Fast sleep spindle reduction in schizophrenia and healthy first-degree relatives: association with impaired cognitive function and potential intermediate phenotype

Abstract

Several studies in patients with schizophrenia reported a marked reduction in sleep spindle activity. To investigate whether the reduction may be linked to genetic risk of the illness, we analysed sleep spindle activity in healthy volunteers, patients with schizophrenia and first-degree relatives, who share an enriched set of schizophrenia susceptibility genes. We further investigated the correlation of spindle activity with cognitive function in first-degree relatives and whether spindle abnormalities affect both fast (12-15 Hz) and slow (9-12 Hz) sleep spindles. We investigated fast and slow sleep spindle activity during non-rapid eye movement sleep in a total of 47 subjects comprising 17 patients with schizophrenia, 13 healthy first-degree relatives and 17 healthy volunteers. Groups were balanced for age, gender, years of education and estimated verbal IQ. A subsample of relatives received additional testing for memory performance. Compared to healthy volunteers, fast spindle density was reduced in patients with schizophrenia and healthy first-degree relatives following a pattern consistent with an assumed genetic load for schizophrenia. The deficit in spindle density was specific to fast spindles and was associated with decreased memory performance. Our findings indicate familial occurrence of this phenotype and thus support the hypothesis that deficient spindle activity relates to genetic liability for schizophrenia. Furthermore, spindle reductions predict impaired cognitive function and are specific to fast spindles. This physiological marker should be further investigated as an intermediate phenotype of schizophrenia. It could also constitute a target for drug development, especially with regard to cognitive dysfunction.

Schizotypal traits are associated with sleep spindles and rapid eye movement in adolescence

“…Even though the effect size is small, our findings suggest that even in healthy adolescents, schizotypal traits may have a neural basis. Although a recent study (Schilling et al., ) has shown reduced spindle activity in first‐order relatives of schizophrenia patients, our study extends this observation further by showing that even among healthy, low‐risk populations the associations between schizotypal traits and lowered spindle activity can be detected.…”

Genetic risk factors for schizophrenia associate with sleep spindle activity in healthy adolescents

“…The amplitude, spindle duration, intensity (spindle duration multiplied by spindle amplitude) and density (number of spindles per 60 s) were measured separately for central and frontal derivations and for fast and slow spindles, using the averages between the left and right hemisphere derivations, respectively. In our sample, sleep spindle density is somewhat lower than in other studies using automatic spindle detection algorithms (Manoach et al, ; Schilling et al, ) because of restriction of sleep spindle duration and strict impedance validity control. A complete description of the spindle detection protocol can be found in our other publication (Merikanto et al, ).…”

Investigation of sleep spindle activity and morphology as predictors of neurocognitive functioning in medicated patients with schizophrenia

“…In this study, we chose to incorporate oscillation frequency in the model to investigate whether the frequency of sleep spindles was associated with cognitive functioning. We supplemented this approach with examination of the association between fast sleep spindle density and slow sleep spindle density because recent data indicate that fast spindles might have more importance in relation to cognitive functioning (Schilling et al., ).…”