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Background: Previously Cloninger’s temperament traits have been researched as a risk factor for depression mostly in cross-sectional studies. In these studies, especially high harm avoidance has been associated with an increased risk of depression. The main objective of this study was to investigate how temperament traits affect the risk of the onset of depression in a previously mentally healthy adult population. Methods: This study includes a follow-up period of 23 years from the age of 31 until 54 in the Northern Finland Birth Cohort 1966 Study. Temperament was measured at the 31-year follow-up using Temperament and Character Inventory (TCI). The outcome of the study was depressive disorder diagnosis during the follow-up in both sexes. To be able to take correlations between temperament traits we also did an analysis using temperament clusters. Results: Our sample size was 3999 individuals, out of which 240 were diagnosed with depression. For women an increase in the TCI score for novelty seeking (NS), harm avoidance (HA) or persistence (P) increased the risk of depression during the follow-up. For men only HA was a significant predictor of depression. An increase in reward dependence (RD) was found to reduce the risk of psychotic depression. In the analysis using the temperament clusters, the cluster including shy and pessimistic individuals was associated with risk for depression diagnosis in men. Conclusions: This prospective general population-based cohort study added to previous knowledge of high HA being a risk factor for depression, but it also found new associations such as higher P and NS.

Background: Several psychological symptoms in adolescence associate with later development of psychosis. However, it is unclear which symptoms specifically predict psychotic disorders rather than psychiatric disorders in general. We conducted a prospective study comparing how specific adolescent psychotic-like symptoms, predicted psychotic and non-psychotic hospital-treated psychiatric disorders in the population-based Northern Finland Birth Cohort 1986 (NFBC1986). Methods: At age 15–16 years, 6632 members of the NFBC1986 completed the PROD-screen questionnaire. New hospital-treated mental disorders of the NFBC1986 participants were detected between age 17 and 30 years from the Finnish Care Register for Health Care. Multiple covariates were used in the analysis. Results: During the follow-up, 1.1% of the participants developed a psychotic and 3.2% a non-psychotic psychiatric disorder. Three symptoms were specifically associated with onset of psychosis compared to non-psychotic psychiatric disorders: ‘Difficulty in controlling one’s speech, behaviour or facial expression while communicating’ (adjusted OR 4.00; 95% CI 1.66–9.92), ‘Difficulties in understanding written text or heard speech’ (OR 2.25; 1.12–4.51), and ‘Difficulty or uncertainty in making contact with other people’ (OR 2.20; 1.03–4.67). Of these, the first one remained statistically significant after Bonferroni correction for multiple comparisons. Conclusions: To our knowledge, this is the first general-population-based prospective study exploring psychiatric symptoms predicting the onset of hospital-treated first-episode psychosis in comparison to non-psychotic disorders. We found three symptoms related with difficulties in social interaction which predicted onset of psychosis. This is a novel finding and should be replicated.

Background: Insufficient physical activity is risk factor for morbidity and premature mortality. This population-based birth cohort study investigated the cross-sectional and longitudinal associations between self-reported temperament at age 31 and self-reported leisure-time moderate to vigorous physical activity (MVPA) levels and changes thereof from the age of 31 to the age of 46 years. Methods: The study population comprised 3,084 subjects (1,359 male and 1,725 female) from the Northern Finland Birth Cohort 1966. MVPA was self-reported at ages 31 and 46 years. Novelty seeking, harm avoidance, reward dependence, and persistence and their subscales were measured using Cloninger’s Temperament and Character Inventory at age 31. Four temperament clusters were used in the analyses: persistent, overactive, dependent, and passive. Logistic regression was used to evaluate the relationship between temperament and MVPA. Results: The persistent and overactive temperament profiles at age 31 were positively associated with higher MVPA levels both in young adulthood and in midlife, while the passive and dependent temperament profiles were associated with lower MVPA levels. The overactive temperament profile was associated with a decrease in MVPA levels from young adulthood to midlife among males. Conclusion: A passive temperament profile characterized by high harm avoidance is associated with a higher risk of low MVPA level than other temperament profiles over the life cycle in females. The results suggest that temperament may play a role in determining the level and sustainability of MVPA. Individual targeting and intervention tailoring for promoting physical activity should consider temperament traits.

Aims: In most population-based epidemiological follow-up studies the aim is not to intervene in the life of the participants. Although the idea is not to intervene, being a member of the longitudinal follow-up study and studies conducted during follow-up may affect the target population. A population-based study including mental health enquiries might reduce the unmet need for psychiatric treatment by motivating people to seek treatment for their psychiatric ill-health. We examined the use of psychiatric care services in the population born in the year 1966 in Northern Finland, of whom 96.3% are participants in the prospective Northern Finland Birth Cohort 1966 (NFBC1966). Methods: As a study cohort we used people born in 1966 in Northern Finland (n = 11 447). The comparison cohort included all the people born in the years 1965 and 1967 in the same geographical area (n = 23 339). The follow-up period was from age 10 to 50 years. The outcome measure was the use of psychiatric care services, which was analysed using Cox Proportional Hazard regression and Zero-Truncated Negative Binomial Regression. Results: People born in 1966 in Northern Finland did not differ from those born in 1965 and 1967 in terms of the outcome measure. Conclusions: We found no association between participation in an epidemiological follow-up study and the use of psychiatric care services. The NFBC1966 may be regarded as a representative at the population level in terms of psychiatric outcomes despite the personal follow-up of the birth cohort. The associations of participation in epidemiological follow-up studies have previously been under-examined, and the results need to be replicated.

Psychiatric illnesses can affect the social transitions of adolescence and young adulthood, such as completing education and entering working life and relationships. However, associations between earlier onset age and long-term outcomes among those with early-onset psychoses (EOP) are unclear, as are the long-term outcomes of EOP compared to non-psychotic disorders. We used national register data of the Northern Finland Birth Cohort 1986 to detect persons with EOP and other early-onset psychiatric disorders. The long-term clinical and work-family outcomes of persons with onset age before 18 years (n = 41 psychoses, n = 495 non-psychoses) or between 18–22 years (n = 61 psychoses, n = 377 non-psychoses) were compared. Individuals with the onset of psychosis between 18–22 years had significantly more unfavourable long-term outcomes when compared to those with psychosis onset before 18 years. Persons with psychosis onset before the age of 18 years had similar outcomes to those with non-psychotic psychiatric disorder onset before 18 years regarding educational level, marital status, having children, and substance use disorders. Individuals with EOP were more often on a disability pension compared to those with other early-onset mental disorders. Adjusting for sex, educational level and substance use only slightly diluted these results. Unexpectedly, later onset age of EOP was associated with worse outcomes. Those with psychosis onset between 18–22 years of age are in a critical period, which underlines the importance of investing on interventions in this age group. Further studies on the effect of the onset age on later outcomes in EOP are needed.

Background: Several observational studies indicate that dietary habits in children and adolescents are associated with school performance. These associations are heavily confounded by socio-economic characteristics, such as household income and parents’ educational attainment, amongst other factors. The objective of this study was to explore the association between diet and school performance in adolescents from the Northern Finland Birth Cohort 1986 (NFBC1986). Methods: Dietary and school performance data were collected using self-reported questionnaires from adolescents in the NFBC1986 cross-sectional, 16-year follow-up study. In this work we derived exploratory factors for the dietary variables, frequency of skipping main meals and school performance variables, performed genome-wide association studies (GWAS) against these factors to obtain genetic association data and conducted one-sample and two-sample Mendelian randomisation (MR) analyses using individual level data for up to 9220 adolescents in NFBC1986 and GWAS results from external cohorts. We report observational and MR effects of diet on school performance and cognition-related phenotypes. Results: The observational study and the one-sample Mendelian randomisation analysis showed that high fat, salt and sugar (HFSS) consumption was associated with poor school performance in general/science subjects (−0.080, −0.128 to −0.033) and staple food consumption with better school performance in general/science subjects (0.071, 0.024 to 0.119) and physical education (0.065, 0.021 to 0.110). Findings from our two-sample MR analysis identified dietary principal components described best as whole brain bread, wheat, cheese, oat cereal and red wine to be associated with higher educational attainment and other cognition-related phenotypes. Conclusion: Using genetics, we highlighted the potential role of HFSS food consumption and consumption of the components of a staple food diet for school performance. However

Background: We studied the association between participation in the longitudinal follow-up study and cardiometabolic disorders in two longitudinal studies which started prospectively in the antenatal period: the Northern Finland Cohort 1966 (NFBC1966) and the Northern Finland Birth Cohort 1986 (NFBC1986). Both birth cohorts have been followed up since birth with multiple follow-ups including questionnaires, and clinical examinations. Methods: The NFBC studies were compared to comparison cohorts of individuals who were born in the same area as the study cohorts, but in different years. The data for the comparison cohort were obtained from registers. The cumulative incidence rates of hospital-treated cardiometabolic disorders were calculated for study and comparison cohorts covering the age of 7–50 years in NFBC1966 and the age of 0–29 years in NFBC1986. Cardiometabolic-related causes of death were analysed in NFBC1966 and the comparison cohort from the age of 0–50 years. The analysed cardiometabolic disorders were diabetes mellitus, coronary artery disease, hyperlipidaemia, obesity, hypertension, and cerebrovascular disorders. The risk ratio (RR) with 95% confidence intervals (CI) was calculated by sex. Results: In NFBC1966, no differences in cumulative incidences of cardiometabolic disorders or cardiometabolic-related deaths compared to the comparison cohort were found. Male members of NFBC1986 had decreased risk of obesity (RR: 0.45, 95% CI: 0.27–0.75) and any cardiometabolic disorders (RR: 0.75, 95% CI: 0.59–0.95) compared to the comparison cohort. Conclusions: The results suggest that participation in the NFBC1986 may have a weak positive health effect among men. Agreement to follow-up studies focusing on diet, substance use, and physical activity, may slightly decrease the incident risk of cardiometabolic disorders in the study population.

Objective: Increasing number of people have been prescribed antipsychotics (APs) off-label in recent decades. This study aimed to identify the characteristics and predictors of receiving prescription of antipsychotics off-label. Methods: The study sample was part of the Northern Finland Birth Cohort 1966 (n = 7071). Data included questionnaires and national register data. Information on prescribed medications was extracted from the national register. The sample was divided into three groups: Persons who had been prescribed APs off-label (n = 137), individuals with non-psychotic mental disorders without APs off label (n = 1478) and individuals who had been diagnosed with psychosis or bipolar disorder and who had been prescribed APs (n = 151). We compared sociodemographic, lifestyle and clinical characteristics between the off-label and the comparison groups using logistic regression. Results: The most common diagnoses in the off-label group were depression (n = 96, 70.1%) and anxiety (n = 55, 40.1%). Compared with individuals with non-psychotic mental disorders who were not prescribed APs off-label, individuals with prescribed off-label APs had a lower level of education, lower socioeconomic status, were less often married, had a higher level of somatic and psychiatric morbidity, were more often smokers and more often had a substance abuse disorder and heavy alcohol consumption. When comparing the off-label group to individuals with psychosis or bipolar disorder who used APs, there were less differences, though individuals with psychosis or bipolar disorder had more markers of morbidity and a lower level of education. Conclusions: Individuals who had been prescribed APs off label had a higher level of mental and somatic morbidity and poorer socioeconomic status than individuals with non-psychotic mental disorders who did not use APs.

Aim: The aim of this study was to explore whether active participation in a longitudinal birth cohort study is associated with study participants’ health behaviour and well-being. Methods: The subjects of this study were part of the Northern Finland Birth Cohort 1966. The follow-up data were collected through clinical examinations and questionnaires when the cohort members were 1, 14, 31 and 46 years old. In this study, cohort participation activity was divided into three categories: active, semiactive and least active. Results: The total number of study participants who participated in the 46-year follow-up on both the survey and clinical trials was 6392, of which 66.5% (n=4268) participated actively in the cohort study. A total of 67.6% were female (p<0.001). Of the participants, 23.7% (n=1519) were semiactive and 9.5% (n=605) were the least active. Women who participated least actively experienced statistically significantly more depressive symptoms and poorer health, were more dissatisfied with their lives and had more addiction problems. In men, there was not a statistically significant association between participation activity and these well-being variables other than addiction problems and mental health. Conclusions: The findings indicate that participation activity is associated with better self-reported health and well-being, especially among women. With this knowledge, people can be encouraged to participate in longitudinal health research and, at the same time, may improve their own health and quality of life.

Aims: Rates of parental separation have increased dramatically in recent decades. We evaluated the association of individuals’ childhood family structure with their somatic health over 46 years of follow-up. Methods: Data were drawn from the Northern Finland Birth Cohort, an ongoing project in which 12,058 participants born in 1966 have been followed from their 24th gestational week. Based on information supplied at age 14 years, family structure was categorised as ‘single-parent family’ and ‘two-parent family’. The anthropometric information, data from blood samples and medical history were collected from postal questionnaires and clinical examinations routinely performed at the ages of 31 and 46 years. Results: The study population comprised a total of 10,895 individuals; 85% (n=9253) were offspring of two-parent families and 15% (n=1642) of single-parent families. Type 2 diabetes (P=0.032) or prediabetes (P=0.007), psychoactive drug problems (P<0.001) and sexually transmitted diseases (P<0.001) were more common in the single-parent family group than in the participants from two-parent families. In addition, among men back diseases (P=0.002), and among women hypertension (P=0.003) and ovary infection (P=0.024) were more frequent in individuals affected by parental death than in those from two-parent families. Conclusions: Our results indicate the association of childhood family structure with offspring morbidity during 46 years’ follow-up. The lifetime morbidity was observed to be higher among offspring from a single-parent family compared to two-parent family offspring. Public and scientific concern about the consequences of parental separation on the offspring’ health exist, therefore support from healthcare professionals and society is warranted.

Purpose: Psychoses are associated with poor labour market attachment, but few studies have compared schizophrenia (SZ) and other psychoses (OP). Moreover, studies on long-term employment trajectories over individuals’ working life courses are lacking. We compared 30 year employment trajectory patterns in a general population sample among individuals with SZ, OP, and those with no psychosis (NP). Methods: Utilising the Northern Finland Birth Cohort 1966, we collected survey data on employment from ages 16 to 45 and detected individuals with register-based history of SZ (n = 62), OP (n = 87), or NP (n = 6464) until age 46. Through gender-specific latent class analyses on annual employment roles, we identified traditional, highly educated, self-employed, delayed and floundering employment trajectories with distinct socioeconomic characteristics. We addressed attrition by conducting weighted analyses. Results: Floundering trajectories were common among individuals with SZ (79% of men, 73% of women) and OP (52% of men, 51% of women). In NP, a traditional employee trajectory was most common in men (31%), and a highly educated trajectory in women (28%). A history of psychosis was associated with heightened odds ratios (ORs; 95% confidence intervals (CIs)) for floundering trajectories in both men (SZ: 32.9 (13.3–81.4); OP: 7.4 (4.0–13.9)) and women (SZ: 9.9 (4.6–21.5); OP: 3.9 (2.1–7.1)) compared to NP. Weighted analyses produced similar results. Conclusion: Most individuals with SZ or OP have floundering employee trajectories reflecting an elevated risk of unemployment and part-time work until midlife. These results indicate the importance of improving labour market attachment during the early phases of psychoses.

Climate warming in Arctic Canada, e.g., permafrost thaw, comprehensively impacts biota and the environment, which then affects the lives of people. This study aimed to investigate which perceived environmental and adaptation factors relate to self-rated well-being, quality of life, satisfaction with life (sum variable = life balance), self-rated health, and feeling of empowerment to face the changes related to permafrost thaw. The study sample was collected from one community using a questionnaire (n = 53) and analyzed by cross-tabulation. Results indicated that most participants had at least good well-being, quality of life, satisfaction with life, and a medium level of health, and over 40% assessed being empowered to face the changes related to permafrost thaw. Problems and challenges associated with permafrost thaw, e.g., health, traditional lifeways, and infrastructure, were recognized; these had impacts on life balance, feeling of empowerment, and self-rated health. Traditional knowledge regarding adaptation to face changes was seen as important. More adaptation actions from the individual to global level seemed to be needed. This study provides an overview of the situation in one area, but more research, with a larger study sample, should be conducted to achieve a deeper understanding of climate-related impacts on life and holistic well-being.

Parental death before adulthood has been shown to increase offspring’s risk of poor health and adverse social consequences. In a sample of 422 subjects with parental death (334 (79.1%) due to natural causes), and 6172 matched controls, those with parental death were given a diagnosis of a psychiatric disorder up to 28 years of age earlier than their controls (10-year survival proportions: 88.6% vs. 93.1%, p = 0.001). Our findings indicate that psychosocial support must be provided as early as when a parent falls ill, especially with those illnesses that are the most common causes of death in the population.

Background: Psychotic depression (PD) is an under-researched disorder with severe symptoms and course of illness. Little is known about gender differences relating to this condition and possible variation of prognosis based on comorbid pathology. Our aim was to analyze the effects of gender and psychiatric comorbidities on the age of illness onset and on the outcome of psychotic depression. Methods: The study was carried out in the Northern Finland Birth Cohort 1966. We utilized register data to acquire information about lifetime psychiatric diagnoses, hospitalization, age of illness onset, rate of disability pensions and mortality. The PD group (n = 58) was defined based on a lifetime register diagnosis. We compared outcome variables in sub-groups based on gender and comorbid alcohol use or personality disorder. Results: The prevalence of comorbid personality disorders was 38% (22/58) and comorbid alcohol use disorders 41% (24/58). PD patients with a personality disorder diagnosis had an earlier onset age (p<0.01) and a higher mortality rate (p = 0.03). Male gender (p = 0.03), comorbid alcohol use disorder (p%lt;0.01) and personality disorder (p %lt; 0.01) were all associated with more psychiatric hospitalization. Comorbid alcohol use disorder was more common among men (males: 61%; females: 29%; p = 0.03). Limitations: National registers were the main source of diagnostic information. Conclusions: Gender and psychiatric comorbidity have significant implications for the course of illness in PD in naturalistic settings, which is an important message for all clinicians. More research into the heterogeneity of PD is needed in order to guide research and clinical practice.

Background: Climate change is a major global challenge, especially for Indigenous communities. It can have extensive impacts on peoples’ lives that may occur through the living environment, health and mental well-being, and which are requiring constant adaptation. Objectives: The overall purpose of this research was to evaluate the impacts of climate change and permafrost thaw on mental wellness in Disko Bay, Greenland. It contained two parts: multidisciplinary fieldwork and a questionnaire survey. The aim of the fieldwork was to learn about life and living conditions and to understand what it is like to live in a community that faces impacts of climate change and permafrost thaw. For the questionnaire the aim was to find out which perceived environmental and adaptation factors relate to very good self-rated well-being, quality of life and satisfaction with life. Analysis: Fieldwork data was analyzed by following a thematic analysis, and questionnaire data statistically by cross-tabulation. First, the associations between perceived environmental and adaptation factors were studied either by the Pearson χ² test or by Fisher's exact test. Second, binary logistic regression analysis was applied to examine more in depth the associations between perceived environmental/adaptation variables and self-rated very good well-being, satisfaction with life and quality of life. The binary logistic regression analysis was conducted in two phases: as univariate and multivariate analyses. Results: Nature and different activities in nature were found to be important to local people, and results suggest that they increase mental wellness, specifically well-being and satisfaction with life. Challenges associated with permafrost thaw, such as changes in the physical environment, infrastructure and impacts on culture were recognized in everyday life. Conclusions: The results offer relevant information for further plans and actions in this field of research and at the policy leve

In the version of this article originally published, the names of the equally contributing authors and jointly supervising authors were switched. The correct affiliations are: “These authors contributed equally: David V. Conti, Burcu F. Darst. These authors jointly supervised this work: David V. Conti, Rosalind A. Eeles, Zsofia Kote-Jarai, Christopher A. Haiman.” The error has been corrected in the HTML and PDF versions of the article.

Prostate cancer is a highly heritable disease with large disparities in incidence rates across ancestry populations. We conducted a multiancestry meta-analysis of prostate cancer genome-wide association studies (107,247 cases and 127,006 controls) and identified 86 new genetic risk variants independently associated with prostate cancer risk, bringing the total to 269 known risk variants. The top genetic risk score (GRS) decile was associated with odds ratios that ranged from 5.06 (95% confidence interval (CI), 4.84-5.29) for men of European ancestry to 3.74 (95% CI, 3.36-4.17) for men of African ancestry. Men of African ancestry were estimated to have a mean GRS that was 2.18-times higher (95% CI, 2.14-2.22), and men of East Asian ancestry 0.73-times lower (95% CI, 0.71-0.76), than men of European ancestry. These findings support the role of germline variation contributing to population differences in prostate cancer risk, with the GRS offering an approach for personalized risk prediction.

Background: Low IQ is a risk factor for psychosis, but the effect of high IQ is more controversial. The aim was to explore the association of childhood school success with prodromal symptoms in adolescence and psychoses in adulthood. Methods: In the general population-based Northern Finland Birth Cohort 1986 (n = 8 229), we studied the relationship between teacher-assessed learning deficits, special talents and general school success at age 8 years and both prodromal symptoms (PROD-screen) at age 15–16 years and the occurrence of psychoses by age 30 years. Results: More prodromal symptoms were experienced by those talented in oral presentation [boys: adjusted odds ratio (OR) 1.49; 95% confidence interval 1.14–1.96; girls: 1.23; 1.00–1.52] or drawing (boys: 1.44; 1.10–1.87). Conversely, being talented in athletics decreased the probability of psychotic-like symptoms (boys: OR 0.72; 0.58–0.90). School success below average predicted less prodromal symptoms with boys (OR 0.68; 0.48–0.97), whereas above-average success predicted more prodromal symptoms with girls (OR 1.22; 1.03–1.44). The occurrence of psychoses was not affected. Learning deficits did not associate with prodromal symptoms or psychoses. Conclusions: Learning deficits in childhood did not increase the risk of prodromal symptoms in adolescence or later psychosis in this large birth cohort. Learning deficits are not always associated with increased risk of psychosis, which might be due to, e.g. special support given in schools. The higher prevalence of prodromal symptoms in talented children may reflect a different kind of relationship of school success with prodromal symptoms compared to full psychoses.

Background and purpose: In the group of severe mental disorders, psychotic depression (PD) is essentially under-researched. Knowledge about the risk factors is scarce and this applies especially to early risk factors. Our aim was to study early childhood and adolescent risk factors of PD in a representative birth cohort sample with a follow-up of up to 50 years. Methods: The study was carried out using the Northern Finland Birth Cohort 1966 (NFBC 1966). We used non-psychotic depression (NPD) (n = 746), schizophrenia (SZ) (n = 195), psychotic bipolar disorder (PBD) (n = 27), other psychoses (PNOS) (n = 136) and healthy controls (HC) (n = 8200) as comparison groups for PD (n = 58). We analysed several potential early risk factors from time of birth until the age of 16 years. Results: The main finding was that parents’ psychiatric illness [HR 3.59 (1.84–7.04)] was a risk factor and a high sports grade in school was a protective factor [HR 0.29 (0.11–0.73)] for PD also after adjusting for covariates in the multivariate Cox regression model. Parental psychotic illness was an especially strong risk factor for PD. The PD subjects had a parent with psychiatric illness significantly more often (p < 0.05) than NPD subjects. Differences between PD and other disorder groups were otherwise small. Conclusions: A low sports grade in school may be a risk factor for PD. Psychiatric illnesses, especially psychoses, are common in the parents of PD subjects. A surprisingly low number of statistically significant risk factors may have resulted from the size of the PD sample and the underlying heterogeneity of the etiology of PD.

Background: We studied the cumulative incidence of physical illnesses, and the effect of early environmental factors (EEFs) on somatic comorbidity in schizophrenia, in nonschizophrenic psychosis and among nonpsychotic controls from birth up to the age of 50 years. Methods: The sample included 10,933 members of the Northern Finland Birth Cohort 1966, of whom, 227 had schizophrenia and 205 had nonschizophrenic psychosis. Diagnoses concerning physical illnesses were based on nationwide registers followed up to the end of 2016 and classified into 13 illness categories. Maternal education and age, family type at birth and paternal socioeconomic status were studied as EEFs of somatic illnesses. Results: When adjusted by gender and education, individuals and especially women with nonschizophrenic psychosis had higher risk of morbidity in almost all somatic illness categories compared to controls, and in some categories, compared to individuals with schizophrenia. The statistically significant adjusted hazard ratios varied from 1.27 to 2.42 in nonschizophrenic psychosis. Regarding EEFs, single-parent family as the family type at birth was a risk factor for a higher somatic score among men with schizophrenia and women with nonschizophrenic psychosis. Maternal age over 35 years was associated with lower somatic score among women with nonschizophrenic psychosis. Conclusions: Persons with nonschizophrenic psychoses have higher incidence of somatic diseases compared to people with schizophrenia and nonpsychotic controls, and this should be noted in clinical work. EEFs have mostly weak association with somatic comorbidity in our study.