---------- Biological Basis of Behavior ------ ----
---------- SPRING, 2005 ----------

                            
                            
                       BIOLOGICAL BASIS OF BEHAVIOR

Psychology 321                     	                   
Spring, 2005					HGH 225
Dr. John M. Morgan                 	MWF, 8am to 9:00                                                   


INTRODUCTION

The drug lithium has been used for a variety of disorders such as 
gout, diabetes, and epilepsy for over 100 years.  It was not until 
1949 when John Cade discovered that lithium had a calming effect 
on guinea pigs that the possibilities of it being used for mania 
were explored (Paykel, 1992).  Since then, lithium has been 
established as one of the primary treatments for manic depression 
disorder.  In the body of this paper we will explore the chemistry 
of lithium, the synaptic transmitters involved, the parts of the 
neuron affected, the inhibitory and excitatory potential changes, 
the ion channels effected, the physiological changes, the primary 
behavior changes, the side effect behavior changes and the effects 
reported by users.

Joselyne Sulzner
CHEMISTRY

Lithium is a chemical element found in group IA of the periodic 
table, along with sodium, rubidium, and cesium. Lithium has an 
atomic number of 3, and an atomic weight of 6.94. In general, 
lithium is more stable than hydrogen, and slightly less stable 
than nitrogen, carbon, and oxygen. When looking at chemical ion 
properties, it is useful to consider three main characteristics: 
the size, or radius, of the ion, the charge, and the ion's 
electron affinity. Lithium has a similar charge to radius ratio to 
that of magnesium, which is in group IIA of the periodic table, 
and so chemists say that the two elements are "chemically 
similar." Lithium has low electron affinity in general, but it is 
strong compared to other alkali metal cations and therefore is 
highly polarizing (Williams, 1973). Lithium is the lightest known 
solid element, and when dissolved in liquid ammonia it has the 
lowest known density (Jefferson and Griest, 1977). In the body, 
lithium ions can easily take the place of both sodium and 
magnesium, although they appear to prefer magnesium receptors 
because sodium is a slightly larger molecule than lithium and has 
a less perfect fit (Williams, 1973). 

When lithium is combined with other atoms, several useful 
molecules can be created. For the purposes of this paper we will 
consider the lithium salts, such as lithium carbonate, lithium 
citrate, and lithium sulfate. These molecules, among others, are 
used in psychiatry for the treatment of bipolar I disorder. 
Lithium carbonate (Li2CO3) has an atomic weight of 73.89, and is 
the most popular of the lithium salts in use today (Johnson, 
1980). It is not clear why this is, as there does not appear to be 
a significant difference between lithium carbonate and the other 
lithium salts. For a complete listing of lithium salts currently 
in use, see table 1. Lithium salts are preferred for medical use 
because they are soluble in water, whereas natural lithium is 
found in silicate form and is therefore not water soluble. Lithium 
salts have a half life of approximately 1830 hours in the body, 
depending on the weight of the subject (Williams, 1973). 

ROUTE OF ACCESS

Lithium is usually taken orally in pill form, or injected directly 
into the bloodstream. In pill form, there are normal and time 
release doses available. Because the margin between a therapeutic 
dose and a toxic dose (therapeutic index) is so small, the time 
release form is more popular. In this way, the patient doesn't 
experience rapid peaking of lithium in the bloodstream (Jefferson 
and Griest, 1977). When taken orally the gastrointestinal tract 
rapidly absorbs lithium, although specific locations along the 
tract have not been identified. Lithium is widely distributed 
throughout the body's water, both intracellular and extracellular, 
though it is absorbed first by the kidneys, then the liver, the 
bones, the muscles, and finally the brain (Williams, 1973). 
Because the brain is so slow to absorb lithium, it can take up to 
a week to normalize lithium concentrations within the body. 
Lithium also leaves the brain very slowly, although not as slowly 
as it leaves the bones. In one case, lithium was still detected at 
high levels in a patient's bones even after he had been of lithium 
for six months (Jefferson and Griest, 1977). 
 
Lithium is not protein bound, and it is not metabolized into any 
other compounds. Instead, it is excreted almost totally by the 
kidneys. Because of this, lithium is contraindicated for those 
with kidney or urinary disorders. Other bodily fluids such as 
sweat, sperm, saliva and feces also excrete lithium, however this 
makes up less than 5% of total lithium absorbed and is not 
clinically significant (Jefferson and Griest, 1977). It is 
important to monitor plasma levels of lithium to prevent toxicity. 
As a point of interest, lithium used to be given as a salt 
substitute to people with coronary heart failure! Needless to say 
this is not longer practiced (Williams, 1973).

SYNAPTIC TRANSMITTERS INVOLVED

I should first state that causes for the therapeutic effect of 
lithium are unknown (Jefferson and Griest, 1977). The brain is 
such a complex structure that it is almost impossible at this 
stage to make statements regarding the correlation and causation 
of a drug and a process. That being said, there have been hundreds 
of studies using rats, dogs, cats, mice, monkeys and various other 
nonhuman animals to try and find out the exact changes lithium 
makes to the brain. Human studies are less numerous and more 
anecdotal, as it is hard to conduct statistically significant 
research on human subjects. For one thing, many studies would 
require the death of the subjects. Aside from ethical concerns, it 
would simply be hard to find volunteers! It is also hard to find 
enough subjects to make any worthwhile comparisons. Mental health 
hospitals have patients with such varying symptoms that it is hard 
to find a group of people similar enough to compare. As a result, 
most of the major studies about lithium involve clinical trials. 
Even though the research is limited at best, it still contributes 
to our knowledge of how this drug works.

Lithium is thought to have an effect on several neurotransmitters, 
especially catecholamines and indoleamines (Davis, Janowsky and El 
Yousef, 1973). Because lithium can act by ion substitution (more 
on this later) it is probable that this is how lithium alters 
these processes. Lithium has also been connected with changes in 
glutamate and gamma aminobutyric acid (GABA), and possibly even 
acetylcholine (Williams, 1973).

When rats are treated with lithium, there is a marked acceleration 
of the disappearance of norepinephrine, and a lower amount of 
norepinephrine in the brain overall (Schildkraut, 1974). When 
norepinephrine is metabolized, it turns into tritiated deaminated 
catechol metabolites. There are higher levels of these metabolites 
found in rats that are treated with lithium (Schildkraut, 1974). 
So, lithium increases the intraneuronal inactivation of 
norepinephrine (by deamination), thereby decreasing the amount of 
norepinephrine available to interact with andrenergic receptors 
(Schildkraut, 1974). Lithium also increases the reuptake of 
norepinephrine in nerve ending cells (synaptosomes). Because the 
studies with rats were so promising, researchers were disappointed 
to find that human subjects had less apparent changes on the 
norepinephrine system (Haskovec and Rysanek, 1969, as cited in 
Gershon and Shopsin, 1973). There were some initial problems 
duplicating the rat studies, but overall the human subjects 
studies confirmed the idea that lithium decreases the amount of 
norepinephrine in the brain. What this tells us about lithium's 
mood stabilizing effects is as yet unclear.

There are similar studies conducted for serotonin, although the 
results are less obvious. A summary of the findings is presented 
below: Corrodi and his associates (1967)(as cited in Gershon and 
Shopsin, 1973) reported that, in rats, acutely administered 
lithium did not affect the metabolism (turnover) of serotonin. 
Schildkraut (1974) reported an increase of brain serotonin in rats 
after acute administration of lithium (decrease in serotonin 
turnover). Later, Corrodi and his associates (as cited in Gershon 
and Shopsin, 1973) again looked at lithium dosing in rats, this 
time looking at chronic administration. This time the authors 
concluded that a prolonged exposure to lithium could lead to 
decreased activity in serotonergic neurons. A study by Ho et. al. 
(1970)(as cited in Gershon and Shopsin, 1973), looked at the same 
thing and found a decrease in the rate of serotonin turnover, and 
yet another study by Bliss and Ailion (1970)(as cited in Gershon 
and Shopsin, 1973), reported no changes. Overall it is perhaps 
possible to say that if there is any effect on serotonin, lithium 
appears to decrease the turnover rates and increased brain levels 
of serotonin. 

Several studies have also looked at the effects of lithium on 
glutamate and GABA in monkeys. Although more information is 
needed, the consensus is that after lithium treatment there is a 
decrease in brain glutamate (Delgado, 1969, as cited in Gershon 
and Shopsin, 1973), an increase in glutamate in the hypothalamus 
and amygdala (Gottesfeld 1971, as cited in Gershon and Shopsin, 
1973), and an increase in GABA in the hypothalamus (Gottesfeld, 
1971, as cited in Gershon and Shopsin, 1973).

Studies about the effects of lithium on Acetylcholine and dopamine 
show mixed results (Schildkraut, 1974) and need further testing.

PART OF THE NEURON AFFECTED

Studies show that lithium acts on the postsynaptic receptor of the 
nerve cell. Although a lithium specific receptor has not been 
identified, studies have shown that lithium interacts with the 
adenyl cyclase cyclic AMP system (Gershon and Shopsin, 1973). 
Regarding the turnover of norepinephrine, lithium has been shown 
to affect cranial nerve terminals (Schildkraut, 1974). In 
crayfish, Obara and Grundfest (As cited in Gershon and Shopsin, 
1973) discovered that lithium acts differently on different parts 
of the nerve cell. This study showed that lithium created a 
stronger depolarization in the soma, or cell body, membrane of the 
nerve than in the axonal membrane. Therefore, during an exposure 
to lithium, the cell fired for a period of time and then declined. 
During this decline, the action potentials first ceased in the 
soma, but they persisted in the axon. In addition, when sodium is 
replaced by lithium in the cervical ganglia, the nerve impulses 
produced are smaller in direct proportion to the percentage of 
sodium that has been replaced (Small and Small, 1973). More on the 
effects of lithium on ion channels will be discussed later in this 
paper.

REFERENCES

Davis, J.M., Janowsky, D.S., and El Yousef, Khaled. 1973. 
Pharmacology: The Biology of Lithium. In Gershon, S. and Baron 
Shopsin (Eds.), Lithium: its Role in Psychiatric Research and 
Treatment. (pp. 167). New York: Plenum.

Enna, S.J., Malick, J.B., Elliott, R. 1980. Antidepressants: 
neurochemical, behavioral, and clinical perspectives. New York: 
New York University Press.

Gershon, S., and Shopsin, B. (Eds.) 1973. Lithium: its role in 
psychiatric research and treatment. New York: Plenum Press.

Jefferson, J., Griest, John. 1977. Primer of lithium therapy. 
Baltimore: Williams and Wilkins.

Johnson, F.N. 1980. Handbook of lithium therapy. Baltimore: 
University Park Press, c1980.

Lithium. Encyclopedia Britannica. Retrieved February 27, 2005, 
from Encyclopedia Britannica Premium Service.  
http://www.britannica.com/eb/article?tocId=9048517

Schildkraut, J.J. 1974. The Effects of Lithium on Norepinephrine 
Turnover and Metabolism: Basic and Clinical Studies. Journal of 
Nervous Mental Disorders, 8:146.

Shou, Mogens. 1973. Preparations, Dosage and Control. In Gershon, 
S. and Baron Shopsin (Eds.), Lithium: its Role in Psychiatric 
Research and Treatment. (pp.189). New York: Plenum.

Small, J, and Small, I. 1973. Pharmacology: Neurophysiology of 
Lithium. In Gershon, S. and Baron Shopsin (Eds.), Lithium: its 
Role in Psychiatric Research and Treatment. (pp.83). New York: 
Plenum.

Williams, R.J.P. 1973. The Chemistry and Biochemistry of Lithium. 
In Gershon, S. and Baron Shopsin (Eds.), Lithium: its Role in 
Psychiatric Research and Treatment. (pp. 15). New York: Plenum.


Jessica O'Donnell
INHIBITORY OR EXCITATORY POTENTIAL CHANGES 

Graded potentials can be either hyperpolarizations (inhibitory) or 
depolarizations (excitatory).  Inhibitory postsynaptic potential, 
also referred to as IPSP, is the temporary hyperpolarization of a 
membrane.  An inhibitory postsynaptic potential occurs when 
synaptic input selectively opens the gates for potassium ions to 
exit the cell (carrying a positive charge with them) or for the 
chloride ions to enter the cell (carrying a negative charge with 
them).  Inhibition is not just the absence of excitation, it is an 
active brake that is able to suppress the excitatory responses 
from occurring (Kalat, 2004).

Excitatory postsynaptic potential, also known as EPSP, is a graded 
depolarization. As a result of sodium ions enter the cell, 
excitatory postsynaptic potential occurs. As a result of the 
synaptic activation, the sodium gates open, allowing an increase 
in the flow of sodium ions crossing the membrane.  Excitatory 
postsynaptic potential is a subthreshold event that decays over 
space and time, meaning its magnitude decreases as it travels 
along the membrane (Kalat, 2004).     

Lithium has both inhibitory and excitatory features. Evidence has 
shown that lithium alters sodium transportation 
(http://www.mentalhealth.com).  In the extracelluar fluid lithium 
may replace sodium.  During the process of depolarization lithium 
has an extremely rapid intracellular influx.  Although, it is not 
effectively removed by the sodium-potassium pump.  According to 
Kalat (2004) the sodium-potassium pump, "[is] a protein complex 
that repeatedly transports three sodium ions out of the cell while 
drawing two potassium ions into the cell" (p. 41).  As a result, 
it prevents the cellular reentry of potassium.  This interferes 
with the electrolyte distribution across the neuronal membrane, 
resulting in a decrease in the membrane potential, changes in 
conduction and neuronal excitability.  As measured by cortical 
evoked potential, for humans lithium alters the excitability of 
the central nervous system (http://www.mentalhealth.com).
 
Lithium enhances the uptake of norepinephrine and serotonin into 
the synaptosomes, thus reducing their action.  Lithium also 
reduces the release of norepinephrine from synaptic vesicles and 
inhibits production of cAMP.  "Lithium inhibits the synthesis of 
cAMP by the adenylyl cyclase in many brain regions, including the 
cerebral cortex, caudate, and hippocampus, but not the brain stem 
or cerebellum"
(Feldman, Meyer & Quenzer, 1997).
 
"The inhibitory action of lithium on NE-sensitive adenylyl cyclase 
is a consistent finding, but lithium clearly has distinctive 
effects on the adenylyl cyclase that is coupled with receptors 
other than NE.  For example, instead of inhibition, lithium seems 
to have a stimulatory effect on DA-sensitive adenylyl cyclase or 
no effect at all in ex vivo studies" (Feldman, Meyer & Quenzer, 
1997).  Since the adenylyl cyclase activation occurs at a point 
beyond the neurotransmitter receptor, the inhibition of their 
actions by lithium suggests an action beyond the receptor 
stage(Feldman, Meyer & Quenzer, 1997).

Lithium might possibly have several inhibitory sites.  Competing 
for Mg² acutely and an inhibitory action on GTP activation.  
Another significant action lithium has on the PI cycle is the 
inhibition of the phosphatase that converts inositol monophosphate 
into inositol.  "Lithium's effects on the PI cycle have generated 
a good deal of excitement: because the phospholipid second 
messenger is coupled to both excitatory and inhibitory 
neurotransmitter receptors, lithium can have an antimanic and/or 
an antidepressant effect" (Feldman, Meyer & Quenzer, 1997). 
"Inhibition of inositol monophosphatases is the only one of the 
potential sites proposed for lithium action on the second 
messenger" (Feldman, Meyer & Quenzer,1997).  

"The dampening of phosphoinositide-mediated signal transduction in 
both inhibitory and excitatory neurons may explain the antimanic 
as well as antidepressant effects of lithium" (Feldman, Meyer & 
Quenzer, 1997).   

ION CHANNELS EFFECTED

The known neurotransmitter receptor produces two different general 
classes of effects, one of which is they can directly control or 
gate the opening of an ion channel (Hyman, Arana & Rosenbaum, 
1995).  "Ion channels are highly specific filters, allowing only 
desired ions through the cell membrane" 
(http://www.omedon.co.uk/shadow).  Evidence has suggested that 
lithium interferes with ion exchange mechanisms and nerve 
conduction.  Within two to four hours after lithium has been 
administered, lithium ions are rapidly absorbed from the 
gastrointestinal tract and plasma (http://www.mentalhealth.com).  

Since lithium is in the same group of elements as potassium and 
sodium and has a monovalent charge when ionized, it has been 
suggested that lithium may produce a therapeutic effect by 
modifying neuronal ionic mechanisms.  Lithium also has an ionic 
radius very similar to those of calcium and magnesium, indicating 
its action may be related to interaction with these divalent 
cations (Feldman, Meyer & Quenzer,
1997).

Many investigators have found that in red blood cells the ration 
of intracellular to extracellular lithium ion is higher for 
bipolar patients in comparison to normal controls when both groups 
have administered lithium.  "The best evidence for an ionic 
mechanism of action for Li involves Ca²" (Feldman, Meyer & 
Quenzer, 1997). 
Along with acting on neuronal ionic mechanisms, lithium has a wide 
range of biological effects on many different systems (Feldman, 
Meyer & Quenzer, 1997).     

PHYSIOLOGICAL CHANGES

"For the majority of patients with bipolar disorder, lithium 
carbonate (Carbolith, Lithane)is the most effective medication and 
is the usual drug of choice" (Feldman, Meyer & Quenzer, 1997).  
The primary purpose of administering lithium carbonate is to treat 
the manic stage of bipolar disorder (manic-depressive illness).  
Bipolar patients experience severe mood changes, ranging from an 
excited or manic state (for example, anger or irritability) to 
depression or sadness(http://www.medlineplus.gov).  Lithium is 
used in order to reduce the frequency and severity of manic 
states.  Evidence has suggested that lithium is less effective in 
preventing the recurrence of depression compared to mania 
(Feldman, Meyer & Quenzer, 1997).  Symptoms of mania involve 
aggressiveness, flight of ideas, grandiosity, hypersomnia, motor 
hyperactivity, and poor judgement.

Dependent on the patient's sensitivity to lithium and the dosage 
prescribed, adverse reactions may vary.  Adverse reactions may 
occur at serum lithium concentrations below 1 mmol/L.  The most 
frequently reported adverse effects are due to the rapid rise in 
serum lithium concentrations are the initial postabsorptive 
symptoms.  Symptoms at this level can include, but are not limited 
to, a dazed feeling, gastrointestinal discomfort, muscle weakness, 
nausea and vertigo.  After the stabilization of therapy these 
symptoms may vanish.  Though the more common and persistent 
adverse reactions are fatigue, fine hand tremors, nephrogenic 
diabetes insipidus (kidney), polyuria (excessive urination) and 
thirst.  It is important to note that having any of these 
reactions does not necessarily mean that a reduction of dosage is 
need.  

Mild to moderate adverse reactions generally occurs at serum 
lithium concentrations ranging from 1.5 to 2 mmol/L.  Moderate to 
severe adverse reactions may occur at serum lithium concentrations 
greater than or equal to 2 mmol/L (http://www.mentalhealth.com).  
In the midrange serum concentration levels of lithium, 1.5 to 2 
mmol/L, might cause diarrhea, drowsiness, lack of coordination, 
muscular weakness, and vomiting.  Under the higher serum 
concentration levels of lithium, 2 mmol/L or more, there is even a 
greater inability to coordinate voluntary muscular movements.  
Their vision may be blurred.  A ringing noise may persist in the 
patient's ear.  Giddy behavior has been noted by some patients.  
The patient may also experience a polyuria, excessive urination, 
producing a large output of dilute urine.  

As the serum concentration levels increase to over 3 mmol/L, 
complex problems involving multiple organs and organ systems may 
occur.  Hence the reason serum concentration levels of lithium are 
recommended not to exceed 2 mmol/L.  Remember individual responses 
will vary to the different lithium serum concentration levels.

Out of all the side effects that have resulted from taking 
lithium, the majority of the side effects are experienced in the 
nervous system.  Within the central nervous system (CNS) there 
have been many adverse effects that have been reported.  
Anesthesia of the skin (a general loss of the senses of feeling, 
such as pain, temperature, or touch) may occur.  Experiencing 
blurred vision can take place.  A patient might experience 
blackout spells, headaches, and possibly seizures.  Their speech 
might become slurred.  Tongue movements and deep tendon reflexes 
have also been noted.  There may be muscle hyperirritability, this 
can range between slight twitching to movement of whole limbs.  
The patient might also become very restless.  These adverse side 
effects, along with others, have been related to the lithium serum 
concentration levels affecting the central nervous system.  In the 
autonomic nervous system the side effects that have been noted are 
blurred vision, dry mouth, and also impotence.


In the cardiovascular system many adverse side effects can occur.  
This can include cardiac arrhythmia (a disturbance in the rhythm 
of the heartbeat) and abnormally low blood pressure.  Bradycardia, 
relatively slow heart action, can lead to a loss of consciousness 
due to insufficient blood flow to the brain.  

Gastrointestinal complications can occur from taking lithium.  The 
adverse side effects include diarrhea, nausea, and vomiting would 
fall under this category.  Anorexia nervosa has been associated 
with lithium.  Patients can suffer from abdominal pain, flatulence 
(having an accumulation of gas in the intestinal tract), and 
indigestion.  A patient's salivary glands might swell or excrete 
an excessive amount of salvia.  Gastritis, inflammation of the 
mucus membrane of the stomach has been reported.

Dermatological effects may occur as a result from lithium therapy.  
Breakouts of acne, itching, and psoriasis (scaly patches) may 
occur.  It is also possible for a patient to lose skin sensation.  
Dryness or thinning of the hair is a potential side effect.  A 
patient could possibly develop leg ulcers due to lithium.

Genitourinary functions adverse reactions are very significant 
since lithium is excreted almost completely by the kidneys.  
Albuminuria, is the presence of albumin in the urine can occur.  
Along with glycosuria, which is the excretion of glucose in the 
urine.  As well as oliguria.  Even though polyuria can take place, 
so can a reduction of urine.       

Usually transient gastrointestinal symptoms (e.g., abdominal pain, 
diarrhea, thirst, vomiting, etc.) the first side effects to occur.  
Throughout the therapy a mild degree of fine hand tremors may 
persist.  In early intoxication, thirst and polyuria may be 
followed by blurred vision, drowsiness, along with other side 
effects.  As the intoxication progresses a patient may experience 
confusion, diarrhea, seizures, and possibly either coma or death 
(http://www.mentalhealth.com).

REFERENCES

Feldman, Robert S., Meyer, Jerrold S., & Quenzer, Linda F. (1997).  
Principles of Neuropsychopharmacology.  Massachusetts: Sinauer 
Associates Inc., Publishers.

Hyman, Steven E., Arana, George W., & Rosenbaum, Jerrold F. 
(1995).  Handbook of Psychiatric Drug Therapy.  New York: Little, 
Brown Company.
        
Kalat, James W. (2004).  Biological Psychology 8th Edition.   
Canada: Thomson Learning, Inc., Wadsworth.

http://www.medlineplus.gov

http://www.mentalhealth.com

http://www.omedon.co.uk/shadow


Aileen "Liz" Johnson
PRIMARY BEHAVIOR CHANGES

Though the drug lithium is used for a number of disorders ranging 
from acute depression to eating and personality disorders (Paykel, 
1992), it's primary use is for bipolar disorder, also known as 
manic depression.  Patients with bipolar disorder "between two 
poles: depression and its opposite, mania" (Kalat,2004), often 
with periods of normal behavior in between (Jamison,1993).  In 
addition, the patient is also prone to "mixed episodes" in which 
symptoms of both mania and depression are present.  Intensity of 
these episodes can range from mild to dangerous, as in the case of 
a manic depressive mother who severed the arms of her 10 month old 
daughter (Associated Press, 2005).   Despite its genetic origin 
(Kalat. 2004; Jamison, 1993; DBSA, 2005), the onset of symptoms 
and behavior is rather late, averaging 18 years of age (Jamison, 
1993).

There are two types of manic episodes: manic and hypomanic.  The 
DSM describes a manic episode as "a distinct period of abnormally 
and persistently elevated, expansive, or irritable mood," 
(Jamison, 1993).  Symptoms include inflated self esteem, a reduced 
need for sleep, increased talkativeness and sociability, flight of 
ideas, distractibility, an increase in goal directed activities 
(such as work, school or sex), and an excessive involvement in 
pleasurable activities (PsychologyNet, 2003).  The occurrence of 
these symptoms must not be able be confused with a mixed state 
(see description below), must impair the individual's ability to 
function normally, and cannot be explained by the effects of a 
substance (i.e. alcohol, hallucinogenics) or a medical condition 
(i.e. hyperthyroidism) in order for the episode to be considered 
"manic."

Hypomanic episodes are similar but shorter and often less intense.  
Behaviors include "increased productivity, often with unusual and 
self imposed working hours," "uninhibited people seeking," 
"hypersexuality," "inappropriate laughing, joking, punning," and 
"excessive involvement in pleasurable activities with lack of 
concern for painful consequences," (Jamison, 1993).  Hypomanic 
individuals also have increased creativity, inflated self esteem, 
decreased need for sleep and an excess of energy (Jamison, 1993).  
As one patient describes it, "At first when I'm high, it's 
tremendous… ideas are fast… like shooting stars you follow until 
brighter ones appear… all shyness disappears, the right words and 
gestures are suddenly there… uninteresting people things, become 
intensely interesting.  Sensuality is pervasive, the desire to 
seduce and be seduced is irresistible.  Your marrow is infused 
with unbelieveable feelings of ease, power, well being, 
omnipotence, euphoria… you can do anything… but, somewhere this 
changes," (Bipolar Disorder Manic Depression Support Group Chat, 
2005).

Depressed periods often follow manic and hypomanic episodes.  
Symptoms such as prolonged sadness, changes in eating and sleeping 
patterns, irritability, anger, worry, agitation, anxiety, apathy, 
feelings of guilt/worthlessness, social withdrawal, inability to 
concentrate, indecisiveness, suicidal or morbid thoughts (DBSA, 
2005), among others over a period of at least two weeks are the 
makings of major depression.

The third type of episode characteristic of bipolar disorder is a 
"mixed state."  Mixed states are periods of time when the patient 
experiences symptoms of both mania and depression.  French 
composer Hector Berlioz described it as a state of mind which was, 
"mocking, active, passionate, malignant," (Jamison, 1993).  They 
last at least one week in length (PsychologyNet, 2003).  Of the 
three types of episodes, the mixed state can be the most dangerous 
as they "are closely associated with the damaging and killing 
sides of manic depression: alcoholism, drug abuse, and suicide," 
(Jamison, 1993).

Bipolar disorder can be divided into two main categories: bipolar 
I and bipolar II.  Bipolar I is your classic case of bipolar 
disorder, incorporating at least one manic/mixed state and one 
depressed state (DBSA, 2005).  Bipolar II is similar, except that 
the subject rarely experiences full blown episodes of mania, 
experiencing hypomania instead (Kalat, 2004).

Lithium has been found most effective in patients with bipolar I 
disorder.  The drug works to "stabilize the mood of a bipolar 
patient, preventing a relapse into either mania or depression," 
(Kalat, 2004).  Lithium (particularly Lithobid, a time released 
version of it) works to treat the following symptoms of mania: 
"pressure of speech, motor hyperactivity, reduced need for sleep, 
flight of ideas, grandiosity, elation, poor judgment, 
aggressiveness, and possible hostility," (Solvay, 2002).  
Stabilization generally occurs within 1 to 3 weeks and when taken 
regularly the drug should also bring down the intensity of future 
highs (Solvay, 2002).

The efficacy of lithium when it comes to the depression side of 
the disorder seems to be debated as it is heralded as effective in 
some texts (Paykel,1992; Kalat, 2004) and ineffective or passed 
over in others (Solvay, 2002; Centerwatch, 2004).  Often lithium 
is relied on primarily for the treatment of mania, paired with an 
antidepressant (i.e. Prozac, etc.) to curb depression (J blue, 
2004; stfelony, 2004).  However, many studies have found lithium 
to be effective in reducing suicidality (Paykel, 1992; Jamison, 
1996).

SIDE EFFECTS

In exchange for response rates as high as 90% (Centerwatch, 2004), 
the use of lithium can bring with it many side effects.  Side 
effects generally come in two waves: initial postabsorptive 
symptoms and more common, persistent adverse reactions (Long, 
2005; Solvay, 2002).

"[A]t first, I experienced mild nausea, drank litres and litres of 
water, and had a mild headache, but on the whole, felt fine.  [A] 
bit dull, but that was sort of the point.  I started sleeping 
again, and by the end of the week was surprisingly functional in 
school," (stfelony, 2004)

The initial symptoms are "believed to be associated with a rapid 
rise in serum lithium concentrations," (Long, 2005).  
"[G]astrointestinal discomfort, nausea, vertigo, muscle weakness 
and a dazed feeling" (Long, 2005) are common initial symptoms.  
Generally, they disappear within a few weeks or as soon as the 
drug therapy has been stabilized (the dosage of lithium is often 
varied initially to gauge the correct level of lithium needed for 
treating the patient).  Signs of an incorrect dosage can include 
anoerexia, metallic taste, weight gain or loss, general muscle 
weakness, slurred speech, blurring of vision, blackout spells, 
headaches, seizures, dryness and thinning of hair, skin rash, 
anemia, and many others (Long, 2005).

The more persistent symptoms include fine hand tremors, fatigue, 
thirst, polyuria (frequent urination), and nephrogenic diabetes 
insipidus (Long, 2005).  In addition, diarrhea and muscle weakness 
have been observed (Paykel, 1992).  These symptoms typically stay 
throughout treatment and are unwavering to dosage change.

More serious side effects, such as hyperthyroidism and kidney 
troubles, have also been observed (Paykel 1992; Long 2005).  Some 
evidence has also shown that long term usage may cause medical 
complications such as hypercalcemia (Bilanakis, 2004).

Due to the proximity of therapeutic and toxic levels of lithium, 
the blood levels of patients must be monitored closely (Long, 
2005; Paykel, 1992).  Unfortunately, the signs of lithium 
intoxication can often overlap or simply be more intense versions 
of the existing side effects.  "Confusion, increasing 
disorientation, muscle twitchings, hyperreflexia, nystagmus, 
seizures, diarrhea, vomiting, and eventually coma and death" 
(Long, 2005), are among the signs of toxicity.  Reduction or 
withdrawal of treatment can remedy the toxicity if caught early 
enough.

EFFECTS REPORTED BY USERS

Lithium, though effective in some individuals, has a wide range of 
effects:

"[I] was feeling slowed down…. [m]y overabundance of racing 
thoughts was still in my head; it just felt as though [I] had to 
work harder to reach out and grab one…. [I] still felt pressed to 
talk incessantly in social situations, only instead of feeling 
exceptionally witty and brilliant, [I] felt as though [I] was 
constantly tripping all over myself or watching myself from afar," 
stfelony, The Icarus Project (stfelony, 2004)

"[M]y focus, my intellect, my memory, all of it has been 
negatively affected by the Lithium…. I can't even read," 
britneyspearsherself, The Icarus Project (J blue, 2004)

The majority of personal accounts of the effects of lithium focus 
on the difficulties of the side effects associated with the drug.  
Most, however, also go on to say that without lithium, their life 
would be even more difficult:

"Lithium robs me of life itself.  I become the walking dead.  A 
big do nothing.  Everything is sooo hard to do.  To do 3 simple 
things in a row, like fill up with gas, go to the bank, go to the 
grocery store… is so hard, as to almost be impossible…. I had only 
2 hours functional a day on Lithium…. I was extremely good at 
staring off into space and not minding doing so…. [However,] 
lithium did make it easier for me to fight and stay alive.  It 
also nearly prevented migraines in me and untangled mixed states 
for me," room42, The Icarus Project (J blue, 2004)

With the right dosage (the finding of which appears to be a 
precise art form), the side effects can be minimized and 
functionality maximized.  Psychiatrist Kay Redfield Jamison (who 
is manic depressive, herself) talks about her experience in her 
memoir "An Unquiet Mind":

"Lowering my lithium level had allowed not only a clarity of 
thinking, but also a vividness and intensity of experience, back 
into my life…. Gradually, as I began to look around me, I realized 
that this was the kind of evenness and predictability most people 
had…."

REFERENCES

Associated Press (2005, February 15). Mom accused of severing 
baby's arms incompetent for trial.  CNN.com. Retrieved February 
28, 2005 from the World Wide Web: 
http://www.cnn.com/2005/LAW/02/15/severed.arms.ap/index.html

Bipolar Disorder Manic Depression Support Group Chat (2005). 
Bipolar disorder, manic depression symptoms.  Support 4 Hope. 
Retrieved March 2, 2005 from the World Wide Web: 
http://support4hope.com/bipolar_disorder/manic_depression_symptoms
.htm

Bilankis, N. & M. Gibiriti. (2003). Lithium intoxication, 
hypercalcemia and "accidentally" induced food and water aversion: 
a case report. Progress in Neuro-Psychopharmacology & Biological 
Psychiatry 28, 201-203.

Centerwatch Newly Approved Drug Therapies Listing. (2004, June 
29). Drugs approved by the FDA: Drug name: Lithobid (lithium 
carbonate). Thomson Centerwatch.  Retrieved March 2, 2005 from the 
World Wide Web: 
http://www.centerwatch.com/patient/drugs/dru50.html

DBSA (2005, February 22). Bipolar disorder. Depression and Bipolar 
Support Alliance.  Retrieved February 28, 2005 from the World Wide 
Web: http://www.dbsalliance.org/info/bipolar.html

PsychologyNet (2003). Diagnostic criteria. PsychologyNet.org. 
Retrieved March 4, 2005 from the World Wide Web: 
http://www.psychologynet.org/bipolar1.html 

Gorman, J., MD (2002, September). Lithium. NAMI. Retrieved 
February 28, 2005 from the World Wide Web: 
http://www.nami.org/Template.cfm?Section-
About_Medications&Template=/TaggedPage/TaggedPageDisplay.cfm&TPLID
=51&ContentID=20820

Jamison, K.R., PhD (1993). Touched with fire: Manic depressive 
illness and the artistic temperament. New York: Free Press.

Jamison, K.R., PhD (1995). An unquiet mind: A memoir of moods and 
madness. New York: Vintage Books.

J blue (2004, November 5). is it lithium or is it me? The Icarus 
Project. Retrieved February 28, 2005 from the World Wide Web: 
http://theicarusproject.net/community/viewtopic.php?t=1197

Kalat, J.W. (2004). Biological psychology (8th ed.). Belmont, CA: 
Wadsworth/Thomson Learning.

Long, P.W., MD (2005). Lithium carbonate. Internet Mental Health. 
Retrieved February 28, 2005 from the World Wide Web: 
http://www.mentalhealth.com/drug/p30-102.html 

Solvay Pharmaceuticals (2002). Lithobid. Solvay Pharmaceuticals, 
Inc. Retrieved March 5, 2005 from the World Wide Web: 
http://www.fda.gov/cder/foi/label/2002/187027s40s46s49s49lbl.pdf 

Paykel, E.S. (1992). Handbook of affective disorders (2nd ed.). New 
York: The Guilford Press.

Rennert, N.J., MD. (2004, April 19). Medical encyclopedia: 
hypercalcemia. Medline Plus.  Retrieved March 2, 2005 from the 
World Wide Web: 
http://www.nlm.nih.gov/medlineplus/ency/article/000365.htm

stfelony (2004, November 7). lithium questions, or "what is wrong 
with me?!" The Icarus Project. Retrieved February 28, 2005 from 
the World Wide Web: 
http://theicarusproject.net/community/viewtopic.php?t=1187

CONCLUSION

Lithium, or, more commonly, Lithium Salt, is an element used to 
treat bipolar disorder in humans. Bipolar disorder consists of 
severe highs and lows of mood, ranging from deep depression to 
extreme mania. The cycling of the disorder depends on the person, 
but it can vary from many shifts within one day (rapid cycling) to 
extended periods of each. Lithium is indicated primarily for 
patients who are not rapid cycling. Like many other medications, 
the exact effects of Lithium are unknown. Psychiatrists and 
Chemists have isolated many of the physiological and behavioral 
changes that occur after the administration of Lithium, and yet 
the exact cause of its therapeutic effect is not fully understood.


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