Top

Published in:

01-02-2018 | Original Article

Neurotrophins and neuroinflammation in fetuses exposed to maternal depression and anxiety disorders during pregnancy: a comparative study on cord blood

Authors: Nursel Akbaba, Bılge Burçak Annagür, Alı Annagür, Hıkmet Akbulut, Fıkret Akyürek, Çetın Çelık

Published in: Archives of Women's Mental Health | Issue 1/2018

Abstract

In recent years, there have been changes in the approach to maternal psychiatric disorders and their effects on the fetus, with the focus redirected to the search for biological markers. Neurotrophic factors and inflammatory processes have received particular attention in the past few years. According to the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV), the study sample (n = 136) consisted of three groups: mothers with major depressive disorder (MDD group, n = 25), mothers with anxiety disorder (AD group, n = 18), and mothers without any psychiatric disorders (not diagnosed (ND) group, n = 93). During the delivery/cesarean section, a blood sample was obtained from the umbilical cord. Serum concentrations of BDNF, NT-3, FGF2, TNF-α, and neopterin were determined by enzyme-linked immunosorbent assay (ELISA), according to the manufacturer’s procedure. Clinical and biochemical characteristics were assessed. We did not find a significant difference among the three study groups with regard to BDNF, NT-3, and TNF-α levels. The ANOVA test indicated statistically significant differences in FGF2 levels and neopterin between the study groups. The newborns of mothers with AD had significantly higher FGF2 levels and significantly higher neopterin levels when compared with those of mothers with MDD and healthy mothers. The present study sheds light on the effects of higher FGF2 and neopterin levels in fetuses exposed to AD. Our results should be replicated through further prospective studies with a larger sample size.

Andersson L, Sundström-Poromaa I et al (2004) Neonatal outcome following maternal antenatal depression and anxiety: a population-based study. Am J Epidemiol 9:872–881CrossRef

Arranz L, Guayerbas N et al (2007) Impairment of several immune functions in anxious women. J Psychosom Res 62:1–8CrossRefPubMed

Berger MA, Barros VG et al (2002) Long-term effects of prenatal stress on dopamine and glutamate receptors in adult rat brain. Neurochem Res 27:1525–1533CrossRefPubMed

Boersma GJ, Lee RS et al (2013) Prenatal stress decreases Bdnf expression and increases methylation of Bdnf exon IV in rats. Epigenetics 9(3):437–447CrossRefPubMedPubMedCentral

Brambilla F, Bellodi L et al (1999) Plasma levels of tumor necrosis factor-alpha in patients with panic disorder: effect of alprazolam therapy. Psychiatry Res 89:21–27CrossRefPubMed

Cacci E, Claasen JH et al (2005) Microglia-derived tumor necrosis factor-alpha exaggerates death of newborn hippocampal progenitor cells in vitro. J Neurosci Res 80:789–797CrossRefPubMed

Christian LM, Franco A et al (2010) Depressive symptoms predict exaggerated inflammatory responses to an in vivo immune challenge among pregnant women. Brain Behav Immun 24(1):49–53CrossRefPubMed

Debnath M, Doyle KM et al (2011) Recent advances in psychoneuroimmunology: inflammation in psychiatric disorders. Translational Neurosciencece 2(2):121–113

Dowlati Y, Herrmann N et al (2010) A meta-analysis of cytokines in major depression. Biol Psychiatry 67:446–457CrossRefPubMed

Duman RS, Monteggia LM (2006) A neurotrophic model for stress-related mood disorders. Biol psychiatry 59(12):1116–1127CrossRefPubMed

Dwivedi Y, Rizavi HS et al (2003) Altered gene expression of brain-derived neurotrophic factor and receptor tyrosine kinase B in postmortem brain of suicide subjects. Arch Gen Psychiatry 60(8):804–815CrossRefPubMed

Frank MG, Der-Avakian A et al (2007) Stress-induced glucocorticoids suppress the antisense molecular regulation of FGF-2 expression. Psychoneuroendocrinology 32(4):376–384CrossRefPubMed

Fuchs D, Weiss G et al (1992) The role of neopterin as a monitor of cellular immune activation in transplantation, inflammatory, infectious, and malignant diseases. Crit Rev Clin Lab Sci 29:307–341CrossRefPubMed

Fuchs D, Avanzas P et al (2009) The role of neopterin in atherogenesis and cardiovascular risk assessment. Curr Med Chem 16:4644–4653CrossRefPubMed

García-Bueno B, Caso JR et al (2008) Stress as a neuroinflammatory condition in brain: damaging and protective mechanisms. Neurosci Biobehav Rev 32(6):1136–1151CrossRefPubMed

Gray SM, Bloch MH (2012) Systematic review of proinflammatory cytokines in obsessive–compulsive disorder. Curr Psychiatry Rep 14:220–228CrossRefPubMedPubMedCentral

Green PJ, Walsh FS et al (1996) Bioessays. Promiscuity of fibroblast growth factor receptors 18(8):639–646

Guo M, Liu T et al (2012) Study on serum cytokine levels in posttraumatic stress disorder patients. Asian Pac J Trop Med 5:323–325CrossRefPubMed

Ipekci SH, Kebapcilar AG et al (2015) Serum levels of neopterin in gestational diabetes mellitus: the relationship with Apgar scores. Arch Gynecol Obstet 292(1):103–109CrossRefPubMed

Kodomari I, Wada E et al (2009) Maternal supply of BDNF to mouse fetal brain through the placenta. Neurochem Int 54(2):95–98CrossRefPubMed

Kofman O (2002) The role of prenatal stress in the etiology of developmental behavioural disorders. Neurosci Biobehav Rev 26(4):457–470CrossRefPubMed

Konuk N, Tekin İO et al (2007) Plasma levels of tumor necrosis factor-alpha and interleukin-6 in obsessive–compulsive disorder. Mediat Inflamm 2007:65704CrossRef

Koubaa S, Hällström T et al (2005) Pregnancy and neonatal outcomes in women with eating disorders. Obstet Gynecol 105(2):255–260CrossRefPubMed

Krause D, Jobst A et al (2014) Prenatal immunologic predictors of postpartum depressive symptoms: a prospective study for potential diagnostic markers. Eur Arch Psychiatry Clin Neurosci 264(7):615–624CrossRefPubMed

Kubera M, Obuchowicz E et al (2011) In animal models, psychosocial stress-induced (neuro)inflammation, apoptosis and reduced neurogenesis are associated to the onset of depression. Prog Neuro-Psychopharmacol Biol Psychiatry 35(3):744–759CrossRef

Liu YP, Lin H et al (2005) Tumor necrosis factor-alpha and interleukin-18 modulate neuronal cell fate in embryonic neural progenitor culture. Brain Res 1054:152–158CrossRefPubMed

Maina G, Saracco P et al (2008) Impact of maternal psychological distress on fetal weight, prematurity and intrauterine growth retardation. J Affect Disord 111:214–220CrossRefPubMed

Molteni R, Calabrese F et al (2010) Depression-prone mice with reduced glucocorticoid receptor expression display an altered stress-dependent regulation of brain-derived neurotrophic factor and activity-regulated cytoskeleton-associated protein. J Psychopharmacol 24(4):595–603CrossRefPubMed

Neeley EW, Berger R et al (2011) Prenatal stress differentially alters brain-derived neurotrophic factor expression and signaling across rat strains. Neuroscience 187:24–35CrossRefPubMedPubMedCentral

Numakawa T, Richards M et al (2014) The role of brain-derived neurotrophic factor in comorbid depression: possible linkage with steroid hormones, cytokines, and nutrition. Front Psych 5:136

Radunovic N, Kuczynski E et al (1999) Neopterin concentrations in fetal and maternal blood: a marker of cell-mediated immune activation. Am J Obstet Gynecol 181(1):170–173CrossRefPubMed

Rahman A, Bunn J et al (2007) Association between antenatal depression and low birthweight in a developing country. Acta Psychiatr Scand 115:481–486CrossRefPubMedPubMedCentral

Rash BG, Lim HD et al (2011) FGF signaling expands embryonic cortical surface area by regulating Notch-dependent neurogenesis. J Neurosci 31(43):15604–15617CrossRefPubMedPubMedCentral

Reuss B, von Bohlen und Halbach O (2003) Fibroblast growth factors and their receptors in the central nervous system. Cell Tissue Res 313:139–157CrossRefPubMed

Riva MA, Molteni R et al (2005) Emerging role of the FGF system in psychiatric disorders. Trends Pharmacol Sci 26:228–231CrossRefPubMed

Sapolsky RM (1996) Stress, glucocorticoids, and damage to the nervous system: the current state of confusion. Stress 1(1):1–19CrossRefPubMed

Seguin JA, Brennan J et al (2009) Proinflammatory cytokines diffentially influence adult hippocampal cell proliferation depending upon the route and chronicity of administration. Neuropsychiatr Dis Treat 5:5–14PubMedPubMedCentral

Tapia-Arancibia L, Rage F et al (2004) Physiology of BDNF: focus on hypothalamic function. Front Neuroendocrinol 25(2):77–107CrossRefPubMed

Terwisscha van Scheltinga AF et al (2010) Fibroblast growth factors in schizophrenia. Schizophr Bull 36(6):1157–1166CrossRefPubMed

Terwisscha van Scheltinga AF, Bakker SC et al (2013) Fibroblast growth factors in neurodevelopment and psychopathology. Neuroscientist 19(5):479–494CrossRefPubMed

Tsankova NM, Berton O et al (2006) Sustained hippocampal chromatin regulation in a mouse model of depression and antidepressant action. Nat Neurosci 9(4):519–525CrossRefPubMed

Turner CA, Akil H et al (2006) The fibroblast growth factor system and mood disorders. Biol Psychiatry 59:1128–1135CrossRefPubMed

Uguz F, Gezginc K et al (2011) Are major depression and generalized anxiety disorder associated with intrauterine growth restriction in pregnant women? A case-control study. Gen Hosp Psychiatry 33(6):640.e7–640.e9

Uguz F, Sonmez EO et al (2013) Maternal generalized anxiety disorder during pregnancy and fetal brain development: a comparative study on cord blood brain-derived neurotrophic factor levels. J Psychosom Res 75(4):346–350CrossRefPubMed

Uguz F, Onder Sonmez E et al (2014) Neuroinflammation in the fetus exposed to maternal obsessive-compulsive disorder during pregnancy: a comparative study on cord blood tumor necrosis factor-alpha levels. Compr Psychiatry 55(4):861–865CrossRefPubMed

Valero De Bernabé J, Soriano T et al (2004) Risk factors for low birth weight: a review. Eur J Obstet Gynecol Reprod Biol 116:3–15CrossRefPubMed

Vlodavsky I, Korner G et al (1990) Extracellular matrix-resident growth factors and enzymes: possible involvement in tumor metastasis and angiogenesis. Cancer Metastasis Rev 9(3):203–226CrossRefPubMed

Wang B, Jin K (2015) Current perspectives on the link between neuroinflammation and neurogenesis. Metab Brain Dis 30(2):355–365CrossRefPubMed

Weinstock M (1997) Does prenatal stress impair coping and regulation of hypothalamic–pituitary–adrenal axis? Neurosci. Biobehav Rev 21:1–10CrossRefPubMed

Zhao HX, Yin SS et al (2015) High plasma neopterin levels in Chinese children with autism spectrum disorders. Int J Dev Neurosci 41:92–97CrossRefPubMed

Title: Neurotrophins and neuroinflammation in fetuses exposed to maternal depression and anxiety disorders during pregnancy: a comparative study on cord blood
Authors: Nursel Akbaba
Bılge Burçak Annagür
Alı Annagür
Hıkmet Akbulut
Fıkret Akyürek
Çetın Çelık
Publication date: 01-02-2018
Publisher: Springer Vienna
Published in: Archives of Women's Mental Health / Issue 1/2018
Print ISSN: 1434-1816
Electronic ISSN: 1435-1102
DOI: https://doi.org/10.1007/s00737-017-0774-1

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Neurotrophins and neuroinflammation in fetuses exposed to maternal depression and anxiety disorders during pregnancy: a comparative study on cord blood

Abstract

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 1/2018

Advanced training in reproductive psychiatry: The case for standardization in training and a path to sub-specialty recognition

Raloxifene as an adjunctive treatment for postmenopausal women with schizophrenia: a meta-analysis of randomized controlled trials

Development of a women’s mental health curriculum and evolution to a Women’s Mental Health Area of Concentration in a psychiatry residency program

Maternal supplementation with small-quantity lipid-based nutrient supplements during pregnancy and lactation does not reduce depressive symptoms at 6 months postpartum in Ghanaian women: a randomized controlled trial

Behavioral, cognitive, and emotional coping strategies of women with endometriosis: a critical narrative review

Stability of the Pregnancy Obsessive-Compulsive Personality Disorder Symptoms Checklist