No association between serotonin 4 receptor brain binding and personality trait Neuroticism - A positron emission tomography study in depressed patients and healthy individuals

Serotonergic neurotransmission has been linked to normal personality functioning, including the five-factor personality trait Neuroticism, which is a robust risk factor for Major Depressive Disorder (MDD). The serotonin 4 receptor (5-HT₄R) is involved in regulating mood and has been shown to be altered in patients with MDD and map onto anxiety levels and memory performance. We here evaluate the link between 5-HT₄R levels and Neuroticism in patients with MDD and replicate a previous study in healthy individuals. Neuroticism scores and brain 5-HT₄R binding potential assessed with [¹¹C]SB207145 positron emission tomography (PET) imaging were available from the CIMBI database for 63 unmedicated patients with MDD (48 W) and 120 healthy individuals (67 W). We investigated the association between Neuroticism and 5-HT₄R binding in six regions of interest: frontal cortex, anterior cingulate cortex, amygdala, hippocampus, neostriatum, and thalamus for each group. There was no association between regional 5-HT₄R binding and total Neuroticism score in patients or healthy individuals (all p_adj > 0.99), although post hoc analyses indicated that in patients, Neuroticism facets of Depression (p_adj = 0.046) and Impulsivity (p_adj = 0.009) were positively associated with thalamic and frontal 5-HT₄R binding respectively. While trait Neuroticism does not appear to be associated with brain 5-HT₄R in either patients with MDD or healthy individuals, we found evidence that the facets Depression and Impulsiveness may be linked to regional 5-HT₄R levels in patients.