Reduced sleep spindle density in early onset schizophrenia: A preliminary finding

Tesler, Noemi; Franscini, Maurizia; Jenni, Oskar G.; Walitza, Susanne; Huber, Reto

doi:10.1016/j.schres.2015.04.042

Cited by 35 publications

(28 citation statements)

References 10 publications

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“…Reduced spindle activity also correlates with increased positive symptom severity in medicated early onset SZ spectrum disorder (77) and in some (31, 75) but not all (72) studies of chronic medicated SZ. In APD-naïve early course SZ, however, reduced spindle density correlated with decreased positive symptoms (80).…”

Section: Reduced Spindles Are Associated With Impaired Cognition and mentioning

confidence: 96%

“…A growing literature, however, reports marked reductions of spindle activity In chronic medicated SZ (31, 72-76) and medicated adolescents with early onset SZ spectrum disorder (77). Importantly, with the exception of increased sleep onset latency in two studies (74, 75), the spindle deficit occurred in the context of normal sleep architecture and quality ( e.g.…”

Section: Sleep Spindle Deficit In Szmentioning

confidence: 99%

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Reduced Sleep Spindles in Schizophrenia: A Treatable Endophenotype That Links Risk Genes to Impaired Cognition?

Manoach

Pan

Purcell

et al. 2016

Biological Psychiatry

184

155

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Although schizophrenia is defined by waking phenomena, abnormal sleep is a common feature. In particular, there is accumulating evidence of a sleep spindle deficit. Sleep spindles, a defining thalamocortical oscillation of non-rapid eye movement Stage 2 sleep, correlate with IQ and are thought to promote long-term potentiation and enhance memory consolidation. Here we review evidence that reduced spindle activity in schizophrenia is an endophenotype that impairs sleep-dependent memory consolidation, contributes to symptoms and is a novel treatment biomarker. Studies showing that spindles can be pharmacologically enhanced in schizophrenia and that increasing spindles improves memory in healthy individuals suggest that treating spindle deficits in schizophrenia may improve cognition. Spindle activity is highly heritable and recent large-scale genome-wide association studies have identified schizophrenia risk genes that may contribute to spindle deficits and illuminate their mechanisms. For example, the schizophrenia risk gene CACNA1I encodes a calcium channel that is abundantly expressed in the thalamic spindle generator and plays a critical role in spindle activity in a mouse knockout. Future genetic studies of animals and humans can delineate the role of this and other genes in spindles. Such cross-disciplinary research, by forging empirical links in causal chains from risk genes to proteins and cellular functions, through to endophenotypes, cognitive impairments, symptoms and diagnosis, has the potential to advance the mechanistic understanding, treatment and prevention of schizophrenia. This review highlights the importance of deficient sleep-dependent memory consolidation among the cognitive deficits of schizophrenia and implicates reduced sleep spindles as a potentially treatable mechanism.

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Section: Reduced Spindles Are Associated With Impaired Cognition and mentioning

confidence: 96%

Section: Sleep Spindle Deficit In Szmentioning

confidence: 99%

Reduced Sleep Spindles in Schizophrenia: A Treatable Endophenotype That Links Risk Genes to Impaired Cognition?

Manoach

Pan

Purcell

et al. 2016

Biological Psychiatry

184

155

View full text Add to dashboard Cite

show abstract

“…A decrease in spindle density and amplitude was also seen in asymptomatic first-degree relatives of schizophrenia patients, which further indicate that spindle impairments are unrelated to antipsychotic medication and may be specific for schizophrenia, though replication in larger samples of patients is required. Of note, reduced sleep spindle density has also been found in nine adolescent meeting criteria for early onset schizophrenia compared to healthy controls (Tesler et al, 2015). …”

Section: Spindle Deficits Have Been Reported In Schizophrenia Includmentioning

confidence: 99%

Reduced sleep spindle activity point to a TRN-MD thalamus-PFC circuit dysfunction in schizophrenia

Ferrarelli

Tononi

2017

Schizophrenia Research

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Sleep disturbances have been reliably reported in patients with schizophrenia, thus suggesting that abnormal sleep may represent a core feature of this disorder. Traditional electroencephalographic studies investigating sleep architecture have found reduced deep Non-Rapid Eye Movement (NREM) sleep, or slow wave sleep (SWS), and increased REM density. However, these findings have been inconsistently observed, and have not survived meta-analysis. By contrast, several recent EEG studies exploring brain activity during sleep have established marked deficits in sleep spindles in schizophrenia, including first-episode and early–onset patients, compared to both healthy and psychiatric comparison subjects. Spindles are waxing and waning, 12–16 Hz NREM sleep oscillations that are generated within the thalamus by the thalamic reticular nucleus (TRN), and are then synchronized and sustained in the cortex. While the functional role of sleep spindles still needs to be fully established, increasing evidence has shown that sleep spindles are implicated in learning and memory, including sleep dependent memory consolidation, and spindle parameters have been associated to general cognitive ability and IQ. In this article we will review the EEG studies demonstrating sleep spindle deficits in patients with schizophrenia, and show that spindle deficits can predict their reduced cognitive performance. We will then present data indicating that spindle impairments point to a TRN-MD thalamus-prefrontal cortex circuit deficit, and discuss about the possible molecular mechanisms underlying thalamo-cortical sleep spindle abnormalities in schizophrenia.

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“…In addition, it is possible that the differences could reflect maladaptive repetitive thinking. A smaller study found that although there were no differences in overall sleep efficiency or sleep architecture, sleep spindle density differed between adolescents with and without early onset schizophrenia (Tesler et al, 2015). The authors discussed how spindle density may be a promising marker to aid in the diagnosis of early onset schizophrenia in adolescents.…”

Section: Critical Periods Of Development?mentioning

confidence: 97%

Future Directions in Sleep and Developmental Psychopathology

Meltzer

2016

Journal of Clinical Child & Adolescent Psychology

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Reduced sleep spindle density in early onset schizophrenia: A preliminary finding

Cited by 35 publications

References 10 publications

Reduced Sleep Spindles in Schizophrenia: A Treatable Endophenotype That Links Risk Genes to Impaired Cognition?

Reduced Sleep Spindles in Schizophrenia: A Treatable Endophenotype That Links Risk Genes to Impaired Cognition?

Reduced sleep spindle activity point to a TRN-MD thalamus-PFC circuit dysfunction in schizophrenia

Future Directions in Sleep and Developmental Psychopathology

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