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Schlagwörter:
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Zusammenfassung:
Recent genome-wide association studies have identified MAD1L1 (mitotic
arrest deficient-like I) as a susceptibility gene for bipolar disorder
and schizophrenia. The minor allele of the single-nucleotide
polymorphism (SNP) rs11764590 in MAD1L1 was associated with bipolar
disorder. Both diseases, bipolar disorder and schizophrenia, are linked
to functional alterations in the reward system. We aimed at
investigating possible effects of the MAD1L1 rs11764590 risk allele on
reward systems functioning in healthy adults. A large homogenous sample
of 224 young (aged 18-31 years) participants was genotyped and underwent
functional magnetic resonance imaging (fMR1). All participants performed
the 'Desire-Reason Dilemma' paradigm investigating the neural correlates
that underlie reward processing and active reward dismissal in favor of
a long-term goal. We found significant hypoactivations of the ventral
tegmental area (VTA), the bilateral striatum and bilateral frontal and
parietal cortices in response to conditioned reward stimuli in the risk
allele carriers compared with major allele carriers. In the dilemma
situation, functional connectivity between prefrontal brain regions and
the ventral striatum was significantly diminished in the risk allele
carriers. Healthy risk allele carriers showed a significant deficit of
their bottom-up response to conditioned reward stimuli in the bilateral
VTA and striatum. Furthermore, functional connectivity between the
ventral striatum and prefrontal areas exerting top-down control on the
mesolimbic reward system was reduced in this group. Similar alterations
in reward processing and disturbances of prefrontal control mechanisms
on mesolimbic brain circuits have also been reported in bipolar disorder
and schizophrenia. Together, these findings suggest the existence of an
intermediate phenotype associated with MAD1L1.
