- Email: [email protected]
Prenatal exposure to SSRI antidepressants and anxious behaviours in childhood
Abstracts / Int. J. Devl Neuroscience 47 (2015) 1–131
rodevelopmental mechanisms. Possible effects of treatment and illness duration were limited because patients were studied during their first-episode. http://dx.doi.org/10.1016/j.ijdevneu.2015.04.115 ISDN2014 0141 Disruption of cortical circuitry development in glycine receptor alpha 2 knockout mice Giovanni Morelli 1,∗ , Ariel Avila 1,2 , Robert J. Harvey 3 , B. Brône 1 , Laurent Nguyen 2 , Jean-Michel Rigo 1 1 Cell physiology, BIOMED institute, Hasselt University, Agoralaan C, Diepenbeek, Belgium 2 GIGA-Neurosciences, Interdisciplinary Cluster for Applied Genoproteomics (GIGA-R), C.H.U. Sart Tilman, University of Liège, Liège, Belgium 3 Department of Pharmacology, UCL School of Pharmacy, 29-39 Brunswick Square, London WC1N 1AX, United Kingdom
Previous studies in our laboratory have revealed an important role of strychnine-sensitive glycine receptors (GlyRs) in the cerebral cortex during neurogenesis. Specifically, the absence of GlyR alpha 2 subunits in a genetically disrupted mouse model leads to interneuronal migration defects. In order to evaluate the long-term consequences of these early defects, we examined the role of GlyRs during postnatal development of the cerebral cortex. Remarkably, GlyR alpha 2 knockout mice displayed a significant reduction in the number of parvalbumin positive interneurons at postnatal day 14. Moreover, morphological and synaptic defects were assessed in the cerebral cortex of knockout mice by performing 3D reconstruction of single neurons and by whole-cell patch-clamp recordings. Morphological studies of biocytin-filled dlx-EGFP expressing interneurons revealed altered growth of dendrites and of spine generation. Furthermore, whole-cell recordings showed a substantial increase in the frequency of spontaneous post-synaptic currents (sPSCs) in cortical interneurons of knockout mice together with a decrease of inhibitory post-synaptic currents (IPSCs) and an increase of excitatory postsynaptic currents (EPSCs). These preliminary findings are consistent with the hypothesis that GlyRs might have an important role during circuit development in the cerebral cortex. http://dx.doi.org/10.1016/j.ijdevneu.2015.04.116 ISDN2014 0142 Prenatal exposure to SSRI antidepressants and anxious behaviours in childhood G.E. Hanley 1,2,∗ , U. Brain 2,3 , T.F. Oberlander 2,3 1
University of British Columbia School of Population and Public Health, Canada 2 Child and Family Research Institute, Canada 3 University of British Columbia, Department of Pediatrics, Canada Background: Early life manipulations of the neurotransmitter serotonin (5HT) following prenatal SSRI antidepressant exposure (pSRI) causes increased anxiety-like behaviours in adulthood in animal models. Increasing use of SSRIs in pregnancy raises questions about whether similar changes in 5HT signaling in humans during critical periods of early brain development are also associated with increased anxiety in exposed children.
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Objective: In a prospective cohort study we examined whether pSRI exposure influenced internalizing and anxious behaviours in children at 3 years and at 6 years of age. Design/Methods: Parent reports of child behaviour were obtained from 44 pSRI exposed and 66 unexposed children at age 3 and again at age 6. Internalizing, and anxious subscales were assessed as 2 different outcome variables using repeated measures ANOVA and random intercept hierarchical regression models. We adjusted for maternal mood during pregnancy, postpartum and at age 3 and 6, sex of the child, maternal smoking and drinking during pregnancy and use of other psychotropic medicines during pregnancy. Results: pSRI exposed children scored significantly higher on internalizing and anxious behaviours at 3 and 6 years of age than children who were not exposed (F = 8.05, p = 0.0049, and F = 8.41, p = 0.0040, respectively). The fully adjusted hierarchical regression models indicated a positive and significant relationship between pSRI exposure and internalizing and anxious behaviours even when controlling for maternal mood during pregnancy, postpartum and childhood (p = 0.046 and p = 0.041, respectively). There was also a positive relationship between concurrent maternal mood and internalizing and anxious behaviours (p < 0.001 and p = 0.004, respectively). Conclusions: pSRI exposure was associated with sustained higher levels of anxious and internalizing behaviours in early childhood, even when controlling for concurrent maternal depression. Independently concurrent maternal depression also had an impact. These findings suggest that in spite of prenatal maternal SSRI treatment, childhood emotional well being continues to be at risk. http://dx.doi.org/10.1016/j.ijdevneu.2015.04.117 ISDN2014 0143 A hybrid electrical and chemical circuit in the spinal cord generates a novel transient embryonic motor behavior Laura D. Knogler 1,2,∗,1 , Joel Ryan 1,1 , Louis Saint-Amant 1 , Pierre Drapeau 1,2 1 Departments of Pathology and Cell Biology, GRSNC, Université de Montréal, Montréal, Québec, Canada 2 Neuroscience, GRSNC, Université de Montréal, Montréal, Québec, Canada E-mail address: [email protected] (L.D. Knogler).
Spontaneous activity occurs in many areas of the developing nervous system including the spinal cord, where it may play an important role in the maturation of locomotor circuitry. The earliest motor behavior in vertebrate embryos is a periodic slow contraction of the trunk. In zebrafish, spontaneous coils initially rely exclusively on electrical and not chemical synaptic activity in the spinal cord. These slow single coils are followed several hours later by the appearance of a response to touch with a series of rapidly alternating coils that depends on newly appearing glutamatergic transmission. Just twelve hours after the appearance of coils, embryos are capable of swimming in response to touch. We describe here a new spontaneous behavior, double coiling, that consists of two alternating contractions of the tail that occur in rapid succession. This behavior appears around the same time as the touch response but is sensory-independent. We show that double coiling is glutamate-dependent, like the touch response, and
1
Co-authors.
rodevelopmental mechanisms. Possible effects of treatment and illness duration were limited because patients were studied during their first-episode. http://dx.doi.org/10.1016/j.ijdevneu.2015.04.115 ISDN2014 0141 Disruption of cortical circuitry development in glycine receptor alpha 2 knockout mice Giovanni Morelli 1,∗ , Ariel Avila 1,2 , Robert J. Harvey 3 , B. Brône 1 , Laurent Nguyen 2 , Jean-Michel Rigo 1 1 Cell physiology, BIOMED institute, Hasselt University, Agoralaan C, Diepenbeek, Belgium 2 GIGA-Neurosciences, Interdisciplinary Cluster for Applied Genoproteomics (GIGA-R), C.H.U. Sart Tilman, University of Liège, Liège, Belgium 3 Department of Pharmacology, UCL School of Pharmacy, 29-39 Brunswick Square, London WC1N 1AX, United Kingdom
Previous studies in our laboratory have revealed an important role of strychnine-sensitive glycine receptors (GlyRs) in the cerebral cortex during neurogenesis. Specifically, the absence of GlyR alpha 2 subunits in a genetically disrupted mouse model leads to interneuronal migration defects. In order to evaluate the long-term consequences of these early defects, we examined the role of GlyRs during postnatal development of the cerebral cortex. Remarkably, GlyR alpha 2 knockout mice displayed a significant reduction in the number of parvalbumin positive interneurons at postnatal day 14. Moreover, morphological and synaptic defects were assessed in the cerebral cortex of knockout mice by performing 3D reconstruction of single neurons and by whole-cell patch-clamp recordings. Morphological studies of biocytin-filled dlx-EGFP expressing interneurons revealed altered growth of dendrites and of spine generation. Furthermore, whole-cell recordings showed a substantial increase in the frequency of spontaneous post-synaptic currents (sPSCs) in cortical interneurons of knockout mice together with a decrease of inhibitory post-synaptic currents (IPSCs) and an increase of excitatory postsynaptic currents (EPSCs). These preliminary findings are consistent with the hypothesis that GlyRs might have an important role during circuit development in the cerebral cortex. http://dx.doi.org/10.1016/j.ijdevneu.2015.04.116 ISDN2014 0142 Prenatal exposure to SSRI antidepressants and anxious behaviours in childhood G.E. Hanley 1,2,∗ , U. Brain 2,3 , T.F. Oberlander 2,3 1
University of British Columbia School of Population and Public Health, Canada 2 Child and Family Research Institute, Canada 3 University of British Columbia, Department of Pediatrics, Canada Background: Early life manipulations of the neurotransmitter serotonin (5HT) following prenatal SSRI antidepressant exposure (pSRI) causes increased anxiety-like behaviours in adulthood in animal models. Increasing use of SSRIs in pregnancy raises questions about whether similar changes in 5HT signaling in humans during critical periods of early brain development are also associated with increased anxiety in exposed children.
41
Objective: In a prospective cohort study we examined whether pSRI exposure influenced internalizing and anxious behaviours in children at 3 years and at 6 years of age. Design/Methods: Parent reports of child behaviour were obtained from 44 pSRI exposed and 66 unexposed children at age 3 and again at age 6. Internalizing, and anxious subscales were assessed as 2 different outcome variables using repeated measures ANOVA and random intercept hierarchical regression models. We adjusted for maternal mood during pregnancy, postpartum and at age 3 and 6, sex of the child, maternal smoking and drinking during pregnancy and use of other psychotropic medicines during pregnancy. Results: pSRI exposed children scored significantly higher on internalizing and anxious behaviours at 3 and 6 years of age than children who were not exposed (F = 8.05, p = 0.0049, and F = 8.41, p = 0.0040, respectively). The fully adjusted hierarchical regression models indicated a positive and significant relationship between pSRI exposure and internalizing and anxious behaviours even when controlling for maternal mood during pregnancy, postpartum and childhood (p = 0.046 and p = 0.041, respectively). There was also a positive relationship between concurrent maternal mood and internalizing and anxious behaviours (p < 0.001 and p = 0.004, respectively). Conclusions: pSRI exposure was associated with sustained higher levels of anxious and internalizing behaviours in early childhood, even when controlling for concurrent maternal depression. Independently concurrent maternal depression also had an impact. These findings suggest that in spite of prenatal maternal SSRI treatment, childhood emotional well being continues to be at risk. http://dx.doi.org/10.1016/j.ijdevneu.2015.04.117 ISDN2014 0143 A hybrid electrical and chemical circuit in the spinal cord generates a novel transient embryonic motor behavior Laura D. Knogler 1,2,∗,1 , Joel Ryan 1,1 , Louis Saint-Amant 1 , Pierre Drapeau 1,2 1 Departments of Pathology and Cell Biology, GRSNC, Université de Montréal, Montréal, Québec, Canada 2 Neuroscience, GRSNC, Université de Montréal, Montréal, Québec, Canada E-mail address: [email protected] (L.D. Knogler).
Spontaneous activity occurs in many areas of the developing nervous system including the spinal cord, where it may play an important role in the maturation of locomotor circuitry. The earliest motor behavior in vertebrate embryos is a periodic slow contraction of the trunk. In zebrafish, spontaneous coils initially rely exclusively on electrical and not chemical synaptic activity in the spinal cord. These slow single coils are followed several hours later by the appearance of a response to touch with a series of rapidly alternating coils that depends on newly appearing glutamatergic transmission. Just twelve hours after the appearance of coils, embryos are capable of swimming in response to touch. We describe here a new spontaneous behavior, double coiling, that consists of two alternating contractions of the tail that occur in rapid succession. This behavior appears around the same time as the touch response but is sensory-independent. We show that double coiling is glutamate-dependent, like the touch response, and
1
Co-authors.