Between Temperament and Psychopathology: Examples from Neuropharmacological Challenge Tests in Healthy Humans.

Background: This paper tries to demonstrate that the questionnaire-based continuum between temperament traits and psychopathology can also be shown on the biochemical level. A common feature is the incapacity to adapt to external demands, as demonstrated by examples of disturbed hormone cycles as well as neurotransmitter (TM) responses related to affective and impulse control disorders.

Methods: Pharmacological challenge tests performed in placebo-controlled balanced crossover experiments with consecutive challenges by serotonin (5-HT), noradrenaline (NA), and dopamine (DA) agonistic drugs were applied to healthy subjects, and individual responsivities of each TM system assessed by respective cortisol and prolactin responses were related to questionnaire-based facets of depressiveness and impulsivity, respectively.

Results: The depression-related traits "Fatigue" and "Physical Anhedonia" were characterized by low and late responses to DA stimulation as opposed to "Social Anhedonia," which rather mirrored the pattern of schizophrenia. Reward-related and premature responding-related impulsivity represented by high scores on "Disinhibition" and "Motor Impulsivity," respectively, as well as the questionnaire-based components of attention deficit hyperactivity disorder, "Cognitive" and "Motor Impulsivity," could be discriminated by their patterns of DA/NA responses. 5-HT responses suggested that instead of the expected low availability of 5-HT claimed to be associated with impulse control disorders, low NA responses indicated lack of inhibition in impulsivity and high NA responses in depression-related "Anhedonia" indicated suppression of approach motivation.

Conclusions: In spite of the flaws of pharmacological challenge tests, they may be suitable for demonstrating similarities in TM affinities between psychopathological disturbances and respective temperament traits and for separating sub-entities of larger disease spectra.