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This cohort study examines the incidence of idiopathic intracranial hypertension (IHH) among individuals in Sweden undergoing gonadotropin-releasing hormone analogue (GnRHa) treatment for gender dysphoria.

IntroductionThere has been a drastic increase in the reported number of people seeking help for gender dysphoria in many countries over the last two decades. Yet, our knowledge of gender dysphoria and related outcomes is restricted due to the lack of high-quality studies employing comprehensive approaches. This longitudinal study aims to enhance our knowledge of gender dysphoria; different aspects will be scrutinised, focusing primarily on the psychosocial and mental health outcomes, prognostic markers and, secondarily, on the underlying mechanisms for its origin.Methods and analysisThe Swedish Gender Dysphoria Study is an ongoing multicentre longitudinal cohort study with 501 registered participants with gender dysphoria who are 15 years old or older. Participants at different phases of their clinical evaluation process can enter the study, and the expected follow-up duration is three years. The study also includes a comparison group of 458 age- and county-matched individuals without gender dysphoria. Data on the core outcomes of the study, which are gender incongruence and experienced gender dysphoria, body satisfaction and satisfaction with gender-affirming treatments, as well as other relevant outcomes, including mental health, social functioning and life satisfaction, are collected via web surveys. Two different research visits, before and after starting on gender-affirming hormonal treatment (if applicable), are planned to collect respective biological and cognitive measures. Data analysis will be performed using appropriate biostatistical methods. A power analysis showed that the current sample size is big enough to analyse continuous and categorical outcomes, and participant recruitment will continue until December 2022.Ethics and disseminationThe ethical permission for this study was obtained from the Local Ethical Review Board in Uppsala, Sweden. Results of the study will be presented at national and international conferences and published in peer-reviewed journals. Dissemination will also be implemented through the Swedish Gender Dysphoria Study network in Sweden.

Introduction Gender 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. Methods Cross-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. Results The 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. Conclusions In this sample of Swedish young adults seeking health care for gender dysphoria, preferences for treatment options varied according to perceived gender identity. Policy Implications The study findings underline the need for individualized care and flexible gender affirming treatment options. The role of somatic comorbidities should be further explored, and support should be offered to transgender people in need. There is an unmet need for facial surgery among aM.

Background Craniosynostosis is one of the most common craniofacial malformations demanding surgical treatment in infancy. Data on overall psychiatric morbidity among children with nonsyndromic craniosynostosis remain limited. This study investigated the risk of psychiatric disorders in nonsyndromic craniosynostosis. Methods The authors reviewed a register-based cohort of all individuals born with nonsyndromic craniosynostosis in Sweden between 1973 to 1986 and 1997 to 2012 (n = 1238). The nonsyndromic craniosynostosis cohort was compared with a matched community cohort (n = 12,380) and with unaffected full siblings (n = 1485). The authors investigated the risk of psychiatric disorders, suicide attempts, and suicides by using Cox regression adjusted for perinatal and somatic factors, season and birth year, sex, parental socioeconomic factors, and parental psychiatric disorders. Results Children with nonsyndromic craniosynostosis had a higher risk of any psychiatric disorder (adjusted Cox-derived hazard ratio, 1.70; 95 percent CI, 1.43 to 2.02), including intellectual disability (adjusted Cox-derived hazard ratio, 4.96; 95 percent CI, 3.20 to 7.70), language disorders (adjusted Cox-derived hazard ratio, 2.36; 95 percent CI, 1.57 to 3.54), neurodevelopmental disorders (adjusted Cox-derived hazard ratio, 1.30; 95 percent CI, 1.01 to 1.69), and other psychiatric disorders (adjusted Cox-derived hazard ratio, 1.43; 95 percent CI, 1.11 to 1.85). Full siblings with nonsyndromic craniosynostosis were more likely, in the crude analyses, to be diagnosed with any psychiatric disorder, including intellectual disability, language disorders, and neurodevelopmental disorders compared with nonaffected siblings. The higher risk for any psychiatric disorder and intellectual disability remained after adjusting for confounders. Conclusions Children with nonsyndromic craniosynostosis demonstrated higher risks of any psychiatric disorder compared with children without nonsyndromic craniosynostosis. This risk cannot fully be explained by familial influences (i.e., genetic or environmental factors). Clinical question/level of evidence Risk, III.

Increasing numbers of transgender and gender diverse children and adolescents have been referred to gender identity clinics in Sweden in the past decade, and previous studies have found an association between media attention and referral counts. Whether the tone of media stories is associated with referrals is not yet known.To investigate whether positive or negative media coverage on transgender and gender diverse issues is associated with referral counts to child and adolescent gender identity clinics.In this cross-sectional study, referrals counts were collected from all 6 specialized gender identity clinics in Sweden, along with information on referral date, sex assigned at birth, and birth year. Participants were all individuals younger than 19 years, referred to a gender identity clinic between January 1, 2017, and December 31, 2019. Data were analyzed from May 2020 to September 2021.Exposures included 3 major media events related to transgender health care in 2019; 1 event was categorized as positive and 2 events were categorized as negative press coverage.Referral counts before and after each of the 3 major media events were assessed, and the moderating association of sex assigned at birth and age was examined with stratified analyses. Weekly referral counts and trends were assessed with interrupted time series analysis.Among 1784 referrals (359 referrals [21.4%] among individuals aged13 years; 1034 referrals [72.1%] among individuals assigned female at birth and 401 referrals [27.9%] among individuals assigned male at birth), a negative association between media coverage and referral counts was found for the first of the negative media events. In the 3 months following the event, referrals decreased by 25.4% (95% CI, -31.9% to -18.9%) overall, by 32.2% (95 CI, -41.8% to -22.8%) for individuals assigned female at birth, and by 25.3% (95 CI, -32.4% to -18.3%) for individuals aged 13 to 18 years. In the interrupted time series analysis, a mean weekly decrease of 3% in the referrals was observed in the extended time interval of 39 weeks (incidence rate ratio, 0.97; 95 CI, 0.95 to 0.99). For the other 2 media events, no changes in referral counts or time trends were observed.These findings suggest that an event of negative media coverage on transgender-specific health care was negatively associated with access to health care for transgender children and adolescents; therefore, nuanced and accurate media coverage, as well as increased awareness of these mechanisms among key stakeholders, is essential.

Aims We compared the incidence of cardiovascular disease (CVD) in transgender participants with a diagnosis of gender dysphoria (GD) with and without gender-affirming hormone therapy (GAHT) to the incidence observed in the general population. Methods and results The population-based cohort included all individuals >10 years in Sweden linked to Swedish nationwide healthcare Registers (2006–16). Two comparator groups without GD/GAHT were matched (1:10) on age, county of residence, and on male and female birth-assigned sex, respectively. Cox proportional models provided hazard ratios (HRs) and 95% confidence intervals (CI) for CVD outcomes. Among 1779 transgender individuals [48% birth-assigned males (AMAB), 52% birth-assigned females (AFAB)], 18 developed CVD, most of which were conduction disorders. The incidence of CVD for AFAB individuals with GD was 3.7 per 1000 person-years (95% CI: 1.4–10.0). Assigned male at birth individuals with GD had an incidence of CVD event of 7.1 per 1000 person-years (95% CI: 4.2–12.0). The risk of CVD event was 2.4 times higher in AMAB individuals (HR: 2.4, 95% CI: 1.3–4.2) compared with cisgender women, and 1.7 higher compared with cisgender men (HR: 1.7, 95% CI: 1.0–2.9). Analysis limited to transgender individuals without GAHT yielded similar results to those with GAHT treatment. Conclusion The incidence of CVD among GD/GAHT individuals was low, although increased compared with matched individuals without GD and similar to the incidence among GD/no GAHT individuals, thus not lending support for a causal relationship between treatment and CVD outcomes. Larger studies with longer follow-up are needed to verify these findings, as well as possible effect modification by comorbidity.

Few studies, with conflicting results, report on the association between memory performance and depressive symptoms during the perinatal period. In this study, we aimed to evaluate whether memory performance during late pregnancy is associated with antepartum (APD) and postpartum depression (PPD) symptoms.We conducted a prospective follow-up of 283 pregnant women, nested within a large cohort of women enrolled in the BASIC study in Uppsala University hospital between 2009 and 2019. The Wechsler Digit Span Task (forward-DSF, backward-DSB and total score-DST) was performed to evaluate short-term memory/attention (DSF) and working memory (DSB) around the 38th gestational week; the Edinburgh Postnatal Depression Scale (EPDS), evaluating depressive symptoms, was filled out at 17, 32, 38 gestational weeks, as well as at 6 weeks postpartum. Unadjusted and multivariate logistic regression was used to assess the association between performance on the Digit Span Task and outcome, namely depressive symptoms (using a cut-off of 12 points on the EPDS) at 38 gestational weeks, as well as at 6 weeks postpartum.APD symptoms were not significantly associated with DSF (There was no significant association between working and short-term memory performance and APD symptoms. Among all women, but especially non-depressed earlier in life and/or at antepartum, those scoring high on the forward memory test, i.e., short-term memory, had a higher risk for PPD. Future studies are required to further explore the pathophysiology behind and the predictive value of these associations.

To utilize modern tools to assess depressive and anxiety symptoms, wellbeing and life conditions in pregnant women during the first two waves of the COVID-19 pandemic in Sweden. Pregnant women (n = 1577) were recruited through the mobile application Mom2B. Symptoms of depression, anxiety and wellbeing were assessed during January 2020–February 2021. Movement data was collected using the phone’s sensor. Data on Google search volumes for “Corona” and Covid-related deaths were obtained. Qualitative analysis of free text responses regarding maternity care was performed. Two peaks were seen for depressive symptoms, corresponding to the two waves. Higher prevalence of anxiety was only noted during the first wave. A moderating effect of the two waves in the association of depression, anxiety, and well-being with Covid deaths was noted; positive associations during the first wave and attenuated or became negative during the second wave. Throughout, women reported on cancelled healthcare appointments and worry about partners not being allowed in hospital. The association of mental health outcomes with relevant covariates may vary during the different phases in a pandemic, possibly due to adaptation strategies on a personal and societal/healthcare level. Digital phenotyping can help healthcare providers and governmental bodies to in real time monitor high-risk groups during crises, and to adjust the support offered.

During pregnancy, the hypothalamic-pituitary-adrenal (HPA) axis, the main regulator of the stress response, undergoes dramatic changes. The acoustic startle response (ASR) and the prepulse inhibition (PPI) of the startle response are neurophysiological research tools and objective measures of an individual’s response to an emotional context or stressor. The ASR and PPI are influenced by psychiatric diseases characterized by anxiety symptoms and are sensitive to cortisol. Hence, the ASR and the PPI can be used to investigate the effects of pregnancy-induced endocrine changes and their contribution to affective disorders. The present study sought to investigate the association between measures of HPA-axis responsiveness, startle reactivity and sensorimotor gating during pregnancy that to date remains unknown. The eye-blink component of the ASR, and its prepulse inhibition, were measured in 107 late third trimester pregnant women. Saliva samples were collected to assess the cortisol awakening response (CAR), a measure of HPA-axis activity. Blood was sampled to measure serum levels of cortisol, cortisone and the cortisone to cortisol ratio. Ongoing anxiety disorders, sleep duration, smoking, and age were considered as potential confounders in the statistical analyses. CAR reactivity, measured as area under the curve (AUC) increase and above baseline, was positively associated with baseline startle magnitude [Cohen’s d = 0.27; F (1, 105) = 4.99; p = 0.028, and Cohen’s d = 0.30; F (1, 105) = 6.25; p = 0.014, respectively] as well as PPI at 86 dB [Cohen’s d = 0.29; F (1, 105) = 5.93; p = 0.017; and Cohen’s d = 0.34; F (1, 105) = 8.38; p = 0.005, respectively]. The observed positive correlation between startle magnitude in pregnant women and greater increase in cortisol during the awakening response may be interpreted as heightened neurophysiological reactivity, likely associated with dysregulation of the stress system.

Antenatal depression affects ~9–19% of pregnant women and can exert persistent adverse effects on both mother and child. There is a need for a deeper understanding of antenatal depression mechanisms and the development of tools for reliable diagnosis and early identification of women at high risk. As the use of untargeted blood metabolomics in the investigation of psychiatric and neurological diseases has increased substantially, the main objective of this study was to investigate whether untargeted gas chromatography–mass spectrometry (GC–MS) plasma metabolomics in 45 women in late pregnancy, residing in Uppsala, Sweden, could indicate metabolic differences between women with and without depressive symptoms. Furthermore, seasonal differences in the metabolic profiles were explored. When comparing the profiles of cases with controls, independently of season, no differences were observed. However, seasonal differences were observed in the metabolic profiles of control samples, suggesting a favorable cardiometabolic profile in the summer vs. winter, as indicated by lower glucose and sugar acid concentrations and lactate to pyruvate ratio, and higher abundance of arginine and phosphate. Similar differences were identified between cases and controls among summer pregnancies, indicating an association between a stressed metabolism and depressive symptoms. No depression-specific differences were apparent among depressed and non-depressed women, in the winter pregnancies; this could be attributed to an already stressed metabolism due to the winter living conditions. Our results provide new insights into the pathophysiology of antenatal depression, and warrant further investigation of the use of metabolomics in antenatal depression in larger cohorts.

Our aim was to explore if different exposure windows for sunshine or temperature are associated with increased suicidal behaviour among people starting antidepressant treatment. 307 completed and 1674 attempted suicides were included as cases in the conditional logistic regression analyses, while controlling for potential confounders, including season, as well as temperature and hours of sunshine when these variables were not the main exposure variable. Ten controls were matched to each case using risk-set sampling. The role of season, age, and sex was examined with likelihood ratio tests (LRTs) with and without the respective interaction terms and with stratified analyses. There was no overall association between temperature or sunshine with suicidal behaviour. Age was a significant effect modifier for suicide and suicide attempt for both sunshine and temperature exposure. In stratified analyses, an increase of one degree Celsius in the average daily temperature during the last 4 weeks was associated, in the unadjusted model, with a 3% increase in the rate of suicide (p = 0.023) amongst older patients (65+). In the same age group, an increase of 1 h in the average daily sunshine during the last 4 weeks was associated with an 8% increase in the rate of suicide attempt (p = 0.002), while the respective increase for the exposure period of 5–8 weeks was 7% (p = 0.007). An increase of one degree Celsius in the average daily temperature during the last 4 weeks was associated with a 3% increase in the rate of suicide attempt (p = 0.007). These associations did not retain statistical significance in the adjusted models. No associations were found in the other age groups. Our results point to a possible effect modification by age, with higher risk of suicidal behavior associated with an increase in sunshine and temperature found in the older age groups.

The aim of this study was to examine the validity of the Gender Dysphoria (GD) diagnoses in the Swedish National Patient Register (NPR), to discuss different register-based definitions of GD and to investigate incidence trends. We collected data on all individuals with registered GD diagnoses between 2001 and 2016 as well as data on the coverage in the NPR. We regarded gender confirming medical intervention (GCMI) as one proxy for a clinically valid diagnosis and calculated the positive predictive value (PPV) for receiving GCMI for increasing number of registered GD diagnoses. We assessed crude and coverage-adjusted time trends of GD during 2004–2015 with a Poisson regression, using assigned sex and age as interaction terms. The PPV for receiving GCMI was 68% for ≥ 1 and 79% for ≥ 4 GD-diagnoses. The incidence of GD was on average 35% higher with the definition of ≥ 1 compared to the definition of ≥ 4 diagnoses. The incidence of GD, defined as ≥ 4 diagnoses increased significantly during the study period and mostly in the age categories 10–17 and 18–30 years, even after adjusting for register coverage. We concluded that the validity of a single ICD code denoting clinical GD in the Swedish NPR can be questioned. For future research, we propose to carefully weight the advantages and disadvantages of different register-based definitions according to the individual study’s needs, the time periods involved and the age-groups under study.

Social robots are rising to prominence as tools in healthcare and mental healthcare. In this paper, we investigate robot-assisted diagnostics of peripartum depression (PPD) in women. To design robots that are accepted by users and comply with trustworthy Artificial Intelligence principles, we use semi-structured interviews to explore the views of potential stakeholders - psychiatrists. We aim to answer three research questions regarding 1) the usefulness of robots in the diagnosis of PPD, 2) potential ethical issues, and 3) the roles that robots and clinicians may play in the diagnostic process. Results show that psychiatrists are only willing to let robots take minor responsibilities, and feel that robots may be more useful in situations where there is a shortage of clinicians.

IntroductionPerinatal complications, such as perinatal depression and preterm birth, are major causes of morbidity and mortality for the mother and the child. Prediction of high risk can allow for early delivery of existing interventions for prevention. This ongoing study aims to use digital phenotyping data from the Mom2B smartphone application to develop models to predict women at high risk for mental and somatic complications.Methods and analysisAll Swedish-speaking women over 18 years, who are either pregnant or within 3 months postpartum are eligible to participate by downloading the Mom2B smartphone app. We aim to recruit at least 5000 participants with completed outcome measures. Throughout the pregnancy and within the first year postpartum, both active and passive data are collected via the app in an effort to establish a participant’s digital phenotype. Active data collection consists of surveys related to participant background information, mental and physical health, lifestyle, and social circumstances, as well as voice recordings. Participants’ general smartphone activity, geographical movement patterns, social media activity and cognitive patterns can be estimated through passive data collection from smartphone sensors and activity logs. The outcomes will be measured using surveys, such as the Edinburgh Postnatal Depression Scale, and through linkage to national registers, from where information on registered clinical diagnoses and received care, including prescribed medication, can be obtained. Advanced machine learning and deep learning techniques will be applied to these multimodal data in order to develop accurate algorithms for the prediction of perinatal depression and preterm birth. In this way, earlier intervention may be possible.Ethics and disseminationEthical approval has been obtained from the Swedish Ethical Review Authority (dnr: 2019/01170, with amendments), and the project fully fulfils the General Data Protection Regulation (GDPR) requirements. All participants provide consent to participate and can withdraw their participation at any time. Results from this project will be disseminated in international peer-reviewed journals and presented in relevant conferences.

Public health emergencies such as the coronavirus (SARS-CoV-2) pandemic have significant impact on mental health, and have been shown to impact on already prevalent affective disorders during and after pregnancy. The aim of this study was to utilize modern tools to assess depressive and anxiety symptoms, as well as wellbeing and life changes in pregnant women during the pandemic in Sweden, where no lockdown has been in place.Data from the Mom2B, a national ongoing mobile application-based study of pregnant and newly-delivered women were utilized. Participants (n= 1345) filled out self-report screeners of depression, anxiety and wellbeing. Questions about COVID symptoms and effects on life and health care were added from March 2020. Movement data was collected using the phone’s GPS sensor. Mood scores were compared with throughout the months of 2020 and to the levels of a previous collected material. Highest levels of depression and anxiety were evident in April and October 2020. Symptoms were higher among those feeling socially isolated, but not for those infected or with symptomatic family members. Wellbeing and mobility were strongly positively correlated and were lowest in April. Women reported on cancelled healthcare appointments and worry about their partners being absent from the delivery.The Mom2B application enabled gathering information at a national level in real-time as the pandemic has been evolving. Levels of perinatal affective symptoms and low wellbeing were elevated compared with previous years as well as with months with fewer cases of SARS-Cov-2. Similar applications can help healthcare providers and governmental bodies to in real time monitor high-risk groups during crises, as well as to adjust measures and the support offered.FundingThis project was funded by the Uppsala Region to AS, the Swedish Association of Local Authorities and Regions (SKR) to the department of Obstetrics and Gynecology, Akademiska University Hospital, the Swedish Research Council (Grant number 2020-01965) to AS, as well as the Fredrik and Inger Thuring’s Foundation to EF.

Background Previous studies have examined whether steroid hormone treatment in transgender individuals may affect cognitive function; yet, their limited power does not allow firm conclusions to be drawn. We leveraged data from to-date literature aiming to explore the effect of gender-affirming hormone administration on cognitive function in transgender individuals. Methods A search strategy of MEDLINE was developed (through June 1, 2019) using the key terms transgender, hormone therapy and cognitive function. Eligible were (i) cohort studies examining the longitudinal effect of hormone therapy on cognition, and (ii) cross-sectional studies comparing the cognitive function between treated and non-treated individuals. Standardized mean differences (Hedges’ g) were pooled using random-effects models. Study quality was evaluated using the Newcastle-Ottawa Scale. Outcomes Ten studies (seven cohort and three cross-sectional) were eligible representing 234 birth-assigned males (aM) and 150 birth-assigned females (aF). The synthesis of cohort studies (n = 5) for visuospatial ability following hormone treatment showed a statistically significant enhancement among aF (g = 0.55, 95% confidence intervals [CI]: 0.29, 0.82) and an improvement with a trend towards statistical significance among aM (g = 0.28, 95%CI: -0.01, 0.58). By contrast, no adverse effects of hormone administration were shown. No heterogeneity was evident in most meta-analyses. Interpretation Current evidence does not support an adverse impact of hormone therapy on cognitive function, whereas a statistically significant enhancing effect on visuospatial ability was shown in aF. New longitudinal studies with longer follow-up should explore the long-term effects of hormone therapy, especially the effects on younger individuals, where there is greater scarcity of data.

The Transgender Congruence Scale (TCS) is a non-binary tool used in Sweden for gender dysphoria (GD) assessment; however, its Swedish version has not been validated. To investigate the psychometric properties of the TCS, its capacity to distinguish individuals with GD and its concurrent validity compared to other scales. Patients with GD (n = 135) and controls (n = 443) filled in a questionnaire containing sociodemographic questions, the TCS, the Utrecht Gender Dysphoria Scale (UGDS), and the Gender Identity/Gender Dysphoria Questionnaire for Adolescents and Adults (GIDYQ-AA). TCS had good discriminatory validity and internal consistency. Patients with GD, stratified by birth-assigned sex, had lower TCS scores compared to controls. Confirmatory factor analysis (CFA) supported the two-factor model of the TCS. Multiple-group CFA suggested measurement invariance between birth-assigned sexes and configural invariance between patients with GD and controls. Area under the ROC curve for birth-assigned males was 0.991 and for females 0.994. A TCS mean value of three provided sensitivity 94.3% and 95.1% as well as specificity 98.6% and 98% for aM and aF, respectively. The TCS was significantly correlated to UGDS and GIDYQ-AA. The TCS may be a valuable tool in the clinical assessment of individuals with GD.

Postpartum depression (PPD) is a devastating disorder affecting not only more than 10% of all women giving birth, but also the baby, the family, and the society. Compiling evidence suggests the involvement of the immune system in the pathophysiology of major depression; yet, the immune response in perinatal depression is not as well studied. The aim of this study was to investigate the alterations in peripheral levels of inflammatory biomarkers in 169 Swedish women with and without depressive symptoms according to the Edinburgh postnatal depression scale or the M.I.N.I neuropsychiatric interview at eight weeks postpartum. Among the 70 markers analyzed with multiplex proximity extension assay, five were significantly elevated in women with postpartum depressive symptoms in the adjusted LASSO logistic regression analysis: Tumor necrosis factor ligand superfamily member (TRANCE) (OR-per 1 SD increase = 1.20), Hepatocyte growth factor (HGF) (OR = 1.17) Interleukin (IL)-18 (OR = 1.06), Fibroblast growth factor 23 (FGF-23) (OR = 1.25), and C-X-C motif chemokine 1 (CXCL1) (OR 1.11). These results indicate that women with PPD have elevated levels of some inflammatory biomarkers. It is, therefore, plausible that PPD is associated with a compromised adaptability of the immune system.

Background:Meteorological parameters and air pollen count have been associated with affective disorders and suicide. Regarding peripartum depression, the literature is restricted and inconclusive.Methods:This cross-sectional study included women (pregnant, n = 3843; postpartum, n = 3757) who participated in the BASIC (Biology, Affect, Stress, Imaging, and Cognition) study 2010–2015 and the UPPSAT (Uppsala-Athens) study (postpartum, n = 1565) in 2006–2007. Cases were defined according to presence of depressive symptoms during pregnancy (gestational week 32) and 6 weeks postpartum, using the Edinburgh Postnatal Depression Scale (EPDS). Exposure of sunshine, temperature, precipitation, snow coverage, and air pollen counts of durations of 1, 7, and 42 days prior to the outcome were studied for associations with depressive symptoms, using negative binomial regression.Results:Prior to Bonferroni correction, the concentration of mugwort pollen, both one week and six weeks before the EPDS assessment at gestational week 32, was inversely associated with depressive symptoms in pregnancy, both before and after adjustment for season. No associations were found between the exposure to meteorological parameters and pollen and depressive symptoms, at the same day of depressive symptoms’ assessment, the previous week, or the six weeks prior to assessment, either during pregnancy or postpartum after Bonferroni correction.Conclusions:There was no evidence that neither short-term nor long-term exposure to meteorological parameters or air pollen counts were associated with self-reported peripartum depressive symptoms in Uppsala, Sweden.

A history of anorexia nervosa has been associated with a reduced risk of developing breast cancer. We investigated survival after breast cancer among women with a prior anorexia nervosa diagnosis compared with women in a population comparison group. This register-based study included combined data from Sweden, Denmark and Finland. A total of 76 and 1462 breast cancer cases identified among 22,654 women with anorexia nervosa and 224,619 women in a population comparison group, respectively, were included in the study. Hazard ratios (HR) for overall and breast cancer-specific mortality after breast cancer diagnosis were estimated using Cox regression. Cause of death was available only for Swedish and Danish women; therefore, the analysis on breast cancer-specific mortality was restricted to these women. We observed 23 deaths after breast cancer among anorexia nervosa patients and 247 among population comparisons. The overall mortality after the breast cancer diagnosis was increased in women with a history of anorexia nervosa compared with population comparisons (HR 2.5, 95% CI 1.6–3.9) after adjustment for age, period and extent of disease. Results were similar for overall (HR 2.3, 95% CI 1.4–3.6) and breast cancer-specific mortality (HR 2.1, 95% CI 1.3–3.6) among Swedish and Danish women. We found that female breast cancer patients with a prior diagnosis of anorexia nervosa have a worse survival compared with other breast cancer patients.

We explored the potential association of depression history and personality, evaluated through a robust questionnaire tool, namely the Eysenck Personality Scale, with disease risk and progression among Greek patients. A total of 106 melanoma patients and their 1 : 1 sex-matched controls were interviewed on the basis of a questionnaire comprising phenotypic, sociodemographic, lifestyle and medical history variables, as well as information on history of lifetime major depression. The Eysenck Personality Questionnaire, measuring the four personality dimensions (extraversion, neuroticism, psychoticism, lie), was thereafter completed. Adjusted odds ratios (ORs) for melanoma risk were derived through multiple logistic regression analyses, whereas potential predictors of survival were explored using Cox proportional hazards models. Sun sensitivity score [OR: 1.55, 95% confidence interval (CI): 1.16-2.06] and major depression history (OR: 5.72, 95% CI: 1.38-23.73) were significantly associated with melanoma, whereas inverse associations of extraversion (OR: 0.90, 95% CI: 0.83-0.97) and psychoticism score (OR: 0.88, 95% CI: 0.78-1.00) were noted. These associations were more pronounced and remained solely among female patients; notably, decreased extraversion (OR: 0.86, 95% CI: 0.76-0.98) and psychoticism score (OR: 0.63, 95% CI: 0.43-0.91), as well as increased depression history (OR: 10.69, 95% CI: 1.43-80.03) were evident. Cox-derived hazard ratios showed nonsignificant associations of depression history and personality with disease outcome. Our data support the hypotheses that depression history and personality are associated with melanoma risk. No effect on survival after cancer diagnosis was observed. If confirmed in future studies, these associations may contribute toward better understanding the etiology of melanoma, enhancing health-related quality of life.

The efficacy of the most widely used tests for dementia screening is limited in populations characterized by low levels of education. This study aimed to validate the face-to-face administered Telephone Interview for Cognitive Status (TICS) for detection of dementia and mild cognitive impairment (MCI) in a population-based sample of community dwelling individuals characterized by low levels of education or illiteracy in rural Greece.The translated Greek version of TICS was administered through face-to-face interview in 133 elderly residents of Velestino of low educational level (12 years). We assessed its internal consistency and test-retest reliability, its correlation with sociodemographic parameters, and its discriminant ability for cognitive impairment and dementia, as defined by a brief neurological evaluation, including assessment of cognitive status and level of independence.TICS was characterized by adequate internal consistency (Cronbach's α: .72) and very high test-retest reliability (intra-class correlation coefficient: .93); it was positively correlated with age and educational years. MCI and dementia were diagnosed in 18 and 10.5% of the population, respectively. Its discriminant ability for detection of dementia was high (Area under the curve, AUC: .85), with a sensitivity and specificity of 86 and 82%, respectively, at a cut-off point of 24/25. TICS did not perform well in differentiating MCI from cognitively normal individuals though (AUC: .67).The directly administered TICS questionnaire provides an easily applicable and brief option for detection of dementia in populations of low educational level and might be useful in the context of both clinical and research purposes.

BackgroundAnorexia nervosa (AN) is a psychiatric disorder with high mortality.MethodA retrospective register study of 609 males who received hospitalized care for AN in Sweden between 1973 and 2010 was performed. The standardized mortality ratios (SMRs) and Cox regression-derived hazard ratios (HRs) were calculated as measures of mortality. The incidence rate ratios (IRRs) were calculated to compare the mortality rates in patients with AN and controls both with and without psychiatric diagnoses.ResultsThe SMR for all causes of death was 4.1 [95% confidence interval (CI) 3.1–5.3]. For those patients with psychiatric co-morbidities, the SMR for all causes of death was 9.1 (95% CI 6.6–12.2), and for those without psychiatric co-morbidity, the SMR was 1.6 (95% CI 0.9–2.7). For the group of patients with alcohol use disorder, the SMR for natural causes of death was 11.5 (95% CI 5.0–22.7), and that for unnatural causes was 35.5 (95% CI 17.7–63.5). The HRs confirmed the increased mortality for AN patients with psychiatric co-morbidities, even after adjusting for confounders. The IRRs revealed no significant difference in mortality patterns between the AN patients with psychiatric co-morbidity and the controls with psychiatric diagnoses, with the exceptions of alcohol use disorder and neurotic, stress-related and somatoform disorders, which seemed to confer a negative synergistic effect on mortality.ConclusionMortality in male AN patients was significantly elevated compared with the general population among only the patients with psychiatric co-morbidities. Specifically, the presence of alcohol and other substance use disorders was associated with more profound excess mortality.

Aims: The aim of this study was to explore the role of self-reported non-binary gender identity in mental health problems, school adjustment, and wish to exert influence on municipal issues in a community sample of adolescents. Methods: In a cross-sectional design, data were collected through an anonymous survey in Uppsala County, Sweden, among 8385 students (response rate 58.2%) in grades 7, 9, and 11, aged 13–17 years. The Strengths and Difficulties Questionnaire (SDQ) self-report was used to assess mental health problems. Gender identity was measured with one item and youth were categorized into those who identified as male or female (i.e. binary youth), and those who did or could not identify with either gender (i.e. non-binary youth). Logistic regressions and qualitative content analysis were used to analyse data. Results: Youth with non-binary gender identity ( n = 137; 1.6%) had higher odds of having mental problems according to the SDQ total score (OR=3.05; 1.77–5.25). The association between non-binary gender identity and mental health problems remained significant after adjusting for confounders. Additionally, compared to their binary peers, the non-binary youth reported more truancy (36.5% vs 49.6%), more often failed a subject (21.5% vs 36.5%), and were more interested in exerting influence on municipal issues such as sociopolitical development, education, municipal services, and drug and alcohol policies (25.3% vs 38.0%). Conclusions: Youth with non-binary gender identity constitute a vulnerable population regarding mental health problems and school adjustment. The willingness to exert influence on municipal issues suggests a possible pathway to engagement.

Seasonal variations have recently been described in biomarkers, cell types, and gene expression associated with the immune system, but so far no studies have been conducted among women in the peripartum period. It is of note that pregnancy complications and outcomes, as well as autoimmune diseases, have also been reported to exhibit seasonal fluctuations. We report here a clear-cut seasonal pattern of 23 inflammatory markers, analysed using proximity-extension assay technology, in pregnant women. The inflammatory markers generally peaked in the spring and had a trough in the autumn. During the postpartum period we found seasonality in one inflammatory marker, namely monocyte chemotactic protein 4 (MCP-4). Our findings suggest that seasonal variations in peripheral inflammatory markers are only observed during pregnancy. The results of this study could be valuable to professionals working within the field of immunology-related areas, and provide insight for the understanding of obstetric complications.

BackgroundAlthough the incidence of suicide among women who have given birth during the past 12 months is lower than that of women who have not given birth, suicide remains one of the most common causes of death during the year following delivery in high-income countries, such as Sweden.AimsTo characterise women who died by suicide during pregnancy and postpartum from a maternal care perspective.MethodWe traced deaths (n= 103) through linkage of the Swedish Cause of Death Register with the Medical Birth and National Patient Registers. We analysed register data and obstetric medical records.ResultsThe maternal suicide ratio was 3.7 per 100 000 live births for the period 1980–2007, with small magnitude variation over time. The suicide ratio was higher in women born in low-income countries (odds ratio 3.1 (95% CI 1.3–7.7)). Violent suicide methods were common, especially during the first 6 months postpartum. In all, 77 women had received psychiatric care at some point, but 26 women had no documented psychiatric care. Antenatal documentation of psychiatric history was inconsistent. At postpartum discharge, only 20 women had a plan for psychiatric follow-up.ConclusionsSuicide prevention calls for increased clinical awareness and cross-disciplinary maternal care approaches to identify and support women at risk.

Objective: To investigate the association of cognitive impairment (COGI) and depression with all-cause mortality and cardiovascular-specific mortality among community-dwelling elderly individuals in rural Greece. Methods: Cognition and depressive symptomatology of 676 Velestino town residents aged ≥60 years were assessed using Mini-Mental State Examination (MMSE) and Geriatric Depression Scale (GDS), respectively. Eight-year all-cause mortality and cardiovascular mortality were explored by multivariate Cox regression models controlling for major confounders. Results: Two hundred and one patients died during follow-up. Cognitive impairment (MMSE ≤ 23) was independently associated with all-cause mortality (hazard ratio [HR]: 1.57, 95% confidence interval [CI]: 1.13-2.18) and cardiovascular mortality (HR: 1.57, 95%CI: 1.03-2.41). Moderate to severe depression (GDS > 10) was significantly associated only with a 51% increase in all-cause mortality. A male-specific association was noted for moderate to severe depression, whereas the effect of COGI was limited to females. Noteworthy, COGI and depression comorbidity, rather than their sole presence, increased all-cause mortality and cardiovascular mortality by 66% and 72%, respectively. The mortality effect of COGI was augmented among patients with depression and of depression among patients with COGI. Conclusion: COGI and depression, 2 entities often coexisting among elderly individuals, appear to increase all-cause mortality and cardiovascular mortality. Gender-specific modes may prevail but their comorbidity should be carefully assessed, as it seems to represent an independent index of increased frailty, which eventually shortens life expectancy.

Children with orofacial clefts (OFC) may have an increased risk of poor mental health. This study aimed to investigate the risk of psychiatric diagnoses in individuals with OFC, stratified by cleft type.A nationwide register-based cohort of all individuals born with nonsyndromic OFC in Sweden between 1973 and 2012 (n = 7,842) was compared to a matched cohort (n = 78,409) as well as to their unaffected siblings (n = 9,637). The risk of psychiatric diagnoses, suicide attempts, and suicides was examined by crude and adjusted Cox regression models. Effect modification by sex was investigated with interaction terms in the models.Children with cleft lip (CL) had a significantly higher risk of any psychiatric disorder, intellectual disability, and language disorders; children with cleft lip and palate (CLP) had, in addition, an increased risk of autism spectrum disorder (ASD). Children with cleft palate only (CPO) had risk increases for the same diagnoses as children with CL and CLP, but with higher hazard ratios, and also for psychotic disorders, attention-deficit/hyperactivity disorder (ADHD), and other behavioral or emotional disorders in childhood. Sex stratification indicated higher risk increases among females in CL and CLP but not in CPO. Siblings without OFC were less likely to be diagnosed with any psychiatric disorder, intellectual disability, language disorder, ASD, or ADHD compared to their siblings with OFC.Children with nonsyndromic clefts had a significantly higher risk of neurodevelopmental disorders. This risk is unlikely to be explained by familial influences such as inherited genetic or shared environmental factors.

Introduction: Postpartum depression predisposes to maternal affective and somatic disorders. It is important to identify which women are at an increased risk of subsequent morbidity and would benefit from an intensified follow-up. Self-harm thoughts (SHTs), with or without other depressive symptomatology, might have prognostic value for maternal health beyond the postpartum period. Aim: This study is to investigate the somatic and psychiatric morbidity of postpartum women with SHTs, with or without other depressive symptoms, over a 7-year follow-up period. Materials and methods: The subjects for this study are derived from a population based Swedish cohort of women who gave birth at Uppsala University Hospital (May 2006-June 2007) and who answered the Edinburgh Postnatal Depression Scale (EPDS) at 5 days, 6 weeks, and 6 months postpartum. Three groups were included: women reporting SHTs (SHT group, n = 107) on item 10 of the EPDS; women reporting depressive symptoms, i.e., EPDS >= 12 at 6 weeks and/or 6 months postpartum, without SHTs (DEP group, n = 94); and randomly selected controls screening negatively for postpartum depression (CTL group, n = 104). The number of diagnostic codes for somatic and psychiatric morbidity according to the International Statistical Classification of Diseases and Related Health Problems system, and the number of medical interventions were retrieved from medical records over 7 years following childbirth and were used as the outcome measures, together with any prescription of antidepressants and sick leave during the follow-up. Results: The SHT group had the highest psychiatric morbidity of all groups and more somatic morbidity than controls. Affective disorders were more common in the SHT and the DEP groups compared with controls, as well as antidepressant prescriptions and sick leave. One-fifth of women with SHTs did not screen positive for depressive symptoms; nevertheless, they had more somatic and psychiatric morbidity than the control group. Conclusion: Women reporting thoughts of self-harm in the postpartum period are at an increased risk of somatic and psychiatric morbidity during a follow-up of 7 years after delivery, and this increased risk may not be fully attributed to depressive symptoms. Results underline the importance of screening for self-harm symptoms postpartum and point to a need for individualized follow-up. Stavros I. Iliadis and Alkistis Skalkidou contributed equally to this work

We read with interest the commentary of Dr. Zablow1 on our publication on neurodevelopmental disorders and orofacial clefts (OFC).2.

To systematically review and meta-analyse existing evidence on the association between folate/B12, and depression among the aged people.Following PRISMA/STROBE guidelines, the Medline abstracts were retrieved using an algorithm comprising relevant MeSH terms. Publications on the association of folate/B12 serum measurements with depression were abstracted independently by two reviewers and included in both gender and gender-specific meta-analyses, following recarculations of published data as appropriate. The Newcastle-Ottawa scale was used to evaluate the quality of included studies.Both gender data were contributed by 11 folate-related (7949 individuals) and 9 B12-related studies (6308 individuals), whereas gender-specific data by 4 folate-related (3409 individuals) and 3 B12-related studies (1934 individuals). A statistically significant overall association between both exposures of interest (low folate and B12 levels) and depression was observed (ORfolate:1.23, 95%CI:1.07-1.43, ORB12:1.20, 95%CI:1.02-1.42). Gender-specific estimates pointed to a statistically significant positive association between low B12 levels and depression only among women (OR:1.33, 95%CI:1.02-1.74); the gender specific associations of low folate levels with depression were, however, non-significant and of counter-direction (ORfemales:1.37, 95%CI:0.90-2.07; ORmales:0.84, 95%CI:0.57-1.25).Low folate and B12 serum levels seem to be associated with depression in the aged. The gender-specific analyses are confined to a positive association of low B12 with depression among older women and call for further research in this direction.

Compared with major depressive disorder, postpartum depression and its relation to immune activation and inflammation is less studied. Postpartum, after vast adaptations of the immune system during pregnancy, the immune system needs to return to a non-pregnant state, during a period of immune challenging events, such as wound healing, sleep loss, and a fall in levels of proteins and hormones. The study aim was to investigate potential differences in peripheral levels of immune related biomarkers in women with and without postpartum depression (n = 62 and 107 respectively). Among the 71 markers analyzed with multiplex proximity extension assay, five were significantly elevated in women with postpartum depressive symptoms in the adjusted LASSO logistic regression analysis, including TRANCE (OR = 1.20), HGF (OR = 1.17), IL-18 (OR = 1.06), FGF-23 (OR = 1.25), and CXCL1 (OR 1.11). Previously, HGF, IL-18 as well as FGF-23 have been reported lower in severe forms of depression while high levels of IL-18 and CXCL1 have been associated to stress responses. The delivery triggers stress-induced immune responses. Our results might be due to an elevated response to stress as immune reactions previously has been associated with exaggerated inflammation in women with depressive symptoms. Future research should evaluate the relevance of the identified markers, in combination with other known risk factors for postpartum depression. .

Caloric restriction in animals is an effective way to reduce carcinogenesis. Anorexia nervosa (AN) is considered a model of extreme caloric restriction in humans. The aim of our study was to assess cancer incidence and mortality in women with AN. A total of 6,009 women with at least one inpatient treatment for AN during the period 1973-2003 were included in the study. Standardized incidence ratios (SIR) and standardized mortality ratios (SMR) were calculated. Overall, there was no statistically significant difference in cancer incidence compared to women in the general population. At a statistically significant or borderline significant level, a higher incidence for lung cancer and cancer of lymphoid, hematopoietic and related tissue was observed along with a reduced breast cancer incidence. Women with AN had twice as high mortality from cancer in general, and more specifically from melanoma, cancers of genital organs and cancers of ill-defined, secondary and unspecified sites. The increased lung cancer incidence may be due to smoking habits among women with AN. The worse prognosis with higher mortality from melanoma, cancers of genital organs and cancers of ill-defined, secondary and unspecified sites may be explained by AN-specific attitudes toward seeking medical care, adherence to treatment or worse biological precondition due to starvation and cachexia.

To investigate the association of dietary habits with cognitive function among elders (>65 years). Complete sociodemographic, dietary information, serum measurements, and Mini-Mental State Examination (MMSE) assessments were available for 237 elderly men and 320 women residing in Velestino, Greece (a rural Greek town). All models were adjusted for age, education, social activity, smoking, depression symptomatology (using the Geriatric Depression Scale), MedDietScore (range 0-55), and metabolic syndrome. About 49.8% men and 66.6% women had MMSE scores

Decreased binding capacity of SERT in the prefrontal cortex has been observed in both suicide victims and suicide attempters. Moreover, some studies have shown that SERT has a seasonal variation with lower binding capacity in the spring and summer, which coincides with a seasonal peak of suicides. Our aim was to explore whether the season of treatment initiation with antidepressants is associated with suicide or suicide attempt and compare it with the underlying suicide seasonality in the general population.Using Swedish registers, patients who initiated treatment with an antidepressant were followed up to three months for suicidal behavior. Cox regression analyses were used. Results were compared with the underlying seasonal pattern by calculating standardized mortality ratios (SMRs) for suicides and standardized incidence ratios (SIRs) for suicide attempts.Patients aged ≥65 years had higher risk for suicide when initiating antidepressant treatment in the summer, and also a higher risk for suicide attempt when initiating treatment in the spring and summer. Young patients (0-24 years) presented a higher risk for suicide attempt when initiating treatment in the autumn. Patients with previous suicide attempt had a seasonal pattern, with a higher risk to carry out a suicide attempt in the summer and autumn. Results from the SMR and SIR calculations numerically support these findings.We used information of filling an antidepressant prescription as a proxy of actual antidepressant treatment. Patients with combination, augmentation therapy or those switching antidepressant during follow-up were excluded. Thus, our results refer to less complicated psychopathology.Our results indicate an interaction between biological and health care-related factors for the observed seasonal pattern of suicidal behavior in the elderly, whereas psychological and societal factors may be more important for the seasonality observed in the younger patients.

Background:In the peripartum period, the literature on seasonality in depression is still scarce and studies present varying findings. The aims of this study were to investigate whether seasonal patterns in postpartum depressive symptoms previously identified in a Swedish study could be replicated in a larger study, as well as to assess seasonal patterns in depressive symptoms during pregnancy.Methods:This was a nested case-control study comprised of 4129 women who participated in the BASIC project and gave birth at Uppsala University Hospital, Uppsala, Sweden, between February 2010 and December 2015.Results:Women who gave birth in October–December 2011 had an increased odds of depressive symptoms at 6 weeks postpartum, when compared with women giving birth in April–June 2011 (aOR = 2.42; 95% CI: 1.12–5.26). The same pattern was found among women with a history of depression. No other seasonal patterns for depressive symptoms during pregnancy or at 6 weeks postpartum were identified.Conclusions:In general, no consistent seasonal patterns were found in peripartum depressive symptoms. Whether the seasonal patterns found in some studies during certain years may be due to other factors relating to specific years and seasons, such as extreme climatic conditions or other particular events, warrants further investigation.

Objective: To assess the association between childbearing and mortality from anorexia nervosa (AN). Method: A total of 5,251 females, from a population-based Swedish registry, admitted with an AN diagnosis during the period 1973–2003 were included. Standardized mortality ratios (SMR) were estimated and hazard ratios (HR) were calculated using Cox regression. Results: Nulliparous women had a sixfold higher mortality due to natural causes and ninefold higher mortality due to unnatural causes compared to the general population. Parous women had higher mortality compared to the general population only due to unnatural causes. Suicide was the most common cause of death. Childbearing was associated with a 65% lower mortality. One hundred forty four women out of 1,941 parous women were hospitalized perinatally for any psychiatric disorder (7.4%). Discussion: Childbearing is associated with lower mortality among women with AN. © 2012 by Wiley Periodicals, Inc. (Int J Eat Disord 2013)