Developmental pathways from prenatal tobacco and stress exposure to behavioral disinhibition

“A uthor M anuscript A uthor M anuscript A uthor M anuscript A uthor M anuscript theoretical interpretability (Nylund et al. 2007).”

“A uthor M anuscript A uthor M anuscript A uthor M anuscript A uthor M anuscript completed comprehensive timeline follow-back interviews (Sobell and Sobell 1992) to assess smoking in the preceding months as well as questionnaire measures of socio-familial background, depression and stress (see…”

“The pathways from PTE and prenatal stress to reduced executive control performance are particularly concerning given the established importance of executive control for children’s school readiness (e.g., Blair & Razza, 2007; Clark, Sheffield, & Espy, 2011).”

“In keeping with several studies that have used similar approaches (reviewed in Evans et al. 2013), a Neurotoxicol Teratol.”

“Introduction There is growing recognition that the prenatal environment shapes health and disease across the lifespan (e.g., Barker, 1998).”

“Similar to PTE, PSE has been linked to a higher likelihood of aggression, conduct disorder and ADHD in children and, more recently, to externalizing behavior in young adults (Talge et al. 2007; Li et al. 2010; Bekkhus et al. 2011; Blair et al. 2011; Glover 2011; Ronald et al. 2011; Grizenko et al. 2012; Class et al. 2…”

“…links to ADHD have been less consistent: while some studies have demonstrated associations between PTE and ADHD symptoms (Mick et al. 2002; e.g., Linnet et al. 2003), others suggest there is no association or that PTE predicts only comorbid ADHD and conduct problems as opposed to ADHD symptoms…”

“In previous studies, outcome variables from these executive control tasks have loaded onto a single executive control factor (Wiebe et al. 2011; Clark et al. 2014), suggesting that they tap a general executive control construct.”

“A uthor M anuscript A uthor M anuscript A uthor M anuscript A uthor M anuscript persistent antisocial behavior and substance abuse (Tarter 2002; Tarter et al. 2003; Iacono et al. 2008; Zucker et al. 2011; Lester et al. 2012).”

“…likelihood of aggression, conduct disorder and ADHD in children and, more recently, to externalizing behavior in young adults (Talge et al. 2007; Li et al. 2010; Bekkhus et al. 2011; Blair et al. 2011; Glover 2011; Ronald et al. 2011; Grizenko et al. 2012; Class et al. 2014; Betts et al. 2015).”

“A uthor M anuscript A uthor M anuscript A uthor M anuscript A uthor M anuscript persistent antisocial behavior and substance abuse (Tarter 2002; Tarter et al. 2003; Iacono et al. 2008; Zucker et al. 2011; Lester et al. 2012).”

“…new experiences or routines, and intense expression of negative emotion, places children at increased risk of externalizing behavior problems later in childhood, particularly when paired with environmental stress (Sanson et al. 1993; Wright Guerin, Allen W. Gottfried, 1997; Fanti and Henrich 2010).”

“In a genetic design study including mothers with and without IVF, PSE was associated with offspring antisocial behavior, although not symptoms of ADHD, after accounting for current maternal depression and anxiety (Rice et al. 2010).”

“However, numerous studies have shown that the number of stressors in a child’s environment has as much, if not greater bearing, on risk for psychopathology (Sameroff et al. 1987; Evans et al. 2013).”

“…prenatal environment triggers the methylation of genes that regulate physiological responses to stress in the developing fetus, thereby permanently altering the child’s ‘set point’ for homeostasis and level of reactivity to the postnatal environment (Beijers et al., 2014; Talge et al., 2007).”

“Deficits in these core control processes have repeatedly been implicated in pathways to externalizing behavior, including ADHD, oppositional defiance and aggression (Hughes et al. 2000; Séguin et al. 2004; Hughes and Ensor 2008; Raaijmakers et al. 2008; Espy et al. 2011b).”

“While research examining the impact of prenatal maternal stress on child executive control generally is lacking, one study of school-aged children reported dose-response reductions in working memory and inhibitory control performance with increasing maternal pregnancyspecific stress (Buss et al. 2011), while another f…”

“…likelihood of aggression, conduct disorder and ADHD in children and, more recently, to externalizing behavior in young adults (Talge et al. 2007; Li et al. 2010; Bekkhus et al. 2011; Blair et al. 2011; Glover 2011; Ronald et al. 2011; Grizenko et al. 2012; Class et al. 2014; Betts et al. 2015).”

“Deficits in these core control processes have repeatedly been implicated in pathways to externalizing behavior, including ADHD, oppositional defiance and aggression (Hughes et al. 2000; Séguin et al. 2004; Hughes and Ensor 2008; Raaijmakers et al. 2008; Espy et al. 2011b).”

“Studies using continuous outcome measures compliment those that have used clinical cut-offs, reporting elevated levels of aggression, impulsivity, hyperactivity and rule-breaking in preschoolers, children and adolescents with PTE relative to their non-exposed peers (Martin et al. 2006; Carter et al. 2008; Galera et al…”

“…likelihood of aggression, conduct disorder and ADHD in children and, more recently, to externalizing behavior in young adults (Talge et al. 2007; Li et al. 2010; Bekkhus et al. 2011; Blair et al. 2011; Glover 2011; Ronald et al. 2011; Grizenko et al. 2012; Class et al. 2014; Betts et al. 2015).”

“…disinhibition is thought to reflect disruptions to prefrontal cognitive networks in the brain, including abnormal reactivity of thalamic and limbic neural structures that feed input to the prefrontal cortex or a deficiency in the prefrontal modulation of these inputs or both (Zucker et al. 2011).”

“Studies have also varied in their definition and approach to the measurement of stress during pregnancy (Nast et al. 2013).”

“…as well as abnormal neurogenesis and synaptogenesis in the hippocampus and prefrontal cortex (Belnoue, Grosjean, Ladeveze, Arbous, & Koehl, 2013; Clarke, Wittwer, Abbott, & Schneider, 1994; Coulon, Wellman, Marjara, Janczak, & Zanella, 2013; Schneider et al, 1992, 2002; Zucchi et al., 2013).”

“…as well as abnormal neurogenesis and synaptogenesis in the hippocampus and prefrontal cortex (Belnoue, Grosjean, Ladeveze, Arbous, & Koehl, 2013; Clarke, Wittwer, Abbott, & Schneider, 1994; Coulon, Wellman, Marjara, Janczak, & Zanella, 2013; Schneider et al, 1992, 2002; Zucchi et al., 2013).”

“…likelihood of aggression, conduct disorder and ADHD in children and, more recently, to externalizing behavior in young adults (Talge et al. 2007; Li et al. 2010; Bekkhus et al. 2011; Blair et al. 2011; Glover 2011; Ronald et al. 2011; Grizenko et al. 2012; Class et al. 2014; Betts et al. 2015).”

“In the Raine study, the number of maternal stressors experienced during pregnancy and PTE were two of the strongest predictors of psychiatric morbidity in early childhood, over and above several measures of postnatal psychosocial adversity (Robinson et al. 2008, 2011).”

“…likelihood of aggression, conduct disorder and ADHD in children and, more recently, to externalizing behavior in young adults (Talge et al. 2007; Li et al. 2010; Bekkhus et al. 2011; Blair et al. 2011; Glover 2011; Ronald et al. 2011; Grizenko et al. 2012; Class et al. 2014; Betts et al. 2015).”

“Deficits in these core control processes have repeatedly been implicated in pathways to externalizing behavior, including ADHD, oppositional defiance and aggression (Hughes et al. 2000; Séguin et al. 2004; Hughes and Ensor 2008; Raaijmakers et al. 2008; Espy et al. 2011b).”

“The inter-stimulus interval was 750ms. Children show significant improvement on this Go/no-go task between age 3 and 5 years and performance correlates with other measures of inhibitory control, supporting its validity (Wiebe et al., 2012).”

“There is accumulating evidence that children with PTE have impairments in executive control, including discrepancies in processing speed, sustained attention, response inhibition and working memory, relative to non-exposed controls in childhood and adolescence (Fried and Watkinson 2001; Willford et al. 2010; Mezzacapp…”

“2.3.5 Externalizing Behavior—Mothers completed the Multidimensional Assessment Profile of Disruptive Behavior (MAP-DB; Wakschlag et al. 2014) during the laboratory assessment at age 5 years, The MAP-DB is a developmentally-sensitive, dimensional measure designed to differentiate normative misbehavior from atypical pat…”

“Difficult temperament in infancy, characterized by irregular feeding and sleeping patterns, high levels of withdrawal from environmental stimuli, difficulties adjusting to new experiences or routines, and intense expression of negative emotion, places children at increased risk of externalizing behavior problems later…”

“A uthor M anuscript A uthor M anuscript A uthor M anuscript A uthor M anuscript persistent antisocial behavior and substance abuse (Tarter 2002; Tarter et al. 2003; Iacono et al. 2008; Zucker et al. 2011; Lester et al. 2012).”

“Deficits in these core control processes have repeatedly been implicated in pathways to externalizing behavior, including ADHD, oppositional defiance and aggression (Hughes et al. 2000; Séguin et al. 2004; Hughes and Ensor 2008; Raaijmakers et al. 2008; Espy et al. 2011b).”

“…number of stressors increases the likelihood of poor functional outcome in a dose-response manner and the accumulation of these risk factors is a stronger predictor of cognitive and behavioral outcome than any single factor (Rutter 1979; Sameroff et al. 1987; Doan et al. 2012; Evans et al. 2013).”

“Children also completed a Go/No-go task (Simpson and Riggs 2006; Wiebe et al. 2012), during which they were instructed to press a button when they saw a fish but to withhold responding when they saw a shark.”

“ECI ratings demonstrate good discriminant validity when compared to chart diagnoses for ADHD and correlates significantly with comparable scales from other behavior checklists (Sprafkin et al. 2002).”

“…in working memory and inhibitory control performance with increasing maternal pregnancyspecific stress (Buss et al. 2011), while another found that sustained attention was reduced in boys, but not girls, whose mothers reported high levels of anxiety during pregnancy (Van den Bergh et al. 2006).”

“These neural networks modulate core executive control processes, which develop rapidly over the course of early childhood, allowing for greater goal-directed control over attentional resources (Clark et al. 2012; Wiebe et al. 2012).”

“Children with PTE are 2 to 4 times more likely to meet criteria for Oppositional Defiance Disorder and Conduct Disorder beginning in early childhood and also are more likely to exhibit substance use disorders and severe antisocial behavior in adolescence and adulthood (Wakschlag and Hans 2002; Gatzke-Kopp and Beauchai…”

“…associations between PTE and ADHD symptoms (Mick et al. 2002; e.g., Linnet et al. 2003), others suggest there is no association or that PTE predicts only comorbid ADHD and conduct problems as opposed to ADHD symptoms per se (Wakschlag et al. 2006a; Huijbregts et al. 2007; Ball et al. 2010).”

“Women who smoke during pregnancy on average experience higher levels of financial stress, reduced social and partner support, more negative life events and trauma, and increased levels of psychological distress and anxiety (Bullock et al. 2001; Goedhart et al. 2009; Holtrop et al. 2010; Lynch et al. 2011).”

“For instance, Fisher et al. (2011) found that prenatal substance exposure predicted neurobehavioral disinhibition in adolescence, but that early cumulative adversity also showed unique, additive effects.”

“…impairments in executive control, including discrepancies in processing speed, sustained attention, response inhibition and working memory, relative to non-exposed controls in childhood and adolescence (Fried and Watkinson 2001; Willford et al. 2010; Mezzacappa et al. 2011; Cornelius et al. 2012).”

“Moreover, high stress levels increase the likelihood of persistent smoking during pregnancy and are associated with reduced cessation self-efficacy (Weaver et al. 2008; Pickett et al. 2009; Prusakowski et al. 2011).”

“Deficits in these core control processes have repeatedly been implicated in pathways to externalizing behavior, including ADHD, oppositional defiance and aggression (Hughes et al. 2000; Séguin et al. 2004; Hughes and Ensor 2008; Raaijmakers et al. 2008; Espy et al. 2011b).”

“Women who smoke during pregnancy on average experience higher levels of financial stress, reduced social and partner support, more negative life events and trauma, and increased levels of psychological distress and anxiety (Bullock et al. 2001; Goedhart et al. 2009; Holtrop et al. 2010; Lynch et al. 2011).”

“In previous studies, outcome variables from these executive control tasks have loaded onto a single executive control factor (Wiebe et al. 2011; Clark et al. 2014), suggesting that they tap a general executive control construct.”

“In keeping with previous research (e.g., Weaver et al. 2008), mothers who smoked during pregnancy reported higher levels of prenatal stress.”

“Although our findings here are based on maternal report, other studies incorporating direct observations of infant neurobehavior have found early differences in temperament in children with PTE (Fried & Watkinson, 1987; Mansi et al., 2007; Sheutze & Eiden, 2007; Picone et al., 1985).”

“PTE and PSE each have been linked to higher negative reactivity, higher activity levels and less adaptable temperament in infants (Martin et al. 2006; Wakschlag et al. 2006a; Willoughby et al. 2007; Carter et al. 2008; Pickett et al. 2008).”

“Studies using continuous outcome measures compliment those that have used clinical cut-offs, reporting elevated levels of aggression, impulsivity, hyperactivity and rule-breaking in preschoolers, children and adolescents with PTE relative to their non-exposed peers (Martin et al. 2006; Carter et al. 2008; Galera et al…”

“Children with PTE are 2 to 4 times more likely to meet criteria for Oppositional Defiance Disorder and Conduct Disorder beginning in early childhood and also are more likely to exhibit substance use disorders and severe antisocial behavior in adolescence and adulthood (Wakschlag and Hans 2002; Gatzke-Kopp and Beauchai…”

“Women who smoke during pregnancy on average experience higher levels of financial stress, reduced social and partner support, more negative life events and trauma, and increased levels of psychological distress and anxiety (Bullock et al. 2001; Goedhart et al. 2009; Holtrop et al. 2010; Lynch et al. 2011).”

“There is accumulating evidence that children with PTE have impairments in executive control, including discrepancies in processing speed, sustained attention, response inhibition and working memory, relative to non-exposed controls in childhood and adolescence (Fried and Watkinson 2001; Willford et al. 2010; Mezzacapp…”

“There is accumulating evidence that children with PTE have impairments in executive control, including discrepancies in processing speed, sustained attention, response inhibition and working memory, relative to non-exposed controls in childhood and adolescence (Fried and Watkinson 2001; Willford et al. 2010; Mezzacapp…”

“A uthor M anuscript A uthor M anuscript A uthor M anuscript A uthor M anuscript persistent antisocial behavior and substance abuse (Tarter 2002; Tarter et al. 2003; Iacono et al. 2008; Zucker et al. 2011; Lester et al. 2012).”

“Studies using continuous outcome measures compliment those that have used clinical cut-offs, reporting elevated levels of aggression, impulsivity, hyperactivity and rule-breaking in preschoolers, children and adolescents with PTE relative to their non-exposed peers (Martin et al. 2006; Carter et al. 2008; Galera et al…”

“Prenatal meditation and relaxation techniques, as well as personalized nursing partnerships offer some promise in this regard (Chan, 2014; Olds et al, 1998).”

“Children with PTE are 2 to 4 times more likely to meet criteria for Oppositional Defiance Disorder and Conduct Disorder beginning in early childhood and also are more likely to exhibit substance use disorders and severe antisocial behavior in adolescence and adulthood (Wakschlag and Hans 2002; Gatzke-Kopp and Beauchai…”

“…likelihood of aggression, conduct disorder and ADHD in children and, more recently, to externalizing behavior in young adults (Talge et al. 2007; Li et al. 2010; Bekkhus et al. 2011; Blair et al. 2011; Glover 2011; Ronald et al. 2011; Grizenko et al. 2012; Class et al. 2014; Betts et al. 2015).”

“PTE and PSE each have been linked to higher negative reactivity, higher activity levels and less adaptable temperament in infants (Martin et al. 2006; Wakschlag et al. 2006a; Willoughby et al. 2007; Carter et al. 2008; Pickett et al. 2008).”

“Moreover, high stress levels increase the likelihood of persistent smoking during pregnancy and are associated with reduced cessation self-efficacy (Weaver et al. 2008; Pickett et al. 2009; Prusakowski et al. 2011).”

“Women who smoke during pregnancy on average experience higher levels of financial stress, reduced social and partner support, more negative life events and trauma, and increased levels of psychological distress and anxiety (Bullock et al. 2001; Goedhart et al. 2009; Holtrop et al. 2010; Lynch et al. 2011).”

“Children with PTE are 2 to 4 times more likely to meet criteria for Oppositional Defiance Disorder and Conduct Disorder beginning in early childhood and also are more likely to exhibit substance use disorders and severe antisocial behavior in adolescence and adulthood (Wakschlag and Hans 2002; Gatzke-Kopp and Beauchai…”

“…Y Y Y SR O Y C 10 Chittleborough (2011) Y Y N Y Y Y Y SR MM Y NS 10 Chong (2016) Y N N N Y Y Y SR MR Y P 6 Claridge (2015) Y N Y N Y Y Y SR MR Y C 8 Clark (2016) N N N Y Y Y Y SR MM Y NS 8 Coplan (2005) N N N M N Y Y SR MR N P 4 Crockenberg (2003) N N N M Y Y Y SR MR Y C 7 Cutrona (1986) N N N Y N…”

“…stress response system can be differentially programmed by experiences over the gestational period, early life and childhood, implicating tobacco exposure, maternal affect, and social interactions and trauma (Brooker et al., 2016; Clark et al., 2016; Del Giudice et al., 2011; Flinn et al., 2011).”

“Indeed, stress exposure in utero has been linked to deleterious outcomes for the child including impaired motor development, lower mental development, heightened behavioral disinhibition, and associated clinical patterns such as attention-deficit/hyperactivity disorder and disruptive behavior[5, 9, 14, 37].”

“Similarly, Clark, Espy, and Wakschlag (2016) found independent effects of prenatal tobacco and prenatal stress in predicting executive control at age 5, which along with difficult temperament predicted elevated levels of disruptive behavior.”

“Future studies are also needed to explicitly characterize potential additive or multiplicative effects of additional substance exposures and non-substance exposures including environmental toxins, poverty, stress, and mental health problems (Clark et al., 2016; Stroud et al., 2014b).”

“Results indicate that effortful control at early-school age may partially mediate the association between tobacco exposure and school-age disruptive behaviors (Clark et al. 2016).”

“Moreover, it is critical that these studies use sensitive, multidimensional measurement approaches to capture the variability in self-regulatory capacities that characterize this age range (Clark et al., 2016; Wakschlag et al., 2010).”

“, 2019), and corollary neural disruptions in early life (Clark et al., 2016; Demir-Lira et al., 2016; O’Connor et al., 2014; Talge et al., 2007).”

“Discussion There is increasing support for the role of early life adversity, in particular, prenatal adversity, in shaping disruptive behavior pathways (Aizer et al., 2015, Chiarella et al., 2015, Clark et al., 2015, Hanson et al., 2015, Ronald et al., 2010).”

“• 36 studies found overall cognitive and cognitive subdomain (attention, executive function, language) scores were lower in cigarette and e-cigarette exposed offspring [6, 7, 23, 46, 64–”

“In an ethnicallydiverse sample in the United States, maternal smoking during pregnancy predicted poorer EF, assessed by the Nebraska Barnyard task and a Go/NoGo task, in 5-year-old children (Clark et al., 2016).”

“As covariates of parenting behavior, we considered infant temperament (Clark et al., 2016), concurrent smoking, impulsivity (White et al., 2014), depressive symptoms (Lovejoy et al., 2000), antisocial behaviors (Ehrensaft et al., 2003), and family conflict (Cooklin et al., 2015).”

“Another prospective study found that children with prenatal exposure to tobacco and stress in conjunction with high postnatal stress exhibited worst executive control and more disruptive behavior (Clark et al., 2016).”

“45,46 as such, increased awareness of the prevalence and impact of aCes on birthing populations is a first step in responding with two-generation strategies that can improve mental health and promote affect regulation to increase lifelong positive parent–child interactions.”

“Children of mothers who had smoked and been stressed during pregnancy had a difficult temperament, lower levels of executive control and more disruptive behaviour [22].”

“…distress is also related to impairments in neurodevelopmental outcomes, including decrements in self-regulation and early emerging psychopathology (Clark et al. 2016 ; Glover 2014 ; Goodman et al. 2011 ; Massey et al. 2017 ; Stein et al. 2014 ), ameliorating maternal distress has the potential to…”

“One proposed genetic-related explanation might be that tobacco toxicants and nicotine are directly transferred via the placenta and influence the expression of nicotinic acetylcholine receptors in the brain of fetus, resulting in the high propensity of smoking for offspring (26, 27).”