Expression of oligodendrocyte and myelin genes is not altered in peripheral blood cells of patients with first‐episode schizophrenia and bipolar disorder

Recent studies have reported oligodendrocyte and myelin abnormalities, as well as the dysregulation of their related genes, in the brains of patients with schizophrenia (SCZ) and bipolar disorder (BD) (1, 2), which suggest that white matter alterations contribute to the pathophysiology of these disorders. SCZ and BD are diseases for which no reliable biological test exists. Thus, it is necessary to find specific biomarkers. There is evidence pointing to a close integration between central nervous system and immunological functions, with lymphocytes playing a central role (3). Comparison of the peripheral blood transcriptome with genes expressed in the brain has revealed that more than 82% of the expressed genes were shared (4). Thus, peripheral blood may be an ideal surrogate tissue as it is readily obtainable and provides a large biosensor pool in the form of gene transcripts. Proof of the principle of this idea has been provided in a recent pioneer study combining whole-genome gene expression differences in blood samples from subjects with BD and changes in gene expression in brain and blood of a mouse pharmacogenomic model (5). Importantly, this study demonstrates that myelin ⁄oligodendrocyte genes are top blood candidate biomarkers of bipolar disease states in chronic patients (5). We have investigated here whether oligodendrocyte and myelin expression alterations in brain are detectable in peripheral blood cells (PBCs) from SCZ and BD patients. To achieve this objective, we examined messenger RNA (mRNA) levels of two major components of oligodendrocytes and myelin, 2¢,3¢-cyclic nucleotide 3¢-phosphodiesterase (CNPase) and myelin basic protein (MBP), in PBCs at the first psychotic episode in drug-naı̈ve patients and after one year of treatment. We recruited 59 patients (mean age ± SEM: 26.5 ± 1 year) from Vitoria (Spain) who experienced a first psychotic episode. Subjects with mental retardation, organic brain disorders, or drug abuse as a primary diagnosis were excluded. Total Positive and Negative Syndrome Scale (PANSS) (6) scores (mean ± SD) were 75.7 ± 23.0 at baseline and 53.5 ± 21.3 at 12 months. The Global Assessment of Functioning (GAF) score was 33.2 ± 10.7 at baseline and 56.8 ± 15.6 at 12 months. A total of 57.2% were smokers, 60.7% consumed alcohol, 12.5% abused alcohol, and 25% abused cannabis. Patients were diagnosed with SCZ (n = 39) or BD (n = 20) using the Structured Clinical Interview for DSM-IV (SCID-I). They were treated after the first episode with atypical antipsychotics (71.9%); lithium or other mood stabilizers together with atypical antipsychotics (22.3%); or typical antipsychotics (5.3%); or they received no treatment (3.5%). A total of 45 healthy volunteers were selected for this study from the same community and matched pairwise for sex and age (mean age ± SEM: 26.9 ± 1 year). The inclusion criteria for controls required the absence of any Axis I disorder, as well as the similar criteria that was applied to the patient group. Peripheral whole-blood samples were collected from patients upon arrival at the emergency room and again 12 months later, and from nonpsychiatric control subjects. Total RNA from PBCs was isolated and processed for real-time polymerase chain reaction (PCR) using primer pairs specific for MBP and CNPase and endogenous housekeeping genes as previously reported (7). Data are illustrated as the relative expression of each target gene normalized to housekeeping genes (7). Comparisons of normalized values between each patient group and controls were made between pairs matched for age and sex using two-tailed, unpaired Student s t-test. We did not find significant differences (all p > 0.5) in the relative expression of CNPase and MBP mRNAs in SCZ or in BD in the PBCs at Bipolar Disorders 2010: 12: 107–111 a 2010 The Authors Journal compilation a 2010 Blackwell Munksgaard