Abstract: Prepulse inhibition of the startle response is defined as the inhibition of the startle reflex to an intense contextual stimulus (named pulse) when a weaker stimulus (named prepulse) precedes it and is considered a measure of sensorimotor gating. Consistent with recent research, it has been observed that this measure might exhibit sex differences in studies of both humans and rodents, although the results in the literature appear to be inconsistent. Therefore, this systematic review aims to analyze the sexual differences observed in human and nonhuman animal studies from a comparative perspective. A comprehensive search was conducted from the inception to the present in the Web of Science, PubMed, and PsycInfo databases. Following the search, 58 studies were included in the review. The average age in human studies ( n = 32) was 31.45 years (range = 4–69), while among nonhuman animal studies ( n = 26), the average age was 75.5 postnatal days (range = 7–360). The results indicated no clear sexual differences in the startle response magnitude. However, consistent sex differences in prepulse inhibition were found, revealing that males exhibited higher levels of sensorimotor gating compared to females in both humans (78.79% of the studies) and nonhuman animal studies (69.23% of the studies). Therefore, the findings corroborate the sex differences of prepulse inhibition and underscore the value of this paradigm in comparative science, emphasizing the importance of considering sex as an independent variable when studying this phenomenon.
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