Perinatal selective serotonin reuptake inhibitor medication (SSRI) effects on social behaviors, neurodevelopment and the epigenome

Abstract

Recent research has linked early life exposure to selective serotonin reuptake inhibitor medications (SSRIs) to modifications of social behaviors in children. Serotonin is a key regulator of neurodevelopment, social behaviors and mental health, and with the growing use of SSRIs to treat maternal affective disorders during the perinatal period, questions have been raised about the benefits and risks of perinatal SSRI exposure on the developing child. This review will highlight how perinatal SSRIs affect maternal care and neurodevelopmental outcomes related to social affiliative behaviors in offspring; such as play behaviors, social interactions, reproductive behaviors, and maternal care of the next generation. We will also review how early life exposure to SSRIs can alter related neurobiology, and the epigenome. Both clinical research and findings from animal models will be discussed. Understanding the impact of perinatal SSRIs on neurobehavioral outcomes will improve the health and well-being of subsequent generations.

Association of Iron Status and Intake During Pregnancy with Neuropsychological Outcomes in Children Aged 7 Years: The Prospective Birth Cohort Infancia y Medio Ambiente (INMA) Study

“…Epidemiological studies have demonstrated that optimizing brain development in early life has been associated with long-term consequences for individuals, for instance, academic performance, the level of education attained [1][2][3], and mental well-being in adulthood [4]. In particular, early-life environmental factors such as smoking, healthy lifestyle, and other factors have been suggested to play a major role in neurodevelopmental processes [5][6][7][8][9][10][11]. Accordingly, some previous studies have evidenced a relationship between suboptimal maternal diet in pregnancy and poorer mental and psychomotor development in offspring [5,6,[12][13][14][15][16].…”

Perinatal fluoxetine has enduring sexually differentiated effects on neurobehavioral outcomes related to social behaviors

“…Data were analyzed using the software Statistica (Dell Inc.). Due to previous findings of sexually differentiated patterns of outcomes in the response to pSSRIs and maternal stress exposure on behavioral measures, HPA axis, hippocampal plasticity, and additional neurobehavioral outcomes (Gemmel et al, 2018a;Gobinath et al, 2016;Rayen et al, 2015), factorial ANOVAs were conducted separately for each sex on behavioral measures, corticosterone, CBG, as well as on measures of hippocampal plasticity and GR density with condition (pre-gestational stress/control) and treatment (fluoxetine/vehicle) as independent factors. Factorial ANOVAs with condition (pre-gestational stress/control), treatment (fluoxetine/vehicle), and sex (male/female) as independent factors can be found in…”

“…Selective Serotonin Reuptake Inhibitor medications (SSRIs) are commonly prescribed during pregnancy to treat maternal stress-related mood disorders (Gemmel et al, 2018a;Oberlander et al, 2006).…”

“…However, perinatal exposure to these medications (pSSRIs) has been linked to poor social development in children highlighted by increased risk of Autism Spectrum Disorder (ASD) (Man et al, 2015) and attention-deficit hyperactivity disorder (ADHD) (Clements et al, 2015) diagnoses. Children prenatally exposed to SSRIs also exhibit low adaptive and social-emotional behavioral scores, and increased externalizing behaviors such as aggression, hyperactivity, and oppositional/defiant behavior (Gemmel et al, 2018a). However, parental depression and poor maternal health in the year prior to conception play an equally, or even more important, role in childhood behavioral outcomes (Brown et al, 2017;Clements et al, 2015;Mezzacappa et al, 2017).…”

Effect of pre-gestational stress and prenatal venlafaxine administration on cardiovascular system of rat offspring

“…Depression is a stress-related, affective disorder, with prevalence of 10-18% among pregnant women all over the world. Exposure to prenatal stress represents a great risk factor for developing pregnancy diseases (preeclampsia, miscarriages, gestational hypertension and hypoxia of the fetus), altered fetal development, low birth weight and a range of neurobehavioral disturbances of a child, including autism, anxiety and depression (St-Pierre et al, 2016; Kiryanova et al, 2017;Gemmel et al, 2018). During gestation, 2-3% women are treated with antidepressants (AD), mostly with selective serotonin reuptake inhibitors (SSRI) or selective serotonin and norepinephrine reuptake inhibitors (SNRI).…”