http://www.iowaaces360.org/uploads/1/0/9/2/10925571/relationship_of_childhood_abuse_and..._1998.pdf

Relationship of childhood abuse and household dysfunction to many of the leading causes of death in adults. The Adverse Childhood Experiences (ACE) Study

In a prospective-longitudinal study of a representative birth cohort, we tested why stressful experiences lead to depression in some people but not in others. A functional polymorphism in the promoter region of the serotonin transporter (5-HT T) gene was found to moderate the influence of stressful life events on depression. Individuals with one or two copies of the short allele of the 5-HT T promoter polymorphism exhibited more depressive symptoms, diagnosable depression, and suicidality in relation to stressful life events than individuals homozygous for the long allele. This epidemiological study thus provides evidence of a gene-by-environment interaction, in which an individual's response to environmental insults is moderated by his or her genetic makeup.

/pdf/influence-of-life-stress-on-depression-moderation-by-a-43dxsjf74s.pdf

Influence of Life Stress on Depression: Moderation by a Polymorphism in the 5-HTT Gene

Attachment--and loss.

The adolescent brain and age-related behavioral manifestations

Childhood maltreatment has been linked to a variety of changes in brain structure and function and stress–responsive neurobiological systems. Epidemiological studies have documented the impact of childhood maltreatment on health and emotional well–being. After a brief review of the neurobiology of childhood trauma, we use the Adverse Childhood Experiences (ACE) Study as an epidemiological “case example” of the convergence between epidemiologic and neurobiological evidence of the effects of childhood trauma. The ACE Study included 17,337 adult HMO members and assessed 8 adverse childhood experiences (ACEs) including abuse, witnessing domestic violence, and serious household dysfunction. We used the number of ACEs (ACE score) as a measure of cumulative childhood stress and hypothesized a "doseresponse" relationship of the ACE score to 18 selected outcomes and to the total number of these outcomes (comorbidity). Based upon logistic regression analysis, the risk of every outcome in the affective, somatic, substance abuse, memory, sexual,and aggressionrelated domains increased in a graded fashion as the ACE score increased (P <0.001). The mean number of comorbid outcomes tripled across the range of the ACE score. The graded relationship of the ACE score to 18 different outcomes in multiple domains theoretically parallels the cumulative exposure of the developing brain to the stress response with resulting impairment in multiple brain structures and functions.

https://traumasensitiveschools.org/wp-content/uploads/2013/06/Anda-Article-Enduring-Effects-of-Abuse.pdf

The enduring effects of abuse and related adverse experiences in childhood: A convergence of evidence from neurobiology and epidemiology

Background Women report higher rates of major depression (MD) than men. Although genetic factors play an important etiologic role in MD, we are uncertain whether genetic factors are of equal importance in men and women, and whether the same genetic factors predispose men and women to MD. Methods We obtained, by telephone interview, a lifetime history of MD, defined by the DSM-III-R , from 3790 complete male-male, female-female, and male-female twin pairs, identified through a population-based registry. Results were analyzed using probandwise concordance, odds ratios, and biometrical twin modeling. Results The odds ratios (plus tetrachoric correlations) for lifetime MD were as follows: (1) male-male monozygotic, 3.29 (+0.37); (2) male-male dizygotic, 1.86 (+0.20); (3) female-female monozygotic, 3.02 (+0.39); (4) female-female dizygotic, 1.59 (+0.18); and (5) male-female dizygotic, 1.39 (+0.11). In the best-fitting twin model, the heritability of liability to MD was the same in men and women and equal to 39%, while the remaining 61% of the variance in liability was due to individual-specific environment. We rejected, with only modest confidence, the hypothesis that the genetic risk factors for MD were the same in men and women. The best-fitting model estimated the genetic correlation in the liability to MD in the 2 sexes to be +0.57. While we found no evidence to suggest a violation of the equal environment assumption, MD was less common in women from opposite-sex vs same-sex twin pairs. Conclusions Major depression is equally heritable in men and women, and most genetic risk factors influence liability to MD similarly in the 2 sexes. However, genes may exist that act differently on the risk for MD in men vs women.

https://jamanetwork.com/journals/jamapsychiatry/articlepdf/204631/yoa8028.pdf

A population-based twin study of lifetime major depression in men and women

OBJECTIVE: Women are at greater risk for major depression than men. The authors sought to determine whether the gender difference in prevalence for major depression was due to more frequent exposure to stressful life events and/or greater sensitivity to their depressogenic effects. METHOD: Male-male, female-female, and male-female twin pairs from a popu-lation-based registry were personally interviewed. Each interview assessed the occurrence, to the nearest month, of 18 personal and social network classes of stressful life events and episode onsets of major depression. Standard logistic regression analyses were conducted for the same-sex pairs, and each female twin in the opposite-sex pairs was compared with her male co-twin by using conditional logistic regression. RESULTS: Women consistently reported higher rates of housing problems, loss of confidant, crises and problems getting along with individuals in their proximal network, and illness of individuals within their distal network. In both the same-se...

Gender differences in the rates of exposure to stressful life events and sensitivity to their depressogenic effects.

Objective: Compared to men, women have larger and more intimate social networks and higher rates of major depression. Prior studies have suggested that women are more sensitive to the depressogenic effects of low social support, but most of these studies had substantial methodologic limitations. Method: In two interview waves at least 1 year apart, 1,057 pairs of opposite-sex dizygotic twin pairs ascertained from a population-based register were assessed. The authors predicted risk of major depression in the year before the wave 2 interview from levels of social support assessed at wave 1. Results: Women reported higher levels of global social support than their twin brothers. Global social support at wave 1 predicted risk for major depression at wave 2 significantly more strongly in female than in male members of these pairs, and the same effect was seen when the analysis controlled for the history of major depression in the year prior to wave 1. Women were more sensitive than men to the depressogenic effects of low levels of social support, particularly from the co-twin, other relatives, parents, and spouses. Levels of social support did not explain the sex difference in risk for major depression. Conclusions: Emotionally supportive social relationships are substantially more protective against major depression for women than for men. While these effects cannot explain sex effects on the prevalence of major depression, they do suggest important sex differences in pathways of risk. Clarification of the nature of the causal links between low social support and depression in women is needed.

https://ajp.psychiatryonline.org/doi/pdf/10.1176/appi.ajp.162.2.250

Sex differences in the relationship between social support and risk for major depression: a longitudinal study of opposite-sex twin pairs.

Background In order to develop informed approaches to prevention and treatment of illicit psychoactive substance use, abuse, and dependence, we need to understand the sources of individual differences in risk. Methods In personal interviews with 1198 male-male twin pairs (708 monozygotic and 490 dizygotic) ascertained from a population-based registry, we assessed lifetime use, heavy use, and abuse of and dependence on cannabis, sedatives, stimulants, cocaine, opiates, and hallucinogens. Twin resemblance was assessed by probandwise concordance, odds ratio, tetrachoric correlations, and biometrical model fitting. Results Twin resemblance for substance use, heavy use, abuse, and dependence was substantial, and consistently greater in monozygotic than in dizygotic twins. For any drug use and for cannabis and hallucinogen use, model fitting suggested that twin resemblance was due to both genetic and familial-environmental factors. Twin resemblance for sedative, stimulant, cocaine, and opiate use, however, was caused solely by genetic factors. With 2 exceptions (cocaine abuse and stimulant dependence), twin resemblance for heavy use, abuse, and dependence resulted from only genetic factors, with heritability of liability usually ranging from 60% to 80%. No consistent evidence was found for violations of the equal environment assumption. Conclusions In accord with prior results in studies of women, the family environment plays a role in twin resemblance for some forms of substance use in men. However, twin resemblance for heavy use, abuse, and dependence in men is largely caused by genetic factors, and heritability estimates are high.

https://jamanetwork.com/journals/jamapsychiatry/articlepdf/481586/yoa9243.pdf

Illicit Psychoactive Substance Use, Heavy Use, Abuse, and Dependence in a US Population-Based Sample of Male Twins

Context While both environmental and genetic factors are important in the etiology of psychoactive substance use (PSU), we know little of how these influences differ through development. Objective To clarify the changing role of genes and environment in PSU from early adolescence through middle adulthood. Design Retrospective assessment by life history calendar, with univariate and bivariate structural modeling. Setting General community. Participants A total of 1796 members of male-male pairs from the Virginia Adult Twin Study of Psychiatric and Substance Use Disorders. Main Outcome Measures Levels of use of alcohol, caffeine, cannabis, and nicotine recorded for every year of the respondent's life. Results For nicotine, alcohol, and cannabis, familial environmental factors were critical in influencing use in early adolescence and gradually declined in importance through young adulthood. Genetic factors, by contrast, had little or no influence on PSU in early adolescence and gradually increased in their effect with increasing age. The sources of individual differences in caffeine use changed much more modestly over time. Substantial correlations were seen among levels of cannabis, nicotine, and alcohol use and specifically between caffeine and nicotine. In adolescence, those correlations were strongly influenced by shared effects from the familial environment. However, as individuals aged, more and more of the correlation in PSU resulted from genetic factors that influenced use of both substances. Conclusions These results support an etiologic model for individual differences in PSU in which initiation and early patterns of use are strongly influenced by social and familial environmental factors while later levels of use are strongly influenced by genetic factors. The substantial correlations seen in levels of PSU across substances are largely the result of social environmental factors in adolescence, with genetic factors becoming progressively more important through early and middle adulthood.

https://jamanetwork.com/journals/jamapsychiatry/articlepdf/482739/yoa70105_674_682.pdf

Carol A. Prescott

Papers

A population-based twin study of lifetime major depression in men and women

Gender differences in the rates of exposure to stressful life events and sensitivity to their depressogenic effects.

Sex differences in the relationship between social support and risk for major depression: a longitudinal study of opposite-sex twin pairs.

Illicit Psychoactive Substance Use, Heavy Use, Abuse, and Dependence in a US Population-Based Sample of Male Twins

Genetic and Environmental Influences on Alcohol, Caffeine, Cannabis, and Nicotine Use From Early Adolescence to Middle Adulthood