About

Avshalom Caspi is a professor affiliated with the Psychology & Neuroscience department at Duke University. His research involves investigating biomarkers related to Alzheimer's disease (AD), particularly focusing on plasma pTau181 as a potential preclinical biomarker in middle-aged community-based cohorts. Caspi's work includes longitudinal studies, such as the Dunedin Multidisciplinary Health and Development Study, which tracks a cohort born in New Zealand in 1972-1973. This study assesses various health and cognitive measures at multiple ages, including age 45, to understand the early indicators of AD risk. Caspi's research has demonstrated a wide range of plasma pTau181 levels in middle-aged individuals, with findings suggesting that blood biomarkers of AD may increase early in middle age, decades before any potential disease onset or measurable cognitive decline. His work contributes to the understanding of how early biomarkers can predict Alzheimer's disease onset later in life, providing valuable insights into the preclinical stages of neurodegenerative disorders.

Research topics

• Psychology
• Medicine
• Internal medicine
• Political Science
• Information Retrieval
• Computer Science
• Clinical psychology
• Neuroscience
• Psychiatry
• Demography
• Pathology
• Pediatrics
• Ophthalmology
• Social psychology
• World Wide Web
• Genetics
• Biology
• Law
• Biomedical engineering
• Data science
• Environmental health
• Cardiology
• Gerontology
• Cognitive psychology

Selected publications

• A methylome-wide association study of major depression with out-of-sample case–control classification and trans-ancestry comparison

  Nature Mental Health · 2025-09-16 · 6 citations

  articleOpen access

  Major depression (MD) is a leading cause of global disease burden, and both experimental and population-based studies suggest that differences in DNA methylation may be associated with the condition. However, previous DNA methylation studies have, so far, not been widely replicated, suggesting a need for larger meta-analysis studies. Here we conducted a meta-analysis of methylome-wide association analysis for lifetime MD across 18 studies of 24,754 European-ancestry participants (5,443 MD cases) and an East Asian sample (243 cases, 1,846 controls). We identified 15 CpG sites associated with lifetime MD with methylome-wide significance. The methylation score created using the methylome-wide association analysis summary statistics was significantly associated with MD status in an out-of-sample classification analysis (area under the curve 0.53). Methylation score was also associated with five inflammatory markers, with the strongest association found with tumor necrosis factor beta. Mendelian randomization analysis revealed 23 CpG sites potentially causally linked to MD, with 7 replicated in an independent dataset. Our study provides evidence that variations in DNA methylation are associated with MD, and further evidence supporting involvement of the immune system.

  PublisherOA PDFDOI

• Examining the relationship between plasma pTau181 and cognitive decline, structural brain integrity, and biological ageing in midlife

  medRxiv · 2025-04-10

  preprintOpen access

  Abstract INTRODUCTION Although plasma pTau181 has been shown to accurately discriminate patients with Alzheimer’s disease from healthy older adults, its utility as a preclinical biomarker in middle-aged community-based cohorts is unclear. METHODS Participants were members of the Dunedin Multidisciplinary Health and Development Study, a longitudinal study of 1037 people born in New Zealand in 1972-1973. Plasma pTau181, MRI-based brain structure, and DunedinPACE (an epigenetic biomarker of biological ageing) were measured at age 45; cognition was measured in childhood and age 45. RESULTS We observed a wide range of pTau181 concentrations in our same-aged sample (n=856; M=13.6pg/mL, SD=9.1pg/mL). Males had significantly higher pTau181 concentrations than females. No statistically significant associations were observed with cognitive decline, lower structural brain integrity, or accelerated biological ageing. DISCUSSION In this midlife cohort, wide variation in pTau181 concentrations was present by age 45, but was not associated with patterns of AD-risk in cognition, brain structure, or biological ageing. Research in context Systematic review Authors reviewed the literature using PubMed and Web of Science databases. While research on plasma biomarkers of AD has largely focused on older people with mild cognitive impairment or AD, there are few studies of plasma biomarkers among general middle-aged populations. Given the potential utility of plasma biomarkers of AD such as pTau181 in early screening for disease risk, examining the concentrations of pTau181 among a younger cohort free of dementia is important for possible future clinical implementation. Interpretation Plasma pTau181 concentrations varied widely among our same-aged sample, yet higher pTau181 was not associated with cognitive decline, lower MRI-estimated structural brain integrity, or accelerated biological ageing. These findings indicate that variability in pTau181 exists in middle-age, but independently of other AD risk factors. Future directions Understanding how variability in pTau181 concentrations in midlife may predict later AD and to what extent this is distinct from other risk factors is important for shaping the translational pathway from lab to clinic.

  PublisherOA PDFDOI

• Parental income and psychiatric disorders from age 10 to 40: a genetically informative population study

  Journal of Child Psychology and Psychiatry · 2025-08-04 · 3 citations

  articleOpen access

  BACKGROUND: Lower parental income is associated with more psychiatric disorders among offspring, but it is unclear if this association reflects effects of parental income (social causation) or shared risk factors (social selection). Prior research finds contradictory results, which may be due to age differences between the studied offspring. METHODS: Here, we studied psychiatric disorders in the entire Norwegian population aged 10 to 40 years between 2006 and 2018 (N = 2,468,503). By linking tax registries to administrative health registries, we described prevalence rates by age, sex, and parental income rank. Next, we grouped observations into age groups (adolescence, ages 10-20 years; early adulthood, 21-30 years; adulthood, 30-40 years) and applied kinship-based models with extended families of twins and siblings to decompose the parent-offspring correlation into phenotypic transmission, passive genetic transmission, and passive environmental transmission. RESULTS: We found that lower parental income rank was associated with higher prevalence of nearly all psychiatric disorders, except for eating disorders, for both men and women at all ages from 10 to 40 years. Comparing the top with the bottom paternal income quartile, the prevalence ratio of any psychiatric disorder was 0.47 among 10-year-olds and decreased to 0.72 among 40-year-olds. The parent-offspring correlation was -.15 in adolescence, -.10 in early adulthood, and -.06 in adulthood. The kinship-based models indicated that phenotypic transmission could account for 39% of the parent-offspring correlation among adolescents (p < .001), but with no significant contribution in early adulthood (p = .181) or adulthood (p = .737). Passive genetic and environmental transmission contributed to the parent-offspring correlation in all age groups (all p's < .001). CONCLUSIONS: Our findings are consistent with a significant role of social causation during adolescence, while social selection could fully explain the parent-offspring correlation in adulthood.

  PublisherOA PDFDOI

• DunedinPACNI estimates the longitudinal Pace of Aging from a single brain image to track health and disease

  Nature Aging · 2025-07-01 · 20 citations

  articleOpen access

  To understand how aging affects functional decline and increases disease risk, it is necessary to develop measures of how fast a person is aging. Using data from the Dunedin Study, we introduce an accurate and reliable measure for the rate of longitudinal aging derived from cross-sectional brain magnetic resonance imaging, that is, the Dunedin Pace of Aging Calculated from NeuroImaging (DunedinPACNI). Exporting this measure to the Alzheimer's Disease Neuroimaging Initiative, UK Biobank and BrainLat datasets revealed that faster DunedinPACNI predicted cognitive impairment, accelerated brain atrophy and conversion to diagnosed dementia. Faster DunedinPACNI also predicted physical frailty, poor health, future chronic diseases and mortality in older adults. When compared to brain age gap, DunedinPACNI was similarly or more strongly related to clinical outcomes. DunedinPACNI is a next-generation brain magnetic resonance imaging biomarker that can help researchers explore aging effects on health outcomes and evaluate the effectiveness of antiaging strategies.

  PublisherOA PDFDOI

• The nature of the relation between mental well-being and ill-being

  Nature Human Behaviour · 2025-10-16 · 6 citations

  articleOpen access
  PublisherOA PDFDOI

• Author response for "Cognitive Abilities and Educational Attainment as Antecedents of Mental Disorders: A Total Population Study of Males"

  2025-05-12

  peer-review
  PublisherDOI

• Author Correction: Prediction of mental health risk in adolescents

  Nature Medicine · 2025-05-19 · 3 citations

  erratumOpen access
  PublisherOA PDFDOI

• Examining the timing of trauma, PTSD onset, and DNA methylation: A multicohort investigation of candidate CpG sites

  Journal of Psychiatric Research · 2025-07-31

  articleOpen access
  PublisherOA PDFDOI

• PTSD and suPAR: A multicohort investigation of chronic inflammation

  Brain Behavior and Immunity · 2025-10-28 · 2 citations

  articleOpen access
  PublisherOA PDFDOI

• Cognitive Abilities and Educational Attainment as Antecedents of Mental Disorders: A Total Population Study of Males

  2025-03-25

  preprintOpen access

  The positive relation between mental health and educational attainment is well-established, yet the extent to which cognitive abilities influence this gradient or independently predict mental health outcomes remains unclear. In this study, we investigated the association between adolescent cognitive abilities, educational attainment, and adult mental health. Cognitive ability was ascertained in Norwegian military conscript test data (N = 272,351; mean age 17.8 years; males only), whereas mental disorders were ascertained using the Norwegian register of primary care diagnoses received between the age of 36–40. Higher cognitive abilities were associated with a monotonically decreasing risk of developing all the studied mental disorders except bipolar disorder. The association held even when comparing the cognitive abilities of brothers raised in the same family, attesting that cognitive ability and mental disorders are not associated because both arise from the same family background circumstances. Similarly, individuals with higher educational attainment had fewer mental health disorders. The association between low cognitive abilities and the risk of mental disorders was notably stronger in males with low educational attainment, compared to those with high educational attainment. These individuals may be an underutilized target group for mental-disorder prevention.

  PublisherOA PDFDOI

Recent grants

• Core B: Program Development

  NIH · $7.9M · 2009–2027

• NIH Grant R01MH077874

  NIH · $1.6M · 2012

• Neuropsychological and genomic signatures of violence exposure in childhood

  NIH · $2.8M · 2013–2019

• Aging in 1000 healthy midlife adults: Phase 52 of the Dunedin Study

  NIH · $9.5M · 2009–2027

• Validating a 3rd-generation methylation measure of accelerated aging: DunedinPoAm4x

  NIH · $2.9M · 2022–2027

Frequent coauthors

• Terrie E. Moffitt

  Center for Genomic Science

  2234 shared

• Richie Poulton

  University of Otago

  657 shared

• Renate Houts

  Duke University

  361 shared

• Sandhya Ramrakha

  University of Otago

  344 shared

• Daniel W. Belsky

  Canadian Institute for Advanced Research

  338 shared

• Karen Sugden

  Duke University

  286 shared

• HonaLee Harrington

  Duke University

  273 shared

• Louise Arseneault

  University of the West of England

  257 shared

Education

• Ph.D., Psychology

  University of Cambridge

  1987

• M.A., Psychology

  University of Cambridge

  1984

• B.A., Psychology

  University of California, Los Angeles

  1981