Bipolar Nutrients: Glutamate and Psychosis

Speaking of glutamate (see previous two posts), a new study on glutamate/dopamine balances
suggests that in vulnerable persons, changes in the relation of hippocampal glutamate to striatal dopamine systems may increase the risk of upcoming psychosis.
Stone JM, Howes OD, et al, Altered Relationship Between Hippocampal Glutamate Levels and Striatal Dopamine Function in Subjects at Ultra High Risk of Psychosis, Biol Psychiatry,2010 Jul 15. [Epub ahead of print]

Bipolar Nutrients: Comments on GABA/ Glutamate

A great introduction to GABA from EJD. (previous post)

Some cautions:

1 Many manics do seem to do better with GABA, taurine, magnesium glycinate, (and skullcap, theanine, etc.),* in various combinations, as per individual requirements. Similarly, see:  Seizural/bipolar connections and inhibitory aminos 

However, keep in mind that attention to inhibitors may not be the only important therapeutic concern, and for some manic subgroups, may not even be productive. 

* And, limiting excitotoxins (like glutamate) is probably always a good idea for manics.   

2 Alcohol is not a good choice for bipolars. Virtually all studies show alcohol use significantly worsens bipolar outcome. And many bipolars (especially manics) will have a hard time keeping intake to the small amount EJD suggests as the mild GABA-increasing benefit wears off. 

Look instead to nutritive supports to increase GABA.

3 Some mania subgroups tend to improve with a few of the foods EJD warns against:
In histapenic manias, dark leafy greens can be useful, due to the high folic acid content.
In high thyroid manias, broccoli, and the sulfur-rich crucifer family, which reduces thyroid access to iodine, generally help reduce stimulation.

For descriptions of inhibitory aminos, bipolar subgroups, etc., see my book, Natural Healing for Bipolar Disorder.

Reminder: The material in this blog is for educational purposes only, and is not intended as medical  diagnosis or treatment recommendations. Treatment must be tailored to each individual's unique biochemical requirements, including contraindications. If you need treatment for bipolar disorder, or any other medical condition, consult a knowledgeable physician. In some cases, this will be an orthomolecular or other nutritionally-oriented physician.

Bipolar Nutrients: GABA/Glutamate Balance, Vitamin K2, Salicylates, Ketones

As an introduction to GABA, let's look at the perspectives of EJD. The responses to his post are also interesting.

In brief, EJD proposes:
1 GABA is the most important factor in bipolar. Low GABA/glutamate ratio fosters bipolar mania
2 Possible ways to increase GABA: valerian, theanine, taurine, skullcap, kavakava, glutamine,  calcium/magnesium, relaxation techniques. And, of course, GABA (if available), 
3 A low carb, ketogenic diet increases GABA. Vinegar before meals, acts similarly, but can gets used up too fast.
4 Vitamin K2 (modest amounts) helps neutralize glutamate, metabolizing it to a bone-building compound.
5 Restrict/avoid salicylates -- by altering dopamine, activating NMDA receptors, and inhibiting GABA -- elevate, then sink mood, and often, as well, cause brain fog (B12 helps).


He also notes that:
Dopamine is the major antidepressant neurotransmitter. Serotonin is more of a regulator of dopamine and mood, than a direct antidepressant.
Genetic changes in enzymes*  that break down catecholamines, may favor preserving adrenalin over dopamine, lending irritability to any manias.

*EJD points to COMT; a responder suggests MAO.

Go to EJD's post for specifics.

I include EJD's ideas here as an interesting intro to GABA, worth thinking about. But do keep in mind that this is just one person's experience and conjectures, and that EJD is neither a physician nor a medical researcher.
And remember that bipolar treatment must be tailored to each individual's unique biochemical requirements.  Not all bipolars respond well to GABA, etc..  More in the next post.

Reminder: If you need treatment for bipolar disorder, or any other medical condition, consult a knowledgeable physician. In some cases, this will be an orthomolecular or other nutritionally-oriented physician.

Seizural/bipolar connections and inhibitory aminos

The amino acids, GABA, taurine, and glycine function as inhibitory neurotransmitters in the brain, reducing stimulation. They are often employed in natural treatments of certain types of seizures. In fact, some epilepsy meds seem to work by acting on the GABA system.
     At the same time, if indicated, GABA and/or taurine (glycine is milder) seem to be among the more potent mood-stabilizing, mania-moderating nutrients.

But does suppression of seizures have anything to do with promotion of mood stability? 

A number of researchers have suggested subconvulsive limbic seizures may underly bipolar disorder, but the jury is still out. Meanwhile, we might want to consider what bipolar and seizural disorders might have in common.

1 Kindling seems to occur in both disorders

(Post 1982, 89, 97, 2001, Ghaemi 1999, Bell 1992, Brewerton 1997) 
In epilepsy, repeated, continuous or excessive exposure to convulsive stimuli eventually increases the intensity and frequency of reactions. Over time, progressively milder stimulation is capable of triggering symptoms, eventually leading to apparently "spontaneous" seizures.
    Sound familiar? Think about the role of amphetamines, antidepressants, allergens, sugar and junk food, hyperthyroid, environmental stressors, and other stimulants in triggering episodes. And of the tendency of a single initial mania, whatever the cause, to lead to a future episode in 90-95% of cases. And how after years of mood disorder without orthomolecular treatment, episodes often become more frequent, but triggers tend to become more minor and more difficult to identify. 

2 Abnormal signalling plus kindling can induce seizures and may trigger mood episodes

Stoll and Severus (1996) suggest the interaction of kindling and abnormal signal transduction may be a primary trigger of mania and mood instability.
     Consider that all established mood stabilizers dampen excess signalling, and so block kindling. (Most inhibit calcium and sodium transfer across the neural membrane. Several interfere with the creation of inositol- and choline-related second messengers, and/or inhibit kinase and G protein activity.)  Thus, fewer messages are conveyed, and mania and seizures are suppressed.

3 Most mood-stabilizing meds are anticonvulsive and antikindling
(Post 1992, 95, 97, Ketter 1994, Ghaemi 1999, Bell 1992, Weiss 1995)
 Carbamazepine (CBZ), valproate (VPA), lamotrigene, and calcium channel blockers all have significant anticonvulsive properties.

     About two-thirds of bipolars have been found to respond best to CBZ or VPA;  two-thirds, to lithium.  Lithium shows minor anticonvulsive activity, while CBZ and VPA are clearly anticonvulsant and antikindling,  especially in the temporal and limbic regions of the brain associated with mood disorders.  Moreover, neurological problems (e.g., history of seizures, head injury, or abnormal EEGs) strongly suggest responsiveness.
     So the question remains, do these drugs work because they are antikindling and anticonvulsant?

4 Similarly, many nutrients identified as helpful to bipolars are also reputed to have antiseizure or antikindling properties — not only taurine, GABA, and glycine, but also most of the nutrients noted in previous posts (magnesium, zinc, C, and certain B vitamins). 
     More on taurine, GABA, and glycine in future posts. 

For further description of inhibitory aminos, seizural/bipolar connections, biotype issues, etc., and for contraindications and references, see my book: Natural Healing for Bipolar Disorder.


Reminder: Treatment must be tailored to each individual's unique biochemical requirements, including contraindications. If you need treatment for bipolar disorder, epilepsy, or any other medical condition, consult a knowledgeable physician. In some cases, this will be an orthomolecular or other nutritionally-oriented physician.