Body Dysmorphic Symptoms in Youth with Obsessive-compulsive Disorder: Prevalence, Clinical Correlates, and Cognitive Behavioral Therapy Outcome.

The aims of the study were to estimate the prevalence of body dysmorphic symptoms in a sample of children and adolescents with obsessive-compulsive disorder, possible clinical correlates and whether BDD symptoms predict poorer treatment outcomes after cognitive behavioral therapy. The study included 269 children and adolescents with OCD, aged 7-17 years, from Denmark, Sweden, and Norway, who were treated with 14 weekly sessions of manualized, exposure-based CBT. Twenty-one patients (7.8%) had BDD symptoms. BDD symptoms were associated with older age (p = 0.003) and a higher prevalence of comorbid anxiety disorders (p = 0.025). In addition, patients with BDD symptoms endorsed a greater number of OCD symptoms than did those without BDD symptoms. Having symptoms of BDD did not affect the CBT outcome on OCD. The results of the study suggest that CBT for OCD is equally effective for those with and without comorbid BDD symptoms.

Business cycles, hypertension and cardiovascular disease: evidence from the Icelandic economic collapse.

BACKGROUND: Business cycles affect people's lives. A growing literature examines their effect on health outcomes. The available studies on the relationship between ambient economic conditions and cardiovascular health show mixed results. They are furthermore limited in their outcome measures, focusing mostly on mortality. METHODS: We examined the relationship between economic conditions and cardiovascular disease and hypertension, using the Icelandic economic collapse of 2008. Logit regression analyses are used to examine the relationship between economic conditions and the probability of reporting a cardiovascular disease or hypertension. We furthermore investigated potential mediators of this relationship. The data used come from a health and lifestyle survey carried out by the Public Health Institute of Iceland in 2007 and 2009. RESULTS: The crisis was positively related to hypertension in males but no statistically significant relationship was found for females. The mediation analyses indicated partial mediation through changes in working hours and stress level, but negligible mediation through changes in income. The male hypertension was, however, suppressed by concurrent changes in smoking and body weight. CONCLUSIONS: Only examining mortality effects of society-wide economic conditions may understate the overall effect on cardiovascular health.

Rare variant associations with birth weight identify genes involved in adipose tissue regulation, placental function and insulin-like growth factor signalling.

Investigating the genetic factors influencing human birth weight may lead to biological insights into fetal growth and long-term health. Genome-wide association studies of birth weight have highlighted associated variants in more than 200 regions of the genome, but the causal genes are mostly unknown. Rare genetic variants with robust evidence of association are more likely to point to causal genes, but to date, only a few rare variants are known to influence birth weight. We aimed to identify genes that harbour rare variants that impact birth weight when carried by either the fetus or the mother, by analysing whole exome sequence data in UK Biobank participants. We annotated rare (minor allele frequency <0.1%) protein-truncating or high impact missense variants on whole exome sequence data in up to 234,675 participants with data on their own birth weight (fetal variants), and up to 181,883 mothers who reported the birth weight of their first child (maternal variants). Variants within each gene were collapsed to perform gene burden tests and for each associated gene, we compared the observed fetal and maternal effects. We identified 8 genes with evidence of rare fetal variant effects on birth weight, of which 2 also showed maternal effects. One additional gene showed evidence of maternal effects only. We observed 10/11 directionally concordant associations in an independent sample of up to 45,622 individuals (sign test P=0.01). Of the genes identified, IGF1R and PAPPA2 (fetal and maternal-acting) have known roles in insulin-like growth factor bioavailability and signalling. PPARG, INHBE and ACVR1C (all fetal-acting) have known roles in adipose tissue regulation and rare variants in the latter two also showed associations with favourable adiposity patterns in adults. We highlight the dual role of PPARG in both adipocyte differentiation and placental angiogenesis. NOS3, NRK, and ADAMTS8 (fetal and maternal-acting) have been implicated in both placental function and hypertension. Analysis of rare coding variants has identified regulators of fetal adipose tissue and fetoplacental angiogenesis as determinants of birth weight, as well as further evidence for the role of insulin-like growth factors.

How sensitive is the compensating income variation to severity and adaptation?

Knowing the monetary value individuals place on health is essential in tackling resource allocation between health and other uses. However, health conditions vary greatly, not only with respect to main characteristics but also by severity and duration. We apply the compensating income variation (CIV) method to data from the Swiss Household Panel, years 2004-2019, to explore the sensitivity of CIV estimates to severity and adaptation across five different health conditions: headaches, back problems, sleep problems, fatigue, and chronic illness. Accounting for income endogeneity in the life-satisfaction equations and adjusting for individual random effects, we found the CIV estimates to range from $3184 for moderate headaches (women) to $100,066 for severe fatigue (men). Individuals with severe conditions needed to be compensated about three times more than those suffering less. Across the five conditions with two severity levels explored for adaptation, individuals only adapted to moderate headaches and severe sleep problems. In conclusion, not only does the value of health conditions vary greatly, but within each health condition its value on average triples when severe condition is reported as opposed to moderate. Adaptation plays a minor role in CIV estimates for the five health conditions explored.

Physical and cognitive impact following SARS-CoV-2 infection in a large population-based case-control study.

BACKGROUND: Persistent symptoms are common after SARS-CoV-2 infection but correlation with objective measures is unclear. METHODS: We invited all 3098 adults who tested SARS-CoV-2 positive in Iceland before October 2020 to the deCODE Health Study. We compared multiple symptoms and physical measures between 1706 Icelanders with confirmed prior infection (cases) who participated, and 619 contemporary and 13,779 historical controls. Cases participated in the study 5-18 months after infection. RESULTS: Here we report that 41 of 88 symptoms are associated with prior infection, most significantly disturbed smell and taste, memory disturbance, and dyspnea. Measured objectively, cases had poorer smell and taste results, less grip strength, and poorer memory recall. Differences in grip strength and memory recall were small. No other objective measure associated with prior infection including heart rate, blood pressure, postural orthostatic tachycardia, oxygen saturation, exercise tolerance, hearing, and traditional inflammatory, cardiac, liver, and kidney blood biomarkers. There was no evidence of more anxiety or depression among cases. We estimate the prevalence of long Covid to be 7% at a median of 8 months after infection. CONCLUSIONS: We confirm that diverse symptoms are common months after SARS-CoV-2 infection but find few differences between cases and controls in objective parameters measured. These discrepancies between symptoms and physical measures suggest a more complicated contribution to symptoms related to prior infection than is captured with conventional tests. Traditional clinical assessment is not expected to be particularly informative in relating symptoms to a past SARS-CoV-2 infection.

Persistent symptoms are commonly reported after SARS-CoV-2 infection, and this is often described as long Covid. We compared different symptoms reported following SARS-CoV- 2 infection with the results obtained during various medical evaluations that are often used to assess health, such as blood tests, smell tests, taste tests, hearing tests, etc. We compared symptoms and test results between 1,706 Icelanders who had been infected previously with SARS-CoV-2 infection (cases) and 14,398 individuals who had not been infected (controls). Out of 88 assessed symptoms, 41 were more common in cases than controls. However, relatively few differences were seen in the results obtained from the various medical evaluations (cases had poorer smell and taste test results, slightly less grip strength, and slightly poorer memory recall than controls). The differences seen between symptoms and results of medical evaluations suggests that conventional clinical tests may not be informative in relating symptoms to a past SARS-CoV-2 infection.

HLA alleles, disease severity, and age associate with T-cell responses following infection with SARS-CoV-2.

Memory T-cell responses following SARS-CoV-2 infection have been extensively investigated but many studies have been small with a limited range of disease severity. Here we analyze SARS-CoV-2 reactive T-cell responses in 768 convalescent SARS-CoV-2-infected (cases) and 500 uninfected (controls) Icelanders. The T-cell responses are stable three to eight months after SARS-CoV-2 infection, irrespective of disease severity and even those with the mildest symptoms induce broad and persistent T-cell responses. Robust CD4+ T-cell responses are detected against all measured proteins (M, N, S and S1) while the N protein induces strongest CD8+ T-cell responses. CD4+ T-cell responses correlate with disease severity, humoral responses and age, whereas CD8+ T-cell responses correlate with age and functional antibodies. Further, CD8+ T-cell responses associate with several class I HLA alleles. Our results, provide new insight into HLA restriction of CD8+ T-cell immunity and other factors contributing to heterogeneity of T-cell responses following SARS-CoV-2 infection.

The genetic architecture of age-related hearing impairment revealed by genome-wide association analysis.

Age-related hearing impairment (ARHI) is the most common sensory disorder in older adults. We conducted a genome-wide association meta-analysis of 121,934 ARHI cases and 591,699 controls from Iceland and the UK. We identified 21 novel sequence variants, of which 13 are rare, under either additive or recessive models. Of special interest are a missense variant in LOXHD1 (MAF = 1.96%) and a tandem duplication in FBF1 covering 4 exons (MAF = 0.22%) associating with ARHI (OR = 3.7 for homozygotes, P = 1.7 × 10-22 and OR = 4.2 for heterozygotes, P = 5.7 × 10-27, respectively). We constructed an ARHI genetic risk score (GRS) using common variants and showed that a common variant GRS can identify individuals at risk comparable to carriers of rare high penetrance variants. Furthermore, we found that ARHI and tinnitus share genetic causes. This study sheds a new light on the genetic architecture of ARHI, through several rare variants in both Mendelian deafness genes and genes not previously linked to hearing.

Loss-of-Function Variants in the Tumor-Suppressor Gene PTPN14 Confer Increased Cancer Risk.

The success of genome-wide association studies (GWAS) in identifying common, low-penetrance variant-cancer associations for the past decade is undisputed. However, discovering additional high-penetrance cancer mutations in unknown cancer predisposing genes requires detection of variant-cancer association of ultra-rare coding variants. Consequently, large-scale next-generation sequence data with associated phenotype information are needed. Here, we used genotype data on 166,281 Icelanders, of which, 49,708 were whole-genome sequenced and 408,595 individuals from the UK Biobank, of which, 41,147 were whole-exome sequenced, to test for association between loss-of-function burden in autosomal genes and basal cell carcinoma (BCC), the most common cancer in Caucasians. A total of 25,205 BCC cases and 683,058 controls were tested. Rare germline loss-of-function variants in PTPN14 conferred substantial risks of BCC (OR, 8.0; P = 1.9 × 10-12), with a quarter of carriers getting BCC before age 70 and over half in their lifetime. Furthermore, common variants at the PTPN14 locus were associated with BCC, suggesting PTPN14 as a new, high-impact BCC predisposition gene. A follow-up investigation of 24 cancers and three benign tumor types showed that PTPN14 loss-of-function variants are associated with high risk of cervical cancer (OR, 12.7, P = 1.6 × 10-4) and low age at diagnosis. Our findings, using power-increasing methods with high-quality rare variant genotypes, highlight future prospects for new discoveries on carcinogenesis. SIGNIFICANCE: This study identifies the tumor-suppressor gene PTPN14 as a high-impact BCC predisposition gene and indicates that inactivation of PTPN14 by germline sequence variants may also lead to increased risk of cervical cancer.

Valuing pain using the subjective well-being method.

Chronic pain clearly lowers utility, but valuing the reduction in utility is empirically challenging. Here, we use improvements over prior applications of the subjective well-being method to estimate the implied trade-off between pain and income using four waves of the Health and Retirement Study (2008-2014), a nationally representative survey on individuals age 50 and older. We model income with a flexible functional form, allowing the trade-off between pain and income to vary across income groups. We control for individual fixed effects in the life-satisfaction equations and instrument for income in some models. We find values for avoiding pain ranging between 56-145 USD per day. These results are lower than previously reported and suggest that the higher previous estimates may be heavily affected by the highest income level and confounded by endogeneity in the income variable. As expected, we find that the value of pain relief increases with pain severity.

Genome-wide association identifies seven loci for pelvic organ prolapse in Iceland and the UK Biobank.

Pelvic organ prolapse (POP) is a downward descent of one or more of the pelvic organs, resulting in a protrusion of the vaginal wall and/or uterus. We performed a genome-wide association study of POP using data from Iceland and the UK Biobank, a total of 15,010 cases with hospital-based diagnosis code and 340,734 female controls, and found eight sequence variants at seven loci associating with POP (P < 5 × 10-8); seven common (minor allele frequency >5%) and one with minor allele frequency of 4.87%. Some of the variants associating with POP also associated with traits of similar pathophysiology. Of these, rs3820282, which may alter the estrogen-based regulation of WNT4, also associates with leiomyoma of uterus, gestational duration and endometriosis. Rs3791675 at EFEMP1, a gene involved in connective tissue homeostasis, also associates with hernias and carpal tunnel syndrome. Our results highlight the role of connective tissue metabolism and estrogen exposure in the etiology of POP.

A compensating income variation approach to valuing 34 health conditions in Iceland.

Using data from an Icelandic health-and-lifestyle survey carried out in 2007, 2009, and 2012, we employ a compensating income variation (CIV) approach to estimate the monetary value sufficient to compensate individuals for the presence of various sub-optimal health conditions. This method is inexpensive and easy on subjects and has been applied to several desiderata that do not have revealed market prices. The CIV literature is, however, still limited in its application to health and thus information about its suitability is limited. With the aim of shedding light on the method́s appropriateness we thus provide a broad-view analysis including a spectrum of diseases and conditions that can be held up against more traditionally used methods. CIV for physical conditions vary greatly, but paralysis, fibromyalgia, chronic back pain, rheumatoid arthritis, urinary incontinence, severe headache and thyroid disease were among those consistently associated with substantial well-being reductions. Mental-health results using this method should be read with caution. The societal value of health interventions is multidimensional, including for example increased productivity in the population. However, one of the main positive aspects of increased health is undoubtedly the increased well-being of the treated subjects. Such quality-of-life effects should thus preferably be taken into account. For this reason, information on the value individuals place on recovery from various sub-optimal health conditions is useful when it comes to prioritizing scarce capital in the health sector. It is therefore vital to estimate the importance individuals place on various health states and hold them up against each other. Furthermore, this paper has scientific value as it sheds light on attributes of a potentially useful method in health evaluations.

The tax-free year in Iceland: A natural experiment to explore the impact of a short-term increase in labor supply on the risk of heart attacks.

Evidence is mixed on whether society-wide economic conditions affect cardiovascular health and the reasons for the suggested relationship are largely untested. We explore whether a short-term increase in labor supply affects the probability of acute myocardial infarctions, using a natural experiment in Iceland. In 1987 personal income taxes were temporarily reduced to zero, resulting in an overall increase in labor supply. We merge and analyze individual-level, registry-based data on earnings and AMIs including all Icelandic men and women aged 45-74 during the period 1982-1992. The results support the prominent hypothesis of increased work as a mechanism explaining worsening heart health in upswings, for men aged 45-64 who were self-employed. We furthermore find a larger increase in probability of AMIs during the tax-free year in men aged 45-54 than men aged 55-64.

The Icelandic economic collapse, smoking, and the role of labor-market changes.

Smoking is related to health deterioration through increased risk of various diseases. Changes in this health behavior could contribute to the documented health improvements during economic downturns. Furthermore, the reasons for changes in behavior are not well understood. We explore smoking behavior in Iceland before and after the sudden and unexpected economic crisis in 2008. Furthermore, to explore the mechanisms through which smoking could be affected we focus on the role of labor-market changes. Both real income and working hours fell significantly and economic theory suggests that such changes can affect health behaviors which in turn affect health. We use individual longitudinal data from 2007 to 2009, incidentally before and after the crisis hit. The data originates from a postal survey, collected by The Public Health Institute in Iceland. Two outcomes are explored: smoking participation and smoking intensity, using pooled ordinary least squares (OLS) and linear probability models. The detected reduction in both outcomes is not explained by the changes in labor-market variables. Other factors in the demand function for tobacco play a more important role. The most notable are real prices which increased in particular for imported goods because of the devaluation of the Icelandic currency as a result of the economic collapse.

Was the economic crisis of 2008 good for Icelanders? Impact on health behaviors.

This study uses the 2008 economic crisis in Iceland to identify the effects of a macroeconomic downturn on a range of health behaviors. We use longitudinal survey data that include pre- and post-reports from the same individuals on a range of health-compromising and health-promoting behaviors. We find that the crisis led to large and significant reductions in health-compromising behaviors (such as smoking, drinking alcohol or soft drinks, and eating sweets) and certain health-promoting behaviors (consumption of fruits and vegetables), but to increases in other health-promoting behaviors (consumption of fish oil and recommended sleep). The magnitudes of effects for smoking are somewhat larger than what has been found in past research in other contexts, while those for alcohol, fruits, and vegetables are in line with estimates from other studies. Changes in work hours, real income, financial assets, mortgage debt, and mental health, together, explain the effects of the crisis on some behaviors (such as consumption of sweets and fast food), while the effects of the crisis on most other behaviors appear to have operated largely through price increases.