5-HT2A receptor density is decreased in the at-risk mental state.
BACKGROUND
Current perspectives on the pathophysiology of schizophrenia direct attention to serotonergic (serotonin, 5-HT) dysregulation in the prodrome or at-risk mental state (ARMS).


OBJECTIVE
To study the cerebral 5-HT(2A) receptor (5-HT(2A)R) in the ARMS with [(18)F]altanserin positron emission tomography (PET) and a bolus-infusion paradigm.


METHODS
We quantified the spatial distribution of 5-HT(2A)R binding potential (BP(1)') in never-medicated subjects assigned to early (n = 6) and late (n = 8) prodromal states of schizophrenia relative to healthy controls (n = 21). Five single nucleotide polymorphisms (SNPs) in the 5-HT(2A)R-encoding gene (HTR2A; 13q14-21) were genotyped to control for a potential bias in BP(1)' due to between-group differences in genotype distributions.


RESULTS
Group comparisons of partial-volume corrected PET data by statistical parametric mapping and confirmatory volume of interest analysis yielded a dissemination of BP(1)' decreases consistent with increasing levels of risk. An additional decrease in caudate BP(1)' was present in subjects who subsequently converted to first-episode psychosis (n = 5), but absent in non-converters (n = 9). Between-group differences were not confounded by a differential distribution of SNP genotypes.


CONCLUSIONS
These results suggest a progressive reduction of cortical 5-HT(2A)R density as a surrogate biological measure of increased risk for schizophrenia, irrespective of conversion. Progressive reductions of subcortical 5-HT(2A)R density could provide an indicator of illness activity and help to predict imminent conversion to schizophrenia. Moreover, our findings substantiate the rationale for establishing a phase-specific psychopharmacological intervention in the ARMS that addresses the serotonergic component of vulnerability to schizophrenia.
Hurlemann
René
R
Brain Imaging Center West, Research Center Juelich, 52425, Juelich, Germany. renehurlemann@gmx.de
Matusch
Andreas
A
Kuhn
Kai-Uwe
KU
Berning
Julia
J
Elmenhorst
David
D
Winz
Oliver
O
Kolsch
Heike
H
Zilles
Karl
K
Wagner
Michael
M
Maier
Wolfgang
W
Bauer
Andreas
A
D000328:Adult; D001921:Brain / Q000000981:diagnostic imaging*; D001931:Brain Mapping; D002540:Cerebral Cortex / Q000000981:diagnostic imaging; D004292:Dominance, Cerebral / Q000502:physiology; D042241:Early Diagnosis; D005260:Female; D005462:Fluorine Radioisotopes; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007650:Ketanserin / Q000031:analogs & derivatives; D008297:Male; D049268:Positron-Emission Tomography; D011569:Psychiatric Status Rating Scales; D044402:Receptor, Serotonin, 5-HT2A / Q000235:genetics*; D012559:Schizophrenia / Q000000981:diagnostic imaging / Q000235:genetics*; D012569:Schizotypal Personality Disorder / Q000000981:diagnostic imaging / Q000235:genetics*
D005462:Fluorine Radioisotopes; D005819:Genetic Markers; D044402:Receptor, Serotonin, 5-HT2A; C071983:altanserin; D007650:Ketanserin