Background: Inflammation has been linked to an increased risk of depression, but there is limited and conflicting research on the role of inflammatory markers in adolescent depression. The purpose of this study was to examine associations between cytokines TNF-α, IL-1β, IL-6, and IL-8 and depression among a community-based sample of adolescents (13-19 years of age). Methods: Salivary samples were self-collected by adolescents for assay of cytokines. The Patient Health Questionnaire-9 (PHQ-9) was used to measure depressive symptoms and clinical depression, where a score ≥11 indicated the threshold for experiencing clinical depression. Multiple linear and logistic regression models were used to examine the relationships between cytokines and depression, adjusting for age, sex, ethnicity, income, and body mass index. Results: The mean age of the 83 participants was 15.86 years. Eight participants screened positive for depression; the mean depressive symptom score was 5.11. Higher levels of IL-6 (Coef = 1.33, p < .001) and IL-8 (Coef = 0.69, p = .025) were associated with more frequent depressive symptoms while higher levels of TNF-α (OR = 2.50, p = .002), IL-1β (OR = 1.98, p = .001), and IL-8 (OR = 2.44, p = .008) were associated with greater odds of meeting criteria for clinical depression. Conclusions: Future research should focus on factors that induce higher cytokine levels and the mechanisms underlying their effects on depression. Cytokines assessed in this study may ultimately have implications as methods for depression screening or targets for biologic interventions to prevent and treat adolescent depression.

Shared genetic risk between schizophrenia (SCZ) and bipolar disorder (BD) is well-established, yet the extent to which they share environmental risk factors remains unclear. We compare the associations between environmental exposures during childhood/prior to disorder onset with the risk of developing SCZ and BD.

We conducted a Swedish register-based nested case-control study using 4184 SCZ cases and 18 681 BD cases diagnosed 1988-2013. Cases were matched to five controls by birth year, birth region, and sex. Conditional logistic regression was used to estimate incidence rate ratios (IRR) for SCZ and BD for each exposure (severe childhood infections, adverse childhood experiences (ACEs), substance use disorders (SUDs), urban birth/longest residence).

All SUD types were associated with very high risk (IRR 4.9-25.5), and all forms of ACEs with higher risk (IRR 1.5-4.3) for both disorders. In the mutually adjusted models, ACEs demonstrated slightly higher risk for BD (SCZ IRR 1.30, 1.19-1.42; BD IRR 1.49, 1.44-1.55), while for SUD, risk was higher for SCZ (SCZ IRR 9.43, 8.15-10.92; BD IRR 5.50, 5.15-5.88). Infections were associated with increased risk of BD (IRR 1.21, 1.17-1.26) but not SCZ. Urban birth and urban longest residence were associated with higher risk of SCZ (IRR 1.19, 1.03-1.37), while only the combination of urban birth and rural longest residence showed higher risk for BD (IRR 1.24, 1.13-1.35).

There were both shared and unique environmental risk factors: SUDs and ACEs were risk factors for both disorders, while infections were more strongly associated with BD and urbanicity with SCZ.

Mood disorders are among the commonest mental disorders worldwide. Epidemiological and clinical evidence suggests that there are close links between infectious diseases and mood disorders, but the strength and direction of these association remain largely unknown. Theoretical models have attempted to explain this link based on evolutionary or immune-related factors, but these have not been empirically verified. The current study examined cross-sectional and longitudinal associations between the incidence of infectious diseases and mood disorders, while correcting for climate and economic factors, based on data from the Global Burden of Disease Studies, 1990-2019. It was found that major depressive disorder was positively associated with lower respiratory infections, while bipolar disorder was positively associated with upper respiratory infections and negatively associated with enteric and tropical infections, both cross-sectionally and over a period of 30 years. These results suggest that a complex, bidirectional relationship exists between these disorders. This relationship may be mediated through the immune system as well as through the gut-brain and lung-brain axes. Understanding the mechanisms that link these groups of disorders could lead to advances in the prevention and treatment of both.

New insights into how depression is linked to physical health throughout the lifespan could potentially inform clinical decision making. The aim of this study was to explore the association of adolescent depression with subsequent prescriptions of anti-infectives and anti-inflammatories in adulthood. The study was based on the Uppsala Longitudinal Adolescent Depression Study (ULADS), a Swedish prospective cohort study initiated in 1991. Depressed (n = 321) and non-depressed (n = 218) adolescents were followed prospectively using patient registries. The associations of adolescent depression (age 16-17 years) with subsequent prescription of anti-infectives and anti-inflammatories (age 30-40 years), were analysed using generalized linear models. Sub-analyses explored the impact of diagnostic characteristics in adolescence and reception of anti-depressants prescriptions in adulthood. The results suggest that females with persistent depressive disorder in adolescence have a higher rate of future prescriptions than non-depressed peers, with adjusted incidence rate ratio of 1.42 (1.06 to 1.92) for anti-infectives and 1.72 (1.10 to 2.70) for anti-inflammatories. These associations were mainly driven by those who were also prescribed antidepressants during the same period. Associations were less robust for females with episodic or subsyndromal depression in adolescence and for males. These findings emphasize the importance of integrated mental health services at the primary healthcare level.