Method and system for diagnosis of neuropsychiatric disorders including chronic alcoholism

• US 20060292547A1
• Filed: 08/23/2005
• Published: 12/28/2006
• Est. Priority Date: 02/07/2002
• Status: Active Grant

• Current Assignee: Jay W. Pettegrew, Kanagasabai Panchalingam
• Original Assignee: Jay W. Pettegrew, Kanagasabai Panchalingam
• Inventors: Pettegrew, Jay W., Panchalingam, Kanagasabai
• Granted Patent: US 7,700,074 B2
• Time in Patent Office: Days
• US Class Current: 435/4
• CPC Class Codes: A23L 33/175 Amino acids
• CPC Class Codes: A23V 2002/00 Food compositions, function of food ingredients or processes for food or foodstuffs
• CPC Class Codes: A23V 2200/322 having an effect on the health of the nervous system or on mental function
• CPC Class Codes: A23V 2250/0612 Carnitine
• CPC Class Codes: A61B 5/055 involving electronic [EMR] or nuclear [NMR] magnetic resonance, e.g. magnetic resonance imaging
• CPC Class Codes: A61B 5/4064 Evaluating the brain A61B5/031, A61B5/369, A61B5/14553 take precedence
• CPC Class Codes: A61B 6/501 for diagnosis of the head, e.g. neuroimaging or craniography
• CPC Class Codes: A61K 31/22 of acyclic acids, e.g. pravastatin
• CPC Class Codes: A61K 36/28 Asteraceae or Compositae (Aster or Sunflower family), e.g. chamomile, feverfew, yarrow or echinacea
• CPC Class Codes: G01N 2800/307 Drug dependency, e.g. alcoholism
• CPC Class Codes: G01R 33/485 based on chemical shift information [CSI] or spectroscopic imaging, e.g. to acquire the spatial distributions of metabolites

Abstract

Chronic alcoholism is a diverse and heterogeneous disorder that can be dichotomized into cognitively intact and cognitively impaired subgroups. At a molecular level, ethanol has been shown to have both acute and chronic effects on: Membrane biophysical properties, Membrane composition and metabolism, Protein phosphorylation, Lipid metabolic signaling, Lipoprotein transport of cholesterol. Actual molecular underpinnings are determined for cognitive impairment seen in some chronic alcoholism subjects including molecular/metabolic alterations of phospholipid and ganglioside metabolisms.

Claims

1. A method for diagnosing alcoholism disease in a human, comprising:

examining molecular alterations in membrane phospholipid and high-energy phosphate metabolism in a human brain with a medical imaging process;

examining molecular alterations in synaptic transport vesicles with the medical imaging process;

examining molecular alternations in phosphorylated proteins with the medical imaging process;

examining molecular alterations in metabolites with N-acetyl moieties and gangliosides are examined with the medical imaging process; and

determining with the plurality of examined molecular alterations whether a conclusion of cognitively impaired chronic alcoholism in the human is suggested.

2. The method of claim 1 wherein the molecular alterations in the membrane phospholipid and high-energy phosphate metabolism includes molecular alterations in phosphomonoesters (PME(s-τ

_c)) in left inferior parietal regions of the human brain.

3. The method of claim 1 wherein the molecular alterations in synaptic transport vesicles includes molecular alterations in phosphodiesters (PDE(i-τ

_c)) in a right inferior parietal region of the human brain.

4. The method of claim 1 wherein the molecular alterations in phosphorylated proteins include molecular alternations in phospholipid cofactors ((α

-γ

)ATP) in a left occipital region of the human brain.

5. The method of claim 1 wherein the molecular alterations in metabolites with N-acetyl moieties and gangliosides include molecular alterations in N-acetylaspartate/phosphocreatine+creatine (NAA/PCr+Cr) reflecting increased N-acetylaspartate or N-acetylated sugars in a left superior temporal region of the human brain.

6. The method of claim 1 wherein the determining step includes determining a conclusion of cognitively impaired chronic alcoholism in the human if the plurality of examined molecular alterations indicate increased neural membrane repair mechanisms which are failing including an increase in phosphomonoesters (PME(s-τ

_c)), an increase in phospholipid cofactors ((α

-γ

)ATP), an increase in N-acetylaspartate/phosphocreatine+creatine (NAA/PCr+Cr) reflecting increased N-acetylaspartate or N-acetylated sugars and a loss of synaptic/transport vesicles reflecting a descrease in phosphodiesters (PDE(i-τ

_c)) in the human brain.

7. The method of claim 1 wherein the medical imaging process includes magnetic resonance imaging or positron emission tomography.

8. The method of claim 1 wherein the molecular alterations are measured with a signal intensity of a magnetic or radioactive signal.

9. The method of claim 1 wherein the medical imaging process includes ₃₁P ¹H magnetic resonance spectroscopic imaging.

10. A method for diagnosing alcoholism disease in a human, comprising:

imaging a brain of a human with a medical imaging process;

determining a first signal intensity for membrane phospholipid building blocks including phosphomonoesters (PME(s-τ

_c)) in left inferior parietal regions of the human brain;

determining a second signal intensity for synaptic/transport vesicles including phosphodiesters (PDE(i-τ

_c)) in right inferior parietal regions of the human brain;

determining a third signal intensity for lipid/protein glycosylation intermediates and membrane including phospholipid cofactors ((α

-γ

)ATP) in left occipital regions of the human brain;

determining a fourth signal intensity for N-acetylaspartate/phosphocreatine+creatine (NAA/PCr+Cr) reflecting increased N-acetylaspartate or N-acetylated sugars in left superior temporal regions of the human brain; and

determining whether a conclusion of cognitively impaired chronic alcoholism in the human is suggested using the plurality of determined signal intensities.

11. The method of claim 10 wherein the medical imaging process includes magnetic resonance imaging or positron emission tomography.

12. The method of claim 10 wherein the steps of determining a first, second third or forth signal intensity includes measuring a signal intensity of a magnetic or radioactive signal.

13. The method of claim 10 wherein the medical imaging process includes ₃₁P ¹H magnetic resonance spectroscopic imaging.

14. The method of claim 10 wherein a conclusion of cognitively impaired chronic alcoholism in the human is suggested if the plurality of determined signal intensities indicate increased neural membrane repair mechanisms which are failing including an increase in phosphomonoesters (PME(s-τ

_c)), an increase in phospholipid cofactors ((α

-γ

)ATP), an increase in N-acetylaspartate/phosphocreatine+creatine (NAA/, PCr+Cr) reflecting increased N-acetylaspartate or N-acetylated sugars and a loss of synaptic/transport vesicles reflecting a decrease in phosphodiesters (PDE(i-τ

_c)) in the human brain.

15. A system for diagnosing alcoholism disease in a human, comprising in combination:

means for examining molecular alterations in membrane phospholipid and high-energy phosphate metabolism in a human brain with a medical imaging process;

means for examining molecular alterations in synaptic transport vesicles with the medical imaging process;

means for examining molecular alternations in phosphorylated proteins with the medical imaging process;

means for examining molecular alterations in metabolites with N-acetyl moieties and gangliosides are examined with the medical imaging process; and

means for determining with the plurality of examined molecular alterations whether a conclusion of cognitively impaired chronic alcoholism in the human is suggested.

16. The system of claim 15 wherein the means for determining with the plurality of examined molecular alterations whether a conclusion of cognitively impaired chronic alcoholism in the human is suggested includes a means for determining a conclusion of cognitively impaired chronic alcoholism in the human if the plurality of examined molecular alterations indicate increased neural membrane repair mechanisms which are failing including an increase in phosphomonoesters (PME(s-τ

_c)), an increase in phospholipid cofactors ((α

-γ

)ATP), an increase in N-acetylaspartate/phosphocreatine+creatine (NAA/PCr+Cr) reflecting increased N-acetylaspartate or N-acetylated sugars and a loss of synaptic/transport vesicles reflecting a descrease in phosphodiesters (PDE(i-τ

_c)) in the human brain.