BIOCHEMICAL IMBALANCE IN BIPOLAR DISEASE

Yyoni A. Redubla C1 Biochemistry FEU-NRMF

B .Types of Bipolar Disease

II. Pathogenesis:

A . Causes

B. Signs and Symptoms

C. Diagnosis

III. Treatment

a. Medications

b. Therapy

IV. Conclusion

INTRODUCTION

Manic-depressive illness is a disorder that causes an individual to experience mood swings from depression to mania. In between these two extremes, a person usually experiences normal emotions and mood. The illness is also called bipolar disorder and it generally strikes a victim before the age of thirty-five.

Bipolar disorder, often called manic depression, is one of the major mood disorders and is distinguished by behavior that fluctuates from extreme highs (mania) to serious lows (depression) interspersed with periods of "normal" mood. Simply put, a person who suffersfromtheconditionisunabletokeepasenseofcalmabouthisorherlife.

Mania is a term used a lot these days (like "basketball mania"), but in medicine, mania refers to behavior that includes profuse and rapidly changing ideas, exaggerated sexuality, extreme gaiety, intense irritability, and decreased sleep.

Depression is used frequently to describe a feeling of sadness. With bipolar disorder, however, the lows of depression are characterized by extreme hopelessness and a feeling of worthlessness accompanied by thoughts of suicide.

Manic depression typically begins in adolescence or early adulthood and continues throughout life. Because manic and depressive episodes may be less extreme in the early stages, or if a person has periods of mild mania, the disorder, unfortunately, is often not recognizedforyearsorevendecades.

Become familiar with the bipolar facts provided on this site so that you or someone you love won't suffer needlessly. Effective treatments greatly alleviate the suffering caused by manic depression and can usually prevent its devastating complications.

Left untreated, major mood disorders often lead to divorce, job loss, substance abuse, and suicide.

Two million Americans suffer from manic depression.
Bipolar disorder affects women and men almost equally.
Bipolar disorder tends to run in families and may be inherited.
Family members of people with bipolar disorder also suffer.
Bipolar disorder is characterized by extreme highs and lows.
Only about one-third of bipolars seek treatment.

Bipolar disorder usually begins in adolescence or early adulthood, although it can sometimes start in early childhood or as late as the 40s or 50s. If bipolar disorder symptoms appear late in life, their occurrence is probably triggered by factors such as excessive stressorsubstanceabuse.

Manic depression behavior typically follows a pattern that cycles—sometimes rapidly—from depression to euphoria or irritability. One person's symptoms may include more mania (excitability) then depression; another person may suffer primarily from depression with mania occurring infrequently. Symptoms of mania and depression may be mixed together in any combination, but the person's mood swings from intense lows to extreme highs.

Bipolarchildrenandteens producing a chronic irritability with few periods of wellness. Bipolar illness is usually diagnosed in children overtheageoftwelve.

Unfortunately, for bipolar children under age twelve, behaviors that should be associated with manic depression are often confused with attention deficit/hyperactivity disorder (ADHD). According to the American Academy of Child and Adolescent Psychiatry a significant number of children diagnosed with ADHD may actually be bipolar, or have bipolar disorder along with ADHD.

The onset of puberty is when the symptoms of adolescent bipolar disorder often manifest. Symptoms typically mirror those of adults with manic depression. For some, adolescent bipolar disorder may initially be triggered by a traumatic event, such as the loss of a loved one, or severe stress. Later episodes may occur even in the absence of stress, or may worsen with stress. Hormones may also trigger adolescent bipolar disorder in girls just starting to menstruate and they may notice that their symptoms vary in severity with theircycle.Because a majority of teens with adolescent bipolar disorder abuse drugs or alcohol, their manic depression behavior is oftenmaskedbythesubstanceabuse. In all cases, an early bipolar disorder diagnosis and start of treatment is vital to establishing moodstabilityandmentalwellness.Thisisespeciallytruewhenitoccursinchildrenandteens.

Types of Bipolar Disease

In "classic" bipolar disorder, or bipolar I disorder, a person has long bouts of depression and long bouts of mania or mixed episodes. Suicide attempts are high, with 10 to 15 percent completed. Abuse and violent behavior is common. This is the most severeformofthedisorder.

Those with bipolar II disorder experience hypomanic and depressive episodes, but never full manic or mixed episodes. Bipolar II disorder is often hard to recognize because the hypomania simply makes the individual feel happy and energetic. They often become more focused and productive. Oftentimes, those with bipolar II disorder may overlook their episodes of hypomania and seek treatmentonlyfortheirdepression.

Cyclothymia produces irregular, short cycles of depression and hypomania. While the episodes are typically less severe than those of either bipolar I or II disorder, they may still interrupt work and social life. With bipolar disorder not otherwise specified (NOS), the person experiences some of the symptoms of bipolar disorder, but doesn't fit into any of the standard bipolar disorder classifications or any other category of mood disorder.

Causes

Where and how bipolar disorder is caused is still a bit of a mystery. Some information is known but nothing concrete, and a lot of dead ends. Genetic predisposition is one possible cause for bipolar disorder. The disease usually can be seen throughout a family tree of an affected individual. Twin studies have been conducted to see if there is a higher chance of identical twins, who have the same genetic make up, both getting the disease. These have shown that there is an increased likely hood of one twin to have bipolar disorder if the other has it, but it is not a certainty. The gene for bipolarity has mainly been traced to chromosome 18 as well as some others. It is uncertain which is responsible because it has been found in some cases that chromosome 18 is unaffected in bipolar patients. It is most likely that bipolar disorder is linked to several genes acting together. Therefore it seems that genetic predisposition for bipolar disorder is a factor in causing the disease, but it does not make it a certainty.

Chemical imbalances may also contribute to bipolar disorder. The brain has a chemical balance that when disrupted can cause a variety of problems. In looking for cause for depression monoamines, a class of neurotransmitters may play a part. It was found that the drug reserpine, which depletes monoamines, caused severe depression and other drugs that inhibit the breakdown of monoamines elevated moods in patients. Monoamine oxidase inhibitors, which block monoamine breakdown, are used as antidepressants. Even more specifically the monoamine norepinephrine is a factor in the cause of depression. In order to regulate the amount of norepinephrine certain drugs are used to block the reuptake of the neurotransmitter blocking it in the synapses. Also, serotonin may affect depression by in turn affecting other parts of the brain through its depletion. The amygdala, involved in emotions, the hypothalamus, involved in appetite, and sleep, and cortical areas, involved in cognition, are all thought to be a part of the cause of depression.

There are many influences that can affect the disease. Most importantly stress, which can cause an episode, or help the disease progress. The hypothalamic-pituitary-adrenal (HPA) axis is the area of the brain that deals with stress. When the body is exposed to certain stresses the HPA releases corticotropin-releasing factor (CRF), which causes the secretion of the hormones adrenocorticotropic hormone (ACTH), which causes the release of cotisol . Cortisol can increase muscle activity, while CRF decreases appetite, sex, and heightens alertness. The continuous activation of this chain of changes can be a cause of depression, and perhaps also mania due to the chemical changes it causes in the brain.

Sleep and the internal clock also affects bipolar disorder. The body's internal rhythm, the circadian clock, is located in the hypothalamus in the suprachaismatic nucleus (SCN), which in addition to other things regulates melatonin. Melatonin is a hormone that is involved in the sleep cycle. Those with bipolar disorders have more difficulty regulating their circadian rhythms, which usually sets itself due to internal and as external conditions. The drastic change of rhythms between mania and depression accompanies cycles suggesting a strong link between the two. The question is does the abnormality of the circadian rhythm cause the bipolar episode, or does the episode cause the change in rhythm. The former seems to be the more likely because the sensitivity of sleep in patients with bipolar disorder. A change in sleeping habits, such as the loss of sleep or change in sleep schedule can cause a manic episode.

Signs and Symptoms

The symptoms of manic depression are based on a persons mood that excessively good then rapidly changing into deep depression. The mood, in both cases, is usually unwarranted considering the person's overall situation or innate personality. The manic-depressive individual may possess an unwarranted optimism and grandiose delusion about their potential. They may feel that they possess a special connection with God, celebrities or political figures. Manic depressive illness can cause a person to become hyperactive. This may cause them to extend themselves too much and they try to engage in more activities than time allows. The manic state can also impair a person's judgment, causing them to drive too fast, spend money unwisely, and engage in sexual behavior unusual for the person.

Other symptoms include racing thoughts, that when spoken, are disorganized and incoherent to the listener. The decreased need for sleep allows the sufferer to go with little or no sleep for days, without feeling tired. The patient is easily distracted and attention is often riveted temporarily on unimportant details. They also experience irritability whe their unrealistic plans and expectations fail to materialize.

More than just mood swings, bipolar disorder symptoms range from elation or irritability to sadness and hopelessness, and back again. The periods of highs and lows are called episodes, with each rotation from one extreme to the other calledacycle.

Cycles can be widely spaced, with long episodes of depression followed by long episodes of mania. Or each cycle can be very short. Cycles can include long or short periods of wellness in which no symptoms are experienced. In some cases, bipolars experience both depressive and manic symptoms of bipolar disorder at thesametimeinwhatiscalleda"mixedstate."

Although many of the indicators of manic episodes appear to be pleasant, they are actually so exaggerated as to be inappropriate and leave you feeling out of control and even desperate.

If left untreated, the manic phase can last as long as three months. As the mania diminishes, the person may have a period of normal mood and behavior, followed by the depressive phase of the illness. The depressive phase has the same symptoms as major depression.

The theories about the cause of manic-depression indicate a strong genetic basis to the biochemical malfunctions in the patient's brain. The disease is usually hereditary with the patient having the ability to identify a close relative with depression or manic-depressive disorder. As with other psychiatric conditions, manic depression is caused by biochemical imbalances.

TheHighs

A manic episode is indicated by an elevated mood or an irritable mood accompanied by several of the symptoms below. The medical professional who is performing the diagnosis is likely to ask many questions about your condition to determine their degree of severity. Most of us have experienced most of these symptoms at one time or another. Someone who has manic depression, though, is likely to experience a number of these symptoms over a significant period of time, in combination, with significant intensity.

restlessness—high energy and activity level
racing thoughts and rapid talking
decreased need for sleep
euphoria
distractibility
agitation
grandiosity—inflated self-esteem
pursuit of reckless or pleasurable activities
increased interest in goal-oriented activities.

TheLows

A depressive episode is indicated by the occurrence of a depressed mood or a loss of interest or pleasure accompanied by many of the symptoms below. Again, these symptoms are indicative of manic depression only if they occur with some persistence and severity.

hopelessness or pessimism
guilt, worthlessness, or helplessness
fatigue
insomnia or hypersomnia (inability to stay awake)
decreased ability to concentrate or make decisions
restlessness or irritability, agitation
loss of appetite and weight, or weight gain
chronic pain not caused by physical disease
recurrent thoughts of death or suicide; suicide attempts.

Diagnosis

Researchers agree that bipolar disorder has no single cause, but is rather a combination of factors. The findings strongly suggest an inborn vulnerability to the disorder interacting with an environmental trigger. This idea is similar to theories about the cause of other medicalconditions,suchasheartdisease.

Some researchers believe that bipolar disorder is caused by biochemical instability in the transmission of nerve impulses in the brain triggered by an upsetting life experience, substance abuse, lack of sleep, or other excessive stimulation.

And finally, the bipolar facts indicate that genetic inheritance is also a possible cause of bipolar disorder and other major mood disorders.

The diagnosis of this disorder begins with a thorough medical evaluation. This allows the treater to either identify or rule the other medical disorders that involve symptoms similar to bipolar disorder. An individual who has the symptoms but not the disorder may be taking steroids or amphetamines. They also could be suffering from thyroid, kidney or liver illness or multiple sclerosis. The medical evaluation is followed by a psychiatric assessment. After these steps are taken, the trained professional can work with the patient to devise the appropriate treatment plan.

Without a professional diagnosis, symptoms of bipolar I or bipolar II disorder can be difficult to track and may be invisible except to those who know the person very well. In the early stages of the disorder, manic depression behavior may actually appear as a different problem: substance abuse, changes in sleep patterns, strained relationships, or poor performance at work or school.

To make a bipolar disorder diagnosis, a doctor, usually a psychiatrist, uses the criteria established by the American Psychiatric Association in the Diagnostic and Statistic Manual of Mental Disorders. The mental health professional takes a detailed family history and a history of manic depression behavior over the patient's lifetime, including age at onset and current symptoms.

Manic-depression has proven to be among the most treatable of the psychiatric illnesses. Lithium is the most commonly prescribed medication for their disorder. It reduces the severity and decreases the frequency of he patient's symptoms. The individuals who have a family history of depressive illness, and who experience relatively normal mood between the highs and lows, seem to respond best to lithium. Lithium is effective in treating both the manic phase, and as a preventive measure to ward off depressive. Scientists believe that lithium impacts the effect neurotransmitters has on brain cells, thus reducing mood swings. Lithium must be monitored by a psychiatrist because of the potential for harmfull side effects.

Treatment

There is no cure for bipolar disorder, but there are two forms of treatment, physiological, and psychotherapeutic. Many medications are used and are being found affective in helping this disorder. This may be because the wide ranging causes and symptoms. Different categories of drugs used are mood stabilizers, anti-depressants as well as anticonvulsants. The two most commonly used medications are lithium and valaproate. Lithium, a mood stabilizer, can control episodes and decrease the likelihood of reoccurrence but it is still unknown exactly how it works and why it works for some and not others. Valaproate, an anticonvulsant or antiepileptic drug (AED), can also be used as a mood stabilizer and is usually used in cases where the patient cannot stand the side effects of or does not respond to lithium. AED's have been found especially helpful in treating the disease in certain cases such as rapid cycling. These drugs prolong the inactivation of voltage sensitive Na+ channels and affect CHS inhibitory neurotransmitters. This suggests some similarity in the biochemical problems of bipolars as well as epileptics. In addition to medication, counseling is important in the control of bipolar disorder. This can include behavioral therapy, family therapy and general education about the disease.

Some people have reported good results from regular acupuncture treatments (twice a week for six months, to start with) as well as herbal and nutritional supplements.

Most people with bipolar disorder—even those with the most severe forms—can be helped by bipolar medication. Because antidepressants alone can actually encourage episodes of mania or set off more frequent cycles, they are not the medication of choice in most cases of bipolar disorder. A mood stabilizer combined with an antipsychotic or anticonvulsant is typically prescribed aspartofthebipolardisordertreatmentplan.

Antidepressants

While antidepressants are typically not prescribed alone for the treatment of manic depression, they are often prescribed in conjunction with another bipolar medication, typically a mood stabilizer, to help manage depressive episodes.

Common antidepressants include certain types of selective serotonin reuptake inhibitors (Zoloft^®, Paxil^®, Prozac^®) and monocyclic aminoketones (Wellbutrin^®). Because they both have a low incidence of causing manic episodes, first choice antidepressants are Zoloft (especially in teens) and Wellbutrin. While Paxil is in the same class of drugs as Zoloft and Prozac, it also has anti-anxiety effects.

MoodStabilizers

One mood stabilizing bipolar medication, lithium, is usually very effective in controlling mania and preventing the occurrence of both manic and depressive episodes. Exactly how lithium works is unknown. Lithium should not be used in cases of severe cardiovascular disease, renal disease, or brain damage, or when evidence of severe debilitation, dehydration or sodium depletion exists.

Anticonvulsants

The anticonvulsants dicalproex (more commonly known as Depakote^®) and valproate are becoming more frequently used in bipolar treatment, and have shown to be especially useful in hard to treat cases. For maximum effect, these medications are often combined with lithium. The FDA has approved both valproate and Depakote for treatment of acute mania.

Antipsychotics

Zyprexa^® is a commonly prescribed antipsychotic medication for the short-term control of bipolar disorder. Zyprexa reduces the symptoms of mania by correcting elements of chemical imbalance that causes manic episodes.

Common Bipolar Medications

Lithium
Depakote
Wellbutrin
Paxil
Zoloft
Zyprexa

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Therapy

ElectroconvulsiveTherapy

Electroconvulsive therapy (ECT), also known as electroshock therapy, was first used to treat schizophrenia in the 1940s. Doctors soon found that ECT was also helpful in relieving the symptoms of mood disorders, including bipolar disorder.

Electroconvulsive therapy is usually given every other day during the first few weeks. Treatments are then reduced to weekly, then every other week, and finally monthly. While the typical three to twelve ECT treatments may take place over a few months, patients often experience a relief in symptoms within the first couple of weeks. Interestingly, ECT is most effective in severe cases of manic depression.

Conclusion

Mental illness, especially bipolar disorder, has been linked to artistic abilities. Many authors, musicians and artists have had the disease, and it is thought that the disease may have enhanced their capabilities. According to some the occurrence of bipolar disorder is 10 to 20 times more prevalent in creative people over the general population. There is an argument for and against this hypothesis. From the discussed possible causes of bipolar disorder it seems as though it causing creative ability is doubtful. According to Temple University psychologist Robert Weisberg, mania increases the energy level, but does not give the person ideas they would not have otherwise. A manic stage causes faster thinking and action in all bipolars, as does depression cause slower thinking and action. It is unlikely that the quality of creations increases, but rather just the quantity. It is more likely that the stressful, emotional, ever changing life.Bipolar disorder, also known as manic-depression, causes mood swings from overly high to deeply depressed. Some people with the disorder experience repeated episodes of depression with only occasional periods of mild mania. Some people experience both mania and depression simultaneously.

Symptoms of bipolar disorder typically begin in adolescence or young adulthood and continue throughout life.Bipolar disorder may be confused with attention deficit/hyperactivity disorder in children.Mood fluctuations may occur over a period of months, weeks or days, depending on the individual.

Bipolar disorder tends to run in families, and the severe behavior problems it causes often affect the entire family.