Emily S Miller1, Allie Sakowicz2, Archana Roy2, Amy Yang3, John T Sullivan4, William A Grobman2, Katherine L Wisner5. 1. Department of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, Northwestern University, Chicago, IL; Department of Psychiatry and Behavioral Sciences, Northwestern University, Chicago, IL. Electronic address: emily-miller-1@northwestern.edu. 2. Department of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, Northwestern University, Chicago, IL. 3. Department of Preventative Medicine, Division of Biostatistics, Northwestern University, Chicago, IL. 4. Department of Anesthesiology, Northwestern University, Chicago, IL. 5. Department of Psychiatry and Behavioral Sciences, Northwestern University, Chicago, IL.
Abstract
BACKGROUND: While perinatal depression is one of the most common complications of pregnancy, there is an insufficient understanding of the mechanistic underpinnings of disease. While an association between peripheral inflammatory cytokines and major depressive disorder has been demonstrated, cytokines cannot freely cross the blood-brain barrier, and thus, they give little insight into alternations in brain function. Because the brain is in direct communication with the cerebrospinal fluid, assessment of inflammation in the cerebrospinal fluid may be more directly related to the biologic markers of affective change. OBJECTIVE: Our objectives were to examine the association between perinatal depression and inflammatory cytokines in plasma, the association between perinatal depression and inflammatory cytokines in cerebrospinal fluid, and the correlations between plasma and cerebrospinal fluid inflammatory cytokines. STUDY DESIGN: This was a prospective, observational study of women with a singleton gestation at term undergoing a scheduled cesarean delivery. Women were screened for depression and those with depressive symptomatology preferentially enrolled. The Mini-International Neuropsychiatric Interview was administered to confirm the clinical diagnosis of depression. Maternal plasma and cerebrospinal fluid were collected preoperatively and cytokines measured via flow cytometry. Bivariable and multivariable analyses were used to determine the association between each cytokine and perinatal depression. Correlations were measured between the cytokines in plasma and cerebrospinal fluid. RESULTS: Of the 117 women who met inclusion criteria, 76 (65%) screened positive for depression, 15 (20%) of whom met the clinical diagnostic criteria for depression. There were no significant associations between any of the plasma cytokines and perinatal depression in our sample. Conversely, in multivariable analyses, higher cerebrospinal fluid interleukin-1β (adjusted odds ratio, 232.7, 95% confidence interval, 5.9-9148.5), interleukin-23 (adjusted odds ratio, 22.1, 95% confidence interval, 1.7-294.5), and interleukin-33 (adjusted odds ratio, 1.7, 95% confidence interval, 1.1-2.6) concentrations were significantly associated with increased odds of perinatal depression. The plasma and cerebrospinal fluid cytokine concentrations were not strongly correlated. CONCLUSION: Higher concentrations of cerebrospinal fluid cytokines were associated with perinatal depression. These cerebrospinal fluid cytokines were not strongly correlated with plasma cytokines, and accordingly, plasma cytokines were not significantly associated with perinatal depression. Central neuroinflammation, as opposed to peripheral inflammation, may represent a mechanistic pathway that contributes to perinatal depression.
BACKGROUND: While perinatal depression is one of the most common complications of pregnancy, there is an insufficient understanding of the mechanistic underpinnings of disease. While an association between peripheral inflammatory cytokines and major depressive disorder has been demonstrated, cytokines cannot freely cross the blood-brain barrier, and thus, they give little insight into alternations in brain function. Because the brain is in direct communication with the cerebrospinal fluid, assessment of inflammation in the cerebrospinal fluid may be more directly related to the biologic markers of affective change. OBJECTIVE: Our objectives were to examine the association between perinatal depression and inflammatory cytokines in plasma, the association between perinatal depression and inflammatory cytokines in cerebrospinal fluid, and the correlations between plasma and cerebrospinal fluid inflammatory cytokines. STUDY DESIGN: This was a prospective, observational study of women with a singleton gestation at term undergoing a scheduled cesarean delivery. Women were screened for depression and those with depressive symptomatology preferentially enrolled. The Mini-International Neuropsychiatric Interview was administered to confirm the clinical diagnosis of depression. Maternal plasma and cerebrospinal fluid were collected preoperatively and cytokines measured via flow cytometry. Bivariable and multivariable analyses were used to determine the association between each cytokine and perinatal depression. Correlations were measured between the cytokines in plasma and cerebrospinal fluid. RESULTS: Of the 117 women who met inclusion criteria, 76 (65%) screened positive for depression, 15 (20%) of whom met the clinical diagnostic criteria for depression. There were no significant associations between any of the plasma cytokines and perinatal depression in our sample. Conversely, in multivariable analyses, higher cerebrospinal fluid interleukin-1β (adjusted odds ratio, 232.7, 95% confidence interval, 5.9-9148.5), interleukin-23 (adjusted odds ratio, 22.1, 95% confidence interval, 1.7-294.5), and interleukin-33 (adjusted odds ratio, 1.7, 95% confidence interval, 1.1-2.6) concentrations were significantly associated with increased odds of perinatal depression. The plasma and cerebrospinal fluid cytokine concentrations were not strongly correlated. CONCLUSION: Higher concentrations of cerebrospinal fluid cytokines were associated with perinatal depression. These cerebrospinal fluid cytokines were not strongly correlated with plasma cytokines, and accordingly, plasma cytokines were not significantly associated with perinatal depression. Central neuroinflammation, as opposed to peripheral inflammation, may represent a mechanistic pathway that contributes to perinatal depression.
Authors: Rachel M Hayes; Pingsheng Wu; Richard C Shelton; William O Cooper; William D Dupont; Ed Mitchel; Tina V Hartert Journal: Am J Obstet Gynecol Date: 2012-04-30 Impact factor: 8.661
Authors: Anniella Isgren; Joel Jakobsson; Erik Pålsson; Carl Johan Ekman; Anette G M Johansson; Carl Sellgren; Kaj Blennow; Henrik Zetterberg; Mikael Landén Journal: Brain Behav Immun Date: 2014-10-14 Impact factor: 7.217
Authors: U H Frommberger; J Bauer; P Haselbauer; A Fräulin; D Riemann; M Berger Journal: Eur Arch Psychiatry Clin Neurosci Date: 1997 Impact factor: 5.270
Authors: Gianluca Pandolfo; Giovanni Genovese; Marco Casciaro; Maria Rosaria Anna Muscatello; Antonio Bruno; Giovanni Pioggia; Sebastiano Gangemi Journal: Medicina (Kaunas) Date: 2021-03-26 Impact factor: 2.430
Authors: Licínia Ganança; Hanga C Galfalvy; Sebastian Cisneros-Trujillo; Zahra Basseda; Thomas B Cooper; Xinguo Ren; Maria Luisa Figueira; Maria A Oquendo; J John Mann; M Elizabeth Sublette Journal: J Psychiatr Res Date: 2020-12-17 Impact factor: 4.791