In their letter to the editor published in this issue of Journal of Clinical Sleep Medicine, Dong and Zhang1 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 study2 included a cohort of military personnel with a high prevalence of traumatic brain injury (TBI), posttraumatic stress disorder (PTSD), and depression. There are significant challenges and limitations in translating animal models of these complex disorders to the clinical setting.3 Briefly, 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 reflect the infinitely varied genotypes of humans that underlie these complex conditions.5
We appreciate the authors highlighting their findings of a weak inverse relationship between decreased expression of insulin-like growth hormone receptor (IGF-1R) and increased concentrations of IGF-1. While this finding 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).6,7
The 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 confirmed 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.
The authors have indicated no financial conflicts of interest.
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