Omega-3 Fatty Acids and Bipolar Disorder

By: Jessica Lepetich

Outline

Overview of Bipolar Disorder

Current Treatments

The Omega-3 FAs Connection

Suggested Functions of Omega-3 FAs

Studies

Conclusions

Bipolar Disorder

Also known as manic-depressive illness

Brain disorder that causes unusual shifts in a person’s mood, energy and ability to function. Image: www.theablecrew.org/ interactive/bip.gif

Bipolar Disorder

Those who suffer may experience periods of mania.– Characterized by euphoric or irritable mood,

increased energy, decreased need for sleep, rapid thinking and speech

As well as periods of depression– Characterized by loss energy, loss of usual

interests and please, difficulty concentration and suicidal ideation

Symptoms of Mania

Increased energy, activity, and restlessness Excessively "high," overly good, euphoric mood Extreme irritability Racing thoughts and talking very fast, jumping from one idea to another Little sleep needed Unrealistic beliefs in one's abilities and powers

Poor judgment Spending sprees A lasting period of behavior that is different from usual Increased sexual drive Abuse of drugs, particularly cocaine, alcohol, and sleeping medications Provocative, intrusive, or aggressive behavior Denial that anything is wrong

Symptoms of Depression

Lasting sad, anxious, or empty mood Feelings of hopelessness or pessimism Feelings of guilt, worthlessness, or helplessness Loss of interest or pleasure in activities once enjoyed, including sex Decreased energy, a feeling of fatigue or of being "slowed down" Restlessness or irritability

Difficulty concentrating, remembering, making decisions Sleeping too much, or can't sleep Change in appetite and/or unintended weight loss or gain Chronic pain or other persistent bodily symptoms that are not caused by physical illness or injury Thoughts of death or suicide, or suicide attempts

Bipolar Facts

More than 2 millions adults (1% of population) suffer from bipolar disorder.

Ranked 6th in worldwide causes of disability

Cause

A definite cause for any type of depression is difficult to determine but include genetics, changes in the brain, and environmental factors like stress and major life changes.

Treatment Options

Medication– Mood Stabilizers:

• Lithium, Valporate, Carbamazepine

Psychosocial Interventions– Psychotherapy

Other– Herbal Supplements, Omega-3 FA

Images: www.bipolaraware.co.uk/ Images/

Lithium

Most popular drug treatment for BPD

Affects the phosphatidylinositol system (PI), by decreasing the concentration of myo-insitol.

Therefore, the PI system cannot resynthesize as fast, so the chance of over-activation is reduced.

Side Effects: tremors, acne, weight gain, sedation, and cognitive dulling

Image:http://www.websters-online-dictionary.org/coreimages/digital+art/83514_9192_by_Morrhigan.jpg

PI System

Image: Stoll et al. (1999)

Valproate

Suggested to have an effect on the GABA neurotransmitter system.Also suggested to directly inhbibit PKC.Positive Aspects: Superior efficacy than lithium and less toxicSide Effects: tremors, GI distress, hair thinning, hepatitis, and weight gain

PKC

http://www.ruf.rice.edu/~rur/issue1_files/Biology/Barron/Barron_3_small.jpg

Omega-3 Fatty Acids

Long chain, polyunsaturated fatty acids (PUFAs) found in marine and plant sources.

EPA and DHA are marine derived.

Alpha-linolenic acid is found in plants, seeds, oils and nuts.

Image:http://www.healthcastle.com/images/salmon.jpg

Why Omega-3 and Bipolar?

In the CNS, phospholipids composed of omega-3 and omega-6 FAs play an essential role in neuronal signal transduction.Correct balance of PUFA = normal neuronal functioning

Abnormal PUFA concentrations have been found in psychiatric disorders.Many epidemiological studies have shown that countries with higher levels of omega-3 fatty acid consumption had lower rates of depression and bipolar disorder.

Bipolar and Seafood Consumption

How do Omega-3 FA’s work?

Inhibition of neuronal signal transduction.– Specifically the PI System

Blockade of Ca2+, which reduces overactive neuronal signal transduction

PKC SystemImage:http://www.suinaka.or.jp/diet/DHA.jpg

PI System

Omega-3 FAs are going to cause a decrease in the concentration of myo-inositol.

Myo-insitol is needed to resynthesize the PI system, so a lower concentration would lead to a reduction in over-active signaling.

Image: Stoll et al. (1999)

PKC and Ca2+

PKC is normally activated by DAG and Ca2+.

Omega-3 FAs are shown to inhibit the catalytic domain of PKC.

Omega-3 FAs are also shown to create a Ca2+ channel blockage.

Image:http://www.biocarta.com/pathfiles/h_pkcPathway.gif

Stoll et al.

Combination of 30 men and women, 18-65 years of age.Met DSM-IV definition for bipolar disorder.½ received placebo (olive oil ethyl esters), ½ received omega-3 FA supplementEach subject took 7 pills a day for a total of 6.2 g of EPA and 3.4 g of DHA per day.Found that omega-3 FAs lead to significant symptom reduction and a better outcome when compared to the group receiving the placebo pill.

Sagduyu et al.

37 total subjects

All met DSM-IV criteria for bipolar disorder.

Average starting dose of omega-3 FAs 1824.32 mg

Average final dose was 2878.38 mg

Found that omega-3 FAs added to current bipolar treatment significantly helped reduce irritability.

Chiu et al.

20 healthy volunteers and 20 patients with bipolar disorder, between the ages of 18 and 65 years.All bipolar patients met the criteria specified in the DSM-IV.Analyzed blood samples in order to look at omega-3 FA levels.Found that there was a decreased concentration of DHA in the blood samples from the bipolar patients.

Conclusions

Much research stills needs to be conducted before a solid relationship can be determined.The exact system(s) that omega-3 FA’s affect need to be determined.– PI,PKC, Ca2+, or all a combination?

More double-blinded placebo studies are need, to see if omega-3 FAs as medication is a plausible ideaBipolar disorder itself needs to clear up many of its own unanswered questions