal, especially during mixed states such as Dysphoric Mania and Agitated Depression.


The Depressive Phase

Depression in Bipolar Depression is similar to that in Clinical Depression. Signs and symptoms include: persistent feelings of sadness, anxiety, guilt, anger, isolation and/or hopelessness, disturbances in sleep and appetite, fatigue and loss of interest in daily activities, escapism, problems concentrating, loneliness, self-loathing, apathy or indifference, depersonalisation, shyness or social anxiety, irritability, chronic pain without a known cause, recurring thoughts of suicide.


In terms of duration, disability, lost years of productivity, and potential for suicide, the depressed periods in Bipolar Disorder are now widely recognised as the most serious problem for the individual, although periods of mania may seem more noticeable or disruptive to others. A 2003 study found Bipolar patients fared worse while depressed than Unipolar patients.


Certain kinds of severe Depression may be accompanied by symptoms of psychosis. These symptoms include hallucinations (hearing, seeing, or otherwise sensing the presence of stimuli that are not there), escapism (creating mental diversions to 'escape' from perceived unpleasant aspects of stress) and delusions (false personal beliefs that are not subject to reason or contradictory evidence and are not explained by a person's cultural concepts). They may also suffer from paranoid thoughts of being persecuted or monitored by some powerful entity such as the government or a hostile force or, more often, become paranoid that those close to them are bullying or conspiring against them or planning to abandon them. Bipolar Depression may involve heavy feelings of anxiety with no one cause. They may feel that their friends or family are leaving them or 'giving up' on them. Intense and unusual religious beliefs may also be present, such as patients' strong insistence that they have a great and historic mission to accomplish or even that they possess supernatural powers - although this is more commonly associated with states of Mania. Delusions in a depression may be far more distressing, sometimes taking the form of intense guilt for supposed wrongs that the patient believes he or she has inflicted on others. There are a number of conflicting theories on what can be considered the cause of Bipolar Depression, and what may be a symptom, none of which are yet widely accepted as correct.


Mania

Mania is a medical condition characterized by severely elevated mood. The 'high' can be so intense it could potentially be dangerous. People who experience a manic state often describe themselves as feeling high and superior. Generally, Mania also provokes racing thoughts and creative ideas. However, it also pushes sufferers into agitation and poor decisions. Classic symptoms of Mania include fast, nonstop talking, pacing aimlessly, staring into space, irritability, and heavy interest in goal oriented activities. One with Mania may complain of racing thoughts, hallucinations, music stuck in their head, and feelings of of enlightenment. Mania is most usually associated with Bipolar Disorder, where episodes of Mania may cyclically alternate with episodes of Depression. (Note: Not all Mania can be classified as Bipolar Disorder, as mania may result from other diseases or causes. However, Bipolar Disorder is the 'classic' manic disease.) Hypomania is a less severe variant of Mania, where there is less loss of control. Many creative talents with Bipolar Disorder associate Mania and Hypomania with creative ideas.


Diagnostic Criteria

Flux is the fundamental nature of Bipolar Disorder. Both within and between individuals with the illness, energy, mood, thought, sleep, and activity are among the continually changing biological markers of the disorder. The diagnostic subtypes of Bipolar Disorder are thus static descriptions - snapshots, perhaps - of an illness in continual change. Individuals may stay in one subtype, or change into another, over the course of their illness. The DSM-V, to be published in 2013, will likely include further and more accurate subtyping (Hagop Akiskal & Nassir Ghaemi, 2006).


There are currently four types of bipolar illness. The DSM-IV-TR (2000) details four categories of Bipolar Disorder: Bipolar I, Bipolar II, Cyclothymia, and Bipolar Disorder NOS (Not Otherwise Specified).


According to the DSM-IV-TR, a diagnosis of Bipolar I disorder requires one or more manic or mixed episodes. A depressive episode is not required for a diagnosis of Bipolar I disorder, although the overwhelming majority of people with Bipolar I suffer from them as well. Bipolar II, the more common but by no means less severe type of the disorder, is usually characterised by one or more episodes of Hypomania and one or more severe depressions. A diagnosis of Bipolar II disorder requires only one hypomanic episode. This stipulation is used mainly to differentiate it from Unipolar Depression. Although a patient may be depressed, it is very important to find out from the patient or the patient's family or friends if Hypomania has ever been present, using careful questioning.


A diagnosis of Cyclothymic Disorder requires the presence of numerous hypomanic episodes, intermingled with depressive episodes that do not meet full criteria for major depressive episodes. The main idea here is that there is a low-grade cycling of mood which appears to the observer as a personality trait, but interferes with functioning.


If an individual clearly seems to be suffering from some type of Bipolar Disorder but does not meet the criteria for one of the subtypes above, they receive a diagnosis of Bipolar Disorder NOS (Not Otherwise Specified).


Misdiagnosis

There are many problems with symptom accuracy, relevance, and reliability in making a diagnosis of Bipolar Disorder using the DSM-IV-TR. These problems can often lead to misdiagnosis.


University of California at San Diego's Dr Hagop Akiskal believes that the way the Bipolar Disorders in the DSM are conceptualised and presented routinely leads many primary care doctors and mental health professionals to misdiagnose bipolar patients with Unipolar Depression, when a careful history from patient, family and/or friends would yield the correct diagnosis. Bipolar disorder often can be - and has been - misdiagnosed as Unipolar Depression, Anxiety Disorders, Obsessive-Compulsive Disorder, ADHD, and various personality disorders, and, in the case of adolescents, could be written off as 'typical' teenage mood swings.


If misdiagnosed with Depression, OCD or anxiety, patients are usually prescribed antidepressants such as SSRIs and MAOIs, which can trigger manic and mixed symptoms in Bipolar individuals or those with family history of the disorder, either ushering in the illness itself or aggravating and increasing the frequency of episodes which were already occurring. The DSM V will likely address these diagnostic issues when published in 2013 (Hagop Akiskal & P Benazzi, 2006).


Causes…?

Heritability or inheritance
The disorder runs in families.
More than 2/3 of people with Bipolar Disorder have at least one close relative with the disorder or with Unipolar Major Depression, indicating that the disease has a genetic component.


Studies seeking to identify the genetic basis of Bipolar Disorder indicate that susceptibility stems from multiple genes. Scientists are continuing their search for these genes, using advanced genetic analytic methods and large samples of families affected by the illness. The researchers are hopeful that identification of susceptibility genes for Bipolar Disorder, and the brain proteins they code for, will make it possible to develop better treatments and preventive interventions targeted at the underlying illness process.


Genetic Research
Bipolar Disorder is considered to be a result of complex interactions between
genes and environment.


The monozygotic concordance rate for the disorder is 70%. This means that if a person has the disorder, an identical twin has a 70% likelihood of having the disorder as well. Dizygotic twins have a 23% concordance rate. These concordance rates are not universally replicated in the literature; recent studies have shown rates of around 40% for monozygotic and <10% for dizygotic twins (Tuula Kieseppa, 2004; A G Cardno, 1999).


In 2003, a group of American and Canadian researchers published a paper that used gene linkage techniques to identify a mutation in the GRK3 gene as a possible cause of up to 10% of cases of Bipolar Disorder. This gene is associated with a kinase enzyme called G protein receptor kinase 3 which appears to be involved in dopamine metabolism and may provide a possible target for new drugs for Bipolar Disorder.


Brain Research
Researchers are using advanced brain imaging techniques to examine brain function and structure in people with Bipolar Disorder, particularly using the
functional MRI and positron emission tomography. An important area of neuroimaging research focuses on identifying and characterising networks of interconnected nerve cells in the brain, interactions among which form the basis for normal and abnormal behaviours. Researchers hypothesise that abnormalities in the structure and/or function of certain brain circuits could underlie Bipolar and other mood disorders, and studies have found anatomical differences in areas such as the prefrontal cortex and hippocampus.


Better understanding of the neural circuits involved in regulating mood states - and genetic factors such as the cadherin gene FAT linked to Bipolar Disorder - may influence the development of new and better treatments, and may ultimately aid in early diagnosis and even a cure


Aetiology
According to the US government's National Institute of Mental Health (NIMH),
"There is no single cause for Bipolar Disorder - rather, many factors act together to produce the illness." "Because Bipolar Disorder tends to run in families, researchers have been searching for specific genes passed down through generations that may increase a person's chance of developing the illness." "In addition, findings from gene research suggest that Bipolar Disorder, like other mental illnesses, does not occur because of a single gene."


It is well established that Bipolar Disorder is a genetically influenced condition which can respond very well to medication (Sheri Johnson & Robert Leahy, 2004; David Miklowitz & Michael Goldstein,1997; Ellen Frank, 2005).

Abnormalities in brain function have been related to feelings of anxiety and lower stress resilience. When faced with a very stressful, negative major life event, such as a failure in an important area, an individual may have his first major depression. Conversely, when an individual accomplishes a major achievement he may experience his first hypomanic or manic episode. Individuals with Bipolar Disorder tend to experience episode triggers involving either interpersonal or achievement-related life events. An example of interpersonal-life events include falling in love or, conversely, the death of a close friend. Achievement-related life events include acceptance into an elite graduate school or, by contrast, being fired from work (Miklowitz & Goldstein, 1997).


The 'kindling' theory asserts that people who are genetically predisposed toward Bipolar Disorder can experience a series of stressful events, each of which lowers the threshold at which mood changes occur. Eventually, a mood episode can start (and becomes recurrent) by itself. Not all individuals experience subsequent mood episodes in the absence of positive or negative life events, however.


Individuals with late-adolescent/early adult onset of the disorder will very likely have experienced childhood anxiety and Depression. Some argue that childhood-onset Bipolar Disorder should be treated early.


A family history of Bipolar spectrum disorders can impart a genetic predisposition towards developing a Bipolar spectrum disorder. Since Bipolar disorders are polygenic (involving many genes), there are apt to be many Unipolar and Bipolar disordered individuals in the same family pedigree. This is very often the case (Samuel Barondes,  1998). Anxiety disorders, Clinical Depression, eating disorders, Premenstrual Dysphoric Disorder, Postpartum Depression, postpartum psychosis and/or Schizophrenia may be part of the patient's family history and reflects a term called 'genetic loading.


Bipolar Disorder is more than just biological and psychological. Since "many factors act together to produce the illness", Bipolar Disorder is called a multifactorial illness, because many genes and environmental factors conspire to create the disorder (Johnson & Leahy, 2004).


Since Bipolar Disorder is so heterogeneous, it is likely that people experience different pathways towards the illness (Miklowitz & Goldstein, 1997).


Recent research done in Japan indicates a hypothesis of dysfunctional mitochondria in the brain (C Stork & P F Renshaw, 2005)


History of Bipolar Disorder

Varying moods and energy levels have been a part of the human experience since time immemorial. The words 'depression' (previously 'melancholia') and 'mania' have their etymologies in Ancient Greek. The word Melancholia is derived from ‘melas’, meaning black, and ‘chole’, meaning bile, indicative of the term’s origins in pre-Hippocratic humoural theories. Within the Humoural 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 are proposed by the 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 (Jules Angst & Andreas Marneros, 2001). 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 mythologies (Angst and Marneros, 2001).


The idea of a relationship between Mania and Melancholia can be traced back to at least the 2nd century AD. Soranus of Ephesus (98-177 AD) described Mania and Melancholia as distinct diseases with separate aetiologies; however, he acknowledged that "many others consider Melancholia a form of the disease of Mania" (Cited in Francis Mondimore, 2005 p.49).


A clear understanding of Bipolar Disorder as a mental illness was recognized by early Chinese authors. The encyclopedist Gao Lian (c 1583) describes the malady in his 'Eight Treatises on the Nurturing of Life' (Ts'un-sheng pa-chien).


The earliest written descriptions of a relationship between Mania and Melancholia are attributed to Aretaeus of Cappadocia. Aretaeus was an eclectic medical philosopher who lived in Alexandria somewhere between 30 and 150 AD (Giuseppe Roccatagliata, 1986; Akiskal, 1996). Aretaeus is recognized as having authored most of the surviving texts referring to a unified concept of Manic-Depressive illness, viewing both Melancholia and Mania as having a common origin in ‘black bile’ (Akiskal 1996; Marneros 2001).


The contemporary psychiatric conceptualisation of Manic-Depressive illness is typically traced back to the 1850s. Marneros (2001) describes the concepts emerging out of this period as the "rebirth of bipolarity in the modern era". On January 31 1854 Jules Baillarger described to the French Imperial Academy of Medicine a biphasic mental illness causing recurrent oscillations between Mania and Depression. 2 weeks later, on February 14 1854, Jean-Pierre Falret presented a description to the Academy on what was essentially the same disorder. This illness was designated folie circulaire (‘circular insanity’) by Falret, and folie à double forme] (‘dual-form insanity’) by Baillarger (M J Sedler,1983).


Emil Kraepelin (1856-1926), a German psychiatrist considered by to be the father of the modern conceptualisation of Bipolar Disorder, categorised and studied the natural course of untreated Bipolar patients long before mood stabilisers were discovered. Describing these patients in 1902, he coined the term 'Manic Depressive Psychosis'. He noted in his patient observations that intervals of acute illness, manic or depressive, were generally punctuated by relatively symptom-free intervals in which the patient was able to function normally.


After World War II Dr John Cade, an Australian psychiatrist, was investigating the effects of various compounds on veteran patients with Manic Depressive Psychosis. In 1949, Cade discovered that lithium carbonate could be used as a successful treatment of Manic Depressive Psychosis. Because there was a fear that table salt substitutes could lead to toxicity or death, Cade's findings didn't immediately lead to treatments. In the 1950's US hospitals began experimenting with lithium on their patients. By the mid-60's reports started appearing in the medical literature regarding lithium's effectiveness. The US Food & Drug Administration did not approve of lithium's use until 1970.


The term 'manic-depressive illness' first appeared in 1958. The current nosology, Bipolar Disorder, became popular only recently and some individuals prefer the older term because it provides a better description of a continually changing multi-dimensional illness.