Body weight in autism spectrum disorder: A systematic review and meta-analysis.

Over the past decades, stress has been recognized as a dynamic, adaptive neurobiological process involving complex brain-body interactions that regulate environmental responses. Under chronic conditions, stress leads to neuroplastic alterations, which further increase vulnerability to neurological conditions such as depression (; ) and cognitive impairment (; ). Stress can impact nearly every system in the body, with adverse effects on both behavior and physiological functioning. Indeed, studies have consistently demonstrated that stress disrupts cognitive processing, recognition memory () and alters exploratory patterns (). Research studies have demonstrated the stress-induced physiological and behavioral alterations in both humans (; ) and animals (). Further, stress can induce persistent, age- and exposure-dependent structural and functional brain alterations, accelerating cognitive decline and neurodegeneration (; ). Chronic stress, particularly cold temperature stress, is an exacerbating environmental factor that has been shown to induce significant behavioral alterations (; ), including reduced locomotor activity, impaired exploratory behavior, and increased anxiety-like responses in animal models (; ; ; ). Several human studies have also demonstrated that chronic or acute cold exposure impairs cognitive performance and increases neurophysiological strain, particularly affecting attention, processing speed, executive function, decision-making, and memory (; ). Chronic cold stress disrupts physiological homeostasis and thermoregulation, characterized by decreased vasoconstriction, lower metabolic heat production, and reduced thermal sensitivity, leading to greater core temperature decline and increased systemic vulnerability predominantly in aging populations (). Interestingly, the exposure to cold stress may affect the behavior in an intensity-dependent manner. For instance, it has been observed that mild intensities of cold exposure enhance exploration and reduce anxiety; however, prolonged exposure may lead to reduced exploration, impaired movement, and elevated anxiety-like responses (). The adverse behavioral impairments associated with cold stress necessitate the need to explore natural, phytotherapeutic interventions (). , commonly known as saffron, contains a rich profile of antioxidant and anti-inflammatory bioactive carotenoids and terpenoids, including crocin and safranal (). These bioactive compounds are recognized for their anxiolytic and neuroprotective properties (; ; ), collectively supporting saffron’s potential benefits for brain health (). Across multiple preclinical models, crocin and saffron extract (SE) have been shown to reduce depressive and anxiety-like behaviors, as evidenced by improved performance in behavioral tests assessing mobility, anhedonia, exploration, and emotional responses (; ; ). Additionally, SE reverses stress-induced dysfunctions in learning, memory, and cognition (). Similarly, using an aged rodent model, reported that saffron supplementation improved cognitive performance and anxiety-like behaviors, highlighting its potential as a multi-target intervention against age-associated neurobehavioral decline (). Clinical findings indicate that SE is at least as effective as standard drugs for depression and anxiety, and improves cognitive outcomes with good tolerability (; ). Importantly, SE has been envisioned as a potential therapeutic against brain aging-related dysfunctions, including neurodegenerative and cardiovascular diseases (; ).