Neuropsychiatric test reports

• US 8,355,927 B2
• Filed: 02/10/2012
• Issued: 01/15/2013
• Est. Priority Date: 11/05/2010
• Status: Active Grant

• Current Assignee: Genomind, LLC
• Original Assignee: Genomind, LLC
• Inventors: Lombard, Jay L.
• Primary Examiner(s): O'Connor, Gerald J.
• Assistant Examiner(s): Patel, Neha
• Application Number:
  US13/371,227
• Publication Number:
  US 20120136680A1
• Time in Patent Office: 340 Days
• Field of Search: 705/2, 705/3
• US Class Current: 705/2
• CPC Class Codes: G06Q 10/10 Office automation; Time management
• CPC Class Codes: G16B 20/00 ICT specially adapted for functional genomics or proteomics, e.g. genotype-phenotype associations
• CPC Class Codes: G16B 20/10 Ploidy or copy number detection
• CPC Class Codes: G16B 20/20 Allele or variant detection, e.g. single nucleotide polymorphism [SNP] detection
• CPC Class Codes: G16H 10/40 for data related to laboratory analysis, e.g. patient specimen analysis
• CPC Class Codes: G16H 15/00 ICT specially adapted for medical reports, e.g. generation or transmission thereof
• CPC Class Codes: G16H 20/10 relating to drugs or medications, e.g. for ensuring correct administration to patients

Abstract

Methods and reports for presenting genetic information that is patient-specific and relevant to treatment of neuropsychiatric disorders, including treatment resistant psychiatric disorders, to aid in patient treatment in a phenotype, genotype or biomarker-specific manner. The methods and reports examine biomarkers for dysfunction of three axes relevant to treating neuropsychiatric disorders and provide interpretive comments to aid in treatment. Combining biomarker information from each of the three axes (the autonomic arousal axis, the emotional valence, attention, reward and executive brain function axis, and the long-term potentiation and long-term depression (LTP-LTD) function axis) provides an unexpectedly comprehensive and effective means for directing treatment of neuropsychiatric disorders, including particularly treatment resistant disorders (TRD).

Claims

1. In a computer processor, a method of generating a report presenting patient-specific and dimensionally based information relevant to the treatment of a neuropsychiatric disorder, the method comprising:

collecting, using the processor, the results of a biomarker test specific to a patient for at least one biomarker for dysfunction in each of the following neuropsychiatric axes;

(1) the patient'"'"'s limbic mediated autonomic arousal system;

(2) the patient'"'"'s prefrontal-subcortical mediated emotional valence, attention, reward and executive brain systems; and

(3) the patient'"'"'s synaptic mediated long-term potentiation and long-term depression (LTP-LTD) system;

selecting, using the processor, an interpretive comment based on the patient'"'"'s results of the biomarker test;

organizing, using the processor, the results of the biomarker tests and one or more interpretive comments in a patient-specific neuropsychiatric report; and

presenting the patient-specific neuropsychiatric report, wherein the report comprises an interpretive analysis of the neuropsychological significance of the result of any biomarker test for dysfunction collected, wherein the interpretive analysis comprises interpretive comments that include a description of an association with a disorder or a dysfunction of brain activity or a disorder and dysfunction of brain activity based on the biomarker test results.

2. The method of claim 1, wherein selecting comprises selecting a recommendation for the prescription of a specified agent which downregulates excessive limbic activity, when the biomarker for dysfunction in the patient'"'"'s autonomic arousal system axis indicates that the patient has the short allelic form of solute carrier family 6 member 4 (SLC6A4).

3. The method of claim 1, wherein selecting comprises selecting a recommendation for other calcium and or sodium channel modulators of the Central nervous system, when the biomarker for dysfunction in the patient'"'"'s synaptic mediated long-term potentiation and depression (LTP-LTD) function axis indicates that the patient has a polymorphism of the calcium channel, voltage-dependent, L type, alpha 1C subunit (CACNA1C) calcium channel gene or sodium channel gene.

4. The method of claim 1, wherein selecting comprises selecting a recommendation for S-adenosyl methionine when the biomarker for dysfunction in the patient'"'"'s prefrontal-subcortical emotional valence, attention, reward and executive brain function axis indicates that the patient has a met/met polymorphism of the catechol-O-methyltransferase (COMT) gene.

5. The method of claim 1, wherein selecting comprises selecting a recommendation for stimulation of the doral lateral prefrontal cortex when the biomarker for dysfunction in the patient'"'"'s prefrontal-subcortical emotional valence, attention, reward and executive brain function axis indicates that the patient has a val/val polymorphism of the catechol-O-methyltransferase (COMT) gene.

6. The method of claim 1, wherein selecting comprises selecting a recommendation for a folic acid when a biomarker for dysfunction indicates that the patient has a polymorphism of the methylenetetrahydrofolate reductase (MTHFR) gene.

7. The method of claim 1, wherein presenting the patient-specific neuropsychiatric report comprises presenting an association with a neuropsychiatric condition based on the biomarker test results.

8. The method of claim 1, wherein the neuropsychiatric disorder is selected from the group including:

depressive disorders, bipolar disorder, anxiety disorders, PTSD, schizophrenia, autism, ADHD, and treatment resistant forms of these disorders.

9. The method of claim 1, further comprising providing a referral to a call center to receive additional interpretive analysis, clinical decision support, psychiatric focused genetic counseling, and/or neuroradiologists for imaging interpretation and analysis.

10. The method of claim 1, wherein collecting comprises collecting biomarker test results specific to the patient for a pharmacokinetic biomarker.

11. The method of claim 10, wherein the pharmacokinetic biomarker comprises gene families and pathways known to be involved in the absorption, distribution, metabolism or elimination of drugs.

12. The method of claim 1, further wherein presenting the patient-specific neuropsychiatric report comprises presenting a visual representation of a brain region associated with any biomarker for dysfunction collected.

13. The method of claim 1, wherein the biomarker test results indicate polymorphism, deletion, repetition, insertion, methylation level, allele specific methylation, expression level, expression localization, activity, or metabolites of one or more gene, gene family, pathway, transcript, protein, neurotransmitter or result acquired from brain imaging.

14. The method of claim 1, wherein the biomarker for dysfunction in the patient'"'"'s limbic autonomic arousal system axis is a marker of a variant of a gene, or a protein encoded or modulated by gene, selected from the group consisting of:

solute carrier family 6 member 4 (SLC6A4), angiotensin I converting enzyme 1 (ACE), neuropeptide Y (NPY), FK506-binding protein 5 (FKBP5), and serotonin 5-HT-1A receptor (HTR1A).

15. The method of claim 1, wherein the biomarker for dysfunction in the patient'"'"'s prefrontal-subcortical emotional valence, attention, reward and executive brain functions axis is a marker of a variant of a gene, or a protein encoded or modulated by gene, selected from the group consisting of:

catechol-O-methyltransferase (COMT), solute carrier family 6 member 31 (SLC6A3), and dopamine receptor D2 (DRD2).

16. The method of claim 1, wherein the biomarker for dysfunction in the patient'"'"'s synaptic mediated long-term potentiation and long-term depression (LTP-LTD) function axis is a marker of a variant of a gene, or a protein encoded or modulated by gene, selected from the group consisting of:

calcium channel, voltage-dependent, L type, alpha 1C subunit (CACNA1C), solute carrier family 1 member 1 (SLC1A1), ankyrn 3 (ANK3U), brain-derived neurotrophic factor (BDNF), and apolipoprotein E (APOE).

17. The method of claim 1, wherein selecting comprises indicating, based on the patient'"'"'s biomarker results, the patient'"'"'s potential heightened response to a neurotherapeutic agent selected from the group consisting of:

norepinephrine modulators, angiotensin receptor blockers, dopamine augmenting agents, monoamine oxidase inhibitors, catechol-O-methyltransferase (COMT) inhibitors, COMT upregulators, mood stabilizers, calcium channel agents, AMPA-receptor potentiators, Tianeptine or dorsal lateral prefrontal cortex stimulation.

18. In a computer processor, a method of generating a report presenting patient-specific and dimensionally based information relevant to the treatment of a neuropsychiatric disorder, the method comprising:

collecting, using the processor, the results of a biomarker test specific to a patient for at least one biomarker for dysfunction in each of the following neuropsychiatric axes;

(1) the patient'"'"'s limbic based autonomic arousal system axis, wherein the biomarker is related to a gene or a protein encoded or modulated by a gene selected from the group consisting of;

solute carrier family 6 member 4 (SLC6A4), angiotensin I converting enzyme 1 (ACE), neuropeptide Y (NPY), FK506-binding protein 5 (FKBP5), and serotonin 5-HT-1A receptor (HTR1A);

(2) the patient'"'"'s prefrontal-subcortical emotional valence, attention, reward and executive brain function axis, the biomarker related to a gene or a protein encoded or modulated by a gene selected from the group consisting of;

catechol-O-methyltransferase (COMT), solute carrier family 6 member 31 (SLC6A3), and dopamine receptor D2 (DRD2); and

(3) the patient'"'"'s synaptic mediated long-term potentiation and depression (LTP-LTD) function axis, the biomarker related to a gene or a protein encoded or modulated by a gene selected from the group consisting of calcium channel, voltage-dependent, L type, alpha 1C subunit (CACNA1C), solute carrier family 1 member 1 (SLC1A1), ankyrn 3 (ANK3), brain-derived neurotrophic factor (BDNF), and apolipoprotein E (APOE);

selecting, using the processor, one or more interpretive comments for the results of the biomarker tests;

associating, using the processor, a visual representation of a brain region with each biomarker test result;

providing a referral to a call center to receive additional interpretive information;

organizing, using the processor, the biomarker results and interpretive comments in a patient-specific neuropsychiatric report; and

digitally presenting the patient-specific neuropsychiatric report wherein the report comprises an interpretive analysis of the neuropsychological significance of the result of any biomarker for dysfunction collected, wherein the interpretive analysis comprises interpretive comments that include a description of an association with a disorder or a dysfunction of brain activity or a disorder and dysfunction of brain activity based on the biomarker test results.