Examining inflammation, health, stress and lifestyle variables linking low socioeconomic status with poorer cognitive functioning during adolescence

Higher C-reactive protein (CRP) is associated with cognitive difficulties. The nature of this association remains unclear given that multiple other variables are linked with both CRP and cognitive difficulties, which may confound the association. The goal of the current study is to determine whether low socioeconomic status (SES) is associated with worse cognitive functioning via higher CRP and whether this association is independent of known associations with other health, stress and lifestyle factors (e.g., depression, physical activity, body mass). Assessments in a longitudinal study of 1,029 Dutch adolescents were based on a combination of self-report and parent-report questionnaires, diagnostic assessment, behavioral testing, and blood assay. We estimated latent variables for cognitive functioning (executive functioning, verbal fluency, episodic memory) and used structural equation analysis to test whether SES (wave 1: 11.08 years (SD=0.55); 55% female] was associated with worse cognitive outcomes (wave 4: aged 18.97 years; SD=0.55) via increased CRP, depression, stress, body mass, substance use or physical inactivity (wave 3: aged 16.17 years; SD=0.61). Low SES was associated with worse cognitive functioning via increased CRP. Additionally, low SES was associated with (i) worse executive func-tioning via higher body mass, higher levels of sedentary behavior, and higher stress, (ii) worse verbal fluency via higher levels of sedentary behavior and (iii) worse episodic memory via sedentary behaviors, body mass, and substance use. These results confirm the link between SES, CRP and cognitive functioning and additionally identify four modifiable lifestyle factors that may be implicated in the link between low SES and worse per-formance on tests of cognitive functioning

Investigating whether a combination of higher CRP and depression is differentially associated with worse executive functioning in a cohort of 43,896 adults

Many depressed individuals experience difficulties in executive functioning that contribute substantially to functional impairment. It is unknown whether a subtype of depression characterized by chronic inflammation is differentially associated with worse executive functioning. This study examined whether the combination of depression and higher C reactive protein (CRP) is differentially associated with worse executive functioning and whether this association is stronger in older adults. This cross-sectional study analyzed data collected from a population-representative sample of 43,896 adults aged 44.13 years (SD = 13.52) who participated in the baseline assessment of the Lifelines cohort study. Multivariate regression models tested whether depressed individuals (established via structured interview) exhibiting higher levels of inflammation (indexed via highsensitivity CRP assay following an overnight fast) performed worse on a behavioral test of executive functioning. Depression (B = -3.66, 95% CI: -4.82, -2.49, p < .001) and higher log-transformed CRP (B = -0.67, 95% CI: -0.87,-0.47, p < .001) were associated with worse executive functioning, after adjustment for age, sex, educational attainment, body mass index, smoking status, exposure to stressful life events and chronic stressors, sedentary behavior, and number of chronic medical conditions. Depressed individuals with higher logtransformed CRP exhibited differentially poorer executive functioning (B = -1.09, 95% CI: -2.07,-0.11, p < .001). This association did not differ based on age (B = 0.01, 95% CI: -0.08, 0.10, p = .82). Executive functioning is poorer in depressed individuals with higher CRP, even in early adulthood. Interventions that reduce inflammation may improve cognitive functioning in depression

Inflammation and depression: Research designs to better understand the mechanistic relationships between depression, inflammation, cognitive dysfunction, and their shared risk factors

There is convergent evidence that the immune system is dysregulated in some depressed individuals. A psychoneuroimmunology-based understanding of depression is advancing rapidly; however, a question of fundamental importance is poorly understood: does inflammation play a causal role in the etiology of depression or are elevated inflammatory biomarkers a downstream effect of depressive behaviors? Although longitudinal studies suggest that the relationship between depression and inflammation is characterized by complex bidirectional associations, existing prospective, longitudinal research designs are poorly equipped to investigate the dynamic interplay of depression and inflammation that unfolds over a relatively short time period. In addition, the precise role played by multiple, shared, and overlapping risk factors (e.g., diet, adiposity, stress, sleep dysregulation) in the etiology of depression and a pro-inflammatory phenotype (or both) is poorly understood. In this manuscript, I highlight the benefits of research designs that (i) manipulate constructs of interest (depression/inflammation) using intervention or treatment designs and (ii) use intensive sampling approaches with an ultimate goal of better understanding the temporal sequence and causal relationships of depression, inflammation, cognitive dysfunction, and their shared risk factors. For instance, are improved depressive symptoms a downstream effect of changes in inflammatory activity caused by increases in exercise or, alternatively, are changes in inflammatory activity and depression sequelae of improvements in sleep quality caused by increases in exercise? Potential benefits of these research designs are discussed in terms of their contribution to a better understanding of the etiology of depression and a pro-inflammatory phenotype, their relevance to structural health inequalities, and better characterizing the heterogeneous clinical presentation of depression, particularly relating to the etiology of cognitive dysfunction in depression