Sara Larsson Lönn

Smoking and Schizophrenia in Population Cohorts of Swedish Women and Men: A Prospective Co-Relative Control Study

OBJECTIVE The purpose of this study was to clarify the causes of the smoking-schizophrenia association. METHOD Using Cox proportional hazard and co-relative control models, the authors predicted future risk for a diagnosis of schizophrenia or nonaffective psychosis from the smoking status of 1,413,849 women and 233,879 men from, respectively, the Swedish birth and conscript registries. RESULTS Smoking was assessed in women at a mean age of 27 and in men at a mean age of 18. The mean age at end of follow-up was 46 for women and 26 for men. Hazard ratios for first-onset schizophrenia were elevated both for light smoking (2.21 [95% CI=1.90-2.56] for women and 2.15 [95% CI=1.25-3.44] for men) and heavy smoking (3.45 [95% CI=2.95-4.03] for women and 3.80 [95% CI=1.19-6.60] for men). These associations did not decline when schizophrenia onsets 3-5 years after smoking assessment were censored. When age, socioeconomic status, and drug abuse were controlled for, hazard ratios declined only modestly in both samples. Women who smoked into late pregnancy had a much higher risk for schizophrenia than those who quit early. Hazard ratios predicting nonaffective psychosis in the general population, in cousins, in half siblings, and in full siblings discordant for heavy smoking were, respectively, 2.67, 2.71, 2.54, and 2.18. A model utilizing all relative pairs predicted a hazard ratio of 1.69 (95% CI=1.17-2.44) for nonaffective psychosis in the heavy-smoking member of discordant monozygotic twin pairs. CONCLUSIONS Smoking prospectively predicts risk for schizophrenia. This association does not arise from smoking onset during a schizophrenic prodrome and demonstrates a clear dose-response relationship. While little of this association is explained by epidemiological confounders, a portion arises from common familial/genetic risk factors. However, in full siblings and especially monozygotic twins discordant for smoking, risk for nonaffective psychosis is appreciably higher in the smoking member. These results can help in evaluating the plausibility of various etiological hypotheses for the smoking-schizophrenia association.

Depression, stroke and gender: evidence of a stronger association in men

Background/aims Depression is associated with an increased risk for stroke. The aim of this study was to examine whether demographic and socioeconomic factors modify this association. Methods This follow-up study comprised 137 305 men and 188 924 women aged ≥30 years from a nationwide sample of primary healthcare centres in Sweden. We identified 4718 first-ever stroke cases (2217 men and 2501 women) during the follow-up period (2005–2007). Multilevel logistic regression models were used to calculate ORs and examine interactions in order to determine whether the association between depression and stroke differs by demographic or socioeconomic factors. Results Depression was associated with significantly greater odds of stroke after adjustment for potential confounding factors (OR=1.22, 95% CI 1.08 to 1.38). Interaction tests showed that the effect of depression on stroke was higher in men compared with women (the difference in OR between men and women was 1.30, 95% CI 1.01 to 1.68), that is, the association between depression and stroke was modified by gender. Conclusions Our findings suggest that the depression–stroke association is modified by gender. Further studies are required to examine the underlying mechanisms in men and women.

Effect of Marriage on Risk for Onset of Alcohol Use Disorder: A Longitudinal and Co-Relative Analysis in a Swedish National Sample

OBJECTIVE The authors sought to clarify the relationship between marriage and risk for alcohol use disorder. METHOD The association between marital status and risk for first registration for alcohol use disorder in medical, criminal, and pharmacy registries was assessed in a population-based Swedish cohort (N=3,220,628) using longitudinal time-dependent survival and co-relative designs. RESULTS First marriage was associated with a substantial decline in risk for onset of alcohol use disorder in men (hazard ratio=0.41, 95% CI=0.40-0.42) and women (hazard ratio=0.27, 95% CI=0.26-0.28). This association was slightly stronger when the spouse had no lifetime alcohol use disorder, while marriage to a spouse with lifetime alcohol use disorder increased risk for subsequent alcohol use disorder registration in both men (hazard ratio=1.29, 95% CI=1.16-1.43) and women (hazard ratio=1.18, 95% CI=1.06-1.30). In both sexes, the protective effect of marriage was significantly stronger in those with than those without a family history of alcohol use disorder. In both men and women, the associations between marriage and risk for alcohol use disorder in cousins, half siblings, full siblings, and monozygotic twins discordant for marital status were as strong as that seen in the general population. CONCLUSIONS First marriage to a spouse with no lifetime alcohol use disorder is associated with a large reduction in risk for alcohol use disorder. This association cannot be explained by standard covariates or, as indicated by co-relative analyses, familial genetic or shared environmental confounders. These results are consistent with the hypothesis that the psychological and social aspects of marriage, and in particular health-monitoring spousal interactions, strongly protect against the development of alcohol use disorder. The protective effects of marriage on risk for alcohol use disorder are increased in those at high familial risk for alcoholism.

Divorce and the Onset of Alcohol Use Disorder: A Swedish Population-Based Longitudinal Cohort and Co-Relative Study

OBJECTIVE The purpose of this study was to clarify the magnitude and nature of the relationship between divorce and risk for alcohol use disorder (AUD). METHOD In a population-based Swedish sample of married individuals (N=942,366), the authors examined the association between divorce or widowhood and risk for first registration for AUD. AUD was assessed using medical, criminal, and pharmacy registries. RESULTS Divorce was strongly associated with risk for first AUD onset in both men (hazard ratio=5.98, 95% CI=5.65-6.33) and women (hazard ratio=7.29, 95% CI=6.72-7.91). The hazard ratio was estimated for AUD onset given divorce among discordant monozygotic twins to equal 3.45 and 3.62 in men and women, respectively. Divorce was also associated with an AUD recurrence in those with AUD registrations before marriage. Furthermore, widowhood increased risk for AUD in men (hazard ratio=3.85, 95% CI=2.81-5.28) and women (hazard ratio=4.10, 95% CI=2.98-5.64). Among divorced individuals, remarriage was associated with a large decline in AUD in both sexes (men: hazard ratio=0.56, 95% CI=0.52-0.64; women: hazard ratio=0.61, 95% CI=0.55-0.69). Divorce produced a greater increase in first AUD onset in those with a family history of AUD or with prior externalizing behaviors. CONCLUSIONS Spousal loss through divorce or bereavement is associated with a large enduring increased AUD risk. This association likely reflects both causal and noncausal processes. That the AUD status of the spouse alters this association highlights the importance of spouse characteristics for the behavioral health consequences of spousal loss. The pronounced elevation in AUD risk following divorce or widowhood, and the protective effect of remarriage against subsequent AUD, speaks to the profound impact of marriage on problematic alcohol use.

A National Swedish Twin-Sibling Study of Alcohol Use Disorders.

The relationship between the genetic and environmental risk factors for alcohol use disorders (AUD) detected in Swedish medical, pharmacy, and criminal registries has not been hitherto examined. Prior twin studies have varied with regard to the detection of shared environmental effects and sex differences in the etiology of AUD. In this report, structural equation modeling in OpenMx was applied to (1) the three types of alcohol registration in a population-based sample of male-male twins and reared-together full and half siblings (total 208,810 pairs), and (2) AUD, as a single diagnosis, in male-male, female-female, and opposite-sex (OS) twins and reared-together full and half siblings (total 787,916 pairs). An independent pathway model fit best to the three forms of registration and indicated that between 70% and 92% of the genetic and 63% and 98% of the shared environmental effects were shared in common with the remainder unique to each form of AUD registration. Criminal registration had the largest proportion of unique genetic and environmental factors. The best fit model for AUD estimated the heritability to be 22% and 57%, respectively, in females and males. Both shared (12% vs. 6%) and special twin environment (29% vs. 2%) were substantially more important in females versus males. In conclusion, AUD ascertained from medical, pharmacy, and criminal Swedish registries largely share the same genetic and environmental risk factors. Large sex differences in the etiology of AUD were seen in this sample, with substantially stronger familial environmental and weaker genetic effects in females versus males.

A Swedish national twin study of criminal behavior and its violent, white-collar and property subtypes.

BACKGROUND We sought to clarify the etiological contribution of genetic and environmental factors to total criminal behavior (CB) measured as criminal convictions in men and women, and to violent (VCB), white-collar (WCCB) and property criminal behavior (PCB) in men only. METHOD In 21 603 twin pairs from the Swedish Twin Registry, we obtained information on all criminal convictions from 1973 to 2011 from the Swedish Crime Register. Twin modeling was performed using the OpenMx package. RESULTS For all criminal convictions, heritability was estimated at around 45% in both sexes, with the shared environment accounting for 18% of the variance in liability in females and 27% in males. The correlation of these risk factors across sexes was estimated at +0.63. In men, the magnitudes of genetic and environmental influence were similar in the three criminal conviction subtypes. However, for violent and white-collar convictions, nearly half and one-third of the genetic effects were respectively unique to that criminal subtype. About half of the familial environmental effects were unique to property convictions. CONCLUSIONS The familial aggregation of officially recorded CB is substantial and results from both genetic and familial environmental factors. These factors are moderately correlated across the sexes suggesting that some genetic and environmental influences on criminal convictions are unique to men and to women. Violent criminal behavior and property crime are substantially influenced respectively by genetic and shared environmental risk factors unique to that criminal subtype.

Psychological strength assessed in late adolescence and risk for criminal behavior: a Swedish prospective cohort and twin analysis.

BACKGROUND Certain personality traits predispose to criminal behavior (CB). We further clarify this relationship in a Swedish national sample. METHOD Psychological strength (PS) was assessed on a nine-point scale at personal interview in 1 653 721 Swedish men aged 18-20 years. We examined the association between PS and total, violent and recurrent CB over the lifetime (logistic regression), prospectively (Cox regression) and by bivariate Cholesky decomposition in 2507 monozygotic and 2244 dizygotic twin pairs (OpenMx). RESULTS Examining linear effects by logistic regression, PS was robustly associated with lifetime risk of total CB (per point, odds ratio = 0.74) and even more strongly associated with risk for violent (0.69) and recurrent CB (0.52). Prospective predictions of these three forms of CB by PS were similar, with hazard ratios of 0.80, 0.73 and 0.54, respectively. Twin modeling demonstrated that, for all three CB types, the association with PS arose almost entirely from familial effects. Common shared environment accounted for 72, 56 and 43% of the phenotypic correlation between PS and, respectively, total, violent and recurrent CB. Parallel figures for common genetic effects were for 24, 37 and 54%, respectively. CONCLUSIONS PS is strongly related to risk for total CB, and even more strongly for violent and, especially, recurrent CB. This association is probably not causal but rather results from shared familial risk factors that make an impact both on PS and risk for CB. PS has a stronger overall correlation with more severe criminal outcomes and a higher proportion of that correlation results from common genetic factors.

Genetics, the rearing environment, and the intergenerational transmission of divorce: a Swedish national adoption study

We used classical and extended adoption designs in Swedish registries to disentangle genetic and rearing-environment influences on the intergenerational transmission of divorce. In classical adoption analyses, adoptees (n = 19,715) resembled their biological parents, rather than their adoptive parents, in their history of divorce. In extended adoption analyses, offspring (n = 82,698) resembled their not-lived-with fathers and their lived-with mothers. There was stronger resemblance to lived-with mothers, providing indirect evidence of rearing-environment influences on the intergenerational transmission of divorce. The heritability of divorce assessed across generations was 0.13. We attempted to replicate our findings using within-generation data from adoptive and biological siblings (ns = 8,523–53,097). Adoptees resembled their biological, not adoptive, siblings in their history of divorce. Thus, there was consistent evidence that genetic factors contributed to the intergenerational transmission of divorce but weaker evidence for a rearing-environment effect of divorce. Within-generation data from siblings supported these conclusions.

The Origin of Spousal Resemblance for Alcohol Use Disorder

Importance Although spouses strongly resemble one another in their risk for alcohol use disorder (AUD), the causes of this association remain unclear. Objectives To examine longitudinally, in first marriages, the association of a first registration for AUD in one spouse with risk of registration in his or her partner and to explore changes in the risk for AUD registration in individuals with multiple marriages as they transition from a spouse with AUD to one without or vice versa. Design, Setting, and Participants Population-wide Swedish registries were used to identify individuals born in Sweden between 1960 and 1990 who were married before the end of study follow-up on December 31, 2013. The study included 8562 marital pairs with no history of AUD registration prior to their first marriage and an AUD registration in 1 spouse during marriage and 4891 individuals with multiple marriages whose first spouse had no AUD registration and second spouse did or vice versa. Final statistical analyses were conducted from August 15 to September 1, 2017. Exposures A spousal onset or history of AUD registration. Main Outcomes and Measures Alcohol use disorder registration in national medical, criminal, or pharmacy registries. Results Among the 8562 marital pairs (5883 female probands and 2679 male probands; mean [SD] age at marriage, 29.2 [5.7] years) in first marriages, the hazard ratio of AUD registration in wives immediately after the first AUD registration in their husbands was 13.82, which decreased 2 years later to 3.75. The hazard ratio of AUD registration in husbands after the first AUD registration in their wives was 9.21, which decreased 2 years later to 3.09. Among the 4891 individuals with multiple marriages (1439 women and 3452 men; mean [SD] age at first marriage, 25.5 [4.2] years), when individuals transitioned from a first marriage to a spouse with AUD to a second marriage to a spouse without AUD, the hazard ratio for AUD registration was 0.50 (95% CI, 0.42-0.59) in women and 0.51 (95% CI, 0.44-0.59) in men. After a first marriage to a spouse without AUD, the hazard ratio for AUD with a second marriage to a spouse with AUD was 7.02 (95% CI, 5.34-9.23) in women and 9.06 (95% CI, 7.55-10.86) in men. These patterns were modestly attenuated when moving from second to third marriages. Controlling for AUD registration prior to first marriage or between first and second marriages produced minimal changes in risk. Conclusions and Relevance The increase in risk for AUD registration in a married individual following a first AUD registration in the spouse is large and rapid. When an individual with serial spouses is married, in either order, to partners with vs without an AUD registration, the risk for AUD registration is substantially increased when the partner has an AUD registration and decreased when the partner does not have an AUD registration. These results suggest that a married individual’s risk for AUD is directly and causally affected by the presence of AUD in his or her spouse.

Transition from HCCI to PPC: Investigation of Fuel Distribution by Planar Laser Induced Fluorescence (PLIF)

In a previous study, in order to investigate the effect of charge stratification on combustion behavior such as combustion efficiency and combustion phasing which also largely affects the emissions, an experiment was conducted in a heavy-duty compression ignition (CI) metal engine. The engine behavior and emission characteristics were studied in the transition from HCCI mode to PPC mode by varying the start of injection (SOI) timing. To gain more detailed information of the mixing process, in-cylinder laser diagnostic measurements, namely fuel-tracer planar laser induced fluorescence (PLIF) imaging, were conducted in an optical version of the heavy-duty CI engine mentioned above. To the authors’ best knowledge, this is the first time to perform fuel-tracer PLIF measurements in an optical engine with a close to production bowl in piston combustion chamber, under transition conditions from HCCI to PPC mode. Results show that four mixing schemes can be distinguished as the SOI timings are varied during the transition. They are linked to the results presented in the reference paper, where emissions were varied in different zones. For SOI at -100 crank angle degree (CAD), fuel distribution is homogeneous as expected. With other SOI timings, a significant part of the fuel mixture was trapped in the squish region and crevice area before start of combustion (SOC) as shown by PLIF results. The observations in the reference metal engine paper were confirmed by this measurement. Results are also in good agreement with computational fluid dynamics (CFD) simulations performed for this engine. (Less)