Active HHV-6A/B found in the cerebellar Purkinje cells in patients with mood disorders

HHV-6 was found more frequently in the Purkinje cells of patients with bipolar and major depressive disorder than in controls. Furthermore, HHV-6A was associated with a reduced Purkinje cell size. In contrast, HHV-6 was not found in patients with schizophrenia.

Although there is a high degree of heritability with bipolar disease, there are also unknown environmental triggers, and signs of a poor immune system (infections and hospitalizations) are associated with a significant increase in the risk of developing bipolar disease. Also, decreased cerebellar volume is associated with bipolar disease.

Investigators in the UK and Germany obtained post-mortem brain samples of patients with bipolar disease, schizophrenia, and major depressive disorder (MDD) from the Stanley Medical Research Institute.

HHV-6B infection in in Purkinje cells (red arrow) and astrocytes (white arrows). Source: Frontiers in Microbiology.

Frozen blocks of cerebellum were tested using quantitative PCR, immunofluorescence analysis, and transmission electron microscopy. Formalin fixed paraffin embedded sections were used for fluorescent in situ hybridization. The HHV-6-infected Purkinje cells were predominantly at the interface between the molecular and granular layers. Some astrocytes and microglia in the vicinity of the Purkinje cells also tested positive.

More women than men were positive for HHV-6A/B. There was no difference in the prevalence of HHV-6 between those with schizophrenia and controls. A gene expression microarray analysis showed that pathways associated with viral infection and immune defense, including toll-like receptor signaling, were overrepresented.

The authors note that a limitation of the study is that only a small region of the posterior lobe was examined. They also recommend that future studies should consider coinfections, since other pathogens have the potential to activate latent HHV-6A/B.

The study was initiated by UK scientists Carla Toro, PhD, and Sheila Govind PhD. They joined forces with Bhupesh Prusty from the University of Würzburg, who was able to examine the tissues with more sophisticated techniques. Next, the group plans to try to learn more about the molecular mechanisms that drive HHV-6A-induced damage.

For more information, read the full paper: Prusty 2018a.