0
Get Alert
Please Wait... Processing your request... Please Wait.
You must sign in to sign-up for alerts.

Please confirm that your email address is correct, so you can successfully receive this alert.

1
Letter to the Editor   |    
The Significance of Homocysteine Levels in Schizophrenia
COLIN O’DONNELL, M.B.B.Ch., M.R.C.Psych.; TIM STEPHENS, B.Sc.
Am J Psychiatry 2005;162:1387-a-1388. doi:10.1176/appi.ajp.162.7.1387-a

To the Editor: We noted with interest the findings of Donald C. Goff, M.D., et al. (1) but question whether the comparison group they used was representative of homocysteine measurement. Differences in age and homocysteine measurement and an absence of dietary history and genotyping for methylenetetrahydrofolate reductase, which are important confounding variables, may have biased the homocysteine analysis.

The study group’s mean age was 20 years younger than the comparison group’s (the sixth Framingham Offspring cohort subgroup). Homocysteine levels rise progressively with age, approximately doubling from childhood to old age. There is a bias toward higher comparison homocysteine levels as a result (2, 3).

The accuracy of homocysteine differs among methods and laboratories. This effect had not been controlled. The Framingham Offspring comparison group’s homocysteine level was measured with high-performance liquid chromatography with fluorescent detection, whereas the study group used fluorescence polarization immunoassay. The use of a local comparison group with the same method and laboratory is recommended (3).

The Framingham Offspring Study shows that mandatory fortification policy has reduced the prevalence of low folate status (i.e., <3.0 ng/ml) by more than 90% and the prevalence of mild fasting hyperhomocysteinemia (homocysteine concentrations >130 mmol/liter) by about 50% among its population-based cohort of middle-age to elderly U.S. citizens (4).

We recommend that the assessment of homocysteine requires the measurement of known confounding variables, especially in smaller group sizes, from folic-acid-fortified regions. Contrary to larger previous studies with local comparison groups showing increased homocysteine levels in schizophrenia, these results should be treated with caution (5, 6).

Goff DC, Bottiglieri T, Arning E, Shih V, Freudenreich O, Evins AE, Henderson DC, Baer L, Coyle J: Folate, homocysteine, and negative symptoms in schizophrenia. Am J Psychiatry  2004; 161:1705–1708
[PubMed]
[CrossRef]
 
Jacques PF, Selhub J, Bostom AG, Wilson PWF, Rosenberg IH: The effect of folic acid fortification on plasma folate and total homocysteine concentrations. N Engl J Med  1999; 340:1449–1454
[PubMed]
[CrossRef]
 
Refsum H, Smith AD, Ueland PM, Nexo E, Clarke R, McPartlin J, Johnston C, Engbaek F, Schneede J, McPartlin C, Scott JM: Facts and recommendations about total homocysteine determinations: an expert opinion. Clin Chem  2004; 50:3–32
[PubMed]
[CrossRef]
 
Bostom AG, Selhub J, Jacques PF, Rosenberg IH: Power shortage: clinical trials testing the "homocysteine hypothesis" against a background of folic acid-fortified cereal grain flour. Ann Intern Med  2001; 135:133–137
[PubMed]
 
Applebaum J, Shimon H, Sela BA, Belmaker RH, Levine J: Homocysteine levels in newly admitted schizophrenic patients. J Psychiatr Res  2004; 38:413–416
[PubMed]
[CrossRef]
 
Levine J, Stahl Z, Ami B, Slava S, Ruderman GV, Belmaker RH: Elevated homocysteine levels in young male patients with schizophrenia. Am J Psychiatry  2002; 159:1790–1792
[PubMed]
[CrossRef]
 
+

References

Goff DC, Bottiglieri T, Arning E, Shih V, Freudenreich O, Evins AE, Henderson DC, Baer L, Coyle J: Folate, homocysteine, and negative symptoms in schizophrenia. Am J Psychiatry  2004; 161:1705–1708
[PubMed]
[CrossRef]
 
Jacques PF, Selhub J, Bostom AG, Wilson PWF, Rosenberg IH: The effect of folic acid fortification on plasma folate and total homocysteine concentrations. N Engl J Med  1999; 340:1449–1454
[PubMed]
[CrossRef]
 
Refsum H, Smith AD, Ueland PM, Nexo E, Clarke R, McPartlin J, Johnston C, Engbaek F, Schneede J, McPartlin C, Scott JM: Facts and recommendations about total homocysteine determinations: an expert opinion. Clin Chem  2004; 50:3–32
[PubMed]
[CrossRef]
 
Bostom AG, Selhub J, Jacques PF, Rosenberg IH: Power shortage: clinical trials testing the "homocysteine hypothesis" against a background of folic acid-fortified cereal grain flour. Ann Intern Med  2001; 135:133–137
[PubMed]
 
Applebaum J, Shimon H, Sela BA, Belmaker RH, Levine J: Homocysteine levels in newly admitted schizophrenic patients. J Psychiatr Res  2004; 38:413–416
[PubMed]
[CrossRef]
 
Levine J, Stahl Z, Ami B, Slava S, Ruderman GV, Belmaker RH: Elevated homocysteine levels in young male patients with schizophrenia. Am J Psychiatry  2002; 159:1790–1792
[PubMed]
[CrossRef]
 
+
+

CME Activity

There is currently no quiz available for this resource. Please click here to go to the CME page to find another.
Submit a Comments
Please read the other comments before you post yours. Contributors must reveal any conflict of interest.
Comments are moderated and will appear on the site at the discertion of APA editorial staff.

* = Required Field
(if multiple authors, separate names by comma)
Example: John Doe



Related Content
Books
APA Practice Guidelines > Chapter 16.  >
The American Psychiatric Publishing Textbook of Substance Abuse Treatment, 4th Edition > Chapter 38.  >
The American Psychiatric Publishing Textbook of Substance Abuse Treatment, 4th Edition > Chapter 38.  >
Topic Collections
Psychiatric News
Read more at Psychiatric News >>
APA Guidelines
PubMed Articles