[Show abstract][Hide abstract] 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.
Full-text · Article · Nov 2015 · The British Journal of Psychiatry
[Show abstract][Hide abstract] ABSTRACT: We aimed to provide unbiased estimates of familial risk and heritability of social anxiety disorder (SAD) and avoidant personality disorder (AVPD).
We identified 18 399 individuals diagnosed with SAD and 2673 with AVPD in the Swedish National Patient Register between 1997 and 2009. Risks (odds ratios; OR) for SAD in all biological and non-biological relatives of probands, compared to relatives of unaffected individuals were calculated. We also estimated the risks for AVPD in relatives of probands with SAD.
The risk for SAD among relatives of SAD probands increased proportionally to the degree of genetic relatedness. The risks for first-degree relatives [OR 4.74, 95% confidence interval (CI) 4.28–5.25] were significantly higher than for second-degree and third-degree relatives. Second-degree relatives (OR 2.30, 95% CI 2.01–2.63) had significantly higher risk than third-degree relatives (OR 1.72, 95% CI 1.52–1.94). Relatives at similar genetic distances had similar risks for SAD, despite different degrees of shared environment. Heritability was estimated to be approximately 56%. There were no significant sex differences in the familial patterns. The risk of AVPD in relatives of SAD probands was significantly elevated, even after excluding individuals with both diagnoses (first-degree OR 3.54, second-degree OR 2.20, third-degree OR 1.62). Non-biological relatives (spouses/partners) also had elevated risks for both SAD (OR 4.01) and AVPD (OR 3.85).
SAD clusters in families primarily due to genetic factors. SAD and AVPD are aetiologically related and may represent different expressions of the same vulnerability. The strong marital concordance observed in SAD/AVPD may indicate assortative mating but the exact mechanisms and implications require further investigation.
Full-text · Article · Sep 2014 · Psychological Medicine
[Show abstract][Hide abstract] ABSTRACT: Objectives
Darier disease is an autosomal dominant skin disorder caused by mutations in the ATPase, Ca++ transporting, cardiac muscle, slow twitch 2 (ATP2A2) gene and previously reported to cosegregate with bipolar disorder and schizophrenia in occasional pedigrees. It is, however, unknown whether these associations exist also in the general population, and the objective of this study was to examine this question.
We compared a national sample of individuals with Darier disease and their first-degree relatives with matched unexposed individuals from the general population and their first-degree relatives, respectively. To examine risks for bipolar disorder and schizophrenia, risk ratios and 95% confidence intervals (CIs) were estimated using conditional logistic regressions.
Individuals with Darier disease had a 4.3 times higher risk of being diagnosed with bipolar disorder (95% CI: 2.6–7.3) and a 2.3 times higher risk of being diagnosed with schizophrenia (95% CI: 1.1–5.2) than matched individuals from the general population. Relatives of individuals with Darier disease had a 1.6 times higher risk of having bipolar disorder (95% CI: 1.1–2.5) than relatives of matched individuals from the general population, but no increased risk of schizophrenia (risk ratio = 0.8, 95% CI: 0.4–1.8).
The association between Darier disease and bipolar disorder is manifest also in the population, and our data suggest that genetic variability within the ATP2A2 gene that causes Darier disease also confers susceptibility for bipolar disorder. The Darier-causing mutations merit additional attention in molecular genetic research on bipolar disorder.
[Show abstract][Hide abstract] ABSTRACT: Objective
To investigate whether persons with bipolar disorder and their siblings have leadership traits and are overrepresented in executive professions.MethodA nested case-control study based on longitudinal Swedish total population registries. Data from officer suitability interviews (n = 1 126 519), and information on occupations were collected. Bipolar patients (n = 68 915) and their healthy siblings were compared with controls.ResultsBipolar patients without comorbidity (pure; n = 22 980) were overrepresented in both the highest and lowest strata of officer suitability; their healthy siblings in the highest strata only. Patients with pure bipolar disorder were underrepresented in executive professions, whereas their siblings were overrepresented in these professions (particularly political professions). Patients with general bipolar disorder (including those with comorbidities) and their healthy siblings were overrepresented only in the lowest strata of officer suitability ratings. General bipolar patients were underrepresented in executive professions, whereas their siblings had similar rates of executive professions as controls. Adjusting results for IQ slightly attenuated point estimates, but resulted in pure bipolar patients and their siblings no longer being significantly overrepresented in superior strata of officer suitability, and siblings no longer being overrepresented in executive professions.Conclusion
Results support that traits associated with bipolar disorder are linked to superior leadership qualities.
Full-text · Article · Jun 2014 · Acta Psychiatrica Scandinavica
[Show abstract][Hide abstract] ABSTRACT: Background
We addressed if immaturity relative to peers reflected in birth month increases the likelihood of ADHD diagnosis and treatment.Methods
We linked nationwide Patient and Prescribed Drug Registers and used prospective cohort and nested case–control designs to study 6–69 year-old individuals in Sweden from July 2005 to December 2009 (Cohort 1). Cohort 1 included 56,263 individuals diagnosed with ADHD or ever used prescribed ADHD-specific medication. Complementary population-representative cohorts provided DSM-IV ADHD symptom ratings; parent-reported for 10,760 9-year-old twins born 1995–2000 from the CATSS study (Cohort 2) and self-reported for 6,970 adult twins age 20–47 years born 1959–1970 from the STAGE study (Cohort 3). We calculated odds ratios (OR:s) for ADHD across age for individuals born in November/December compared to January/February (Cohort 1). ADHD symptoms in Cohorts 2 and 3 were studied as a function of calendar birth month.ResultsADHD diagnoses and medication treatment were both significantly more common in individuals born in November/December versus January/February; peaking at ages 6 (OR: 1.8; 95% CI: 1.5–2.2) and 7 years (OR: 1.6; 95% CI: 1.3–1.8) in the Patient and Prescribed Drug Registers, respectively. We found no corresponding differences in parent- or self-reported ADHD symptoms by calendar birth month.Conclusion
Relative immaturity compared to class mates might contribute to ADHD diagnosis and pharmacotherapy despite absence of parallel findings in reported ADHD symptom loads by relative immaturity. Increased clinical awareness of this phenomenon may be warranted to decrease risk for imprecise diagnostics and treatment. We speculate that flexibility regarding age at school start according to individual maturity could reduce developmentally inappropriate demands on children and improve the precision of ADHD diagnostic practice and pharmacological treatment.
Full-text · Article · Mar 2014 · Journal of Child Psychology and Psychiatry
[Show abstract][Hide abstract] ABSTRACT: Data on familial recurrence rates of complex diseases such as multiple sclerosis give important hints to aetiological factors such as the importance of genes and environment. By linking national registries, we sought to avoid common limitations of clinic-based studies such as low numbers, poor representation of the population and selection bias. Through the Swedish Multiple Sclerosis Registry and a nationwide hospital registry, a total of 28 396 patients with multiple sclerosis were identified. We used the national Multi-Generation Registry to identify first and second degree relatives as well as cousins, and the Swedish Twin Registry to identify twins of patients with multiple sclerosis. Crude and age corrected familial risks were estimated for cases and found to be in the same range as previously published figures. Matched population-based controls were used to calculate relative risks, revealing lower estimates of familial multiple sclerosis risks than previously reported, with a sibling recurrence risk (λs = 7.1; 95% confidence interval: 6.42-7.86). Surprisingly, despite a well-established lower prevalence of multiple sclerosis amongst males, the relative risks were equal among maternal and paternal relations. A previously reported increased risk in maternal relations could thus not be replicated. An observed higher transmission rate from fathers to sons compared with mothers to sons suggested a higher transmission to offspring from the less prevalent sex; therefore, presence of the so-called 'Carter effect' could not be excluded. We estimated the heritability of multiple sclerosis using 74 757 twin pairs with known zygosity, of which 315 were affected with multiple sclerosis, and added information from 2.5 million sibling pairs to increase power. The heritability was estimated to be 0.64 (0.36-0.76), whereas the shared environmental component was estimated to be 0.01 (0.00-0.18). In summary, whereas multiple sclerosis is to a great extent an inherited trait, the familial relative risks may be lower than usually reported.
[Show abstract][Hide abstract] ABSTRACT: Schizophrenia, bipolar disorder, autism spectrum disorders and ADHD might be overrepresented in Klinefelter syndrome, but previous investigations have yielded inconclusive results.
We compared a national sample of 860 Klinefelter patients in Sweden with 86 000 matched population controls. To assess the risks of schizophrenia, bipolar disorder, autism spectrum disorder and ADHD in Klinefelter patients, we estimated odds ratios and 95% confidence intervals using conditional logistic regressions.
Klinefelter patients had almost four times higher risks of schizophrenia, odds ratio (OR) = 3.6, 95% confidence interval (CI) 2.0-6.7 and bipolar disorder (OR = 3.8, CI 1.8-7.6) and about six times higher risk of autism spectrum disorder (OR = 6.2, CI 4.0-9.4) and ADHD (OR = 5.6, CI 4.0-7.8).
The risk of psychosis, autism and ADHD is increased in Klinefelter patients. These findings indicate an X chromosome-related factor in the etiology of the studied psychiatric disorders, and may also have implications for treatment of patients with Klinefelter syndrome.
Full-text · Article · Oct 2013 · Journal of Psychiatric Research
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND: Attention-deficit hyperactivity disorder (ADHD) is associated with bipolar disorder and schizophrenia, and it has been suggested that combined bipolar disorder and ADHD is aetiologically distinct from the pure disorders. AIMS: To clarify whether ADHD shares genetic and environmental factors with bipolar disorder and schizophrenia. RESULTS: First-degree relatives of the ADHD proband group were at increased risk of both bipolar disorder (odds ratio (OR) = 1.84-2.54 for parents, offspring and full siblings) and schizophrenia (OR = 1.71-2.22 for parents, offspring and full siblings). The risks of bipolar disorder and schizophrenia among second-degree relatives were substantially lower than among full siblings. CONCLUSIONS: These findings suggest that the co-occurrence of ADHD and bipolar disorder as well as ADHD and schizophrenia is due to shared genetic factors, rather than representing completely aetiologically distinct subsyndromes.
Preview · Article · May 2013 · The British journal of psychiatry: the journal of mental science
[Show abstract][Hide abstract] ABSTRACT: IMPORTANCE Controlled family studies have consistently found that obsessive-compulsive disorder (OCD) aggregates in families but have typically relied on samples recruited from specialist clinics. Furthermore, previous studies could not disentangle genetic from environmental factors contributing to the observed familiality. OBJECTIVE To provide unbiased estimates of familial risk for and heritability of OCD at the population level. DESIGN AND SETTING Population-based, multigenerational, case-control family and twin studies using the Swedish National Patient Register, Multi-Generation Register, and Twin Register. PARTICIPANTS All individuals diagnosed as having OCD between January 1, 1969, and December 31, 2009 (n = 24 768) and all their available first-, second-, and third-degree relatives, as well as nonbiological relatives and matched general population control subjects. Twins (n = 16 383) were included from the population-based Twin Register. MAIN OUTCOME AND MEASURE The risk for OCD among relatives of OCD probands. RESULTS The risk for OCD among relatives of OCD probands increased proportionally to the degree of genetic relatedness. The risk for first-degree relatives was significantly higher than that for second- and third-degree and nonbiological relatives. Second-degree relatives had higher risk for OCD than third-degree relatives. Relatives at similar genetic distances had similar risks for OCD, despite different degrees of shared environment. Separate twin modeling analyses confirmed that familial risk for OCD was largely attributable to additive genetic factors (47%; 95% CI, 42%-52%), with no significant effect of shared environment. Nonbiological relatives (spouses or partners who have at least 1 child together) also had an elevated risk for OCD (odds ratio, 2.61; 95% CI, 1.99-3.42). Early-onset probands (3907 individuals; mean age, 13.7 years) had slightly (nonsignificantly) higher familial risk than the total sample, although this was substantially lower than previously reported. There were no significant sex differences in the familial pattern or heritability estimates. CONCLUSIONS AND RELEVANCE Obsessive-compulsive disorder clusters in families primarily due to genetic factors. Nonshared environmental factors are at least as important. The finding of possible assortative mating in OCD is intriguing and should be investigated further.
[Show abstract][Hide abstract] ABSTRACT: We previously demonstrated that patients with schizophrenia or bipolar disorder and their relatives are overrepresented in creative occupations. Here, we use a new dataset with a considerably larger sample of patients (n = 1,173,763) to survey other psychiatric diagnoses and to validate previous findings. The specific aims of this study were to i) investigate if creativity is associated with all psychiatric disorders or restricted to those with psychotic features, and ii) to specifically investigate authors in relationship to psychopathology. We conducted a nested case-control study using longitudinal Swedish total population registries, where the occurrence of creative occupations in patients and their non-diagnosed relatives was compared to that of matched population controls. Diagnoses included were schizophrenia, schizoaffective disorder, bipolar disorder, unipolar depression, anxiety disorders, alcohol abuse, drug abuse, autism, ADHD, anorexia nervosa, and completed suicide. Creative professions were defined as scientific and artistic occupations. Data were analyzed using conditional logistic regression. Except for bipolar disorder, individuals with overall creative professions were not more likely to suffer from investigated psychiatric disorders than controls. However, being an author was specifically associated with increased likelihood of schizophrenia, bipolar disorder, unipolar depression, anxiety disorders, substance abuse, and suicide. In addition, we found an association between creative professions and first-degree relatives of patients with schizophrenia, bipolar disorder, anorexia nervosa, and for siblings of patients with autism. We discuss the findings in relationship to some of the major components of creativity.
Full-text · Article · Oct 2012 · Journal of Psychiatric Research
[Show abstract][Hide abstract] ABSTRACT: CONTEXT The clinical and etiologic relation between autism spectrum disorders (ASDs) and schizophrenia is unclear. The degree to which these disorders share a basis in etiology has important implications for clinicians, researchers, and those affected by the disorders. OBJECTIVE To determine whether a family history of schizophrenia and/or bipolar disorder is a risk factor for ASD. DESIGN, SETTING, AND PARTICIPANTS We conducted a case-control evaluation of histories of schizophrenia or bipolar disorder in first-degree relatives of probands in 3 samples-population registers in Sweden, Stockholm County (in Sweden), and Israel. Probands met criteria for ASD, and affection status of parents and siblings for schizophrenia and bipolar disorder were established. RESULTS The presence of schizophrenia in parents was associated with an increased risk for ASD in a Swedish national cohort (odds ratio [OR], 2.9; 95% CI, 2.5-3.4) and a Stockholm County cohort (OR, 2.9; 95% CI, 2.0-4.1). Similarly, schizophrenia in a sibling was associated with an increased risk for ASD in a Swedish national cohort (OR, 2.6; 95% CI, 2.0-3.2) and an Israeli conscription cohort (OR, 12.1; 95% CI, 4.5-32.0). Bipolar disorder showed a similar pattern of associations but of lesser magnitude. CONCLUSIONS Findings from these 3 registers along with consistent findings from a similar study in Denmark suggest that ASD, schizophrenia, and bipolar disorder share common etiologic factors.
Full-text · Article · Jul 2012 · Archives of general psychiatry
[Show abstract][Hide abstract] ABSTRACT: There is a long-standing belief that creativity is coupled with psychopathology.
To test this alleged association and to investigate whether any such association is the result of environmental or genetic factors.
We performed a nested case-control study based on Swedish registries. The likelihood of holding a creative occupation in individuals who had received in-patient treatment for schizophrenia, bipolar disorder or unipolar depression between 1973 and 2003 and their relatives without such a diagnosis was compared with that of controls.
Individuals with bipolar disorder and healthy siblings of people with schizophrenia or bipolar disorder were overrepresented in creative professions. People with schizophrenia had no increased rate of overall creative professions compared with controls, but an increased rate in the subgroup of artistic occupations. Neither individuals with unipolar depression nor their siblings differed from controls regarding creative professions.
A familial cosegregation of both schizophrenia and bipolar disorder with creativity is suggested.
Full-text · Article · Jun 2011 · The British journal of psychiatry: the journal of mental science
[Show abstract][Hide abstract] ABSTRACT: The treatment for transsexualism is sex reassignment, including hormonal treatment and surgery aimed at making the person's body as congruent with the opposite sex as possible. There is a dearth of long term, follow-up studies after sex reassignment.
To estimate mortality, morbidity, and criminal rate after surgical sex reassignment of transsexual persons.
A population-based matched cohort study.
All 324 sex-reassigned persons (191 male-to-females, 133 female-to-males) in Sweden, 1973-2003. Random population controls (10:1) were matched by birth year and birth sex or reassigned (final) sex, respectively.
Hazard ratios (HR) with 95% confidence intervals (CI) for mortality and psychiatric morbidity were obtained with Cox regression models, which were adjusted for immigrant status and psychiatric morbidity prior to sex reassignment (adjusted HR [aHR]).
The overall mortality for sex-reassigned persons was higher during follow-up (aHR 2.8; 95% CI 1.8-4.3) than for controls of the same birth sex, particularly death from suicide (aHR 19.1; 95% CI 5.8-62.9). Sex-reassigned persons also had an increased risk for suicide attempts (aHR 4.9; 95% CI 2.9-8.5) and psychiatric inpatient care (aHR 2.8; 95% CI 2.0-3.9). Comparisons with controls matched on reassigned sex yielded similar results. Female-to-males, but not male-to-females, had a higher risk for criminal convictions than their respective birth sex controls.
Persons with transsexualism, after sex reassignment, have considerably higher risks for mortality, suicidal behaviour, and psychiatric morbidity than the general population. Our findings suggest that sex reassignment, although alleviating gender dysphoria, may not suffice as treatment for transsexualism, and should inspire improved psychiatric and somatic care after sex reassignment for this patient group.
[Show abstract][Hide abstract] ABSTRACT: The effect of genetic variants underlying atherosclerosis is thought to be mediated through intermediate phenotypes such as serum cholesterol levels. Localization of quantitative trait loci influencing levels of serum lipids and (apo)lipoproteins may aid in the search for determinants of susceptibility to atherosclerotic diseases. Since apolipoprotein A-I is the primary protein constituent of high-density lipoprotein, it is considered to be critical for the antiatherogenic effect of high-density lipoproteins. We describe here an effort to map loci influencing apolipoprotein A-I levels. Measurements of apolipoprotein A-I levels and genome scans with more than 1000 microsatellite markers were successfully performed in both members of 501 pairs of fraternal twins from Sweden. Variance component linkage analysis was undertaken to map quantitative trait loci. In the total study sample, two loci showed comparable suggestive evidence of linkage, 6p21-12 (LOD=2.4) and 12q23 (LOD=2.4). Sex-limited analyses revealed significant female-specific linkage at marker D15S156 on 15q11-13 (LOD=4.1). The loci on 12q and 15q in the present study confirm previously reported loci for apolipoprotein A-I, while the peak on chromosome 6p lends further support to a locus influencing several phenotypes related to atherosclerosis. Intriguingly, the presence of genes belonging to the phospholipase A2 superfamily under three out of four observed linkage peaks would lend some support to the view that this group of genes might collectively represent candidates as apolipoprotein A-I level regulators.
Full-text · Article · Apr 2008 · European Journal of HumanGenetics