Posted by Toby on January 26, 1999, at 12:51:23
In reply to Re: OCD and dopamine (Need Toby!) or other expert!, posted by Mike on January 23, 1999, at 15:17:08
The biological basis of OCD remains unknown. Some data suggest genes play a role, but abnormal genes or gene products have not yet been identified. Some evidence exists that indicates abnormal neuronal activity and perhaps some alterations in neurotransmitters, but it is not known if this is a cause or an effect of OCD. There is also a longstanding belief of an abnormal neurological site that causes OCD due to the success of psychosurgery in some patients.
If we look at neurotransmitter hypotheses about OCD, we find three. One is the serotonin hypothesis. For more than 25 years Anafranil has been effective in reducing OCD symptoms. Anafranil is a potent serotonin reuptake inhibitor. Other antidepressants that have less potent serotonin inhibition are ineffective in OCD. The SSRI's have also demonstrated antiobsessional effects and lends support that serotonin is involved in this disorder. In studies that look at cerebrospinal fluid levels of serotonin and platelet serotonin levels, there is a correlation between improvement in OC symptoms and a decrease in serotonin in those areas.
The second hypothesis is related to dopamine. Up to 40% of OCD patients do not respond to SSRI's. Also, some OCD patients do not have any dysregulation of serotonin in the CSF or platelets. So this indicates other neurotransmitters are involved in OCD, at least in some patients. Evidence for this was found in animal studies that showed that high doses of various dopamine-raising agents like amphetamine, bromocriptine and L-DOPA induce stereotyped movements in animals that resemble compulsive behaviors in OCD patients (the same thing happens in humans who abuse amphetamines or cocaine in high doses). Very strong evidence of this is found in patients with neurological disorders associated with dysfunction of dopamine in the basal ganglia like Sydenham's chorea, certain kinds of encephalitis and Tourette's syndrome. Between 45 and 90% of Tourette's patients also have obsessions and compulsions. Also supportive of dopamine involvement in OCD is that antipsychotic therapy reduces the severity of OCD symptoms in patients resistant to SSRI treatment alone.
The third hypothesis is a combo if the above two. It is not clear whether the primary abnormality is in serotonin function, dopamine function or a balance of the two. Anatomically, neuron tracks containing both run alongside each other. So it could be that decreases in serotonin (which normally inhibits dopamine neurons to some extent) leads to increased dopamine function in some patients causing resistance to SSRI's and Anafranil.
So, in regard to the questions: some patients do respond to antipsychotics which lower dopamine in certain parts of the brain, but usually not by themselves (although I have seen it and heard a couple of reports of this). Bromocriptine and amantadine raise dopamine levels and would likely worsen OCD. SSRI's don't lower absolute dopamine levels, they just put the ratio back in order.
poster:Toby
thread:2406
URL: http://www.dr-bob.org/babble/19990101/msgs/2689.html