Childhood Stressful Life Events Research Articles

Childhood Psychosocial Cumulative Risks and Carotid Intima-Media Thickness in Adulthood: The Cardiovascular Risk in Young Finns Study.

Adverse experiences in childhood may influence cardiovascular risk in adulthood. We examined the prospective associations between types of psychosocial adversity and having multiple adversities (e.g., cumulative risk) with carotid intima-media thickness (IMT) and its progression among young adults. Higher cumulative risk score in childhood was expected to be associated with higher IMT and its progression. Participants were 2265 men and women (age range, 24-39 years in 2001) from the ongoing Cardiovascular Risk in Young Finns study whose carotid IMTs were measured in 2001 and 2007. A cumulative psychosocial risk score, assessed at the study baseline in 1980, was derived from four separate aspects of the childhood environment that may impose risk (childhood stressful life events, parental health behavior family, socioeconomic status, and childhood emotional environment). The cumulative risk score was associated with higher IMT in 2007 (b = 0.004, standard error [SE] = 0.001, p < .001) and increased IMT progression from 2001 to 2007 (b = 0.003, SE = 0.001, p = .001). The associations were robust to adjustment for conventional cardiovascular risk factors in childhood and adulthood, including adulthood health behavior, adulthood socioeconomic status, and depressive symptoms. Among the individual childhood psychosocial risk categories, having more stressful life events was associated with higher IMT in 2001 (b = 0.007, SE = 0.003, p = .016) and poorer parental health behavior predicted higher IMT in 2007 (b = 0.004, SE = 0.002, p = .031) after adjustment for age, sex, and childhood cardiovascular risk factors. Early life psychosocial environment influences cardiovascular risk later in life, and considering cumulative childhood risk factors may be more informative than individual factors in predicting progression of preclinical atherosclerosis in adulthood.

Age of Onset in Schizophrenia Spectrum Disorders: Complex Interactions between Genetic and Environmental Factors.

In this study we evaluated the role of a candidate gene for major psychosis, Sialyltransferase (ST8SIA2), in the risk to develop a schizophrenia spectrum disorders, taking into account exposure to stressful life events (SLEs). Eight polymorphisms (SNPs) were tested in 94 Schizophreniainpatients and 176 healthy controls. Schizophrenia patients were also evaluated for SLEs in different life periods. None of the SNPs showed association with schizophrenia. Nevertheless, when crossing genetic variants with childhood SLEs, we could observe trends of interaction with age of onset. Though several limitations, our results support a protective role of ST8SIA2 in individuals exposed to moderate childhood stress.

The effect of childhood stress on the development of mental disorders in adults

There is evidence that not only severe stressful events, but also common low-threat events, in particular chronic ones, may cause or provoke some mental disorders. The literature data on the degree of pathogenicity of stress factors are insufficient. Authors attempted to summarize the established facts in the following aspects: current conceptions on the physiology and pathology of stress in the frames of the problem of psychosomatic disorders, deprivation in childhood, neurobiological consequences of childhood stress, psychiatric consequences of stress in childhood. Authors believe that this problem demands further investigation to find possible predictors of mental disorders in patients who had experienced stressful life events in childhood.

Genes involved in neuroplasticity and stressful life events act on the short-term response to antidepressant treatment: a complex interplay between genetics and environment.

During the last few years, an increasing number of studies have focused on the association between neuroplasticity and affective disorders. The aim of the study is to evaluate the interactive effect of stressful life events (SLEs) and genes involved in neuroplasticity (BDNF and ST8SIA) on the short-term response to antidepressant treatment. A total of 114 patients affected by mood or anxiety disorders under antidepressant treatment were enrolled in the study. We evaluated the interactive effects of three BDNF single-nucleotide polymorphisms (SNPs) and five ST8SIA SNPs and SLEs at different time points (childhood SLEs, SLEs at illness onset, and SLEs reported over the last preceding treatment) over 1-month of antidepressant treatment. Carriers of some genetic variants in both BDNF and ST8SIA had a slower response to antidepressants if non-exposed to the onset SLEs, whereas they had a similar trend compared with the carriers of the opposite variant if exposed (allelic analysis: BDNF p = 0.00003, p = 0.00609; ST8SIA p = 0.04, p = 0.033). The BDNF haplotype analysis confirmed this trend (p = 0.00016). Though our results are limited by the small sample size, variants in BDNF and ST8SIA may slow down the early response to antidepressants in subjects non-exposed to stressors at the illness onset, with a remarkable gene-environment interaction.

Glucocorticoid receptor gene (NR3C1) methylation following stressful events between birth and adolescence. The TRAILS study

Stress early in life is a known risk factor for the development of affective disorders later in life. Epigenetic mechanisms, such as DNA methylation, may have an important role in mediating that risk. Recent epigenetic research reported on the long-term relationship between traumatic stress in childhood and DNA methylation in adulthood. In this study, we examined the impact of various types of stress (perinatal stress, stressful life events (SLEs) and traumatic youth experiences) on methylation of the glucocorticoid receptor gene (NR3C1) in the blood of a population sample of 468 adolescents (50.4% female, mean age 16.1 years). Second, we determined whether stress at different ages was associated with higher NR3C1 methylation. NR3C1 methylation rates were higher after exposure to SLEs and after exposure to traumatic youth experiences. NR3C1 methylation in adolescence was not higher after exposure to perinatal stress. Experience of SLEs in adolescence was associated with a higher NR3C1 methylation, independently of childhood SLEs. We demonstrate that not only traumatic youth experiences but also (more common) SLEs are associated with higher NR3C1 methylation. In addition, our findings underline the relevance of adolescent stress for epigenetic changes in the NR3C1 gene.

Stressful life-events in childhood and risk of multiple sclerosis: a Danish nationwide cohort study

Background: Current knowledge concerning the association between exposure to stressful life-events (SFLEs) in childhood and later risk of multiple sclerosis (MS) is sparse. Objectives: We studied the associations between SFLEs in childhood and subsequent risk of MS in a nationwide cohort of 2.9 million Danes born from 1968 to 2011. Methods: A SFLE in childhood was defined as exposure before age 18 years to parental divorce, parental death, or death of a sibling, using information from the Danish Civil Registration System. MS cases in the cohort were identified in the Danish Multiple Sclerosis Registry. Associations of SFLE with MS risk were evaluated by incidence rate ratios (RR) of MS obtained in log-linear Poisson regression models. Results: Persons exposed to any SFLE in childhood were at 11% elevated risk of MS (RR = 1.11; 95% confidence interval: 1.03–1.20), compared to non-exposed persons. Stratification by subtype of SFLE showed that parental death and death of a sibling were not associated with MS risk. However, persons exposed to parental divorce were at 13% increased risk of developing MS compared to non-exposed (RR = 1.13; 1.04–1.23). Conclusions: Associations of SFLEs in childhood with risk of MS are weak. However, parental divorce is somehow associated with modestly increased risk of MS.

The relationships between stressful life events during childhood and differentiation of self and intergenerational triangulation in adulthood.

This study examined the relationships between stressful life events in childhood and differentiation of self and intergenerational triangulation in adulthood. The sample included 217 students (173 females and 44 males) from a college in northern Israel. Participants completed the Hebrew versions of Life Events Checklist (LEC), Differentiation of Self Inventory-Revised (DSI-R) and intergenerational triangulation (INTRI). The main findings were that levels of stressful life events during childhood and adolescence among both genders were positively correlated with the levels of fusion with others and intergenerational triangulation. The levels of positive life events were negatively related to levels of emotional reactivity, emotional cut-off and intergenerational triangulation. Levels of stressful life events in females were positively correlated with emotional reactivity. Intergenerational triangulation was correlated with emotional reactivity, emotional cut-off, fusion with others and I-position. Findings suggest that families that experience higher levels of stressful life events may be at risk for higher levels of intergenerational triangulation and lower levels of differentiation of self.

Stressful Life Events Across the Life Span and Insecure Attachment Following Combat Trauma

Attachment orientations are mostly considered to be stable interpersonal patterns. Still, a growing body of literature shows changes in attachment orientations following stressful and traumatic events. This study examined the implications of stressful life events (SLEs) throughout the life cycle in insecure attachment orientations (anxious attachment and avoidant attachment). The sample included 664 Israeli war veterans from the 1982 Lebanon War, of whom 363 suffered from acute combat stress reaction (CSR) on the battlefield, and 301 comprised a matched control group without antecedent CSR. The findings reveal a positive correlation between insecure attachment and both acute (CSR) and chronic (post-traumatic stress disorder) stress reactions. In addition, post-war SLEs were more powerful predictors of insecure attachment than other types of SLEs. Combat exposure, as well as pre-war SLEs in childhood and adulthood, made differential contributions to both types of insecure attachment orientations. Theoretical and practical implications of these findings are discussed.

What Is the Nature of Serotonergic Abnormalities in Human Aggression?

T he archival report by Rylands et al. (1) in this issue of Biological Psychiatry represents exciting new work in the biology of human aggression. Although a role for central serotonin (5-HT) in human aggression has been studied for more than 30 years, the very specific aspects of how the 5-HT system may be altered in aggressive individuals are only now being examined because of newer technologies and the willingness to look beyond basic biologic principles. Rylands et al. (1) performed ligand-binding positron emission tomography studies, targeting the 5-HT transporter (SERT) and the 5-HT-2a receptor, in 14 subjects characterized as being impulsive aggressive and 13 subjects characterized as compared being not impulsive aggressive. In brief, the investigators reported that SERT availability is significantly increased in brain stem areas and reduced, although nonsignificantly, in cortical brain areas. More importantly, although the investigators reported a direct association between SERT availability and several measures of impulsivity and aggression in their subjects, they reported that the strongest association was with measures of adversity and stressful life events in childhood. They suggest, furthermore, that this latter finding points to an exciting, potential, etiologic link to altered 5-HT function and impulsive aggression in humans. In this commentary, I will discuss several aspects of this report in terms of methodology and in terms of how it relates to the field as it has developed since the late 1970s. The idea that brain 5-HT has any relationship with aggression was first proposed in the 1970s when demonstrated that altering brain levels of 5-HT uncovered an inverse relationship with aggression in animal models. In other words, when 5-HT was experimentally reduced, aggressive responding in the model animal increased, and when 5-HT was experimentally enhanced, aggressive responding decreased. The first evidence of this in human subjects was published in 1979 when Brown et al. (2) reported an inverse correlation between lifetime levels of actual aggressive behavior and lumbar cerebrospinal fluid (CSF) levels of the major 5-HT metabolite, 5-hydroxyindolacetic acid (CSF 5HIAA) in personality-disordered subjects. This was followed by the work of Linnoila et al. (3), who reported that reduced CSF 5HIAA levels in humans were linked to aggressive behavior that was specifically impulsive in nature. At the same time, Stanley et al. reported that victims of violent suicide, compared with those who also died violently but by accident, had lower numbers of SERT (4), and higher numbers of 5-HT-2, receptors in frontal cortex (5). Together this suggested that presynaptic 5HT activity was low and that postsynaptic receptors had

Interaction between BDNF Val66Met and childhood stressful life events is associated to affective memory bias in men but not women

Recent meta-analyses point towards a pathogenic role of the Val66Met variant of the brain-derived neurotrophic factor (BDNF) in major depressive disorder, specifically in males. We investigated whether BDNF Val66Met shows a male-specific interaction with childhood stressful life events on affective memory bias, a cognitive susceptibility factor for depression. Healthy volunteers (n=430; 272 females and 158 males) were genotyped for BDNF Val66Met (rs6265) and completed the self-referent encoding task and a childhood stressful life events scale. BDNF Met carriers reporting childhood events tended to recall a lower proportion of positive words compared to Val/Val homozygotes reporting childhood events. Sex-specific analyses revealed that the BDNF genotype×childhood events interaction was significant in male participants and not in female participants. The results suggest that in males, BDNF Val66Met interacts with childhood life events, increasing the cognitive susceptibility markers of depression. In females, this effect may be independent of BDNF Val66Met.

P1-310 Stressful life-events in childhood and depression in adulthood: the role of the social integration according to individual and neighbourhood socioeconomic status

IntroductionSocial integration could constitute a pathway and/or a buffer in the association between stressful life events in childhood (SLEC) and depression in adulthood and this may differ according to the...

Early Life Traumatic Stressors and the Mediating Role of PTSD in Incident HIV Infection Among US Men, Comparisons by Sexual Orientation and Race/Ethnicity: Results From the NESARC, 2004–2005

Stressful life events in childhood during critical periods of development have long-term psychological and neurobiological sequelae, which may affect risk for HIV infection across the life course. Data were from a nationally representative sample of 13,274 US men (National Epidemiologic Survey on Alcohol and Related Conditions, 2004-2005). Weighted multivariable logistic regression models examined (1) the association of childhood violent events before age 18 on 12-month incident HIV infection and (2) whether posttraumatic stress disorder (PTSD) diagnosis (clinical interview) mediated the association between early life events and HIV. Overall, the 12-month HIV incidence was <1% (0.35%); 44% of new infections were among racial/ethnic minorities and 31% among men who have sex with men). One-third of the sample (33.5%) reported one or more early life stressors (physical abuse, sexual abuse, neglect, verbal violence, or witnessed violence). In a weighted multivariable logistic regression model adjusted for age, education, family's socioeconomic position, and sexual behaviors, each additional early life violent event was associated with an elevated odds of HIV infection [adjusted odds ratio (aOR) = 1.32; 95% confidence interval (CI): 1.16 to 1.50]. Adding PTSD to this adjusted model, PTSD was highly associated with incident HIV infection (aOR = 5.75; 95% CI: 4.76 to 6.95). There was evidence that PTSD partially mediated the relationship between early life events and HIV (aOR = 1.14; 95% CI: 1.02 to 1.28). Experiencing early life violent family stressors was associated with HIV infection among men. Early life events and HIV infection were mediated by PTSD, which has implications for understanding disparities in HIV infection. Interventions are urgently needed that address the long-term sequelae of childhood violence.

Stressful life events in childhood and risk of infectious disease hospitalization

Individuals exposed to high levels of stress might have an increased risk of infectious diseases. However, most of the previous studies have been conducted among adults. To examine the effect of childhood stress, we conducted a nationwide cohort study including all Danish children born from 1977 to 2004. Stressful life events (SFLE) included parental death, death of sibling or parental divorce. Outcome was defined as hospitalizations due to less severe (LSID) or severe infectious diseases (SID). Children were followed until the age of 15 years. The association between SFLE and risk of infections was evaluated through rate ratios (RR) comparing infectious disease incidence ratios in children with and without a history of SFLE. Overall, children exposed to SFLE were at 13% increased risk of LSID (RR = 1.13 (1.10-1.15)), but at no increased risk of SID hospitalization (RR = 1.05 (0.97-1.14)). Looking at the specific type of SFLE, parental divorce increased the risk of LSID (RR = 1.11 (1.09-1.14)) and SID hospitalization (1.11 (1.02-1.21)) by 11%, whereas no increased risk of LSID and SID hospitalization was observed following parental death. Finally, a 34% increased risk of LSID hospitalization (RR = 1.34 (1.23-1.45)) was observed following death of sibling, in contrast to no increased risk of SID hospitalization. Childhood exposure to SFLE, especially parental divorce seems to increase the risk of infectious disease hospitalization. Although we cannot determine whether our observations are the result of a biological effect of stress, adoption of unhealthy behaviours or increased likelihood of hospitalization, our findings do have public health relevance as a considerable proportion of the children today will be exposed to SFLE, the majority to parental divorce.

Timing, quantity and quality of stressful life events in childhood and preceding the first episode of bipolar disorder

A large body of evidence supports the importance of genetic risk factors in bipolar disorder (BPD), but less is known about the role of stressful life events (SLE). This study assessed the role of SLE in childhood, adulthood and one year prior to first episodes of both depression and mania in BPD. Three groups of 50 matched subjects each were assessed: patients with BPD, with borderline personality disorder (BLPD) and healthy controls. Structured clinical interviews were used for diagnoses. The Coddington Life Events Schedule and the Israel Psychiatric Epidemiology Research Interview Life Event Scale measured life events and were confirmed with a semi-structured interview for subjective experience for each SLE. In BPD, the total number of SLE was lower during childhood and higher in the year preceding the first depression compared to controls and the proportion of loss-related events in childhood was higher. In the year preceding the first depressive episode, BPD subjects had more total, negative uncontrolled and independent but not positive SLE. In the year preceding the first episode of mania, the total number of uncontrolled, negative SLE were higher in BPD, whereas positive and separation-related SLE were not. After the first episode, BPD subjects had less SLE than controls. Negative and loss-related SLE are common in BPD subjects, occur in the year preceding the first episodes of depression and mania and are less common in childhood or after the onset of the disorder.

Factors associated with reported childhood depressive symptoms at age 8 and later self-reported depressive symptoms among boys at age 18

This study aimed to study conditions associated with depressive symptoms at ages 8 and 18 in a representative birth cohort of Finnish males. The participants in this community-based 10-year follow-up study consisted of 2,348 boys born in 1981. At age 8, three informant sources were used: parents, teachers, and the children themselves. Depressive symptoms were established using the Children's Depression Inventory (CDI). At age 18, self-report questionnaires were used to study the boys' family factors, life events, adaptive functioning, and substance use. Depressive symptoms at age 18 were established using Beck's Depression Inventory (BDI). Poor adaptive functioning at age 18 was independently associated with both child and late adolescent depressive symptoms. Use of illicit drugs and somatic health problems were independently associated with later depressive symptoms. Parental divorce in early childhood independently predicted depressive symptoms both in childhood and in late adolescence. Teacher reports of child's total problems at age 8 independently predicted depressive symptoms at age 18. Depression in males at ages 8 and 18 is particularly associated with stressful life events in childhood, whereas late depression is associated with somatic health problems and substance use. Further population-based studies comparing conditions associated with childhood and adolescent depression are needed.

Suicide, stress and serotonin receptor 1A promoter polymorphism -1019C&gt;G in Slovenian suicide victims

Implication of serotonergic system in suicide and suicide attempts has been discussed for several years. One of the most abundant serotonin receptors in the mammalian brain is the receptor 1A (5-HT1A); studies of its polymorphisms and suicide have provided very inconsistent results so far. The suggestion that the G allele depresses HTR1A autoreceptor expression, and therefore reduces serotonergic neurotransmission that might predispose to depression and suicide, made the promoter polymorphism -1019C>G a very promising candidate gene. In our study we analyzed promoter polymorphism -1019C>G on 323 suicide victims and 190 controls (all of Slovenian origin), taking into account sex, suicide method, and in case of suicide victims also stressful life events. Differences in the distributions of genotype and allele frequencies were not statistically significant between suicide victims and control group, and the same was found for distributions according to sex and suicide method. For 62 suicide victims information about stressful life events in the month prior to the suicide and in childhood was provided. For analysis we combined CG/GG genotypes and compared them to the CC genotype. More stressful life events in the month prior to the suicide were reported for the subgroup with CC genotype (mean number of events = 2.53; SD = 1.50) in comparison to subgroup with CG/GG genotypes (mean number of events = 1.58; SD = 1.32; P < 0.05). However, subgroups of suicide victims with CC or CG/GG genotypes did not differ regarding numbers of reported stressful life events in childhood (P > 0.05). Our study provides no evidence for the implication of HTR1A promoter polymorphism in suicide in general, but it suggests further studies that would take into account the interconnected network of suicide completion, genetic background and stress, beside other risk factors.

Breast Cancer and Psychosocial Factors: Early Stressful Life Events, Social Support, and Well-Being

The allostasis theory postulates that stress causes the body to activate physiologic systems in order to maintain stability. The authors sought to examine the relationship between earlier stress and later development of breast cancer (BC). Authors correlated discrete and interactive relationships of stressful life events, social support, and well-being during childhood and adolescence with the occurrence of BC in adulthood among 300 women with primary BC and 305 matched control subjects. BC patients and control subjects reported similar childhood experiences. Yet, although childhood stressful life events were associated with reports of less family support and well being among the controls, those in the BC group who experienced high stress in early childhood actually expressed higher levels of family support and well-being than did those who had experienced lower levels of stress. These findings may reflect a tendency toward a repressive coping style among the BC group, which may be either a risk factor for the disease or a result of having it.

Childhood Stressful Life Events and Bipolar Spectrum Disorders

In a cross–sectional study, we investigated the association of reported childhood stressful life events and bipolar spectrum disorders in an undergraduate sample. Specifically, we tested the harsh environment and stress generation explanations of the childhood stress and bipolar disorder relationship. The final sample included 155 bipolar spectrum participants and 155 demographically matched normal controls. Consistent with the harsh environment hypothesis, we found that the total number of reported childhood events, and particularly events independent of one's behavior that occurred prior to bipolar individuals' age of onset (using the same cutoff age for their matched normal controls) were associated with bipolar versus normal control status. Also, in partial support of the harsh environment hypothesis, total number and independent events predicted an earlier onset of bipolar episodes, but inconsistent with the hypothesis, so did dependent events. In contrast to the stress generation hypothesis, a bipolar spectrum diagnosis did not predict the number of total childhood stressors, particularly events dependent on one's behavior occurring after the bipolar individuals' age of onset. These findings suggest that the relationship of childhood stressors and bipolarity may be best explained by a harsh environment effect.

Potentially Stressful Life Events and Emotional Closeness Between Grandparents and Adult Grandchildren

The purpose of this study is to explore the variation in emotional closeness in the adult grandchild and grandparent relationship in relation to the occur-rence of potentially stressful life events in childhood. A sample of university students ( N = 119) completed a questionnaire measuring elements of inter-generational solidarity. Comparisons were made on emotional closeness between groups that had and had not experienced a life event, revealing it was the grandparent’s enactment of normative solidarity, as perceived by the adult grandchild, that produced greater emotional closeness. Complementing the findings of Bengston and Roberts, this research supports the theoretical view that high levels of normative solidarity lead to greater affectual solidarity, which in turn produces higher associational solidarity.

Life events in childhood, adolescence and adulthood and the relationship to panic disorder.

The aim of this study was to explore the association between stressful life events (SLE) and the development of panic disorder (PD) in an Israeli sample. A total of 44 PD patients and a matched control group were studied with regard to SLE over the life cycle (in childhood, adolescence, adulthood and the year preceding the outbreak of the disorder). The major findings were as follows. (i) With regard to the total number of life events experienced in childhood and adolescence, the PD group had experienced significantly more life events than the control group. (ii) No differences were detected in the total amount of SLE between the PD group and the control group with regard to adulthood and the year preceding the outbreak of the disorder, although the PD group had more life events relating to loss in adulthood, whereas in the year before the outbreak of PD life events relating to 'love and family', negative and loss events were more prevalent. These results expand previous findings by demonstrating that SLE in childhood and adolescence may contribute to the development of PD in adulthood.