Fast sleep spindle density is associated with rs4680 (Val108/158Met) genotype of catechol-O-methyltransferase (COMT).

Study Objectives: Sleep spindles are a hallmark of NREM stage 2 sleep. Fast sleep spindles correlate with cognitive functioning and are reduced in schizophrenia. Although spindles are highly genetically determined, distinct genetic mechanisms influencing sleep spindle activity have not been identified so far. Spindles are generated within a thalamocortical network. Dopaminergic neurotransmission modulates activity within this network and importantly depends on activity of catechol-O-methyltransferase (COMT). We aimed at testing whether the common functional rs4680 (Val108/158Met) polymorphism of COMT modulates fast spindle activity in healthy participants.

Methods: In 150 healthy participants (93 women, 57 men; mean age 30.9 ± 11.6 years) sleep spindle density was analyzed during the second of two nights of polysomnography. We investigated the effect of the COMT Val108/158Met genotype on fast spindle density in whole-night NREM sleep stages N2 and N3.

Results: As predicted, higher Val allele dose correlates with reduced fast spindle density. Additional exploratory analysis of the effect of COMT genotype revealed that slow spindle density in heterozygote participants was lower than that of both homozygote groups. Morphological characteristics of fast and slow spindles did not show significant differences between genotypes. COMT genotype had also no significant effect on measures of general sleep quality.

Conclusions: This is the first report of a distinct gene effect on sleep spindle density in humans. As variation in the COMT Val108/158Met polymorphism is associated with differential expression of fast spindles in healthy participants, genetically determined dopaminergic neurotransmission may modulate spindle oscillations during NREM sleep.

Clinical Trial Registration: DRKS00008902.