Study Report

Reference	Reif, A.,2005 PMID: 16055253
Citation	Reif, A., B. Pfuhlmann, et al. (2005). Homocysteinemia as well as methylenetetrahydrofolate reductase polymorphism are associated with affective psychoses. Prog Neuropsychopharmacol Biol Psychiatry 29(7): 1162-1168.
Disease Type	Bipolar Disorder & Major Depressive Disorder
Study Design	case-control
Study Type	Candidate-gene association study
Sample Size	136 patientsI(91 with bipolar affective disorders and 45 with unipolar depression) and 284 control subjects
SNP/Region/Marker Size	2 polymorphisms
Predominant Ethnicity	Caucasian
Population	German
Age Group	Adults : The average age was 50 years for the Bip , 59 years for the MD group and 35 years for the control group.

Sample Diagnosis	DSM
Sample Status	For MTHFR genotyping, a total of 136 patients (of both sexes) from Lower Franconia (Germany) were recruited, which were ascertained as inpatients of the Department of Psychiatry. Ninety-one patients suffered from bipolar affective (Bip) disorder; only patients with a minimum of one manic plus one depressive episode were classified as Bip (i.e., strict bipolar-I criteria). A further 45 patients with unipolar depression (MD) were also included in the study,however only when absolutely no signs of bipolarity were present throughout the whole disease course. Those patients fulfilled the DSM-IV criteria of recurring depressive disorder (American Psychiatric Association, 1994),and had at least two depressive episodes. The average age was 50 years for the Bip and 59 years for the MD group,respectively.A sample of DNA probes has been collected from of 284 control subjects consisting of healthy blood donors from the same region as the patient group; the sample was not screened for a history of psychiatric disorders. All control subjects were free of medication, and the study was explained to them, so that the chance that severe psychiatric disorders were present in the control sample was low. Mean age of controls was 35 years. In all patients, routine laboratory tests and thorough clinical examination were assessed as were smoking status and psychotropic medication. Only patients and volunteers who gave written informed consent after oral as well as written explanation about the investigation were enrolled.
Technique	genotyping
Statistical Method	Statistical analysis of homocysteine levels was performed using the X2 and Student's t-test test by the Statistica 6 software package (StatSoft Germany, Hamburg, Germany).
Result Summary	To further explore the connection between homocysteinemia and affective psychoses, a case-control study examining the C677T and the A1298C variants of methylenetetrahydrofolate reductase was conducted. The latter polymorphism not only was associated with affective psychoses in general, but also when divided in unipolar depression and bipolar affective disorder. In conclusion, we suggest that in females homocysteinemia is an unspecific risk factor for organic brain disorders like dementia, and possibly depression, but not for schizophrenia.