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Examines views on sex reassignment and attitudes towards transsexuals in Sweden. Possibility for transsexuals to undergo sexual reassignment; Support for the transsexual's right to marriage with the preferred sex and the right to raise children; Evidence on a more restrictive views among men and older group regarding the issue.

[Display omitted] • C1QA expression is reduced in prefrontal cortex tissue of individuals with schizophrenia. • C1QA brain co-expression networks do not exhibit genetic enrichment for schizophrenia independent of C4A. • Already during the first acute psychotic episode, cerebrospinal fluid C1qA protein levels are reduced in schizophrenia. Recent evidence has implicated complement component (C) 4A in excessive elimination of synapses in schizophrenia. C4A is believed to contribute to physiological synapse removal through signaling within the C1q initiated classical activation axis of the complement system. So far, a potential involvement of C1q in the pathophysiology of schizophrenia remains unclear. In this study, we first utilized large-scale gene expression datasets (n = 586 patients with schizophrenia and n = 986 controls) to observe lower C1QA mRNA expression in prefrontal cortex tissue of individuals with schizophrenia (P = 4.8x10-05), while C1QA seeded co-expression networks displayed no enrichment for schizophrenia risk variants beyond C4A. We then used targeted liquid chromatography-mass spectrometry (LS-MS) to measure cerebrospinal fluid (CSF) levels of C1qA in 113 individuals with first-episode psychosis (FEP), among which 66 individuals was later diagnosed with schizophrenia, and 87 healthy controls. CSF concentrations of C1qA were lower in individuals diagnosed with FEP (P = 0.0001), also after removing subjects with a short-term prescription of an antipsychotic agent (P = 0.0005). We conclude that C1q mRNA and protein levels are lower in schizophrenia and that further experimental studies are needed to understand the functional implications. [ABSTRACT FROM AUTHOR]

Background: Clinical guidelines recommend monitoring of creatinine and lithium throughout treatment with lithium. We here assessed the extent to which this occurs in healthcare in Sweden. Methods: This is an observational study of all adults with bipolar disorder starting lithium therapy in Stockholm, Sweden, during 2007–2018. The main outcome was monitoring of blood lithium and creatinine at therapy initiation and/or once annually. The secondary outcome was monitoring of calcium and thyroid‐stimulating hormone (TSH). Patients were followed up until therapy cessation, death, out‐migration, or to the end of 2018. Results: We identified 4428 adults with bipolar disorder who started lithium therapy and were followed up for up to 11 years. Their median age was 39 years, and 63% were women. The median duration on lithium therapy was 4.3 (IQR: 1.9–7.45) years, and the majority who discontinued therapy started another mood stabilizer soon after. Overall, 21% started lithium therapy without assessing the serum/plasma concentration of creatinine. The proportion of people who did not have both lithium and creatinine measured increased from 21% in the first year to 33% in the eleventh year. The proportion with annual testing for TSH or calcium was slightly lower. As few as 16% of patients had both lithium and creatinine tested once annually during their complete time on lithium. Conclusions: In a Swedish community sample, lithium and creatinine monitoring was inconsistent with guideline recommendations that call for measurement of annual biomarker levels. [ABSTRACT FROM AUTHOR]

Prior findings from genome-wide association studies (GWAS) have highlighted different loci for the mechanistic action of lithium. This may, in part, be due to different measures of lithium response and small sample sizes. In addition, past polygenic risk score analyses were only calculated using samples from ConLi+Gen. The aim of the present study is to report a much-enlarged University College London (UCL) sample of participants with bipolar disorder taking lithium and conduct GWAS meta-analyses with other compatible European samples. We report data from 1259 participants with BD recruited at University College London who had been treated with lithium. The data comes from three waves of genotyping on different arrays. The GWAS data from each array was analysed separately. Then we meta-analysed our GWAS results with the summary statistics from Song et al. and Hou et al. (ConLi+Gen), the two largest sets of GWAS on the European population to date. We conducted sign tests and fitted a one-factor model using Genomic Structural equation modelling (GSEM) to investigate potential response definition heterogeneity. We estimated SNP heritability for a good lithium response, and we conducted exploratory analyses based on the GWAS meta-analysis outputs as follow-up. Finally, schizophrenia and major depressive disorder PRSs were calculated in the samples to replicate past findings. We found no evidence for lithium response definition heterogeneity. SNP rs116927879 (A/G) was associated with a good lithium response at a genome-wide level of significance (p = 4.509 × 10-8), with a consistent effect across all cohorts. rs116927879 is located on chromosome 7 and maps to the protein coding gene ADCY1 and two pseudo-genes, GTF2IP13 and SEPT7P2. The eQTL and sQTL results suggested that rs116927879 genotypes may influence the expression and splicing of ADCY1 across different brain regions. We estimated the SNP heritability (h2) for a good lithium response as 20.3% and 15.6% for subjective/objective response definitions, respectively. We did not observe any genetic correlation or PRS association between the lithium response and schizophrenia or major depressive disorder. However, we found weak evidence to suggest that males were more likely to be good responders. We identified one SNP, rs116927879, that reached the genome-wide significance level. The genomic interval implicated by this finding included the ADCY1 (Adenylate Cyclase 1) gene and two pseudo-genes, GTF2IP13 and SEPT7P2. While the functions of GTF2IP13 and SEPT7P2 remain poorly understood, ADCY1 plays a role in mediating responses to increased cellular Ca2+/calmodulin levels, which is relevant to regulatory processes in the central nervous system, as well as memory and learning. Sleep disturbances and circadian rhythm dysfunction have been commonly noted among patients with BD. It has been suggested that the circadian modulation of contrast sensitivity is associated with Dopamine D4 Receptors (D4Rs) primarily through the ADCY1 signalling pathway. In addition, the sQTL data suggested that rs116927879 genotypes may influence the splicing of ADCY1 across different brain regions. [ABSTRACT FROM AUTHOR]

The World Professional Association for TransgenderHealth (WPATH) currently publishes the Standards of Care (SOC), to provide clinical guidelines for health care of transsexual, transgender and gender non-conforming persons in order to maximize health and well-being by revealing gender dysphoria. An updated version (7th version, 2011) of the WPATH SOC is currently available. Differences between the 6th and the 7th versions of the SOC are shown; the SOC relevant to penile reconstruction in female-tomale (FtM) persons are emphasized, and we analyze how the 2011 WPATH SOC is influencing the daily practice of physicians involved in performing a penile reconstruction procedure for these patients. Depending by an individual's goals and expectations, the most appropriate surgical technique should be performed: the clinic performing penile reconstruction should be able to offer the whole range of techniques, such as: metoidioplasty, pedicle and free flaps phalloplasty procedures. The goals that physicians and health care institutions should achieve in the next years, in order to improve the care of female-to-male persons, consist in: informing in details the individuals applying for penile reconstruction about all the implications; referring specific individuals to centers capable to deliver a particular surgical technique; implementing the surgery with the most updated refinements. [ABSTRACT FROM AUTHOR]

Background: Bipolar disorder (BD) is a chronic psychiatric disorder characterized by recurrent mood episodes interspersed with euthymic periods. A growing number of studies have indicated that zinc plays an important role in coordinating immune responses, as well as being involved in synaptic transmission. In the current study, we set out to measure serum levels of zinc in a meticulously phenotyped cohort of 121 euthymic BD subjects and 30 matched controls. Methods: Serum levels of zinc were measured by photometry. To assess the interplay between zinc levels and immune activation in BD, we measured serum levels of high‐sensitive C‐reactive protein (hsCRP) levels by immunoturbidimetric assay, and serum levels of monocyte chemoattractant protein‐1 (MCP‐1), chitinase 3‐like protein 1 (YKL‐40), and soluble cluster of differentiation 14 (sCD14) by electrochemiluminescence enzyme‐linked immunosorbent assays. The baseline clinical diagnostic instrument for BD was the Affective Disorder Evaluation, and executive functioning was assessed by using the Delis–Kaplan Executive Function System. Results: Controlling for potential confounding factors, BD patients displayed increased serum levels of zinc unrelated to hsCRP, MCP‐1, YKL‐40, and sCD14 levels. Serum levels of zinc did not associate with executive functioning or measurements of disease severity. Discussion: This study suggests that the zinc homeostasis is disturbed in BD and that this dyshomeostasis is not related to ongoing mood symptoms or immune activation. Of note, serum levels were increased and hence do not support continuous zinc supplementation in BD. [ABSTRACT FROM AUTHOR]

A common goal in data-analysis is to sift through a large data-matrix and detect any significant submatrices (i.e., biclusters) that have a low numerical rank. We present a simple algorithm for tackling this biclustering problem. Our algorithm accumulates information about 2-by-2 submatrices (i.e., ‘loops’) within the data-matrix, and focuses on rows and columns of the data-matrix that participate in an abundance of low-rank loops. We demonstrate, through analysis and numerical-experiments, that this loop-counting method performs well in a variety of scenarios, outperforming simple spectral methods in many situations of interest. Another important feature of our method is that it can easily be modified to account for aspects of experimental design which commonly arise in practice. For example, our algorithm can be modified to correct for controls, categorical- and continuous-covariates, as well as sparsity within the data. We demonstrate these practical features with two examples; the first drawn from gene-expression analysis and the second drawn from a much larger genome-wide-association-study (GWAS). [ABSTRACT FROM AUTHOR]

Background:The treatment of choice for cycloid psychosis has traditionally been electroconvulsive therapy (ECT), but there is a lack of studies on its effectiveness. Aims:The primary aim of this register study was to determine the rates of remission and response after ECT for cycloid psychosis. The secondary aim was to examine possible predictors of outcome. Methods:Data were obtained from the National Quality Register for ECT in Sweden. The study population was patients (n = 42) who received ECT for acute polymorphic psychotic disorder without symptoms of schizophrenia or for cycloid psychosis between 2011–2015 in 13 hospitals. Remission and response rates were calculated using Clinical Global Impression-Severity (CGI-S) and -Improvement scores, respectively. Variables with possible predictive value were tested using Chi-square and Fisher’s exact test. Results:The response rate was 90.5%. The remission rate was 45.2%. Of 42 patients, 40 improved their CGI-S score after ECT (p < 0.001). The mean number of ECT treatments was 2.5 for non-responders and 7.0 for responders (p = 0.010). The mean number of ECT treatments did not differ significantly between remitters and non-remitters (7.2 vs 6.1,p = 0.31). None of the other investigated potential predictors was statistically significantly associated with outcome. Conclusions:ECT is an effective treatment for cycloid psychosis. Future studies need to compare the outcome of ECT to that of other treatment strategies.Clinical implications: The high response rate with ECT indicates that cycloid psychosis is a clinically useful diagnosis. [ABSTRACT FROM AUTHOR]

The article discusses research that aims to know the extent to which clonal expansions occur and precede cancer to understand the pathogenesis of proliferative diseases. Topics mentioned include blood samples obtained for deoxyribonucleic acid sequencing from 12,380 Swedish persons, a strategy for identification of somatic mutations based on allelic fractions, and characteristic mutations and candidate drivers in clonal hematopoiesis.

Context: Rapid cycling is a severe form of bipolar disorder with an increased rate of episodes that is particularly treatmentresponsive to chronotherapy and stable sleep-wake cycles. We hypothesized that the P2RX7 gene would be affected by sleep deprivation and be implicated in rapid cycling. Objectives: To assess whether P2RX7 expression is affected by total sleep deprivation and if variation in P2RX7 is associated with rapid cycling in bipolar patients. Design: Gene expression analysis in peripheral blood mononuclear cells (PBMCs) from healthy volunteers and case-case and case-control SNP/haplotype association analyses in patients. Participants: Healthy volunteers at the sleep research center, University of California, Irvine Medical Center (UCIMC), USA (n = 8) and Swedish outpatients recruited from specialized psychiatric clinics for bipolar disorder, diagnosed with bipolar disorder type 1 (n = 569; rapid cycling: n = 121) and anonymous blood donor controls (n = 1,044). Results: P2RX7 RNA levels were significantly increased during sleep deprivation in PBMCs from healthy volunteers (p = 2.3*10-9). The P2RX7 rs2230912 0A allele was more common (OR = 2.2, p = 0.002) and the ACGTTT haplotype in P2RX7 (rs1718119 to rs1621388) containing the protective rs2230912_G allele (OR = 0.45--0.49, p = 0.003--0.005) was less common, among rapid cycling cases compared to non-rapid cycling bipolar patients and blood donor controls. Conclusions: Sleep deprivation increased P2RX7 expression in healthy persons and the putatively low-activity P2RX7 rs2230912 allele A variant was associated with rapid cycling in bipolar disorder. This supports earlier findings of P2RX7 associations to affective disorder and is in agreement with that particularly rapid cycling patients have a more vulnerable diurnal system. [ABSTRACT FROM AUTHOR]

Abstract: It has repeatedly been shown that the serotonergic system is involved in the symptomatology of premenstrual dysphoric disorder (PMDD). Women with PMDD are reported to differ from symptom-free controls with regard to serotonin-related biological markers. Evidence from family and twin studies suggests a genetic contribution to the aetiology of PMDD. The expression of human transcription factor AP-2β in neural crest cell lineages and neuroectodermal cells suggests that this protein may be of importance for functional characteristics of neurons by regulating the expression of target genes. Within the monoaminergic systems, several genes have binding sites for AP-2β in regulatory regions, suggesting an involvement of AP-2β in these systems. The gene encoding AP-2β is located on chromosome 6p12–p21.1 and includes a polymorphic region consisting of a variable number of [CAAA] repeats located in the second intron. We have earlier shown that AP-2β genotype is associated with serotonergic phenotypes and that brainstem levels of AP-2β correlate positively to serotonin metabolism in rat frontal cortex. The aim of this study was to investigate the relationship between PMDD and transcription factor AP-2β genotype. The participants included 176 women with PMDD and 91 healthy controls. Genotyping was performed by polymerase chain reactions. We did not observe any differences in AP-2β genotype frequencies between PMDD subjects and controls. Our results suggest that AP-2β genotype is not a risk factor for PMDD. To our knowledge, this is the first study investigating transcription factor AP-2β genotype in women with PMDD. Hence, these results should be considered preliminary until replicated. [Copyright &y& Elsevier]

B Abstract: b Early age at onset (AAO) is associated with an unfavourable clinical outcome. BD and schizophrenia (SCZ) multiplex families can show a high number of early AAO cases, suggesting a genetic contribution to early AAO. Previous GWAS did not identify AAO-associated variants for BD, indicating that larger samples and a more accurately defined AAO phenotype are required for the detection of AAO-associated common variants. [Extracted from the article]

Bipolar Disorder (BD) is associated with higher Body Mass Index (BMI). In a prior Genome-Wide Association Study (GWAS) of BD, we found that rs12772424 in TCF7L2, a transcription factor in the Wnt signaling pathway, modified the association between BMI and BD (Winham et al., 2014), and subsequently replicated this finding in an independent sample (Cuellar-Barboza et al., 2016). Preliminary data further suggested that the TCF7L2-BMI interaction association with BD may be sex-specific, with stronger effects observed in females. Additional studies are needed to validate these findings and determine the role of other clinical factors and genetic modifiers in the BMI-BD association. Here, using data from the Psychiatric Genomics Consortium (PGC), we seek to identify additional genetic variations that may be contributing to the association of BD with elevated BMI. Data from nine PGC sites were included in this study (3165 cases, 2645 controls); five sites provided BMI data for cases and controls, whereas four sites had BMI data only for cases. In all analyses, BMI was log-transformed. Separately for each site, case-only GWAS analyses were conducted to investigate SNP⁎BMI interaction effects by examining SNP effects with BMI as the outcome variable using linear regression, for SNPs that have not shown evidence of genome-wide significant BMI association in prior studies. Additionally, for sites with controls, case-control analyses were conducted using logistic regression, adjusted for BMI. Two tests were performed: 1 df test of SNP⁎BMI interaction, and 2 df test of SNP effect and the SNP⁎BMI interaction effect. Results of the site-specific analyses were then meta-analyzed for SNPs observed across all sites. Sex-stratified analyses were also conducted. No evidence of study heterogeneity was observed for the top SNPs. In case-only and case-control analyses of SNP-BMI interaction effects, no results were genome-wide significant (overall or sex-stratified). The top result in the case-control analysis for SNP-BMI interaction was rs736893 in GLIS3 (OR=1.03, P=3.6E-5), with a stronger result in males in sex-stratified analyses (OR=1.07, P=5.7E-6). The top result in the case-only analysis of SNP-BMI interaction was rs4285452 in GSDMC (beta=0.02, P=3.3E-6), which showed similar results in males and females. In sex-stratified case-only analyses, the strongest result was in females for rs7994174 in DCLK1 (beta=0.05, p=4.5E-6), where no effect was observed in males. Although no genome-wide significant findings were identified in analyses of SNP⁎BMI effects on BD risk, overall or stratified by sex, interesting candidate variants were observed in genes including GLIS3 and DCLK1. GLIS3 encodes a zinc finger protein that has been associated with neonatal diabetes and congenital hypothyroidism. DCLK1 encodes doublecortin like kinase 1, which is involved in neuronal migration, transport, neuronal apotosis, and neurogenesis; it is upregulated by BDNF, previously implicated in both BD and BMI. The retrospective data analyzed here can only identify associations, and does not allow us to determine directionality of these associations, so further investigation is needed to determine if SNP effects modify the effect of BMI on BD or vice versa. Future directions include analysis of imputed data, gene set analyses, analyses of secondary phenotypes related to BMI (e.g. binge eating disorder and weight gain), and analyses to investigate possible medication effects. [ABSTRACT FROM AUTHOR]

Highlights from the article: B Background: b Bipolar disorder (BD) is a common, severe mood disorder that affects more than 1% of the worldwide population. Exome sequencing has revealed a significant burden of deleterious rare variants in patients with schizophrenia, which overlaps with bipolar disorder clinically and genetically. B Methods: b 1169 blood-derived DNA samples from bipolar disorder patients were collected as part of the Sweden dataset, which also includes 4970 schizophrenia cases and 6245 controls.

Highlights from the article: B Background: b Despite the overlap in genetic etiology and clinical presentations, bipolar disorder (BD), schizophrenia (SCZ) and major depressive disorder (MDD) display distinguishing characteristics. B Results: b PRS of BD and PRS of SCZ/MDD showed associations with clinical symptoms of BD in opposite directions. PRSs of BD, SCZ and MDD were positively associated with hospitalization due to suicide attempt/self-harm, but the associations did not hold after adjustment of BD status.

Background Inflammatory mechanisms have been implicated in the pathophysiology and progression of bipolar disorder. Markers of inflammation circulating in blood are often used in these investigations, but demonstrate little relationship to central nervous system inflammation and related biomarkers in the cerebrospinal fluid (CSF). This study investigates the genetic mediation of inflammation biomarkers in CSF and serum from subjects with bipolar disorder and healthy controls. Methods Subjects were drawn from the St. Göran Bipolar Project which enrolls patients from bipolar disorder clinics in Gothenburg and Stockholm in addition to age and sex-matched healthy controls. For the inflammation-related biomarkers YKL40, MCP1, sCD14, TIMP1, and TIMP2, CSF and serum levels were quantified, as well as CSF levels of IL8 and serum levels of CRP and MMP9. Subjects were genotyped using the Affymetrix 6.0 and Illumina OmniExpress arrays. Genome-wide association studies of these biomarkers were conducted for the 51-57 controls and 101-164 cases with available data using PLINK and included covariates for age, sex, and principle components accounting for population substructure. Results Genome-wide significant associations (p<5x10-8) resulted from all analyses with the exception of CSF derived levels of TIMP1. Multiple genomic regions exert regulatory effects for the majority of biomarkers tested, but there was little concordance between associated regions for CSF and serum-derived measures when both were available for a given biomarker. Discussion Levels of inflammatory biomarkers in CSF and serum are both genetically mediated but probably differentially. The associated genetic markers, in conjunction with the biomarker levels previously associated with bipolar disorder, could be used to aid diagnoses and as possible targets for the development of novel therapeutics. [ABSTRACT FROM AUTHOR]