The Relationship between Insulin Resistance, Antioxidants, and Eye Blink Startle Reflex during International Affective Picture System Presentation
Authors: Wolf Tovah , Willette Auriel 
Published: November 2023

Approximately one in three U.S. adults have pre‐diabetes (CDC). Pre‐diabetes etiology is characterized by insulin resistance (IR), a reduced cellular response to insulin, and lower glucose uptake in the brain. IR is also related to deficits in cognitive and affective processing, particularly reactivity to psychological stress. Additional data supports a role for inflammation in the pathogenesis of IR. The goal of our analysis was to determine how IR or hyperglycemia predicted eye blink startle reflex (EBR) magnitude and amplitude, an objective index of the startle response, in response to positive, negative and neutral pictures using the International Affective Picture System (IAPS). We also assessed if specific antioxidants predicted EBR. We hypothesized that individuals with higher IR and lower levels of antioxidants would show greater EBR. The analysis consisted of healthy adults (N=331 participants), aged 36–84 years old, from the University of Wisconsin‐Madison's MIDUS (Midlife in the United States) II longitudinal study. As described in the MIDUS protocol, fasted blood samples were collected during an overnight stay. EBR in response to IAPS visual stimuli paired with acoustic startle was measured by placing two mini electrodes below the eye. Picture duration was 4,000ms. For a given trial, the acoustic startle stimuli (105 dB) was administered for 50ms during one of three phases: 1) The “early” phase at 2,900ms after picture onset while the picture was on the screen to assess reactivity; 2) the “middle” phase at 400ms after picture onset; and 3) the “late” phase at 1,900ms after picture offset and removal to assess longer‐term recovery. Data was analyzed using SPSS 23.0. Linear mixed models were used to analyze the main effect of log‐transformed homeostasis model assessment of insulin resistance (HOMA‐IR) on antioxidants and EBR, as well as its interaction with IAPS picture valence (positive, neutral, negative). Antioxidants were also used to predict EBR and its interaction with IAPS picture valence. Higher log10 HOMA‐IR predicted greater EBR amplitude during negative versus positive pictures (n=290, p<.05, r2=0.127). Higher blood lutein (n=261, p<.05, early r2=.100, late r2=.130) and E‐selectin (n=259, p<.05, early r2=.201, late r2=.053) predicted greater EBR magnitude during negative verses positive pictures in the early phase, but hypo‐responsivity in the late phase. Blood zeaxanthin predicted greater EBR magnitude during the same phase early on, but not during the late phase after the image disappeared (n=259, p<.05, early r2=.157, late r2=.013). In conclusion, higher IR and antioxidant levels (lutein, e‐selectin, zeaxanthin) may be selective biomarkers of different phases of psychological stress reactivity.Support or Funding InformationThis work was supported by Iowa State University and NIH AG047282. Neither funding source had any involvement in the report. MIDUS is funded by the National Institute on Aging (PO1‐AG020166; Carol D. Ryff, Principal Investigator). John D. Catherine and Catherine T. MacArthur of the Foundation Research Network on Successful Midlife Development were the supporters of the original project.