Fw: Bipolar Child Newsletter - Spring, 2001/ Information on Omega-3's

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The Bipolar Child Newsletter

Spring, 2001 Vol. 7

THE A-Zs of OMEGA-3's

--Demitri and Janice Papolos

There is a contact section on our web site that allows visitors to make

comments and to tell us what they would like to read about in our seasonal

newsletters. For months now, we have had a significant number of readers

request information on omega-3 essential fatty acids as a treatment for mood

stabilization. Ever since Dr. Stoll at Harvard published provocative

findings about the greater stabilization of rapidly-cycling adult bipolar

patients with the supplementary use of high doses of fish oils (the majority

of these patients were on traditional mood stabilizers), a large percentage

of parents have opted to add omega-3's to their children's' regimens of

pills and capsules.

When we were young, fish (a very unpalatable item on the dinner table) was

inexplicably referred to as " brain food. " Today, studies are concluding that

the oils of certain fatty fish not only have health benefits for the heart

and help mitigate other diseases, but they may be quite helpful in treating

psychiatric illnesses such as depression, bipolar disorder, and

schizophrenia. Studies in midpoint are also examining whether fish oils are

effective for attention-deficit disorder with hyperactivity and learning

disabilities such as dyslexia.

So we thought it was a good time to write about omega-3's for children

suffering with bipolar disorder. Some early reports are encouraging - but

far from conclusive - and we will attempt in the pages below to inform

readers of what is known and also what is not yet proven about the

intriguing link between essential fatty acids and mood stabilization.

Why Are They Called Essential Fatty Acids?

Essential fatty acids are called so because - though they are crucial for

growth and development - they cannot be manufactured in the body, but must

be consumed through the diet we eat or from supplements we swallow.

There are two families of essential fatty acids: omega-6 fatty acids and

omega-3 fatty acids. Omega-6 fatty acids are found in common vegetable oils

such as corn, safflower, sunflower, and cottonseed; omega-3 fatty acids are

found in the tissues of oily fish such as mackerel, anchovies, herring, and

salmon, and in green leafy vegetables, canola oil, flaxseed, and walnuts.

The omega fatty acids are named for the position of the first double bond in

their carbon chains. Thus, the first double bond in the omega-6's begins at

the sixth carbon atom from the end of the chain. The first double bond in

the omega-3's begins at the third carbon position from the end of the chain.

Once in the body, both omega-6 and omega-3 fatty acids are biochemically

converted and impact the body initially in two ways. First, they become

incorporated into the cell membranes and keep the cell membrane optimally

fluid. If there are not enough omega-3 and omega-6 fatty acids, these cell

walls will incorporate saturated and other fats and become less fluid (not

good).

In fact, essential fatty acids are the major building blocks of cellular

membranes surrounding every cell in the body. Known as lipid bilayers

because they are made up of two layers of fat, these fatty acid walls help

control the opening and closing of the cell's channels that allow the

passage of important messenger molecules into and out of the cell.

In the second pathway, the omegas convert to hormone-like substances called

eicosanoids (ee-KO-sah-noids) that influence metabolic activities, blood

clotting, inflammation, vasoconstriction and vasodilation, blood pressure,

and immune function. In addition, the eicosanoids appear to have some role

in regulating mood.

Because the eicosanoids derived from omega-6's are pro-inflammatory and

those derived from omega-3's are anti-inflammatory, it's important that the

body has a proper balance.

A Closer Look at Omega-3's

There are three important omega-3 fatty acids:

LNA (Alpha-linolenic acid ) EPA (eicosapentanoic acid) This is pronounced

EE-ko-sa--pehn-ta-NO-ic acid. DHA (docosahexaenoic acid) This is

pronounceddo-ko-sa-HEX-eh-noic acid). LNA is a shorter chain omega-3 that

comes from walnuts, flaxseed, canola oil, and other green leafy plants. It

is an 18-chain molecule that can be converted - sometimes inefficiently -

into the longer-chain EPA and DHA molecules.

EPA and DHA are the fatty acids parents most often read about. The " eico " of

eicosapentanoic acid means 20 in Greek, and, indeed, EPA is a fatty acid

with a chain length of 20 carbon atoms and 5 double bonds. DHA is formed

when EPA lengthens by losing hydrogen and increasing its number of double

bonds. Thus, DHA is a fatty acid with 22 carbon atoms and 6 double bonds.

While omega-6 fatty acids are distributed throughout the body, both EPA and

DHA (the long-chain omega-3's found primarily in fish oils) are needed in

the brain to an extraordinary degree. The brain needs more of these omega-3

fatty acids than any other organ in the body. For instance, the

musculoskeletal system is rich in proteins and minerals, but the major

structural component of the brain and its cells is fat and water. In fact,

the dry weight of an adult brain is 60 percent fat.

During gestation, DHA builds the structure of the brain and the retina of

the eye. According to Artemis Simopoulos, M.D., author of The Omega Diet,

this brain-building DHA comes from the mother, goes through the placenta to

the bloodstream of the baby and on to the baby's brain during the last

trimester of pregnancy.

When we asked her how mothers who eat no fish can supply that DHA, she

answered: " Pregnant women make DHA from eating green leafy vegetables,

walnuts, etc. that contain alpha-linolenic acid. A full-term baby is born

with adequate stores of DHA. " She did write that premature babies are

deficient in omega-3 fatty acids.

Butalpha-linolenic acid converts rather inefficiently to EPA and DHA, and

the greatest concentrated form of these fatty acids comes from the tissues

of fish.

If We Get Omega-3's from Fish, Where Do the Fish Get Them From?

Essential fatty acids are synthesized in the chloroplasts of plants. These

are the green, chlorophyll-containing structures in plant cells that convert

sunlight and carbon dioxide into oxygen and a complex of organic molecules,

including sugars, proteins, and lipids (fats).

Only the chloroplasts of marine and fresh water algae produce high

quantities of long-chain omega-3 fatty acids. And these are eaten by small

aquatic animals and shrimp, which are in turn eaten by slightly larger fish

which are in turn eaten by humans (IF THEY EAT FISH!).

Unfortunately, most of us eat insufficient quantities of fish, and most of

the fish we eat today is farmed (so the fish are not out in the wild eating

all those chloroplasts but are instead fed some kind of commercial fish

foods).

Not only are our diets relatively fish-free (or wild fish-free), but thanks

to the Industrial Revolution we have upended the ratios of omega-3's to

omega 6s in our diets. While ratios of 2:1 of omega-6's to omega-3's were in

the diet eaten for thousands of years by human beings, today's American diet

pegs this ratio at more like 20 to one or higher.

What Does the Industrial Revolution Have to Do With It?

For some 40,000 years, evolving humans were hunters and gatherers and

existed on a diet that was extraordinarily rich in omega-3 and omega-6 fatty

acids. In a beautiful chapter in Stoll's new book, The Omega

Connection, he writes that essential polyunsaturated fatty acids produced by

land-and water-based plants were plentiful during the Paleolithic era that

ushered in the ascent of modern humans. Because early humans emerged around

the freshwater lakes of the Rift Valley of East Africa and the fatty acids

were so plentiful, it may explain why humans never evolved (or lost through

evolution) the enzymes needed to synthesize these essential fatty acids.

Perhaps Mother Nature did not foresee the Industrial Revolution where any

omega-3 intake would be completely overwhelmed by an omega-6 excess.

Where does the evolutionary diet get turned on its head?

In our escalating use of vegetable oils which began in the 1960s and 70s

(right about the time we began to notice higher rates and an earlier onset

of mood disorders).

Corn oils were never a part of the evolutionary diet because they were

nearly impossible to extract. According to Artemis Simoupoulos, MD in her

book The Omega Diet, 100 ears of corn crushed under a stone wheel would

produce approximately 5 tablespoons of corn oil. Traditional society used

olive oil, which was not only easier to press, but actually helps the body

synthesize omega-3's.

But, advances in the 20th century gave us sophisticated equipment that,

using high temperature, hydraulic pressure and chemical solvents, allows us

to manufacture tons of corn oil at a time. (It's important to remember that

omega-6's are not the bad guys. In fact, they are crucial for proper body

functioning and there is almost as much arachidonic acid - an omega-6 fatty

acid - in the brain as DHA, and it is important as a signal transduction

agent at almost all neurotransmitter receptors.)

The big problem started when someone came up with the process of

hydrogenation - the process of making foods made with vegetable oil less

perishable. Vegetable oils could be heated, exposed to ametal catalyst such

as nickel or copper, and converted into a less perishable fat that could be

added to all kinds of convenience foods. These foods would last and last

through shipping and shelving. According to Dr. Simopoulos, " by 1979, the

American public was consuming an estimated 10 billion pounds of fat and oil

per year, of which 60 percent was partially hydrogenated oil. "

That paragraph doesn't quite give the graphic picture of the hydrogenation

process. Listen to how Kane, Ph.D. describes it in his booklet Fats:

The Inside Story:

It's a " process in which vegetable oils are treated, under pressure with

temperatures up to 360 F, with hydrogen in the presence of a catalyst e.g.

nickel and are thus converted into substances closely resembling solid

animal fat. This produces a material dark and smelly like grease which is

then bleached and deodorized to become a white tasteless synthetic " fat "

(plastic maybe - but not a fat) that can be flavored and colored and sold to

imitate butter or used for lard or other shortening or frying fat. "

We now know that hydrogenation reduces the essential fatty acid content of

oils (both omega-6's and omega-3's) and by rearranging the bonds of fatty

acids, transforms them into trans-fatty acids. Not only do these trans-fatty

acids push the LDL (bad cholesterol) levels higher, but they lower good

cholesterol (HDL) levels. This increases the risk of cardiovascular disease.

They also insinuate themselves in the cell membranes - thus blocking the

essential fatty acids and they commandeer some of the enzymes needed to

create necessary eicosanoids.

Any label on a package that contains the phrase " partially hydrogenated "

means that these trans-fatty acids were used to manufacture the food stuff.

Do not use margarine, and the next time the person at the concession stand

at the movies asks you or your child if you want butter on the popcorn

remember that their " butter " is little more than hydrogenated soy oil.

The Increasing Rates of Depression and Bipolar Disorder

Something has been going on since 1945: the rates of depression have

increased world wide, and the age of onset is shifting downward - younger

people are being affected. This trend called " the cohort phenomenon " was

noted in the 1980s by Drs. Gerald Klerman, Myrna Weissman, and Elliot

Gershon who found that each successive generation of individuals born since

World War II appears to have a higher incidence and earlier age of onset of

both major depression and bipolar disorder.

While there are many theories attempting to explain this striking increase,

one of them points to the increase in our diets of sources of omega-6 oils

(corn and soy as two examples) and the corresponding marked decrease in

omega-3 fats (this has not been proven, however).

The association between depression and the types of fats we consume was made

when ph R. Hibbeln, of the National Institute of Health examined the

consumption rate of omega-3 in countries around the world. In an important

paper published in 1998 in the British Journal The Lancet, he reported that

the rates of depression were lower in countries that consumed a lot of fish.

He found that rates of depression could actually be predicted based on fish

consumption.

An association had been established. A year later, in April 1999, in the

Archives of General Psychiatry, Dr. Stoll from Harvard and his

colleagues published the first double-blind placebo study which examined

what happens when rapidly-cycling bipolar patients had their medications

supplemented with high doses of fish oils. (It should be noted that eight of

the 30 were not on medications of any type.)

The thirty patients were divided into two groups and one group got a placebo

of olive oil capsules; the other 9 grams of pharmaceutical quality EPA and

DHA fatty acids. While the study was designed for a nine-month period, a

preplanned preliminary analysis of the data found a significant discrepancy

between the placebo control group and the omega-3 fatty acid group: the

patients on the placebo relapsed or failed to improve, while many of the

patients taking the omega 3 supplements experienced dramatic recoveries.

Why might this be? To paraphrase Dr. Stoll in his book The Omega Connection:

When a neurotransmitter binds to a receptor, the receptor sets in motion

within the cell a series of chemical processes known as signal

transduction,amplifying the original signal and ultimately altering the

activity of theca. We know that mood stabilizers inhibit signal

transduction.

He goes on to say that " inhibiting signal transduction in bipolar disorder

would be analogous to building a dam across a raging river, quieting the

downstream waters. "

Lithium and the anticonvulsants inhibit signal transduction....so too do

omega-3 fatty acids.

A Host of Questions

Since the Stoll findings were published and received a lot of media

attention, a number of parents have placed their children suffering with

bipolar disorder on fish oil supplements. Some parents report a difference

in their children's behaviors: they seem less explosive, calmer and their

moods appeared more stable. One mother whose very young child was being

given only omega-3's said: " He went from a 10 (in severity) to a two. "

Another mother wrote of her child's diagnosis at eight following a

hospitalization. Her daughter was stabilized on lithium, but last year - at

the age of 13 - she began taking 1 g of an enriched EPA omega-3 product in

addition to the lithium. " She's gained a higher level of stability than we'd

ever seen before, " the mother reported.

But questions abound about this treatment. How many grams of omega-3's a day

must a child ingest (often in addition to many pills and capsules of

prescription medications)? Which brand should they take? How much EPA and

DHA should they be taking (what should the ratio of one to the other be)?

We turned to a neuroendocrinologist in Scotland, Horrobin, MD who is a

pioneer in lipid metabolism, and who has been researching and reporting on

essential fatty acids for over two decades.

First we told him that many parents want to know how they are supposed to

get their children to swallow so many capsules of omega-3's. (They are

extrapolating from Dr. Stoll's study which gave 9 grams of omega-3's to the

patients with bipolar disorder.)

Dr. Horrobin responded that he could answer dosing questions only about

unipolar depression and schizophrenia because he and his research team had

conducted dose ranging studies with pure ethyl-EPA looking at 1g, 2g, and 4

g per day. In schizophrenia the optimum dose was 2g per day with 4 g giving

less benefit. In depression, the optimum dose was 1g, with 2g and 4g giving

less benefit.

In other words, there were diminishing returns when giving higher doses - in

those two illnesses.

Then we raised the question about the amounts of EPA and DHA in each

capsule: what should they be?; and why, if the brain is constructed of

mostly DHA, is the impression growing that pure EPA, or ratios high in EPA

compared to DHA may be preferable. (This has also not been proven in bipolar

disorder.)

He answered that the impression of EPA's greater importance is derived from

the conclusions of three studies in depression and schizophrenia which

compared placebos to an EPA-rich oil and a DHA-rich oil and found that the

EPA preparation was effective, but the DHA preparation was not. In some

studies, mixed EPA/DHA preparations were effective, however.

Why should EPA be more important? Dr. Horrobin replied: " The whole issue of

EPA versus DHA is a controversial one. There is no doubt that in the brain

there is an abundance of DHA whereas EPA levels are very low and possibly

mainly found in the microvessals. There is no doubt at all that DHA is vital

when the brain is growing rapidly in utero and in the first 2-3 years of

independent life. But beyond that it looks as though EPA is more important.

Ralph Holman from the University of Minnesota and the Grand Master of

essential fatty acid studies in humans, once summed up the situation by

saying 'DHA is structure, EPA is function.' "

So ratios of EPA versus DHA (or whether the supplement should be pure EPA)

are unknown and the answers will have to wait future research reports.

Presently there are several ongoing studies of omega-3 fatty acids in

bipolar disorder. Dr. Stoll is repeating his Archives study with the same

dose of mixed EPA/DHA in a larger number of patients. Dr. same dose

Network is doing a 200 patient study of 6 grams a day of ethyl EPA versus

placebo in about eight centers in the U.S. and Europe. Dr. ph Biederman

of Harvard Medical School is planning a pilot study of ethyl-EPA in both

depressed and bipolar children prior to doing a randomized study. Dr.

Belmaker in Israel is planning a randomized study in adults. (We will report

any and all findings as they are published.)

In addition, studies are being conducted by Drs. Burgess and

s at Purdue University with children with ADHD using a higher DHA

product. There are also studies looking at the effects of DHA in dyslexia.

So What's A Parent to Buy?

We are not endorsing any brands, but the following companies (in

alphabetical order) manufacture pharmaceutical-grade omega-3 fatty acids,

and a certain brand may be more suited to each individual child. For

instance, if he or she has trouble swallowing capsules, the size of the

capsule may be very important to a family ( a 500 mg capsule is much smaller

than a 1,000mg capsule). One product, Coromega, is in pudding form and no

capsule-swallowing is required.

We have seen one brand have a greater effect on a child's mood than another,

and we can't explain why that might be, so it behooves a parent to try more

than one brand if the first produces little effect.

You also want to look at the source of fish oils. Anchovies and sardines are

lower on the food chain and so have less chance of incorporating mercury and

other contaminants such as PCBs.

COROMEGA -Each packet contains: EPA: 350 mg DHA: 230 mg Plus Vitamins C and

E and Folic Acid

Coromega takes fish oils and delivers them in a creamy, pudding-like

orange-flavored emulsion that is packaged in a squeeze-pak (think Go-Yort).

The advantage of this delivery system is that there are no pills to swallow

and that three packets would give a child over a gram of EPA (although we

still don't know what a child needs).

We found that the pudding alone has a long aftertaste, but if the pudding is

mixed with orange juice it's almost smoothie-like (with lumps; however a

blender might be a great help here).

Boxes of 28 packets cost $19.99 and we found them at the local Stop & Shop.

Go to www.oilofpisces.com and punch in your zipcode to find out who in your

area is selling this brand.

KIRUNAL: 4 capsules provide EPA: 420 mg DHA: 140 mg Each bottle of 240

capsules costs $29.95.

Kirunal capsules are manufactured by Dr. Horrobin's company in

Scotland and are distributed by Emerson Ecologics (www.emersonecologics.com

or 1-). The main fish source are sardines caught off the coast

of Africa. The capsule size is 500 mg so they are smaller and easier to

swallow.

Dr. Horrobin suggests starting with 4 capsules - two in the morning; two in

the evening for four weeks. If the response is good, stay there. If not,

move up to eight capsules for another 4 weeks. If there is a partial

response, try 12 capsules for four weeks.

NORDIC NATURALS: Pro DHA (500mg capsules,strawberry-flavored) 250 mg of DHA

150 mg of EPA small amounts of Vitamin E and C for freshness. A bottle of 90

gel caps costs $19.95

Pro EPA (1,000mg capsules, lemon flavored) 450 mg of EPA 100 mg of DHA. A

bottle of 60 gel caps costs $22.00

To order: Go to www.nordicnaturals.com or call 1-.

OMEGABRITE: 3 -500 mg capsules provide 1,125 mg of EPA 165 mg of DHA. A

bottle of 60 softgels costs $19.95.

To order go to www.omegaBrite.com or call 1-.

What Are the Downsides of Omega-3 Supplements?

There seems to be the smallest possibility of mania induced by omega-3

supplements. We have read about 6 cases to date. Interestingly, 5 of the 6

occurred with EPA-enriched products (higher doses of EPA than DHA). Despite

this, there is some impression amongst the researchers that mania would more

likely happen on a DHA-enriched product. Again, there are many questions and

very few answers.

Fish oils should not be used by people allergic to iodine, or those who are

using blood thinners, or who are anticipating surgery. Pregnant women and

people with diabetes, as well as those using high-dose aspirin or ibuprofen

should consult with their doctors before using fish oils of any kind.

The Diet of the Child is of Utmost Importance. Parents need to look not only

to capsules, however, but to the total diet of their children. Because, as

we said earlier, other lipids compete in the cell membranes for the spots

that the omega-3's would occupy, a diet high in fat and trans-fatty acids

will interfere with omega-3 integration in the cell membrane and the

membranes will become stiff and inflexible.

Examine food labels carefully and if you read the words " partially

hydrogenated, " avoid purchasing that food stuff, or letting your child

consume it outside the home. (Since almost all packaged cookies, crackers,

chips, donuts etc. contain these trans-fattyacids, and these foods are so

kid-important, we sympathize with the difficulty of this. We also understand

that a craving for carbohydrates is one of the symptoms of a bipolar

disorder, so a parent's policing snack foods becomes a Herculean task)

Switch to olive oil or canola oil for cooking and salad dressings, find a

way to incorporate walnuts and leafy green vegetables in the diet, and see

if you can buy eggs that are omega-3 enriched.

We contacted Eggland's Best whose hens are fed an all-natural, vegetarian

diet containing canola oil as the principal source of fat. Their Director of

Nutrition Services wrote us that: " Since canola oil is the lowest saturated

fat oil and contains appreciable levels of linolenic acid(ALA), the result

is an egg with increased levels of omega-3 fatty acids (100 mg vs. 35 mg for

ordinary eggs). An egg like Eggland's has approximately 48 mg of

alpha-linolenic acid, and 50 mg of its derivatives, DHA and 2 mg of EPA and

25% of less saturated fat. "

Country Hen makes an enriched omega-3 egg also, and there are other brands

out there if you check at the supermarket or health food store.

Last Words

It's obvious from everything we've said above that much research needs to be

done before we understand if children with bipolar disorder are deficient in

essential fatty acids or are not metabolizing them correctly, or whether

supplementation will correct this; and if so, what should the doses of

supplementation or the ratio of EPA to DHA be? Hopefully, studies published

in the not distant future will provide better guidance.

It is possible to have lipid profiles done by taking a blood draw and

analyzing the red blood cell membranes. This allows a profile of 12-16 weeks

of metabolism (if one analyzes the plasma only, it tells one what the blood

donor ate yesterday). One of these tests that is performed at s Hopkins

can read elevations of trans-fattyacids, the ratios of lipids themselves,

and the amount in percentage to each other. This test costs about $420 and

is available only to the medical profession through www.bodybio.com.

We are not recommending lipid profiles as of yet and are looking into them

further. We just wish that we could know whether a child needs more of this

or that essential fatty acid before we barrage them with high doses of

anything Parents should know that the FDA has approved up to 3 grams per day

of fish oil as safe for humans of all ages.

As always, we'll keep you posted via this newsletter as to any new study

results that will help clarify the picture. We wish you happy summer days

and nights.

All best, Janice Papolos and Demitri Papolos, MD

References:

Burgess, R., s, et al. " Long-chain polyunsaturated fatty

acids in children with attention-deficit hyperactivity disorder. " American

Journal pard of Clinical Nutrition, 2000:71 (supplement):327-329.

Gershon, Elliot etal. " Birth-cohort changes in manic and depressive

disorders in relatives of bipolar and schizoaffective patients. " Archives of

General Psychiatry 44 (1987):314-319.

Hibbeln, ph. " Fish consumption and major depression. " The Lancet 351

(1998):1213.

Horrobin, . " Depression and bipolar disorder: relationships to impaired

fatty acid and phospholipid metabolism and to diabetes, cardiovascular

disease, immunological abnormalities,cancer, aging and osteoporosis:

possible candidate genes. " Prostaglandins, Leukotrienes and Essential Fatty

Acids 60 (1999): 2!7-234.

Horrobin,. E-mail correspondence April 20, 2001.

Kane,. Fats: The Inside Story. Millville, NJ: BodyBio,1999.

Klerman, Gerald L. et al. " Birth cohort trends in rates of major depressive

disorder among relatives of patients with affective disorder. Archives of

General Psychiatry 42 (1985):689-693.

, A. J. et al. " Fatty acid deficiency signs predict the severity

of reading and related difficulties in dyslexic children. "

Prostoglandins,Leukotrines and Essential Fatty Acids 63 (2000): 69-74.

Simoupoulos, Artemis P. The Omega Diet. New York:Harper , 1999.

s, L.J. Zentall SS et al. " Essential fatty acid metabolism in boys with

attention deficit hyperactivity disorder. " American Journal of Clinical

Nutrition 62 (Oct 1995): 761-768.

s L.J. and SS Zentall et al. " Omega-3 fatty acids in boys with

behavior, learning and health problems. " Physiological Behavior April-May

(1996):915-920.

Stoll,. " Omega 3 fatty acids in bipolar disorder: A

preliminary,double- blind, placebo-controlled trial. " Archives of General

Psychiatry 56 (May 1999): 407-412.

Stoll, . The Omega Connection. New York: The Free Press, 2001.

(The FDA approval of fish oil at dosages up to 3 grams per day as safe in

all age groups can be found in the Federal Register Vol. 62, No. 108, June

5, 1997.)

The authors wish to thank Horrobin, MD, Martha Hellander, Artemis

Simopoulos, MD, Dorie Geraci, R.N., Kane, Ph.D. and Michele Opheim

for their kind help in preparing this newsletter.

------------------------------------------------------------------------

Because so many parents signed on after the launch of this newsletter, we'd

like to index previous editions. They can all be found under

http://www.bipolarchild.com if you click on " Info and Articles. " To date,

we've covered the following topics:

Bipolar Disorder, Co-Occurring Conditions, and the Need for Extreme Caution

Before Initiating Drug Treatment - November 1999

Millennium Issue: Aggression and the Overarousal of the Limbic System in

Children with Bipolar Disorder - January 2,000

Mood Stabilizers: An Update - March 2000

Night Terrors in Children with Bipolar Disorder - July 2,000

Atypical Antipsychotics: Should They Be Prescribed as a Monotherapy? -

October2000

What Can the Amish Teach Us About Early-Onset Bipolar Disorder? - January

2001

The A-Zs of Omega-3's: Essential Fatty Acids in the Treatment of Bipolar

Disorder - May 2001