Reduced hippocampal brain-derived neurotrophic factor precursor ([pro]BDNF) expression is common to both major depressive disorder (MDD) and bipolar disorder, UK investigators have discovered.

Brain-derived neurotrophic factor (BDNF) and (pro)BDNF are expressed in the developing and adult hippocampus, and other brain areas linked to schizophrenia and mood disorders. Several studies have also linked BDNF and BDNF polymorphisms to the pathophysiology of psychiatric illness.

To examine alterations in hippocampal levels of (pro)BDNF and receptor proteins TrkB and p75 and the impact of genetic variations on protein expression, C Toro, from Cranfield University, and colleagues studied anterior hippocampal sections from the Stanley Foundation Neuropathology Consortium.

The sections included samples from 15 patients with schizophrenia, 15 with MDD, 15 with bipolar disorder, and 13 age- and gender-matched controls. Immunoautoradiography was used to determine (pro)BDNF, TrkB, and p75 protein densities, and extracted DNA was genotyped for several single nucleotides (SNPs) in the BDNF, NTRK2, and NGFR genes.

All of the mood disorder groups had reduced (pro)BDNF density compared with controls. However, the overall differences were not significant, as any reductions in hippocampal layers were offset by an absence of change in the dentate gyrus.

Specifically, MDD patients had significantly reduced (pro)BDNF density in all three layers of the right hippocampus, while bipolar disorder patients had reductions in the right striatal oriens and striatal radiatum.

The results also show that bipolar disorder patients had bilateral reductions in p75 values compared with MDD, schizophrenia, and control groups in the hippocampus but not in the dentate gyrus. The differences were particularly marked compared with MDD patients.

The team also notes in the Journal of Psychiatric Research that, of the 31 SNPs studied, five were associated with changes in protein density across all hippocampal subregions that may affect hippocampal development.

Discussing the findings, they write: “It is tempting to speculate that a combined impairment of (pro)BDNF and p75 receptor function in bipolar disorder relates to the chronicity of depression rather than the occurrence of mania, however further larger-scale studies are necessary to test this theory.”

MedWire (www.medwire-news.md) is an independent clinical news service provided by Current Medicine Group, a part of Springer Science+Business Media. © Current Medicine Group Ltd; 2009

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