Subtle fluctuations in psychotic phenomena as functional states of abnormal dopamine reactivity in individuals at risk.
BACKGROUND
Subjects at increased risk for psychosis experience continuous variation in the intensity of subtle psychotic experiences in response to minor stressors. It was investigated whether this psychotic reactivity in individuals at risk for psychosis is the exophenotypic expression of an underlying endophenotype characterized by a hyperreactive dopamine (DA) system.


METHODS
First-degree relatives (n = 47) and control subjects (n = 49) were studied with the Experience Sampling Method (ESM), a structured diary technique assessing current context and psychopathology in daily life, to assess psychotic experiences in response to stress. A metabolic perturbation paradigm (administration of 2-deoxy-D-glucose inducing a mild state of glucoprivation) causing plasma elevation of homovanillic acid (HVA) was used as a proxy of DA reactivity.


RESULTS
Multilevel regression analyses revealed that the interaction between HVA reactivity and daily stress in their effect on psychotic experiences differed according to underlying vulnerability. In the first-degree relatives, underlying HVA reactivity modified the psychotic experiences to daily stress, whereas no such effect was found in control subjects.


CONCLUSIONS
These results suggest that psychotic experiences in response to minor stresses in the flow of daily life may be functional states of an underlying abnormal DA reactivity in subjects at risk to develop psychosis. The results add credence to the suggestion that abnormal DA reactivity may be part of the substrate that increases risk for psychotic symptoms in individuals at risk.
Myin-Germeys
Inez
I
Department of Psychiatry and Neuropsychology, South Limburg Mental Health Research and Teaching Network, EURON, Maastricht University, Maastricht, The Netherlands. i.germeys@sp.unimaas.nl
Marcelis
Machteld
M
Krabbendam
Lydia
L
Delespaul
Philippe
P
van Os
Jim
J
D000328:Adult; D004198:Disease Susceptibility / Q000378:metabolism; D004298:Dopamine / Q000235:genetics / Q000378:metabolism*; D005260:Female; D020022:Genetic Predisposition to Disease; D006719:Homovanillic Acid / Q000097:blood; D006801:Humans; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D011618:Psychotic Disorders / Q000235:genetics / Q000378:metabolism* / Q000523:psychology; D012044:Regression Analysis; D012307:Risk Factors; D013315:Stress, Psychological / Q000235:genetics / Q000378:metabolism*
D004298:Dopamine; D006719:Homovanillic Acid