Genetic polymorphisms of serotonergic and dopaminergic neurotransmission differentially affect neurofunctional subsystems of working memory

In schizophrenia but also in other psychiatric disorders, e.g. in bipolar affective disorder and in attention-deficit/hyperactivity disorder, working memory impairments are considered to be core deficits and potential endophenotypic markers. Important to note, working memory is not a unitary system but comprises a set of different neurofunctional systems. Neuropharmacological studies suggest that these neurofunctional systems may be differentially modulated by serotonergic and dopaminergic neurotransmission. In the present study, we investigated the influence of genetic polymorphisms with direct impact on either the serotonergic or the dopaminergic system on the functional capacities of brain systems underlying verbal and visuospatial working memory. Consistent with our hypothesis, the DAT1 polymorphism had a significant and selective effect on visuospatial working memory capacity whereas presence of the “short“ allele of the 5HTT polymorphism significantly (and selectively) affected verbal working memory capacity. These findings provide evidence that genetic polymorphisms of serotonergic and dopaminergic neurotransmission differentially affect neurofunctional subsystems of working memory, and this may have implications for further systematic study of the pathophysiology of psychoses and for the development of individualized therapies.