[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.
Journal of psychiatric research 10/2013; · 3.72 Impact Factor
[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.
The British journal of psychiatry: the journal of mental science 05/2013; · 6.62 Impact Factor
[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.
Journal of psychiatric research 10/2012; · 3.72 Impact Factor
[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.
Archives of general psychiatry 07/2012; · 12.26 Impact Factor
[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.
The British journal of psychiatry: the journal of mental science 06/2011; 199(5):373-9. · 6.62 Impact Factor
[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.
PLoS ONE 01/2011; 6(2):e16885. · 3.73 Impact Factor