Inter-individual differences in the impulsive/compulsive dimension: deciphering related dopaminergic and serotonergic metabolisms at rest.
Françoise Dellu-HagedornMarion RivalanAurélie FitoussiPhilippe De DeurwaerderePublished in: Philosophical transactions of the Royal Society of London. Series B, Biological sciences (2019)
Several impulse control disorders such as ADHD, mania, personality disorders or substance abuse share common behavioural traits, like impulsiveness, risk-taking or inflexible behaviour. These disorders are treated with drugs targeting dopamine (DA) and/or serotonin (5-HT). However, the patient's monoamine imbalance that these neurotransmitters compensate is unclear. This study aims to investigate the patterns of DA and 5-HT metabolisms at rest within selected brain regions related to inter-individual variability in six main components of impulsivity/compulsivity (anticipatory hyperactivity, premature responses, delay discounting, risk-taking, perseveration, flexibility). Rats with adaptive and highly inadaptive behaviours were identified in each task and a sensitive biochemical approach allowed mapping of post-mortem endogenous monoamine tissue content in 20 brain areas. Distinct patterns of 5-HT and DA metabolisms were revealed according to the behavioural traits. Except for hyperactive responses, lower control of actions was mainly associated with a lower DA or 5-HT metabolism in prefrontal and/or subcortical areas (i.e. in orbitofrontal cortex (DA), amygdala and anterior cingulate cortex (5-HT) for inflexible and risk-prone rats). Our results reveal the complex nature of behavioural traits related to impulse control disorders through their associated monoaminergic networks at rest, paving the way for understanding the link between mental disorders and drug therapeutic actions.This article is part of the theme issue 'Diverse perspectives on diversity: multi-disciplinary approaches to taxonomies of individual differences'.
Keyphrases
- functional connectivity
- resting state
- genome wide
- white matter
- working memory
- attention deficit hyperactivity disorder
- bipolar disorder
- emergency department
- autism spectrum disorder
- obsessive compulsive disorder
- single cell
- gene expression
- mass spectrometry
- dna methylation
- metabolic syndrome
- drug induced
- brain injury
- newly diagnosed
- cerebral ischemia