Investigating the Role of BDNF in Insomnia: Current Insights

Figures & data

Table 1 Summary of findings of studies on the subject of BDNF in insomnia

No.	Authors, year	Study population, insomnia definition	Biomaterial	Findings
1.	Sanchez-Garcia et al 2023^Citation102	Twenty-one insomnia patients and 22 healthy controls. Insomnia was defined as scoring at least 6 points on the AIS questionnaire.	Serum	Participants with insomnia showed decreased BDNF serum levels; BDNF serum level was negatively correlated with insomnia severity.
2.	Satyanarayanan et al 2020^Citation103	Sixteen patients diagnosed with primary insomnia and 10 healthy controls. Criteria for insomnia diagnosis were not included in the manuscript.	Plasma	Levels of plasma BDNF protein were lower in subjects with insomnia compared to the controls.
3.	Zhang et al 2020^Citation104	Twenty-seven patients with chronic insomnia disorder and 10 healthy controls. Insomnia was diagnosed according to ICSD-3 criteria.	Serum	Patients with insomnia exhibited lower serum BDNF levels than healthy controls.
4.	Furihata et al 2019^Citation97	Five-hundred and seventy-seven female nurses: 123 reported insomnia, 72 insomnia with short sleep duration. Sleep was assessed with a self-reported questionnaire based on DSM-IV criteria for insomnia, which included questions about sleep duration, difficulty initiating sleep (DIS), difficulty maintaining, sleep (DMS), early-morning awakening (EMA), and sleep duration. Insomnia with short sleep duration was defined as: DIS, or DMS, or EMA; and <6 hours sleep duration.	Serum	There were no differences in serum BDNF protein between participants with normal sleep time (at least 6 hours/night), regardless of the presence of insomnia. In participants with short sleep duration (<6 hours/night), those with insomnia showed decreased BDNF serum levels compared to counterparts without sleep problems.
5.	Fan et al 2019^Citation101	Fifty-seven patients with insomnia (30 with sleep duration <6 hours/night, 27 with normal sleep duration), and 29 healthy controls. Insomnia diagnosis was made according to DSM-V criteria.	Serum	Participants with insomnia with short sleep duration but not normal sleep duration had a lower serum BDNF protein level compared to healthy controls. In a within-group analysis, participants with insomnia with short sleep duration also exhibited a lower serum BDNF level than those with normal sleep duration.
6.	Mikoteit et al 2019^Citation105	Sixty patients with insomnia and 30 healthy controls. Insomnia was assessed with the ISI questionnaire, based on DSM-IV diagnostic criteria for insomnia.	Serum	Serum BDNF was decreased in the insomnia group compared to controls. Insomnia severity was predictive of lower BDNF levels.
7.	Deuschle et al 2018^Citation106	Thirty-five patients with insomnia and 37 healthy controls. Insomnia diagnosis was made according to the ICSD-2 criteria.	Serum	BDNF serum levels did not differ between subjects with insomnia and healthy controls.
8.	Giese et al 2014^Citation98	Twenty-six insomnia patients (including 19 with restless leg syndrome/periodic limb movement) and 24 healthy controls. Insomnia was defined as scoring more than 8 points on the ISI questionnaire based on the DSM-IV diagnostic criteria for insomnia.	Serum	Insomnia was associated with lower serum BDNF levels compared with healthy controls. Serum BDNF concentration was negatively correlated with insomnia severity as assessed by ISI.

Abbreviations: AIS, Athens Insomnia Scale; DSM, Diagnostic And Statistical Manual of Mental Disorders; ICSD, International Classification of Sleep Disorders, ISI, Insomnia Severity Index.

Figure 1 The possible mechanism of interactions between sleep deficiency and BDNF.

Notes: Acute sleep deficiency induces BDNF production that might promote glutamatergic signaling in the PFC, improving adaptation to a new stressor. Overtime, increased exposure to BDNF leads to desensitization and insufficiency of positive autoregulatory feedback loops, ie, decreased expression of TrkB and CREB pathway activity, which fails to maintain adequate levels of this neurotrophin.

Abbreviations: BDNF, brain-derived neurotrophic factor; CREB, cAMP response element-binding protein; prefrontal cortex, PFC; tropomyosin receptor kinase B, TrkB.

Sanchez-Garcia S, Moreno-Tamayo K, Ramirez-Aldana R, et al. Insomnia impairs both the Pro-BDNF and the BDNF levels similarly to older adults with cognitive decline: an exploratory study. Int J Mol Sci. 2023;24(8):7387. doi:10.3390/ijms24087387

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Satyanarayanan SK, Chien YC, Chang JP, et al. Melatonergic agonist regulates circadian clock genes and peripheral inflammatory and neuroplasticity markers in patients with depression and anxiety. Brain Behav Immun. 2020;85:142–151. doi:10.1016/j.bbi.2019.03.003

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Zhang P, Li YX, Zhang ZZ, et al. Astroglial mechanisms underlying chronic insomnia disorder: a clinical study. Nat Sci Sleep. 2020;12:693–704. doi:10.2147/nss.S263528

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Furihata R, Saitoh K, Otsuki R, et al. Association between reduced serum BDNF levels and insomnia with short sleep duration among female hospital nurses. Sleep Med. 2020;68:167–172. doi:10.1016/j.sleep.2019.12.011

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Fan TT, Chen WH, Shi L, et al. Objective sleep duration is associated with cognitive deficits in primary insomnia: BDNF may play a role. Sleep. 2019;42(1). doi:10.1093/sleep/zsy192

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Mikoteit T, Brand S, Eckert A, Holsboer-Trachsler E, Beck J. Brain-derived neurotrophic factor is a biomarker for subjective insomnia but not objectively assessable poor sleep continuity. J Psychiatr Res. 2019;110:103–109. doi:10.1016/j.jpsychires.2018.12.020

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Deuschle M, Schredl M, Wisch C, et al. Serum brain-derived neurotrophic factor (BDNF) in sleep-disordered patients: relation to sleep stage N3 and rapid eye movement (REM) sleep across diagnostic entities. J Sleep Res. 2018;27(1):73–77. doi:10.1111/jsr.12577

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Giese M, Unternährer E, Hüttig H, et al. BDNF: an indicator of insomnia? Mol Psychiatry. 2014;19(2):151–152. doi:10.1038/mp.2013.10

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