Posted by Michael Bell on March 4, 2003, at 23:01:38
In reply to Re: Dopamine agonists » Michael Bell, posted by daizy on March 4, 2003, at 7:44:45
Daizy, this is what I think about Social Phobia and neurotransmitters. This theory comes from my own experience, discussions in chat rooms and surfing the net for countless hours. I'll take the transmitter systems one at a time.
Serotonin: High levels: linked with harm avoidance and anxiety, including General Anxiety Disorder. Low levels: linked with some forms of depression, obsessions, deviant thoughts and aggression. I don't believe serotonin is a major player in SP, though it's probably involved on some level (maybe levels are slightly high), uin a complex way we don't know about. My main reason for this belief comes from my own experience as well as what I've encountered regarding SSRIs. One common result that I have found across many chatboards and various studies is that SSRIs do NOT help with SP, and in fact often make the symptoms worse. Those that have noticed an effect often say that they feel emotionally numb as a result of taking these medications. My own feeling is that a medication that removes anxiety through dulling of emotions may be "effective" to some degree, but not in a pleasant way. An interesting things about serotonin - it increases when we "freeze" in frightful situations (similar to mind going blank in social settings)
Norepinephrine -- since this is the fight or flight neurotransmitter, it probably also has a role in SP. Caffeine induces panic attacks in people with SP twice as much as people without SP. Also, beta blockers inhibit norepinephrine from reaching receptors, and are useful for people with performance anxiety. However, studies have shown that people with generalized SP actually have similar NE levels to "normal" people. Also, beta blockers are not very effective for generalized SP. Our receptors are probably hypersensitive to NE, so that we have stronger reactions to situations that should only cause minimal stress.
GABA: I believe most of the evidence points to GABA dysfunction as being the primary culprit in SP. Here's why: The two most effective prescription drugs for SP are Klonopin and Nardil. No other drugs come close. KLONOPIN - works by enabling GABA to bind more easily to its receptors. Klonopin sometimes works so well that it causes disinhibition in some patients, the very opposite of SP. NARDIL - one of the older, irreversible MAOIs, it increases the levels of dopamine, serotonin and norepinephrine in the body and brain. However, other MAOIs, such as Parnate, do the same, and are not nearly as effective as Nardil for SP. The difference is Nardil also a powerful inhibitor of the enzyme that breaks down GABA. I believe it is this action on GABA that makes Nardil such an effective tool. The two other substances that I have heard miraculous results about are ALCOHOL and GHB. In my own experience, alcohol is the single most effective substance I have ever tried for SP, too bad it's dangerous! Most researchers attribute the "wellbeing" effect of alcohol to be due to its potentiation of GABA, however there is also some increased dopamine transmission that takes place as well. The effects of GHB are two-fold. First, it increases the effectiveness of GABA for several hours, causing feelings of wellbeing and disinhibition. Over the course of these hours, it also blocks the transmission of dopamine, causing dopamine levels to build up in the brain. Then the user falls asleep and all the built up dopamine is released, causing the user to wake up refreshed and alert. So here we have four drugs, all which act primarily on GABA, and they are the most effective drugs for SP that we know about. Also, GABA is the most abundant modulator in the brain, around 30% of all transmitters. Low levels have been associated with panic attacks, anxiety disorders, insomnia and a variety of other problems.
DOPAMINE: I believe this to be the second most important neurotransmitter involved in SP, but I actually disagree with people who claim dopamine levels are too low. Quite the opposite, I think we have high levels of dopamine but LOW NUMBER OF RECEPTORS/POOR TRANSMISSION. Here's why: High levels of dopamine linked with paranoia, schizophrenia, stress and panic disorders, all of which have high incidences of SP. Also, in animal studies it has been shown that dopamine levels skyrocket after incidences of social defeat. THis dopamine release leads to reducing binding potential of dopamine to its receptors by decreasing number of dopamine receptors. Finnish studies have shown that people with SP have substantially less number of D2 receptors than normal subjects, and they speculate that this may be a result of downregulation due to chronically high levels of dopamine in the brain. Additionally, although there are some exceptions, almost every post I've read where someone tries a dopamine med on its own to combat SP actually experiences increased anxiety. In my own experience, L-tyrosine and selegiline caused additional anxiety and paranoia. Usually dopamine meds are most helpful as adding an activating effect to drugs such as Klonopin, Valium, Neurontin, etc. This all ties in with low levels of GABA, b/c GABA actually inhibits dopamine production, and low levels of GABA lead to higher levels of dopamine.
So basically: Low GABA = High Dopamine levels = downregulation of Dopamine receptors = reduced sensitivity of receptors = low GABA... and the cycle continues.
So to sum it up, it seems to me that GABA dysfunction is the main reason for SP, with poor dopamine transmission due to chronically excess levels in brain as a result of low GABA. Sorry for writing a novel, but it was clogging up my brain! Good luck.