Translational Psychiatry (2023)13:190

Despite the biologically plausible conceptual links between
neuroinﬂammation, depression, and HIV (described in detail
elsewhere [24]), few studies have previously attempted to
quantitatively test this hypothesis. Amongst participants living
with HIV (but not those without HIV), Saloner et al. [25] observed a
trend between depression severity and composite neuroinﬂammation scores while Woods et al. [26] similarly saw a signiﬁcant
association between speciﬁc dimensions of depression and
plasma BDNF. In line with our ﬁndings in the current study,
Musinguzi et al. [27] previously demonstrated that participants
living with HIV recruited in Uganda who exhibited increased TNF-α
were at signiﬁcantly higher risk for depression. Our study offered
the additional advantage of replicating this mediation effect in a
sample of participants living with and without HIV. Given that TNFα appears to mediate the relationship between HIV and depressive
symptoms in two independent and demographically distinct
samples, it is plausible that the effect of plasma TNF-α on this
association is robust and reliable.
We found CSF IL-6 to have a considerable mediating role in
depressive symptoms, which is compatible with previous evidence
consistently implicating IL-6 in the risk for depression, although
our study is one of the ﬁrst to demonstrate this speciﬁcally in the
context of HIV. We also saw sub-threshold but notable mediation
of the association between HIV and depressive symptoms by
plasma IL-6. The association between IL-6 and depression has
been observed repeatedly with varying strengths [28]. Longitudinal twin studies and meta-analyses indicate that elevation in
IL-6 may be a risk factor leading to depression, rather than a
consequence of depression [29, 30]. Our ﬁndings therefore
suggest that IL-6 may play a role in mediating the risk for
depression in people living with HIV.

### Language ###
English

### Assessment ###
The text discusses IL-6's role in depression and HIV, and we could ask about this specific relationship.

### Query ###
Is there a connection between IL-6 and depression risk?
Is there a connection between IL-6 and depression risk?