| 1. |
- Herrera-Rivero, Marisol, et al.
(författare)
-
Immunogenetics of lithium response and psychiatric phenotypes in patients with bipolar disorder.
- 2023
-
Ingår i: Research square.
-
Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- The link between bipolar disorder (BP) and immune dysfunction remains controversial. While epidemiological studies have long suggested an association, recent research has found only limited evidence of such a relationship. To clarify this, we investigated the contributions of immune-relevant genetic factors to the response to lithium (Li) treatment and the clinical presentation of BP. First, we assessed the association of a large collection of immune-related genes (4,925) with Li response, defined by the Retrospective Assessment of the Lithium Response Phenotype Scale (Alda scale), and clinical characteristics in patients with BP from the International Consortium on Lithium Genetics (ConLi+Gen, N = 2,374). Second, we calculated here previously published polygenic scores (PGSs) for immune-related traits and evaluated their associations with Li response and clinical features. We found several genes associated with Li response at p < 1×10- 4 values, including HAS3, CNTNAP5 and NFIB. Network and functional enrichment analyses uncovered an overrepresentation of pathways involved in cell adhesion and intercellular communication, which appear to converge on the well-known Li-induced inhibition of GSK-3β. We also found various genes associated with BP's age-at-onset, number of mood episodes, and presence of psychosis, substance abuse and/or suicidal ideation at the exploratory threshold. These included RTN4, XKR4, NRXN1, NRG1/3 and GRK5. Additionally, PGS analyses suggested serum FAS, ECP, TRANCE and cytokine ligands, amongst others, might represent potential circulating biomarkers of Li response and clinical presentation. Taken together, our results support the notion of a relatively weak association between immunity and clinically relevant features of BP at the genetic level.
|
|
| 2. |
- Kurtz, Joachim, et al.
(författare)
-
An experimental test of the immunocompetence handicap hypothesis in a teleost fish: 11-ketotestosterone suppresses innate immunity in three-spined sticklebacks
- 2007
-
Ingår i: American Naturalist. - : University of Chicago Press. - 0003-0147 .- 1537-5323. ; 170:4, s. 509-519
-
Tidskriftsartikel (refereegranskat)abstract
- The immunocompetence handicap hypothesis (ICHH) provides a functional explanation for how sexual ornaments can provide honest signals of male quality. A key aspect of this hypothesis is that testosterone (T) has a bimodal effect: a higher T level enhances the expression of ornaments (increasing mating success and, ultimately, fitness); however, at the same time, it suppresses immune function. Tests of the latter assumption, which have focused mainly on aspects of adaptive immunity in birds, led to equivocal results. We performed a hormone‐implant experiment in male three‐spined sticklebacks (Gasterosteus aculeatus) to test the key assumptions of the ICHH in a fish, where the dominant circulating androgen is 11‐ketotestosterone (11kT) rather than T. Males were implanted with 11‐ketoandrostenedione, which is a natural precursor of 11kT. Each individual's circulating 11kT level, ornamentation, and immunocompetence were measured 2 weeks later. In addition, we quantified oxidative tissue damage because the ICHH has been hypothesized to work via oxidative stress. We found that the males' 11kT levels correlated positively with ornamentation but negatively with immunocompetence, in particular, measures of innate immunity. Moreover, there was a trend for fish with high 11kT levels to suffer more from oxidative stress. Thus, our data provide support for the ICHH.
|
|
