Personality and serotonin transporter genotype interact with social context to affect immunity and viral set-point in simian immunodeficiency virus disease

Abstract

From the beginning of the AIDS epidemic, stress has been a suspected contributor to the wide variation seen in disease progression, and some evidence supports this idea. Not all individuals respond to a stressor in the same way, however, and little is known about the biological mechanisms by which variations in individuals' responses to their environment affect disease-relevant immunologic processes. Using the simian immunodeficiency virus/rhesus macaque model of AIDS, we explored how personality (Sociability) and genotype (serotonin transporter promoter) independently interact with social context (Stable or Unstable social conditions) to influence behavioral expression, plasma cortisol concentrations, SIV-specific IgG, and expression of genes associated with Type I interferon early in infection. SIV viral RNA set-point was strongly and negatively correlated with survival as expected. Set-point was also associated with expression of interferon-stimulated genes, with CXCR3 expression, and with SIV-specific IgG titers. Poorer immune responses, in turn, were associated with display of sustained aggression and submission. Personality and genotype acted independently as well as in interaction with social condition to affect behavioral responses. Together, the data support an "interactionist" perspective [Eysenck, H.J., 1991. Personality, stress and disease: an interactionist perspective. Psychol. Inquiry 2, 221-232] on disease. Given that an important goal of HIV treatment is to maintain viral set-point as low as possible, our data suggest that supplementing anti-retroviral therapy with behavioral or pharmacologic modulation of other aspects of an organism's functioning might prolong survival, particularly among individuals living under conditions of threat or uncertainty.

Figure 1

An interactionist model on disease, which shows expected relationships between host factors, social condition, coping responses, measures of endocrine and immune function, and disease outcome.

Figure 2

Schematic of experimental design.

Figure 3

Significant relationships among variables for animals in Unstable social conditions (left panels), and nonsignificant relationships for animals in Stable social conditions (right panels). In the Unstable condition, animals that displayed more submissive behavior during the first two weeks p.i. a) were lower in Sociability, b) had greater expression of interferon stimulated genes (ISG), and d) had lower basal plasma cortisol concentrations at Week 4 p.i. Sociability was also directly related to ISG mRNA expression (c).

Figure 4

At six weeks post-inoculation, genotype for the rhesus serotonin transporter promoter polymorphism is associated with number of biweekly periods that individuals displayed aggression.