Methods for diagnosis and prognosis of psychotic disorders

• US 20080009010A1
• Filed: 05/18/2007
• Published: 01/10/2008
• Est. Priority Date: 05/18/2006
• Status: Active Grant

• Current Assignee: Mclean Hospital (Mass General Brigham, Inc.)
• Original Assignee: Mclean Hospital (Mass General Brigham, Inc.)
• Inventors: Konradi, Christine
• Granted Patent: US 8,163,475 B2
• Time in Patent Office: Days
• US Class Current: 435/006
• CPC Class Codes: C12Q 1/6883 for diseases caused by alterations of genetic material
• CPC Class Codes: C12Q 2600/158 Expression markers
• CPC Class Codes: G01N 2800/304 Mood disorders, e.g. bipolar, depression
• CPC Class Codes: G01N 2800/7004 Stress
• CPC Class Codes: G01N 33/6896 Neurological disorders, e.g. Alzheimer's disease

Abstract

The invention features methods diagnostic of a psychotic disorder such as bipolar disorder or schizophrenia. The methods include obtaining a cell sample from a subject, subjecting a cell from the sample to stress (e.g., nutrient stress), and measuring nucleic acid or polypeptide expression in the cell, where an alteration in expression is indicative of the subject having or being at increased risk of developing a psychotic disorder. The invention also features prognostic monitoring methods for subjects having a psychotic disorder, useful in determining the progression of a psychotic disorder in a subject or the effectiveness of a therapy.

Claims

1. A method for diagnosing a psychotic disorder or propensity thereto in a subject, said method comprising the steps:

(a) obtaining a cellular sample from said subject;

(b) subjecting a cell from said sample to stress; and

(c) measuring expression in said cell of at least one nucleic acid or polypeptide listed in Table 3 or FIG. 1A(I)-1A(IV), wherein an alteration in said expression as compared to the expression in a corresponding cell from a cell sample taken from a control subject is indicative of said subject having a psychotic disorder or propensity thereto.

2. The method of claim 1, wherein said psychotic disorder is bipolar disorder or schizophrenia.

3. The method of claim 1, wherein said cellular sample is a fluid sample.

4. The method of claim 3, wherein said fluid sample is a blood sample.

5. The method of claim 1, wherein said cell sample comprises a lymphocyte.

6. The method of claim 1, wherein step (b) subjecting comprises culturing said cell.

7. The method of claim 1, wherein said stress is nutrient stress, oxygen stress, temperature stress, or osmotic stress.

8. The method of claim 7, wherein said nutrient stress is glucose stress.

9. The method of claim 1, wherein said alteration is a decrease in expression.

10. The method of claim 1, wherein expression of at least 2 different nucleic acids or polypeptides are measured.

11. The method of claim 1, wherein expression of at least 10 different nucleic acids or polypeptides are measured.

12. A method for diagnosing a psychotic disorder or propensity thereto in a subject, said method comprising the steps:

(a) obtaining a cell sample from said subject;

(b) subjecting a cell from said sample to stress; and

(c) measuring the level of expression in said cell of at least one mitochondrial energy metabolism nucleic acid or polypeptide, wherein an alteration in said level of expression as compared to the expression in a cell from a sample obtained from a control subject is indicative of said subject having a psychotic disorder or propensity thereto.

13. The method of claim 12, wherein said psychotic disorder is bipolar disorder or schizophrenia.

14. The method of claim 12, wherein said cell sample is a fluid sample.

15. The method of claim 14, wherein said fluid sample is a blood sample.

16. The method of claim 12, wherein said cell sample comprises a lymphocyte.

17. The method of claim 12, wherein step (b) subjecting comprises culturing said cell.

18. The method of claim 12, wherein said stress is nutrient stress, oxygen stress, temperature stress, or osmotic stress.

19. The method of claim 18, wherein said nutrient stress is glucose stress.

20. The method of claim 12, wherein said alteration is a decrease in expression.

21. The method of claim 12, wherein expression of at least 2 different nucleic acids or polypeptides are measured.

22. The method of claim 12, wherein expression of at least 10 different nucleic acids or polypeptides are measured.

23. A method for monitoring a psychotic disorder in a subject having said disorder, said method comprising the steps:

(a) obtaining a cell sample from said subject;

(b) subjecting a cell from said sample to stress;

(c) measuring the level of expression in said cell of (i) at least one mitochondrial energy metabolism nucleic acid or polypeptide or (ii) at least one nucleic acid or polypeptide from in Table 3 or FIGS. 1A(I)-1(A)(IV); and

(d) repeating steps (a)-(c) within one year, thereby providing a second measurement of expression, wherein an alteration in the second measurement as compared to the level measured in step (c) is indicative of the progression of said psychotic disorder in said subject.

24. The method of claim 23, wherein said psychotic disorder is bipolar disorder or schizophrenia.

25. The method of claim 23, further comprising, between steps (c) and (d), a step of administering a therapy to said subject.

26. The method of claim 25, wherein said therapy was not administered to said subject within six months prior to performing step (a).

27. The method of claim 25, wherein said therapy is an anti-psychotic.

28. The method of claim 23, wherein step (d) is performed within six months of step (c).