Higher HHV-6 viral load in oral mucosa cells in people with major depression

Combination of viral load and presence of specific polymorphism in the TNF-α gene associated with major depression.

There is increasing evidence of a role for neuroinflammation in major depressive disorder (MDD). One possible cause of neuroinflammation would be chronic infection with a neurotropic virus.

Investigators from several academic medical institutions in Thailand evaluated the viral load of HHV-6 in buccal mucosa cells as well as the TNF-α (-308G/A) polymorphism and levels of several cytokines in four different groups: people with MDD (N=59), blood relatives of people with MDD (N=36), non-blood relatives of people with MDD (N=16), and healthy control subjects without a current or lifetime history of depression (N=360). (There is no mention of whether the relatives of people with MDD were, themselves, screened for depression.)

The percent of people in whom HHV-6 was detected, and viral loads in these people, were significantly higher in people with MDD and their relatives than in the healthy control subjects. Specifically, those numbers for each of the four groups were: MDD patients: 26% and 14,473 copies/μL DNA; blood relatives 47% and 8146 copies/μL DNA; non‑blood relatives 44% and 20,721 copies/μL DNA; healthy controls 14% and 6303 copies/μL DNA.

There was no significant difference in the frequency of the TNFα (‑308G/A) mutation in the different groups. However, people with the TNFα (‑308G/A) mutation more frequently (46%) had detectable HHV-6 than people with wild‑type TNFα (‑308G) (26%). Moreover, people with both the TNFα (‑308G/A) mutation and detectable HHV-6 had significantly higher levels of TNF‑α, IL‑6, and IL‑10.

The authors conclude that HHV-6 may play a role in either the initiation and/or perpetuation of major depression, and that it may do so through inducing neuroinflammation, particularly in those susceptible to developing inflammation (such as those with the TNFα (‑308G/A) mutation.  However, it is puzzling that the presence and viral load of HHV-6 were the same or greater in both blood relatives and non-blood relatives of people with MDD than in the people with MDD, themselves. And the fact that the presence of MDD in these relatives was not reported makes interpretation of the data even harder.  Finally, it has not been established that the viral load of HHV-6 in buccal mucosa (oral) samples correlates with evidence of neuroinflammation—the presumed mechanism by which HHV-6 might render people vulnerable to MDD.  Thus, the study does not present strong evidence that HHV-6 contributes to the pathogenesis of depression, although that remains plausible: one study of brain tissue has linked HHV-6 to bipolar disorder, a particular depressive disorder (Prusty 2018).

Read the full article:  Sumala 2023