Association of an UCP4 (SLC25A27) haplotype with ultra-resistant schizophrenia

Neuronal uncoupling proteins are involved in the regulation of reactive oxygen species production and intracellular calcium homeostasis, and thus, play a neuroprotective role. In order to explore the potential consequences of neuronal uncoupling proteins variants we examined their association in a sample of Caucasian patients suffering from schizophrenia and phenotyped them according to antipsychotic response.

Using a case-control design, we compared the frequencies of 15 genetic variants spanning UCP2, UCP4 and UCP5 in 106 French Caucasian patients suffering from schizophrenia and 127 healthy controls. In addition, patients with schizophrenia who responded to antipsychotic treatment were compared with patients with ultra-resistant schizophrenia (URS). This latter population presented no clinical, social and/or occupational remission despite at least two periods of treatment with conventional or atypical antipsychotic drugs and also with clozapine.

There were no differences in the distribution of the respective alleles between URS and responding patients. However, one haplotype spanning UCP4 was found to be significantly under-represented in URS patients. This relationship remained significant after multiple testing corrections.

Although our sample is of limited size and not representative of schizophrenia as a whole, the association found between the URS group and the UCP4 haplotype is noteworthy as it may influence treatment outcome in schizophrenia.