A quantitative electrophysiological biomarker of duplication 15q11.2-q13.1 syndrome

Joel Frohlich, Damla Senturk, Vidya Saravanapandian, Peyman Golshani, Lawrence Reiter, Raman Sankar, Ronald L. Thibert, Charlotte DiStefano, Scott Huberty, Edwin H. Cook, Shafali S. Jeste

Research output: Contribution to journalArticle

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Abstract

Background Duplications of 15q11.2-q13.1 (Dup15q syndrome) are highly penetrant for autism spectrum disorder (ASD). A distinct electrophysiological (EEG) pattern characterized by excessive activity in the beta band has been noted in clinical reports. We asked whether EEG power in the beta band, as well as in other frequency bands, distinguished children with Dup15q syndrome from those with non-syndromic ASD and then examined the clinical correlates of this electrophysiological biomarker in Dup15q syndrome. Methods In the first study, we recorded spontaneous EEG from children with Dup15q syndrome (n = 11), age-and-IQ-matched children with ASD (n = 10) and age-matched typically developing (TD) children (n = 9) and computed relative power in 6 frequency bands for 9 regions of interest (ROIs). Group comparisons were made using a repeated measures analysis of variance. In the second study, we recorded spontaneous EEG from a larger cohort of individuals with Dup15q syndrome (n = 27) across two sites and examined age, epilepsy, and duplication type as predictors of beta power using simple linear regressions. Results In the first study, spontaneous beta1 (12-20 Hz) and beta2 (20-30 Hz) power were significantly higher in Dup15q syndrome compared with both comparison groups, while delta (1-4 Hz) was significantly lower than both comparison groups. Effect sizes in all three frequency bands were large (|d| > 1). In the second study, we found that beta2 power was significantly related to epilepsy diagnosis in Dup15q syndrome. Conclusions Here, we have identified an electrophysiological biomarker of Dup15q syndrome that may facilitate clinical stratification, treatment monitoring, and measurement of target engagement for future clinical trials. Future work will investigate the genetic and neural underpinnings of this electrophysiological signature as well as the functional consequences of excessive beta oscillations in Dup15q syndrome.

Original languageEnglish (US)
Article numbere0167179
JournalPloS one
Volume11
Issue number12
DOIs
StatePublished - Dec 1 2016

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Biomarkers
Frequency bands
biomarkers
epilepsy
Analysis of variance (ANOVA)
Linear regression
oscillation
clinical trials
Monitoring
analysis of variance
Epilepsy
monitoring
autism
Linear Models
Analysis of Variance
Power (Psychology)
Clinical Trials
methodology

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Frohlich, J., Senturk, D., Saravanapandian, V., Golshani, P., Reiter, L., Sankar, R., ... Jeste, S. S. (2016). A quantitative electrophysiological biomarker of duplication 15q11.2-q13.1 syndrome. PloS one, 11(12), [e0167179]. https://doi.org/10.1371/journal.pone.0167179

A quantitative electrophysiological biomarker of duplication 15q11.2-q13.1 syndrome. / Frohlich, Joel; Senturk, Damla; Saravanapandian, Vidya; Golshani, Peyman; Reiter, Lawrence; Sankar, Raman; Thibert, Ronald L.; DiStefano, Charlotte; Huberty, Scott; Cook, Edwin H.; Jeste, Shafali S.

In: PloS one, Vol. 11, No. 12, e0167179, 01.12.2016.

Research output: Contribution to journalArticle

Frohlich, J, Senturk, D, Saravanapandian, V, Golshani, P, Reiter, L, Sankar, R, Thibert, RL, DiStefano, C, Huberty, S, Cook, EH & Jeste, SS 2016, 'A quantitative electrophysiological biomarker of duplication 15q11.2-q13.1 syndrome', PloS one, vol. 11, no. 12, e0167179. https://doi.org/10.1371/journal.pone.0167179
Frohlich J, Senturk D, Saravanapandian V, Golshani P, Reiter L, Sankar R et al. A quantitative electrophysiological biomarker of duplication 15q11.2-q13.1 syndrome. PloS one. 2016 Dec 1;11(12). e0167179. https://doi.org/10.1371/journal.pone.0167179
Frohlich, Joel ; Senturk, Damla ; Saravanapandian, Vidya ; Golshani, Peyman ; Reiter, Lawrence ; Sankar, Raman ; Thibert, Ronald L. ; DiStefano, Charlotte ; Huberty, Scott ; Cook, Edwin H. ; Jeste, Shafali S. / A quantitative electrophysiological biomarker of duplication 15q11.2-q13.1 syndrome. In: PloS one. 2016 ; Vol. 11, No. 12.
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abstract = "Background Duplications of 15q11.2-q13.1 (Dup15q syndrome) are highly penetrant for autism spectrum disorder (ASD). A distinct electrophysiological (EEG) pattern characterized by excessive activity in the beta band has been noted in clinical reports. We asked whether EEG power in the beta band, as well as in other frequency bands, distinguished children with Dup15q syndrome from those with non-syndromic ASD and then examined the clinical correlates of this electrophysiological biomarker in Dup15q syndrome. Methods In the first study, we recorded spontaneous EEG from children with Dup15q syndrome (n = 11), age-and-IQ-matched children with ASD (n = 10) and age-matched typically developing (TD) children (n = 9) and computed relative power in 6 frequency bands for 9 regions of interest (ROIs). Group comparisons were made using a repeated measures analysis of variance. In the second study, we recorded spontaneous EEG from a larger cohort of individuals with Dup15q syndrome (n = 27) across two sites and examined age, epilepsy, and duplication type as predictors of beta power using simple linear regressions. Results In the first study, spontaneous beta1 (12-20 Hz) and beta2 (20-30 Hz) power were significantly higher in Dup15q syndrome compared with both comparison groups, while delta (1-4 Hz) was significantly lower than both comparison groups. Effect sizes in all three frequency bands were large (|d| > 1). In the second study, we found that beta2 power was significantly related to epilepsy diagnosis in Dup15q syndrome. Conclusions Here, we have identified an electrophysiological biomarker of Dup15q syndrome that may facilitate clinical stratification, treatment monitoring, and measurement of target engagement for future clinical trials. Future work will investigate the genetic and neural underpinnings of this electrophysiological signature as well as the functional consequences of excessive beta oscillations in Dup15q syndrome.",
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AU - Reiter, Lawrence

AU - Sankar, Raman

AU - Thibert, Ronald L.

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N2 - Background Duplications of 15q11.2-q13.1 (Dup15q syndrome) are highly penetrant for autism spectrum disorder (ASD). A distinct electrophysiological (EEG) pattern characterized by excessive activity in the beta band has been noted in clinical reports. We asked whether EEG power in the beta band, as well as in other frequency bands, distinguished children with Dup15q syndrome from those with non-syndromic ASD and then examined the clinical correlates of this electrophysiological biomarker in Dup15q syndrome. Methods In the first study, we recorded spontaneous EEG from children with Dup15q syndrome (n = 11), age-and-IQ-matched children with ASD (n = 10) and age-matched typically developing (TD) children (n = 9) and computed relative power in 6 frequency bands for 9 regions of interest (ROIs). Group comparisons were made using a repeated measures analysis of variance. In the second study, we recorded spontaneous EEG from a larger cohort of individuals with Dup15q syndrome (n = 27) across two sites and examined age, epilepsy, and duplication type as predictors of beta power using simple linear regressions. Results In the first study, spontaneous beta1 (12-20 Hz) and beta2 (20-30 Hz) power were significantly higher in Dup15q syndrome compared with both comparison groups, while delta (1-4 Hz) was significantly lower than both comparison groups. Effect sizes in all three frequency bands were large (|d| > 1). In the second study, we found that beta2 power was significantly related to epilepsy diagnosis in Dup15q syndrome. Conclusions Here, we have identified an electrophysiological biomarker of Dup15q syndrome that may facilitate clinical stratification, treatment monitoring, and measurement of target engagement for future clinical trials. Future work will investigate the genetic and neural underpinnings of this electrophysiological signature as well as the functional consequences of excessive beta oscillations in Dup15q syndrome.

AB - Background Duplications of 15q11.2-q13.1 (Dup15q syndrome) are highly penetrant for autism spectrum disorder (ASD). A distinct electrophysiological (EEG) pattern characterized by excessive activity in the beta band has been noted in clinical reports. We asked whether EEG power in the beta band, as well as in other frequency bands, distinguished children with Dup15q syndrome from those with non-syndromic ASD and then examined the clinical correlates of this electrophysiological biomarker in Dup15q syndrome. Methods In the first study, we recorded spontaneous EEG from children with Dup15q syndrome (n = 11), age-and-IQ-matched children with ASD (n = 10) and age-matched typically developing (TD) children (n = 9) and computed relative power in 6 frequency bands for 9 regions of interest (ROIs). Group comparisons were made using a repeated measures analysis of variance. In the second study, we recorded spontaneous EEG from a larger cohort of individuals with Dup15q syndrome (n = 27) across two sites and examined age, epilepsy, and duplication type as predictors of beta power using simple linear regressions. Results In the first study, spontaneous beta1 (12-20 Hz) and beta2 (20-30 Hz) power were significantly higher in Dup15q syndrome compared with both comparison groups, while delta (1-4 Hz) was significantly lower than both comparison groups. Effect sizes in all three frequency bands were large (|d| > 1). In the second study, we found that beta2 power was significantly related to epilepsy diagnosis in Dup15q syndrome. Conclusions Here, we have identified an electrophysiological biomarker of Dup15q syndrome that may facilitate clinical stratification, treatment monitoring, and measurement of target engagement for future clinical trials. Future work will investigate the genetic and neural underpinnings of this electrophysiological signature as well as the functional consequences of excessive beta oscillations in Dup15q syndrome.

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