To save content items to your account,
please confirm that you agree to abide by our usage policies.
If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account.
Find out more about saving content to .
To save content items to your Kindle, first ensure email@example.com
is added to your Approved Personal Document E-mail List under your Personal Document Settings
on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part
of your Kindle email address below.
Find out more about saving to your Kindle.
Note you can select to save to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi.
‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.
Subthreshold/attenuated syndromes are established precursors of full-threshold mood and psychotic disorders. Less is known about the individual symptoms that may precede the development of subthreshold syndromes and associated social/functional outcomes among emerging adults.
We modeled two dynamic Bayesian networks (DBN) to investigate associations among self-rated phenomenology and personal/lifestyle factors (role impairment, low social support, and alcohol and substance use) across the 19Up and 25Up waves of the Brisbane Longitudinal Twin Study. We examined whether symptoms and personal/lifestyle factors at 19Up were associated with (a) themselves or different items at 25Up, and (b) onset of a depression-like, hypo-manic-like, or psychotic-like subthreshold syndrome (STS) at 25Up.
The first DBN identified 11 items that when endorsed at 19Up were more likely to be reendorsed at 25Up (e.g., hypersomnia, impaired concentration, impaired sleep quality) and seven items that when endorsed at 19Up were associated with different items being endorsed at 25Up (e.g., earlier fatigue and later role impairment; earlier anergia and later somatic pain). In the second DBN, no arcs met our a priori threshold for inclusion. In an exploratory model with no threshold, >20 items at 19Up were associated with progression to an STS at 25Up (with lower statistical confidence); the top five arcs were: feeling threatened by others and a later psychotic-like STS; increased activity and a later hypo-manic-like STS; and anergia, impaired sleep quality, and/or hypersomnia and a later depression-like STS.
These probabilistic models identify symptoms and personal/lifestyle factors that might prove useful targets for indicated preventative strategies.
To determine associations of alcohol use with cognitive aging among middle-aged men.
1,608 male twins (mean 57 years at baseline) participated in up to three visits over 12 years, from 2003–2007 to 2016–2019. Participants were classified into six groups based on current and past self-reported alcohol use: lifetime abstainers, former drinkers, very light (1–4 drinks in past 14 days), light (5–14 drinks), moderate (15–28 drinks), and at-risk drinkers (>28 drinks in past 14 days). Linear mixed-effects regressions modeled cognitive trajectories by alcohol group, with time-based models evaluating rate of decline as a function of baseline alcohol use, and age-based models evaluating age-related differences in performance by current alcohol use. Analyses used standardized cognitive domain factor scores and adjusted for sociodemographic and health-related factors.
Performance decreased over time in all domains. Relative to very light drinkers, former drinkers showed worse verbal fluency performance, by –0.21 SD (95% CI –0.35, –0.07), and at-risk drinkers showed faster working memory decline, by 0.14 SD (95% CI 0.02, –0.20) per decade. There was no evidence of protective associations of light/moderate drinking on rate of decline. In age-based models, light drinkers displayed better memory performance at advanced ages than very light drinkers (+0.14 SD; 95% CI 0.02, 0.20 per 10-years older age); likely attributable to residual confounding or reverse association.
Alcohol consumption showed minimal associations with cognitive aging among middle-aged men. Stronger associations of alcohol with cognitive aging may become apparent at older ages, when cognitive abilities decline more rapidly.
Previous research has shown that self-reports of the amount of social support are heritable. Using the Kessler perceived social support (KPSS) measure, we explored sex differences in the genetic and environmental contributions to individual differences. We did this separately for subscales that captured the perceived support from different members of the network (spouse, twin, children, parents, relatives, friends and confidant). Our sample comprised 7059 male, female and opposite-sex twin pairs aged 18−95 years from the Australian Twin Registry. We found tentative support for different genetic mechanisms in males and females for support from friends and the average KPSS score of all subscales, but otherwise, there are no sex differences. For each subscale alone, the additive genetic (A) and unique environment (E) effects were significant. By contrast, the covariation among the subscales was explained — in roughly equal parts — by A, E and the common environment, with effects of different support constellations plausibly accounting for the latter. A single genetic and common environment factor accounted for between half and three-quarters of the variance across the subscales in both males and females, suggesting little heterogeneity in the genetic and environmental etiology of the different support sources.
The ‘16Up’ study conducted at the QIMR Berghofer Medical Research Institute from January 2014 to December 2018 aimed to examine the physical and mental health of young Australian twins aged 16−18 years (N = 876; 371 twin pairs and 18 triplet sets). Measurements included online questionnaires covering physical and mental health as well as information and communication technology (ICT) use, actigraphy, sleep diaries and hair samples to determine cortisol concentrations. Study participants generally rated themselves as being in good physical (79%) and mental (73%) health and reported lower rates of psychological distress and exposure to alcohol, tobacco products or other substances than previously reported for this age group in the Australian population. Daily or near-daily online activity was almost universal among study participants, with no differences noted between males and females in terms of frequency or duration of internet access. Patterns of ICT use in this sample indicated that the respondents were more likely to use online information sources for researching physical health issues than for mental health or substance use issues, and that they generally reported partial levels of satisfaction with the mental health information they found online. This suggests that internet-based mental health resources can be readily accessed by adolescent Australians, and their computer literacy augurs well for future access to online health resources. In combination with other data collected as part of the ongoing Brisbane Longitudinal Twin Study, the 16Up project provides a valuable resource for the longitudinal investigation of genetic and environmental contributions to phenotypic variation in a variety of human traits.
Clarifying the relationship between depression symptoms and cardiometabolic and related health could clarify risk factors and treatment targets. The objective of this study was to assess whether depression symptoms in midlife are associated with the subsequent onset of cardiometabolic health problems.
The study sample comprised 787 male twin veterans with polygenic risk score data who participated in the Harvard Twin Study of Substance Abuse (‘baseline’) and the longitudinal Vietnam Era Twin Study of Aging (‘follow-up’). Depression symptoms were assessed at baseline [mean age 41.42 years (s.d. = 2.34)] using the Diagnostic Interview Schedule, Version III, Revised. The onset of eight cardiometabolic conditions (atrial fibrillation, diabetes, erectile dysfunction, hypercholesterolemia, hypertension, myocardial infarction, sleep apnea, and stroke) was assessed via self-reported doctor diagnosis at follow-up [mean age 67.59 years (s.d. = 2.41)].
Total depression symptoms were longitudinally associated with incident diabetes (OR 1.29, 95% CI 1.07–1.57), erectile dysfunction (OR 1.32, 95% CI 1.10–1.59), hypercholesterolemia (OR 1.26, 95% CI 1.04–1.53), and sleep apnea (OR 1.40, 95% CI 1.13–1.74) over 27 years after controlling for age, alcohol consumption, smoking, body mass index, C-reactive protein, and polygenic risk for specific health conditions. In sensitivity analyses that excluded somatic depression symptoms, only the association with sleep apnea remained significant (OR 1.32, 95% CI 1.09–1.60).
A history of depression symptoms by early midlife is associated with an elevated risk for subsequent development of several self-reported health conditions. When isolated, non-somatic depression symptoms are associated with incident self-reported sleep apnea. Depression symptom history may be a predictor or marker of cardiometabolic risk over decades.
This article describes Dr Nathan Gillespie’s PhD training and supervision under Professor Nick Martin and their ongoing collaborations. Drs Gillespie and Martin have collaborated on numerous biometrical genetic analyses applied to cross-sectional and longitudinal twin data, combined molecular and phenotypic modeling, as well as genomewide meta-analyses of psychoactive substance use and misuse. Dr Gillespie remains an active collaborator with Professor Martin, including ongoing data collection, analysis and publications related to the Brisbane Longitudinal Twin Study.
The International Cannabis Consortium (ICC) was founded in 2013 by Jacqueline Vink, Nathan Gillespie, Karin Verweij and Eske Derks. The largest contribution to the first meta-analysis was made by Prof. Nick Martin. The ICC has published two primary publications, in Translational Psychiatry and Nature Neuroscience, and many secondary publications. The study’s principal investigators will always be grateful for Nick’s contribution to science as they would not have been able to do any of this work without the contributions of Nick and others who collected samples. Nick has made unique contributions to the careers of many junior researchers by supporting their development and growth into senior positions.
The aim of the 25 and Up (25Up) study was to assess a wide range of psychological and behavioral risk factors behind mental illness in a large cohort of Australian twins and their non-twin siblings. Participants had already been studied longitudinally from the age of 12 and most recently in the 19Up study (mean age = 26.1 years, SD = 4.1, range = 20–39). This subsequent wave follows up these twins several years later in life (mean age = 29.7 years, SD = 2.2, range = 22–44). The resulting data set enables additional detailed investigations of genetic pathways underlying psychiatric illnesses in the Brisbane Longitudinal Twin Study (BLTS). Data were collected between 2016 and 2018 from 2540 twins and their non-twin siblings (59% female, including 341 monozygotic complete twin-pairs, 415 dizygotic complete pairs and 1028 non-twin siblings and singletons). Participants were from South-East Queensland, Australia, and the sample was of predominantly European ancestry. The 25Up study collected information on 20 different mental disorders, including depression, anxiety, substance use, psychosis, bipolar and attention-deficit hyper-activity disorder, as well as general demographic information such as occupation, education level, number of children, self-perceived IQ and household environment. In this article, we describe the prevalence, comorbidities and age of onset for all 20 examined disorders. The 25Up study also assessed general and physical health, including physical activity, sleep patterns, eating behaviors, baldness, acne, migraines and allergies, as well as psychosocial items such as suicidality, perceived stress, loneliness, aggression, sleep–wake cycle, sexual identity and preferences, technology and internet use, traumatic life events, gambling and cyberbullying. In addition, 25Up assessed female health traits such as morning sickness, breastfeeding and endometriosis. Furthermore, given that the 25Up study is an extension of previous BLTS studies, 86% of participants have already been genotyped. This rich resource will enable the assessment of epidemiological risk factors, as well as the heritability and genetic correlations of mental conditions.
While snus has been the focus of increasing public health interest, twin studies have examined neither sources of individual variation for its use nor the sources of resemblance between snus and cigarette use. Twins from the Norwegian Institute of Public Health Panel were assessed by self-report questionnaire for the initiation of regular use and maximal quantity used for snus and cigarettes. Twin modeling was performed using OpenMx on data from 2767 twins including 856 complete pairs. Fitting univariate twin models produced similar results for cigarette initiation and quantity with estimates of additive genetic, shared environmental and unique environmental effects of approximately 77%, 0% and 23%, respectively. Estimates of snus initiation and quantity were, respectively, approximately 53%, 26% and 21%. Joint analyses suggested that the genetic, shared environmental and unique environmental correlations between cigarette and snus initiation and quantity were +.82, 0 and +.42, respectively. However, these results could not be statistically distinguished from a model which postulated that resemblance between cigarette initiation and quantity resulted from genetic and unique environmental correlations of +.47 and +.43. Compared with cigarette initiation and quantity of use in Norwegian twins, the role of genes was less prominent and shared environment more prominent for initiation and quantity of use of snus. Joint analyses of both tobacco phenotypes suggested, but did not confirm definitively, that genetic risk factors for cigarette and snus use were similar but not identical, while shared environmental factors existed that were specific to snus use.
Despite established clinical associations among major depression (MD), alcohol dependence (AD), and alcohol consumption (AC), the nature of the causal relationship between them is not completely understood. We leveraged genome-wide data from the Psychiatric Genomics Consortium (PGC) and UK Biobank to test for the presence of shared genetic mechanisms and causal relationships among MD, AD, and AC.
Linkage disequilibrium score regression and Mendelian randomization (MR) were performed using genome-wide data from the PGC (MD: 135 458 cases and 344 901 controls; AD: 10 206 cases and 28 480 controls) and UK Biobank (AC-frequency: 438 308 individuals; AC-quantity: 307 098 individuals).
Positive genetic correlation was observed between MD and AD (rgMD−AD = + 0.47, P = 6.6 × 10−10). AC-quantity showed positive genetic correlation with both AD (rgAD−AC quantity = + 0.75, P = 1.8 × 10−14) and MD (rgMD−AC quantity = + 0.14, P = 2.9 × 10−7), while there was negative correlation of AC-frequency with MD (rgMD−AC frequency = −0.17, P = 1.5 × 10−10) and a non-significant result with AD. MR analyses confirmed the presence of pleiotropy among these four traits. However, the MD-AD results reflect a mediated-pleiotropy mechanism (i.e. causal relationship) with an effect of MD on AD (beta = 0.28, P = 1.29 × 10−6). There was no evidence for reverse causation.
This study supports a causal role for genetic liability of MD on AD based on genetic datasets including thousands of individuals. Understanding mechanisms underlying MD-AD comorbidity addresses important public health concerns and has the potential to facilitate prevention and intervention efforts.
Can the structure of genetic and environmental influences on normative personality traits (NPTs), abnormal personality traits (APTs), and DSM-IV criteria for personality disorders (PD) fit a high or low congruence model positing, respectively, close or more limited etiologic continuity?
Exploratory factor analysis was applied to transformed correlation matrices from Cholesky twin decompositions obtained in OpenMx. In 2801 adult twins from the Norwegian Institute of Public Health Twin Panel, NPTs and APTs were assessed by self-report using the Big Five Inventory (BFI) and PID-5-Norwegian Brief Form (PID-5-NBF), respectively. PDs were assessed at interview using the Structured Interview for DSM-IV Personality (SIDP-IV).
The best model yielded three genetic and three unique environmental factors. Genetic factors were dominated, respectively, by (i) high loadings on nearly all PDs and NPT/APT neuroticism and compulsivity, (ii) negative loadings on NPT agreeableness/conscientiousness and positive loadings on APT/PD measures of antisocial traits, and (iii) negative loadings on NPT extraversion and histrionic PD, and positive loadings on APT detachment and schizoid/avoidant PD. Unique environmental factors were dominated, by (i) high loadings on all PDs, (ii) high loadings on all APT dimensions and NPT neuroticism, and (iii) negative loadings on NPT extraversion and positive loadings on NPT detachment/avoidant PD.
Two genetic and one environmental common factor were consistent with a high congruence model while one genetic and two environmental factors were more supportive of a low congruence model. The relationship between genetic and environmental influences on personality assessed by NPTs, APTs, and PDs is complex and does not fit easily into a low or high congruence model.
We recently reported an association of offspring educational attainment with polygenic risk scores (PRS) computed on parent’s non-transmitted alleles for educational attainment using the second GWAS meta-analysis article on educational attainment published by the Social Science Genetic Association Consortium. Here we test the replication of these findings using a more powerful PRS from the third GWAS meta-analysis article by the Consortium. Each of the key findings of our previous paper is replicated using this improved PRS (N = 2335 adolescent twins and their genotyped parents). The association of children’s attainment with their own PRS increased substantially with the standardized effect size, moving from β = 0.134, 95% CI = 0.079, 0.188 for EA2, to β = 0.223, 95% CI = 0.169, 0.278, p < .001, for EA3. Parent’s PRS again predicted the socioeconomic status (SES) they provided to their offspring and increased from β = 0.201, 95% CI = 0.147, 0.256 to β = 0.286, 95% CI = 0.239, 0.333. Importantly, the PRS for alleles not transmitted to their offspring — therefore acting via the parenting environment — was increased in effect size from β = 0.058, 95% CI = 0.003, 0.114 to β = 0.067, 95% CI = 0.012, 0.122, p = .016. As previously found, this non-transmitted genetic effect was fully accounted for by parental SES. The findings reinforce the conclusion that genetic effects of parenting are substantial, explain approximately one-third the magnitude of an individual’s own genetic inheritance and are mediated by parental socioeconomic competence.
Vulnerability to depression can be measured in different ways. We here examine how genetic risk factors are inter-related for lifetime major depression (MD), self-report current depressive symptoms and the personality trait Neuroticism.
We obtained data from three population-based adult twin samples (Virginia n = 4672, Australia #1 n = 3598 and Australia #2 n = 1878) to which we fitted a common factor model where risk for ‘broadly defined depression’ was indexed by (i) lifetime MD assessed at personal interview, (ii) depressive symptoms, and (iii) neuroticism. We examined the proportion of genetic risk for MD deriving from the common factor v. specific to MD in each sample and then analyzed them jointly. Structural equation modeling was conducted in Mx.
The best fit models in all samples included additive genetic and unique environmental effects. The proportion of genetic effects unique to lifetime MD and not shared with the broad depression common factor in the three samples were estimated as 77, 61, and 65%, respectively. A cross-sample mega-analysis model fit well and estimated that 65% of the genetic risk for MD was unique.
A large proportion of genetic risk factors for lifetime MD was not, in the samples studied, captured by a common factor for broadly defined depression utilizing MD and self-report measures of current depressive symptoms and Neuroticism. The genetic substrate for MD may reflect neurobiological processes underlying the episodic nature of its cognitive, motor and neurovegetative manifestations, which are not well indexed by current depressive symptom and neuroticism.
Studies on the stability of genetic risk for depression have relied on self-reported symptoms rather than diagnoses and/or short follow-up time. Our aim is to determine to what degree genetic and environmental influences on clinically assessed major depressive disorder (MDD) are stable between age 18 and 45.
A population-based sample of 11 727 twins (6875 women) born between 1967 and 1991 was followed from 2006 to 2015 in health registry data from primary care that included diagnoses provided by treating physicians. Individuals with schizophrenia or bipolar disorder (n = 163) were excluded. We modelled genetic and environmental risk factors for MDD in an accelerated longitudinal design.
The best-fitting model indicated that genetic influences on MDD were completely stable from ages 18 to 45 and explained 38% of the variance. At each age, the environmental risk of MDD was determined by the risk at the preceding observation, plus new environmental risk, with an environmental correlation of +0.60 over 2 years. The model indicated no effects of shared environment and no environmental effects stable throughout the observational period. All long-term stability was therefore explained by genetic factors.
Different processes unfolded in the genetic and environmental risk for MDD. The genetic component is stable from later adolescence to middle adulthood and accounted for nearly all long-term stability. Therefore, molecular genetic studies can use age-heterogenous samples when investigating genetic risk variants of MDD. Environmental risk factors were stable over a short span of years with associations rapidly decreasing and no evidence of permanent environmental scarring.
Normative and pathological personality traits have rarely been integrated into a joint large-scale structural analysis with psychiatric disorders, although a recent study suggested they entail a common individual differences continuum.
We explored the joint factor structure of 11 psychiatric disorders, five personality-disorder trait domains (DSM-5 Section III), and five normative personality trait domains (the ‘Big Five’) in a population-based sample of 2796 Norwegian twins, aged 19‒46.
Three factors could be interpreted: (i) a general risk factor for all psychopathology, (ii) a risk factor specific to internalizing disorders and traits, and (iii) a risk factor specific to externalizing disorders and traits. Heritability estimates for the three risk factor scores were 48% (95% CI 41‒54%), 35% (CI 28‒42%), and 37% (CI 31‒44%), respectively. All 11 disorders had uniform loadings on the general factor (congruence coefficient of 0.991 with uniformity). Ignoring sign and excluding the openness trait, this uniformity of factor loadings held for all the personality trait domains and all disorders (congruence 0.983).
Based on our findings, future research should investigate joint etiologic and transdiagnostic models for normative and pathological personality and other psychopathology.
Psychological distress (PSYCH), somatic distress (SOMA), affective disorders (AD), and substance use (SU) frequently co-occur. The genetic relationship between PSYCH and SOMA, however, remains understudied. We examined the genetic and environmental influences on these two disorders and their comorbid AD and SU using structural equation modeling. Self-reported PSYCH and SOMA were measured in 1,548 twins using the two subscales of a 12-item questionnaire, the Somatic and Psychological Health Report. Its reliability and psychometric properties were examined. Six ADs, involvement of licit and illicit substance, and two SU disorders were obtained from 1,663–2,132 twins using the World Mental Health Composite International Diagnostic Interview and/or from an online adaption of the same. SU phenotypes (heritability: 49–79%) were found to be more heritable than the affective disorder phenotypes (heritability: 32–42%), SOMA (heritability: 25%), and PSYCH (heritability: 23%). We fit separate non-parametric item response theory models for PSYCH, SOMA, AD, and SU. The IRT scores were used as the refined phenotypes for fitting multivariate genetic models. The best-fitting model showed the similar amount of genetic overlap between PSYCH–AD (genetic correlation rG = 0.49) and SOMA–AD (rG =0.53), as well as between PSYCH–SU (rG = 0.23) and SOMA–SU (rG = 0.25). Unique environmental factors explained 53% to 76% of the variance in each of these four phenotypes, whereas additive genetic factors explained 17% to 46% of the variance. The covariance between the four phenotypes was largely explained by unique environmental factors. Common genetic factor had a significant influence on all the four phenotypes, but they explained a moderate portion of the covariance.
Research on environmental and genetic pathways to complex traits such as educational attainment (EA) is confounded by uncertainty over whether correlations reflect effects of transmitted parental genes, causal family environments, or some, possibly interactive, mixture of both. Thus, an aggregate of thousands of alleles associated with EA (a polygenic risk score; PRS) may tap parental behaviors and home environments promoting EA in the offspring. New methods for unpicking and determining these causal pathways are required. Here, we utilize the fact that parents pass, at random, 50% of their genome to a given offspring to create independent scores for the transmitted alleles (conventional EA PRS) and a parental score based on alleles not transmitted to the offspring (EA VP_PRS). The formal effect of non-transmitted alleles on offspring attainment was tested in 2,333 genotyped twins for whom high-quality measures of EA, assessed at age 17 years, were available, and whose parents were also genotyped. Four key findings were observed. First, the EA PRS and EA VP_PRS were empirically independent, validating the virtual-parent design. Second, in this family-based design, children's own EA PRS significantly predicted their EA (β = 0.15), ruling out stratification confounds as a cause of the association of attainment with the EA PRS. Third, parental EA PRS predicted the SES environment parents provided to offspring (β = 0.20), and parental SES and offspring EA were significantly associated (β = 0.33). This would suggest that the EA PRS is at least as strongly linked to social competence as it is to EA, leading to higher attained SES in parents and, therefore, a higher experienced SES for children. In a full structural equation model taking account of family genetic relatedness across multiple siblings the non-transmitted allele effects were estimated at similar values; but, in this more complex model, confidence intervals included zero. A test using the forthcoming EA3 PRS may clarify this outcome. The virtual-parent method may be applied to clarify causality in other phenotypes where observational evidence suggests parenting may moderate expression of other outcomes, for instance in psychiatry.
Until now, data have not been available to elucidate the genetic and environmental sources of comorbidity between all 10 DSM-IV personality disorders (PDs) and cocaine use. Our aim was to determine which PD traits are linked phenotypically and genetically to cocaine use. Cross-sectional data were obtained in a face-to-face interview between 1999 and 2004. Subjects were 1,419 twins (µage = 28.2 years, range = 19–36) from the Norwegian Institute of Public Health Twin Panel, with complete lifetime cocaine use and criteria for all 10 DSM-IV PDs. Stepwise multiple and Least Absolute Shrinkage and Selection Operator (LASSO) regressions were used to identify PDs related to cocaine use. Twin models were fitted to estimate genetic and environmental associations between the PD traits and cocaine use. In the multiple regression, antisocial (OR = 4.24, 95% CI [2.66, 6.86]) and borderline (OR = 2.19, 95% CI [1.35, 3.57]) PD traits were significant predictors of cocaine use. In the LASSO regression, antisocial, borderline, and histrionic were significant predictors of cocaine use. Antisocial and borderline PD traits each explained 72% and 25% of the total genetic risks in cocaine use, respectively. Genetic risks in histrionic PD were not significantly related to cocaine use. Importantly, after removing criteria referencing substance use, antisocial PD explained 65% of the total genetic variance in cocaine use, whereas borderline explained only 4%. Among PD traits, antisocial is the strongest correlate of cocaine use, for which the association is driven largely by common genetic risks.