Inflammatory state augments orbitofrontal cortex responses to negative pictures

While there have been several interesting studies reporting associations between inflammatory state and clinical depression (see, for instance, Irwin & Miller 2007), the potential underlying neural mechanisms have remained largely unexplored. In a recent study by Jennifer Kullmann et al. published in Human Brain Mapping (currently available online as a pre-publication "early view" article), healthy volunteers were given an injection of either saline or bacterial lipopolysaccharide (0.4 ng/kg) that caused an acute inflammatory reaction, including rise in body temperature, and increase in plasma levels of pro- and anti-inflammatory cytokines and cortisol. The effects of acute inflammation on brain responses to negative-valence aversive pictures vs. emotionally neutral pictures was then investigated using functional magnetic resonance imaging.

The authors observed that the activation to presentation of negative-valence pictures of especially right-hemisphere inferior orbitofrontal cortex (at lower statistical threshold also several other brain structures) was augmented during acute inflammatory response. Given that the orbitofrontal cortex has been in previous studies associated with emotion-regulation (e.g., inhibition of amygdala activity during suppression of emotional responses) and production of affective states in response to emotional stimuli, the authors interpreted their findings as indicating that the subjects were more susceptible to the emotion-inducing effects of the aversive pictorial stimuli during the peripheral inflammatory response. These findings are highly interesting as they disclose a potential mechanism through which inflammatory state modulates affective processing and may thus play a role in the development of mood disorders.

Curiously, a recent Cochrane meta analysis indicated that mirtazapine, an older antidepressant that has antihistaminergic effects (that reduce inflammatory response) in addition to it's effects on various 5-HT receptors, was more effective in the treatment of clinical depression than the newer selective serotonin re-uptake inhibitors (Watanabe N et al. 2011). There are also findings suggesting that co-administration of an anti-inflammatory drug with selective serotonin re-uptake inhibitors improves treatment outcome in patients suffering from clinical depression (Akhondzadeh S et al. 2009). Overall, these findings highlight the important principle that the brain, and thus disorders of brain function, is never quite separate from the rest of the body (or the environment), but rather that brain function is significantly intertwined with bodily functions.

References:

Akhondzadeh S, Jafari S, Raisi F, Nasehi AA, Ghoreishi A, Salehi B, Mohebbi-Rasa S, Raznahan M, Kamalipour A. Clinical trial of adjunctive celecoxib treatment in patients with major depression: a double blind and placebo controlled trial. Depression and Anxiety (2009) 26: 607-611. http://dx.doi.org/10.1002/da.20589

Irwin MR, Miller AH. Depressive disorders and immunity: 20 years of progress and discovery. Brain, Behavior, and Immunity (2007) 21: 374-383. http://dx.doi.org/10.1016/j.bbi.2007.01.010

Kullmann JS, Grigoleit JS, Lichte P, Kobbe P, Rosenberger C, Banner C, Wolf OT, Engler H, Oberbeck R, Elsenbruch S, Bingel U, Forsting M, Gizewski ER, Schedlowski M. Neural response to emotional stimuli during experimental human endotoxemia. Human Brain Mapping (2012). http://dx.doi.org/10.1002/hbm.22063

Watanabe N, Omori IM, Nakagawa A, Cipriani A, Barbui C, Churchill R, Furukawa TA. Mirtazapine versus other antidepressive agents for depression. Cochrane Database of Systematic Reviews (2011) 12. Art. No.: CD006528. http://dx.doi.org/10.1002/14651858.CD006528.pub2