Randomized Controlled Trial

. 2025 Sep 15:385:119448.

doi: 10.1016/j.jad.2025.119448. Epub 2025 May 19.

Exploring the link between waking gamma and sleep delta power in healthy volunteers and individuals with treatment-resistant depression

Mina Kheirkhah¹, Nadia S Hejazi², Allison C Nugent³, Jessica R Gilbert⁴, Lutz Leistritz⁵, Martin Walter⁶, Wallace C Duncan Jr⁷, David Goldman⁸, Carlos A Zarate Jr⁹

Affiliations

¹ Experimental Therapeutics and Pathophysiology Branch, Intramural Research Program, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA; Department of Psychiatry and Psychotherapy, Jena University Hospital, 07740 Jena, Germany.
² Experimental Therapeutics and Pathophysiology Branch, Intramural Research Program, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA. Electronic address: nadia.hejazi@nih.gov.
³ Magnetoencephalography Core, National Institute of Mental Health, Bethesda, MD, USA. Electronic address: nugenta@mail.nih.gov.
⁴ Experimental Therapeutics and Pathophysiology Branch, Intramural Research Program, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA. Electronic address: jessica.gilbert@nih.gov.
⁵ Institute of Medical Statistics, Computer and Data Sciences, Jena University Hospital, 07740 Jena, Germany. Electronic address: lutz.leistritz@med.uni-jena.de.
⁶ Department of Psychiatry and Psychotherapy, Jena University Hospital, 07740 Jena, Germany. Electronic address: martin.walter@med.uni-jena.de.
⁷ Experimental Therapeutics and Pathophysiology Branch, Intramural Research Program, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA. Electronic address: wduncan@mail.nih.gov.
⁸ National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD, USA. Electronic address: davidgoldman@mail.nih.gov.
⁹ Experimental Therapeutics and Pathophysiology Branch, Intramural Research Program, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA. Electronic address: zaratec@mail.nih.gov.

PMID: 40398609
PMCID: PMC12172513 (available on 2026-09-15)
DOI: 10.1016/j.jad.2025.119448

Randomized Controlled Trial

Exploring the link between waking gamma and sleep delta power in healthy volunteers and individuals with treatment-resistant depression

Mina Kheirkhah et al. J Affect Disord. 2025.

. 2025 Sep 15:385:119448.

doi: 10.1016/j.jad.2025.119448. Epub 2025 May 19.

Authors

Mina Kheirkhah¹, Nadia S Hejazi², Allison C Nugent³, Jessica R Gilbert⁴, Lutz Leistritz⁵, Martin Walter⁶, Wallace C Duncan Jr⁷, David Goldman⁸, Carlos A Zarate Jr⁹

Affiliations

¹ Experimental Therapeutics and Pathophysiology Branch, Intramural Research Program, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA; Department of Psychiatry and Psychotherapy, Jena University Hospital, 07740 Jena, Germany.
² Experimental Therapeutics and Pathophysiology Branch, Intramural Research Program, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA. Electronic address: nadia.hejazi@nih.gov.
³ Magnetoencephalography Core, National Institute of Mental Health, Bethesda, MD, USA. Electronic address: nugenta@mail.nih.gov.
⁴ Experimental Therapeutics and Pathophysiology Branch, Intramural Research Program, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA. Electronic address: jessica.gilbert@nih.gov.
⁵ Institute of Medical Statistics, Computer and Data Sciences, Jena University Hospital, 07740 Jena, Germany. Electronic address: lutz.leistritz@med.uni-jena.de.
⁶ Department of Psychiatry and Psychotherapy, Jena University Hospital, 07740 Jena, Germany. Electronic address: martin.walter@med.uni-jena.de.
⁷ Experimental Therapeutics and Pathophysiology Branch, Intramural Research Program, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA. Electronic address: wduncan@mail.nih.gov.
⁸ National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD, USA. Electronic address: davidgoldman@mail.nih.gov.
⁹ Experimental Therapeutics and Pathophysiology Branch, Intramural Research Program, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA. Electronic address: zaratec@mail.nih.gov.

PMID: 40398609
PMCID: PMC12172513 (available on 2026-09-15)
DOI: 10.1016/j.jad.2025.119448

Abstract

Background: Sleep disruptions are a core feature of both major depressive disorder and treatment-resistant depression (TRD), which is defined by persistent symptoms despite multiple treatment efforts. In addition, disruptions in wakeful gamma power and sleep-related delta power have been observed in individuals with TRD. This study explored the association between gamma oscillations (30-100 Hz) occurring during wakefulness and delta power (0.5-4 Hz) in non-rapid eye movement (NREM) sleep-both of which have separately been implicated in plasticity-in healthy volunteers (HVs) and individuals with TRD. Specifically, the study explored whether a relationship exists between daytime wake gamma power and sleep NREM delta power in HVs and those with TRD.

Methods: Brain activity was measured via electroencephalography (night-time) and magnetoencephalography (daytime resting state) in 23 HVs (9M/14F; 20-56 yrs) and 40 medication-free TRD participants (20 M/20F; 18-63 yrs).

Results: In HVs, NREM episode (NREM1) sleep delta power correlated with daytime wake gamma power (r = 0.417; p = 0.04). This correlation was absent in TRD participants (r = 0.108; p = 0.50).

Limitations: The sample size of the HVs (n = 23) was smaller than the TRD participants (n = 40), and the measurement order for wake gamma power and sleep delta power varied.

Conclusions: These findings identify a possible link between daytime wake gamma power and NREM1 sleep delta power in HVs, supporting an association between gamma and delta power in sleep homeostasis. The lack of such a relationship in medication-free individuals with TRD suggests disrupted synaptic homeostasis that may contribute to impaired synaptic plasticity in TRD. Clinical Trials Identifiers: NCT00088699 and NCT01204918.

Keywords: Daytime wake gamma power; Healthy volunteers; NREM sleep delta power; Synaptic homeostasis hypothesis; Treatment-resistant depression.

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Conflict of interest statement

Declaration of competing interest Dr. Zarate is listed as a co-inventor on a patent for the use of ketamine in major depression and suicidal ideation; as a co-inventor on a patent for the use of (2R,6R)-hydroxynorketamine, (S)-dehydronorketamine, and other stereoisomeric dehydroxylated and hydroxylated metabolites of (R,S)-ketamine metabolites in the treatment of depression and neuropathic pain; and as a co-inventor on a patent application for the use of (2R,6R)-hydroxynorketamine and (2S,6S)-hydroxynorketamine in the treatment of depression, anxiety, anhedonia, suicidal ideation, and post-traumatic stress disorders. He has assigned his patent rights to the U.S. government but will share a percentage of any royalties that may be received by the government. All other authors have no conflict of interest to disclose, financial or otherwise.

References

1. Akar SA, Kara S, Agambayev S, Bilgic V, 2015. Nonlinear analysis of EEG in major depression with fractal dimensions. Annu Int Conf IEEE Eng Med Biol Soc 2015, 7410–7413. - PubMed
1. Altevogt BM, Colten HR, 2006. Sleep Disorders and Sleep Deprivation: An Unmet Public Health Problem. National Academies Press, Washington, DC. - PubMed
1. Armitage R, Calhoun JS, Rush AJ, Roffwarg HP, 1992. Comparison of the delta EEG in the first and second non-REM periods in depressed adults and normal controls. Psychiatry Res 41, 65–72. - PubMed
1. Armitage R, Hoffmann R, Trivedi M, Rush AJ, 2000. Slow-wave activity in NREM sleep: sex and age effects in depressed outpatients and healthy controls. Psychiatry Res 95, 201–213. - PubMed
1. Atallah BV, Scanziani M, 2009. Instantaneous modulation of gamma oscillation frequency by balancing excitation with inhibition. Neuron 62, 566–577. - PMC - PubMed

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Exploring the link between waking gamma and sleep delta power in healthy volunteers and individuals with treatment-resistant depression

Affiliations

Exploring the link between waking gamma and sleep delta power in healthy volunteers and individuals with treatment-resistant depression

Authors

Affiliations

Abstract

Conflict of interest statement

References

Publication types

MeSH terms

Associated data

Grants and funding

LinkOut - more resources

Full Text Sources

Medical