BIPOLAR DISORDER

The diagnosis of bipolar I disorder requires the presence of a manic episode of at least 1 week's
duration that leads to hospitalization or other significant impairment in occupational or social
functioning. The episode of mania cannot be caused by another medical illness or by substance
abuse. These criteria are based on the specifications of the Diagnostic and Statistical Manual of
Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR).[9]

Manic episodes are characterized by at least 1 week of profound mood disturbance,

characterized by elation, irritability, or expansiveness. Three or more of the following symptoms
must also be present:

• Grandiosity
• Diminished need for sleep
• Excessive talking or pressured speech
• Racing thoughts or flight of ideas
• Clear evidence of distractibility
• Increased level of goal-focused activity at home, at work, or sexually
• Excessive pleasurable activities, often with painful consequences
The mood disturbance is sufficient to cause impairment at work or danger to the patient or others.

The mood is not the result of substance abuse or a medical condition.

Hypomanic episodes are characterized by an elevated, expansive, or irritable mood of at least 4

days' duration. Three or more of the following symptoms are also present:

• Grandiosity or inflated self-esteem

• Diminished need for sleep
• Pressured speech
• Racing thoughts or flight of ideas
• Clear evidence of distractibility
• Psychomotor agitation at home, at work, or sexually
• Engaging in activities with a high potential for painful consequences
The mood disturbance is observable to others.

The mood is not the result of substance abuse or a medical condition.

Major depressive episodes are characterized by the following: For the same 2 weeks, the person
experiences 5 or more of the following symptoms, with at least 1 of them being either a
depressed mood or characterized by a loss of pleasure or interest:

• Depressed mood
• Markedly diminished pleasure or interest in nearly all activities
• Significant weight loss or gain or significant loss or increase in appetite
• Hypersomnia or insomnia
• Psychomotor retardation or agitation
• Loss of energy or fatigue
• Decreased concentration ability or marked indecisiveness
• Preoccupation with death or suicide; patient has a plan or has attempted suicide
• The symptoms cause significant impairment and distress.
• The mood is not the result of substance abuse or a medical condition.
Mixed episodes are characterized by the following:

• Persons must meet both the criteria for mania and major depression; the depressive
event is required to be present for 1 week only.
• The mood disturbance results in marked disruption in social or vocation function.
 • The mood is not the result of substance abuse or a medical condition.
• The mixed symptomology is quite common in patients presenting with bipolar
symptomology. This often causes a diagnostic dilemma.

Signs and symptoms

Bipolar disorder is a condition in which people experience abnormally elevated (manic or
hypomanic) and, in many cases, abnormally depressed states for periods of time in a way that
interferes with functioning. Not everyone's symptoms are the same, and there is no simple
physiological test to confirm the disorder. Bipolar disorder can appear to be unipolar depression.
Diagnosing bipolar disorder is often difficult, even for mental health professionals. What
distinguishes bipolar disorder from unipolar depression is that the affected person experiences
states of mania and depression. Often bipolar is inconsistent among patients because some
people feel depressed more often than not and experience little mania whereas others
experience predominantly manic symptoms. Additionally, the younger the age of onset—bipolar
disorder starts in childhood or early adulthood in most patients—the more likely the first few
episodes are to be depression.[6] Because a bipolar diagnosis requires a manic or hypomanic
episode, many patients are initially diagnosed and treated as having major depression.

Causes
The causes of bipolar disorder likely vary between individuals. Twin studies have been limited by
relatively small sample sizes but have indicated a substantial genetic contribution, as well as
environmental influence. For bipolar I, the (probandwise) concordance rates in modern studies
have been consistently put at around 40% in monozygotic twins (same genes), compared to 0 to
10% in dizygotic twins.[24] A combination of bipolar I, II and cyclothymia produced concordance
rates of 42% vs 11%, with a relatively lower ratio for bipolar II that likely reflects heterogeneity.
The overall heritability of the bipolar spectrum has been put at 0.71.[25] There is overlap
with unipolar depression and if this is also counted in the co-twin the concordance with bipolar
disorder rises to 67% in monozigotic twins and 19% in dizigotic.[26] 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.[25]

Genetic
Genetic studies have suggested many chromosomal regions and candidate genes appearing to
relate to the development of bipolar disorder, but the results are not consistent and often not
replicated.[27]
Although the first genetic linkage finding for mania was in 1969,[28] the linkage studies have been
inconsistent.[29] Meta-analyses of linkage studies detected either no significant genome-wide
findings or, using a different methodology, only two genome-wide significant peaks, on
chromosome 6q and on 8q21.[citation needed] Genome-wide association studies neither brought a
consistent focus — each has identified new loci.[29]

Findings point strongly to heterogeneity, with different genes being implicated in different families.
[30]
A review seeking to identify the more consistent findings suggested several genes related
to serotonin (SLC6A4 and TPH2), dopamine (DRD4 and SLC6A3), glutamate (DAOA and
DTNBP1), and cell growth and/or maintenance pathways (NRG1, DISC1 and BDNF), although
noting a high risk of false positives in the published literature. It was also suggested that
individual genes are likely to have only a small effect and to be involved in some aspect related to
the disorder (and a broad range of "normal" human behavior) rather than the disorder per se.[31]

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.[32]

Physiological
Abnormalities in the structure and/or function of certain brain circuits could underlie bipolar. Two
meta-analyses of MRI studies in bipolar disorder report a increase in the volume of thelateral
ventricles, globus pallidus and increase in the rates of deep white matter hyperintensities.[33][34]

The "kindling" theory asserts that people who are genetically predisposed toward bipolar disorder
can experience a series of stressful events,[35] each of which lowers the threshold at which mood
changes occur. Eventually, a mood episode can start (and become recurrent) by itself. There is
evidence of hypothalamic-pituitary-adrenal axis (HPA axis) abnormalities in bipolar disorder due
to stress.[36]

Other brain components which have been proposed to play a role are the mitochondria,[37] and a
sodium ATPase pump,[38] causing cyclical periods of poor neuron firing (depression) and
hypersensitive neuron firing (mania). This may only apply for type one, but type two apparently
results from a large confluence of factors.[citation needed] Circadian rhythms and melatonin activity also
seem to be altered.[39]

Environmental
Evidence suggests that environmental factors play a significant role in the development and
course of bipolar disorder, and that individual psychosocial variables may interact with genetic
dispositions.[31] There is fairly consistent evidence from prospective studies 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.[40] There have
been repeated findings that between a third and a half of adults diagnosed with bipolar disorder
report traumatic/abusive experiences in childhood, which is associated on average with earlier
onset, a worse course, and more co-occurring disorders such as PTSD.[41]The total 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.[42] Early experiences of adversity and
conflict are likely to make subsequent developmental challenges in adolescence more difficult,
and are likely a potentiating factor in those at risk of developing bipolar disorder.[43]

Course

The course of bipolar disorder is dependent on a number of factors, such as the severity of the illness, the age of
onset, comorbid conditions, frequency of episodes, cycle pattern and the presence or absence of 'rapid cycling'.

Frequency of Episodes

The time between the first, second and third episodes is much greater than that between subsequent episodes.
After the first three episodes there is a general increase in frequency and relative stabilisation (Suppes et al,
2000). There is a sub-group of patients who experience four or more mood episodes per year and this is termed
'rapid cycling'. Occurring in 5–20% of adults with bipolar disorder, rapid cycling is more common in women than
men. In one study 72% of women compared with 28% of men experienced rapid cycling (Suppes et al, 2000).
Bipolar disorder with an onset in adolescence is often rapid cycling with stabilisation of periods occurring over
time.

Cycling

Some patients have a well-established cycle pattern – moving from depression to mania or mania to depression,
while other patients have a varied and unpredictable pattern. The cycle of episodes may have an affect on the
course of the illness, as there is some evidence that patients with a mania to depression pattern respond better
to pharmacological treatment with mood stabilisers than patients with a depression to mania pattern (Suppes et
al, 2000).

Mixed Epsiodes

A mixed episode is defined by sufficient depressive and manic symptoms occurring simultaneously, such that
both diagnostic criteria are met. The effect that this concurrency of symptoms has on the course of bipolar
disorder is unclear. Some research suggests that patients with mixed episodes take longer to recover from an
episode and have poorer outcomes than those who experience pure mania or hypomania. Mixed episodes are
associated with an increased incidence of substance abuse and suicide ideation and attempts (Suppes et al,
2000). In addition, manic episodes that occur in adolescence and early adulthood may be more likely to be mixed
episodes.

Age of Onset

The majority of bipolar patients will experience their first symptoms before the age of 25 years; earlier if there is
a family history of affective disorder (Bland, 1997; Suppes et al, 2000). However, in many cases, depressive
episodes will usually precede a manic episode (Marnevos & Angst, 2000). A particularly early age of onset is often
associated with a more severe course of illness; this may be related to the number and severity of the depressive
episodes. The early onset of depressive episodes has also been associted with an increase in the risk (Suppes et
al, 2000).
Comorbid Conditions

The lifetime prevalence rates of other psychiatric and medical conditions are greatly increased in patients with
bipolar disorder and these comorbid conditions can make the course of the illness more difficult to treat and
manage (Suppes et al, 2000). The two most common comorbid conditions are anxiety disorderand substance
abuse; the National Comorbidity Study in 1999 reported a prevalence of 93% for anxiety disorder and of 64% for
substance abuse in patients with bipolar I disorder (Marnevos & Angst, 2000). Patients with bipolar disorder and
comorbid anxiety disorder experience a more severe course of disease than those without comorbid anxiety.
Patients with bipolar disorder who also have a history of substance abuse have a more complicated disease
course than those with no history of substance abuse (Suppes et al, 2000).

Find out more about comorbid conditions.

Suicide

Suicide is one of the major causes of increased mortality in patients with mood disorders, and patients with
bipolar disorder are at higher risk of committing suicide than patients with other psychiatric disorders. The
lifetime prevalence of suicide in bipolar disorder patients is 15% compared with 6% in mood disorder patients.
Most studies on the suicide risk of patients with bipolar disorder have enrolled severely ill, hospitalised patients,
this results in a sampling bias and means that the actual rate of suicide in the overall bipolar population may be
lower. The Epidemiologic Catchement Area Study showed that 25–50% of patients with bipolar disorder attempt
suicide at least once in their lifetime, and that patients often showed detailed planning and a resolute intent to
die. Increased risk of suicide is associated with past suicide attempts, alcohol abuse and the length of time
elapsed after hospital discharge. Women attempt suicide 2–3 times more often than men, but generally use less
lethal means (Jamison, 2000).

Other Factors

Other factors that can influence the course of bipolar disorder include: stress; lifestyle; the sleep-wake schedule;
the use of substances and alcohol and the long-term use of prescription medication (Suppes et al, 2000)