| 1. |
- Amare, Azmeraw, et al.
(författare)
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Association of Polygenic Score and the involvement of Cholinergic and Glutamatergic Pathways with Lithium Treatment Response in Patients with Bipolar Disorder.
- 2023
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Ingår i: Research square. - : Research Square Platform LLC.
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Tidskriftsartikel (refereegranskat)abstract
- Lithium is regarded as the first-line treatment for bipolar disorder (BD), a severe and disabling mental disorder that affects about 1% of the population worldwide. Nevertheless, lithium is not consistently effective, with only 30% of patients showing a favorable response to treatment. To provide personalized treatment options for bipolar patients, it is essential to identify prediction biomarkers such as polygenic scores. In this study, we developed a polygenic score for lithium treatment response (Li+PGS) in patients with BD. To gain further insights into lithium's possible molecular mechanism of action, we performed a genome-wide gene-based analysis. Using polygenic score modeling, via methods incorporating Bayesian regression and continuous shrinkage priors, Li+PGS was developed in the International Consortium of Lithium Genetics cohort (ConLi+Gen: N=2,367) and replicated in the combined PsyCourse (N=89) and BipoLife (N=102) studies. The associations of Li+PGS and lithium treatment response - defined in a continuous ALDA scale and a categorical outcome (good response vs. poor response) were tested using regression models, each adjusted for the covariates: age, sex, and the first four genetic principal components. Statistical significance was determined at P<����������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������.
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| 2. |
- Amare, Azmeraw T, et al.
(författare)
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Association of polygenic score and the involvement of cholinergic and glutamatergic pathways with lithium treatment response in patients with bipolar disorder.
- 2023
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Ingår i: Molecular psychiatry. - 1476-5578. ; 28, s. 5251-5261
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Tidskriftsartikel (refereegranskat)abstract
- Lithium is regarded as the first-line treatment for bipolar disorder (BD), a severe and disabling mental healthdisorder that affects about 1% of the population worldwide. Nevertheless, lithium is not consistently effective, with only 30% of patients showing a favorable response to treatment. To provide personalized treatment options for bipolar patients, it is essential to identify prediction biomarkers such as polygenic scores. In this study, we developed a polygenic score for lithium treatment response (Li+PGS) in patients with BD. To gain further insights into lithium's possible molecular mechanism of action, we performed a genome-wide gene-based analysis. Using polygenic score modeling, via methods incorporating Bayesian regression and continuous shrinkage priors, Li+PGS was developed in the International Consortium of Lithium Genetics cohort (ConLi+Gen: N=2367) and replicated in the combined PsyCourse (N=89) and BipoLife (N=102) studies. The associations of Li+PGS and lithium treatment response - defined in a continuous ALDA scale and a categorical outcome (good response vs. poor response) were tested using regression models, each adjusted for the covariates: age, sex, and the first four genetic principal components. Statistical significance was determined at P<0.05. Li+PGS was positively associated with lithium treatment response in the ConLi+Gen cohort, in both the categorical (P=9.8×10-12, R2=1.9%) and continuous (P=6.4×10-9, R2=2.6%) outcomes. Compared to bipolar patients in the 1st decile of the risk distribution, individuals in the 10th decile had 3.47-fold (95%CI: 2.22-5.47) higher odds of responding favorably to lithium. The results were replicated in the independent cohorts for the categorical treatment outcome (P=3.9×10-4, R2=0.9%), but not for the continuous outcome (P=0.13). Gene-based analyses revealed 36 candidate genes that are enriched in biological pathways controlled by glutamate and acetylcholine. Li+PGS may be useful in the development of pharmacogenomic testing strategies by enabling a classification of bipolar patients according to their response to treatment.
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| 3. |
- Amare, Azmeraw T, et al.
(författare)
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Association of Polygenic Score for Schizophrenia and HLA Antigen and Inflammation Genes With Response to Lithium in Bipolar Affective Disorder: A Genome-Wide Association Study.
- 2018
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Ingår i: JAMA psychiatry. - : American Medical Association (AMA). - 2168-6238 .- 2168-622X. ; 75:1, s. 65-74
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Tidskriftsartikel (refereegranskat)abstract
- Lithium is a first-line mood stabilizer for the treatment of bipolar affective disorder (BPAD). However, the efficacy of lithium varies widely, with a nonresponse rate of up to 30%. Biological response markers are lacking. Genetic factors are thought to mediate treatment response to lithium, and there is a previously reported genetic overlap between BPAD and schizophrenia (SCZ).To test whether a polygenic score for SCZ is associated with treatment response to lithium in BPAD and to explore the potential molecular underpinnings of this association.A total of 2586 patients with BPAD who had undergone lithium treatment were genotyped and assessed for long-term response to treatment between 2008 and 2013. Weighted SCZ polygenic scores were computed at different P value thresholds using summary statistics from an international multicenter genome-wide association study (GWAS) of 36989 individuals with SCZ and genotype data from patients with BPAD from the Consortium on Lithium Genetics. For functional exploration, a cross-trait meta-GWAS and pathway analysis was performed, combining GWAS summary statistics on SCZ and response to treatment with lithium. Data analysis was performed from September 2016 to February 2017.Treatment response to lithium was defined on both the categorical and continuous scales using the Retrospective Criteria of Long-Term Treatment Response in Research Subjects with Bipolar Disorder score. The effect measures include odds ratios and the proportion of variance explained.Of the 2586 patients in the study (mean [SD] age, 47.2 [13.9] years), 1478 were women and 1108 were men. The polygenic score for SCZ was inversely associated with lithium treatment response in the categorical outcome, at a threshold P<5×10-2. Patients with BPAD who had a low polygenic load for SCZ responded better to lithium, with odds ratios for lithium response ranging from 3.46 (95% CI, 1.42-8.41) at the first decile to 2.03 (95% CI, 0.86-4.81) at the ninth decile, compared with the patients in the 10th decile of SCZ risk. In the cross-trait meta-GWAS, 15 genetic loci that may have overlapping effects on lithium treatment response and susceptibility to SCZ were identified. Functional pathway and network analysis of these loci point to the HLA antigen complex and inflammatory cytokines.This study provides evidence for a negative association between high genetic loading for SCZ and poor response to lithium in patients with BPAD. These results suggest the potential for translational research aimed at personalized prescribing of lithium.
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| 4. |
- Axfors, Cathrine, et al.
(författare)
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Preferences for Gender Affirming Treatment and Associated Factors Among Transgender People in Sweden
- 2023
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Ingår i: Sexuality Research & Social Policy. - : Springer Nature. - 1868-9884 .- 1553-6610. ; 20:2, s. 479-490
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Tidskriftsartikel (refereegranskat)abstract
- IntroductionGender affirming surgery of primary and/or secondary sex characteristics has been shown to alleviate gender dysphoria. A descriptive snapshot of current treatment preferences is useful to understand the needs of the transgender population seeking health care. This study aimed to describe preferences for gender affirming treatment, and their correlates, among individuals seeking health care for gender dysphoria in Sweden after major national legislative reforms.MethodsCross-sectional study where transgender patients (n = 232) recruited from all six Gender Dysphoria centers in Sweden 2016–2019, answered a survey on treatment preferences and sociodemographic, health, and gender identity-related information during the same time-period. Factors associated with preferring top surgery (breast augmentation or mastectomy), genital surgery, and other surgery (e.g., facial surgery) were examined in univariable and multivariable regression analyses in the 197 people without prior such treatment. Main study outcomes were preferences for feminizing or masculinizing hormonal and surgical gender affirming treatment.ResultsThe proportion among birth assigned male and assigned female patients preferring top surgery was 55.6% and 88.7%, genital surgery 88.9% and 65.7%, and other surgery (e.g., facial surgery) 85.6% and 22.5%, respectively. Almost all participants (99.1%) wanted or had already received hormonal treatment and most (96.7%) wished for some kind of surgical treatment; 55.0% wanted both top and genital surgery. Preferring a binary pronoun (he/she) and factors indicating more severe gender incongruence were associated with a greater wish for surgical treatment. Participants with somatic comorbidities were less likely to want genital surgery, while aF with lacking social support were less likely to want internal genital surgery, in the multivariable analyses.ConclusionsIn this sample of Swedish young adults seeking health care for gender dysphoria, preferences for treatment options varied according to perceived gender identity.Policy ImplicationsThe study fndings underline the need for individualized care and fexible gender afrming treatmentoptions. The role of somatic comorbidities should be further explored, and support should be ofered to transgender peoplein need. There is an unmet need for facial surgery among aM
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| 5. |
- Backlund, Lena, et al.
(författare)
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Cognitive manic symptoms associated with the P2RX7 gene in bipolar disorder.
- 2011
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Ingår i: Bipolar disorders. - : Wiley. - 1399-5618 .- 1398-5647. ; 13:5-6, s. 500-8
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Tidskriftsartikel (refereegranskat)abstract
- Several genetic loci have been suggested to be associated with bipolar disorder but results have been inconsistent. Studying associations between bipolar symptoms and candidate genes may better expose this relationship. Here we investigate the association between bipolar key symptoms and the P2RX7 gene.
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| 6. |
- Bejerot, Susanne, 1955-, et al.
(författare)
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Evidence-Based Brief Obsessive-Compulsive Scale
- 2017
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Ingår i: Journal of Central Nervous System Disease. - : Sage Publications. - 1179-5735. ; 9
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 7. |
- Bejerot, Susanne, 1955-, et al.
(författare)
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The Brief Obsessive-Compulsive Scale (BOCS) : a self-report scale for OCD and obsessive-compulsive related disorders
- 2014
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Ingår i: Nordic Journal of Psychiatry. - : Informa Healthcare. - 0803-9488 .- 1502-4725. ; 68:8, s. 549-559
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Tidskriftsartikel (refereegranskat)abstract
- Background: The Brief Obsessive Compulsive Scale (BOCS), derived from the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) and the children's version (CY-BOCS), is a short self-report tool used to aid in the assessment of obsessive-compulsive symptoms and diagnosis of obsessive-compulsive disorder (OCD). It is widely used throughout child, adolescent and adult psychiatry settings in Sweden but has not been validated up to date.Aim: The aim of the current study was to examine the psychometric properties of the BOCS amongst a psychiatric outpatient population.Method: The BOCS consists of a 15-item Symptom Checklist including three items (hoarding, dysmorphophobia and self-harm) related to the DSM-5 category "Obsessive-compulsive related disorders", accompanied by a single six-item Severity Scale for obsessions and compulsions combined. It encompasses the revisions made in the Y-BOCS-II severity scale by including obsessive-compulsive free intervals, extent of avoidance and excluding the resistance item. 402 adult psychiatric outpatients with OCD, attention-deficit/hyperactivity disorder, autism spectrum disorder and other psychiatric disorders completed the BOCS.Results: Principal component factor analysis produced five subscales titled "Symmetry", "Forbidden thoughts", "Contamination", "Magical thoughts" and "Dysmorphic thoughts". The OCD group scored higher than the other diagnostic groups in all subscales (P < 0.001). Sensitivities, specificities and internal consistency for both the Symptom Checklist and the Severity Scale emerged high (Symptom Checklist: sensitivity = 85%, specificities = 62-70% Cronbach's alpha = 0.81; Severity Scale: sensitivity = 72%, specificities = 75-84%, Cronbach's alpha = 0.94).Conclusions: The BOCS has the ability to discriminate OCD from other non-OCD related psychiatric disorders. The current study provides strong support for the utility of the BOCS in the assessment of obsessive-compulsive symptoms in clinical psychiatry.
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| 8. |
- Butwicka, Agnieszka, et al.
(författare)
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Association of Childhood-Onset Inflammatory Bowel Disease With Risk of Psychiatric Disorders and Suicide Attempt
- 2019
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Ingår i: JAMA pediatrics. - : American Medical Association. - 2168-6203 .- 2168-6211. ; 173:10, s. 969-978
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Tidskriftsartikel (refereegranskat)abstract
- Importance: Inflammatory bowel disease (IBD) has been associated with psychiatric morbidity in adults, although previous studies have not accounted for familial confounding. In children, IBD has an even more severe course, but the association between childhood-onset IBD and psychiatric morbidity remains unclear.Objective: To examine the risk of psychiatric morbidity in individuals with childhood-onset IBD, controlling for potential confounding shared between siblings.Design, Setting, and Participants: A population-based cohort study was conducted using data from the Swedish national health care and population registers of all children younger than 18 years born from 1973 to 2013. The study included 6464 individuals with a diagnosis of childhood-onset IBD (3228 with ulcerative colitis, 2536 with Crohn disease, and 700 with IBD unclassified) who were compared with 323 200 matched reference individuals from the general population and 6999 siblings of patients with IBD. Cox proportional hazards regression was used to estimate hazard ratios (HRs) with 95% CIs. Statistical analysis was performed from January 1, 1973, to December 1, 2013.Main Outcomes and Measures: The primary outcome was any psychiatric disorder and suicide attempt. Secondary outcomes were the following specific psychiatric disorders: psychotic, mood, anxiety, eating, personality, and behavioral disorders; substance misuse; attention-deficit/hyperactivity disorder; autism spectrum disorders; and intellectual disability.Results: The study included 6464 individuals with a diagnosis of childhood-onset IBD (2831 girls and 3633 boys; mean [SD] age at diagnosis of IBD, 13 [4] years). During a median follow-up time of 9 years, 1117 individuals with IBD (17.3%) received a diagnosis of any psychiatric disorder (incidence rate, 17.1 per 1000 person-years), compared with 38 044 of 323 200 individuals (11.8%) in the general population (incidence rate, 11.2 per 1000 person-years), corresponding to an HR of 1.6 (95% CI, 1.5-1.7), equaling 1 extra case of any psychiatric disorder per 170 person-years. Inflammatory bowel disease was significantly associated with suicide attempt (HR, 1.4; 95% CI, 1.2-1.7) as well as mood disorders (HR, 1.6; 95% CI, 1.4-1.7), anxiety disorders (HR, 1.9; 95% CI, 1.7-2.0) eating disorders (HR, 1.6; 95% CI, 1.3-2.0), personality disorders (HR, 1.4; 95% CI, 1.1-1.8), attention-deficit/hyperactivity disorder (HR, 1.2; 95% CI, 1.1-1.4), and autism spectrum disorders (HR, 1.4; 95% CI, 1.1-1.7) Results were similar for boys and girls. Hazard ratios for any psychiatric disorder were highest in the first year of follow-up but remained statistically significant after more than 5 years. Psychiatric disorders were particularly common for patients with very early-onset IBD (<6 years) and for patients with a parental psychiatric history. Results were largely confirmed by sibling comparison, with similar estimates noted for any psychiatric disorder (HR, 1.6; 95% CI, 1.5-1.8) and suicide attempt (HR, 1.7; 95% CI, 1.2-2.3).Conclusions and Relevance: Overall, childhood-onset IBD was associated with psychiatric morbidity, confirmed by between-sibling results. Particularly concerning is the increased risk of suicide attempt, suggesting that long-term psychological support be considered for patients with childhood-onset IBD.
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| 9. |
- Butwicka, Agnieszka, et al.
(författare)
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Celiac disease is associated with childhood psychiatric disorders : A Population-Based Study
- 2017
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Ingår i: Journal of Pediatrics. - : Elsevier. - 0022-3476 .- 1097-6833. ; 184, s. 87-93.e1
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: To determine the risk of future childhood psychiatric disorders in celiac disease, assess the association between previous psychiatric disorders and celiac disease in children, and investigate the risk of childhood psychiatric disorders in siblings of celiac disease probands.STUDY DESIGN: This was a nationwide registry-based matched cohort study in Sweden with 10 903 children (aged <18 years) with celiac disease and 12 710 of their siblings. We assessed the risk of childhood psychiatric disorders (any psychiatric disorder, psychotic disorder, mood disorder, anxiety disorder, eating disorder, psychoactive substance misuse, behavioral disorder, attention-deficit hyperactivity disorder [ADHD], autism spectrum disorder [ASD], and intellectual disability). HRs of future psychiatric disorders in children with celiac disease and their siblings was estimated by Cox regression. The association between previous diagnosis of a psychiatric disorder and current celiac disease was assessed using logistic regression.RESULTS: Compared with the general population, children with celiac disease had a 1.4-fold greater risk of future psychiatric disorders. Childhood celiac disease was identified as a risk factor for mood disorders, anxiety disorders, eating disorders, behavioral disorders, ADHD, ASD, and intellectual disability. In addition, a previous diagnosis of a mood, eating, or behavioral disorder was more common before the diagnosis of celiac disease. In contrast, siblings of celiac disease probands were at no increased risk of any of the investigated psychiatric disorders.CONCLUSIONS: Children with celiac disease are at increased risk for most psychiatric disorders, apparently owing to the biological and/or psychological effects of celiac disease.
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| 10. |
- Butwicka, Agnieszka, et al.
(författare)
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Hypospadias and increased risk for neurodevelopmental disorders
- 2014
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Ingår i: Journal of Child Psychology and Psychiatry. - Stockholm : Karolinska Institutet, Dept of Medical Epidemiology and Biostatistics. - 0021-9630 .- 1469-7610.
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Hypospadias (aberrant opening of the urethra on the underside of the penis) occurs in 1 per 300 newborn boys. It has been previously unknown whether this common malformation is associated with increased psychiatric morbidity later in life. Studies of individuals with hypospadias also provide an opportunity to examine whether difference in androgen signaling is related to neurodevelopmental disorders. To elucidate the mechanisms behind a possible association, we also studied psychiatric outcomes among brothers of the hypospadias patients. METHODS: Registry study within a national cohort of all 9,262 males with hypospadias and their 4,936 healthy brothers born in Sweden between 1973 and 2009. Patients with hypospadias and their brothers were matched with controls by year of birth and county. The following outcomes were evaluated (1) any psychiatric (2) psychotic, (3) mood, (4) anxiety, (5) eating, and (6) personality disorders, (7) substance misuse, (8) attention-deficit hyperactivity disorder (ADHD), (9) autism spectrum disorders (ASD), (10) intellectual disability, and (11) other behavioral/emotional disorders with onset in childhood. RESULTS: Patients with hypospadias were more likely to be diagnosed with intellectual disability (OR 3.2; 95% CI 2.8-3.8), ASD (1.4; 1.2-1.7), ADHD (1.5; 1.3-1.9), and behavioral/emotional disorders (1.4; 1.2-1.6) compared with the controls. Brothers of patients with hypospadias had an increased risk of ASD (1.6; 1.3-2.1) and other behavioral/emotional disorders with onset in childhood (1.2; 0.9-1.5) in comparison to siblings of healthy individuals. A slightly higher, although not statistically significant, risk was found for intellectual disability (1.3; 1.0-1.9). No relation between other psychiatric diagnosis and hypospadias was found. CONCLUSIONS: This is the first study to identify an increased risk for neurodevelopmental disorders in patients with hypospadias, as well as an increased risk for ASD in their brothers, suggesting a common familial (genetic and/or environmental) liability.
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| 11. |
- Butwicka, Agnieszka, et al.
(författare)
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Increased Risk for Substance Use-Related Problems in Autism Spectrum Disorders : A Population-Based Cohort Study
- 2017
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Ingår i: Journal of autism and developmental disorders. - New York, USA : Springer. - 0162-3257 .- 1573-3432. ; 47:1, s. 80-89
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Tidskriftsartikel (refereegranskat)abstract
- Despite limited and ambiguous empirical data, substance use-related problems have been assumed to be rare among patients with autism spectrum disorders (ASD). Using Swedish population-based registers we identified 26,986 individuals diagnosed with ASD during 1973-2009, and their 96,557 non-ASD relatives. ASD, without diagnosed comorbidity of attention deficit hyperactivity disorder (ADHD) or intellectual disability, was related to a doubled risk of substance use-related problems. The risk of substance use-related problems was the highest among individuals with ASD and ADHD. Further, risks of substance use-related problems were increased among full siblings of ASD probands, half-siblings and parents. We conclude that ASD is a risk factor for substance use-related problems. The elevated risks among relatives of probands with ASD suggest shared familial (genetic and/or shared environmental) liability.
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| 12. |
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| 13. |
- Butwicka, Agnieszka, et al.
(författare)
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Risks of psychiatric disorders and suicide attempts in children and adolescents with type 1 diabetes : a population-based cohort study
- 2015
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Ingår i: Diabetes Care. - Stockholm : Karolinska Institutet, Dept of Medical Epidemiology and Biostatistics. - 0149-5992 .- 1935-5548.
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To assess the risk of psychiatric disorders and suicide attempts in children with type 1 diabetes and their healthy siblings. Research Design and Methods: We performed a population-based case cohort study of individuals born in Sweden between 1973 and 2009. Children with type 1 diabetes (n=17,122) and their healthy siblings (n=18,847) were identified and followed until their 18th birthday. Their risk of psychiatric disorders was compared with matched controls. Results: The risk of psychiatric morbidity in children with type 1 diabetes compared to the general population was tripled within 6 months after the onset of diabetes (hazard ratio, HR 3.0, 95% confidence interval, CI 2.7-3.4) and doubled within the total observation period (HR 2.1, CI 2.0-2.2). An increased risk was noted in suicide attempts (HR 1.7, CI 1.4-2.0) and in most categories of psychiatric disorders. The risk of psychiatric disorders in probands declined from HR 2.7 (CI 2.2-3.3) for those in the cohort born 1973-1986 to 1.9 (CI 1.8-2.0) in those born 1997-2009. The risk for any psychiatric disorders among siblings of patients with type 1 diabetes was estimated to be HR 1.1 (CI 1.0-1.1) and there was no increased risk in any of the specific category of disorders. Conclusions: Children with type 1 diabetes are at high risk of psychiatric disorders, which seems to be a consequence of the disease rather than due to a common familial etiology. The results support recommendations on comprehensive mental health surveillance in children with type 1 diabetes, especially in recently diagnosed children.
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| 14. |
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| 15. |
- Coombes, Brandon J, et al.
(författare)
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Association of Attention-Deficit/Hyperactivity Disorder and Depression Polygenic Scores with Lithium Response: A Consortium for Lithium Genetics Study.
- 2021
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Ingår i: Complex psychiatry. - : S. Karger AG. - 2673-3005 .- 2673-298X. ; 7:3-4, s. 80-89
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Tidskriftsartikel (refereegranskat)abstract
- Response to lithium varies widely between individuals with bipolar disorder (BD). Polygenic risk scores (PRSs) can uncover pharmacogenomics effects and may help predict drug response. Patients (N = 2,510) with BD were assessed for long-term lithium response in the Consortium on Lithium Genetics using the Retrospective Criteria of Long-Term Treatment Response in Research Subjects with Bipolar Disorder score. PRSs for attention-deficit/hyperactivity disorder (ADHD), major depressive disorder (MDD), and schizophrenia (SCZ) were computed using lassosum and in a model including all three PRSs and other covariates, and the PRS of ADHD (β = -0.14; 95% confidence interval [CI]: -0.24 to -0.03; p value = 0.010) and MDD (β = -0.16; 95% CI: -0.27 to -0.04; p value = 0.005) predicted worse quantitative lithium response. A higher SCZ PRS was associated with higher rates of medication nonadherence (OR = 1.61; 95% CI: 1.34-1.93; p value = 2e-7). This study indicates that genetic risk for ADHD and depression may influence lithium treatment response. Interestingly, a higher SCZ PRS was associated with poor adherence, which can negatively impact treatment response. Incorporating genetic risk of ADHD, depression, and SCZ in combination with clinical risk may lead to better clinical care for patients with BD.
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| 16. |
- Engberg, Hedvig, et al.
(författare)
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Congenital adrenal hyperplasia and risk for psychiatric disorders in girls and women born between 1915 and 2010: A total population study.
- 2015
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Ingår i: Psychoneuroendocrinology. - : Elsevier BV. - 1873-3360 .- 0306-4530. ; 60, s. 195-205
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Tidskriftsartikel (refereegranskat)abstract
- Congenital adrenal hyperplasia (CAH) is a chronic condition and individuals are exposed to elevated androgen levels in utero as a result of the endogenous cortisol deficiency. Prenatal androgen exposure has been suggested to influence mental health, but population based studies on psychiatric morbidity among girls and women with CAH are lacking. Therefore, we performed a cohort study based on Swedish nationwide registers linked with the national CAH register. Girls and women with CAH due to 21-hydroxylase deficiency (n=335) born between January 1915 and January 2010 were compared with aged-matched female (n=33500) and male controls (n=33500). Analyses were stratified by phenotype [salt wasting (SW), simple virilizing (SV), and non-classical type (NC)] and by CYP21A2 genotype subgroups (null, I2splice, I172N, and P30L). Results are presented as estimated risks (OR, 95%CI) of psychiatric disorders among girls and women with CAH compared with age-matched controls. Any psychiatric diagnoses were more common in CAH females compared with female and male population controls [1.9 (1.4-2.5), and 2.2 (1.7-2.9)]. In particular, the risk of alcohol misuse was increased compared with female and male population controls [2.8 (1.7-4.7) and 2.1 (1.2-3.5)], and appeared most common among the girls and women with the most severe null genotype [6.7 (2.6-17.8)]. The risk of stress and adjustment disorders was doubled compared with female population controls [2.1 (1.3-3.6)]. Girls and women with CAH have an increased risk of psychiatric disorders in general and substance use disorders in particular compared with unexposed females, with the highest risk among those with the most severe genotype. Prenatal androgen exposure and deficient endogenous cortisol and/or adrenaline production may provide explanations for these findings, but other factors related to CAH cannot be excluded.
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| 17. |
- Falck, Felicitas A O K, et al.
(författare)
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Subjective Experiences of Pregnancy, Delivery, and Nursing in Transgender Men and Non-Binary Individuals : A Qualitative Analysis of Gender and Mental Health Concerns
- 2024
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Ingår i: Archives of Sexual Behavior. - 0004-0002 .- 1573-2800. ; 53:5, s. 1981-2002
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Tidskriftsartikel (refereegranskat)abstract
- Studies of how gender-diverse individuals experience pregnancy, childbirth, and nursing remain few, mainly focus on the US and contain scarce information about mental health concerns peri-partum. This hinders informed reproductive health decisions and counseling. We used in-depth interviews to examine how gestational gender-diverse individuals in Sweden experience the process of planning and undergoing pregnancy, delivery, and nursing. In total, 12 participants, identifying on the masculine side of the gender spectrum or as non-binary, who had attended Swedish antenatal care and delivered a live birth, were included in the study. Data were analyzed using qualitative thematic content analysis. The analysis resulted in one overarching theme: sustaining gender congruence during pregnancy and three main categories: (1) considering pregnancy; (2) undergoing pregnancy and childbirth; and (3) postnatal reflections. The association between childbearing and being regarded as female permeated narratives. Participants renegotiated the feminine connotations of pregnancy, accessed gender-affirming treatment, and concealed their pregnancy to safeguard their gender congruence. Mis-gendering and breast enlargement triggered gender dysphoria. Social judgment, loneliness, information shortages, hormonal influence and cessation of testosterone increased gender dysphoria and strained their mental health. Depression exacerbated gender dysphoria and made it harder to claim one's gender identity. Dissociation was used to handle a feminized body, vaginal delivery, and nursing. Pregnancy was easier to envision and handle after masculinizing gender-affirming treatments. The results deepen the understanding of gender dysphoria and may be used to inform reproductive counseling and healthcare development. Research outcomes on mental health concerns provide a basis for further research.
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| 18. |
- Falck, Felicitas, et al.
(författare)
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Undergoing pregnancy and childbirth as trans masculine in Sweden : Experiencing and dealing with structural discrimination, gender norms and microaggressions in antenatal care, delivery and gender clinics
- 2021
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Ingår i: International Journal of Transgender Health. - : Taylor & Francis. - 2689-5269 .- 2689-5277. ; 22:1-2, s. 42-53
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Tidskriftsartikel (refereegranskat)abstract
- Background: A sterilization requirement to change legal gender was removed from Swedish law in 2013, facilitating pregnancy in trans masculine individuals. The limited number of studies investigating pregnancy and childbirth among trans masculine individuals indicate increased gender dysphoria and negative experiences of pre- and post-natal healthcare, highlighting a need to improve care. Research focusing on Europe or contexts where sterilization to change legal gender was previously required by national law remains minimal.Aims: This study aimed to investigate how trans masculine individuals experience healthcare encounters in connection with pregnancy, delivery and nursing, in a setting where mandatory sterilization to change legal gender was recently removed.Methods: In-depth face-to-face interviews were conducted with 12 trans masculine individuals who attended Swedish prenatal care and delivered a child after the law on legal gender recognition was amended. Thematic content analysis was used.Results: Providers in gender clinics, antenatal care and delivery were perceived to regard a masculine gender identity and pregnancy as incompatible. The main categories encompassed expectations and experiences of pregnancy related care and participant responses to it. Participants took charge of their care to ensure that their needs were fulfilled. The quality of care was inconsistent.Discussion: A lack of knowledge, narrow gender norms and the legacy of the former legal sterility requirement limited access to diagnostic evaluation of gender dysphoria, information on reproduction and gender-affirming treatment. Medical safety during pregnancy, childbirth and nursing was impeded, gender dysphoria increased, and participants experienced minority stress. Attempts to avoid microaggressions guided healthcare encounters and birth wishes. Navigating healthcare required considerable attention, personal resources and energy, leaving particularly vulnerable individuals at risk of a lower quality of care. The paper concludes with clinical recommendations.
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| 19. |
- Falhammar, Henrik, et al.
(författare)
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Increased cardiovascular and metabolic morbidity in patients with 21-hydroxylase deficiency : a Swedish population-based national cohort study
- 2015
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Ingår i: The Journal of Clinical Endocrinology & Metabolism. - Stockholm : Karolinska Institutet, Dept of Medical Epidemiology and Biostatistics. - 0021-972X. ; 100:9, s. 3520-3528
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Tidskriftsartikel (refereegranskat)abstract
- CONTEXT: Congenital adrenal hyperplasia (CAH) is lethal in its most severe forms if not treated with glucocorticoids. However, glucocorticoids may increase the risk of cardiovascular and metabolic morbidity. OBJECTIVE: This study aimed to study cardiovascular and metabolic morbidity in CAH. DESIGN, SETTING, AND PARTICIPANTS: Patients with CAH due to 21-hydroxylase deficiency (n = 588; >80% with known CYP21A2 mutations) were compared with controls matched for sex, year, and place of birth (n = 58 800). Data were obtained by linking national population-based registers. Subgroup analyses were performed regarding sex, clinical severity (salt wasting, simple virilizing, nonclassic), CYP21A2 genotype (null, I2 splice, I172N, P30L), and stratified by the introduction of neonatal screening, age groups, and nonobesity. MAIN OUTCOME MEASURES: To study cardiovascular and metabolic morbidity in CAH. RESULTS: In CAH, both any cardiovascular and metabolic disorders (OR [odds ratio], 3.9; 95% CI [confidence interval], 3.1-5.0), and cardiovascular disease (OR, 2.7; 95% CI, 1.9-3.9) were increased. Separate analyses of the individual diseases showed higher frequencies in CAH of hypertension, hyperlipidemia, atrial fibrillation, venous thromboembolism, obesity, diabetes (mainly type 2), obstructive sleep disorder, thyrotoxicosis, and hypothyroidism. Similar results were seen in the stratified groups. On the subgroup level, females were generally more affected (especially I172N and the nonclassic group), as were males with the null genotype. CONCLUSIONS: CAH was associated with excess cardiovascular and metabolic morbidity but the mechanism is not certain as the glucocorticoids were not assessed. Hypothyroidism and obesity may be an effect of close observation. However, more severe conditions were presumably detected equally in patients and controls. Screening for diabetes and other metabolic disorders that increase cardiovascular risk is important.
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| 20. |
- Falhammar, Henrik, et al.
(författare)
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Increased mortality in patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency
- 2014
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Ingår i: The Journal of Clinical Endocrinology & Metabolism. - Stockholm : Karolinska Institutet, Dept of Medical Epidemiology and Biostatistics. - 0021-972X .- 1945-7197.
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Tidskriftsartikel (refereegranskat)abstract
- Context: Reports on mortality in patients with congenital adrenal hyperplasia (CAH) are lacking. Objective: To study mortality and causes of death in CAH. Design, Setting and Participants: We studied patients with CAH (21-hydroxylase deficiency, n=588; CYP21A2 mutations known, >80%), and compared them with controls (n=58800). Data were derived through linkage of national population-based registers. Main Outcome Measures: Mortality and causes of death. Results: The mean age of death was 41.2±26.9 years in CAH patients and 47.7±27.7 years in controls (P<0.001). Among CAH patients 23 (3.9%) had deceased compared to 942 (1.6%) of controls. The hazard ratio (and 95% confidence interval) of death was 2.3(1.2-4.3) in CAH males and 3.5(2.0-6.0) in CAH females. Including only patients born 1952-2009, gave similar total results but only patients with salt-wasting or with unclear phenotype had an increased mortality. The causes of death in CAH patients were adrenal crisis (42%), cardiovascular (32%), cancer (16%), and suicide (10%). There were seven additional deaths in CAH individuals with incomplete or reused personal identification number that could not be analyzed using linkage of registers. Of the latter all except one were deceased before the introduction of neonatal screening in 1986 and most of them in the first weeks of life, probably in an adrenal crisis. Conclusions: CAH is a potentially lethal condition and was associated with excess mortality due to adrenal crisis. The salt-wasting phenotype seemed to have worse outcome also in children and adults due to adrenal crisis and not only before the introduction of neonatal screening.
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| 21. |
- Falhammar, Henrik, et al.
(författare)
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Increased psychiatric morbidity in men with congenital adrenal hyperplasia due to 21-hydroxylase deficiency.
- 2014
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Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 99:3
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Tidskriftsartikel (refereegranskat)abstract
- Context:Reports on psychiatric morbidity in males with congenital adrenal hyperplasia (CAH) are lacking.Objective:To study psychiatric disorders in CAH males.Design, Setting and Participants:We studied males with CAH (21-hydroxylase deficiency, n=253; CYP21A2 mutations known, n=185), and compared them with controls (n=25300). Data were derived through linkage of national population-based registers. We assessed the subgroups of CYP21A2 genotype separately (null, I2splice, I172N, P30L and NC), as well as outcomes before and after the introduction of national neonatal screening in 1986.Main Outcome Measures:Psychiatric disorders including attempted and completed suicide (suicidality).Results:Psychiatric disorders (suicidality not included), suicidality and alcohol misuse were increased in CAH males compared with controls (OR 1.5, 2.3, and 1.9; 95%CI 1.1-2.2, 1.1-5.0, and 1.0-3.5). In the null genotype group, no increased rates were seen; in the I2splice group, psychiatric disorders, personality disorders and alcohol misuse were increased; in the I172N group suicide attempt and drug misuse were increased; and in the P30L and NC group psychotic disorders were increased. In CAH males born before the neonatal screening, the rate of psychiatric disorders and suicidality were increased, but only psychotic disorders in those born after. There was no increased risk for any neurodevelopmental disorder.Conclusions:CAH males have an increased psychiatric morbidity. Psychiatric morbidity was not raised in the most severe genotype group. Late diagnosis of CAH may explain some of the findings. Those born before the introduction of neonatal screening were more affected, which may be explained by the higher age.
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| 22. |
- Frisén, Louise
(författare)
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Genetic studies of hypospadias
- 2002
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Hypospadias is defined as an abnormal opening of the urethra on the underside of the penis. It is a frequently found malformation with an incidence of 3 per 1000 males. The aim of this thesis was to identify genetic and environmental factors in the pathogenesis of hypospadias. For this purpose, a variety of genetic methods were used in a nation-wide material corresponding to half of all registered cases of hypospadias in Sweden. We identified 18 monozygotic twins discordant for hypospadias. In 16 of these, the twin with lowest birth weight was affected with hypospadias. This shows that low birth weight is important for hypospadias, regardless of the genetic constitution (paper 1). We investigated the familial rate and analyzed the association with low birth weight in 2138 families with at least one boy with hypospadias. There was a familial rate of 7% and a significant lower birth weight in cases with hypospadias compared with their respective brothers, used as controls (p=5x10-13). An increased frequency of dizygotic as well as monozygotic male-male twins was found, with a skewed distribution towards monozygotic twins. This paper (II) also includes a description of the ethnic background in the material and the distribution of phenotypes. A complex segregation analysis was performed to define the mode of inheritance in a material consisting of 2005 pedigrees. We found a best fit for the multifactorial model and a heritability of 0.99. This is interpreted as monogenic effects acting in some of the families but a multifactorial cause in the majority (paper III). A genome-wide linkage analysis based on a non-parametric affected relative pair method was used in 69 families. All available family members were genotyped with 360 polymorphic PCR based microsatellite markers with a mean interval of 9.5 cM. Five chromosomal regions reaching the level of suggestive significance were identified (paper IV). These need to be investigated further to identify hypospadias susceptibility genes. Linkage analysis and subsequent mutation analysis in a family with autosomal dominant inheritance of hypospadias revealed a novel mutation in the HOXA13 gene (paper V). This suggests the diagnosis of hand-foot-genital syndrome although the phenotype in this family is atypical compared with previously reported families. In this thesis, several lines of evidence suggesting genetic factors in the pathogenesis of hypospadias are presented, including the identification of five chromosomal regions in which genes for hypospadias are likely to be located and a novel mutation in the HOXA13 gene. It is also shown that low birth weight is an important risk factor for hypospadias.
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| 24. |
- Gotby, A. O., et al.
(författare)
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Congenital Adrenal Hyperplasia, Polycystic Ovary Syndrome and criminal behavior: A Swedish population based study
- 2015
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Ingår i: Psychiatry Research. - : Elsevier BV. - 0165-1781 .- 1872-7123. ; 229:3, s. 953-959
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Tidskriftsartikel (refereegranskat)abstract
- Both prenatal and circulating testosterone and other androgens have been suggested to influence the individual's propensity to commit crime, but empirical evidence is limited and inconsistent. Congenital Adrenal Hyperplasia (CAH) and Polycystic Ovary Syndrome (PCOS) are both hyperandrogenic conditions but with an important difference; whereas subjects with CAH are exposed to high concentrations of androgens in utero, women with PCOS are subjected to high androgens in adulthood. Comparing these groups can therefore yield important insights of androgenic effects on behavior. In the current study, information on medical diagnoses and convicted crimes were gathered from Swedish population-based registers. The associations between diagnoses of CAH or PCOS and any crime, violent crime or sex crime were estimated with conditional logistic regression. Results showed that CAH in women and men did not predict criminality, whereas an increased risk for any crime and violent crime was found in PCOS women. Our findings indicate that female hyperandrogenism in adulthood, but not prenatal hyperandrogenism, is associated with risk for criminal behavior. Further research into hyperandrogenic conditions holds opportunities to deepen our understanding of the etiology of crime and psychopathology. (C) 2015 Elsevier Ireland Ltd. All rights reserved.
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