Women with multiple chemical sensitivity have increased harm avoidance and reduced 5-HT(1A) receptor binding potential in the anterior cingulate and amygdala

Abstract

Multiple chemical sensitivity (MCS) is a common condition, characterized by somatic distress upon exposure to odors. As in other idiopathic environmental intolerances, the underlying mechanisms are unknown. Contrary to the expectations it was recently found that persons with MCS activate the odor-processing brain regions less than controls, while their activation of the anterior cingulate cortex (ACC) is increased. The present follow-up study was designed to test the hypotheses that MCS subjects have increased harm avoidance and deviations in the serotonin system, which could render them intolerant to environmental odors. Twelve MCS and 11 control subjects, age 22-44, all working or studying females, were included in a PET study where 5-HT(1A) receptor binding potential (BP) was assessed after bolus injection of [(11)C]WAY100635. Psychological profiles were assessed by the Temperament and Character Inventory and the Swedish universities Scales of Personality. All MCS and 12 control subjects were also tested for emotional startle modulation in an acoustic startle test. MCS subjects exhibited significantly increased harm avoidance, and anxiety compared to controls. They also had a reduced 5-HT(1A) receptor BP in amygdala (p = 0.029), ACC (p = 0.005) (planned comparisons, significance level 0.05), and insular cortex (p = 0.003; significance level p<0.005 with Bonferroni correction), and showed an inverse correlation between degree of anxiety and the BP in the amygdala (planned comparison). No group by emotional category difference was found in the startle test. Increased harm avoidance and the observed changes in the 5-HT(1A) receptor BP in the regions processing harm avoidance provides a plausible pathophysiological ground for the symptoms described in MCS, and yields valuable information for our general understanding of idiopathic environmental intolerances.

Figure 1. Personality dimensions in TCI (raw scores) in MCS subjects and controls (Boxes represent first quartile, median and third quartile, whiskers represent values within 1.5 interquartile range, a circle is an outlier value more than 1.5 IQR from the end of the box).

Temperament dimensions: novelty seeking (NS), harm avoidance (HA), reward dependence (RD), and persistence (PS). Character dimensions: self-directedness (SD), cooperativeness (CO), self-transcendence (ST). *Hypothesis testing: one-sided p value, significance level 0.05 (HA = 0.01).

Figure 2. SSP raw scores in MCS subjects and controls (Boxes represent first quartile, median and third quartile, whiskers represent values within 1.5 interquartile range (IQR), a circle is an outlier value more than 1.5 IQR from the end of the box).

Scales: Somatic trait anxiety (SSPSTA), Psychic trait anxiety (SSPPSTA), Stress susceptibility (SSPSS), Lack of assertiveness (SSPLA), Impulsiveness (SSPI), Adventure seeking (SSPAS), Detachment (SSPD), Social desirability (SSPSD), Embitterment (SSPE), Trait irritability (SSPTI), Mistrust (SSPM), Verbal trait aggression (SSPVTA) and Physical trait aggression (SSPPHTA). *Hypothesis testing: one-sided p value, significance level 0.05 (SSPSTA p = 0.04, SSPPSTA p = 0.006).

Figure 3. Summated positron emission tomography (PET) images representing average regional uptake of [11C] WAY100635 15–63 minutes after i.v. injection of the ligand in a control woman (left) and a MCS woman (right).

The PET images show lower [11C] WAY100635 uptake in regions of amygdale (upper raw), anterior cingulate and insular cortex (lower raw) in MCS woman compared to control woman. The scale (nCi/cc) applies to both subjects, and the color coding was adjusted for the difference in injected radioactivity.

Figure 4. Startle magnitude (mean) during habituation before start of test during picture display.

Habituation is more pronounced in the MCS group (p = 0.006). A.U. =  Arbitrary units.