Our study utilized the Mendelian randomization (MR) method to thoroughly assess the connection between "skipping breakfast" and five prominent psychiatric disorders, including cognitive performance and frailty. The investigation revealed that "skipping breakfast" has a causal relationship with attention deficit hyperactivity disorder (OR = 2.738, 95%CI:1.538–4.876, P < 0.001) and depression (OR = 1.502, 95%CI:1.011–2.231, P = 0.044), both indicating a positive correlation. However, no significant causal relationship was discovered between "skipping breakfast" and the remaining three psychiatric disorders (Alzheimer’s disease, bipolar disorder, narcolepsy). Furthermore, our research discovered causal connections between "skipping breakfast" and cognitive performance (β=-0.164, 95%CI: -0.291-0.036, P=-0.012) as well as frailty (β = 0.288, 95%CI:0.121–0.454, P < 0.001).
Many studies have shown that breakfast is essential for psychiatric and physical health. Some meta-analyses of observational studies concluded that skipping breakfast might be associated with higher risk of diabetes2, primary dysmenorrhea36, cardiovascular disease37, overweight and obesity. Notably, a recent meta-analysis of 14 previous studies, involving a total sample of 399,550 individuals, identified a significant positive association between skipping breakfast and the Odds Ratio (OR) of depression (pooled OR: 1.39; 95% CI: 1.34–1.44). Interestingly, this aligns with the finding in our study that "skipping breakfast" can significantly reduce the risk of depression. A preceding study delved into the association between breakfast consumption and its impact on depression, focusing on carbohydrate ingestion. The study proposed that as blood glucose levels decrease during nocturnal fasting, cortisol release occurs. Elevated cortisol levels are correlated with increased inflammatory cytokines, particularly those that attenuate serotonin, a neurotransmitter implicated in mood regulation and depression alleviation38. Therefore, skipping breakfast may be a potential factor that increases the risk of depression. On the contrary, the act of consuming breakfast may modulate metabolic responses during fasting conditions, ensuring a sustained supply of nutrients to the central nervous system. This could potentially influence nutrient intake and status39. Given the fundamental role of nutrition in central nervous system functioning, including the regulation of neurotransmitters such as serotonin and dopamine, breakfast consumption emerges as a factor that may contribute to the association between nutrition and depressive symptoms40.
Studies have also shown that skipping breakfast is associated with an increased risk of ADHD41, which supports our findings. However, the etiological model of the causal association between breakfast and ADHD remains unknown. Several potential reasons may explain this causal association. Previous studies have identified a link between ADHD and eating disturbances. The shared biological mechanism in ADHD and binge eating does not function typically, leading to the utilization of immediate rewards, such as altered eating behavior and risk-taking42. In addition, an unbalanced diet can lead to deficiencies in essential nutrients42. For instance, iron and zinc, which contribute to healthy neurocognitive and physical growth, are cofactors for dopamine and norepinephrine production, which play an essential role in the etiology of ADHD. What’s more, Omega-3 fatty acids seem also to have a relationship with ADHD.
So far, studies on breakfast and cognitive performance have been mainly cross-sectional, which eliminates the author's ability to determine the directionality of the relationship. Furthermore, cross-sectional studies demonstrated contradicting findings and have been inconclusive. Some found little or no effect between breakfast consumption and cognitive performance43. However, recently Increasing research has concluded that breakfast benefits various aspects of cognition in adults, children, and adolescents44, which supports our findings. One possible mechanistic pathway through which breakfast enhances cognition could be through the immediate cognitive impact of breakfast consumption. Studies have suggested that breakfasts rich in complex carbohydrates aid cognitive performance throughout the morning, which may be mediated by the glycemic index (GI) or glycemic load (GL)45. Recently, a random-effects meta-analysis model revealed no effect of GL on cognition up to 119 minutes post-consumption. However, after 120 min, immediate episodic memory scores were better following a low GL than a high GL46. Furthermore, lower daily intakes of major vitamins44 and proteins among breakfast skippers are associated with cognitive decline. It is worth noting that the long-term effect of skipping breakfast on cognitive function may be related to its connection to an increased cardiometabolic risk47.
Numerous epidemiological studies have investigated the potential association between the habitual practice of "skipping breakfast" and frailty. For example, a cross-sectional survey study conducted among 723 adult residents in Chongqing communities has demonstrated that regular breakfast consumption may significantly lower the relative likelihood of developing frailty48. Research among 3758 participants aged ≥ 60 has reported that having breakfast daily, as a potential mediator, contributes to a decrease in the risk of prefrailty and frailty49. Importantly, breakfast skippers showed a higher odds ratio for frailty than daily breakfast consumers, and they were characterized by lower dietary intake and poorer nutrient density than daily breakfast consumers50. In line with the preceding reports, we observed a causal association between "skipping breakfast" and frailty using the MR study. However, more randomized clinical trials were needed to confirm this hypothesis.
Limitations
Certain limitations persisted in this study. Firstly, in the two-sample Mendelian randomization investigation, we adopted a more permissive significance threshold (P < 1×10− 7) to encompass an expanded set of single nucleotide polymorphisms (SNPs) linked to the "skipping breakfast" phenotype. Under this more lenient threshold, we implemented SNP clumping for independence, retaining only a single representative SNP when SNPs exhibited a correlation coefficient (r2) exceeding 0.001. The execution of this process relied on European ancestry reference data derived from the 1000 Genomes Project.
This approach of relaxing the statistical threshold for genetic instruments aligns with practices observed in psychiatric Mendelian randomization research, particularly when confronted with limited availability of significant SNPs51. Another limitation of this study stems from the utilization of GWAS data originating exclusively from European populations, thereby limiting the generalizability of the findings to other ethnic groups. Future research efforts should include validation studies to assess the transferability of the results to diverse populations. Additionally, the Two-Sample Mendelian Randomization (TSMR) analysis in this study did not integrate gender stratification, preventing an exploration of potential gender differences. It is advisable that future GWAS databases incorporate gender-specific data to facilitate more comprehensive investigations in subsequent research endeavors.