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      Testing Causal Effects of Maternal Smoking During Pregnancy on Offspring’s Externalizing and Internalizing Behavior

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          Abstract

          Maternal smoking during pregnancy (SDP) is associated with increased risk of externalizing and internalizing behaviors in offspring. Two explanations (not mutually exclusive) for this association are direct causal effects of maternal SDP and the effects of genetic and environmental factors common to parents and offspring which increase smoking as well as problem behaviors. Here, we examined the associations between parental SDP and mother rated offspring externalizing and internalizing behaviors (rated by the Child Behavior Checklist/2–3) at age three in a population-based sample of Dutch twins (N = 15,228 pairs). First, as a greater effect of maternal than of paternal SDP is consistent with a causal effect of maternal SDP, we compared the effects of maternal and paternal SDP. Second, as a beneficial effect of quitting smoking before pregnancy is consistent with the causal effect, we compared the effects of SDP in mothers who quit smoking before pregnancy, and mothers who continued to smoke during pregnancy. All mothers were established smokers before their pregnancy. The results indicated a greater effect of maternal SDP, compared to paternal SDP, for externalizing, aggression, overactive and withdrawn behavior. Quitting smoking was associated with less externalizing, overactive behavior, aggression, and oppositional behavior, but had no effect on internalizing, anxious depression, or withdrawn behavior. We conclude that these results are consistent with a causal, but small, effect of smoking on externalizing problems at age 3. The results do not support a causal effect of maternal SDP on internalizing behaviors.

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          The structure of genetic and environmental risk factors for common psychiatric and substance use disorders in men and women.

          Patterns of comorbidity suggest that the common psychiatric and substance use syndromes may be divisible into 2 broad groups of internalizing and externalizing disorders. We do not know how genetic and environmental risk factors contribute to this pattern of comorbidity or whether the etiologic structure of these groups differ in men and women. Lifetime diagnoses for 10 psychiatric syndromes were obtained at a personal interview in more than 5600 members of male-male and female-female twin pairs ascertained from a population-based registry. Multivariate twin modeling was performed using the program Mx. We first fit models to the following 7 syndromes: major depression, generalized anxiety disorder, phobia, alcohol dependence, drug abuse/dependence, adult antisocial behavior, and conduct disorder. The full model, which could be constrained to equality in male and female subjects, identified 2 genetic factors. The first had strongest loadings on alcohol dependence, drug abuse/dependence, adult antisocial behavior, and conduct disorder; the second, on major depression, generalized anxiety disorder, and phobia. Alcohol dependence and drug abuse/dependence had substantial disorder-specific genetic risk factors. Shared environmental factors were most pronounced for conduct disorder and adult antisocial behavior. No clear internalizing/externalizing structure was seen for the unique environmental common factors. We then fit models to 5 internalizing syndromes. The full model, which could also be constrained to equality in men and women, revealed one genetic factor loading most heavily on major depression and generalized anxiety disorder and another loading most strongly on animal and situational phobia. The underlying structure of the genetic and environmental risk factors for the common psychiatric and drug abuse disorders in men and women is very similar. Genetic risk factors predispose to 2 broad groups of internalizing and externalizing disorders. Within the internalizing disorders, 2 genetic factors are seen that predispose to disorders dominated by anxious-misery and fear. Substance use disorders have disorder-specific genetic risks. The externalizing disorders of conduct disorder and adult antisocial behavior are significantly influenced by the shared environment. The pattern of lifetime comorbidity of common psychiatric and substance use disorders results largely from the effects of genetic risk factors.
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            Intergenerational Class Mobility in Three Western European Societies: England, France and Sweden

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              Fetal origins of mental health: evidence and mechanisms.

              The concept of fetal programming states that changes in the fetal environment during sensitive periods of organ development may cause long-lasting changes in the structure and functioning of these organs later in life and influence the risk for chronic diseases such as coronary heart disease and type 2 diabetes. Fetal growth is a summary marker of the fetal environment and is reflected by relatively easy-to-obtain measures of size at birth such as birth weight. In the last two decades, a body of evidence emerged linking fetal growth with behavioural and mental health outcomes later in life. Cognitive functioning and behavioural problems in childhood, in particular inattention/hyperactivity, have been shown to be inversely related to fetal growth. Although results are mixed, risk for personality disorders and schizophrenia seems to be linked with fetal growth and adversity, while the evidence for mood disorders is weak. Vulnerability for psychopathology may also be influenced by prenatal adversity. There is evidence for associations of fetal growth with temperament in childhood as well as stress reactivity and distress. The associations of fetal growth with mental health later in life are potentially caused by specific prenatal factors such as maternal smoking, alcohol, toxins/drugs, nutrition, psychosocial stress and infection during pregnancy. The mechanisms likely involve changes in neurodevelopment and in the set point of neuroendocrine systems, and there is evidence that prenatal adversity interacts with genetic and postnatal environmental factors. Future studies should examine the effects of specific prenatal factors and attempt to disentangle genetic and prenatal environmental effects.
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                Author and article information

                Contributors
                di.boomsma@vu.nl
                Journal
                Behav Genet
                Behav. Genet
                Behavior Genetics
                Springer US (New York )
                0001-8244
                1573-3297
                1 September 2015
                1 September 2015
                2016
                : 46
                : 378-388
                Affiliations
                [ ]Department of Biological Psychology, Netherlands Twin Register, VU University Amsterdam, Van der Boechorststraat 1, 1081 BT Amsterdam, The Netherlands
                [ ]Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, VA USA
                [ ]EMGO+ Institute for Health and Care Research, VU University Medical Centre, Amsterdam, The Netherlands
                [ ]Neuroscience Campus Amsterdam, Amsterdam, The Netherlands
                Article
                9738
                10.1007/s10519-015-9738-2
                4826626
                26324285
                2f132374-edbc-4e22-af5c-f123652c853d
                © The Author(s) 2015

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

                History
                : 7 April 2015
                : 18 August 2015
                Funding
                Funded by: ERC Starting Grant
                Award ID: 284167
                Award Recipient :
                Funded by: NIDA Grant
                Award ID: DA-018673
                Award Recipient :
                Funded by: ZonMW Addiction Program
                Award ID: 60-60600-97-135
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/501100000781, European Research Council;
                Award ID: ERC-230374
                Award Recipient :
                Funded by: NWO
                Award ID: SPI 56-464-14192
                Award ID: 480- 04-004
                Award Recipient :
                Categories
                Original Research
                Custom metadata
                © Springer Science+Business Media New York 2016

                Genetics
                parental prenatal smoking,pleiotropic effects,childhood behavioral problems,causality
                Genetics
                parental prenatal smoking, pleiotropic effects, childhood behavioral problems, causality

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