- Email: [email protected]
Are maternal depression symptoms related to umbilical cord cortisol and neurological integrity in the newborn?
Abstracts / Psychoneuroendocrinology 71S (2016) 1–77
terone levels were highest in individuals with the average number of repeats, and declined at either end of the CAG repeat distribution. The lowest testosterone levels were observed in participants with at least one copy of the 4 allele and a short repeat length. APOE2 and APOE-3 carriers demonstrated only small, linear effects in which CAG repeat length was positively associated with testosterone levels. Conclusions: These results provide the first evidence from human studies of an interaction between APOE genotype and a functional polymorphism of the AR gene. Individuals with the 4 allele and a short version of the AR CAG repeat had the lowest testosterone levels, which suggests that APOE might influence androgen action by regulating AR sensitivity. Both the APOE-4 allele and low testosterone have been found to be risk factors for late onset Alzheimer’s disease. These results suggest that these two risk factors may be more closely related than has previously been considered. Funding: Supported by NIA grants: ROI AG022381; RO1 AG018384; RO1 AG018386; RO1 AG022982; and K08 AG047903. http://dx.doi.org/10.1016/j.psyneuen.2016.07.097 Are maternal depression symptoms related to umbilical cord cortisol and neurological integrity in the newborn? Alina Rodriguez 1,2 1
University of Lincoln, United Kingdom Imperial College London, United Kingdom E-mail address: [email protected]. 2
Background: Blood levels of cortisol surge dramatically just before birth. Cortisol is the major regulatory hormone for neonatal adaption in the transition to extra uterine life at birth. Blunted cortisol concentrations have been observed in infants born by Cesarean section and in preterm birth. Cortisol is also indicative of stress. Thus, individual variation in cortisol level at birth may reflect exposure to stress prior to birth. Infants born to women who report high depression symptoms have shown signs of less neurological integrity in the neonatal period. It is unknown whether or not the levels of cortisol in the cord blood of newborns, whose mothers reported depression symptoms during pregnancy, are disturbed and whether this disturbance is related to neurological integrity in the neonate. Methods: Women were recruited in the Obstetrics Department Clinic of Lithuania Health University in Kaunas. A consecutive sample of 135 mothers who delivered full-term (≥37 weeks of gestation) and their newborns were recruited. Umbilical cord blood sample was taken at delivery and Apgar scores were recorded at one, five, and 10 min after birth. The Neurological and Adaptive Capacity Scale was administered by neonatologists at 2 and 24 h after birth to assess neurological integrity of the newborn. On the second day post-delivery, mothers completed the Edinburgh Postnatal Depression Scale (EPDS) to assess depression symptoms during the preceding week as well as sociodemographic and lifestyle characteristics. Results: Cord blood cortisol was related to Apgar score at 1 min and, in turn, was related to poorer neurological integrity at two and 24 h. EPDS scores were related to Apgar scores at one and five minutes and poorer neurological integrity at two hours. Conclusions: The objective of this study was to relate cortisol level measured in umbilical cord blood in term infants at birth with neonatal neurological integrity and maternal depression symptoms. We report here novel associations showing an immediate impact of stress on the newborn infant, though this impact appears
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to be transient and the magnitude of the association was small in comparison to the impact of mode of delivery. http://dx.doi.org/10.1016/j.psyneuen.2016.07.098 Association of DNA methylation marks in the stress response regulating gene KITLG to schizophrenia and bipolar disorder Marco P. Boks ∗ , Lotte C. Houtepen, Yujie He, Hans van Mierlo, René S. Kahn, Lot D. de Witte, Christiaan H. Vinkers Brain Center Rudolf Magnus, Utrecht, The Netherlands E-mail address: [email protected] (M.P. Boks). Background: Transcriptional regulation of the KITLG gene by DNA methylation marks at cg27512205 is associated with cortisol stress response in healthy controls and early exposure to childhood adversities. Compelling evidence shows a higher prevalence of childhood adversities in psychotic disorders, but what the role of this methylation mark is in bipolar disorder and schizophrenia is not clear. Methods: We investigated the association of KITLG methylation to schizophrenia and bipolar disorder and the relationship to childhood adversities in whole blood DNA of a sample of 50 patients with bipolar disorder, 15 with schizophrenia and 91 healthy controls. To further tie KITLG function to stress response regulation we analyses the response of KITLG expression to dexamethasone exposure in vitro using 4 human fibroblasts cultures. Results: KITLG methylation was significantly different between the diagnostics groups (F(187,2) = 22.0, p < 0.001). KITLG methylation was lower in bipolar disorder patients (B = −0.33, p < 0.001) and schizophrenia patients (B = −0.33, p < 0.001) also after adjustment for increased KITLG methylation related to childhood adversities in these patient groups (BP; B = 0.009, p = 0.003, Scz; B = 0.012, p = 0.004). Dexamethasone exposure lead to a 50 percent reduction of KITLG expression (FC = 0.45). Conclusions: The results shed new light on the relationship between epigenetic modifications associated with childhood adversities and increased rates of psychotic disorders. The results are consistent with a model whereby failure to increase KITLG methylation in response to childhood adversities leads to maladaptive epigenetic regulation of the stress response in psychotic disorders Houtepen et al. (2016). Reference Houtepen, L.C., Vinkers, C.H., Carrillo-Roa, T., Hiemstra, M., van Lier, P.A., Meeus, W., Branje, S., Heim, C.M., Nemeroff, C.B., Mill, J., Schalkwyk, L.C., Creyghton, M.P., Kahn, R.S., Joëls, M., Binder, E.B., Boks, M.P., 2016. Genome-wide DNA methylation levels and altered cortisol stress reactivity following childhood trauma in humans. Nat. Commun. 21 (March), 10967.
http://dx.doi.org/10.1016/j.psyneuen.2016.07.099
terone levels were highest in individuals with the average number of repeats, and declined at either end of the CAG repeat distribution. The lowest testosterone levels were observed in participants with at least one copy of the 4 allele and a short repeat length. APOE2 and APOE-3 carriers demonstrated only small, linear effects in which CAG repeat length was positively associated with testosterone levels. Conclusions: These results provide the first evidence from human studies of an interaction between APOE genotype and a functional polymorphism of the AR gene. Individuals with the 4 allele and a short version of the AR CAG repeat had the lowest testosterone levels, which suggests that APOE might influence androgen action by regulating AR sensitivity. Both the APOE-4 allele and low testosterone have been found to be risk factors for late onset Alzheimer’s disease. These results suggest that these two risk factors may be more closely related than has previously been considered. Funding: Supported by NIA grants: ROI AG022381; RO1 AG018384; RO1 AG018386; RO1 AG022982; and K08 AG047903. http://dx.doi.org/10.1016/j.psyneuen.2016.07.097 Are maternal depression symptoms related to umbilical cord cortisol and neurological integrity in the newborn? Alina Rodriguez 1,2 1
University of Lincoln, United Kingdom Imperial College London, United Kingdom E-mail address: [email protected]. 2
Background: Blood levels of cortisol surge dramatically just before birth. Cortisol is the major regulatory hormone for neonatal adaption in the transition to extra uterine life at birth. Blunted cortisol concentrations have been observed in infants born by Cesarean section and in preterm birth. Cortisol is also indicative of stress. Thus, individual variation in cortisol level at birth may reflect exposure to stress prior to birth. Infants born to women who report high depression symptoms have shown signs of less neurological integrity in the neonatal period. It is unknown whether or not the levels of cortisol in the cord blood of newborns, whose mothers reported depression symptoms during pregnancy, are disturbed and whether this disturbance is related to neurological integrity in the neonate. Methods: Women were recruited in the Obstetrics Department Clinic of Lithuania Health University in Kaunas. A consecutive sample of 135 mothers who delivered full-term (≥37 weeks of gestation) and their newborns were recruited. Umbilical cord blood sample was taken at delivery and Apgar scores were recorded at one, five, and 10 min after birth. The Neurological and Adaptive Capacity Scale was administered by neonatologists at 2 and 24 h after birth to assess neurological integrity of the newborn. On the second day post-delivery, mothers completed the Edinburgh Postnatal Depression Scale (EPDS) to assess depression symptoms during the preceding week as well as sociodemographic and lifestyle characteristics. Results: Cord blood cortisol was related to Apgar score at 1 min and, in turn, was related to poorer neurological integrity at two and 24 h. EPDS scores were related to Apgar scores at one and five minutes and poorer neurological integrity at two hours. Conclusions: The objective of this study was to relate cortisol level measured in umbilical cord blood in term infants at birth with neonatal neurological integrity and maternal depression symptoms. We report here novel associations showing an immediate impact of stress on the newborn infant, though this impact appears
37
to be transient and the magnitude of the association was small in comparison to the impact of mode of delivery. http://dx.doi.org/10.1016/j.psyneuen.2016.07.098 Association of DNA methylation marks in the stress response regulating gene KITLG to schizophrenia and bipolar disorder Marco P. Boks ∗ , Lotte C. Houtepen, Yujie He, Hans van Mierlo, René S. Kahn, Lot D. de Witte, Christiaan H. Vinkers Brain Center Rudolf Magnus, Utrecht, The Netherlands E-mail address: [email protected] (M.P. Boks). Background: Transcriptional regulation of the KITLG gene by DNA methylation marks at cg27512205 is associated with cortisol stress response in healthy controls and early exposure to childhood adversities. Compelling evidence shows a higher prevalence of childhood adversities in psychotic disorders, but what the role of this methylation mark is in bipolar disorder and schizophrenia is not clear. Methods: We investigated the association of KITLG methylation to schizophrenia and bipolar disorder and the relationship to childhood adversities in whole blood DNA of a sample of 50 patients with bipolar disorder, 15 with schizophrenia and 91 healthy controls. To further tie KITLG function to stress response regulation we analyses the response of KITLG expression to dexamethasone exposure in vitro using 4 human fibroblasts cultures. Results: KITLG methylation was significantly different between the diagnostics groups (F(187,2) = 22.0, p < 0.001). KITLG methylation was lower in bipolar disorder patients (B = −0.33, p < 0.001) and schizophrenia patients (B = −0.33, p < 0.001) also after adjustment for increased KITLG methylation related to childhood adversities in these patient groups (BP; B = 0.009, p = 0.003, Scz; B = 0.012, p = 0.004). Dexamethasone exposure lead to a 50 percent reduction of KITLG expression (FC = 0.45). Conclusions: The results shed new light on the relationship between epigenetic modifications associated with childhood adversities and increased rates of psychotic disorders. The results are consistent with a model whereby failure to increase KITLG methylation in response to childhood adversities leads to maladaptive epigenetic regulation of the stress response in psychotic disorders Houtepen et al. (2016). Reference Houtepen, L.C., Vinkers, C.H., Carrillo-Roa, T., Hiemstra, M., van Lier, P.A., Meeus, W., Branje, S., Heim, C.M., Nemeroff, C.B., Mill, J., Schalkwyk, L.C., Creyghton, M.P., Kahn, R.S., Joëls, M., Binder, E.B., Boks, M.P., 2016. Genome-wide DNA methylation levels and altered cortisol stress reactivity following childhood trauma in humans. Nat. Commun. 21 (March), 10967.
http://dx.doi.org/10.1016/j.psyneuen.2016.07.099