Women with Multiple Chemical Sensitivity Have Increased Harm Avoidance and Reduced 5-HT1A 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-HT1A receptor binding potential (BP) was assessed after bolus injection of [11C]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-HT1A 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-HT1A 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.

Left and Right Amygdala - Mediofrontal Cortical Functional Connectivity Is Differentially Modulated by Harm Avoidance

“…Within the vmPFC, more in particular the sgACC, this area is related to arousal processes and implicated in a corticolimbic neurocircuit associated with ‘visceromotor’ functions playing an important role in modulating affect, such as sadness activation and ruminative thought patterns [47]. This functional amygdala - sgACC coupling has also been reported in female anxiety patients scoring higher than controls on HA [48]. However, our findings seem to be in disagreement with the study of Kim and colleagues [13] where reverse amygdala –vmPFC FC results were reported in relation to higher scores on the State and Trait Anxiety Inventory self-report questionnaires (STAI-S, STAI-T [49]).…”

Relationship between Personality Traits and Endogenous Analgesia: The Role of Harm Avoidance

“…However, our findings revealed an opposite direction of associations in which higher HA was correlated with less‐efficient CPM responses. Previous studies indeed reported that high activity in the serotonergic system characterized individuals with high HA, however, others did not find these relationships . Furthermore, one study reported findings in the opposite direction: low basal levels of central serotonin were related to higher HA scores .…”

“…Previous studies indeed reported that high activity in the serotonergic system characterized individuals with high HA, 41-44 however, others did not find these relationships. [45][46][47] Furthermore, one study reported findings in the opposite direction: low basal levels of central serotonin were related to higher HA scores. 48 Additionally, use of tricyclic antidepressants (TCA) or selective serotonin reuptake inhibitors (SSRI) was followed by reduction in HA scores in studies of patients with depression and generalized anxiety disorders.…”

Involvement of Subcortical Brain Structures During Olfactory Stimulation in Multiple Chemical Sensitivity

“…The relative FDG uptake increase found in the present study in MCS patients OLF at rest when compared to HC is in line with those theories assessing CNS hypereactivity and limbic kindling as key nodes in pathophysiological underpinnings of MCS (Bascom et al 1997;Winder 2002). Agreeing with those arguments suggesting both attention bias and over-ridden neural behaviour to chemical exposure in MCS patients (Andersson et al 2009;Witthöft et al 2006;Winder 2002), this finding could depict for the first time a subcortical resting state correlate of hyper-sensitized neural structure before reaching those secondary/associative olfactory ones (such as OFC, PHG) in which emotional/affective/over-attentional processes could be residing (Qureshy et al 2000;Kroupi et al 2012;Keller 2011) and secondary MCS disease-related processes could be nestled (Hillert et al 2007;Orriols et al 2009;Hillert et al 2013). Further, these data appear more relevant especially when merged with the wider FDG uptake found at rest in frontal-prefrontal cortex and ACC in the same sample of HC subjects with respect to the same sample of MCS patients (Chiaravalloti et al 2015).…”