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But because the pattern of highs and lows varies for each person, bipolar disorder is a
complex disease to diagnose. For some people, mania or depression can last for weeks
or months, even for years. For other people, bipolar disorder takes the form of frequent
and dramatic mood shifts (WebMD,2008).
2-Risk factors:
lifestyle habits increase the risk of bipolar disorder, that lack of sleep increases the
risk of having an episode of mania, In addition, antidepressant medications, particularly
when taken as the only medication, may also trigger a switch into a manic state.
Excessive use of alcohol or drugs can also trigger bipolar symptoms. Research has
shown that about 50% of bipolar sufferers have a substance abuse or alcohol problem.
Sufferers often use alcohol or drugs to self-medicate during their high and low moods.
Also environmental stress that include seasonal changes, holidays, and major life
changes such as starting a new job, losing a job, going to college, family disagreements,
marriage, or a death in the family, increase the risk of bipolar disorder (WebMD,2008).
3-Epidemiology:
Approximately 5% of the adult population has either bipolar I or II disorder, with the
full spectrum of recurrent mood disorders (American Psychiatric Association ,2000).
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The lifetime prevalence of bipolar I disorder (one or more manic or mixed episodes) is
0.4% to 1.6%; that for bipolar II disorder (recurrent major depressive episodes with
hypomanic episodes) is approximately 0.5%, Bipolar I disorder occurs equally in men
and women, whereas bipolar II disorder is more common in women (American Psychiatric
Association,2000 ; American Psychiatric Association,2002).
4-Etiology:
The exact etiology of bipolar disorder is unknown. Bipolar disorder is thought to be a
complex genetic disease that is environmentally influenced and caused by a wide range
of neurobiologic abnormalities. Stressful life events, alcohol or substance use, and
changes in the sleep-wake cycle can elicit the expression of genetic or biologic
vulnerabilities that cause dysregulation of neurotransmitters, neuroendocrine pathways,
and second messenger systems (Goldberg et al,1999).
4.1-Neurochemical theories:
Dysregulation between neurotransmitters, neuropeptides, hormones, and secondary
messenger systems can produce a cyclic rhythm disturbance in the central nervous
system (Torrey, Knable, 2002).
The "permissive serotonin hypothesis" proposes that serotonin (5-HT) plays a critical
role in modulating brain activity (e.g., stabilization of the catecholamine system and
inhibition of dopamine (DA) release), and is low in both mania and depression, The
type of affective state that is expressed with the permissive hypothesis is determined
secondarily by the level of norepinephrine (NE) (e.g., increased amounts of NE lead to
mania, decreased amounts lead to depression), 5-HT deficiency and changes in the
light–dark cycle may result in reduced melatonin secretion from the pineal gland that
disrupts the sleep wake cycle, alters circadian rhythms, and causes seasonal affective
changes (Goodnick et al, 1998; Mahmood et al, 2001).
The catecholamine hypothesis of mood disorders suggests that increased DA and NE
activity contribute to hyperactivity and psychosis associated with the severe stages of
mania, and reduced activity causes depression (Goodnick et al, 1998; Goldberg et al, 1999).
A γ-aminobutyric acid (GABA) deficiency theory has been proposed for mania as it
inhibits NE and DA activity (Goodnick et al, 1998; Goldberg et al, 1999).
Glutamate and aspartate, excitatory amino acid neurotransmitters, may be overactive
and involved in causing manic episodes (Manji et al, 2000).
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Cholinergic under activity has been proposed to cause mania and over activity of
acetylcholine to cause depression (Goodnick et al, 1998; Manji et al, 2000).
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Deficiency in essential fatty acids (e.g., omega-3 fatty acids) can cause a
dysregulation of neurotransmitter activity.
• Neurotransmitter/neuroendocrine/hormonal theories:
Dysregulation between excitatory and inhibitory neurotransmitter systems;
excitatory: NE, DA, glutamate, and aspartate; inhibitory: 5-HT and GABA.
• Monoamine hypothesis:
An excess of catecholamines (primarily NE and DA) cause mania.
Agents that decrease catecholamines are used for the treatment of mania (e.g.,
DA antagonists and α2-adrenergic agonists).
Deficit of neurotransmitters (primarily NE, DA, and/or 5-HT) cause depression.
Agents that increase neurotransmitter activity are used for the treatment of
depression (e.g., 5-HT and NE/DA reuptake inhibitors and MAOIs).
• Dysregulation of amino acid neurotransmitters:
Deficiency of GABA or excessive glutamate activity causes dysregulation of
neurotransmitters (e.g., increased DA and NE activity).
Agents that increase GABA activity or decrease glutamate activity are used for
the treatment of mania and for mood stabilization (e.g., benzodiazepines,
lamotrigine, lithium, or valproic acid).
• Cholinergic hypothesis:
Deficiency of acetylcholine causes an imbalance in cholinergic-adrenergic
activity and can increase the risk of manic episodes.
Agents that increase acetylcholine activity can decrease manic symptoms (e.g.,
use of cholinesterase inhibitors or augmentation of muscarinic cholinergic
activity).
Increased central acetylcholine levels can increase the risk of depressive
episodes.
Agents that decrease acetylcholine activity can alleviate depressive symptoms
(i.e., anticholinergic agents).
• Secondary messenger system dysregulation:
Abnormal G protein functioning dysregulates adenylate cyclase activity,
phosphoinositide responses, sodium/potassium/calcium channel exchange, and
activity of phospholipases.
Abnormal cyclic adenosine monophosphate and phosphoinositide secondary
messenger system activity.
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Abnormal protein kinase C activity and signaling pathways.
• Hypothalamic-pituitary-thyroid axis dysregulation:
Hyperthyroidism can precipitate manic-like symptoms.
Hypothyroidism can precipitate a depression and be a risk factor for rapid
cycling; thyroid supplementation can be used for refractory rapid cycling and
augmentation of antidepressants in unipolar depression.
Positive antithyroid antibody titers reported in patients with bipolar disorder.
Hormonal changes during the female life cycle can cause dysregulation of
neurotransmitters (e.g., premenstrual, postpartum, and perimenopause).
• Membrane and cation theories:
Abnormal neuronal calcium and sodium activity and homeostasis cause
neurotransmitter dysregulation.
Hypocalcemia has been associated with causing anxiety, mood irritability,
mania, psychosis, and delirium.
Hypercalcemia has been associated with causing depression, stupor, and coma.
Extra cellular and intracellular calcium concentrations may affect the synthesis
and release of NE, DA, and 5-HT, as well as the excitability of neuronal firing.
• Sensitization and kindling theories:
Recurrences of mood episodes causes behavioral sensitivity and electro
physiologic kindling (similar to the amygdalakindling models for seizures in
animals) and can result in rapid or continuous mood cycling (Dipiro et al, 2008).
5-Clinical presentation:
The essential feature of bipolar spectrum disorders are a history of mania or hypomania
that is not caused by any other medical condition, substance, or psychiatric disorder.
Bipolar disorder is divided into four subtypes based on the identification of specific
mood episodes: bipolar I, bipolar II, cyclothymic disorder, and bipolar disorder not
otherwise specified.
Mood Disorders Defined by Episodes:
Disorder Subtype: Episode(s)
Major depressive disorder, Major depressive episode
single episode
The length and severity of a mood episode and the interval between episodes varies
from patient to patient. Manic episodes are usually briefer and end more abruptly than
major depressive episodes. The average length of untreated manic episodes ranges from
4 to 13 months. Episodes can occur regularly (at the same time or season of the year)
and often cluster at 12-month intervals. Women have more depressive episodes than
manic episodes, whereas men have a more even distribution of episodes. For bipolar I
disorder, 90% of individuals who experience a manic episode later have multiple
recurrent major depressive, manic, hypomanic, or mixed episodes alternating with a
normal mood state. Approximately 5–15% of patients with bipolar II disorder will
develop a manic episode over a 5-year period. If a manic or mixed episode develops in
a patient with bipolar II disorder, the diagnosis is changed to bipolar I disorder. Patients
with cyclothymic disorder have a 15–50% risk of later developing a bipolar I or II
disorder (American Psychiatric Association,2002).
5.1-Symptoms of the depressive phase of bipolar disorder may consist of the
following:
Insomnia or oversleeping.
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Thoughts of suicide or dying.
Unexplainable aching.
Euphoria or irritability.
Inflated self-esteem.
Hallucinations and or delusions (in extreme cases of bipolar disorder with psychotic
features) (WebMD,2008).
But bipolar disorder can be sneaky, Symptoms can defy the expected manic-depressive
sequence, Infrequent episodes of mild mania can go undetected, Depression can
overshadow other aspects of the illness, And substance abuse can cloud the picture.
Taken together, these factors make bipolar disorder surprisingly difficult to diagnose.
About half of people with bipolar disorder have seen three professionals before
being diagnosed correctly.
It takes an average of 10 years for people to enter treatment for bipolar disorder after
symptoms begun. Partly, this is due to delays in diagnosis (WebMD,2008).
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family history of mood swings or suicide. Other disorders must be ruled out particularly
such childhood problems as school phobia and attention deficit disorder, aging
problems of dementia, schizophrenia, schizoaffective disorder, and other psychotic
states induced solely by alcohol or drugs. Drug or alcohol abuse is common in persons
with bipolar disorder and can mask the symptoms, thus complicating diagnosis and
treatment. Recognizing and treating any drug abuse is a priority, since it is a strong
predictor of suicide, especially in men. Before treatment begins, the patient receives a
careful physical exam, and blood and urine are tested to detect conditions that could put
medical constraints on the choice of treatment. A thyroid analysis is particularly
important both because hyperthyroidism can look like mania and because lithium "the
principal drug treatment for bipolar disorder" is known to lower thyroid function and/or
impair kidney function. During treatment, frequent blood tests are necessary to see that
adequate drug levels have been reached and to detect adverse reactions at an early stage
(WebMD,2008).
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7. Lumbar puncture.
8. Electroencephalogram.
7-Course of illness:
The average age of onset of a first manic episode is 21 years. More than 80% of bipolar
patients have more than four episodes during their lifetime. Usually there is normal
functioning between episodes. Rapid cyclers (10% to 20% of bipolar patients) have four
or more episodes per year (major depressive, manic, mixed, or hypomanic). Rapid-
cycling and mixed states are associated with a poorer prognosis and nonresponse to
antimanic agents. Risk factors for rapid cycling include biologic rhythm dysregulation,
antidepressant or stimulant use, hypothyroidism, and premenstrual and postpartum
states.
Suicide attempts occur in up to 50% of patients with bipolar disorder, and
approximately 10% to 19% of individuals with bipolar I disorder commit suicide.
Bipolar II patients may be more likely than bipolar I patients to attempt suicide. Bipolar
patients with substance abuse disorders are more likely to have an earlier onset of
illness, mixed states, higher relapse rates, poorer response to treatment, higher suicide
risk, and more hospitalizations. Episodes may become longer in duration and more
frequent with aging (American Psychiatric Association,2002).
8-Treatment:
8.1-General principles for the management of bipolar disorder:
Goals of treatment:
• Eliminate mood episode with complete remission of symptoms (i.e., acute
treatment).
• Prevent recurrences or relapses of mood episodes (i.e., continuation phase
treatment).
• Return to complete psychosocial functioning.
• Maximize adherence with therapy.
• Minimize adverse effects.
• Use medications with the best tolerability and fewest drug interactions.
• Treat comorbid substance use and abuse.
• Eliminate alcohol, marijuana, cocaine, amphetamines, and hallucinogens.
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• Minimize nicotine use and stop caffeine intake at least 8 hours prior to bedtime.
• Avoidance of stressors or substances that precipitate an acute episode.
Cognitive therapy: This type of approach involves learning to identify and modify the
patterns of thinking that accompany mood shifts.
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Interpersonal therapy: This involves relationships and aims to reduce strains that the
illness may place upon them.
Social rhythm therapy: This helps them develop and maintain daily routines.
Support groups also help patients with bipolar disorder, that receive encouragement,
learn coping skills, and share concerns, they may feel less isolated as a result. Family
members and friends may also benefit from a support group. They can gain a better
understanding of the illness, share their concerns, and learn how to best support loved
ones with bipolar disorder (WebMD,2008).
Light therapy has proved effective as an additional treatment when bipolar disorder has
a connection to the winter depression condition seasonal affective disorder. For those
people who usually become depressed in winter, sitting for 20-30 minutes a day in front
of a special light box with a full-spectrum light can effectively treat their depression
(WebMD,2008).
The use of ECT for severe episodes of mania, depression, psychotic features (e.g.,
hallucinations or delusions), mixed episodes, or rapid cycling is still considered the best
acute treatment approach for those patients who do not respond to first-line mood
stabilizers such as lithium and valproate (Goldberg et al,1999).
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8.2.3-Dietary intake:
Disturbances in 5-HT neurotransmission secondary to inadequate dietary L-tryptophan
or abnormalities in tryptophan hydroxylase, 5-HT transporters, and 5-HT receptors was
implicated in the pathophysiology of manic depressive illness as early as 1958, If
available 5-HT is low, the synthesis and secretion of melatonin can be disrupted, thus
causing circadian rhythm changes (Goodnick et al, 1998).
A dietary deficiency in essential fatty acids (found in certain fish oils and flaxseed oil
that contains α-linolenic acid) has been proposed as a potential cause of mood
disorders, Omega-3 fatty acids have been shown to suppress neuronal pathways and
inhibit kindling processes by several mechanisms (e.g., inhibition of
phosphatidylinositol and G-protein secondary messengers and blocking L-type calcium
channels). Seafood and fish are rich dietary sources of omega-3 essential fatty acids,
specifically docosahexaenoic acid and eicosapentaenoic acid (Parker et al, 2006).
8.3-Pharmacologic therapy:
Pharmacotherapy is crucial for the acute and maintenance treatment of bipolar disorder
and includes lithium, valproate, carbamazepine, lamotrigine, atypical antipsychotics,
and adjunctive agents such as antidepressants and benzodiazepines (Dipiro et al, 2008).
The term mood stabilizer is often used to describe the class of medications used in the
treatment of bipolar disorder, but this may not be accurate as some medications are
more effective for acute mania, some for the depressive episode, and others for the
maintenance phase. Lithium, valproate (or divalproex sodium), aripiprazole,
olanzapine, quetiapine, risperidone, and ziprasidone are currently approved by the Food
and Drug Administration (FDA) for the treatment of acute mania in bipolar disorder;
only lithium, olanzapine, and lamotrigine are approved for the maintenance treatment of
bipolar disorder. Quetiapine is the only antipsychotic that is FDA approved for bipolar
depression. Lithium is the drug of choice for bipolar disorder with euphoric mania,
whereas valproate has better efficacy for mixed states, irritable/dysphoric mania, and
rapid cycling compared to lithium (American Psychiatric Association,2002).
Combination therapies (e.g., lithium plus valproate or carbamazepine; lithium or
valproate plus an atypical antipsychotic) can provide better acute response and long-
term prevention of relapse and recurrence than monotherapy in some bipolar patients
particularly those with mixed states or rapid cycling. There are few controlled studies in
children and adolescents with bipolar disorder, thus little is known about the long-term
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efficacy and safety of specific agents or for combination therapies in this population
(American Psychiatric Association,2002; Goldberg et al,1999).
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potential to cause adverse effects such as extrapyramidal reactions, sedation, emotional
blunting, sexual dysfunction, metabolic syndrome, and orthostatic hypotension (Goodnick
et al, 1998; Yatham LN, 2002).
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Nimodipine, a dihydropyridine, can be more effective than verapamil for rapid-cycling
bipolar disorder because of its anticonvulsant properties, high lipid solubility, and good
penetration into the brain (American Psychiatric Association,2002; Goldberg et al,1999; Manji et al, 2000;
Goodnick et al, 1998).
Calcium channel blockers are generally well tolerated, and the most common adverse
effects are bradycardia and hypotension. The low teratogenic effects of these agents can
make them a preferable choice over lithium or anticonvulsants during pregnancy and
breastfeeding (Goodnick et al, 1998).
Before and during pregnancy, women should not take lithium and other bipolar
medications, says Michael Aronson, a clinical psychiatrist and consultant for WebMD.
"The interesting thing is, sometimes pregnancy by itself will stabilize someone with
bipolar disorder. At other times, it can destabilize them. The best alternative for
someone who is pregnant, who is having problems with depression or mania and cannot
be placed on an adequate dose of medication, is using ECT (electroconvulsive therapy).
It's very effective and it's safe." (WebMD,2008).
The hormone fluctuations of perimenopause and menopause can cause mood disorders
in any woman not just those with bipolar disorder. However, for those already having
troubles with major depression, bipolar, or anxiety disorders there usually is an increase
in symptoms during this time. Especially during perimenopause, women may be
especially vulnerable to depressive symptoms because of declining estrogen levels,
During menopause, hormone therapy may help. A change in antidepressant or mood
stabilizing drug also may be the answer (WebMD,2008).
11-Related news:
Beginning in 1995 to 1998, the researchers examined 115 children diagnosed with
bipolar disorder with an average age of 11. At the beginning of the study and again
during nine follow-up visits conducted over eight years, the children and their parents
were interviewed separately about their symptoms, diagnoses, daily cycles of mania and
depression, and interactions with others.
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During the eight-year follow-up, the researchers found that the children's first, second,
and third episodes of mania included psychosis and daily cycling between mania and
depression for long periods of time. Many of them recovered from these episodes, but
about 73% of them relapsed.
After the follow-up period, Geller and her colleagues found that about 44% of those
who had bipolar disorder as children and who turned 18 by the end of the study period
continue to have manic episodes as young adults. 35% of them had substance use
disorders, a rate similar to those diagnosed with bipolar disorder as adults.
"The study provides validation that the illness continues into adulthood in a very large
proportion of the children, and unfortunately like adults with the disease, they have a
high rate of substance dependence," says Geller.
The study concluded that the severity and chronic nature of this disorder highlights the
need for a greater effort toward understanding the neurobiology behind the disease and
for developing prevention and intervention strategies.
11.2-Study shows age of dad is a factor in risk of child developing bipolar disorder:
Sept. 2, 2008 A new study suggests that children born from older fathers are at
increased risk of developing bipolar disorder.
Overall, children born to fathers in their mid-50s and older were found to have a 37%
higher risk for bipolar disorder than children born to dads in their early 20s.
The risk of developing the mood disorder before the age of 20 was roughly 2.5-times
greater for children born to men age 50 and older than for children born to men between
the ages of 20 and 24.
According to the National Institute of Mental Health, about 5.7 million American adults
have bipolar disorder, a serious mental illness characterized by dramatic, episodic mood
swings. While the mood disorder tends to run in families, suggesting a genetic link,
little else is known about the causes of bipolar disorder.
Older maternal age was associated with a slight, but nonsignificant, overall increase in
risk, but no association was seen between maternal age and the risk for a bipolar
diagnosis before age 20.
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The fact that paternal age appears to be a more important risk factor for bipolar disorder
than maternal age suggests that genetic mutations in sperm may be to blame. Men add
more mutations to the gene pool than women because their reproductive cells continue
to divide throughout their lives. Women have only about 23 divisions in the cells that
produce their eggs, and these divisions occur before birth, More divisions mean more
potential mutations or DNA damage that could be driving the increased risk for bipolar
disorder and other genetically influenced mental disorders.
Jan. 15, 2009 The largest study ever to track bipolar disorder and schizophrenia within
families offers evidence that the two psychiatric disorders share a common genetic
cause.
For more than a century the psychiatric community has debated whether schizophrenia
and bipolar disorder were two distinct disorders or were more connected.
Over the course of their illnesses, many patients experience similarities in certain
symptoms characteristic of both, such as manic mood swings in bipolar disorder and
psychosis in schizophrenia.
Recent genetic studies suggest a common genetic cause for the two conditions. But
earlier studies in families have not supported this conclusion, finding no increase in
bipolar disorder in family members of schizophrenics and vice versa (WebMD,2008).
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12-References:
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DiPiro J., Talbert R., Yee G., Matzke G., Wells B., Posey L., Pharmacotherapy A
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Goldberg JF, Harrow M, eds. Bipolar Disorders: Clinical Course and Outcome.
Washington, DC: American Psychiatric Press, 1999.
Goodnick PJ, ed. Mania: Clinical and Research Perspectives. Washington, DC:
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Sachs GS, Koslow CL, Ghaemi SN. The treatment of bipolar depression. Bipolar
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Patients, Families, and Providers. New York: Basic Books, 2002.
WebMD Medical Reference with The Cleveland Clinic: "Bipolar Disorder (Manic
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