dopamine

[kim]

This is one study that I found really interesting regarding dopamine. Again, reading these studies is kind of like a ping pong match!

 

http://www.med.nyu.edu/research/pdf/brasij...e%20in%20TS.pdf

 

Excerpt...bolding mine

 

The difference in relative dopamine release in the putamen between

Tourette’s syndrome and comparison subjects approached

significance when the less sensitive constrained

method of analysis was used. Although the change in

dopamine release appears unrelated to age, tic severity,

and OCD, whether it is associated with other symptoms,

such as ADHD, remains unclear. Dopamine transporter

density, measured by SPECT, has been shown to be greater

in adults with ADHD than in healthy comparison subjects

(39). Although global tic severity ranking did not correlate

with the degree of dopamine release, potential explanations

include the small number of study subjects and

characteristics relating to tics, i.e., their natural variability,

possible improvement over time, and exacerbation by external

factors such as stress, anxiety, fatigue, or the presence

of infection

[Chemar]

Hi Kim

 

good topic!

 

from my understanding, it isnt the increased level of dopamine that is the tic trigger in Tourette Syndrome, but that the dopamine receptors over react to even small changes in dopamine levels. The way I have understood it, even small spikes in dopamine can result in an exagerated response in those with TS, because of this "hypersensitivity" to dopamine fluctuations by the receptors.

 

gotta run, but that is how I have always understood the dopamine issue re TS. I am sure there must be a lot of more recent research on this, which I havent kept up with.

 

Cheri

[kim]

Cheri,

 

After all of this time, I don't think they fully understand how this works, and the variability from person to person. There is still a lot of credibility to the "older ideas" but.. the same old questions remain.

 

This is a good overview of some of the structures and pathways invoved. Second 1/2 contains PANDAS info. Published 2006

 

http://jcn.sagepub.com/cgi/reprint/21/8/678.pdf

 

The theory of low phasic dopamine within the axon, resulting in higher tonic supersensitivity reception caught my attention here.

 

The PANDAS summery provides more questions than answers IMHO.

 

I have many articles collected now, that I want to go back thru slowly. I'm just going to post them as I go. This RLS, Parkinson's, tics connection really has my neurons firing. If I short circuit, you guys will be the first to know.

[michele]

Kim,

Thanks for bringing this topic forward. I find it very important and relative to my son. Dr. Demio said he has too much dopamine in the brain. I don't really understand the connection maybe it is from the yeast overgrowth? How do we treat this? What is the best supplement for this? I thought taurine was to help with this. I think this is one of the reasons he wanted Andrew on Actos. It is to help with th1 and th2 and autoantibodies. TMG is also to help with this I believe and the natural lithium oratate. What about tryptophan 5HTP? I think it is the excess of dopamine that really causes trouble for these kids with the ADHD and over the top behaviors. Do you give any of these supplements? How do they work if you do? Again thanks for bringing this up.

Michele

This is one study that I found really interesting regarding dopamine. Again, reading these studies is kind of like a ping pong match!

 

http://www.med.nyu.edu/research/pdf/brasij...e%20in%20TS.pdf

 

Excerpt...bolding mine

 

The difference in relative dopamine release in the putamen between

Tourette’s syndrome and comparison subjects approached

significance when the less sensitive constrained

method of analysis was used. Although the change in

dopamine release appears unrelated to age, tic severity,

and OCD, whether it is associated with other symptoms,

such as ADHD, remains unclear. Dopamine transporter

density, measured by SPECT, has been shown to be greater

in adults with ADHD than in healthy comparison subjects

(39). Although global tic severity ranking did not correlate

with the degree of dopamine release, potential explanations

include the small number of study subjects and

characteristics relating to tics, i.e., their natural variability,

possible improvement over time, and exacerbation by external

factors such as stress, anxiety, fatigue, or the presence

of infection

[kim]

Michelle,

 

I don't think any of these Dr.s know exactly what is going on. I think that they use tests and try to get a child/persons levels of different things as close to "normal" controls as possible. If you read through these three studies, you'll see how confusing and confounding it gets. I have an artcle around here that explains how some of the drugs used to "treat" these disorders aren't smart enough to know what receptor they are supposed to be blocking or stimulating. Some have a higher affiity for specific binding than others, but with many, they just keep trying different meds at different levels, until they find what seems to be helping.

 

I think it is the excess of dopamine that really causes trouble for these kids with the ADHD and over the top behaviors

That's part of what's making me crazy here. The meds used to treat ADHD they think increase some of the exact things that they think cause tics. I simply can't find any reason to think that these are structural defects. I don't think the problem originates in these area's.

 

Something I wanted to ask you Michelle, do you know what form of phenylalanine was recommended in the amino acid complex that Andrew's Dr. wanted him on? Is it specified? I have been told that I need to get my youngest son's amino acids corrected, to get him to eat more normally. I really have not gotten into all of that yet.

 

This is just something quickly copied from this site.

 

http://www.healingpeople.com/index.php?opt...ia/pg000141.htm

 

Phenylalanine occurs in two chemical forms: L-phenylalanine, a natural amino acid found in proteins; and its mirror image, D-phenylalanine, a form synthesized in a laboratory. Some research has involved the L-form, others the D-form, and still others a combination of the two known as DL-phenylalanine.

 

In the body, phenylalanine is converted into another amino acid called tyrosine. Tyrosine in turn is converted into L-dopa, norepinephrine, and epinephrine, three key neurotransmitters (chemicals that transmit signals between nerve cells). Because some antidepressants work by raising levels of norepinephrine, various forms of phenylalanine have been tried as a possible treatment for depression.

 

D-phenylalanine (but not L-phenylalanine) has been proposed to treat chronic pain. It blocks enkephalinase, an enzyme that may act to increase pain levels in the body. Phenylalanine (various forms) has also been suggested as a treatment for vitiligo, a disease characterized by abnormal white blotches of skin due to loss of pigmentation.

 

Requirements/Sources

 

L-phenylalanine is an essential amino acid, meaning that we need it for life and our bodies can't manufacture it from other chemicals. It is found in protein-rich foods such as meat, fish, poultry, eggs, dairy products, and beans. Provided you eat enough protein, you are likely to get enough L-

phenylalanine for your nutritional needs. There is no nutritional need for D-phenylalanine

 

Back to neuro transmitters.

 

http://www.nature.com/npp/journal/vaop/ncu...3A1DC9D477C554E

 

Received 23 February 2006; Revised 11 June 2007; Accepted 16 July 2007; Published online 7 November 2007.

 

Top of pageAbstract

Tourette syndrome (TS) is a neuropsychiatric disorder with childhood onset characterized by motor and phonic tics. Obsessive-compulsive disorder (OCD) is often concomitant with TS. Dysfunctional tonic and phasic dopamine (DA) and serotonin (5-HT) metabolism may play a role in the pathophysiology of TS. We simultaneously measured the density, affinity, and brain distribution of dopamine D2 receptors (D2-R's), dopamine transporter binding potential (BP), and amphetamine-induced dopamine release (DArel) in 14 adults with TS and 10 normal adult controls. We also measured the brain distribution and BP of serotonin 5-HT2A receptors (5-HT2AR), and serotonin transporter (SERT) BP, in 11 subjects with TS and 10 normal control subjects. As compared with controls, DArel was significantly increased in the ventral striatum among subjects with TS. Adults with TS+OCD exhibited a significant D2-R increase in left ventral striatum. SERT BP in midbrain and caudate/putamen was significantly increased in adults with TS (TS+OCD and TS-OCD). In three subjects with TS+OCD, in whom D2-R, 5-HT2AR, and SERT were measured within a 12-month period, there was a weakly significant elevation of DArel and 5-HT2A BP, when compared with TS–OCD subjects and normal controls. The current study confirms, with a larger sample size and higher resolution PET scanning, our earlier report that elevated DArel is a primary defect in TS. The finding of decreased SERT BP, and the possible elevation in 5-HT2AR in individuals with TS who had increased DArel, suggest a condition of increased phasic DArel modulated by low 5-HT in concomitant OCD.

 

 

 

http://www.med.nyu.edu/research/pdf/brasij...e%20in%20TS.pdf

 

 

A second possibility is a decrease in tonic dopamine

levels. We favor this latter concept on the basis of

lower levels of CSF HVA (6, 8, 9) and evidence for elevated

D2 receptors in some subgroups of Tourette’s syndrome

patients (13). If this is indeed the case, how does the decrease

in tonic dopamine occur? Diminished tonic dopamine

levels could be secondary to a decrease in phasic

overflow from the synaptic cleft to the extracellular space,

but this is not likely because it conflicts with the observation

of an increase in phasic dopamine release. A decrease

in tonic dopamine could be secondary to a diminished

cortical afferent input, i.e., tonic dopamine release is regulated

by cortical glutamatergic afferents (49). To our knowledge,

however, postmortem and neuroimaging studies

have not identified reduced cortical gray matter volume or

abnormal efferent output. Anderson et al. (51) evaluated

postmortem 13 brain regions from four Tourette’s syndrome

patients and reported lower glutamate levels in the

globus pallidus and substantia nigra pars reticulata but

not in the putamen. Last, a decrease in tonic dopamine

levels could be secondary to an increase in activity of the

dopamine transporter, since the reuptake transporter determines

the concentration of extrasynaptic dopamine.

Hence, we propose that the essential underlying mechanism

in Tourette’s syndrome could be an overactive dopamine

transporter system. This situation would create

reduced levels of extracellular dopamine, higher concentrations

of dopamine in the axon terminal, an increase in

stimulus-dependent dopamine release, autoreceptor supersensitivity

at the presynaptic site, and an increase in

sensitivity to low-dose neuroleptics. Several clinical findings

in Tourette’s syndrome patients support the overactive

dopamine transporter hypothesis. For example, the

exacerbation of tics by stimulant medications (52, 53)

could be secondary to greater dopamine release from the

axon terminal. Environmental stimuli, such as stress, anxiety,

and medications, well known to exacerbate tics, have

been shown to increase phasic bursts of dopamine. Last,

tic suppression with very low doses of neuroleptics (54)

may occur because there is less tonic dopamine available

for the neuroleptic to block.

Future PET studies involving larger numbers of Tourette’s

syndrome subjects and using techniques in which

measurements of D2 receptors, dopamine transporter, and

dopamine release are available for each subject should

provide further clarification of the dopaminergic system in

adults with Tourette’s syndrome. Confirmation of a release

abnormality in larger numbers of patients with Tourette’s

syndrome could, in turn, lead to the development of new

tic-suppressing pharmacotherapies.

 

 

 

http://www.nature.com/npp/journal/vaop/ncu...3A1DC9D477C554E

 

Received 23 February 2006; Revised 11 June 2007; Accepted 16 July 2007; Published online 7 November 2007.

 

Top of pageAbstract

Tourette syndrome (TS) is a neuropsychiatric disorder with childhood onset characterized by motor and phonic tics. Obsessive-compulsive disorder (OCD) is often concomitant with TS. Dysfunctional tonic and phasic dopamine (DA) and serotonin (5-HT) metabolism may play a role in the pathophysiology of TS. We simultaneously measured the density, affinity, and brain distribution of dopamine D2 receptors (D2-R's), dopamine transporter binding potential (BP), and amphetamine-induced dopamine release (DArel) in 14 adults with TS and 10 normal adult controls. We also measured the brain distribution and BP of serotonin 5-HT2A receptors (5-HT2AR), and serotonin transporter (SERT) BP, in 11 subjects with TS and 10 normal control subjects. As compared with controls, DArel was significantly increased in the ventral striatum among subjects with TS. Adults with TS+OCD exhibited a significant D2-R increase in left ventral striatum. SERT BP in midbrain and caudate/putamen was significantly increased in adults with TS (TS+OCD and TS-OCD). In three subjects with TS+OCD, in whom D2-R, 5-HT2AR, and SERT were measured within a 12-month period, there was a weakly significant elevation of DArel and 5-HT2A BP, when compared with TS–OCD subjects and normal controls. The current study confirms, with a larger sample size and higher resolution PET scanning, our earlier report that elevated DArel is a primary defect in TS. The finding of decreased SERT BP, and the possible elevation in 5-HT2AR in individuals with TS who had increased DArel, suggest a condition of increased phasic DArel modulated by low 5-HT in concomitant OCD.

 

 

http://www.ncbi.nlm.nih.gov/sites/entrez?c...pt=AbstractPlus

 

Grace AA.

Department of Behavioral Neuroscience, University of Pittsburgh, PA 15260.

 

A novel mechanism for regulating dopamine activity in subcortical sites and its possible relevance to schizophrenia is proposed. This hypothesis is based on the regulation of dopamine release into subcortical regions occurring via two independent mechanisms: (1) transient or phasic dopamine release caused by dopamine neuron firing, and (2) sustained, "background" tonic dopamine release regulated by prefrontal cortical afferents. Behaviorally relevant stimuli are proposed to cause short-term activation of dopamine cell firing to trigger the phasic component of dopamine release. In contrast, tonic dopamine release is proposed to regulate the intensity of the phasic dopamine response through its effect on extracellular dopamine levels. In this way, tonic dopamine release would set the background level of dopamine receptor stimulation (both autoreceptor and postsynaptic) and, through homeostatic mechanisms, the responsivity of the system to dopamine in these sites. In schizophrenics, a prolonged decrease in prefrontal cortical activity is proposed to reduce tonic dopamine release. Over time, this would elicit homeostatic compensations that would increase overall dopamine responsivity and thereby cause subsequent phasic dopamine release to elicit abnormally large responses

 

 

http://www.springerlink.com/content/e511014uhj124137/

 

 

Takashi Hamamura1 and Toshiki Harada2

 

(1) Hamamura Clinic, 5-1-17 Kojima Ogawa Kurashiki, Okayama 711-0911, Japan

(2) Takahashi Hospital, 2200 Abe Ochiai-cho Takahashi, Okayama 716-0061, Japan

 

Received: 26 September 2006 Accepted: 15 November 2006 Published online: 5 January 2007

 

Abstract

Rationale Aripiprazole is a recently introduced antipsychotic with a unique pharmacological profile, a dopamine partial agonist. Dopaminergic neural transmission has two different components, tonic and phasic, which have different physiological functions, but the effects of aripiprazole on tonic and phasic components are not reported.

Objective Studies on antipsychotics including aripiprazole and tonic/phasic dopamine transmission are summarized.

 

Results Antipsychotics exert efficacy without extrapyramidal side effects (EPS’s) when their occupation of dopamine D2 receptors reaches 65–80%. When a “tightly binding” antipsychotic binds 70% of D2 receptors, the remaining 30% are available for endogenous dopamine to bind. These tight antipsychotics suppress dopamine transmission in both tonic/phasic components equally so that similar proportions are kept. Aripiprazole is effective when >90% of D2 receptors are occupied. In this condition, less than 10% of D2 receptors are available for endogenous dopamine to bind; however, EPS’s do not occur because aripiprazole exerts partial dopaminergic agonistic activity. Because the concentration of aripiprazole in the brain is relatively constant and it binds to D2 receptors tightly, the added dopaminergic agonism may show a tonic nature. Thus, aripiprazole suppresses the phasic component relatively more than the tonic component. In contrast, under treatment with “loosely binding” antipsychotics, phasic dopaminergic transmission is relatively preserved.

Conclusions Tight antipsychotics suppress both tonic and phasic components equally. Aripiprazole suppresses the phasic component relatively more than the tonic; that is, aripiprazole is a tonic component buster. By contrast, suppression of the phasic component by loosely binding antipsychotics may be relatively weak.

An erratum to this article can be found at http://dx.doi.org/10.1007/s00213-007-0716-0

 

my note... ABILIFY= aripiprazole —

[michele]

Alot of the technical terms are over my head. Here is a list of amino acids specific to his needs. arginine, histidine, isoleucine, leucine, methionine,ornithine,phenylalanine,proline,serine,threonine,valine. Tryptophan is not checked. amino acid powder daily one gram each p.o. per day divided on an empty stomach 30 min before meals. juice is okay. Start with one quarter of a full dose and work up to a full dose in two weeks.

Michelle,

 

I don't think any of these Dr.s know exactly what is going on. I think that they use tests and try to get a child/persons levels of different things as close to "normal" controls as possible. If you read through these three studies, you'll see how confusing and confounding it gets. I have an artcle around here that explains how some of the drugs used to "treat" these disorders aren't smart enough to know what receptor they are supposed to be blocking or stimulating. Some have a higher affiity for specific binding than others, but with many, they just keep trying different meds at different levels, until they find what seems to be helping.

 

I think it is the excess of dopamine that really causes trouble for these kids with the ADHD and over the top behaviors

That's part of what's making me crazy here. The meds used to treat ADHD they think increase some of the exact things that they think cause tics. I simply can't find any reason to think that these are structural defects. I don't think the problem originates in these area's.

 

Something I wanted to ask you Michelle, do you know what form of phenylalanine was recommended in the amino acid complex that Andrew's Dr. wanted him on? Is it specified? I have been told that I need to get my youngest son's amino acids corrected, to get him to eat more normally. I really have not gotten into all of that yet.

 

This is just something quickly copied from this site.

 

http://www.healingpeople.com/index.php?opt...ia/pg000141.htm

 

Phenylalanine occurs in two chemical forms: L-phenylalanine, a natural amino acid found in proteins; and its mirror image, D-phenylalanine, a form synthesized in a laboratory. Some research has involved the L-form, others the D-form, and still others a combination of the two known as DL-phenylalanine.

 

In the body, phenylalanine is converted into another amino acid called tyrosine. Tyrosine in turn is converted into L-dopa, norepinephrine, and epinephrine, three key neurotransmitters (chemicals that transmit signals between nerve cells). Because some antidepressants work by raising levels of norepinephrine, various forms of phenylalanine have been tried as a possible treatment for depression.

 

D-phenylalanine (but not L-phenylalanine) has been proposed to treat chronic pain. It blocks enkephalinase, an enzyme that may act to increase pain levels in the body. Phenylalanine (various forms) has also been suggested as a treatment for vitiligo, a disease characterized by abnormal white blotches of skin due to loss of pigmentation.

 

Requirements/Sources

 

L-phenylalanine is an essential amino acid, meaning that we need it for life and our bodies can't manufacture it from other chemicals. It is found in protein-rich foods such as meat, fish, poultry, eggs, dairy products, and beans. Provided you eat enough protein, you are likely to get enough L-

phenylalanine for your nutritional needs. There is no nutritional need for D-phenylalanine

 

Back to neuro transmitters.

 

http://www.nature.com/npp/journal/vaop/ncu...3A1DC9D477C554E

 

Received 23 February 2006; Revised 11 June 2007; Accepted 16 July 2007; Published online 7 November 2007.

 

Top of pageAbstract

Tourette syndrome (TS) is a neuropsychiatric disorder with childhood onset characterized by motor and phonic tics. Obsessive-compulsive disorder (OCD) is often concomitant with TS. Dysfunctional tonic and phasic dopamine (DA) and serotonin (5-HT) metabolism may play a role in the pathophysiology of TS. We simultaneously measured the density, affinity, and brain distribution of dopamine D2 receptors (D2-R's), dopamine transporter binding potential (BP), and amphetamine-induced dopamine release (DArel) in 14 adults with TS and 10 normal adult controls. We also measured the brain distribution and BP of serotonin 5-HT2A receptors (5-HT2AR), and serotonin transporter (SERT) BP, in 11 subjects with TS and 10 normal control subjects. As compared with controls, DArel was significantly increased in the ventral striatum among subjects with TS. Adults with TS+OCD exhibited a significant D2-R increase in left ventral striatum. SERT BP in midbrain and caudate/putamen was significantly increased in adults with TS (TS+OCD and TS-OCD). In three subjects with TS+OCD, in whom D2-R, 5-HT2AR, and SERT were measured within a 12-month period, there was a weakly significant elevation of DArel and 5-HT2A BP, when compared with TS–OCD subjects and normal controls. The current study confirms, with a larger sample size and higher resolution PET scanning, our earlier report that elevated DArel is a primary defect in TS. The finding of decreased SERT BP, and the possible elevation in 5-HT2AR in individuals with TS who had increased DArel, suggest a condition of increased phasic DArel modulated by low 5-HT in concomitant OCD.

 

 

 

http://www.med.nyu.edu/research/pdf/brasij...e%20in%20TS.pdf

 

 

A second possibility is a decrease in tonic dopamine

levels. We favor this latter concept on the basis of

lower levels of CSF HVA (6, 8, 9) and evidence for elevated

D2 receptors in some subgroups of Tourette’s syndrome

patients (13). If this is indeed the case, how does the decrease

in tonic dopamine occur? Diminished tonic dopamine

levels could be secondary to a decrease in phasic

overflow from the synaptic cleft to the extracellular space,

but this is not likely because it conflicts with the observation

of an increase in phasic dopamine release. A decrease

in tonic dopamine could be secondary to a diminished

cortical afferent input, i.e., tonic dopamine release is regulated

by cortical glutamatergic afferents (49). To our knowledge,

however, postmortem and neuroimaging studies

have not identified reduced cortical gray matter volume or

abnormal efferent output. Anderson et al. (51) evaluated

postmortem 13 brain regions from four Tourette’s syndrome

patients and reported lower glutamate levels in the

globus pallidus and substantia nigra pars reticulata but

not in the putamen. Last, a decrease in tonic dopamine

levels could be secondary to an increase in activity of the

dopamine transporter, since the reuptake transporter determines

the concentration of extrasynaptic dopamine.

Hence, we propose that the essential underlying mechanism

in Tourette’s syndrome could be an overactive dopamine

transporter system. This situation would create

reduced levels of extracellular dopamine, higher concentrations

of dopamine in the axon terminal, an increase in

stimulus-dependent dopamine release, autoreceptor supersensitivity

at the presynaptic site, and an increase in

sensitivity to low-dose neuroleptics. Several clinical findings

in Tourette’s syndrome patients support the overactive

dopamine transporter hypothesis. For example, the

exacerbation of tics by stimulant medications (52, 53)

could be secondary to greater dopamine release from the

axon terminal. Environmental stimuli, such as stress, anxiety,

and medications, well known to exacerbate tics, have

been shown to increase phasic bursts of dopamine. Last,

tic suppression with very low doses of neuroleptics (54)

may occur because there is less tonic dopamine available

for the neuroleptic to block.

Future PET studies involving larger numbers of Tourette’s

syndrome subjects and using techniques in which

measurements of D2 receptors, dopamine transporter, and

dopamine release are available for each subject should

provide further clarification of the dopaminergic system in

adults with Tourette’s syndrome. Confirmation of a release

abnormality in larger numbers of patients with Tourette’s

syndrome could, in turn, lead to the development of new

tic-suppressing pharmacotherapies.

 

 

 

http://www.nature.com/npp/journal/vaop/ncu...3A1DC9D477C554E

 

Received 23 February 2006; Revised 11 June 2007; Accepted 16 July 2007; Published online 7 November 2007.

 

Top of pageAbstract

Tourette syndrome (TS) is a neuropsychiatric disorder with childhood onset characterized by motor and phonic tics. Obsessive-compulsive disorder (OCD) is often concomitant with TS. Dysfunctional tonic and phasic dopamine (DA) and serotonin (5-HT) metabolism may play a role in the pathophysiology of TS. We simultaneously measured the density, affinity, and brain distribution of dopamine D2 receptors (D2-R's), dopamine transporter binding potential (BP), and amphetamine-induced dopamine release (DArel) in 14 adults with TS and 10 normal adult controls. We also measured the brain distribution and BP of serotonin 5-HT2A receptors (5-HT2AR), and serotonin transporter (SERT) BP, in 11 subjects with TS and 10 normal control subjects. As compared with controls, DArel was significantly increased in the ventral striatum among subjects with TS. Adults with TS+OCD exhibited a significant D2-R increase in left ventral striatum. SERT BP in midbrain and caudate/putamen was significantly increased in adults with TS (TS+OCD and TS-OCD). In three subjects with TS+OCD, in whom D2-R, 5-HT2AR, and SERT were measured within a 12-month period, there was a weakly significant elevation of DArel and 5-HT2A BP, when compared with TS–OCD subjects and normal controls. The current study confirms, with a larger sample size and higher resolution PET scanning, our earlier report that elevated DArel is a primary defect in TS. The finding of decreased SERT BP, and the possible elevation in 5-HT2AR in individuals with TS who had increased DArel, suggest a condition of increased phasic DArel modulated by low 5-HT in concomitant OCD.

 

 

http://www.ncbi.nlm.nih.gov/sites/entrez?c...pt=AbstractPlus

 

Grace AA.

Department of Behavioral Neuroscience, University of Pittsburgh, PA 15260.

 

A novel mechanism for regulating dopamine activity in subcortical sites and its possible relevance to schizophrenia is proposed. This hypothesis is based on the regulation of dopamine release into subcortical regions occurring via two independent mechanisms: (1) transient or phasic dopamine release caused by dopamine neuron firing, and (2) sustained, "background" tonic dopamine release regulated by prefrontal cortical afferents. Behaviorally relevant stimuli are proposed to cause short-term activation of dopamine cell firing to trigger the phasic component of dopamine release. In contrast, tonic dopamine release is proposed to regulate the intensity of the phasic dopamine response through its effect on extracellular dopamine levels. In this way, tonic dopamine release would set the background level of dopamine receptor stimulation (both autoreceptor and postsynaptic) and, through homeostatic mechanisms, the responsivity of the system to dopamine in these sites. In schizophrenics, a prolonged decrease in prefrontal cortical activity is proposed to reduce tonic dopamine release. Over time, this would elicit homeostatic compensations that would increase overall dopamine responsivity and thereby cause subsequent phasic dopamine release to elicit abnormally large responses

 

 

http://www.springerlink.com/content/e511014uhj124137/

 

 

Takashi Hamamura1 and Toshiki Harada2

 

(1) Hamamura Clinic, 5-1-17 Kojima Ogawa Kurashiki, Okayama 711-0911, Japan

(2) Takahashi Hospital, 2200 Abe Ochiai-cho Takahashi, Okayama 716-0061, Japan

 

Received: 26 September 2006 Accepted: 15 November 2006 Published online: 5 January 2007

 

Abstract

Rationale Aripiprazole is a recently introduced antipsychotic with a unique pharmacological profile, a dopamine partial agonist. Dopaminergic neural transmission has two different components, tonic and phasic, which have different physiological functions, but the effects of aripiprazole on tonic and phasic components are not reported.

Objective Studies on antipsychotics including aripiprazole and tonic/phasic dopamine transmission are summarized.

 

Results Antipsychotics exert efficacy without extrapyramidal side effects (EPS’s) when their occupation of dopamine D2 receptors reaches 65–80%. When a “tightly binding” antipsychotic binds 70% of D2 receptors, the remaining 30% are available for endogenous dopamine to bind. These tight antipsychotics suppress dopamine transmission in both tonic/phasic components equally so that similar proportions are kept. Aripiprazole is effective when >90% of D2 receptors are occupied. In this condition, less than 10% of D2 receptors are available for endogenous dopamine to bind; however, EPS’s do not occur because aripiprazole exerts partial dopaminergic agonistic activity. Because the concentration of aripiprazole in the brain is relatively constant and it binds to D2 receptors tightly, the added dopaminergic agonism may show a tonic nature. Thus, aripiprazole suppresses the phasic component relatively more than the tonic component. In contrast, under treatment with “loosely binding” antipsychotics, phasic dopaminergic transmission is relatively preserved.

Conclusions Tight antipsychotics suppress both tonic and phasic components equally. Aripiprazole suppresses the phasic component relatively more than the tonic; that is, aripiprazole is a tonic component buster. By contrast, suppression of the phasic component by loosely binding antipsychotics may be relatively weak.

An erratum to this article can be found at http://dx.doi.org/10.1007/s00213-007-0716-0

 

my note... ABILIFY= aripiprazole —

[kim]

Thanks Michelle

 

 

 

Alot of the technical terms are over my head

I know how that feels. I am just getting to the point where I can read these things and actually get something out of them the first time around. I find the diagrams really helpful. If you can visualise what they're talking about, it's a lot easier. The abbreviations like DArel throw you too, but when you go back and see that it just means the dopamine release, it gets easier. I have spent an inordinate amt of time at this, though. I probably read all of this stuff quite a while ago, and had no idea what they were talking about either. You just get more familiar as you go.

 

As I was reading back through this, I realised that I hadn't answered any of your questions. I'm sorry I don't think I have anything very useful to add.

 

Dr. Demio said he has too much dopamine in the brain

 

Again, I think the Cheri used the term "disordered" at one time. Personally, I think that would be a better way of describing it.

 

I don't really understand the connection maybe it is from the yeast overgrowth?

I think the yeast overgrowth is just one more sign of an immune system that isn't functioning properly. I have read of kids with high ammonia levels related to yeast, inadequate protein digestion, etc. being linked to drunken behavior. Do you see ammonia levels on any of Andrew's test results? Also, with high yeast, kids tend to have depleted levels of some B vitamins. When you start to supplement the B's, it can feed yeast so it can be a cycle, until you get ahead of it. If you have low B's and low magnesium, zinc etc. it can have an effect on how the neurotransmitters function, so yes, yeast overgrowth can make things worse.

 

I thought taurine was to help with this.

 

If there was nothing to suggest that taurine levels weren't already high, yes it should be helpful. We have had a couple of people here, post that their childs levels were super high. Since Andrew had testing, I'm assuming that that isn't a problem.

 

TMG is also to help with this I believe and the natural lithium oratate

.

 

The only thing that I know about TMJ, is that it is supposed to help with methionine (from homocysteine) conversion. Lithium, i really don't know anything about (except that it's found in rock)

 

What about tryptophan 5HTP?

 

Since it isn't checked, there may be a specific reason that your Dr. doesn't want you to use it. Yes, my oldest son uses it. It's very helpful for sleep issues. You can also just open the capsule and use a sprinkle here and there, for calming and help with tics. I would check with your Dr. first though.

[kim]

This is another article that i had saved. I only have the excerpt here. i haven't read the whole thing in a while. At the time I copied this, i was looking for an inbalance ( low dopamine level/deficiency) in one brain region, that may result in the supersensitive receptors in another area, as Cheri made mention of.

 

Interestingly, this is also part of the hypothesis that Bonnie had, that i never picked up on, until i read this article for the 20th time

 

http://www.bio.net/bionet/mm/neur-sci/1996...ary/022416.html

 

I found that L-dopa doesn't readily form dopamine in B6 deficiency,

so probably dopamine is reduced causing an increase in

dopamine receptor sites along with an increase the norepinephrine

and epinephrine (which are formed from dopamine) receptors sites.

These increased receptor sites make the nerves more excitable and

false transmitters or true neurotransmitters can set them off with

explosive qualities.

In this article it's important to remember that levodopa is used to treat Parkinson's. They INCREASED levels of dopamine. These were ADULT patients however and it doesn't say what drugs they had used through out the years. It also doesn't say what effect levodopa had on tic activity/severity.

 

It's important to read this carefully and understand that the tasks were completed equally well in both groups (interesting...but these were adults, not children with ADHD and tics). What was demonstrated was how an area of the brain was working differently and how an infusion of levodopa normalized it.

 

This impression that i get here, and something i hope others are aware of and pay attention to, is when your DAN or other Dr. recommends things that can be involved in dopamine production, it may not be something to automatically shy away from. Slow application and careful observation and reporting of reactions could go along way in helping the Dr. figure out what brain region is affected, and how to balance dopamine levels most effectively to reduce symptoms.

 

These are the ramblings of a totally medically uneducation parent!! This is posted for discussion purposes only. I'm not suggesting that anyone start trying to increase dopamine levels in themselves or their children but this concept, is IMHO important.

 

http://www.sciencedaily.com/releases/2004/...40406083500.htm

 

To determine whether the results were related to dopamine abnormalities, Hershey, Black and colleagues gave all participants an intravenous infusion of the drug levodopa.

 

When the two groups then repeated the original working memory task, brain activity in healthy participants was unchanged. In TS patients, however, the areas that had been abnormally overactive were substantially less active after treatment.

 

"Levodopa seems to normalize the excess activity we had seen in the parietal cortex in the group with tics," Hershey says. "There were changes in activity in the other structures, too, but the changes in the parietal cortex were the most dramatic."