| 5011. |
- Kendler, Kenneth S., et al.
(författare)
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Risk for psychiatric and substance use disorders as a function of transitions in Sweden's public educational system : a national study
- 2024
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Ingår i: Psychological Medicine. - 1469-8978. ; 54:1, s. 117-124
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: To clarify, in a national sample, associations between risk for seven psychiatric and substance use disorders and five key transitions in Sweden's public educational system. METHODS: Swedish-born individuals (1972-1995, N = 1 997 910) were followed through 12-31-2018, at mean age 34.9. We predicted, from these educational transitions, risk for major depression (MD), obsessive-compulsive disorder (OCD), bipolar disorder (BD), schizophrenia (SZ), anorexia nervosa (AN), alcohol use disorder (AUD), and drug use disorder (DUD), assessed from Swedish national registers, by Cox regression, censoring individuals with onsets ⩽17. We also predicted risk from the deviation of grades from family-genetic expectations (deviation 1) and from changes in grades from ages 16 to 19 (deviation 2). RESULTS: We observed four major risk patterns across transitions in our disorders: (i) MD and BD, (ii) OCD and SZ, (iii) AUD and DUD, and (iv) AN. Failing early educational transitions had the greatest impact on risk for OCD and SZ while for other disorders, not progressing from basic to upper high school had the largest effect. Completing vocational v. college-prep upper high school was strongly associated with risk for AUD and DUD, had little relation with MD, OCD, BD, and SZ risk, and was protective for AN. Deviation 1 predicted risk most strongly for SZ, AN, and MD. Deviation 2 predicted risk most strongly for SZ, AUD, and DUD. CONCLUSIONS: The pattern of educational transitions and within family and within person development deviations are strongly and relatively specifically associated with future risk for seven psychiatric and substance-use disorders.
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| 5012. |
- Kendler, Kenneth S., et al.
(författare)
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Selecting cases of major psychiatric and substance use disorders in Swedish national registries on the basis of clinical features to maximize the strength or specificity of the genetic risk
- 2023
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Ingår i: Molecular Psychiatry. - 1359-4184. ; 28, s. 5195-5205
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Tidskriftsartikel (refereegranskat)abstract
- We investigate how selection of psychiatric cases by phenotypic criteria can alter the strength and specificity of their genetic risk by examining samples from national Swedish registries for five disorders: major depression (MD, N = 158,557), drug use disorder (DUD, N = 69,841), bipolar disorder (BD, N = 13,530)) ADHD (N = 54,996) and schizophrenia (N = 11,227)). We maximized the family genetic risk score (FGRS) for each disorder and then the specificity of the FGRS in six disorder pairs by univariable and multivariable regression. We use split-half methods to divide our cases for each disorder into deciles for prediction of genetic risk magnitude and quintiles for prediction of specificity by FGRS differences between two disorders. We utilized seven predictor groups: demography/sex, # registrations, site of diagnosis, severity, comorbidity, treatment, and educational/social variables. The ratio of the FGRS in the upper vs two lower deciles from our multivariable prediction model was, in order, DUD – 12.6, MD – 4.9, BD – 4.5, ADHD – 3.3 and schizophrenia 1.4. From the lowest to highest quintile, our measures of genetic specificity increased more than five-fold for i) MD vs. Anxiety Disorders, ii) MD vs BD, iii) MD versus alcohol use disorder (AUD), iv) BD vs schizophrenia and v) DUD vs AUD. This increase was nearly two-fold for ADHD vs DUD. We conclude that the level of genetic liability for our psychiatric disorders could be substantially enriched by selection of cases with our predictors. Specificity of genetic risk could also be substantially impacted by these same predictors.
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| 5013. |
- Kendler, Kenneth S., et al.
(författare)
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The actions and interactions of family genetic risk scores for alcohol use disorder and major depression on the risk for these two disorders
- 2022
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Ingår i: American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics. - : Wiley. - 1552-4841 .- 1552-485X. ; 189:5, s. 128-138
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Tidskriftsartikel (refereegranskat)abstract
- We know little about how genetic risk factors for two disorders jointly act and interact in predisposing to illness. Therefore, in the Swedish population, born 1970–1990 (n = 2,116,082) and followed through 2015, we examine, using additive Cox models, the impact of the family genetic risk scores (FGRS) for alcohol use disorder (AUD) and major depression (MD), their interaction with each other and with the relevant comorbid disorder on risk for AUD and MD. FGRS scores are constructed using rates of illness in first-fourth degree relatives. FGRS for AUD and MD interacted in predicting of both disorders and one FRGS (e.g., for AUD) interacted with the phenotype of MD to predict that disorder (e.g., AUD). These FGRS interactions were not substantially attenuated by adding interactions with the disorders. These results replicated across sexes. In predicting risk for a given disorder, we rarely consider genetic liabilities for other disorders. But such effects were here significant and interactive. Furthermore, the primary disorder genetic risk interacts with comorbid disorders. The pathways to risk for disorders from their and other disorders' genetic liability may be more complex than commonly considered.
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| 5014. |
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| 5015. |
- Kendler, Kenneth S., et al.
(författare)
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The genetic epidemiology of schizotypal personality disorder
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Ingår i: Psychological Medicine. - 0033-2917.
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Tidskriftsartikel (refereegranskat)abstract
- Background. The concept of schizotypal personality disorder (SPD) emerged from observations of personality characteristics common in relatives of schizophrenic patients. While often studied in family designs, few studies and none with genetic measures, have examined SPD in epidemiological samples. Methods. We studied individuals born in Sweden 1940–2000 with an ICD-10 diagnosis of SPD with no prior schizophrenia (SZ) diagnosis (n = 2292). Demographic features, patterns of comorbidity, and Family Genetic Risk Scores (FGRS) were assessed from multiple Swedish registries. Prediction of progression to SZ was assessed by Cox models. Results. SPD was rare, with a prevalence of 0.044%, and had high levels of comorbidity with autism spectrum disorder (ASD), OCD, ADHD, and major depression (MD), and increased rates of being single, unemployed and in receipt of welfare. Affected individuals had elevated levels of FGRS for SZ (+0.42), ASD (+0.30), MD (+0.29), and ADHD (+0.20). Compared to cases of schizophrenia, they had significantly lower rates of FGRSSZ, but significantly elevated rates of genetic risk for ASD, MD, and ADHD. Over a mean follow-up of 8.7 years, 14.6% of SPD cases received a first diagnosis of SZ, the risk for which was significantly increased by levels of FGRSSZ, male sex, young age at SPD diagnosis and an in-patient SPD diagnosis and significantly decreased by comorbidity with MD, ASD, and ADHD. Conclusions. Our results not only support the designation of SPD as a schizophrenia spectrum disorder but also suggest potentially important etiologic links between SPD and ASD and, to a lesser extent, ADHD, OCD, and MD.
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| 5016. |
- Kendler, Kenneth S., et al.
(författare)
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The impact of sex, age at onset, recurrence, mode of ascertainment and medical complications on the family genetic risk score profiles for alcohol use disorder
- 2023
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Ingår i: Psychological Medicine. - 0033-2917. ; 53:5, s. 1732-1740
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Tidskriftsartikel (refereegranskat)abstract
- Background Alcohol use disorder (AUD) is clinically heterogeneous. We examine its potential genetic heterogeneity as a function of sex, age, clinical features and mode of ascertainment. Methods In the Swedish population born 1932-1995 (n = 5 829 952), we examined the genetic risk profiles for AUD, major depression (MD), anxiety disorders, bipolar disorder, drug use disorder (DUD), attention deficit-hyperactivity disorder (ADHD) and criminal behavior (CB) in 361 124 cases of AUD subdivided by sex, age at onset (AAO), recurrence, mode of ascertainment and medical complications. Family genetic risk scores (FGRS), calculated from 1st to 5th-degree relatives controlling of cohabitation, assesses genetic risk from phenotypes in the family, not from DNA variants. Results FGRS profiles differed modestly across sex with all scores higher in females. Differences were more pronounced for AAO and recurrence with the FGRS for AUD, DUD, ADHD and CB substantially higher in cases with early AAO or high recurrence rates. Genetic profiles differed considerably by mode of ascertainment, with higher FGRS for AUD and most other disorders in patients seen in hospital v. primary care settings. Cases of AUD with medical complications had higher FGRS for AUD. AUD cases comorbid with MD and DUD had higher FGRS risk for AUD, but this genetic may be less specific given increases in FGRS for multiple other disorders. Conclusions From a genetic perspective, AUD differs substantially as a function of AAO, recurrence, mode of ascertainment and patterns of comorbidity, suggesting caution in cross-sample comparisons of AUD cohorts that differ in these features.
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| 5017. |
- Kendler, K. S., et al.
(författare)
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The joint impact of cognitive performance in adolescence and familial cognitive aptitude on risk for major psychiatric disorders : a delineation of four potential pathways to illness
- 2018
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Ingår i: Molecular Psychiatry. - : Springer Science and Business Media LLC. - 1359-4184 .- 1476-5578. ; 23, s. 1076-1083
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Tidskriftsartikel (refereegranskat)abstract
- How do joint measures of premorbid cognitive ability and familial cognitive aptitude (FCA) reflect risk for a diversity of psychiatric and substance use disorders? To address this question, we examined, using Cox models, the predictive effects of school achievement (SA) measured at age 16 and FCA—assessed from SA in siblings and cousins, and educational attainment in parents—on risk for 12 major psychiatric syndromes in 1 140 608 Swedes born 1972–1990. Four developmental patterns emerged. In the first, risk was predicted jointly by low levels of SA and high levels of FCA—that is a level of SA lower than would be predicted from the FCA. This pattern was strongest in autism spectrum disorders and schizophrenia, and weakest in bipolar illness. In these disorders, a pathologic process seems to have caused cognitive functioning to fall substantially short of familial potential. In the second pattern, seen in the internalizing conditions of major depression and anxiety disorders, risk was associated with low SA but was unrelated to FCA. Externalizing disorders—drug abuse and alcohol use disorders—demonstrated the third pattern, in which risk was predicted jointly by low SA and low FCA. The fourth pattern, seen in eating disorders, was directly opposite of that observed in externalizing disorders with risk associated with high SA and high FCA. When measured together, adolescent cognitive ability and FCA identified four developmental patterns leading to diverse psychiatric disorders. The value of cognitive assessments in psychiatric research can be substantially increased by also evaluating familial cognitive potential.Molecular Psychiatry advance online publication, 18 April 2017; doi:10.1038/mp.2017.78.
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| 5018. |
- Kendler, Kenneth S., et al.
(författare)
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The Nature of the Familial Risk for Psychosis in Bipolar Disorder
- 2024
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Ingår i: Schizophrenia Bulletin. - 0586-7614. ; 50:1, s. 157-165
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Tidskriftsartikel (refereegranskat)abstract
- Background and Hypothesis: To clarify whether the familial liability to psychosis associated with bipolar disorder (BD) is nonspecific or has a greater effect on risk for psychosis in cases with prominent mood symptoms and/or a remitting course. Study Design: We examined, in 984 809 offspring raised in intact families in Sweden, born 1980-1996 and followed-up through 2018, by multivariable Cox proportional hazards regression, risk in offspring of parents with BD for 7 psychotic disorders: Psychotic MD (PMD), psychotic BD (PBD), schizoaffective disorder (SAD), acute psychoses, psychosis NOS, delusional disorder (DD) and schizophrenia (SZ). Diagnoses were obtained from national registers. Study Results: In the offspring of BD parents, the hazard ratios (HR) for these 7 disorders formed an inverted U-shaped curve, rising from 2.98 for PMD, to peak at 4.49 for PBD and 5.25 for SAD, and then declining to a HR of 3.48 for acute psychoses and 3.22 for psychosis NOS, to a low of 2.19 for DD and 2.33 for SZ. A similar pattern of risks was seen in offspring of mothers and fathers affected with BD and in offspring predicted from age at onset in their BD parent. Conclusions: The BD-Associated risk for psychosis impacts most strongly on mood disorders, moderately on episodic psychotic syndromes, and least on chronic psychotic disorders. These results support prior clinical studies suggesting a qualitative difference in the familial substrate for psychosis occurring in BD and SZ.
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| 5019. |
- Kendler, Kenneth S., et al.
(författare)
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The patterns of family genetic risk scores for eleven major psychiatric and substance use disorders in a Swedish national sample
- 2021
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Ingår i: Translational Psychiatry. - : Springer Science and Business Media LLC. - 2158-3188. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- To clarify the structure of genetic risks for 11 major psychiatric disorders, we calculated, from morbidity risks for disorders in 1st–5th degree relatives controlling for cohabitation effects, in the Swedish population born between 1932 and 1995 (n = 5,830,014), the family genetic risk scores (FGRS) for major depression (MD), anxiety disorders (AD), obsessive-compulsive disorder (OCD), bipolar disorder (BD), schizophrenia (SZ), bulimia (BUL), anorexia nervosa (AN), alcohol use disorder (AUD), drug use disorder (DUD), ADHD, and autism-spectrum disorder (ASD). For all affected individuals, we calculated their mean standardized FGRS for each disorder. The patterns of FGRS were quite similar for MD and AD, and for AUD and DUD, but substantially less similar for BUL and AN, BD and SZ, and ADHD and ASD. While OCD had high levels of FGRS for MD and AD, the overall FGRS profile differed considerably from MD and AD. ADHD FGRS scores were substantially elevated in AUD and DUD. FGRS scores for BD, OCD, AN, ASD, ADHD, and especially SZ were relatively disorder-specific while genetic risk for MD and AD had more generalized effects. The levels of FGRS for BMI, coronary artery disease, and educational attainment across our disorders replicated prior associations found using molecular genetic methods. All diagnostic categories examined had elevated FGRS for many disorders producing, for each condition, an informative FGRS profile. Using a novel method which approximates, from pedigree data, aggregate genetic risk, we have replicated and extended prior insights into the structure of genetic risk factors for key psychiatric illnesses.
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| 5020. |
- Kendler, Kenneth S., et al.
(författare)
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The predictive effect of family genetic risk scores as an indirect measure of causal effects of one disorder on another
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Ingår i: Psychological Medicine. - 0033-2917.
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Tidskriftsartikel (refereegranskat)abstract
- Background One potential cause of comorbidity is the direct causal effect of one disorder - A - on risk for subsequent onset of disorder B. Could genetic risk scores be utilized to test for such an effect? If disorder A causally impacts on risk for disorder B, then genetic risk for disorder A should be lower in cases of disorder A with v. without a prior onset of B. Methods In all individuals (n = 905 736) born in Sweden from 1980 to 1990, from six psychiatric and drug use disorders (major depression, anxiety disorders, alcohol use disorder, drug use disorder, bipolar disorder, and schizophrenia), we formed 14 pairs of disorders A and B. In these pairs, we compared, using Cox proportional hazards models, the predictive effect of the familial-genetic risk score (FGRS) for disorder B in those who had v. had not had a prior onset of disorder A. Results In all pairs, the impact of the FGRS for disorder B was significantly stronger in cases without v. with a prior history of disorder A. These effects were similar across sex, stable across levels of FGRS and not likely due to clinician bias. In many of our disorder pairs, previous clinical studies suggest a mechanism for a causal effect of disorder A on B. Conclusions Our findings provide indirect evidence that the occurrence of one psychiatric or substance use disorder often has a causal effect on risk for subsequent disorders. This mechanism may substantially contribute to the widespread comorbidity among psychiatric conditions.
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