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  • 1.
    Ahlsson, Fredrik
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Pediatrics.
    Akerud, Helena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Schijven, Dick
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Olivier, Jocelien
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology. Univ Groningen, Dept Behav Physiol, Groningen, Netherlands.;Karolinska Inst, Ctr Gender Med, Stockholm, Sweden..
    Sundström Poromaa, Inger
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Gene Expression in Placentas From Nondiabetic Women Giving Birth to Large for Gestational Age Infants2015In: Reproductive Sciences, ISSN 1933-7191, E-ISSN 1933-7205, Vol. 22, no 10, p. 1281-1288Article in journal (Refereed)
    Abstract [en]

    Gestational diabetes, obesity, and excessive weight gain are known independent risk factors for the birth of a large for gestational age (LGA) infant. However, only 1 of the 10 infants born LGA is born by mothers with diabetes or obesity. Thus, the aim of the present study was to compare placental gene expression between healthy, nondiabetic mothers (n = 22) giving birth to LGA infants and body mass index-matched mothers (n = 24) giving birth to appropriate for gestational age infants. In the whole gene expression analysis, only 29 genes were found to be differently expressed in LGA placentas. Top upregulated genes included insulin-like growth factor binding protein 1, aminolevulinate synthase 2, and prolactin, whereas top downregulated genes comprised leptin, gametocyte-specific factor 1, and collagen type XVII 1. Two enriched gene networks were identified, namely, (1) lipid metabolism, small molecule biochemistry, and organismal development and (2) cellular development, cellular growth, proliferation, and tumor morphology.

  • 2.
    Comasco, Erika
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neuro-psycho-pharmacology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Hellgren, Charlotte
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Olivier, Jocelien D A
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Skalkidou, Alkistis
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Sundström Poromaa, Inger
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Supraphysiological hormonal status, anxiety disorders, and COMT Val/Val genotype are associated with reduced sensorimotor gating in women2015In: Psychoneuroendocrinology, ISSN 0306-4530, E-ISSN 1873-3360, Vol. 60, p. 217-23Article in journal (Refereed)
    Abstract [en]

    Pregnancy is a period characterized by a supraphysiological hormonal status, and greater anxiety proneness, which can lead to peripartum affective symptoms with dramatic consequences not only for the woman but also for the child. Clinical psychiatry is heavily hampered by the paucity of objective and biology-based intermediate phenotypes. Prepulse inhibition (PPI) of the startle response, a neurophysiological measure of sensorimotor gating, has been poorly investigated in relation to anxiety and in pregnant women. In the present study, the PPI of healthy non-pregnant women (n=82) and late pregnant women (n=217) was investigated. Age, BMI, depression and anxiety symptoms, tobacco use, and antidepressant medication were considered. We investigated and provided evidence of lower PPI: (i) in healthy pregnant women compared to healthy non-pregnant controls, (ii) in pregnant women with anxiety disorders compared to healthy pregnant women, (iii) in pregnant women with anxiety disorders using SSRI compared to un-medicated pregnant women with anxiety disorders, and (iv) in healthy pregnant women carrying the COMT Val158Met Val/Val genotype compared to Met carriers. Altogether, a reduced sensorimotor gating as an effect of supraphysiological hormonal status, anxiety disorders, SSRIs, and catecholaminergic genotype, implicate the putative relevance of lower PPI as an objective biological correlate of anxiety proneness in pregnant women. These findings call for prospective studies to dissect the multifactorial influences on PPI in relation to mental health of pregnant women.

  • 3.
    Comasco, Erika
    et al.
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Comasco: Neuropsychopharmacology.
    Schijven, Dick
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    de Maeyer, Hanne
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Vrettou, Maria
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Comasco: Neuropsychopharmacology.
    Nylander, Ingrid
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Sundström-Poromaa, Inger
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Reproductive Health.
    Olivier, Jocelien D. A.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health. Department Neurobiology, Unit Behavioural Neuroscience, Groningen Institute for Evolutionary Life Sciences, University of Groningen, Groningen 9712 CP, The Netherlands.
    Constitutive serotonin transporter reduction resembles maternal separation with regard to stress-related gene expression2019In: ACS Chemical Neuroscience, ISSN 1948-7193, E-ISSN 1948-7193, Vol. 10, no 7, p. 3132-3142Article in journal (Refereed)
    Abstract [en]

    Interactive effects between allelic variants of the serotonin transporter (5-HTT) promoter-linked polymorphic region (5-HTTLPR) and stressors on depression symptoms have been documented, as well as questioned, by meta-analyses. Translational models of constitutive 5-htt reduction and experimentally controlled stressors often led to inconsistent behavioral and molecular findings and often did not include females. The present study sought to investigate the effect of 5-htt genotype, maternal separation, and sex on the expression of stress-related candidate genes in the rat hippocampus and frontal cortex. The mRNA expression levels of Avp, Pomc, Crh, Crhbp, Crhr1, Bdnf, Ntrk2, Maoa, Maob, and Comt were assessed in the hippocampus and frontal cortex of 5-htt± and 5-htt+/+ male and female adult rats exposed, or not, to daily maternal separation for 180 min during the first 2 postnatal weeks. Gene- and brain region-dependent, but sex-independent, interactions between 5-htt genotype and maternal separation were found. Gene expression levels were higher in 5-htt+/+ rats not exposed to maternal separation compared with the other experimental groups. Maternal separation and 5-htt+/− genotype did not yield additive effects on gene expression. Correlative relationships, mainly positive, were observed within, but not across, brain regions in all groups except in non-maternally separated 5-htt+/+ rats. Gene expression patterns in the hippocampus and frontal cortex of rats exposed to maternal separation resembled the ones observed in rats with reduced 5-htt expression regardless of sex. These results suggest that floor effects of 5-htt reduction and maternal separation might explain inconsistent findings in humans and rodents.

  • 4.
    Hannerfors, Anna-Karin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Hellgren, Charlotte
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Schijven, Dick
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Iliadis, Stavros I.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Comasco, Erika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neuro-psycho-pharmacology.
    Skalkidou, Alkistis
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Olivier, Jocelien D. A.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Sundström-Poromaa, Inger
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Treatment with serotonin reuptake inhibitors during pregnancy is associated with elevated corticotropin-releasing hormone levels2015In: Psychoneuroendocrinology, ISSN 0306-4530, E-ISSN 1873-3360, Vol. 58, p. 104-113Article in journal (Refereed)
    Abstract [en]

    Treatment with serotonin reuptake inhibitors (SSRI) has been associated with an increased risk of preterm birth, but causality remains unclear. While placental CRH production is correlated with gestational length and preterm birth, it has been difficult to establish if psychological stress or mental health problems are associated with increased CRH levels. This study compared second trimester CRH serum concentrations in pregnant women on SSRI treatment (n=207) with untreated depressed women (n=56) and controls (n=609). A secondary aim was to investigate the combined effect of SSRI treatment and CRH levels on gestational length and risk for preterm birth. Women on SSRI treatment had significantly higher second trimester CRH levels than controls, and untreated depressed women. CRH levels and SSRI treatment were independently associated with shorter gestational length. The combined effect of SSRI treatment and high CRH levels yielded the highest risk estimate for preterm birth. SSRI treatment during pregnancy is associated with increased CRH levels. However, the elevated risk for preterm birth in SSRI users appear not to be mediated by increased placental CRH production, instead CRH appear as an independent risk factor for shorter gestational length and preterm birth.

  • 5.
    Iliadis, Stavros I
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Sylvén, Sara
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Hellgren, Charlotte
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Olivier, Jocelien D
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology. Dept. of Behavioural Neuroscience, Groningen Institute for Evolutionary Life Sciences, Nijenborgh, 7, 9747 AG, University of Groningen, Groningen, The Netherlands.
    Schijven, Dick
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Comasco, Erika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology. Dept. of Neuroscience, Uppsala University, 751 24, Uppsala, Sweden.
    Chrousos, George P
    Dept. of Pediatrics, Athens University Medical School, Athens, Greece.
    Sundström Poromaa, Inger
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Skalkidou, Alkistis
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Mid-pregnancy corticotropin-releasing hormone levels in association with postpartum depressive symptoms2016In: Depression and anxiety (Print), ISSN 1091-4269, E-ISSN 1520-6394, Vol. 33, no 11, p. 1023-1030Article in journal (Refereed)
    Abstract [en]

    Background: Peripartum depression is a common cause of pregnancy and postpartum related morbidity. The production of corticotropin-releasing hormone (CRH) from the placenta alters the profile of hypothalamus-pituitary-adrenal axis hormones and may be associated with postpartum depression. The purpose of this study was to assess, in non-depressed pregnant women, the possible association between CRH levels in pregnancy and depressive symptoms postpartum.

    Methods: A questionnaire containing demographic data and the Edinburgh Postnatal Depression Scale was filled in gestational weeks 17 and 32, and six weeks postpartum. Blood samples were collected in week 17 for assessment of CRH. A logistic regression model was constructed, using postpartum Edinburgh Postnatal Depression Scale score as the dependent variable and log transformed CRH levels as the independent variable. Confounding factors were included in the model. Sub-analyses after exclusion of study subjects with preterm birth, small for gestational age newborns, and women on corticosteroids were performed.

    Results: 535 women without depressive symptoms during pregnancy were included. Logistic regression showed an association between high CRH levels in gestational week 17 and postpartum depressive symptoms, before and after controlling for several confounders (unadjusted Odds Ratio = 1.11; 95% CI 1.01 – 1.22, adjusted Odds Ratio = 1.13; 95% CI 1.02 – 1.26, per 0.1 unit increase in log corticotropin-releasing hormone). Exclusion of women with preterm birth and newborns small for gestational age as well as women who used inhalation corticosteroids during pregnancy did not alter the results.

    Conclusions: This study suggests an association between high CRH levels in gestational week 17 and the development of postpartum depressive symptoms, among women without depressive symptoms during pregnancy.

  • 6.
    Kaihola, Helena
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Olivier, Jocelien D A
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Sundström Poromaa, Inger
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Åkerud, Helena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    The effect of antenatal depression and selective serotonin reuptake inhibitor treatment on nerve growth factor signaling in human placenta2015In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, no 1, article id e0116459Article in journal (Refereed)
    Abstract [en]

    Depressive symptoms during pregnancy are common and may have impact on the developing child. Selective serotonin reuptake inhibitors (SSRIs) are the most prescribed antidepressant treatment, but unfortunately, these treatments can also negatively affect the behavioral development and health of a child during pregnancy. In addition, serotonin (5-HT) exerts neurotrophic actions with thus far not fully known effects in the offspring. The neurotrophic growth factor (NGF) is involved in neuronal cell survival and differentiation, and altered placenta levels have been found to increase the risk for pregnancy complications, similar to those found in women treated with SSRIs. We therefore investigated whether the NGF signaling pathway was altered in the placenta from women treated with SSRIs (n = 12) and compared them with placenta from depressed (n = 12) and healthy mothers (n = 12). Results from immunohistochemical stainings revealed that placental NGF protein levels of SSRI-treated women were increased in both trophoblasts and endothelial cells compared with depressed and control women. In addition, downstream of the NGF receptor TrkA, increased levels of the signaling proteins ROCK2 and phosphorylated Raf-1 were found in stromal cells and a tendency towards increased levels of ROCK2 in trophoblasts and endothelial cells in SSRI-treated women when compared to healthy controls. SSRI-treated women also displayed increased levels of phosphorylated ROCK2 in all placental cell types studied in comparison with depressed and control women. Interestingly, in placental endothelial cells from depressed women, NGF levels were significantly lower compared to control women, but ROCK2 levels were increased compared with control and SSRI-treated women. Taken together, these results show that the NGF signaling and downstream pathways in the placenta are affected by SSRI treatment and/or antenatal depression. This might lead to an altered placental function, although the clinical relevance of our findings still needs to be investigated.

  • 7.
    Olivier, Jocelien D A
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Akerud, Helena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Sundström Poromaa, Inger
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Antenatal depression and antidepressants during pregnancy: Unraveling the complex interactions for the offspring2015In: European Journal of Pharmacology, ISSN 0014-2999, E-ISSN 1879-0712, Vol. 753, p. 257-262Article in journal (Refereed)
    Abstract [en]

    During pregnancy the risk for a woman to develop a depressive episode is as high as 20%. Antenatal depression is not harmless for the developing child as several changes, including neurodevelopmental alterations, have been reported. Sometimes it is unavoidable to treat a pregnant mother with antidepressants, especially when she is suicidal. Currently, selective serotonin reuptake inhibitors (SSRIs) are the pharmacological choice of antidepressant treatment. SSRIs do not cause gross teratogenic alterations and are generally considered safe for use in pregnancy. However, although SSRIs may relieve the maternal symptoms, they definitively cross the placenta partially influencing the neurodevelopment of the fetus. In this review an overview is given of the effects on the offspring of maternal antenatal depression and the putative neurodevelopmental effects of SSRI treatment during pregnancy. Although we primarily focus on human data, some animal data are discussed to describe possible mechanisms on how SSRIs are affecting underlying biological mechanisms associated with depression. In summary, maternal depression may have long-lasting effects on the offspring, whereas prenatal SSRI exposure also increases the risk for long-lasting effects. It remains to be determined whether the effects found after SSRI treatment in pregnant women are only due to the SSRI exposure or if the underlying depression is also contributing to these effects. The possibility of epigenetic alterations as one of the underlying mechanisms that is altered by SSRI exposure is discussed. However much more research in this area is needed to explain the exact role of epigenetic mechanisms in SSRI exposure during pregnancy.

  • 8.
    Olivier, Jocelien D A
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Vinkers, Christiaan H
    Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences and Rudolf Magnus Institute of Neuroscience, Utrecht University, Netherlands.
    Olivier, Berend
    Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences and Rudolf Magnus Institute of Neuroscience, Utrecht University, Netherlands.
    The role of the serotonergic and GABA system in translational approaches in drug discovery for anxiety disorders2013In: Frontiers in Pharmacology, ISSN 1663-9812, E-ISSN 1663-9812, Vol. 4, no Article 74, p. 1-17Article in journal (Refereed)
    Abstract [en]

    There is ample evidence that genetic factors play an important role in anxiety disorders. In support, human genome-wide association studies have implicated several novel candidate genes. However, illumination of such genetic factors involved in anxiety disorders has not resulted in novel drugs over the past decades. A complicating factor is the heterogeneous classification of anxiety disorders in the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR) and diverging operationalization of anxiety used in preclinical and clinical studies. Currently, there is an increasing focus on the gene × environment (G × E) interaction in anxiety as genes do not operate in isolation and environmental factors have been found to significantly contribute to the development of anxiety disorders in at-risk individuals. Nevertheless, extensive research on G × E mechanisms in anxiety has not resulted in major breakthroughs in drug discovery. Modification of individual genes in rodent models has enabled the specific study of anxiety in preclinical studies. In this context, two extensively studied neurotransmitters involved in anxiety are the gamma-aminobutyric acid (GABA) and 5-HT (5-hydroxytryptamine) system. In this review, we illustrate the complex interplay between genes and environment in anxiety processes by reviewing preclinical and clinical studies on the serotonin transporter (5-HTT), 5-HT1A receptor, 5-HT2 receptor, and GABAA receptor. Even though targets from the serotonin and GABA system have yielded drugs with known anxiolytic efficacy, the relation between the genetic background of these targets and anxiety symptoms and development of anxiety disorders is largely unknown. The aim of this review is to show the vast complexity of genetic and environmental factors in anxiety disorders. In light of the difficulty with which common genetic variants are identified in anxiety disorders, animal models with translational validity may aid in elucidating the neurobiological background of these genes and their possible role in anxiety. We argue that, in addition to human genetic studies, translational models are essential to map anxiety-related genes and to enhance our understanding of anxiety disorders in order to develop potentially novel treatment strategies.

  • 9.
    Olivier, Jocelien D A
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Åkerud, Helena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Kaihola, Helena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Pawluski, J. L.
    GIGA-Neurosciences, University of Liège, Liège, Belgium.
    Skalkidou, Alkistis
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Högberg, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Sundström Poromaa, Inger
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    The effects of maternal depression and maternal selective serotonin reuptake inhibitor exposure on offspring2013In: Frontiers in Cellular Neuroscience, ISSN 1662-5102, E-ISSN 1662-5102, Vol. 7, p. 73-Article, review/survey (Refereed)
    Abstract [en]

    It has been estimated that 20% of pregnant women suffer from depression and it is well-documented that maternal depression can have long-lasting effects on the child. Currently, common treatment for maternal depression has been the selective serotonin reuptake inhibitor medications (SSRIs) which are used by 2-3% of pregnant women in the Nordic countries and by up to 10% of pregnant women in the United States. Antidepressants cross the placenta and are transferred to the fetus, thus, the question arises as to whether children of women taking antidepressants are at risk for altered neurodevelopmental outcomes and, if so, whether the risks are due to SSRI medication exposure or to the underlying maternal depression. This review considers the effects of maternal depression and SSRI exposure on offspring development in both clinical and preclinical populations. As it is impossible in humans to study the effects of SSRIs without taking into account the possible underlying effects of maternal depression (healthy pregnant women do not take SSRIs), animal models are of great value. For example, rodents can be used to determine the effects of maternal depression and/or perinatal SSRI exposure on offspring outcomes. Unraveling the joint (or separate) effects of maternal depression and SSRI exposure will provide more insights into the risks or benefits of SSRI exposure during gestation and will help women make informed decisions about using SSRIs during pregnancy.

  • 10.
    Olivier, Jocelien D A
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Åkerud, Helena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Skalkidou, Alkistis
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Kaihola, Helena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Sundström-Poromaa, Inger
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    The effects of antenatal depression and antidepressant treatment on placental gene expression2015In: Frontiers in Cellular Neuroscience, ISSN 1662-5102, E-ISSN 1662-5102, Vol. 8, p. 465-Article in journal (Refereed)
    Abstract [en]

    The effects of antenatal depression and antidepressant treatment during pregnancy on both mother and child are vigorously studied, but the underlying biology for these effects is largely unknown. The placenta plays a crucial role in the growth and development of the fetus. We performed a gene expression study on the fetal side of the placenta to investigate gene expression patterns in mothers with antenatal depression and in mothers using antidepressant treatment during pregnancy. Placental samples from mothers with normal pregnancies, from mothers with antenatal depression, and from mothers using antidepressants were collected. We performed a pilot microarray study to investigate alterations in the gene expression and selected several genes from the microarray for biological validation with qPCR in a larger sample. In mothers with antenatal depression 108 genes were differentially expressed, whereas 109 genes were differentially expressed in those using antidepressants. Validation of the microarray revealed more robust gene expression differences in the seven genes picked for confirmation in antidepressant-treated women than in depressed women. Among the genes that were validated ROCK2 and C12orf39 were differentially expressed in both depressed and antidepressant-treated women, whereas ROCK1, GCC2, KTN1, and DNM1L were only differentially expressed in the antidepressant-treated women. In conclusion, antenatal depression and antidepressant exposure during pregnancy are associated with altered gene expression in the placenta. Findings on those genes picked for validation were more robust among antidepressant-treated women than in depressed women, possibly due to the fact that depression is a multifactorial condition with varying degrees of endocrine disruption. It remains to be established whether the alterations found in the gene expression of the placenta are found in the fetus as well.

  • 11.
    Schijven, Dick
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Sousa, V C
    Department of Clinical Neuroscience, Karolinska Institute, Sweden.
    Roelofs, J
    Department of Clinical Neuroscience, Karolinska Institute, Sweden.
    Olivier, B
    Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences and Rudolf Magnus Institute of Neuroscience, Utrecht University, The Netherlands.
    Olivier, J D A
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Serotonin 1A receptors and sexual behavior in a genetic model of depression2014In: Pharmacology, Biochemistry and Behavior, ISSN 0091-3057, E-ISSN 1873-5177, Vol. 121, no SI, p. 82-87Article in journal (Refereed)
    Abstract [en]

    The Flinder Sensitive Line (FSL) is a rat strain that displays distinct behavioral and neurochemical features of major depression. Chronic selective serotonin reuptake inhibitors (SSRIs) are able to reverse these symptoms in FSL rats. It is well known that several abnormalities in the serotonergic system have been found in FSL rats, including increased 5-HT brain tissue levels and reduced 5-HT synthesis. SSRIs are known to exert (part of) their effects by desensitization of the 5-HT1A receptor and FSL rats appear to have lower 5-HT1A receptor densities compared with Flinder Resistant Line (FRL) rats. We therefore studied the sensitivity of this receptor on the sexual behavior performance in both FRL and FSL rats. First, basal sexual performance was studied after saline treatment followed by treatment of two different doses of the 5-HT1A receptor agonist ±8-OH-DPAT. Finally we measured the effect of a 5-HT1A receptor antagonist to check for specificity of the 5-HT1A receptor activation. Our results show that FSL rats have higher ejaculation frequencies compared with FRL rats which do not fit with a more depressive-like phenotype. Moreover FRL rats are more sensitive to effects of ±8-OH-DPAT upon EL and IF than FSL rats. The blunted response of FSL rats to the effects of ±8-OH-DPAT may be due to lower densities of 5-HT1A receptors.

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