Over the past few decades, the prevalence of comorbid mental and physical diseases has risen dramatically, posing a major challenge for health services across the world (Launders et al., 2022; Ronaldson et al., 2021). In particular, multiple large studies have shown a substantial degree of comorbidity between common mood disorders, such as depression and anxiety, and cardio-metabolic conditions, including diabetes, obesity and cardiovascular disease (Fisher et al., 2014; Gold et al., 2020; Souama et al., 2023). Mounting evidence is further suggesting an early origin of these psycho-physical comorbidity patterns, involving shared risk factors and pathophysiological pathways that begin already in utero (Milaneschi et al., 2019). One of such risk factors is psychosocial stress – including for instance family conflict, financial difficulties or victimization, experienced in the first years of life – here collectively defined as early-life stress (ELS). For example, a recent study conducted in two independent population-based samples reported that exposure to ELS during gestation and throughout the first 10 years of life prospectively associated with increased internalizing symptoms,2 adiposity, as well as their co-occurrence in adolescence (Defina et al., 2023). The study focused on broad, pre-clinical measures of depression/anxiety (i.e. internalizing symptoms) and cardio-metabolic risk (i.e. adiposity) respectively. However, these associations were also shown to persist into mid- and late adulthood and manifest into clinical diagnoses (Bright et al., 2016; Milaneschi et al., 2019; Souama et al., 2023), highlighting the early developmental origins of these risk pathways.

While these findings certainly support the importance of primary prevention programmes aimed at reducing the incidence of ELS, preventing ELS may not always be possible. As such, there is a need to identify alternative modifiable factors that could mitigate the negative impact of ELS on later health, and inform the development of complementary intervention strategies.

Healthy lifestyle factors, including physical activity, sleep and diet have been robustly linked to both emotional and physical wellbeing (Briguglio et al., 2020; Firth et al., 2020). For example, regular physical activity was associated with reduced internalizing (Wheatley et al., 2020) and depressive symptoms (Oberste et al., 2020), as well as with lower body mass index (BMI) (Schwarzfischer et al., 2017) in children and adolescents. Adolescents reporting longer sleep durations have also been shown to be at lower odds of developing depression and obesity (Owens et al., 2014). Moreover, diet quality, particularly adherence to a Mediterranean diet, was associated with reduced internalizing symptoms (Orlando et al., 2022) and risk of depression (Shafiei et al., 2023), as well as with lower adiposity (Tognon et al., 2014) in childhood.

However, it remains unclear whether any of these lifestyle factors could effectively attenuate the association between ELS exposure and the risk of comorbidity between mental and physical health problems, in early adolescence.

To address this gap, we replicated and extended Defina et al. (2023) approach, by investigating the interaction between cumulative ELS exposure and (a) participation in physical activity, (b) sleep duration, and (c) adherence to a Mediterranean diet, on adolescent psycho-physical comorbidity, defined as the co-occurrence of high internalizing symptoms and high adiposity.