TNF Levels Implicated in Response to Antidepressant Treatment in Pregnant Women

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Among pregnant women with depression, proinflammatory cytokine levels are lowest in those who respond to antidepressant therapy, according to findings from a new study. By comparison, inflammatory markers are higher in pregnant women with untreated depression or depression that persists despite standard antidepressant treatment.

Emily S. Miller, MD, of the Division of Maternal Fetal Medicine at Northwestern University Feinberg School of Medicine in Chicago, IL, presented results from the study at the 37th Annual Pregnancy Meeting of the Society for Maternal Fetal Medicine held January 23 to 28, 2017, in Las Vegas, NV. Douglas Williamson, PhD, of the Department of Psychiatry and Behavioral Sciences at Duke University, was a coinvestigator of the study.

Depression and systemic inflammation often co-occur, resulting in higher levels of proinflammatory cytokines among depressed individuals. Recent evidence suggests that antidepressant medications that target monoamine pathways may exert their beneficial effects by reducing systemic inflammation.

The study was designed to evaluate the potential association between depressive symptoms, inflammatory markers, and responsiveness to antidepressant therapy in pregnant women. A total of 85 pregnant women between 12 and 21 weeks of gestation were enrolled.

All of the participants were assessed for use of antidepressant medications and current depressive symptoms using the Center for Epidemiologic Studies Depression (CESD) scale. Based on their CESD scores, the women were categorized into 3 groups:

  • Untreated depression: CESD score ≥ 23 with no self-reported medication use
  • Depression unresponsive to medication: CESD score ≥ 23 despite medication use
  • Depression responsive to medication: CESD score < 16 with medication use

Participants also underwent laboratory tests between 12 and 21 weeks of gestation to determine the serum concentrations of multiple inflammatory markers. Interferon γ, interleukin (IL) 6, IL-8, IL-13, C-reactive protein, and tumor necrosis factor (TNF) α levels were measured.

Of the 85 study participants, 67% had untreated depression, 14% had depression that did not respond to medication, and 19% had depression that responded to medication. Several demographic characteristics significantly differed across the groups (Table 1), including:

  • Race/ethnicity
  • Household income
  • Marital status
  • Insurance type
  • Educational level
  • Employment status

Table 1. Baseline Characteristics By Depression Category

Characteristic Untreated Depression
(n = 57)
Depression Unresponsive to Medication
(n = 12)
Depression Responsive to Medication
(n = 16)
P Value
Maternal age, y 28 31 31 NS
Gestational age at screening, wk 16 16 17 NS
Race/ethnicity, % < .001
Non-Hispanic white  33.3 75.0 93.8  
Non-Hispanic black  31.6 0 0  
Hispanic  31.6 25.0 0  
Household income ($), % .004
> 15,000 41.2  20.0 6.7  
15,000 to < 30,000 15.7 0 0  
30,000 to < 50,000 19.6  40.0 13.0  
50,000 to 100,000  15.7 30.0 46.7  
> 100,000  7.8 10.0 33.3  
Insurance type, %       < .001
Private  23.2 33.3 93.8  
Public 69.6 50.0 0
Other 5.4  8.3 6.3  
None 1.8  8.3 0  
Education level, %       .002
High school or less 44.6 33.3 12.5  
Some college 42.9  41.7 25.0  
College degree or above 12.5  25.0 62.5  
Employed, % 49.1  25.0 81.3 .011 
Married, % 26.8  33.3 75.0  .002
BMI at first prenatal visit, kg/m²  28 33 29  .758

BMI = body mass index, NS = nonsignificant.

Among the inflammatory markers measured, TNF-α was the only cytokine with levels that significantly differed across the patient groups (Table 2).

Table 2. Inflammatory Marker Concentrations By Depression Category

Cytokine, pg/mL Untreated Depression
(n = 57)
Depression Unresponsive to Medication
(n = 12)
Depression Responsive to Medication
(n = 16)
P Value
CRP 7.30 6.60 4.20 .514
IFN-γ 3.03 3.37 2.51 .347
IL-6 0.60 0.57 0.47 .483
IL-8 1.61 2.34 1.50 .108
IL-13 2.07 2.75 1.89 .509
TNF-α 0.98 1.06 0.74 .016

C-reactive protein, IFN = interferon, IL = interleukin, TNF = tumor necrosis factor.

Women with depression/anxiety responsive to medication had significantly lower concentrations of TNF-α compared with women who had untreated depression (P = .013) or unresponsive depression (P = .018). No difference was observed in the mean TNF-α concentrations between those with untreated or unresponsive depression (P = .762).

“These findings support the theory that antidepressant/anxiety medications used in pregnancy may exert at least some of their effect via modulation of inflammation,” Miller said. Alternatively, higher baseline levels of TNF-α may predict a poorer response to standard antidepressant medication among women with perinatal depression.

Future research will focus on whether proinflammatory cytokines are true mediators of antidepressant responses or whether they identify the likelihood of treatment response.

Source: Miller ES, Grobman WA, Culhane J, et al. Do psychotropic medications reduce inflammation in women with antenatal depression/anxiety? Presented at: Society for Maternal-Fetal Medicine 37th Annual Pregnancy Meeting; January 23-28, 2017; Las Vegas, NV. Abstract 688.