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1.  Familial transmission of parental mood disorders: unipolar and bipolar disorders in offspring 
Bipolar disorders  2013;15(7):764-773.
Objectives
Offspring of depressed parents are at increased risk for psychiatric disorders. Although bipolar disorder (BD) and major depressive disorder (MDD) are both found in the same families, it is not clear whether transmission to offspring of BD or MDD tends to occur from parents with the same mood disorder subtype. The primary hypothesis was that offspring of parents with BD would be at increased risk for BD and other comorbid disorders common to BD such as anxiety and substance use relative to offspring of parents with MDD. Offspring of parents with BD versus those with MDD were also hypothesized to be at greater risk for externalizing disorders, i.e., conduct disorder, attention-deficit hyperactivity disorder, or antisocial personality disorder.
Methods
Parents (n = 320) with mood disorders and their offspring (n = 679) were studied. Adult offspring were administered the Structured Clinical Interview for DSM-IV Axis I Disorders to establish the presence of psychopathology. Offspring aged 10 to 18-years-old were assessed with the School Aged Schedule for Affective Disorders and Schizophrenia, Present and Lifetime version, and parents of children under age 10 completed the Child Behavioral Checklist. Data were examined using Cox Proportional Hazard regression.
Results
There was no difference in hazard of mood disorders in the offspring of parents with BD as compared to offspring of parents with MDD. However, a number of other parent and offspring characteristics increased risk for mood, anxiety, externalizing, and substance use disorders in offspring, including self-reported childhood abuse in parent or offspring, offspring impulsive aggression, and age of onset of parental mood disorder.
Conclusions
Mood disorders are highly familial independent of whether the parent’s condition is unipolar or bipolar, and considerable overlap in the familial basis of MDD and BD was found. Although parental characteristics had limited influence on risk of offspring psychopathology, reported childhood adversity, be it in the parent or child, is a harbinger of negative outcomes. These risk factors extend previous findings, and are consistent with diathesis-stress conceptualizations.
doi:10.1111/bdi.12107
PMCID: PMC3855182  PMID: 23909952
bipolar disorder; familial transmission; major depressive disorder
2.  An Extended Swedish National Adoption Study of Alcohol Use Disorder 
JAMA psychiatry  2015;72(3):211-218.
IMPORTANCE
Alcohol use disorder (AUD) runs strongly in families. It is unclear to what extent the cross-generational transmission of AUD results from genetic vs environmental factors.
OBJECTIVE
To determine to what extent genetic and environmental factors contribute to the risk for AUD.
DESIGN, SETTING, AND PARTICIPANTS
Follow-up in 8 public data registers of adoptees, their biological and adoptive relatives, and offspring and parents from stepfamilies and not-lived-with families in Sweden. In this cohort study, subtypes of AUD were assessed by latent class analysis. A total of 18 115 adoptees (born 1950–1993) and 171 989 and 107 696 offspring of not-lived-with parents and stepparents, respectively (born 1960–1993).
MAIN OUTCOMES AND MEASURES
Alcohol use disorder recorded in medical, legal, or pharmacy registry records.
RESULTS
Alcohol use disorder in adoptees was significantly predicted by AUD in biological parents (odds ratio, 1.46; 95% CI, 1.29–1.66) and siblings (odds ratio, 1.94; 95% CI, 1.55–2.44) as well as adoptive parents (odds ratio, 1.40; 95% CI, 1.09–1.80). Genetic and environmental risk indices created from biological and adoptive relatives acted additively on adoptee AUD liability. Results from biological and adoptive relatives were replicated and extended from examinations of, respectively, not-lived-with parents and stepparents. Multivariate models in these families showed that AUD in offspring was significantly predicted by AUD, drug abuse, psychiatric illness, and crime in not-lived-with parents and by AUD, drug abuse, crime, and premature death in stepparents. Latent class analyses of adoptees and offspring of not-lived-with parents with AUDs revealed 3 AUD classes characterized by (1) female preponderance and high rates of psychiatric illness, (2) mild nonrecurrent symptoms, and (3) early-onset recurrence, drug abuse, and crime. These classes had distinct genetic signatures in the patterns of risk for various disorders in their not-lived-with parents and striking differences in the rates of recorded mood disorders.
CONCLUSIONS AND RELEVANCE
Parent-offspring transmission of AUD results from both genetic and environmental factors. Genetic risk for AUD reflects both a specific liability to AUD and to other externalizing disorders. Environmental risk reflects features of both parental psychopathology and other aspects of the rearing environment. Alcohol use disorder is a heterogeneous syndrome and meaningful subtypes emerged from latent class analysis, which were validated by patterns of disorders in biological parents and specific psychiatric comorbidities. The general population contains informative family constellations that can complement more traditional adoption designs in clarifying the sources of parent-offspring resemblance.
doi:10.1001/jamapsychiatry.2014.2138
PMCID: PMC4351126  PMID: 25565339
3.  Familial Transmission and Heritability of Childhood Disruptive Disorders 
The American journal of psychiatry  2010;167(9):1066-1074.
Objective:
There is substantial evidence of a link between parental substance use disorders and antisocial behavior and childhood disruptive disorders in their offspring, but it is unclear whether this transmission is specific to particular disorders, or if a general liability accounts for familial resemblance. The current study examined if the association between parental externalizing disorders and childhood disruptive disorders in their pre-adolescent offspring is due to the transmission of general or disorder-specific liabilities, and estimated the genetic and environmental contributions to variation in these general and specific liability indicators.
Method:
Participants were 1069 families consisting of 11-year-old twins and their biological mother and father. We used structural equation modeling to simultaneously estimate the general and specific transmission effects of four parental externalizing disorders (conduct disorder, adult antisocial behavior, alcohol dependence, and drug dependence) on childhood disruptive disorders (attention deficit/hyperactivity disorder, conduct disorder, and oppositional defiant disorder).
Results:
Parent-child resemblance was accounted for by the transmission of a general liability to externalizing disorders, and this general liability was highly heritable. Specific effects were also detected, but for sibling rather than parental transmission. Specific genetic and nonshared environmental effects were detected for each childhood disruptive disorder, but only conduct disorder exhibited a significant shared environmental effect.
Conclusions:
A highly heritable general liability accounts for the parent-child transmission of externalizing psychopathology from parents to their pre-adolescent offspring. This general liability should be a focus of research for both etiology and intervention.
doi:10.1176/appi.ajp.2010.09091272
PMCID: PMC2936682  PMID: 20634367
4.  The Long-Term Health Consequences of Child Physical Abuse, Emotional Abuse, and Neglect: A Systematic Review and Meta-Analysis 
PLoS Medicine  2012;9(11):e1001349.
Rosana Norman and colleagues conduct a systematic review and meta-analysis to assess the relationship between child physical abuse, emotional abuse, and neglect, and subsequent mental and physical health outcomes.
Background
Child sexual abuse is considered a modifiable risk factor for mental disorders across the life course. However the long-term consequences of other forms of child maltreatment have not yet been systematically examined. The aim of this study was to summarise the evidence relating to the possible relationship between child physical abuse, emotional abuse, and neglect, and subsequent mental and physical health outcomes.
Methods and Findings
A systematic review was conducted using the Medline, EMBASE, and PsycINFO electronic databases up to 26 June 2012. Published cohort, cross-sectional, and case-control studies that examined non-sexual child maltreatment as a risk factor for loss of health were included. All meta-analyses were based on quality-effects models. Out of 285 articles assessed for eligibility, 124 studies satisfied the pre-determined inclusion criteria for meta-analysis. Statistically significant associations were observed between physical abuse, emotional abuse, and neglect and depressive disorders (physical abuse [odds ratio (OR) = 1.54; 95% CI 1.16–2.04], emotional abuse [OR = 3.06; 95% CI 2.43–3.85], and neglect [OR = 2.11; 95% CI 1.61–2.77]); drug use (physical abuse [OR = 1.92; 95% CI 1.67–2.20], emotional abuse [OR = 1.41; 95% CI 1.11–1.79], and neglect [OR = 1.36; 95% CI 1.21–1.54]); suicide attempts (physical abuse [OR = 3.40; 95% CI 2.17–5.32], emotional abuse [OR = 3.37; 95% CI 2.44–4.67], and neglect [OR = 1.95; 95% CI 1.13–3.37]); and sexually transmitted infections and risky sexual behaviour (physical abuse [OR = 1.78; 95% CI 1.50–2.10], emotional abuse [OR = 1.75; 95% CI 1.49–2.04], and neglect [OR = 1.57; 95% CI 1.39–1.78]). Evidence for causality was assessed using Bradford Hill criteria. While suggestive evidence exists for a relationship between maltreatment and chronic diseases and lifestyle risk factors, more research is required to confirm these relationships.
Conclusions
This overview of the evidence suggests a causal relationship between non-sexual child maltreatment and a range of mental disorders, drug use, suicide attempts, sexually transmitted infections, and risky sexual behaviour. All forms of child maltreatment should be considered important risks to health with a sizeable impact on major contributors to the burden of disease in all parts of the world. The awareness of the serious long-term consequences of child maltreatment should encourage better identification of those at risk and the development of effective interventions to protect children from violence.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Child maltreatment—the abuse and neglect of children—is a global problem. There are four types of child maltreatment—sexual abuse (the involvement of a child in sexual activity that he or she does not understand, is unable to give consent to, or is not developmentally prepared for), physical abuse (the use of physical force that harms the child's health, survival, development, or dignity), emotional abuse (the failure to provide a supportive environment by, for example, verbally threatening the child), and neglect (the failure to provide for all aspects of the child's well-being). Most child maltreatment is perpetrated by parents or parental guardians, many of whom were maltreated themselves as children. Other risk factors for parents abusing their children include poverty, mental health problems, and alcohol and drug misuse. Although there is considerable uncertainty about the frequency and severity of child maltreatment, according to the World Health Organization (WHO) about 20% of women and 5%–10% of men report being sexually abused as children, and the prevalence of physical abuse in childhood may be 25%–50%.
Why Was This Study Done?
Child maltreatment has a large public health impact. Sometimes this impact is immediate and direct (injuries and deaths), but, more often, it is long-term, affecting emotional development and overall health. For child sexual abuse, the relationship between abuse and mental disorders in adult life is well-established. Exposure to other forms of child maltreatment has also been associated with a wide range of psychological and behavioral problems, but the health consequences of physical abuse, emotional abuse, and neglect have not been systematically examined. A better understanding of the long-term health effects of child maltreatment is needed to inform maltreatment prevention strategies and to improve treatment for children who have been abused or neglected. In this systematic review and meta-analysis, the researchers quantify the association between exposure to physical abuse, emotional abuse, and neglect in childhood and mental health and physical health outcomes in later life. A systematic review uses predefined criteria to identify all the research on a given topic; a meta-analysis is a statistical approach that combines the results of several studies.
What Did the Researchers Do and Find?
The researchers identified 124 studies that investigated the relationship between child physical abuse, emotional abuse, or neglect and various health outcomes. Their meta-analysis of data from these studies provides suggestive evidence that child physical abuse, emotional abuse, and neglect are causally linked to mental and physical health outcomes. For example, emotionally abused individuals had a three-fold higher risk of developing a depressive disorder than non-abused individuals (an odds ratio [OR] of 3.06). Physically abused and neglected individuals also had a higher risk of developing a depressive disorder than non-abused individuals (ORs of 1.54 and 2.11, respectively). Other mental health disorders associated with child physical abuse, emotional abuse, or neglect included anxiety disorders, drug abuse, and suicidal behavior. Individuals who had been non-sexually maltreated as children also had a higher risk of sexually transmitted diseases and/or risky sexual behavior than non-maltreated individuals. Finally, there was weak and inconsistent evidence that child maltreatment increased the risk of chronic diseases and lifestyle risk factors such as smoking.
What Do These Findings Mean?
By providing suggestive evidence of a causal link between non-sexual child maltreatment and mental health disorders, drug use, suicide attempts, and sexually transmitted diseases and risky sexual behavior, these findings contribute to our understanding of the non-injury health impacts of child maltreatment. Although most of the studies included in the meta-analysis were undertaken in high-income countries, the findings suggest that this link occurs in both high- and low-to-middle-income countries. They also suggest that neglect may be as harmful as physical and emotional abuse. However, they need to be interpreted carefully because of the limitations of this meta-analysis, which include the possibility that children who have been abused may share other, unrecognized factors that are actually the cause of their later mental health problems. Importantly, this confirmation that physical abuse, emotional abuse, and neglect in childhood are important risk factors for a range of health problems draws attention to the need to develop evidence-based strategies for preventing child maltreatment both to reduce childhood suffering and to alleviate an important risk factor for later health problems.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001349.
The World Health Organization provides information on child maltreatment and its prevention (in several languages); Preventing Child Maltreatment: A Guide to Taking Action and Generating Evidence is a 2006 report produced by WHO and the International Society for Prevention of Child Abuse and Neglect
The US Centers for Disease Control and Prevention provides information on child maltreatment and links to additional resources
The National Society for the Prevention of Cruelty to Children (NSPCC) is a not-for-profit organization that aims to end all cruelty to children in the UK; Childline is a resource provided by the NSPCC that provides help, information, and support to children who are being abused
The Hideout is a UK-based website that helps children and young people understand domestic abuse
Childhelp is a US not-for-profit organization dedicated to helping victims of child abuse and neglect; its website includes a selection of personal stories about child maltreatment
doi:10.1371/journal.pmed.1001349
PMCID: PMC3507962  PMID: 23209385
5.  Maternal Smoking and Drinking during Pregnancy and the Risk for Child and Adolescent Psychiatric Disorders* 
Journal of studies on alcohol  2000;61(5):661-668.
Objective
To examine the relative importance of prenatal exposure to cigarettes and alcohol and familial/genetic susceptibility for alcohol dependence in the etiology of childhood psychopathology.
Method
A longitudinal prospective study of 150 children/adolescents (51.3% male), who were at either high or low risk for developing alcohol dependence because of their familial loading for alcoholism, provided multiple diagnostic assessments (N = 318) of these subjects. High-risk families were identified through the presence of two adult alcoholic sisters; low-risk control families were selected from the community. Annual assessments of offspring from these families included an in-depth psychiatric interview of each child and his/her parent to determine the presence or absence of childhood disorders. Mothers were interviewed concerning their prenatal use of substances, and information was gathered concerning their personal and familial loading for psychiatric disorders.
Results
Using conventional logistic regression analyses, internalizing and externalizing disorders were found to be associated with familial loading for alcoholism and prenatal exposure to cigarettes and alcohol. In addition, a specialized statistical analysis, a multivariate confounder score approach, was conducted using familial risk status and the child’s exposure to maternal prenatal use of alcohol and cigarettes. This analysis demonstrated that only one relationship between a single variable and a childhood disorder was significant while controlling for the other two variables: Oppositional disorder remained significant in association with familial risk status. Three additional analyses were performed to evaluate the effects of familial risk status, prenatal alcohol exposure and prenatal cigarette exposure on childhood psychopathology while controlling for two known risk factors (SES and parental ASPD) for externalizing disorders. Results of these analyses revealed that the only childhood disorder that was elevated was ADHD, and that this was the result of the familial risk variable only.
Conclusions
Familial loading for alcohol dependence is an important risk factor for the development of childhood psychopathology and may account for the previously reported associations between prenatal exposure to nicotine and alcohol. Studies of substance abuse/dependence etiology and childhood psychopathology need to include consideration of both prenatal exposures and familial loading for alcohol dependence and other psychiatric disorders.
PMCID: PMC4128282  PMID: 11022804
6.  Parent, Sibling and Peer Associations with Subtypes of Psychiatric and Substance Use Disorder Comorbidity in Offspring 
Drug and alcohol dependence  2012;128(1-2):20-29.
BACKGROUND
Parental substance use disorder (SUD) is associated with a range of negative offspring outcomes and psychopathology, but the clustering of these outcomes into subtypes has seldom been examined, nor have the familial and environmental contexts of these subtypes been reported. The present study examines the clustering of offspring lifetime substance use and psychiatric disorders into subtypes and characterizes them in terms of familial and non-familial influences using an offspring-of-twins design.
METHOD
Telephone-administered diagnostic interviews were used to collect data on psychiatric disorders and SUD from 488 twin fathers, 420 biological mothers and 831 offspring. Latent class analysis (LCA) was used to derive subtypes of lifetime comorbidity in offspring. Familial risk and environmental variables associated with each subtype (i.e. parenting, childhood physical or sexual abuse, perceived sibling and peer substance use) were identified using multinomial logistic regression.
RESULTS
Four classes identified by LCA were characterized as 1) unaffected, 2) alcohol abuse/dependence, 3) alcohol abuse/dependence comorbid with anxiety and depression, and 4) alcohol, cannabis abuse/dependence and nicotine dependence comorbid with conduct disorder. Inconsistent parenting, childhood physical/sexual abuse, and perceived sibling and peer substance use were significantly associated with profiles of offspring comorbidity after adjusting for familial vulnerability. Some associations were specific (i.e. perceived peer alcohol use to the AUD class), while others were general (peer smoking to all 3 comorbidity classes).
CONCLUSIONS
We observed distinct subtypes of psychiatric and SUD comorbidity in adolescents and young adults. Subtypes of offspring psychopathology have varied associations with parental psychopathology, family environment, and sibling and peer behaviors.
doi:10.1016/j.drugalcdep.2012.07.015
PMCID: PMC3514649  PMID: 22921146
substance use disorder; anxiety; depression; twin; comorbid
7.  The Influence of Parental Psychopathology on Offspring Suicidal Behavior across the Lifespan 
PLoS ONE  2015;10(7):e0134970.
Suicide tends to occur in families, and parental psychopathology has been linked to offspring suicidal behaviors. This study explores the influence of parental mental disorders across the lifespan. Data are from the Sao Paulo Megacity Mental Health Survey, a cross-sectional household study with a representative sample of the adult population living in the Sao Paulo Metropolitan Area, Brazil (N=2,942). Survival models examined bivariate and multivariate associations between a range of parental disorders and offspring suicidality. After controlling for comorbidity, number of mental disorders and offspring psychopathology, we found that parental psychopathology influences suicidal behaviors throughout most part of the life cycle, from childhood until young adult years. Generalized anxiety disorder (GAD) and antisocial personality were associated with offspring suicidal ideation (OR 1.8 and 1.9, respectively), panic and GAD predicted suicidal attempts (OR 2.3 and 2.7, respectively), and panic was related to the transition from ideation to attempts (OR 2.7). Although noticed in many different stages of the lifespan, this influence is most evident during adolescence. In this period, depression and antisocial personality increased the odds of suicidal ideation (OR 5.1 and 3.2, respectively), and depression, panic disorder, GAD and substance abuse predicted suicidal attempts (OR varying from 1.7 to 3.8). In short, parental disorders characterized by impulsive-aggression and anxiety-agitation were the main predictors of offspring suicidality across the lifespan. This clinically relevant intergenerational transmission of suicide risk was independent of offspring mental disorders, and this underscores the need for a family approach to psychopathology.
doi:10.1371/journal.pone.0134970
PMCID: PMC4521747  PMID: 26230321
8.  Autism and attention-deficit/hyperactivity disorder among individuals with a family history of alcohol use disorders 
eLife  2014;3:e02917.
Recent studies suggest de novo mutations may involve the pathogenesis of autism and attention-deficit/hyperactivity disorder (ADHD). Based on the evidence that excessive alcohol consumption may be associated with an increased rate of de novo mutations in germ cells (sperms or eggs), we examine here whether the risks of autism and ADHD are increased among individuals with a family history of alcohol use disorders (AUDs). The standardized incidence ratios (SIRs) of autism and ADHD among individuals with a biological parental history of AUDs were 1.39 (95% CI 1.34–1.44) and 2.19 (95% CI 2.15–2.23), respectively, compared to individuals without an affected parent. Among offspring whose parents were diagnosed with AUDs before their birth, the corresponding risks were 1.46 (95% CI 1.36–1.58) and 2.70 (95% CI 2.59–2.81), respectively. Our study calls for extra surveillance for children with a family history of AUDs, and further studies examining the underlying mechanisms are needed.
DOI: http://dx.doi.org/10.7554/eLife.02917.001
eLife digest
Children learn to talk, manage their emotions, and control their behavior in a period when the brain is developing rapidly. The first signs of several developmental disorders, such as autism and attention-deficit/hyperactivity disorder (ADHD), may also emerge during this period. Children with autism may have difficulties with social interactions and communication, while those with attention-deficit/hyperactivity disorder may struggle to pay attention to a task and may be more active than other children.
Autism or ADHD are diagnosed based on the child's behavior because the underlying causes of the disorders are not well understood. Both genes and the environment have been linked to the conditions; and it was recently suggested that certain common genetic mutations are more common in children with ADHD or autism. However, as some of the mutations linked to autism are not found in the genes of the affected children's parents, it is likely that they occurred in either of the sperm or the egg cell from the parents.
Exposure to harmful substances in the environment can cause mutations in egg or sperm cells, or alter the expression of genes without changing the gene sequence. Excessive alcohol consumption is one environmental factor that can mutate genes or alter gene expression. Here, Sundquist et al. have looked to see if there is a relationship between a child having a parent with an alcohol use problem and the child's risk of developing autism or ADHD.
Examining national medical registries identified 24,157 people with autism and 49,348 with ADHD in Sweden between 1987 and 2010. Sundquist et al. discovered that autism and ADHD were more common in individuals who had a parent with a history of an alcohol use disorder than in those whose parents had no history of an alcohol use disorder. There was also an even greater risk of either condition if the parent had been diagnosed with an alcohol use problem before the birth of the child.
Adopted children who had a biological parent with an alcohol use disorder were at a greater risk of autism and ADHD than those whose adoptive parent had an alcohol use disorder. However, as very few adopted parents were diagnosed with an alcohol use problem, it is important to be cautious about drawing firm conclusions from this observation.
Sundquist et al. estimate that around 4% of autism cases and 11% of ADHD cases could be avoided if parents abstained from heavy alcohol consumption. Though these findings are consistent with parents with an alcohol use disorder being more likely to pass on mutations to their children, there are also other possible explanations. As such, further research examining the underlying cause is still needed.
DOI: http://dx.doi.org/10.7554/eLife.02917.002
doi:10.7554/eLife.02917
PMCID: PMC4135348  PMID: 25139954
autism; ADHD; alcohol use disorders; human
9.  Familial Pathways to Early-Onset Suicide Attempt 
JAMA psychiatry  2015;72(2):160-168.
IMPORTANCE
Suicide attempts are strong predictors of suicide, a leading cause of adolescent mortality. Suicide attempts are highly familial, although the mechanisms of familial transmission are not understood. Better delineation of these mechanisms could help frame potential targets for prevention.
OBJECTIVE
To examine the mechanisms and pathways by which suicidal behavior is transmitted from parent to child.
DESIGN, SETTING, AND PARTICIPANTS
In this prospective study conducted from July 15, 1997, through June 21, 2012, a total of 701 offspring aged 10 to 50 years (mean age, 17.7 years) of 334 clinically referred probands with mood disorders, 191 (57.2%) of whom had also made a suicide attempt, were followed up for a mean of 5.6 years.
MAIN OUTCOMES AND MEASURES
The primary outcome was a suicide attempt. Variables were examined at baseline, intermediate time points, and the time point proximal to the attempt. Participants were assessed by structured psychiatric assessments and self-report and by interview measures of domains hypothesized to be related to familial transmission (eg, mood disorder and impulsive aggression).
RESULTS
Among the 701 offspring, 44 (6.3%) had made a suicide attempt before participating in the study, and 29 (4.1%) made an attempt during study follow-up. Multivariate logistic regression revealed that proband suicide attempt was a predictor of offspring suicide attempt (odds ratio [OR], 4.79; 95% CI, 1.75–13.07), even controlling for other salient offspring variables: baseline history of mood disorder (OR, 4.20; 95% CI, 1.37–12.86), baseline history of suicide attempt (OR, 5.69; 95% CI, 1.94–16.74), and mood disorder at the time point before the attempt (OR, 11.32; 95% CI, 2.29–56.00). Path analyses were consistent with these findings, revealing a direct effect of proband attempt on offspring suicide attempt, a strong effect of offspring mood disorder at each time point, and impulsive aggression as a precursor of mood disorder.
CONCLUSIONS AND RELEVANCE
Parental history of a suicide attempt conveys a nearly 5-fold increased odds of suicide attempt in offspring at risk for mood disorder, even after adjusting for the familial transmission of mood disorder. Interventions that target mood disorder and impulsive aggression in high-risk offspring may attenuate the familial transmission of suicidal behavior.
doi:10.1001/jamapsychiatry.2014.2141
PMCID: PMC4419699  PMID: 25548996
10.  Parental Divorce, Parental Depression, and Gender Differences in Adult Offspring Suicide Attempt 
Research suggests parental divorce during childhood increases risk of suicide attempt for male but not female offspring. The negative impact on offspring associated with parental divorce may be better explained by parental psychopathology, such as depression. We examined whether adult offspring of parental divorce experience elevated risk of suicide attempt, controlling for parental history of depression, and whether the risk varies by the gender of the offspring. Using the 2001 to 2002 National Epidemiologic Survey on Alcohol and Related Conditions (NESARC), the sample consists of respondents who experienced parental divorce (N = 4895). Multivariable regressions controlled for age, race/ethnicity, income, marital status, and parental history of depression. Females living with their fathers were significantly more likely to report lifetime suicide attempts than females living with their mothers, even after controlling for parental depression. Findings suggest that childhood/adolescent parental divorce may have a stronger impact on suicide attempt risk in female offspring than previously recognized.
doi:10.1097/NMD.0b013e3181c299ac
PMCID: PMC3767404  PMID: 20010025
Parental divorce; gender; offspring; suicide attempt; depression
11.  Understanding mother-adolescent conflict discussions: Concurrent and across-time prediction from youths’ dispositions and parenting 
Adolescence is often thought of as a period during which the quality of parent–child interactions can be relatively stressed and conflictual. There are individual differences in this regard, however, with only a modest percent of youths experiencing extremely conflictual relationships with their parents. Nonetheless, there is relatively little empirical research on factors in childhood or adolescence that predict individual differences in the quality of parent–adolescent interactions when dealing with potentially conflictual issues. Understanding such individual differences is critical because the quality of both parenting and the parent–adolescent relationship is predictive of a range of developmental outcomes for adolescents.
The goals of the research were to examine dispositional and parenting predictors of the quality of parents’ and their adolescent children’s emotional displays (anger, positive emotion) and verbalizations (negative or positive) when dealing with conflictual issues, and if prediction over time supported continuity versus discontinuity in the factors related to such conflict. We hypothesized that adolescents’ and parents’ conflict behaviors would be predicted by both childhood and concurrent parenting and child dispositions (and related problem behaviors) and that we would find evidence of both parent- and child-driven pathways.
Mothers and adolescents (N = 126, M age = 13 years) participated in a discussion of conflictual issues. A multimethod, multireporter (mother, teacher, and sometimes adolescent reports) longitudinal approach (over 4 years) was used to assess adolescents’ dispositional characteristics (control/regulation, resiliency, and negative emotionality), youths’ externalizing problems, and parenting variables (warmth, positive expressivity, discussion of emotion, positive and negative family expressivity). Higher quality conflict reactions (i.e., less negative and/or more positive) were related to both concurrent and antecedent measures of children’s dispositional characteristics and externalizing problems, with findings for control/regulation and negative emotionality being much more consistent for daughters than sons. Higher quality conflict reactions were also related to higher quality parenting in the past, positive rather than negative parent–child interactions during a contemporaneous nonconflictual task, and reported intensity of conflict in the past month. In growth curves, conflict quality was primarily predicted by the intercept (i.e., initial levels) of dispositional measures and parenting, although maintenance or less decrement in positive parenting, greater decline in child externalizing problems, and a greater increase in control/regulation over time predicted more desirable conflict reactions. In structural equation models in which an aspect of parenting and a child dispositional variable were used to predict conflict reactions, there was continuity of both type of predictors, parenting was a unique predictor of mothers’ (but not adolescents’) conflict reactions (and sometimes mediated the relations of child dispositions to conflict reactions), and child dispositions uniquely predicted adolescents’ reactions and sometimes mothers’ conflict reactions. The findings suggest that parent–adolescent conflict may be influenced by both child characteristics and quality of prior and concurrent parenting, and that in this pattern of relations, child effects are more evident than parent effects.
doi:10.1111/j.1540-5834.2008.00470.x
PMCID: PMC2553724  PMID: 18702792
12.  Explaining risk for suicidal ideation in adolescent offspring of mothers with depression 
Psychological Medicine  2015;46(2):265-275.
Background
It is well-established that offspring of depressed mothers are at increased risk for suicidal ideation. However, pathways involved in the transmission of risk for suicidal ideation from depressed mothers to offspring are poorly understood. The aim of this study was to examine the contribution of potential mediators of this association, including maternal suicide attempt, offspring psychiatric disorder and the parent–child relationship.
Method
Data were utilized from a population-based birth cohort (ALSPAC). Three distinct classes of maternal depression symptoms across the first 11 years of the child's life had already been identified (minimal, moderate, chronic-severe). Offspring suicidal ideation was assessed at age 16 years. Data were analysed using structural equation modelling.
Results
There was evidence for increased risk of suicidal ideation in offspring of mothers with chronic-severe depression symptoms compared to offspring of mothers with minimal symptoms (odds ratio 3.04, 95% confidence interval 2.19–4.21). The majority of this association was explained through maternal suicide attempt and offspring psychiatric disorder. There was also evidence for an independent indirect effect via the parent–child relationship in middle childhood. There was no longer evidence of a direct effect of maternal depression on offspring suicidal ideation after accounting for all three mediators. The pattern of results was similar when examining mechanisms for maternal moderate depression symptoms.
Conclusions
Findings highlight that suicide prevention efforts in offspring of depressed mothers should be particularly targeted at both offspring with a psychiatric disorder and offspring whose mothers have made a suicide attempt. Interventions aimed at improving the parent–child relationship may also be beneficial.
doi:10.1017/S0033291715001671
PMCID: PMC4682478  PMID: 26303275
Adolescence; maternal depression; mechanisms; parent-child relationship; suicidal ideation
13.  Pathways to Suicide-Related Behavior in Offspring of Mothers With Depression: The Role of Offspring Psychopathology 
Objective
Offspring of mothers with depression are a high-risk group for the development of suicide-related behavior. These offspring are therefore a priority for preventive interventions; however, pathways contributing to risk, including specific aspects of offspring psychopathology, remain unclear. The aim of this study was to examine whether offspring symptoms of major depressive disorder (MDD), generalized anxiety disorder (GAD), disruptive behavior disorder (DBD), attention-deficit/hyperactivity disorder (ADHD), and alcohol abuse independently mediate the association between maternal depression and offspring suicide-related behavior.
Method
Data were used from a population-based birth cohort, the Avon Longitudinal Study of Parents and Children (ALSPAC). Three distinct classes of depression symptoms across the mothers’ first 11 years of their child’s life were identified (minimal, moderate, chronic-severe). Offspring psychopathology was assessed at age 15 years and suicide-related behavior at age 16 years. Data were analyzed using structural equation modeling.
Results
There was evidence for increased risk of suicidal ideation in offspring of mothers with chronic-severe depression symptoms in comparison to offspring of mothers with minimal symptoms (odds ratio = 3.04, 95% CI = 2.19, 4.21). This association was independently mediated by offspring MDD, GAD, and DBD symptoms. The same mechanisms were found for offspring of mothers with moderate depression symptoms over time. Results were similar for offspring suicide attempt except for additional evidence of an indirect effect through offspring ADHD symptoms.
Conclusion
Findings highlight that suicide prevention efforts in offspring of mothers with depression should not only be targeted at offspring with MDD; it is also important to consider offspring with other forms of psychopathology.
doi:10.1016/j.jaac.2015.02.006
PMCID: PMC4411216  PMID: 25901775
suicide-related behavior; ALSPAC; maternal depression; psychopathology
14.  Parental Psychopathology and the Risk of Suicidal Behavior in their Offspring: Results from the World Mental Health Surveys 
Molecular psychiatry  2010;16(12):1221-1233.
Prior research suggests that parental psychopathology predicts suicidal behavior among offspring; however, the more fine-grained associations between specific parental disorders and distinct stages of the pathway to suicide are not well-understood. We set out to test the hypothesis that parental disorders associated with negative mood would predict offspring suicide ideation, whereas disorders characterized by impulsive-aggression (e,g., antisocial personality) and anxiety/agitation (e.g., panic disorder) would predict which offspring act on their suicide ideation and make a suicide attempt. Data were collected during face-to-face interviews conducted on nationally representative samples (N=55,299; age 18+) from 21 countries around the world. We tested the associations between a range of parental disorders and the onset and persistence over time (i.e., time-since-most-recent-episode controlling for age-of-onset and time-since-onset) of subsequent suicidal behavior (suicide ideation, plans, and attempts) among offspring. Analyses tested bivariate and multivariate associations between each parental disorder and distinct forms of suicidal behavior. Results revealed that each parental disorder examined increased the risk of suicide ideation among offspring, parental generalized anxiety and depression emerged as the only predictors of the onset and persistence (respectively) of suicide plans among offspring with ideation, whereas parental anti-social personality and anxiety disorders emerged as the only predictors of the onset and persistence of suicide attempts among ideators. A dose-response relation between parental disorders and respondent risk of suicide ideation and attempt also was found. Parental death by suicide was a particularly strong predictor of persistence of suicide attempts among offspring. These associations remained significant after controlling for comorbidity of parental disorders and for the presence of mental disorders among offspring. These findings should inform future explorations of the mechanisms of inter-generational transmission of suicidal behavior.
doi:10.1038/mp.2010.111
PMCID: PMC3142278  PMID: 21079606
suicide; parent and family history; intergenerational transmission
15.  Parental psychopathology moderates the influence of parental divorce on lifetime alcohol use disorders among Israeli adults 
Drug and alcohol dependence  2014;141:85-91.
Background
Parental divorce and psychopathology are well-documented risk factors for alcohol use disorders (AUD) in the United States and other countries where divorce is common and per capita total alcohol consumption is moderate to high. However, little is known about these relationships in countries where divorce and alcohol problems are less common, such as Israel.
Methods
Israeli adult household residents (N=797) age 21–45 were interviewed in person between 2007 and 2009. Logistic regression models were used to examine main and additive interaction effects of parental divorce and psychopathology on lifetime DSM-IV AUD, adjusting for age, gender, and ethnicity.
Results
Parental divorce (OR=2.18, p≤.001) and parental psychopathology (OR=1.61, p≤.01) were independently associated with lifetime AUD and, when considered together, showed significant interaction (p=.026). Specifically, the effect of divorce on AUD was only significant among those who also reported parental psychopathology.
Conclusions
This is the first study showing the influence of parental divorce and psychopathology on risk for AUD among Israeli adults, where both divorce and AUD are less common than in the United States. Alcohol prevention and treatment professionals should recognize that children who experience parental divorce and/or psychopathology could be more vulnerable to later developing AUD than those whose parents remain together and without psychopathology.
doi:10.1016/j.drugalcdep.2014.05.009
PMCID: PMC4104554  PMID: 24939440
alcohol use disorders; parental divorce; parental psychopathology; Israel
16.  Time to hospitalization for suicide attempt by the timing of parental suicide during offspring early development 
JAMA psychiatry (Chicago, Ill.)  2013;70(2):149-157.
Context
Previous studies have suggested that children who experience parental suicide at earlier ages are at higher risk of future hospitalization for suicide attempt. However, how the trajectories of risk differ by offspring age at the time of parental suicide is currently unknown.
Objective
To study time at risk to hospitalization for suicide attempt among offspring after experiencing parental suicide or accidental death by offspring developmental period at the time of parental death.
Design
Population-based retrospective cohort study
Setting
Sweden
Participants
26,096 offspring who experienced parental suicide and 32,395 offspring of accident decedents prior to age 25 from 1973-2003.
Main Outcome Measures
Hospitalization for suicide attempt. Parametric survival analysis was used to model the time to hospitalization for suicide attempt across offspring who lost a parent during early childhood (0-5 years old), later childhood (6-12), adolescence (13-17) and young adulthood (18-24).
Results
The risk in offspring who lost a parent during early or late childhood surpassed the other two age groups’ hazards approximately 5 years after the origin and, for the youngest group, continued to rise over the course of decades. Offspring who lost a parent during adolescence or young adulthood were at greatest risk within 1 to 2 years after parental suicide, and risk declined over time. The shape of hospitalization risk was similar among those who experienced parental fatal accident. When the shape of hospitalization for suicide attempt at each developmental period was fixed to be the same between the two groups, offspring who lost a parent to suicide had earlier risk to hospitalization for suicide attempt hospitalization than offspring who lost a parent to an accident.
Conclusion
The hospitalization risk for suicide attempt in offspring who lost a parent during their childhood is different from those who lost a parent during adolescence or young adulthood. The results suggest critical windows for careful monitoring and intervention for suicide attempt risk, especially 1-2 years after parental death for the older age groups and over decades for childhood survivors of parental death.
doi:10.1001/jamapsychiatry.2013.274
PMCID: PMC3664187  PMID: 23229861
17.  Mortality after Parental Death in Childhood: A Nationwide Cohort Study from Three Nordic Countries 
PLoS Medicine  2014;11(7):e1001679.
Jiong Li and colleagues examine mortality rates in children who lost a parent before 18 years old compared with those who did not using population-based data from Denmark, Sweden, and Finland.
Please see later in the article for the Editors' Summary
Background
Bereavement by spousal death and child death in adulthood has been shown to lead to an increased risk of mortality. Maternal death in infancy or parental death in early childhood may have an impact on mortality but evidence has been limited to short-term or selected causes of death. Little is known about long-term or cause-specific mortality after parental death in childhood.
Methods and Findings
This cohort study included all persons born in Denmark from 1968 to 2008 (n = 2,789,807) and in Sweden from 1973 to 2006 (n = 3,380,301), and a random sample of 89.3% of all born in Finland from 1987 to 2007 (n = 1,131,905). A total of 189,094 persons were included in the exposed cohort when they lost a parent before 18 years old. Log-linear Poisson regression was used to estimate mortality rate ratio (MRR). Parental death was associated with a 50% increased all-cause mortality (MRR = 1.50, 95% CI 1.43–1.58). The risks were increased for most specific cause groups and the highest MRRs were observed when the cause of child death and the cause of parental death were in the same category. Parental unnatural death was associated with a higher mortality risk (MRR = 1.84, 95% CI 1.71–2.00) than parental natural death (MRR = 1.33, 95% CI 1.24–1.41). The magnitude of the associations varied according to type of death and age at bereavement over different follow-up periods. The main limitation of the study is the lack of data on post-bereavement information on the quality of the parent-child relationship, lifestyles, and common physical environment.
Conclusions
Parental death in childhood or adolescence is associated with increased all-cause mortality into early adulthood. Since an increased mortality reflects both genetic susceptibility and long-term impacts of parental death on health and social well-being, our findings have implications in clinical responses and public health strategies.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
When someone close dies, it is normal to grieve, to mourn the loss of that individual. Initially, people who have lost a loved one often feel numb and disorientated and find it hard to grasp what has happened. Later, people may feel angry or guilty, and may be overwhelmed by feelings of sadness and despair. They may become depressed or anxious and may even feel suicidal. People who are grieving can also have physical reactions to their loss such as sleep problems, changes in appetite, and illness. How long bereavement—the period of grief and mourning after a death—lasts and how badly it affects an individual depends on the relationship between the individual and the deceased person, on whether the death was expected, and on how much support the mourner receives from relatives, friends, and professionals.
Why Was This Study Done?
The loss of a life-partner or of a child is associated with an increased risk of death (mortality), and there is also some evidence that the death of a parent during childhood leads to an increased mortality risk in the short term. However, little is known about the long-term impact on mortality of early parental loss or whether the impact varies with the type of death—a natural death from illness or an unnatural death from external causes such as an accident—or with the specific cause of death. A better understanding of the impact of early bereavement on mortality is needed to ensure that bereaved children receive appropriate health and social support after a parent's death. Here, the researchers undertake a nationwide cohort study in three Nordic countries to investigate long-term and cause-specific mortality after parental death in childhood. A cohort study compares the occurrence of an event (here, death) in a group of individuals who have been exposed to a particular variable (here, early parental loss) with the occurrence of the same event in an unexposed cohort.
What Did the Researchers Do and Find?
The researchers obtained data on everyone born in Denmark from 1968 to 2008 and in Sweden from 1973 to 2006, and on most people born in Finland from 1987 to 2007 (more than 7 million individuals in total) from national registries. They identified 189,094 individuals who had lost a parent between the age of 6 months and 18 years. They then estimated the mortality rate ratio (MRR) associated with parental death during childhood or adolescence by comparing the number of deaths in this exposed cohort (after excluding children who died on the same day as a parent or shortly after from the same cause) and in the unexposed cohort. Compared with the unexposed cohort, the exposed cohort had 50% higher all-cause mortality (MRR = 1.50). The risk of mortality in the exposed cohort was increased for most major categories of cause of death but the highest MRRs were seen when the cause of death in children, adolescents, and young adults during follow-up and the cause of parental death were in the same category. Notably, parental unnatural death was associated with a higher mortality risk (MRR = 1.84) than parental natural death (MRR = 1.33). Finally, the exposed cohort had increased all-cause MRRs well into early adulthood irrespective of child age at parental death, and the magnitude of MRRs differed by child age at parental death and by type of death.
What Do These Findings Mean?
These findings show that in three high-income Nordic countries parental death during childhood and adolescence is associated with an increased risk of all-cause mortality into early adulthood, irrespective of sex and age at bereavement and after accounting for baseline characteristics such as socioeconomic status. Part of this association may be due to “confounding” factors—the people who lost a parent during childhood may have shared other unknown characteristics that increased their risk of death. Because the study was undertaken in high-income countries, these findings are unlikely to be the result of a lack of material or health care needs. Rather, the increased mortality among the exposed group reflects both genetic susceptibility and the long-term impacts of parental death on health and social well-being. Given that increased mortality probably only represents the tip of the iceberg of the adverse effects of early bereavement, these findings highlight the need to provide long-term health and social support to bereaved children.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001679.
The UK National Health Service Choices website provides information about bereavement, including personal stories; it also provides information about children and bereavement and about young people and bereavement, including links to not-for-profit organizations that support children through bereavement
The US National Cancer Institute has detailed information about dealing with bereavement for the public and for health professionals that includes a section on children and grief (in English and Spanish)
The US National Alliance for Grieving Children promotes awareness of the needs of children and teens grieving a death and provides education and resources for anyone who wants to support them
MedlinePlus provides links to other resources about bereavement (in English and Spanish)
doi:10.1371/journal.pmed.1001679
PMCID: PMC4106717  PMID: 25051501
18.  Psychopathology Risk Transmission in Children of Parents With Substance Use Disorders 
The American journal of psychiatry  2004;161(4):685-691.
Objective
Children of fathers with substance use disorders are at increased risk for psychopathology, including conduct disorder, attention deficit hyperactivity disorder (ADHD), major depressive disorder, and anxiety disorders. This study examined the distinct influences of parent substance use disorder and other psychopathology in the transmission of the risk for psychopathology to their children.
Method
The subjects were 1,167 children (ages 6–14 years; 62% were male, 38% were female) from 613 families recruited according to a high-risk paradigm. Of these families, 294 had fathers with a substance use disorder (high-risk group), and 319 had fathers without a substance use disorder or other mental disorder (low-risk group). In all families, father, mother, and children were directly assessed. Mixed-effects ordinal regression analyses controlled for the nested data structure.
Results
For conduct disorder, ADHD, major depression, and anxiety disorders, the results indicated that the predominant predictor of specific mental disorders in offspring was a history of the corresponding disorders in both parents.
Conclusions
These results support specific parent-child transmission for childhood psychopathology.
PMCID: PMC3155941  PMID: 15056515
19.  Psychosocial Impairment in Offspring of Depressed Parents 
Psychological medicine  2005;35(10):1493-1503.
Background
Offspring of depressed parents experience impairment in a number of domains of functioning. Few studies have examined the impact of both maternal and paternal depression and comorbid psychopathology on offspring functioning.
Method
Participants in the Oregon Adolescent Depression Project (OADP) were administered diagnostic interviews and completed measures of psychosocial functioning during adolescence and again during young adulthood. Diagnostic interviews were also conducted with the mothers and fathers of the target individual.
Results
After controlling for relevant demographic characteristics, parental comorbid psychopathology, and offspring psychopathology, maternal depression was associated with greater levels of physical symptoms during adolescence, and with higher levels of minor stressors and a greater risk for using mental health services in young adulthood. Paternal depression was associated with offspring experiencing more major stressors, having lower perceived social competence, and being at greater risk for suicide attempts during adolescence, as well as lower perceived social competence in young adulthood.
Conclusions
Offspring of depressed parents demonstrate impairment in a variety of domains, regardless of the presence of their own psychopathology. Further research on the mechanisms that lead to these impairments, as well as research that examines the role of these psychosocial impairments in the subsequent development of psychopathology is warranted.
doi:10.1017/S0033291705005350
PMCID: PMC1351338  PMID: 16164773
20.  Advanced Paternal Age Is Associated with Impaired Neurocognitive Outcomes during Infancy and Childhood 
PLoS Medicine  2009;6(3):e1000040.
Background
Advanced paternal age (APA) is associated with an increased risk of neurodevelopmental disorders such as autism and schizophrenia, as well as with dyslexia and reduced intelligence. The aim of this study was to examine the relationship between paternal age and performance on neurocognitive measures during infancy and childhood.
Methods and Findings
A sample of singleton children (n = 33,437) was drawn from the US Collaborative Perinatal Project. The outcome measures were assessed at 8 mo, 4 y, and 7 y (Bayley scales, Stanford Binet Intelligence Scale, Graham-Ernhart Block Sort Test, Wechsler Intelligence Scale for Children, Wide Range Achievement Test). The main analyses examined the relationship between neurocognitive measures and paternal or maternal age when adjusted for potential confounding factors. Advanced paternal age showed significant associations with poorer scores on all of the neurocognitive measures apart from the Bayley Motor score. The findings were broadly consistent in direction and effect size at all three ages. In contrast, advanced maternal age was generally associated with better scores on these same measures.
Conclusions
The offspring of older fathers show subtle impairments on tests of neurocognitive ability during infancy and childhood. In light of secular trends related to delayed fatherhood, the clinical implications and the mechanisms underlying these findings warrant closer scrutiny.
Using a sample of children from the US Collaborative Perinatal Project, John McGrath and colleagues show that the offspring of older fathers exhibit subtle impairments on tests of neurocognitive ability during infancy and childhood.
Editors' Summary
Background.
Over the last few decades, changes in society in the developed world have made it increasingly common for couples to wait until their late thirties to have children. In 1993, 25% of live births within marriage in England and Wales were to fathers aged 35–54 years, but by 2003 it was 40%. It is well known that women's fertility declines with age and that older mothers are more likely to have children with disabilities such as Down's syndrome. In contrast, many men can father children throughout their lives, and little attention has been paid to the effects of older fatherhood.
More recent evidence shows that a man's age does affect both fertility and the child's health. “Advanced paternal age” has been linked to miscarriages, birth deformities, cancer, and specific behavioral problems such as autism or schizophrenia.
Rates of autism have increased in recent decades, but the cause is unknown. Studies of twins and families have suggested there may be a complex genetic basis, and it is suspected that damage to sperm, which can accumulate over a man's lifetime, may be responsible. A woman's eggs are formed largely while she is herself in the womb, but sperm-making cells divide throughout a man's lifetime, increasing the chance of mutations in sperm.
Why Was This Study Done?
There is good evidence linking specific disorders with older fathers, but the link between a father's age and a child's more general intelligence is not as clear. A recent study suggested a link between reduced intelligence and both very young and older fathers. The authors wanted to use this large dataset to test the idea that older fathers have children who do worse on tests of intelligence. They also wanted to re-examine others' findings using this same dataset that older mothers have more intelligent children.
What Did the Researchers Do and Find?
The researchers gathered no new data but reanalyzed data on children from the US Collaborative Perinatal Project (CPP), which had used a variety of tests given to children at ages 8 months, 4 years, and 7 years, to measure cognitive ability—the ability to think and reason, including concentration, memory, learning, understanding, speaking, and reading. Some tests included assessments of “motor skills”—physical co-ordination.
The CPP dataset holds information on children of 55,908 expectant mothers who attended 12 university-affiliated hospital clinics in the United States from 1959 to 1965. The researchers excluded premature babies and multiple births and chose one pregnancy at random for each eligible woman, to keep their analysis simpler. This approach reduced the number of children in their analysis to 33,437.
The researchers analyzed the data using two models. In one, they took into account physical factors such as the parents' ages. In the other, they also took into account social factors such as the parents' level of education and income, which are linked to intelligence. In addition, the authors grouped the children by their mother's age and, within each group, looked for a link between the lowest-scoring children and the age of their father.
The researchers found that children with older fathers had lower scores on all of the measures except one measure of motor skills. In contrast, children with older mothers had higher scores. They found that the older the father, the more likely was this result found.
What Do These Findings Mean?
This study is the first to show that children of older fathers perform less well in a range of tests when young, but cannot say whether those children catch up with their peers after the age of 7 years. Results may also be biased because information was more likely to be missing for children whose father's age was not recorded.
Previous researchers had proposed that children of older mothers may perform better in tests because they experience a more nurturing home environment. If this is the case, children of older fathers do not experience the same benefit.
However, further work needs to be done to confirm these findings. Especially in newer datasets, current trends to delay parenthood mean these findings have implications for individuals, couples, and policymakers. Individuals and couples need to be aware that the ages of both partners can affect their ability to have healthy children, though the risks for individual children are small. Policymakers should consider promoting awareness of the risks of delaying parenthood or introducing policies to encourage childbearing at an optimal age.
Additional Information.
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1000040.
Mothers 35+ is a UK Web site with resources and information for older mothers, mothers-to-be, and would-be mothers, including information on the health implications of fathering a child late in life
The American Society for Reproductive Medicine published a Patient Information Booklet on Age and Fertility in 2003, which is available online; it contains a small section called “Fertility in the Aging Male,” but otherwise focuses on women
The online encyclopedia Wikipedia has a short article on the “Paternal age effect” (note that Wikipedia is a free online encyclopedia that anyone can edit; available in several languages)
In 2005, the UK Office of National Statistics published a booklet entitled “Perpetual postponers? Women's, men's and couple's fertility intentions and subsequent fertility behaviour” looking at data from the British Household Panel Survey
doi:10.1371/journal.pmed.1000040
PMCID: PMC2653549  PMID: 19278291
21.  Comparison of parent, peer, psychiatric, and cannabis use influences across stages of offspring alcohol involvement: Evidence from the COGA Prospective Study 
Background
All stages of development of alcohol use disorder (AUD) have not been equally studied. While initiation of drinking has been given considerable attention, other stages have not been as thoroughly investigated. It is not clear if the same factors are associated consistently across early and late transitions in AUD involvement. High risk family samples that are enriched for AUD vulnerability and transitions in AUD development offer an opportunity to examine influences across multiple stages of AUD development.
Methods
Data from adolescents and young adults from high risk families were used to study four transitions in AUD development –time to first drink, first drink to first problem, first drink to first diagnosis, and first problem to first diagnosis. Cox modeling was used to compare associations of parental AUD, parental separation, peer substance use, offspring ever-use of cannabis, trauma exposures and internalizing and externalizing psychopathology across transitions.
Results
Hazards of most transitions were elevated for those who had ever used cannabis, those who attributed substance use to their peers, those with externalizing disorders and those with parents with AUD. Many risk factors were linked to early initiation of alcohol, particularly cannabis use. Internalizing disorders were associated with later stages. Non-assaultive trauma was associated only with early initiation; assaultive trauma was not associated with any transition. .
Conclusions
In this large, ethnically-diverse sample of high risk youth, significant influences across transitions were fairly consistent, with externalizing disorders and cannabis ever-use elevating the likelihood of each stage, and peer and parental (and especially maternal AUD) influences linked to initiation and some later stages. Finally, in light of the increasingly permissive legal and social stances toward cannabis in the U.S., the marked elevations of all alcohol outcomes observed for cannabis use underscore the importance of studying the underpinnings of this relationship.
doi:10.1111/acer.13293
PMCID: PMC5272776  PMID: 28073157
22.  Parents' and informal caregivers' views and experiences of communication about routine childhood vaccination: a synthesis of qualitative evidence 
Background
Childhood vaccination is an effective way to prevent serious childhood illnesses, but many children do not receive all the recommended vaccines. There are various reasons for this; some parents lack access because of poor quality health services, long distances or lack of money. Other parents may not trust vaccines or the healthcare workers who provide them, or they may not see the need for vaccination due to a lack of information or misinformation about how vaccinations work and the diseases they can prevent.
Communication with parents about childhood vaccinations is one way of addressing these issues. Communication can take place at healthcare facilities, at home or in the community. Communication can be two-way, for example face-to-face discussions between parents and healthcare providers, or one-way, for instance via text messages, posters or radio programmes. Some types of communication enable parents to actively discuss vaccines and their benefits and harms, as well as diseases they can prevent. Other communication types simply give information about vaccination issues or when and where vaccines are available. People involved in vaccine programmes need to understand how parents experience different types of communication about vaccination and how this influences their decision to vaccinate.
Objectives
The specific objectives of the review were to identify, appraise and synthesise qualitative studies exploring: parents' and informal caregivers' views and experiences regarding communication about childhood vaccinations and the manner in which it is communicated; and the influence that vaccination communication has on parents' and informal caregivers' decisions regarding childhood vaccination.
Search methods
We searched MEDLINE (OvidSP), MEDLINE In-process and Other Non-Index Citations (Ovid SP), Embase (Ovid), CINAHL (EbscoHOST), and Anthropology Plus (EbscoHost) databases for eligible studies from inception to 30 August 2016. We developed search strategies for each database, using guidelines developed by the Cochrane Qualitative Research Methods Group for searching for qualitative evidence as well as modified versions of the search developed for three related reviews of effectiveness. There were no date or geographic restrictions for the search.
Selection criteria
We included studies that utilised qualitative methods for data collection and analysis; focused on the views and experiences of parents and informal caregivers regarding information about vaccination for children aged up to six years; and were from any setting globally where information about childhood vaccinations was communicated or distributed.
Data collection and analysis
We used maximum variation purposive sampling for data synthesis, using a three-step sampling frame. We conducted a thematic analysis using a constant comparison strategy for data extraction and synthesis. We assessed our confidence in the findings using the GRADE-CERQual approach. High confidence suggests that it is highly likely that the review finding is a reasonable representation of the phenomenon of interest, while very low confidence indicates that it is not clear whether the review finding is a reasonable representation of it. Using a matrix model, we then integrated our findings with those from other Cochrane reviews that assessed the effects of different communication strategies on parents' knowledge, attitudes and behaviour about childhood vaccination.
Main results
We included 38 studies, mostly from high-income countries, many of which explored mothers' perceptions of vaccine communication. Some focused on the MMR (measles, mumps, rubella) vaccine.
In general, parents wanted more information than they were getting (high confidence in the evidence). Lack of information led to worry and regret about vaccination decisions among some parents (moderate confidence).
Parents wanted balanced information about vaccination benefits and harms (high confidence), presented clearly and simply (moderate confidence) and tailored to their situation (low confidence in the evidence). Parents wanted vaccination information to be available at a wider variety of locations, including outside health services (low confidence) and in good time before each vaccination appointment (moderate confidence).
Parents viewed health workers as an important source of information and had specific expectations of their interactions with them (high confidence). Poor communication and negative relationships with health workers sometimes impacted on vaccination decisions (moderate confidence).
Parents generally found it difficult to know which vaccination information source to trust and challenging to find information they felt was unbiased and balanced (high confidence).
The amount of information parents wanted and the sources they felt could be trusted appeared to be linked to acceptance of vaccination, with parents who were more hesitant wanting more information (low to moderate confidence).
Our synthesis and comparison of the qualitative evidence shows that most of the trial interventions addressed at least one or two key aspects of communication, including the provision of information prior to the vaccination appointment and tailoring information to parents' needs. None of the interventions appeared to respond to negative media stories or address parental perceptions of health worker motives.
Authors' conclusions
We have high or moderate confidence in the evidence contributing to several review findings. Further research, especially in rural and low- to middle-income country settings, could strengthen evidence for the findings where we had low or very low confidence. Planners should consider the timing for making vaccination information available to parents, the settings where information is available, the provision of impartial and clear information tailored to parental needs, and parents' perceptions of health workers and the information provided.
What are parents' and informal caregivers' views and experiences of communication about routine early childhood vaccination?
The aim of this Cochrane review was to explore how parents experience communication about vaccination for children under six years of age. We searched for and analysed qualitative studies that could answer this question.
Qualitative research explores how people perceive and experience the world around them. This review of qualitative research supplements other Cochrane reviews that assess the effect of different communication strategies on parents' knowledge, attitudes and behaviour about childhood vaccination.
Key messages
We are quite confident in the evidence we found that parents want clear, timely and balanced information, but that they often find this information to be lacking. The amount of information parents want and the sources they trust appear to be linked to their acceptance of vaccination; however, our confidence in this last finding is only low to moderate.
What did we study in the review?
Childhood vaccination is an effective way of preventing serious childhood illnesses. However, many children do not receive all of the recommended immunisations. There may be different reasons for this. Some parents do not have access to the vaccine, for instance because of poor quality health services, distance from their home to a health facility or lack of money. Some parents do not trust the vaccine itself or the healthcare worker who provides it, while others do not see the need to vaccinate their children at all. Parents may not know how vaccinations work or about the diseases that they prevent. They may also have received information that is misleading or incorrect.
To address some of these issues, governments and health agencies often try to communicate with parents about childhood vaccinations. This communication can take place at healthcare facilities, at home or in the community. Communication can be two-way, for instance face-to-face discussions between parents and healthcare providers. It can also involve one-way communication, for instance information provided through text messaging, posters, leaflets, or radio or television programmes. Some types of communication allow parents to actively discuss the vaccine, its benefits and harms, and the disease it aims to prevent. Other types of communication simply give information about these issues or about when and where vaccines are available. People involved in vaccine programmes need to understand how parents experience different types of communication about vaccination and how this influences their decision to vaccinate their child.
What are the main findings of the review?
We included 38 studies in our review. Most of the studies were from high-income countries and explored mothers' perceptions of vaccine communication. Some of the studies also included the views of fathers, grandmothers and other caregivers.
In general, parents wanted more information than they were getting (high confidence). For some parents, a lack of information led to worry and regret about their vaccination decision (moderate confidence).
Parents wanted balanced information about both the benefits and risks of vaccination (high confidence), presented in a clear and simple manner (moderate confidence) and tailored to their situation (low confidence). Parents wanted vaccination information to be available outside of the health services (low confidence). They wanted this information in good time before each vaccination appointment and not while their child was being vaccinated (moderate confidence).
Parents viewed health workers as an important source of information and had specific expectations of their interactions with them (high confidence). Poor communication and negative relationships with health workers sometimes impacted on vaccination decisions (moderate confidence).
Parents generally found it difficult to know which vaccination information source to trust and found it difficult to find information that they felt was unbiased and balanced (high confidence).
The amount of information parents wanted and the sources they felt they could trust seem to be linked to their acceptance of vaccination, with parents who were more hesitant wanting more information (low to moderate confidence).
How up-to-date is this review?
We searched for studies published before 30 August 2016.
doi:10.1002/14651858.CD011787.pub2
PMCID: PMC5461870  PMID: 28169420
23.  Maternal depression and co-occurring antisocial behaviour: testing maternal hostility and warmth as mediators of risk for offspring psychopathology 
Background
Disruption in the parent-child relationship is a commonly hypothesised risk factor through which maternal depression may increase risk for offspring psychopathology. However, maternal depression is commonly accompanied by other psychopathology, including antisocial behaviour. Few studies have examined the role of co-occurring psychopathology in depressed mothers. Using a longitudinal study of offspring of mothers with recurrent depression, we aimed to test whether maternal warmth/hostility mediated links between maternal depression severity on child outcomes, and how far direct and indirect pathways were robust to controls for co-occurring maternal antisocial behaviour.
Methods
Mothers with a history of recurrent major depressive disorder and their adolescent offspring (9–17 years at baseline) were assessed three times between 2007 and 2010. Mothers completed questionnaires assessing their own depression severity and antisocial behaviour at Time 1 (T1). The parent-child relationship was assessed using parent-rated questionnaire and interviewer-rated five-minute speech sample at Time 2 (T2). Offspring symptoms of depression and disruptive behaviours were assessed using the Child and Adolescent Psychiatric Assessment at Time 3 (T3).
Results
Maternal hostility and warmth respectively mediated the association between maternal depression severity and risk for offspring psychopathology. However, the effects were attenuated when maternal antisocial behaviour was included in the analysis. In tests of the full theoretical model, maternal antisocial behaviour predicted both maternal hostility and low warmth, maternal hostility predicted offspring disruptive behaviour disorder symptoms but not depression, and maternal warmth was not associated with either child outcome.
Conclusions
Parenting interventions aimed at reducing hostility may be beneficial for preventing or reducing adolescent disruptive behaviours in offspring of depressed mothers, especially when depressed mothers report co-occurring antisocial behaviour.
doi:10.1111/jcpp.12111
PMCID: PMC4573624  PMID: 23808575
Hostility; warmth; mediation; depression; antisocial behaviour; disruptive behaviour
24.  Pregnancy Weight Gain and Childhood Body Weight: A Within-Family Comparison 
PLoS Medicine  2013;10(10):e1001521.
David Ludwig and colleagues examine the within-family relationship between pregnancy weight gain and the offspring's childhood weight gain, thereby reducing the influence of genes and environment.
Please see later in the article for the Editors' Summary
Background
Excessive pregnancy weight gain is associated with obesity in the offspring, but this relationship may be confounded by genetic and other shared influences. We aimed to examine the association of pregnancy weight gain with body mass index (BMI) in the offspring, using a within-family design to minimize confounding.
Methods and Findings
In this population-based cohort study, we matched records of all live births in Arkansas with state-mandated data on childhood BMI collected in public schools (from August 18, 2003 to June 2, 2011). The cohort included 42,133 women who had more than one singleton pregnancy and their 91,045 offspring. We examined how differences in weight gain that occurred during two or more pregnancies for each woman predicted her children's BMI and odds ratio (OR) of being overweight or obese (BMI≥85th percentile) at a mean age of 11.9 years, using a within-family design. For every additional kg of pregnancy weight gain, childhood BMI increased by 0.0220 (95% CI 0.0134–0.0306, p<0.0001) and the OR of overweight/obesity increased by 1.007 (CI 1.003–1.012, p = 0.0008). Variations in pregnancy weight gain accounted for a 0.43 kg/m2 difference in childhood BMI. After adjustment for birth weight, the association of pregnancy weight gain with childhood BMI was attenuated but remained statistically significant (0.0143 kg/m2 per kg of pregnancy weight gain, CI 0.0057–0.0229, p = 0.0007).
Conclusions
High pregnancy weight gain is associated with increased body weight of the offspring in childhood, and this effect is only partially mediated through higher birth weight. Translation of these findings to public health obesity prevention requires additional study.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Childhood obesity has become a worldwide epidemic. For example, in the United States, the number of obese children has more than doubled in the past 30 years. 7% of American children aged 6–11 years were obese in 1980, compared to nearly 18% in 2010. Because of the rising levels of obesity, the current generation of children may have a shorter life span than their parents for the first time in 200 years.
Childhood obesity has both immediate and long-term effects on health. The initial problems are usually psychological. Obese children often experience discrimination, leading to low self-esteem and depression. Their physical health also suffers. They are more likely to be at risk of cardiovascular disease from high cholesterol and high blood pressure. They may also develop pre-diabetes or diabetes type II. In the long-term, obese children tend to become obese adults, putting them at risk of premature death from stroke, heart disease, or cancer.
There are many factors that lead to childhood obesity and they often act in combination. A major risk factor, especially for younger children, is having at least one obese parent. The challenge lies in unravelling the complex links between the genetic and environmental factors that are likely to be involved.
Why Was This Study Done?
Several studies have shown that a child's weight is influenced by his/her mother's weight before pregnancy and her weight gain during pregnancy. An obese mother, or a mother who puts on more pregnancy weight than average, is more likely to have an obese child.
One explanation for the effects of pregnancy weight gain is that the mother's overeating directly affects the baby's development. It may change the baby's brain and metabolism in such a way as to increase the child's long-term risk of obesity. Animal studies have confirmed that the offspring of overfed rats show these kinds of physiological changes. However, another possible explanation is that mother and baby share a similar genetic make-up and environment so that a child becomes obese from inheriting genetic risk factors, and growing up in a household where being overweight is the norm.
The studies in humans that have been carried out to date have not been able to distinguish between these explanations. Some have given conflicting results. The aim of this study was therefore to look for evidence of links between pregnancy weight gain and children's weight, using an approach that would separate the impact of genetic and environmental factors from a direct effect on the developing baby.
What Did the Researchers Do and Find?
The researchers examined data from the population of the US state of Arkansas recorded between 2003 and 2011. They looked at the health records of over 42,000 women who had given birth to more than one child during this period. This gave them information about how much weight the women had gained during each of their pregnancies. The researchers also looked at the school records of the children, over 91,000 in total, which included the children's body mass index (BMI, which factors in both height and weight). They analyzed the data to see if there was a link between the mothers' pregnancy weight gain and the child's BMI at around 12 years of age. Most importantly, they looked at these links within families, comparing children born to the same mother. The rationale for this approach was that these children would share a similar genetic make-up and would have grown up in similar environments. By taking genetics and environment into account in this manner, any remaining evidence of an impact of pregnancy weight gain on the children's BMI would have to be explained by other factors.
The results showed that the amount of weight each mother gained in pregnancy predicted her children's BMI and the likelihood of her children being overweight or obese. For every additional kg the mother gained during pregnancy, the children's BMI increased by 0.022. The children of mothers who put on the most weight had a BMI that was on average 0.43 higher than the children whose mothers had put on the least weight.
The study leaves some questions unanswered, including whether the mother's weight before pregnancy makes a difference to their children's BMI. The researchers were not able to obtain these measurements, nor the weight of the fathers. There may have also been other factors that weren't measured that might explain the links that were found.
What Do These Findings Mean?
This study shows that mothers who gain excessive weight during pregnancy increase the risk of their child becoming obese. This appears to be partly due to a direct effect on the developing baby.
These results represent a significant public health concern, even though the impact on an individual basis is relatively small. They could contribute to several hundred thousand cases of childhood obesity worldwide. Importantly, they also suggest that some cases could be prevented by measures to limit excessive weight gain during pregnancy. Such an approach could prove effective, as most mothers will not want to damage their child's health, and might therefore be highly motivated to change their behavior. However, because inadequate weight gain during pregnancy can also adversely affect the developing fetus, it will be essential for women to receive clear information about what constitutes optimal weight gain during pregnancy.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001521.
The US Centers for Disease Control and Prevention provide Childhood Obesity Facts
The UK National Health Service article “How much weight will I put on during my pregnancy?” provides information on pregnancy and weight gain and links to related resources
doi:10.1371/journal.pmed.1001521
PMCID: PMC3794857  PMID: 24130460
25.  Gender differences in the transmission of risk for antisocial behavior problems across generations 
PLoS ONE  2017;12(5):e0177288.
Previous studies have shown that children of alcohol use disorder (AUD) parents are more likely to develop alcohol problems as well as antisocial and other behavior problems. The purpose of this study was to examine gender discordance in the effect of early maternal and paternal influences on antisocial behaviors of boys and girls, as well as the environmental factors that moderate the parental effects. Specifically, we examined the effects of childhood and adulthood antisocial behavior of the parents on offspring antisocial behavior as young adults. We also examined whether mothers’ and fathers’ drinking problems when offspring were young children (6–8 years) affected offspring antisocial behavior as young adults (18–21 years). We evaluated 655 children from 339 families in the Michigan Longitudinal Study (MLS), a prospective study of AUD and non-AUD families. Path models were constructed in order to test for the parental contributions to offspring outcomes. We found that both mothers’ and fathers’ antisocial behavior contributed to the children’s young adult antisocial behavior. Only mothers’ drinking problems while their children were little had a significant effect on their sons’ later drinking, but not on their daughters’. These different parental effects suggest that maternal and paternal influences may be mediated by different mechanisms.
doi:10.1371/journal.pone.0177288
PMCID: PMC5432185  PMID: 28505162

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