Paul Lichtenstein

University of Oxford, Oxford, England, United Kingdom

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Publications (498)3422.79 Total impact

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    ABSTRACT: Prominent developmental theories posit a causal link between early-life exposures and later functioning. Yet, observed associations with early exposures may not reflect causal effects because of genetic and environmental confounding. The current manuscript describes how a systematic series of epidemiologic analyses that combine several genetically-informative designs and statistical approaches can help distinguish between competing theories. In particular, the manuscript details how combining the use of measured covariates with sibling-comparisons, cousin-comparisons, and additional designs can help elucidate the sources of covariation between early-life exposures and later outcomes, including the roles of (a) factors that are not shared in families, including a potential causal effect of the exposure; (b) carryover effects from the exposure of one child to the next; and (c) familial confounding. We also describe key assumptions and how they can be critically evaluated. Furthermore, we outline how subsequent analyses, including effect decomposition with respect to measured, plausible mediators, and quantitative genetic models can help further specify the underlying processes that account for the associations between early-life exposures and offspring outcomes.
    Behavior Genetics 11/2015; DOI:10.1007/s10519-015-9769-8 · 3.21 Impact Factor
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    ABSTRACT: Couples are similar in their pair-bonding behavior, yet the reasons for this similarity are often unclear. A common explanation is phenotypic assortment, whereby individuals select partners with similar heritable characteristics. Alternatively, social homogamy, whereby individuals passively select partners with similar characteristic due to shared social backgrounds, is rarely considered. We examined whether phenotypic assortment and/or social homogamy can contribute to mate similarity using a twin-partner design. The sample came from the Twin and Offspring Study in Sweden, which included 876 male and female monozygotic and same-sex dizygotic twins plus their married or cohabitating partners. Results showed that variance in pair-bonding behavior was attributable to genetic and nonshared environmental factors. Furthermore, phenotypic assortment accounted for couple similarity in pair-bonding behavior. This suggests that individuals' genetically based characteristics are involved in their selection of mates with similar pair-bonding behavior.
    Behavior Genetics 11/2015; DOI:10.1007/s10519-015-9766-y · 3.21 Impact Factor
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    ABSTRACT: Background Mortality has been suggested to be increased in autism spectrum disorder (ASD).AimsTo examine both all-cause and cause-specific mortality in ASD, as well as investigate moderating role of gender and intellectual ability.Method Odds ratios (ORs) were calculated for a population-based cohort of ASD probands (n = 27 122, diagnosed between 1987 and 2009) compared with gender-, age- and county of residence-matched controls (n = 2 672 185).ResultsDuring the observed period, 24 358 (0.91%) individuals in the general population died, whereas the corresponding figure for individuals with ASD was 706 (2.60%; OR = 2.56; 95% CI 2.38-2.76). Cause-specific analyses showed elevated mortality in ASD for almost all analysed diagnostic categories. Mortality and patterns for cause-specific mortality were partly moderated by gender and general intellectual ability.Conclusions Premature mortality was markedly increased in ASD owing to a multitude of medical conditions.
    The British Journal of Psychiatry 11/2015; DOI:10.1192/bjp.bp.114.160192 · 7.99 Impact Factor
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    ABSTRACT: Lithium is the mainstay prophylactic treatment for bipolar disorder (BD), but treatment response varies considerably across individuals. Patients who respond well to lithium treatment might represent a relatively homogeneous subtype of this genetically and phenotypically diverse disorder. Here, we performed genome-wide association studies (GWAS) to identify (i) specific genetic variations influencing lithium response and (ii) genetic variants associated with risk for lithium-responsive BD. Patients with BD and controls were recruited from Sweden and the United Kingdom. GWAS were performed on 2698 patients with subjectively defined (self-reported) lithium response and 1176 patients with objectively defined (clinically documented) lithium response. We next conducted GWAS comparing lithium responders with healthy controls (1639 subjective responders and 8899 controls; 323 objective responders and 6684 controls). Meta-analyses of Swedish and UK results revealed no significant associations with lithium response within the bipolar subjects. However, when comparing lithium-responsive patients with controls, two imputed markers attained genome-wide significant associations, among which one was validated in confirmatory genotyping (rs116323614, P=2.74 × 10−8). It is an intronic single-nucleotide polymorphism (SNP) on chromosome 2q31.2 in the gene SEC14 and spectrin domains 1 (SESTD1), which encodes a protein involved in regulation of phospholipids. Phospholipids have been strongly implicated as lithium treatment targets. Furthermore, we estimated the proportion of variance for lithium-responsive BD explained by common variants (‘SNP heritability’) as 0.25 and 0.29 using two definitions of lithium response. Our results revealed a genetic variant in SESTD1 associated with risk for lithium-responsive BD, suggesting that the understanding of BD etiology could be furthered by focusing on this subtype of BD.
    Molecular Psychiatry 10/2015; DOI:10.1038/mp.2015.165 · 14.50 Impact Factor
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    ABSTRACT: Acute intermittent porphyria (AIP) has been associated with schizophrenia in some studies, but prior research is limited by the absence of comparison populations. Here, we linked Swedish registers to examine the risk of schizophrenia and bipolar disorder in 717 individuals diagnosed with AIP and their first-degree relatives, compared with matched individuals without AIP and their first-degree relatives. Individuals with AIP had a fourfold increased risk of schizophrenia or bipolar disorder. Similarly, relatives of individuals with AIP had double the risk of schizophrenia or bipolar disorder, suggesting that these associations may be as a result of common genetic influences.
    The British journal of psychiatry: the journal of mental science 10/2015; DOI:10.1192/bjp.bp.114.157073 · 7.99 Impact Factor
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    ABSTRACT: In epidemiological and twin populations, prior interview studies have identified an externalizing spectrum of disorders. Could this be detected utilizing objective registry data? In 20,603 twin pairs from the Swedish Twin Registry, we obtained information from national medical, criminal and pharmacy records on drug abuse (DA), criminal behavior (CB) and alcohol use disorders (AUD). Multivariate twin modeling was performed with the OpenMx package. A common pathway model with quantitative but not qualitative sex effects fit best with twin resemblance for the latent liability to externalizing syndromes due to both genetic and shared environmental factors. Heritability of the liability was higher in females (76 vs. 62 %) while shared environmental influences were considerably stronger in males (23 vs. 3 %). In both sexes, this latent liability was most strongly indexed by DA and least by CB. All three syndromes had specific genetic influences (especially CB and AUD in males, and CB in females) and specific shared environmental effects (especially DA and CB in males, and AUD in females). For DA, CB and AUD in men, and DA and AUD in women, at least 75 % of the genetic risk arose through the common factor. The best fit model assumed that genetic and environmental influences on these externalizing syndromes in males and females were the same. We identified, in registry data, a highly heritable externalizing spectrum. DA, CB and AUD share substantial genetic and modest to moderate shared environmental influences. The nature of the externalizing spectrum differed meaningfully between the sexes.
    Behavior Genetics 10/2015; DOI:10.1007/s10519-015-9741-7 · 3.21 Impact Factor
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    ABSTRACT: Studies suggest associations between childhood autistic traits and adolescent psychotic experiences. However, recent research suggests that a general neuropsychiatric problems factor predicts adverse outcomes better than specific diagnostic entities. To examine if the alleged association between autistic traits and psychotic experiences could rather be explained by a general neuropsychiatric problems factor comprising symptoms of ADHD, tic disorder, developmental coordination disorder, and learning disorder, we conducted a prospective cohort study based on the Child and Adolescent Twin Study in Sweden. In addition, we examined the genetic and environmental influences on the associations. A total of 9,282 twins with data on childhood autistic traits and other neuropsychiatric problems, and follow-up data on psychotic experiences at ages 15 and/or 18 years were included. First, psychotic experiences were regressed on autistic traits and second, the general neuropsychiatric problems factor was added to the model. Auditory hallucinations were analyzed separately from the other psychotic experiences. Finally, twin analyses were employed to disentangle genetic from environmental influences in the observed associations. Replicating prior research, significant associations were found between autistic traits in childhood and auditory hallucinations at ages 15 and 18. However, after controlling for the general neuropsychiatric problems factor, the associations between autistic traits and auditory hallucinations disappeared, whereas the association between the general neuropsychiatric problems factor and auditory hallucinations persisted after controlling for autistic traits. Twin analyses revealed that the association between the general neuropsychiatric problems factor and auditory hallucinations was driven by shared genetic influences.
    American Journal of Medical Genetics Part B Neuropsychiatric Genetics 10/2015; 9999:1-7. DOI:10.1002/ajmg.b.32386 · 3.42 Impact Factor
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    ABSTRACT: The dopamine (DA) and serotonin (5-HT) neurotransmission systems are of fundamental importance for normal brain function and serve as targets for treatment of major neuropsychiatric disorders. Despite central interest for these neurotransmission systems in psychiatry research, little is known about the regulation of receptor and transporter density levels. This lack of knowledge obscures interpretation of differences in protein availability reported in psychiatric patients. In this study, we used positron emission tomography (PET) in a twin design to estimate the relative contribution of genetic and environmental factors, respectively, on dopaminergic and serotonergic markers in the living human brain. Eleven monozygotic and 10 dizygotic healthy male twin pairs were examined with PET and [ 11 C]raclopride binding to the D 2-and D 3-dopamine receptor and [ 11 C]WAY100635 binding to the serotonin 5-HT 1A receptor. Heritability, shared environmental effects and individual-specific non-shared effects were estimated for regional D 2/3 and 5-HT 1A receptor availability in projection areas. We found a major contribution of genetic factors (0.67) on individual variability in striatal D 2/3 receptor binding and a major contribution of environmental factors (pairwise shared and unique individual; 0.70–0.75) on neocortical 5-HT 1A receptor binding. Our findings indicate that individual variation in neuroreceptor availability in the adult brain is the end point of a nature–nurture interplay, and call for increased efforts to identify not only the genetic but also the environmental factors that influence neurotransmission in health and disease.
    Molecular Psychiatry 10/2015; DOI:10.1038/mp.2015.147 · 14.50 Impact Factor
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    ABSTRACT: Background Although the genetics of asthma has been extensively studied using both quantitative and molecular genetic analysis methods, both approaches lack studies specific to the childhood phenotype and including other allergic diseases. This study aimed to give specific estimates for the heritability of childhood asthma and other allergic diseases, to attempt to replicate findings from genome-wide association studies (GWAS) for childhood asthma and to test the same variants against other allergic diseases.Methods In a cohort of 25,306 Swedish twins aged 9 or 12, data on asthma were available from parental interviews and population-based registers. The interviews also inquired about wheeze, hay fever, eczema and food allergy. Through structural equation modeling, the heritability of all phenotypes was calculated. A subset of 10,075 twins was genotyped for 16 single nucleotide polymorphisms (SNPs) selected from previous GWAS; these were first tested for association with asthma and significant findings also against the other allergic diseases.ResultsThe heritability of any childhood asthma was 0.82 (95% CI 0.79-0.85). For the other allergic diseases the range was approximately 0.60-0.80. Associations for six SNPs with asthma were replicated, including rs2305480 in the GSDMB gene (OR 0.80, 95% CI 0.74-0.86, p= 1.5*10-8; other significant associations all below p=3.5*10-4). Of these, only rs3771180 in IL1RL1 was associated with any other allergic disease (for hay fever, OR 0.64, 95%CI 0.53-0.77, p=2.5*10-6).Conclusion Asthma and allergic diseases of childhood are highly heritable, and these high-risk genetic variants associated specifically with childhood asthma, except for one SNP shared with hay fever.This article is protected by copyright. All rights reserved.
    Allergy 10/2015; DOI:10.1111/all.12783 · 6.03 Impact Factor
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    ABSTRACT: We examined associations of maternal age at childbearing (MAC) with gestational age and fetal growth (i.e., birth weight adjusting for gestational age), using two genetically informed designs (cousin and sibling comparisons) and data from two cohorts, a population-based Swedish sample and a nationally representative United States sample. We also conducted sensitivity analyses to test limitations of the designs. The findings were consistent across samples and suggested that, associations observed in the population between younger MAC and shorter gestational age were confounded by shared familial factors; however, associations of advanced MAC with shorter gestational age remained robust after accounting for shared familial factors. In contrast to the gestational age findings, neither early nor advanced MAC was associated with lower fetal growth after accounting for shared familial factors. Given certain assumptions, these findings provide support for a causal association between advanced MAC and shorter gestational age. The results also suggest that there are not causal associations between early MAC and shorter gestational age, between early MAC and lower fetal growth, and between advanced MAC and lower fetal growth.
    Behavior Genetics 09/2015; DOI:10.1007/s10519-015-9748-0 · 3.21 Impact Factor
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    ABSTRACT: The quantitative genetic contribution to antisocial behavior is well established, but few, if any, genetic variants are established as risk factors. Emerging evidence suggests that the neuropeptide oxytocin (OXT) may modulate interpersonal aggression. We here investigated whether single-nucleotide polymorphisms (SNPs) in the OXT receptor gene (OXTR) are associated with the expression of antisocial behavior. A discovery sample, including both sexes, was drawn from the Child and Adolescent Twin Study in Sweden (CATSS; n=2372), and a sample from the Twin Study of Child and Adolescent Development (TCHAD; n=1232) was used for replication. Eight SNPs in OXTR, selected on previous associations with social and antisocial behavior, were genotyped in the participants of CATSS. Significant polymorphisms were subsequently genotyped in TCHAD for replication. Participants completed self-assessment questionnaires-Life History of Aggression (LHA; available only in CATSS), and Self-Reported Delinquency (SRD; available in both samples)-designed to capture antisocial behavior as continuous traits. In the discovery sample, the rs7632287 AA genotype was associated with higher frequency of antisocial behavior in boys, and this was then replicated in the second sample. In particular, overt aggression (directly targeting another individual) was strongly associated with this genotype in boys (P=6.2 × 10(-7) in the discovery sample). Meta-analysis of the results for antisocial behavior from both samples yielded P=2.5 × 10(-5). Furthermore, an association between rs4564970 and LHA (P=0.00013) survived correction in the discovery sample, but there was no association with the SRD in the replication sample. We conclude that the rs7632287 and rs4564970 polymorphisms in OXTR may independently influence antisocial behavior in adolescent boys. Further replication of our results will be crucial to understanding how aberrant social behavior arises, and would support the OXT receptor as one potential target in the treatment of aggressive antisocial behavior.Molecular Psychiatry advance online publication, 22 September 2015; doi:10.1038/mp.2015.144.
    Molecular Psychiatry 09/2015; DOI:10.1038/mp.2015.144 · 14.50 Impact Factor
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    ABSTRACT: Background: Although selective serotonin reuptake inhibitors (SSRIs) are widely prescribed, associations with violence are uncertain. Methods and findings: From Swedish national registers we extracted information on 856,493 individuals who were prescribed SSRIs, and subsequent violent crimes during 2006 through 2009. We used stratified Cox regression analyses to compare the rate of violent crime while individuals were prescribed these medications with the rate in the same individuals while not receiving medication. Adjustments were made for other psychotropic medications. Information on all medications was extracted from the Swedish Prescribed Drug Register, with complete national data on all dispensed medications. Information on violent crime convictions was extracted from the Swedish national crime register. Using within-individual models, there was an overall association between SSRIs and violent crime convictions (hazard ratio [HR] = 1.19, 95% CI 1.08-1.32, p < 0.001, absolute risk = 1.0%). With age stratification, there was a significant association between SSRIs and violent crime convictions for individuals aged 15 to 24 y (HR = 1.43, 95% CI 1.19-1.73, p < 0.001, absolute risk = 3.0%). However, there were no significant associations in those aged 25-34 y (HR = 1.20, 95% CI 0.95-1.52, p = 0.125, absolute risk = 1.6%), in those aged 35-44 y (HR = 1.06, 95% CI 0.83-1.35, p = 0.666, absolute risk = 1.2%), or in those aged 45 y or older (HR = 1.07, 95% CI 0.84-1.35, p = 0.594, absolute risk = 0.3%). Associations in those aged 15 to 24 y were also found for violent crime arrests with preliminary investigations (HR = 1.28, 95% CI 1.16-1.41, p < 0.001), non-violent crime convictions (HR = 1.22, 95% CI 1.10-1.34, p < 0.001), non-violent crime arrests (HR = 1.13, 95% CI 1.07-1.20, p < 0.001), non-fatal injuries from accidents (HR = 1.29, 95% CI 1.22-1.36, p < 0.001), and emergency inpatient or outpatient treatment for alcohol intoxication or misuse (HR = 1.98, 95% CI 1.76-2.21, p < 0.001). With age and sex stratification, there was a significant association between SSRIs and violent crime convictions for males aged 15 to 24 y (HR = 1.40, 95% CI 1.13-1.73, p = 0.002) and females aged 15 to 24 y (HR = 1.75, 95% CI 1.08-2.84, p = 0.023). However, there were no significant associations in those aged 25 y or older. One important limitation is that we were unable to fully account for time-varying factors. Conclusions: The association between SSRIs and violent crime convictions and violent crime arrests varied by age group. The increased risk we found in young people needs validation in other studies.
    PLoS Medicine 09/2015; 12(9):e1001875. DOI:10.1371/journal.pmed.1001875 · 14.43 Impact Factor
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    ABSTRACT: Objective: Neurodevelopmental problems (NDPs) may influence the transition from childhood to adolescence. Our aim was to study long-term psychosocial outcomes of NDPs, focusing on ADHD. Method: Data was collected through a telephone interview with parents of twins at ages 9 or 12 years. NDP screen-positive children were clinically assessed at age 15; N = 450. Psychosocial outcome concerning peers, school, internalizing problems, antisocial behavior, alcohol misuse, drug misuse, and impaired daily functioning was examined. Results: Even after controlling for other NDP comorbidity, screen-positivity for ADHD doubled or tripled the odds of later psychosocial problems. When controlling for parental education level, the significant effect of ADHD remained only for antisocial behavior and impaired daily functioning. Conclusions: Signs of NDPs as well as other psychiatric diagnoses at ages 9 or 12 years are associated with a more problematic adolescence. However, despite the presence of comorbidity, early ADHD symptoms stand out as the most important risk factor for later antisocial development and impaired daily functioning.
    PLoS ONE 09/2015; 10(9):e0137475. DOI:10.1371/journal.pone.0137475 · 3.23 Impact Factor
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    ABSTRACT: Importance: Low resting heart rate is a well-replicated physiological correlate of aggressive and antisocial behavior in children and adolescents, but whether low resting heart rate increases the risk of violence and other antisocial and risk-taking behaviors in adulthood has not been studied in representative samples. Objective: To study the predictive association of resting heart rate with violent and nonviolent criminality and with fatal and nonfatal injuries owing to assaults and unintentional injuries in the population. Design, setting, and participants: We conducted a study of data from several Swedish national registers on 710 264 Swedish men in the general population born from 1958 to 1991, with a follow-up of up to 35.7 years. Outcome data were available and analyzed from January 1, 1973, through December 31, 2009. Resting heart rate was measured together with blood pressure at mandatory military conscription testing at a mean (SD) age of 18.2 (0.5) years. Main outcomes and measures: Violent and nonviolent criminal convictions and medical treatments or deaths owing to assaults and unintentional injuries. Results: In models adjusted for physical, cardiovascular, psychiatric, cognitive, and socioeconomic covariates, compared with 139 511 men in the highest quintile of the distribution of resting heart rate (≥83 beats/min), 132 595 men with the lowest quintile (heart rate, ≤60 beats/min) had a 39% (95% CI, 35%-44%) higher hazard of being convicted of violent crimes and a 25% (95% CI, 23%-28%) higher hazard of being convicted of nonviolent crimes. The corresponding hazard was 39% higher for assault injuries (95% CI, 33%-46%) and for unintentional injuries (95% CI, 38%-41%). Further adjustment for cardiorespiratory fitness in a subset of 572 610 men with data from an exercise test did not reduce the associations. Similar associations were found between low systolic blood pressure and violent and nonviolent criminality and for assault injuries when systolic blood pressure was studied instead of resting heart rate in more than 1 million men. Conclusions and relevance: Among men, low resting heart rate in late adolescence was associated with an increased risk for violent criminality, nonviolent criminality, exposure to assault, and unintentional injury in adulthood. Most of these results were replicated with low systolic blood pressure. Resting heart rate and other autonomic measures merit further study in the development and prevention of violence and antisocial behavior.
    JAMA Psychiatry 09/2015; 72(10):1-8. DOI:10.1001/jamapsychiatry.2015.1165 · 12.01 Impact Factor
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    Zheng Chang · Henrik Larsson · Paul Lichtenstein · Seena Fazel ·
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    ABSTRACT: Background: Reoffending and presence of psychiatric disorders are common in prisoners worldwide. However, whether psychiatric disorders are risk factors for reoffending is still unknown. We aimed to examine the association between psychiatric disorders, including substance use disorder, and violent reoffending. Methods: We did a longitudinal cohort study of 47 326 prisoners who were imprisoned since Jan 1, 2000, and released before Dec 31, 2009, in Sweden. We obtained data for diagnosed psychiatric disorders from both inpatient and outpatient registers, and sociodemographic and criminological factors from other population-based registers. We calculated hazard ratios (HRs) for violent reoffending with Cox regression. To control for potential familial confounding, we compared sibling prisoners with and without psychiatric disorders. We calculated population attributable fraction to assess the population effect. Findings: Diagnosed psychiatric disorders were associated with an increased hazard of violent reoffending in male (adjusted HR 1·63 [95% CI 1·57-1·70]) and female (2·02 [1·54-2·63]) prisoners, and these associations were independent of measured sociodemographic and criminological factors, and, in men, remained substantial after adjustment for unmeasured familial factors (2·01 [1·66-2·43]). However, findings differed between individual diagnoses and sex. We found some evidence of stronger effects on violent reoffending of alcohol and drug use disorders and bipolar disorder than of other psychiatric disorders. Alcohol use disorder seemed to have a greater effect in women than in men (women 2·08 [1·66-2·60]; men 1·63 [1·56-1·71]). The overall effects of psychiatric disorders did not differ with severity of crime. The hazard of violent reoffending increased in a stepwise way with the number of diagnosed psychiatric disorders. Assuming causality, up to 20% (95% CI 19-22) of violent reoffending in men and 40% (27-52) in women was attributable to the diagnosed psychiatric disorders that we investigated. Interpretation: Certain psychiatric disorders are associated with a substantially increased hazard of violent reoffending. Because these disorders are prevalent and mostly treatable, improvements to prison mental health services could counteract the cycle of reoffending and improve both public health and safety. National violence prevention strategies should consider the role of prison health. Funding: Wellcome Trust, Swedish Research Council, and Swedish Research Council for Health, Working Life and Welfare.
    The Lancet Psychiatry 09/2015; 2(10). DOI:10.1016/S2215-0366(15)00234-5
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    ABSTRACT: A trend toward greater body size in dizygotic (DZ) than in monozygotic (MZ) twins has been suggested by some but not all studies, and this difference may also vary by age. We analyzed zygosity differences in mean values and variances of height and body mass index (BMI) among male and female twins from infancy to old age. Data were derived from an international database of 54 twin cohorts participating in the COllaborative project of Development of Anthropometrical measures in Twins (CODATwins), and included 842,951 height and BMI measurements from twins aged 1 to 102 years. The results showed that DZ twins were consistently taller than MZ twins, with differences of up to 2.0 cm in childhood and adolescence and up to 0.9 cm in adulthood. Similarly, a greater mean BMI of up to 0.3 kg/m 2 in childhood and adolescence and up to 0.2 kg/m 2 in adulthood was observed in DZ twins, although the pattern was less consistent. DZ twins presented up to 1.7% greater height and 1.9% greater BMI than MZ twins; these percentage differences were largest in middle and late childhood and decreased with age in both sexes. The variance of height was similar in MZ and DZ twins at most ages. In contrast, the variance of BMI was significantly higher in DZ than in MZ twins, particularly in childhood. In conclusion, DZ twins were generally taller and had greater BMI than MZ twins, but the differences decreased with age in both sexes.
    Twin Research and Human Genetics 09/2015; 18(5):1-14. DOI:10.1017/thg.2015.57 · 2.30 Impact Factor
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    ABSTRACT: The authors investigated the relative importance of genetic and environmental influences on perinatal depression, and the genetic overlap between perinatal depression and nonperinatal depression. Analyses were conducted using structural equation modeling for 1) the lifetime version of the Edinburgh Postnatal Depression Scale in 3,427 Swedish female twins and 2) clinical diagnoses of depression separated into perinatal depression and nonperinatal depression in a Swedish population-based cohort of 580,006 sisters. In the twin study, the heritability of perinatal depression was estimated at 54% (95% CI=35%-70%), with the remaining variance attributable to nonshared environment (46%; 95% CI=31%-65%). In the sibling design, the heritability of perinatal depression was estimated at 44% (95% CI=35%-52%) and the heritability of nonperinatal depression at 32% (95% CI=24%-41%). Bivariate analysis showed that 14% of the total variance (or 33% of the genetic variance) in perinatal depression was unique for perinatal depression. The heritability of perinatal depression was estimated at 54% and 44%, respectively, in separate samples, and the heritability of nonperinatal depression at 32%. One-third of the genetic contribution was unique to perinatal depression and not shared with nonperinatal depression, suggesting only partially overlapping genetic etiologies for perinatal depression and nonperinatal depression. The authors suggest that perinatal depression constitutes a subset of depression that could be prioritized for genomic discovery efforts. The study findings have direct translational impact that can assist clinicians in the counseling of their patients regarding risk and prognosis of perinatal depression.
    American Journal of Psychiatry 09/2015; DOI:10.1176/appi.ajp.2015.15010085 · 12.30 Impact Factor

  • European Respiratory Journal 09/2015; 46(suppl 59):OA1469. DOI:10.1183/13993003.congress-2015.OA1469 · 7.64 Impact Factor
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    ABSTRACT: Obsessive-compulsive disorder (OCD) often co-occurs with anorexia nervosa (AN), a comorbid profile that complicates the clinical management of both conditions. This population-based study aimed to examine patterns of comorbidity, longitudinal risks, shared familial risks and shared genetic factors between OCD and AN at the population level. Participants were individuals with a diagnosis of OCD (N=519,814) or AN (N=58,462) in the Swedish National Patient Register between January 1992 and December 2009; their first-, second-and third-degree relatives; and population-matched (1:10 ratio) unaffected comparison individuals and their relatives. Female twins from the population-based Swedish Twin Register (N=58,550) were also included. Females with OCD had a 16-fold increased risk of having a comor-bid diagnosis of AN, whereas males with OCD had a 37-fold increased risk. Longitudinal analyses showed that individuals first diagnosed with OCD had an increased risk for a later diagnosis of AN (risk ratio, RR 53.6), whereas individuals first diagnosed with AN had an even greater risk for a later diagnosis of OCD (RR 59.6). These longitudinal risks were about twice as high for males than for females. First-and second-degree relatives of probands with OCD had an increased risk for AN, and the magnitude of this risk tended to increase with the degree of genetic relatedness. Bivariate twin models revealed a moderate but significant degree of genetic overlap between self-reported OCD and AN diagnoses (ra 0.52, 95% CI: 0.26-0.81), but most of the genetic variance was disorder-specific. The moderately high genetic correlation supports the idea that this frequently observed comorbid pattern is at least in part due to shared genetic factors, though disorder-specific factors are more important. These results have implications for current gene-searching efforts and for clinical practice.
    World psychiatry: official journal of the World Psychiatric Association (WPA) 09/2015; 14(3):333-338. DOI:10.1002/wps.20251 · 14.23 Impact Factor
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    E Pettersson · H Larsson · P Lichtenstein ·
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    ABSTRACT: Recent studies have shown that different mental-health problems appear to be partly influenced by the same set of genes, which can be summarized by a general genetic factor. To date, such studies have relied on surveys of community-based samples, which could introduce potential biases. The goal of this study was to examine whether a general genetic factor would still emerge when based on a different ascertainment method with different biases from previous studies. We targeted all adults in Sweden (n=3 475 112) using national registers and identified those who had received one or more psychiatric diagnoses after seeking or being forced into mental health care. In order to examine the genetic versus environmental etiology of the general factor, we examined whether participants' full- or half-siblings had also received diagnoses. We focused on eight major psychiatric disorders based on the International Classification of Diseases, including schizophrenia, schizoaffective disorder, bipolar disorder, depression, anxiety, attention-deficit/hyperactivity disorder, alcohol use disorder and drug abuse. In addition, we included convictions of violent crimes. Multivariate analyses demonstrated that a general genetic factor influenced all disorders and convictions of violent crimes, accounting for between 10% (attention-deficit/hyperactivity disorder) and 36% (drug abuse) of the variance of the conditions. Thus, a general genetic factor of psychopathology emerges when based on both surveys as well as national registers, indicating that a set of pleiotropic genes influence a variety of psychiatric disorders.Molecular Psychiatry advance online publication, 25 August 2015; doi:10.1038/mp.2015.116.
    Molecular Psychiatry 08/2015; DOI:10.1038/mp.2015.116 · 14.50 Impact Factor

Publication Stats

20k Citations
3,422.79 Total Impact Points


  • 2014-2015
    • University of Oxford
      Oxford, England, United Kingdom
  • 1989-2015
    • Karolinska Institutet
      • • Department of Medical Epidemiology and Biostatistics
      • • Institute of Environmental Medicine - IMM
      Сольна, Stockholm, Sweden
  • 2013-2014
    • Indiana University Bloomington
      • Department of Psychological and Brain Sciences
      Bloomington, Indiana, United States
    • University of Southern California
      • Department of Psychology
      Los Ángeles, California, United States
    • Indiana University Health
      Bloomington, Indiana, United States
  • 2010-2014
    • Harvard University
      Cambridge, Massachusetts, United States
  • 2005-2014
    • University of Gothenburg
      • • Institute of Neuroscience and Physiology
      • • Department of Pharmacology
      • • Department of Psychology
      Goeteborg, Västra Götaland, Sweden
  • 2001-2014
    • Karolinska University Hospital
      Tukholma, Stockholm, Sweden
  • 2012
    • University of North Carolina at Chapel Hill
      • Department of Psychiatry
      North Carolina, United States
  • 2009-2010
    • Lund University
      • • Department of Clinical Sciences, Malmö
      • • School of Social Work
      Lund, Skåne, Sweden
    • Uppsala University
      • Department of Neuroscience
      Uppsala, Uppsala, Sweden
  • 2008-2009
    • Stockholm School of Economics
      • Department of Economics
      Tukholma, Stockholm, Sweden
  • 2007
    • George Washington University
      • Department of Psychology
      Washington, Washington, D.C., United States
  • 2004
    • Stockholm University
      Tukholma, Stockholm, Sweden
  • 2003
    • Max Planck Institute for Demographic Research
      Rostock, Mecklenburg-Vorpommern, Germany
  • 1993
    • Pennsylvania State University
      University Park, Maryland, United States