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BARCELONA – Prenatal exposure to selective serotonin reuptake inhibitors late in pregnancy was associated with a significantly increased risk of anxious and/or depressed behaviors at 5 years of age in the prospective Norwegian Mother and Child Cohort Study.
Other than that specific red flag, however, the outcomes of in utero exposure to maternal SSRIs were reassuringly benign. Prenatal exposure during early- or mid-pregnancy was not associated with increased risk of anxious/depressed behaviors, compared with nonexposure; that adverse effect was restricted to exposure at week 29 of pregnancy or later. Nor did in utero exposure to maternal SSRIs during any time in pregnancy pose an increased risk for pediatric externalizing, emotional, or social problems in this observational study of 8,359 Norwegian mother-child dyads, Josefina Castro-Fornieles, MD, PhD, observed at the annual congress of the European College of Neuropsychopharmacology.
The huge Norwegian study was among what she considers the four most important studies in child/adolescent psychiatry published through the first three quarters of 2018. The others she highlighted were a large longitudinal observational study that demonstrated that persistent maternal postnatal depression was strongly associated with a variety of pediatric behavioral disturbances documented during assessments at ages 3.5, 16, and 18 years; a Philadelphia study showing that multiple traumatic stressful events or any assaultive trauma experienced by children or adolescents were independently associated with significant psychopathology and neurocognitive deficits; and a Dutch brain MRI study that pinpointed a reduction in gray matter volume in the anterior cingulate cortex as a potential key mediator of the neurobiologic aftereffects of childhood sexual abuse.
She selected those studies because they shared a common theme, one that constituted her key take-home message: “When recording antecedents during a clinical assessment, both with adults and children, it is clear that we have to ask in a more detailed way – using validated scales and interviews if possible – about the mother’s prenatal problems, including psychopharmacological treatment. That is something we often don’t do in a sufficiently detailed way in our clinical practice. And it’s also important to ask about life events; abuse during childhood and adolescence can be really important. We can modulate our treatment depending upon whether there is an influence of any of these aspects,” said Dr. Castro-Fornieles, director of the Clinical Institute of Neuroscience at the Hospital Clinic of Barcelona and a recent past-president of the Spanish Society for Child and Adolescent Psychiatry.
The following are her Top 4 studies:
The Norwegian Mother and Child Cohort Study
The increased risk of anxious and/or depressed behaviors in children exposed to selective serotonin reuptake inhibitors (SSRIs) late in pregnancy did not emerge until the year-5 assessment; it wasn’t evident at the 1.5- or 3-year evaluations.
The investigators emphasized a key lesson from their study: The importance of following children with late-pregnancy exposure to maternal SSRI therapy for development of symptoms of anxiety and/or depression (J Am Acad Child Adolesc Psychiatry. 2018 Mar;57[3]:200-8). Dr. Castro-Fornieles strongly endorsed that recommendation. However, she noted what she considers an important limitation to the study: even though the University of Oslo investigators adjusted for numerous potential confounders in their risk models – including maternal body mass index, parity, education, smoking, substance use, breastfeeding, folic acid use, and other medications used during pregnancy – it’s not possible in a study such as this to control for genetic and environmental risk factors, which she suspects also were at work.
The Avon Longitudinal Study of Parents and Children in the United Kingdom
Maternal postnatal depression is common, affecting roughly 10% of mothers. But it is not invariably associated with adverse mental health outcomes in their children. This study of nearly 10,000 mothers and their children sought to identify which children were at most risk. Using the Edinburgh Postnatal Depression Scale, the international team of investigators categorized maternal postnatal depression as moderate, marked, or severe. The affective disorder was deemed persistent if scores on the Edinburgh scale were elevated at both 2 and 8 months after delivery.
Postnatal depression, whether persistent or not, was associated with roughly a 2- to 2.4-fold increase for child behavioral disturbances when assessed at age 3.5 years using the Rutter Total Problems Scale. But postnatal depression that was persistent was the real difference maker: It carried a much higher risk of adverse behavioral outcomes and cognitive deficits than did the nonpersistent version. Indeed, persistent severe postnatal depression was associated a 4.8-fold increased risk of behavioral problems at age 3.5 years, a 2.65-fold greater risk of markedly lower grades in mathematics at age 16 years, and a 7.4-fold increased prevalence of depression at 18 years of age. The investigators advised screening mothers during the first postpartum year in order to identify those with persistent postpartum depression (JAMA Psychiatry. 2018 Mar 1;75[3]:247-53).
Dr. Castro-Fornieles said an important shortcoming of the Avon study was that it did not record paternal data.
“The study didn’t consider depression or other functional measures in the father, his commitment to childrearing, and whether the family was together or divorced. I feel this is an important limitation in many studies. For me, it’s really important to consider what’s happening with the fathers,” she said.
Traumatic stress load, psychopathology, and cognition
An eye-opening report from the Philadelphia Neurodevelopmental Cohort documented a surprisingly high level of lifetime exposure to traumatic events among 9,498 youth aged 8-21 years, and the stepwise manner by which a greater traumatic stress load was associated with increasing severity of psychopathology and cognitive deficits. Notably, the study participants were recruited from general pediatric clinics in the Children’s Hospital of Philadelphia health care network; they were not patients seeking psychiatric help. And yet, extensive structured psychiatric evaluation showed that 23% of them had a history of one traumatic stressful event, 12% had two, and 1% had three or more.
In analyses adjusted for lifetime history of depression or PTSD, a higher traumatic event load was associated with increased risk of externalizing behaviors, mood/anxiety disorders, psychosis spectrum, and fear. Moreover, a high trauma stress load was associated with a 5.3-fold increased risk of suicidal thoughts and a 3.2-fold increased likelihood of cannabis use, compared with youth who had never been exposed to a traumatic event. Increased stress load also was associated with worse cognitive performance on tests of executive functioning, social cognition, and complex reasoning.
A history of assaultive trauma – being badly beaten, threatened with a weapon, or sexually abused – was associated with more severe psychopathology than in subjects with a history of nonassaultive traumatic events (Psychol Med. 2018 Apr 15:1-10).
Session moderator Carmen Moreno, MD, a child and adolescent psychiatrist at Gregorio Marañón University Hospital in Madrid, commented, “It was striking to me that the prevalence of childhood traumatic events was so high in a pediatric community sample. Is the measure the investigators chose the right measure?”
Dr. Castro-Fornieles replied that it was a very sensitive measure, in that an event many would consider part of normal life – for example, seeing a relative’s body on display in a funeral home – was scored as a traumatic exposure.
“Only one exposure is not that important,” she said. “The impact increases as you increase the number of traumatic events. And also the assaultive ones.”
Sexual abuse leaves a fingerprint
Investigators at Leiden (the Netherlands) University performed neuroimaging that looked at numerous brain regions of interest in 21 adolescents with childhood sexual abuse–related PTSD and 25 matched healthy controls. The standout finding was that the dorsal gray matter volume of the anterior cingulate cortex was significantly smaller in the teens with PTSD and a history of childhood sexual abuse (Eur Neuropsychopharmacol. 2017 Nov;27[11]:1163-71).
The investigators wanted a pure sample of patients with PTSD after childhood sexual abuse, so they excluded individuals who had experienced childhood sexual abuse and had a diagnosis of attention-deficit/hyperactivity disorder, oppositional defiant disorder, obsessive-compulsive disorder, conduct disorder, pervasive developmental disorder, bipolar disorder, or a psychotic disorder. That is both a strength and a limitation of the study, in Dr. Castro-Fornieles’ view.
“To me, that excludes too many of the children we see in our clinical settings. This work needs to be corroborated in a bigger sample, including patients with other diagnoses,” she said.
She reported having no financial conflicts regarding her presentation.
BARCELONA – Prenatal exposure to selective serotonin reuptake inhibitors late in pregnancy was associated with a significantly increased risk of anxious and/or depressed behaviors at 5 years of age in the prospective Norwegian Mother and Child Cohort Study.
Other than that specific red flag, however, the outcomes of in utero exposure to maternal SSRIs were reassuringly benign. Prenatal exposure during early- or mid-pregnancy was not associated with increased risk of anxious/depressed behaviors, compared with nonexposure; that adverse effect was restricted to exposure at week 29 of pregnancy or later. Nor did in utero exposure to maternal SSRIs during any time in pregnancy pose an increased risk for pediatric externalizing, emotional, or social problems in this observational study of 8,359 Norwegian mother-child dyads, Josefina Castro-Fornieles, MD, PhD, observed at the annual congress of the European College of Neuropsychopharmacology.
The huge Norwegian study was among what she considers the four most important studies in child/adolescent psychiatry published through the first three quarters of 2018. The others she highlighted were a large longitudinal observational study that demonstrated that persistent maternal postnatal depression was strongly associated with a variety of pediatric behavioral disturbances documented during assessments at ages 3.5, 16, and 18 years; a Philadelphia study showing that multiple traumatic stressful events or any assaultive trauma experienced by children or adolescents were independently associated with significant psychopathology and neurocognitive deficits; and a Dutch brain MRI study that pinpointed a reduction in gray matter volume in the anterior cingulate cortex as a potential key mediator of the neurobiologic aftereffects of childhood sexual abuse.
She selected those studies because they shared a common theme, one that constituted her key take-home message: “When recording antecedents during a clinical assessment, both with adults and children, it is clear that we have to ask in a more detailed way – using validated scales and interviews if possible – about the mother’s prenatal problems, including psychopharmacological treatment. That is something we often don’t do in a sufficiently detailed way in our clinical practice. And it’s also important to ask about life events; abuse during childhood and adolescence can be really important. We can modulate our treatment depending upon whether there is an influence of any of these aspects,” said Dr. Castro-Fornieles, director of the Clinical Institute of Neuroscience at the Hospital Clinic of Barcelona and a recent past-president of the Spanish Society for Child and Adolescent Psychiatry.
The following are her Top 4 studies:
The Norwegian Mother and Child Cohort Study
The increased risk of anxious and/or depressed behaviors in children exposed to selective serotonin reuptake inhibitors (SSRIs) late in pregnancy did not emerge until the year-5 assessment; it wasn’t evident at the 1.5- or 3-year evaluations.
The investigators emphasized a key lesson from their study: The importance of following children with late-pregnancy exposure to maternal SSRI therapy for development of symptoms of anxiety and/or depression (J Am Acad Child Adolesc Psychiatry. 2018 Mar;57[3]:200-8). Dr. Castro-Fornieles strongly endorsed that recommendation. However, she noted what she considers an important limitation to the study: even though the University of Oslo investigators adjusted for numerous potential confounders in their risk models – including maternal body mass index, parity, education, smoking, substance use, breastfeeding, folic acid use, and other medications used during pregnancy – it’s not possible in a study such as this to control for genetic and environmental risk factors, which she suspects also were at work.
The Avon Longitudinal Study of Parents and Children in the United Kingdom
Maternal postnatal depression is common, affecting roughly 10% of mothers. But it is not invariably associated with adverse mental health outcomes in their children. This study of nearly 10,000 mothers and their children sought to identify which children were at most risk. Using the Edinburgh Postnatal Depression Scale, the international team of investigators categorized maternal postnatal depression as moderate, marked, or severe. The affective disorder was deemed persistent if scores on the Edinburgh scale were elevated at both 2 and 8 months after delivery.
Postnatal depression, whether persistent or not, was associated with roughly a 2- to 2.4-fold increase for child behavioral disturbances when assessed at age 3.5 years using the Rutter Total Problems Scale. But postnatal depression that was persistent was the real difference maker: It carried a much higher risk of adverse behavioral outcomes and cognitive deficits than did the nonpersistent version. Indeed, persistent severe postnatal depression was associated a 4.8-fold increased risk of behavioral problems at age 3.5 years, a 2.65-fold greater risk of markedly lower grades in mathematics at age 16 years, and a 7.4-fold increased prevalence of depression at 18 years of age. The investigators advised screening mothers during the first postpartum year in order to identify those with persistent postpartum depression (JAMA Psychiatry. 2018 Mar 1;75[3]:247-53).
Dr. Castro-Fornieles said an important shortcoming of the Avon study was that it did not record paternal data.
“The study didn’t consider depression or other functional measures in the father, his commitment to childrearing, and whether the family was together or divorced. I feel this is an important limitation in many studies. For me, it’s really important to consider what’s happening with the fathers,” she said.
Traumatic stress load, psychopathology, and cognition
An eye-opening report from the Philadelphia Neurodevelopmental Cohort documented a surprisingly high level of lifetime exposure to traumatic events among 9,498 youth aged 8-21 years, and the stepwise manner by which a greater traumatic stress load was associated with increasing severity of psychopathology and cognitive deficits. Notably, the study participants were recruited from general pediatric clinics in the Children’s Hospital of Philadelphia health care network; they were not patients seeking psychiatric help. And yet, extensive structured psychiatric evaluation showed that 23% of them had a history of one traumatic stressful event, 12% had two, and 1% had three or more.
In analyses adjusted for lifetime history of depression or PTSD, a higher traumatic event load was associated with increased risk of externalizing behaviors, mood/anxiety disorders, psychosis spectrum, and fear. Moreover, a high trauma stress load was associated with a 5.3-fold increased risk of suicidal thoughts and a 3.2-fold increased likelihood of cannabis use, compared with youth who had never been exposed to a traumatic event. Increased stress load also was associated with worse cognitive performance on tests of executive functioning, social cognition, and complex reasoning.
A history of assaultive trauma – being badly beaten, threatened with a weapon, or sexually abused – was associated with more severe psychopathology than in subjects with a history of nonassaultive traumatic events (Psychol Med. 2018 Apr 15:1-10).
Session moderator Carmen Moreno, MD, a child and adolescent psychiatrist at Gregorio Marañón University Hospital in Madrid, commented, “It was striking to me that the prevalence of childhood traumatic events was so high in a pediatric community sample. Is the measure the investigators chose the right measure?”
Dr. Castro-Fornieles replied that it was a very sensitive measure, in that an event many would consider part of normal life – for example, seeing a relative’s body on display in a funeral home – was scored as a traumatic exposure.
“Only one exposure is not that important,” she said. “The impact increases as you increase the number of traumatic events. And also the assaultive ones.”
Sexual abuse leaves a fingerprint
Investigators at Leiden (the Netherlands) University performed neuroimaging that looked at numerous brain regions of interest in 21 adolescents with childhood sexual abuse–related PTSD and 25 matched healthy controls. The standout finding was that the dorsal gray matter volume of the anterior cingulate cortex was significantly smaller in the teens with PTSD and a history of childhood sexual abuse (Eur Neuropsychopharmacol. 2017 Nov;27[11]:1163-71).
The investigators wanted a pure sample of patients with PTSD after childhood sexual abuse, so they excluded individuals who had experienced childhood sexual abuse and had a diagnosis of attention-deficit/hyperactivity disorder, oppositional defiant disorder, obsessive-compulsive disorder, conduct disorder, pervasive developmental disorder, bipolar disorder, or a psychotic disorder. That is both a strength and a limitation of the study, in Dr. Castro-Fornieles’ view.
“To me, that excludes too many of the children we see in our clinical settings. This work needs to be corroborated in a bigger sample, including patients with other diagnoses,” she said.
She reported having no financial conflicts regarding her presentation.
BARCELONA – Prenatal exposure to selective serotonin reuptake inhibitors late in pregnancy was associated with a significantly increased risk of anxious and/or depressed behaviors at 5 years of age in the prospective Norwegian Mother and Child Cohort Study.
Other than that specific red flag, however, the outcomes of in utero exposure to maternal SSRIs were reassuringly benign. Prenatal exposure during early- or mid-pregnancy was not associated with increased risk of anxious/depressed behaviors, compared with nonexposure; that adverse effect was restricted to exposure at week 29 of pregnancy or later. Nor did in utero exposure to maternal SSRIs during any time in pregnancy pose an increased risk for pediatric externalizing, emotional, or social problems in this observational study of 8,359 Norwegian mother-child dyads, Josefina Castro-Fornieles, MD, PhD, observed at the annual congress of the European College of Neuropsychopharmacology.
The huge Norwegian study was among what she considers the four most important studies in child/adolescent psychiatry published through the first three quarters of 2018. The others she highlighted were a large longitudinal observational study that demonstrated that persistent maternal postnatal depression was strongly associated with a variety of pediatric behavioral disturbances documented during assessments at ages 3.5, 16, and 18 years; a Philadelphia study showing that multiple traumatic stressful events or any assaultive trauma experienced by children or adolescents were independently associated with significant psychopathology and neurocognitive deficits; and a Dutch brain MRI study that pinpointed a reduction in gray matter volume in the anterior cingulate cortex as a potential key mediator of the neurobiologic aftereffects of childhood sexual abuse.
She selected those studies because they shared a common theme, one that constituted her key take-home message: “When recording antecedents during a clinical assessment, both with adults and children, it is clear that we have to ask in a more detailed way – using validated scales and interviews if possible – about the mother’s prenatal problems, including psychopharmacological treatment. That is something we often don’t do in a sufficiently detailed way in our clinical practice. And it’s also important to ask about life events; abuse during childhood and adolescence can be really important. We can modulate our treatment depending upon whether there is an influence of any of these aspects,” said Dr. Castro-Fornieles, director of the Clinical Institute of Neuroscience at the Hospital Clinic of Barcelona and a recent past-president of the Spanish Society for Child and Adolescent Psychiatry.
The following are her Top 4 studies:
The Norwegian Mother and Child Cohort Study
The increased risk of anxious and/or depressed behaviors in children exposed to selective serotonin reuptake inhibitors (SSRIs) late in pregnancy did not emerge until the year-5 assessment; it wasn’t evident at the 1.5- or 3-year evaluations.
The investigators emphasized a key lesson from their study: The importance of following children with late-pregnancy exposure to maternal SSRI therapy for development of symptoms of anxiety and/or depression (J Am Acad Child Adolesc Psychiatry. 2018 Mar;57[3]:200-8). Dr. Castro-Fornieles strongly endorsed that recommendation. However, she noted what she considers an important limitation to the study: even though the University of Oslo investigators adjusted for numerous potential confounders in their risk models – including maternal body mass index, parity, education, smoking, substance use, breastfeeding, folic acid use, and other medications used during pregnancy – it’s not possible in a study such as this to control for genetic and environmental risk factors, which she suspects also were at work.
The Avon Longitudinal Study of Parents and Children in the United Kingdom
Maternal postnatal depression is common, affecting roughly 10% of mothers. But it is not invariably associated with adverse mental health outcomes in their children. This study of nearly 10,000 mothers and their children sought to identify which children were at most risk. Using the Edinburgh Postnatal Depression Scale, the international team of investigators categorized maternal postnatal depression as moderate, marked, or severe. The affective disorder was deemed persistent if scores on the Edinburgh scale were elevated at both 2 and 8 months after delivery.
Postnatal depression, whether persistent or not, was associated with roughly a 2- to 2.4-fold increase for child behavioral disturbances when assessed at age 3.5 years using the Rutter Total Problems Scale. But postnatal depression that was persistent was the real difference maker: It carried a much higher risk of adverse behavioral outcomes and cognitive deficits than did the nonpersistent version. Indeed, persistent severe postnatal depression was associated a 4.8-fold increased risk of behavioral problems at age 3.5 years, a 2.65-fold greater risk of markedly lower grades in mathematics at age 16 years, and a 7.4-fold increased prevalence of depression at 18 years of age. The investigators advised screening mothers during the first postpartum year in order to identify those with persistent postpartum depression (JAMA Psychiatry. 2018 Mar 1;75[3]:247-53).
Dr. Castro-Fornieles said an important shortcoming of the Avon study was that it did not record paternal data.
“The study didn’t consider depression or other functional measures in the father, his commitment to childrearing, and whether the family was together or divorced. I feel this is an important limitation in many studies. For me, it’s really important to consider what’s happening with the fathers,” she said.
Traumatic stress load, psychopathology, and cognition
An eye-opening report from the Philadelphia Neurodevelopmental Cohort documented a surprisingly high level of lifetime exposure to traumatic events among 9,498 youth aged 8-21 years, and the stepwise manner by which a greater traumatic stress load was associated with increasing severity of psychopathology and cognitive deficits. Notably, the study participants were recruited from general pediatric clinics in the Children’s Hospital of Philadelphia health care network; they were not patients seeking psychiatric help. And yet, extensive structured psychiatric evaluation showed that 23% of them had a history of one traumatic stressful event, 12% had two, and 1% had three or more.
In analyses adjusted for lifetime history of depression or PTSD, a higher traumatic event load was associated with increased risk of externalizing behaviors, mood/anxiety disorders, psychosis spectrum, and fear. Moreover, a high trauma stress load was associated with a 5.3-fold increased risk of suicidal thoughts and a 3.2-fold increased likelihood of cannabis use, compared with youth who had never been exposed to a traumatic event. Increased stress load also was associated with worse cognitive performance on tests of executive functioning, social cognition, and complex reasoning.
A history of assaultive trauma – being badly beaten, threatened with a weapon, or sexually abused – was associated with more severe psychopathology than in subjects with a history of nonassaultive traumatic events (Psychol Med. 2018 Apr 15:1-10).
Session moderator Carmen Moreno, MD, a child and adolescent psychiatrist at Gregorio Marañón University Hospital in Madrid, commented, “It was striking to me that the prevalence of childhood traumatic events was so high in a pediatric community sample. Is the measure the investigators chose the right measure?”
Dr. Castro-Fornieles replied that it was a very sensitive measure, in that an event many would consider part of normal life – for example, seeing a relative’s body on display in a funeral home – was scored as a traumatic exposure.
“Only one exposure is not that important,” she said. “The impact increases as you increase the number of traumatic events. And also the assaultive ones.”
Sexual abuse leaves a fingerprint
Investigators at Leiden (the Netherlands) University performed neuroimaging that looked at numerous brain regions of interest in 21 adolescents with childhood sexual abuse–related PTSD and 25 matched healthy controls. The standout finding was that the dorsal gray matter volume of the anterior cingulate cortex was significantly smaller in the teens with PTSD and a history of childhood sexual abuse (Eur Neuropsychopharmacol. 2017 Nov;27[11]:1163-71).
The investigators wanted a pure sample of patients with PTSD after childhood sexual abuse, so they excluded individuals who had experienced childhood sexual abuse and had a diagnosis of attention-deficit/hyperactivity disorder, oppositional defiant disorder, obsessive-compulsive disorder, conduct disorder, pervasive developmental disorder, bipolar disorder, or a psychotic disorder. That is both a strength and a limitation of the study, in Dr. Castro-Fornieles’ view.
“To me, that excludes too many of the children we see in our clinical settings. This work needs to be corroborated in a bigger sample, including patients with other diagnoses,” she said.
She reported having no financial conflicts regarding her presentation.
REPORTING FROM THE ECNP CONGRESS