Personality traits in psychosis and psychosis risk linked to TSPO expression: a neuroimmune marker

Abstract

Personality has been correlated with differences in cytokine expression, an indicator of peripheral inflammation; however, the associations between personality and central markers of inflammation have never been investigated in vivo in humans. Microglia are the resident macrophages of the central nervous system, and the first responders to tissue damage and brain insult. Microglial activation is associated with elevated expression of translocator protein 18kDa (TSPO), which can be imaged with positron emission tomography (PET) to quantify immune activation in the human brain. This study aimed to investigate the association between personality and TSPO expression across the psychosis spectrum. A total of 61 high-resolution [18F]FEPPA PET scans were conducted in 28 individuals at clinical high risk (CHR) for psychosis, 19 First-Episode Psychosis (FEP), and 14 healthy volunteers (HVs), and analyzed using a two-tissue compartment model and plasma input function to obtain a total volume of distribution (VT) as an index of brain TSPO expression (controlling for the rs6971 TSPO polymorphism). Personality was assessed using the Revised NEO Personality Inventory (NEO-PI-R). We found TSPO expression to be specifically associated with neuroticism. A positive association between TSPO expression and neuroticism was found in HVs, in contrast to a nonsignificant, negative association in CHR and significant negative association in FEP. The TSPO-associated neuroticism trait indicates an unexplored connection between neuroimmune activation and personality that varies across the psychosis spectrum.

Connecting quantitatively derived personality–psychopathology models and neuroscience

“…The articles included in this special issue offer excellent examples of research on the interrelations between neural systems and quantitative, dimensional models of personality-psychopathology. Empirical studies in this issue used a variety of neuroscientific methodologies, spanning functional magnetic resonance imaging (fMRI; Hyatt et al, 2020;Neumann, 2020;Sun et al, 2020;Weiss et al, 2021), electrophysiology (event-related potentials [ERPs]; Palumbo et al, 2020;Suzuki, Novak, Ait Oumeziane, Foti, & Samuel, 2020), positron emission tomography (PET; Gerritsen et al, 2020), and structural neuroimaging (Lahey et al, 2020). A number of quantitative methodologies were also employed, including structural equation modeling (SEM; e.g., Neumann, 2020) and "psychoneurometric" operationalizations (e.g., Palumbo et al, 2020).…”

“…In an in-vivo neuroimaging study, Gerritsen et al (2020) used PET to quantify neuroimmune activation and personality traits across the psychosis spectrum in individuals with clinical high risk of psychosis, first-episode psychosis, and controls (total n = 61). Expression of a marker of central inflammation (translocator protein 18 kDa) was specifically associated with neuroticism, but with different signs across the three groups.…”