A Caspi’s research while affiliated with University of Oslo and other places

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Publications (147)


Testing whether multi-level factors protect poly-victimised children against psychopathology in early adulthood: a longitudinal cohort study
  • Article
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November 2024

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23 Reads

Epidemiology and Psychiatric Sciences

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A Caspi

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Aims Exposure to multiple forms of victimisation in childhood (often referred to as poly-victimisation) has lifelong adverse effects, including an elevated risk of early-adulthood psychopathology. However, not all poly-victimised children develop mental health difficulties and identifying what protects them could inform preventive interventions. The present study investigated whether individual-, family- and/or community-level factors were associated with lower levels of general psychopathology at age 18, among children exposed to poly-victimisation. Additionally, it examined whether these factors were specific to poly-victimised children or also associated with fewer mental health difficulties in young adults regardless of whether they had been poly-victimised. Methods We used data from the Environmental Risk (E-Risk) Longitudinal Twin Study, a population-representative cohort of 2,232 children born in 1994–1995 across England and Wales and followed to 18 years of age (with 93% retention, n = 2,066). Poly-victimisation (i.e., exposure to two or more of physical abuse, sexual abuse, emotional abuse and neglect, physical neglect, bullying by peers, and domestic violence) and nine putative protective factors (intelligence quotient, executive functioning, temperament, maternal and sibling warmth, atmosphere at home, maternal monitoring, neighbourhood social cohesion, and presence of a supportive adult) were measured prospectively between ages 5 and 12 years from interviews with mothers and children, surveys of neighbours, child-protection referrals, and researchers’ observations. Early-adulthood psychopathology was assessed in interviews with each twin at age 18 and used to construct a latent factor of general psychopathology. Results Approximately a third (n = 720) of participants were prospectively defined as exposed to poly-victimisation (53% male). Poly-victimised children had greater levels of general psychopathology at age 18 than non-poly-victimised children (adjusted [adj.] β = 4.80; 95% confidence interval [95% CI] 3.13, 6.47). Presence of a supportive adult was the only factor robustly associated with lower levels of general psychopathology among poly-victimised children (adj.β = −0.61; 95% CI −0.99, −0.23). However, this association was also evident in the whole sample regardless of poly-victimisation exposure (adj.β = −0.52; 95% CI −0.81, −0.24) and no significant interaction was observed between the presence of a supportive adult and poly-victimisation in relation to age-18 general psychopathology. Conclusions Having at least one adult to turn to for support was found to be associated with less psychopathology in early adulthood among both poly-victimised and non-poly-victimised children. This suggests that strategies to promote better availability and utilisation of supportive adults should be implemented universally. However, it may be beneficial to target these interventions at poly-victimised children, given their higher burden of psychopathology in early adulthood.

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Fig. 2. Genetic risk Z-scores and 95% confidence intervals (indicated by doubleheaded lines) across (a) adolescent psychotic experiences scores, and (b) the cumulative environmental risk scale. Note: PRS, polygenic risk score.
Association between genetic and socioenvironmental risk for schizophrenia during upbringing in a UK longitudinal cohort

September 2020

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94 Reads

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30 Citations

Psychological Medicine

Background: Associations of socioenvironmental features like urbanicity and neighborhood deprivation with psychosis are well-established. An enduring question, however, is whether these associations are causal. Genetic confounding could occur due to downward mobility of individuals at high genetic risk for psychiatric problems into disadvantaged environments. Methods: We examined correlations of five indices of genetic risk [polygenic risk scores (PRS) for schizophrenia and depression, maternal psychotic symptoms, family psychiatric history, and zygosity-based latent genetic risk] with multiple area-, neighborhood-, and family-level risks during upbringing. Data were from the Environmental Risk (E-Risk) Longitudinal Twin Study, a nationally-representative cohort of 2232 British twins born in 1994-1995 and followed to age 18 (93% retention). Socioenvironmental risks included urbanicity, air pollution, neighborhood deprivation, neighborhood crime, neighborhood disorder, social cohesion, residential mobility, family poverty, and a cumulative environmental risk scale. At age 18, participants were privately interviewed about psychotic experiences. Results: Higher genetic risk on all indices was associated with riskier environments during upbringing. For example, participants with higher schizophrenia PRS (OR = 1.19, 95% CI = 1.06-1.33), depression PRS (OR = 1.20, 95% CI = 1.08-1.34), family history (OR = 1.25, 95% CI = 1.11-1.40), and latent genetic risk (OR = 1.21, 95% CI = 1.07-1.38) had accumulated more socioenvironmental risks for schizophrenia by age 18. However, associations between socioenvironmental risks and psychotic experiences mostly remained significant after covariate adjustment for genetic risk. Conclusion: Genetic risk is correlated with socioenvironmental risk for schizophrenia during upbringing, but the associations between socioenvironmental risk and adolescent psychotic experiences appear, at present, to exist above and beyond this gene-environment correlation.




Figure 2. E-Risk and Dunedin participants with a criminal record had lower polygenic scores for education than participants without a criminal record The figure shows mean education polygenic scores among participants with versus without a criminal record, through age 19 years in the E-Risk cohort and age 38 years in the Dunedin cohort. Error bars reflect standard errors, with robust standard errors in the E-Risk cohort. 
Figure 3. The majority of E-Risk participants with criminal records received their first caution or conviction before school-leaving age The figure shows the cumulative distribution of first appearance in police records of cautions and convictions, by age, in the n=196 participants with criminal records in the E-Risk cohort. In the UK, compulsory schooling ends at age 16 years. 
Figure 4. A polygenic score for education is associated with the timing and persistence of antisocial behavior across the life-course 
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Genetics and Crime: Integrating New Genomic Discoveries Into Psychological Research About Antisocial Behavior

March 2018

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1,720 Reads

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81 Citations

Psychological Science

Drawing on psychological and sociological theories of crime causation, we tested the hypothesis that genetic risk for low educational attainment (assessed via a genome-wide polygenic score) is associated with criminal offending. We further tested hypotheses of how polygenic risk relates to the development of antisocial behavior from childhood through adulthood. Across the Dunedin and Environmental Risk (E-Risk) birth cohorts of individuals growing up 20 years and 20,000 kilometers apart, education polygenic scores predicted risk of a criminal record with modest effects. Polygenic risk manifested during primary schooling in lower cognitive abilities, lower self-control, academic difficulties, and truancy, and it was associated with a life-course-persistent pattern of antisocial behavior that onsets in childhood and persists into adulthood. Crime is central in the nature-nurture debate, and findings reported here demonstrate how molecular-genetic discoveries can be incorporated into established theories of antisocial behavior. They also suggest that improving school experiences might prevent genetic influences on crime from unfolding.



Fig. 1. Mean (z-scored) sleep quality among 193 monozygotic twin pairs discordant for loneliness. Lonely and non-lonely groups were defined by taking a median split of the total loneliness score. For a colour figure, see the online version of the paper. 
Table 1 . Descriptive statistics of covariates
Fig. 2. Exacerbating effect of violence victimization in adolescence and maltreatment in childhood on the association between loneliness and sleep quality in young adulthood. Higher scores on the y-axis reflect poorer sleep quality. For a colour figure, see the online version of the paper. 
Table 3 . Associations between loneliness and components of sleep quality in young adulthood OR (95% CI)
Sleeping with one eye open: loneliness and sleep quality in young adults

May 2017

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272 Reads

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134 Citations

Psychological Medicine

Background: Feelings of loneliness are common among young adults, and are hypothesized to impair the quality of sleep. In the present study, we tested associations between loneliness and sleep quality in a nationally representative sample of young adults. Further, based on the hypothesis that sleep problems in lonely individuals are driven by increased vigilance for threat, we tested whether past exposure to violence exacerbated this association. Method: Data were drawn from the Environmental Risk (E-Risk) Longitudinal Twin Study, a birth cohort of 2232 twins born in England and Wales in 1994 and 1995. We measured loneliness using items from the UCLA Loneliness Scale, and sleep quality using the Pittsburgh Sleep Quality Index. We controlled for covariates including social isolation, psychopathology, employment status and being a parent of an infant. We examined twin differences to control for unmeasured genetic and family environment factors. Results: Feelings of loneliness were associated with worse overall sleep quality. Loneliness was associated specifically with subjective sleep quality and daytime dysfunction. These associations were robust to controls for covariates. Among monozygotic twins, within-twin pair differences in loneliness were significantly associated with within-pair differences in sleep quality, indicating an association independent of unmeasured familial influences. The association between loneliness and sleep quality was exacerbated among individuals exposed to violence victimization in adolescence or maltreatment in childhood. Conclusions: Loneliness is robustly associated with poorer sleep quality in young people, underscoring the importance of early interventions to mitigate the long-term outcomes of loneliness. Special care should be directed towards individuals who have experienced victimization.


Childhood body mass index and endothelial dysfunction evaluated by peripheral arterial tonometry in early midlife

May 2017

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25 Reads

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13 Citations

International Journal of Obesity

Background/objectives: Endothelial dysfunction predicts mortality but it is unknown whether childhood obesity predicts adult endothelial dysfunction. The aim of this study was to determine whether anthropometric indices of body fat in childhood, adolescence and early midlife are associated with endothelial dysfunction in early midlife. Subjects/methods: Participants belonged to a representative birth cohort of 1037 individuals born in Dunedin, New Zealand in 1972 and 1973 and followed to age 38 years, with 95% retention (the Dunedin Multidisciplinary Health and Development Study). We assessed anthropometric indices of obesity at ages 3, 5, 7, 9, 11, 13, 15, 18, 21, 26, 32 and 38 years. We tested associations between endothelial function assessed by peripheral arterial tonometry (PAT) at age 38 and; age 38 cardiovascular risk factors; age 3 body mass index (BMI); and four BMI trajectory groups from childhood to early midlife. Results: Early midlife endothelial dysfunction was associated with BMI, large waist circumference, low high-density lipoprotein cholesterol, low cardiorespiratory fitness and increased high-sensitivity C-reactive protein. After adjustment for sex and childhood socioeconomic status, 3-year-olds with BMI 1 s.d. above the mean had Framingham-reactive hyperemia index (F-RHI) ratios that were 0.10 below those with normal BMI (β=-0.10, 95% confidence interval (CI) -0.17 to -0.03, P=0.007) at age 38. Cohort members in the 'overweight', 'obese' and 'morbidly obese' trajectories had F-RHI ratios that were 0.08 (β=-0.08, 95% CI -0.14 to -0.03, P=0.003), 0.13 (β=-0.13, 95% CI -0.21 to -0.06, P<0.001) and 0.17 (β=-0.17, 95% CI -0.33 to -0.01, P=0.033), respectively, below age-peers in the 'normal' trajectory. Conclusions: Childhood BMI and the trajectories of BMI from childhood to early midlife predict endothelial dysfunction evaluated by PAT in early midlife.


Long-Term Effect of Endothelin Receptor Antagonism With Bosentan on the Morbidity and Mortality of Patients With Severe Chronic Heart Failure

May 2017

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239 Reads

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121 Citations

JACC Heart Failure

Objectives The objective of this clinical trial was to evaluate the long-term effect of endothelin receptor antagonism with bosentan on the morbidity and mortality of patients with severe chronic heart failure. Background Endothelin may play a role in heart failure, but short-term clinical trials with endothelin receptor antagonists have reported disappointing results. Long-term trials are lacking. Methods In 2 identical double-blind trials, we randomly assigned 1,613 patients with New York Heart Association functional class IIIb to IV heart failure and an ejection fraction <35% to receive placebo or bosentan (target dose 125 mg twice daily) for a median of 1.5 years. The primary outcome for each trial was clinical status at 9 months (assessed by the hierarchical clinical composite); the primary outcome across the 2 trials was death from any cause or hospitalization for heart failure. Results Bosentan did not influence clinical status at 9 months in either trial (p = 0.928 and p = 0.263). In addition, 321 patients in the placebo group and 312 patients in the bosentan group died or were hospitalized for heart failure (hazard ratio [HR]: 1.01; 95% confidence interval [CI]: 0.86 to 1.18; p = 0.90). The bosentan group experienced fluid retention within the first 2 to 4 weeks, as evidenced by increased peripheral edema, weight gain, decreases in hemoglobin, and an increased risk of hospitalization for heart failure, despite intensification of background diuretics. During follow-up, 173 patients died in the placebo group and 160 patients died in the bosentan group (HR: 0.94; 95% CI: 0.75 to 1.16). About 10% of the bosentan group showed meaningful increases in hepatic transaminases, but none had acute or chronic liver failure. Conclusions Bosentan did not improve the clinical course or natural history of patients with severe chronic heart failure and but caused early and important fluid retention.


Citations (63)


... According to the results of a new review, the beneficial effects of exercise can be related to its modulating effects on the serotonergic system. It has been found that physical activity can change the metabolism of serotonin, change the expression of serotonin receptors, and produce anti-anxiety and anti-depressant effects (55)(56)(57)(58). The positive effects of exercise on the hippocampus, like neurogenesis, depend on serotonin's function (59). ...

Reference:

Analysis of the effect of childhood stress on the expression of serotonin system genes in the hippocampus and cortex in adult mail rats
Influence of life stress on depression: moderation by a polymorphism in the 5-HTT gene (Science. — 2003 Jul — 18. — 301(5631). — P. 386—389: англ.)

Neurology Bulletin

... Multivariate measures of physiological ageing present a more holistic snapshot of physiological state than any single biomarker [28], and have been used to capture theoretical concepts, such as 'allostatic load', where chronic stressors induce cumulative biological burdens that disrupt homeostatic processes [29,30]. Since individual biomarkers are embedded in complex regulatory networks, a growing consensus suggests that increasing and irreversible dysregulation may be a fundamental feature of physiological ageing [28,31,32]. ...

Telomere, epigenetic clock, and biomarker-composite quantifications of biological aging: Do they measure the same thing?

... In this review, we analyzed a variety of reports, with the majority being extensive studies conducted in the Global North (which refers mostly to Australia, North America, and Western Europe), [41][42][43][44][45][46][47][48][49][50][51] including the United Kingdom (n = 11), 41-51 Denmark (n = 11), 52-62 Germany (n = 5), [63][64][65][66][67] Sweden (n = 4), [68][69][70][71] the Netherlands (n = 4), [72][73][74][75] Australia (n = 3), [76][77][78] Greece (n = 2), 79,80 the United States (n = 2), 81,82 and France (n = 1). 83 More recent studies have reported data from regions in the Global South, such as China (n = 3), [84][85][86] Brazil (n = 1), 15 Chile (n = 1), 17 India (n = 1), 87 Indonesia (n = 1), 88 Romania (n = 1), 89 Taiwan (n = 1), 90 Turkey (n = 2), 91,92 and Uganda (n = 1). ...

Association between genetic and socioenvironmental risk for schizophrenia during upbringing in a UK longitudinal cohort

Psychological Medicine

... For instance, one study has estimated genetic correlations between youth ASB and 46 psychiatric and behavioral phenotypes, revealing the strongest genetic correlations with ADHD, autism spectrum disorder, and depression (Ip et al. 2021). It has also been shown that individuals in the life-course-persistent versus adolescencelimited ASB trajectory exhibit a significantly lower polygenic score for educational attainment, suggesting that genetic factors linked with poorer educational outcomes may be associated with increased risk of life-course-persistent ASB (Wertz et al. 2018). The association between a low polygenic score for educational attainment and ASB has been found to persist after adjusting for familial risk factors, including parental ASB and socioeconomic disadvantage (Wertz et al. 2018). ...

Genetics and Crime: Integrating New Genomic Discoveries Into Psychological Research About Antisocial Behavior

Psychological Science

... Treatment with vitamin D supplements was not effective in reversing cognitive impairment (Lerner, Sharony, & Miodownik, 2018). Patients with MDD show poor cognitive performance that could not be clearly attributed to specific depressive symptoms (Crowe & Lowe, 2016;Schaefer, Caspi, Cook, & Moffitt, 2017). ...

A-81Are Cognitive Inefficiencies a Predictor or Consequence of Major Depressive Disorder?
  • Citing Article
  • September 2017

Archives of Clinical Neuropsychology

... These sociodemographic and contextual conditions create a complicated web of social determinants of health 13 . However, To add to this complexity, social isolation and loneliness are also significantly associated with health risk behaviors, sleep hygiene, blood pressure, inflammatory processes, and metabolic dysregulation, among others 1, [14][15][16] . As loneliness is important to cancer-related outcomes, such as incidence and mortality, it is essential to understand the prevalence of and risk factors for loneliness in people with cancer. ...

Sleeping with one eye open: loneliness and sleep quality in young adults

Psychological Medicine

... The prevalence of obesity among Paci c (29%) and Māori (13%) children is disproportionately higher than for European/Other (7%) and Asian (3%) children [8]. It has been well established that childhood obesity is a life-course predictor of being overweight in young adulthood [9], and it is associated with obesity related co-morbidities (e.g., T2DM and cardiovascular disease) in adulthood [10]. Further, it has been reported that persistent obesity is established in early childhood, before 11-years-old [11]. ...

Childhood body mass index and endothelial dysfunction evaluated by peripheral arterial tonometry in early midlife
  • Citing Article
  • May 2017

International Journal of Obesity

... ET-1 antagonists have proven beneficial in treating pulmonary arterial hypertension (PAH) (Correale et al., 2018), and been shown to reduce proteinuria and potentially improve outcomes in patients with diabetic kidney disease (DKD) (de Zeeuw et al., 2014;Heerspink et al., 2019). However, their utility in treating cardiovascular diseases has been limited by adverse events related to fluid retention (Packer et al., 2017;Waijer et al., 2021).The mechanisms underlying this effect have proven difficult to fully understand, in part because of the complex physiology of the endothelin system. ...

Long-Term Effect of Endothelin Receptor Antagonism With Bosentan on the Morbidity and Mortality of Patients With Severe Chronic Heart Failure
  • Citing Article
  • May 2017

JACC Heart Failure

... The predictive power of family history of psychosis was not found in this study. One possible explanation for this is that information about psychosis family history may be easily overlooked or hidden ( Roy et al. 1996;Milne et al. 2009) in our study participants due to the lack of mental health resources available to the older generation and the stigmatised diagnostic labels. Moreover, family history of psychosis may not predict psychosis within the time period studied. ...

The validity of the family history screen for assessing family history of mental disorders
  • Citing Article
  • January 2008

American Journal of Medical Genetics Part B Neuropsychiatric Genetics

... Self-reported violent behaviour: modified from the Pittsburg Youth Study's measure of serious violence [172]. Violent offences: self-reported via a modified version of the Overt Victimization subscale of the Low No significant differences in self-reported violent behaviour between rural and urban participants was reported. ...

The development of male offending: Key findings from fourteen years of the Pittsburgh Youth Study
  • Citing Article
  • January 2003