Table 1.

Assessing the likelihood of heightened inflammation: Risk factors that raise the index of suspicion

Risk factor	Comments
Older age	Inflammation rises with age (177) A large prospective study showed that older depressed adults gained visceral fat over five years, while non–depressed adults lost visceral fat (178) Among the genes upregulated during late life, more than half regulate inflammation-related processes, one mechanism for exaggerated proinflammatory responses (179)
Early life stress	Adults who experienced abuse or neglect as children have a substantially heightened risk for inflammation as well as depression (60, 61) Low childhood socioeconomic status confers enduring risk for depression and elevated inflammation, independent of concurrent risk factors such as abuse and neglect (180)
Comorbidities	Both the number and the severity of comorbid inflammatory disorders or diseases influence inflammation and risk of depression; risk is further heightened by the pain and sleep disturbances that often occur in tandem with the comorbidities (181)
Atypical depression	Atypical MDD with features including hypersomnia, fatigue, increased appetite, and weight gain is associated with greater inflammatory dysregulation than melancholic depression (181)
Chronic/recurrent depression	A more chronic course of depression is associated with higher inflammation (7, 182)
Obesity	Adipocytes (fat cells) produce and secrete IL-6 and TNF-α, and abdominal fat is a major inflammatory source (129) Central adiposity and greater body fat are associated with larger stress-induced inflammatory responses(126, 127) There is a medium-sized relationship between BMI and CRP in adults (r = 0.36) (183)
Poor sleep	Sleep loss stimulates production of proinflammatory cytokines and cellular inflammatory signaling. (184) Disturbed sleep accompanies many inflammation-associated comorbidities Both decreased sleep (<5 hours) and increased sleep (> 9 hours) share a medium-sized relationship with CRP, d = 0.29 and d = 0.34 respectively (185)
Unhealthy diet	“Western” diets (e.g., high in red and processed meats, sweets, desserts, French fries, and refined grains) have higher associated inflammation than healthier diets, e.g., Mediterranean diets (186) Adherence to a Mediterranean diet was associated with lower IL-6 (85)
Sedentary lifestyle	Physically active individuals have lower inflammation than their sedentary counterparts (116) Better cardiorespiratory fitness is associated with lower inflammation (187)
Fatigue	Fatigue, pain, and depression function as a troublesome symptom cluster across multiple medical and community populations (188). Like pain and depression, fatigue has strong inflammatory ties (189)
Pain	Pain generates inflammatory responses (69, 70) Amplified pain sensitivity serves as an additional inflammatory source that in turn provokes negative affect (69, 71, 72, 190)
Smoking	Current smokers have higher values across multiple inflammatory markers than non-smokers (159) Some former smokers have persistently elevated inflammation compared to those who never smoked (159)
Alcohol dependence	CRP and proinflammatory cytokines are higher among heavy drinkers and abstainers than moderate drinkers (191)
Female sex	More women than men have elevated CRP levels (192) IL-6 and TNF-α responses to low-dose endotoxin did not differ between men and women, but women’s reports of depressed mood and social disconnection increased more than those of men, suggesting women may be more sensitive to heightened inflammation (193) Obesity and CRP are more strongly related in women than in men (183) Sleep loss stimulates longer-lasting elevations in inflammation in women compared to men (75)