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    Topic review

    Mood Dysregulations in GDM

    Subjects: Others
    View times: 29
    Submitted by: Amira Ali


    Gestational diabetes mellitus (GDM) is a metabolic condition of increased maternal blood glucose leve. GDM affects up to 36% of pregnant women. Mood dysregulations (MDs, e.g., depression, distress, and anxiety) are common among women with GDM. Symptoms of depression and anxiety usually overlap with one another as well as with distress symptoms; they develop in up to 27% and 24% of pregnancies, respectively.

    1. Overview

    The co-occurrence of GDM and MDs is high, and it is closely linked to poor glycemic control, poor self-care ability, functional disability, low quality of life, and premature death. Depression in diabetics is hard to treat given the complex nature of diabetes, especially when it occurs during pregnancy [1]. Both conditions share common risk factors, pathologies and adverse effects for mothers and their offspring[2].

    2. Adverse effects of GDM and MDs

    GDM is associated with numerous morbid maternal and fetal outcomes: miscarriage, dystocia, cesarean section, neonatal death, premature birth, congenital anomalies, macrosomia (large for gestational age), respiratory distress, neonatal jaundice, hypoglycemia, hypocalcemia, and polycythemia [3][4][5]. Meanwhile, MDs increase the likelihood of prematurity, birth weight abnormalities, stunted growth, cognitive and neurodevelopmental deficits, infants’ temperament, anxiety, and depression, delays in fine motor and language development[6][7], not initiating breastfeeding, early termination of breastfeeding, increased formula usage[8][9] [15,16], poor maternal antenatal attachment, and higher postpartum parenting stress[8].

    3. Risk factors and pathophysiological mechanisms common in GDM and MDs

    The accelerated prevalence of GDM and MDs is associated with common risk factors such as poverty, unhealthy diet and sedentary lifestyle, which contribute to chronic inflammatory conditions such as obesity and type 2 diabetes mellitus (T2DM)[10][11][12][13]. Sleep disturbances, some of them develop in mood disorders (e.g., apnea, poor sleep quality, and short sleep), trigger the development of GDM[10][11]. Both GDM and MDs share common mechanisms[2] illustrated in Figure 1 and described in detail in this section.

    Figure 1. Schematic summary of key risk factors and pathologies contributing to gestational diabetes and maternal mood dysregulation along with the therapeutic role of dietary interventions and physical activity in reverting these conditions.

    Unhealthy food (rich in fat and refined carbohydrates and deficient in dietary fibers that exist in fruits and vegetables) and physical inactivity promote the propagation of toxic endobacteria and inhibit the growth of beneficial gut microflora[14][15][16]. Such imbalance result in a deficiency of nutritive metabolites produced by beneficial bacteria, which are necessary for proper immune function and overall health[2][17][18][19]. In addition, toxic bacterial metabolites cause injury to the intestinal wall to cause disseminated tissue damage e.g., in the brain leading to MDs and in the pancreas leading to GDM[2].

    The inflammatory reaction and associated oxidative stress conducive to GDM and MDs is accelerated by fetal tissue and placental-related molecules [4,27-29]. Secretions of these tissues bind the receptor of advanced glycation end products (RAGE) and toll-like receptors (TLR2 and TLR4), which indirectly activate C-X-C chemokine receptor type 4 (CXCR4) [20][21][22][23].

    Estrogen is a key modulators of signal transduction that regulate cognition and mood[15][24]. Alterations in estrogen are a key contributor to the high development of negative emotional states among women at different stages of life [24][25]. Estrogen dysfunction occurs in GDM due to oxidation of estrogen by cytochrome P450 enzymes resulting in genotoxic metabolites such as 2-hydroxyestrogen and 4-hydroxyestrogen. These metabolites exist in the blood, and they induce DNA damages in various tissues. They also bind insulin, neuroglobin, human serum albumin, and immunoglobulin. Their binding to insulin, a process known as insulin estrogenization, hinders insulin affinity of binding to insulin receptor resulting in vivid insulin resistance [26]. In the meantime, dysfunctional estrogen is uncapable of modulating brain structures

    MDs in pregnancy may occur in response to the psychosocial stress imposed by pregnancy, hormonal fluctuations associated with pregnancy, as well as the inflammatory milieu generated by GDM and its underlying pathologies[2].

    4. Common non-pharmacological interventions for GDM and MDs

    Physical exercise is well-known to increase the sensitivity of body tissue to insulin resulting into glycemic control[16][19]. It is also an effective treatment for mood disorders[27][28]. Its therapeutic effects take place through the regulation of key signaling molecules involved in cellular activities as well as correction of gut dysbiosis, thus preventing gut-related systemic inflammation[16][19][29][30].

    A plethora of research emphasize the role of functional foods in the control of GDM and MDs[28][31][32]. Such foods correct gut microbiome dysfunction, modulate signaling involved in metabolism, immune function, antioxidant production, autophagy, etc.[17][18][33][34]. A considerable attention is paid to refraining from high fat/high carbohydrate diets and adopting dietary patterns that involve the intake of fresh fruits, vegetables, sea foods, complex carbohydrates (whole grains and bran of wheat and rice), bee products, etc.[2][16][35][36]. Intermittent fasting (IF) as a form of dietary restriction has been effectively used to correct pathologies that underlie T2DM and MDs. We have recently demonstrated a case of GDM properly managed by IF indicating that this modality may prove to be effective if investigated on a large scale[2].

    5. Conclusion

    Both GDM and mood disorders are common in pregnancy, and their co-occurrence leads to grave effects on mothers and their fetus. Both conditions can be exacerbated by unhealthy diet and sedentary behaviors while dietary patterns such as IF, the intake of functional foods, and physical exercise can reverse the pathologies that underlie these conditions leading to better outcomes.

    This entry is adapted from 10.3390/ijerph17249379


    1. Mendez, D.D.; Thorpe, R.J.; Amutah, N.; Davis, E.M.; Walker, R.E.; Chapple-McGruder, T.; Bodnar, L. Neighborhood racial composition and poverty in association with pre-pregnancy weight and gestational weight gain. SSM-Popul. Health 2016, 2, 692–699, doi:10.1016/j.ssmph.2016.09.008.
    2. Santangelo, C.; Filardi, T.; Perrone, G.; Mariani, M.; Mari, E.; Scazzocchio, B.; Masella, R.; Brunelli, R.; Lenzi, A.; Zicari, A.; et al. Cross-talk between fetal membranes and visceral adipose tissue involves HMGB1-RAGE and VIP-VPAC2 pathways in human gestational diabetes mellitus. Acta Diabetol. 2019, 56, 681–689, doi:10.1007/s00592-019-01304-x.
    3. Abdel Wahed, W.Y.; Hassan, S.K.; Eldessouki, R. Malnutrition and Its Associated Factors among Rural School Children in Fayoum Governorate, Egypt. J Environ. Public Health 2017, 2017, 4783791, doi:10.1155/2017/4783791.
    4. Amer, H.M.; Abd El Baky, R.S.; Nasr, M.S.; Hendawy, L.M.; Ibrahim, W.A.; Taha, M.O. Anti-islet Cell Antibodies in a Sample of Egyptian Females with Gestational Diabetes and its Relation to Development of Type 1 Diabetes Mellitus. Curr. Diabetes Rev. 2018, 14, 389–394, doi:10.2174/1573399813666170502110559.
    5. Saif Elnasr, I.; Ammar, H. Ultrasound markers for prediction of gestational diabetes mellitus in early pregnancy in Egyptian women: Observational study. J. Matern. Fetal Neonatal Med. 2020, 1–7, doi:10.1080/14767058.2019.1678132.
    6. El Sagheer, G.; Hamdi, L. Prevalence and risk factors for gestational diabetes mellitus according to the Diabetes in Pregnancy Study Group India in comparison to International Association of the Diabetes and Pregnancy Study Groups in El-Minya, Egypt. Egypt. J. Intern. Med. 2018, 30, 131–139, doi:10.4103/ejim.ejim_11_18.
    7. Salem, M.L.; Zeid, W.A.; Ismail, M.A. Prevalence and Predictors of Gestational Diabetes Mellitus among Pregnant Women Attending Fanara Family Center, in Egypt. Suez Canal Univ. Med J. 2019, 22, 64–72, doi:10.21608/scumj.2019.65162.
    8. Khalil, N.A.; Fathy, W.M.; Mahmoud, N.S. Screening for Gestational Diabetes Among Pregnant Women Attending a Rural Family Health Center- Menoufia Governorate- Egypt. J. Fam. Med. Health Care 2017, 3, 6–11, doi:10.11648/j.jfmhc.20170301.12.
    9. Muche, A.A.; Olayemi, O.O.; Gete, Y.K. Prevalence and determinants of gestational diabetes mellitus in Africa based on the updated international diagnostic criteria: A systematic review and meta-analysis. Arch. Public Health 2019, 77, 36, doi:10.1186/s13690-019-0362-0.
    10. Filardi, T.; Catanzaro, G.; Mardente, S.; Zicari, A.; Santangelo, C.; Lenzi, A.; Morano, S.; Ferretti, E. Non-Coding RNA: Role in Gestational Diabetes Pathophysiology and Complications. Int. J. Mol. Sci. 2020, 21, 4020, doi:10.3390/ijms21114020.
    11. Nguyen-Ngo, C.; Jayabalan, N.; Haghvirdizadeh, P.; Salomon, C.; Lappas, M. Role of adipose tissue in regulating fetal growth in gestational diabetes mellitus. Placenta 2020, 102, 39–48, doi:10.1016/j.placenta.2020.05.006.
    12. Filardi, T.; Tavaglione, F.; Di Stasio, M.; Fazio, V.; Lenzi, A.; Morano, S. Impact of risk factors for gestational diabetes (GDM) on pregnancy outcomes in women with GDM. J. Endocrinol. Invest. 2018, 41, 671–676, doi:10.1007/s40618-017-0791-y.
    13. Chmurzynska, A.; Mlodzik, M.A.; Radziejewska, A.; Szwengiel, A.; Malinowska, A.M.; Nowacka-Woszuk, J. Caloric restriction can affect one-carbon metabolism during pregnancy in the rat: A transgenerational model. Biochimie 2018, 152, 181–187, doi:10.1016/j.biochi.2018.07.007.
    14. Hernandez, T.L.; Friedman, J.E.; Barbour, L.A. Insulin Resistance in Pregnancy: Implications for Mother and Offspring. In Insulin Resistance: Childhood Precursors of Adult Disease, Zeitler, P.S., Nadeau, K.J., Eds. Springer International Publishing: Cham, Switzerland, 2020; pp. 67–94.
    15. Pintaudi, B.; Fresa, R.; Dalfrà, M.; Dodesini, A.R.; Vitacolonna, E.; Tumminia, A.; Sciacca, L.; Lencioni, C.; Marcone, T.; Lucisano, G.; et al. The risk stratification of adverse neonatal outcomes in women with gestational diabetes (STRONG) study. Acta Diabetol. 2018, 55, 1261–1273, doi:10.1007/s00592-018-1208-x.
    16. Filardi, T.; Panimolle, F.; Lenzi, A.; Morano, S. Bisphenol A and Phthalates in Diet: An Emerging Link with Pregnancy Complications. Nutrients 2020, 12, 525, doi:10.3390/nu12020525.
    17. Soubry, A.; Murphy, S.K.; Huang, Z.; Murtha, A.; Schildkraut, J.M.; Jirtle, R.L.; Wang, F.; Kurtzberg, J.; Demark-Wahnefried, W.; Forman, M.R.; et al. The effects of depression and use of antidepressive medicines during pregnancy on the methylation status of the IGF2 imprinted control regions in the offspring. Clin. Epigenetics 2011, 3, 2, doi:10.1186/1868-7083-3-2.
    18. Meers, J.M.; Nowakowski, S. Sleep, premenstrual mood disorder, and women’s health. Curr. Opin. Psychol. 2020, 34, 43–49, doi:10.1016/j.copsyc.2019.09.003.
    19. Sadurni, C.; Schneider, B.; Perez Delgadillo, P.; Rodriguez, M.; Tourgerman, I. A-72The Effects of Maternal Prenatal Mental Health Stress on Neurodevelopmental Deficits. Arch. Clin. Neuropsychol. 2016, 31, 611–611, doi:10.1093/arclin/acw043.72.
    20. Hernandez, T.L.; Brand-Miller, J.C. Nutrition Therapy in Gestational Diabetes Mellitus: Time to Move Forward. Diabetes Care 2018, 41, 1343–1345, doi:10.2337/dci18-0014.
    21. Aoyagi, S.S.; Tsuchiya, K.J. Does maternal postpartum depression affect children's developmental outcomes? J. Obstet. Gynaecol. Res. 2019, 45, 1809–1820, doi:10.1111/jog.14064.
    22. Ali, A.M.; Ahmed, A.H.; Smail, L. Psychological Climacteric Symptoms and Attitudes toward Menopause among Emirati Women. Int. J. Environ. Res. Public Health 2020, 17, 5028, doi:10.3390/ijerph17145028.
    23. Ecklund-Flores, L.; Myers, M.M.; Monk, C.; Perez, A.; Odendaal, H.J.; Fifer, W.P. Maternal depression during pregnancy is associated with increased birth weight in term infants. Dev. Psychobiol. 2017, 59, 314–323, doi:10.1002/dev.21496.
    24. Alqahtani, A.H.; Al Khedair, K.; Al-Jeheiman, R.; Al-Turki, H.A.; Al Qahtani, N.H. Anxiety and depression during pregnancy in women attending clinics in a University Hospital in Eastern province of Saudi Arabia: Prevalence and associated factors. Int. J. Women Health 2018, 10, 101–108, doi:10.2147/IJWH.S153273.
    25. Ali, A.M.; Green, J. Factor structure of the depression anxiety stress Scale-21 (DASS-21): Unidimensionality of the Arabic version among Egyptian drug users. Subst. Abus. Treat. Prev. Policy 2019, 14, 40, doi:10.1186/s13011-019-0226-1.
    26. Howdeshell, K.L.; Ornoy, A. Depression and Its Treatment During Pregnancy: Overview and Highlights. Birth Defects Res. 2017, 109, 877–878, doi:10.1002/bdr2.1080.
    27. Galbally, M.; Watson, S.J.; Boyce, P.; Nguyen, T.; Lewis, A.J. The mother, the infant and the mother-infant relationship: What is the impact of antidepressant medication in pregnancy. J. Affect. Disord. 2020, 272, 363–370, doi:10.1016/j.jad.2020.03.116.
    28. Stuebe, A.M.; Meltzer-Brody, S.; Propper, C.; Pearson, B.; Beiler, P.; Elam, M.; Walker, C.; Mills-Koonce, R.; Grewen, K. The Mood, Mother, and Infant Study: Associations Between Maternal Mood in Pregnancy and Breastfeeding Outcome. Breastfeed. Med 2019, 14, 551–559, doi:10.1089/bfm.2019.0079.
    29. Ali, A.M.; Hassan, A.A.; Hendawy, A.O. The Adverse Effects of Antidepressant Medication Treatments on the Offspring of Women with Perinatal Depression. Sci. J. Res. Rev. 2019, 1, SJRR.MS.ID.000508, doi:10.33552/SJRR.2019.01.000509.
    30. Malheiros, R.T.; Delgado, H.O.; Felber, D.T.; Kraus, S.I.; Dos Santos, A.R.S.; Manfredini, V.; da Silva, M.D. Mood disorders are associated with the reduction of brain derived neurotrophic factor in the hypocampus in rats submitted to the hipercaloric diet. Metab. Brain Dis. 2020, 1–7, doi:10.1007/s11011-020-00625-z.
    31. Viana, L.V.; Gross, J.L.; Azevedo, M.J. Dietary Intervention in Patients With Gestational Diabetes Mellitus: A Systematic Review and Meta-analysis of Randomized Clinical Trials on Maternal and Newborn Outcomes. Diabetes Care 2014, 37, 3345–3355, doi:10.2337/dc14-1530.
    32. Gilbert, L.; Gross, J.; Lanzi, S.; Quansah, D.Y.; Puder, J.; Horsch, A. How diet, physical activity and psychosocial well-being interact in women with gestational diabetes mellitus: An integrative review. BMC Pregnancy Childbirth 2019, 19, 60, doi:10.1186/s12884-019-2185-y.
    33. Ali, A.M.; Hendawy, A.O. So, Antidepressant Drugs have Serious Adverse Effects, but what are the Alternatives? Nov. Appro Drug Des. Dev. 2018, 4, 555636, doi:10.19080/NAPDD.2018.04.555636.
    34. Mudry, J.M.; Lassiter, D.G.; Nylen, C.; Garcia-Calzon, S.; Naslund, E.; Krook, A.; Zierath, J.R. Insulin and Glucose Alter Death-Associated Protein Kinase 3 (DAPK3) DNA Methylation in Human Skeletal Muscle. Diabetes 2017, 66, 651–662, doi:10.2337/db16-0882.
    35. Mijatovic-Vukas, J.; Capling, L.; Cheng, S.; Stamatakis, E.; Louie, J.; Cheung, N.W.; Markovic, T.; Ross, G.; Senior, A.; Brand-Miller, J.C.; et al. Associations of Diet and Physical Activity with Risk for Gestational Diabetes Mellitus: A Systematic Review and Meta-Analysis. Nutrients 2018, 10, 698, doi:10.3390/nu10060698.
    36. Gómez-Donoso, C.; Sánchez-Villegas, A.; Martínez-González, M.A.; Gea, A.; Mendonça, R.D.; Lahortiga-Ramos, F.; Bes-Rastrollo, M. Ultra-processed food consumption and the incidence of depression in a Mediterranean cohort: The SUN Project. Eur. J. Nutr. 2020, 59, 1093–1103, doi:10.1007/s00394-019-01970-1.