Effect of Acute Sleep Disturbance and Recovery on Insulin-Like Growth Factor-1 (IGF-1): Possible Connections and Clinical Implications

Abstract

In their letter to the editor published in this issue of Journal of Clinical Sleep Medicine, Dong and Zhang 1 indicate a concern about our study that arises from their own related animal model study. Since the authors did not provide a citation for their associated research, we have limited insight into their perspective. Our study 2 included a cohort of military personnel with a high prevalence of traumatic brain injury (TBI), posttraumatic stress disorder (PTSD), and depression. There are signifi cant challenges and limitations in translating animal models of these complex disorders to the clinical setting. 3Briefl y, neurotrauma models often fail to consider appropriate blast scaling methods and PTSD models have yet to characterize the gestalt of the disorder.3,4 Moreover, genetically homogeneous rodent colonies fail to refl ect the infi nitely varied genotypes of humans that underlie these complex conditions. 5We appreciate the authors highlighting their fi ndings of a weak inverse relationship between decreased expression of insulin-like growth hormone receptor (IGF-1R) and increased concentrations of IGF-1. While this fi nding is interesting, reduced receptor expression doesn't necessarily indicate a reduced signaling capacity. An alternative interpretation may be that the receptor plays a vital role in protein homeostasis and thus there is a slight decrease in IGF-1R in response to the increase in IGF-1 (i.e., a negative feedback mechanism). It is also possible to increase the signaling capacity of a receptor without increasing its quantity, such as in the mechanism of selective serotonin reuptake inhibitors (SSRI). 6,7The authors also state that our paper leads readers to the conclusion that increased concentrations of IGF-1 improve the cognitive functioning of our participants. It's not clear how this conclusion was inferred, as we did not assess a cognitive outcome and explicitly reported that concentration levels of IGF-1 were not associated with a diagnosis of depression, PTSD, or TBI. The current data indicated that IGF-1 concentrations increased in participants who endorsed improved sleep quality following a 12-week sleep intervention, and that improved sleep quality was associated with reductions in depression and posttraumatic arousal symptoms.We agree with the authors that IGF-1 may protect against the effects of stress and that IGF-1 regulates critical hippocampal processes, some of which play a functionally important role in the pathogenesis of PTSD. 8 We echo the author's sentiments that it's not evident from our current study that administration of IGF-1 will improve insomnia or attenuate comorbid symptoms. However, since there was a positive association between sleep quality improvements and IGF-1 increases, which is also confi rmed by a recent Cochrane meta-analysis, 9 it may be a treatment intervention worth exploring. We thank Mr. Dong and Dr. Zhang for taking a special interest in our research and sharing their ideas with us. CITATION

Effects of gabapentin on slow‐wave sleep period in critically ill adult patients: A randomized controlled trial

“…As mentioned earlier, IGF-1 concentrations increased during SWS. Chennaoui et al 38 and Rusch et al 27 found that improved sleep quality led to increased IGF-1 concentrations. We found that IGF-1 levels at baseline (34.21 ± 8.20 ng/mL in the control group and 41.75 ± 11.09 ng/mL in the gabapentin group) were much lower than the normal range.…”

“…Chennaoui et al 38 . and Rusch et al 27 . found that improved sleep quality led to increased IGF‐1 concentrations.…”

“…IGF‐1 also has beneficial metabolic effects such as increased PPAR‐γ transcription, stimulated glucose uptake through GLUT‐4, and decreased hepatic glucose production 26 . Importantly, disruptions in sleep, whether acute or chronic, have been observed to induce a catabolic state, resulting in reduced circulating levels of IGF‐1 27 . Conversely, interventions aimed at improving sleep quality, such as treatment for obstructive sleep apnea (OSA), have been associated with increased concentrations of IGF‐1, suggesting a close relationship between sleep and IGF‐1 regulation 6,11 .…”

“… 26 Importantly, disruptions in sleep, whether acute or chronic, have been observed to induce a catabolic state, resulting in reduced circulating levels of IGF‐1. 27 Conversely, interventions aimed at improving sleep quality, such as treatment for obstructive sleep apnea (OSA), have been associated with increased concentrations of IGF‐1, suggesting a close relationship between sleep and IGF‐1 regulation. 6 , 11 Therefore, we included IGF‐1 levels as one of the parameters for evaluating SWS.…”

Effects of gabapentin on slow-wave sleep period in critically ill adult patients: a randomized controlled trial

“…As mentioned earlier, IGF-1 concentrations increased during SWS. Chennaoui [44] and Rusch [45] found that improved sleep quality led to increased IGF-1 concentrations. We found that IGF-1 levels at baseline (34.21 ± 8.20 ng/mL in the control group and 41.75 ± 11.09 ng/mL in the gabapentin group) were much lower than the normal range.…”