PET provides a link between the genetic endowment and higher brain functions

Lars Farde

Department of Clinical Neuroscience, Psychiatry section, Karolinska Institute and Hospital, Stockholm


Research now benefits from new PET-based strategies to reveal the role of neurotransmission systems in relation to personality traits, cognitive functions and neuropsychiatric disorders. The strategies will be exemplified from research on the dopamine system which was early established during phylogenesis. The dopamine system has an important role in motor and endocrine functions. Later lines of research indicate that the dopamine system is involved also in higher brain functions.

The dopamine system and human psychopharmacology

Pharmacological drug challenges is a classical approach to reveal the functional correlates of a neurotransmission system. In man, the effect of antipsychotic drugs can thus provide clues to the role of the dopamine system in the human brain. Using PET, it has been well established that schizophrenic patients responding to classical neuroleptics have a uniformly high D2-dopamine receptor occupancy. In healthy subjects and patients there is a high risk of extrapyramidal side effects (EPS) at a D2-receptor occupancy above 80%. The EPSs includes akathisia, a syndrome with motor restlessness  subjective unease or distress and observable as well as cases of irritability and violence. The many faces of akathisia and its quantitative relation to high occupancy of D2-receptors corroborates a role for the dopamine system not only in motor functions but also in relation to emotional functions.

The dopamine system and personality traits

The concept of personality refers to stable behavioral patterns that are established early in life. The dopaminergic neurotransmission system has been given an important role in psychobiological models of personality. In a PET-study, the density of the D2-dopamine receptor subtype in brain varied more than two-fold in normal subjects. The D2-density correlated strongly with detachment and irritability, two of the fifteen traits that were assessed using the Karolinska Scales of Personality. Detachment is a trait that includes lack of closeness and warmth in personal relations and resembles negative symptoms of schizophrenia. The finding illustrates a new research strategy. Neuroreceptor density can be viewed as a directly accessible biochemical link in the chain of events that relate genetic structure to human personality traits. Indeed, associations between polymorphisms in the dopamine D2 receptor gene and D2-density has more recently been demonstrated.

The dopamine system and cognitive functions

Preliminary studies in controls and patients with Huntington´s disease emphasize a role for the dopamine system in cognitive functions such as episodic memory and perceptual speed. Interestingly, a decline in these two functions has consistently been reported in normal aging. Several recent study have examined  the influence of losses in dopaminergic function on age-related cognitive deficits. A consistent finding is that D2 receptor binding is a more important factor than age in accounting for variation in cognitive performance across the adult life span. It can be concluded that changes in dopaminergic neurotransmission play an important role in aging-related cognitive decline.