Using a symptom-based approach, the findings of this study contribute to a growing body of evidence that underscores the significance of both lifestyle/environmental factors and systemic inflammation in the pathology of MDD.
In terms of psychosocial factors, our findings show a link between religious practices and lower severity of depressive symptoms and somatic symptoms of depression suggesting religiosity as a protective factor (Braam & Koenig, 2019). Contrary to literature, the effect of meditation was insignificant, possibly due to variations in the type of practice, the consistency and duration of practice, and the quality of the practices. This might also highlight the cultural element involved here given the Egyptian context where the belief in religious practices outweigh other spiritual and mindful practices.
As another significant lifestyle factor, moderate/high intensity sports, rather than low-intensity physical activity, has been shown to reduce risk of depression severity, in addition to severity of cognitive-affective symptoms and somatic symptoms. Sleep problems have been shown to be a core symptom in depression in addition to a prospective risk factor for non-depressed individuals (Nutt et al., 2022). Our findings also suggest that poor sleep quality, rather than number of hours of sleep, and number of hours using internet as two risk factors for high severity of depressive symptoms, somatic symptoms and cognitive-affective symptoms, and severity of depressive symptoms and cognitive-affective symptoms respectively. This is well-documented in research highlighting the effects of problematic smartphone use on both sleep quality and depression (Jiaxin et al., 2020).
Another major psychosocial factor that has been conceptualized in research as a risk factor for mental health problems is exposure to different types of abuse. In the current study exposure to verbal abuse has been linked with both depression severity and more specifically, the severity of the cognitive-affective symptoms of depression. This can be explained in terms of the mediating role of self-criticism in individuals exposed to verbal abuse (Sachs-Ericsson et al., 2006) as they internalize what they have been exposed to and start incorporating it into their own self-narratives.
Our findings also demonstrate the negative association between employment status and severity of depressive symptoms which can be interpreted in terms of the disability burden of depression leaving patients unable to be functional, or the protective role of employment in relation to depression. Similarly, the link between BMI and severity of depressive symptoms can be interpreted from two directions. First, the metabolic consequences of high BMI increase the biological risk factors for depression including neuroinflammation (Fulton et al., 2021). Alternatively, depression can increase the risk of emotional eating problems which therefore increase one’s risk of obesity (Konttinen, 2020).
Although none of the dietary or supplementary factors have shown to influence MDD outcomes, caffeine did. As having psychostimulant effects and modulatory effects on the dopaminergic pathways, caffeine is hypothesized and proven to have protective effects against depression (Alasmari, 2020). However, the current findings shows the opposite which might be attributed to the unhealthy lifestyle factors that are usually associated with high caffeine intake including poor sleep which increase the risk and severity of depression.
Moving towards the foundational influences in early life, the link between being breastfed and a higher risk of depressive symptoms is contrary to the little, yet positive, research body highlighting the effects of breastmilk on lowering risk of psychological distress in adulthood (Cable et al., 2012). Although the mechanism of action by which this relationship exists is not fully understood, it can be at least partially explained in terms of the immunological components of breastmilk (Hosea Blewett et al., 2008). Our findings, however, might be confounded by other variables that were not necessarily examined such as maternal diet, maternal mental health prenatally and postnatally, and family history of mental health disorders all of which might affect an infant’s brain health.
Finally in terms of broader environmental exposures, in a city that is heavily populated and largely urbanized with little greenery such as Cairo, our study supports other findings showing a negative correlation between exposure to greenery and depressive symptoms (Zhang et al., 2023). This does not only shed light on the interaction between environment and mental health, but also on the importance of urban planning that takes into consideration different biopsychosocial elements.
In terms of biomarkers, despite the study's inability to demonstrate statistically significant differences in levels of inflammatory and neurotrophic factors between healthy controls and individuals with current MDD episodes, a notable merit is its contribution with a reference for different biomarkers derived from an Egyptian sample, which is particularly valuable given the lack of such clinical benchmarks from local research.
More specifically, as a less examined inflammatory biomarker in depression, the link between white blood cells and severity of depressive symptoms confirms similar findings by other studies (Shafiee et al., 2017), other findings suggesting a positive correlation between WBC and somatic symptoms of depression specifically (Gialluisi et al., 2020), and between MCH and MCHC and the severity of depressive symptoms (Jong Oh et al., 2020). IL-10 has been shown to be positively correlated with the overall severity of cognitive-affective symptoms of depression. Such findings support the growing body of research indicating the role of inflammatory factors in neural and behavioral processes in MDD.
While this study has provided insights into the exposome of major depressive disorder in a pilot Egyptian sample, it has several limitations including the study design, sample size, and sampling strategy limiting the generalizability of the findings. Other methodological limitations such the single-time blood analysis may not illustrate the dynamic nature and the complexity of biomarker fluctuations under different conditions.