Association between Mental Disorders and Subsequent Medical Conditions.

BACKGROUND: Persons with mental disorders are at a higher risk than the general population for the subsequent development of certain medical conditions. METHODS: We used a population-based cohort from Danish national registries that included data on more than 5.9 million persons born in Denmark from 1900 through 2015 and followed them from 2000 through 2016, for a total of 83.9 million person-years. We assessed 10 broad types of mental disorders and 9 broad categories of medical conditions (which encompassed 31 specific conditions). We used Cox regression models to calculate overall hazard ratios and time-dependent hazard ratios for pairs of mental disorders and medical conditions, after adjustment for age, sex, calendar time, and previous mental disorders. Absolute risks were estimated with the use of competing-risks survival analyses. RESULTS: A total of 698,874 of 5,940,299 persons (11.8%) were identified as having a mental disorder. The median age of the total population was 32.1 years at entry into the cohort and 48.7 years at the time of the last follow-up. Persons with a mental disorder had a higher risk than those without such disorders with respect to 76 of 90 pairs of mental disorders and medical conditions. The median hazard ratio for an association between a mental disorder and a medical condition was 1.37. The lowest hazard ratio was 0.82 for organic mental disorders and the broad category of cancer (95% confidence interval [CI], 0.80 to 0.84), and the highest was 3.62 for eating disorders and urogenital conditions (95% CI, 3.11 to 4.22). Several specific pairs showed a reduced risk (e.g., schizophrenia and musculoskeletal conditions). Risks varied according to the time since the diagnosis of a mental disorder. The absolute risk of a medical condition within 15 years after a mental disorder was diagnosed varied from 0.6% for a urogenital condition among persons with a developmental disorder to 54.1% for a circulatory disorder among those with an organic mental disorder. CONCLUSIONS: Most mental disorders were associated with an increased risk of a subsequent medical condition; hazard ratios ranged from 0.82 to 3.62 and varied according to the time since the diagnosis of the mental disorder. (Funded by the Danish National Research Foundation and others; COMO-GMC ClinicalTrials.gov number, NCT03847753.).

School performance and genetic propensities for educational attainment and depression in the etiology of self-harm: a Danish population-based study.

BACKGROUND: Poor school performance is linked to higher risks of self-harm. The association might be explained through genetic liabilities for depression or educational attainment. We investigated the association between school performance and self-harm in a population-based sample while assessing the potential influence of polygenic risk scores (PRSs) for depression (PRSMDD) and for educational attainment (PRSEDU). METHOD: We conducted a follow-up study of individuals born 1987-98 and followed from age 18 until 2016. The total sample consisted of a case group (23,779 diagnosed with mental disorders; schizophrenia, bipolar disorder, depression, autism, and attention deficit hyperactivity disorder (ADHD) and a randomly sampled comparison group (n = 10,925). Genome-wide data were obtained from the Neonatal Screening Biobank and information on school performance, family psychiatric history, and socioeconomic status from national administrative registers. RESULTS: Individuals in the top PRSMDD decile were at higher self-harm risk in the case group (IRR: 1.30; 95% CI 1.15-1.46), whereas individuals in the top PRSEDU decile were at lower self-harm risk (IRR: 0.63; 95% CI: 0.55-0.74). Poorer school performance was associated with higher self-harm risk in persons diagnosed with any mental disorder (IRR: 1.69; 95% CI: 1.44-1.99) and among the comparison group (IRR: 7.93; 95% CI: 4.47-15.18). Observed effects of PRSMDD and PRSEDU on self-harm risk were strongest for individuals with poor school performance. CONCLUSION: Associations between PRSMDD and self-harm risk and between PRSEDU and self-harm risk were found. Nevertheless, these polygenic scores seem currently of limited clinical utility for identifying individuals at high self-harm risk.

Intergenerational transmission of suicide attempt in a cohort of 4.4 million children.

BACKGROUND: The association between suicide attempts (SAs) in parents and children is unclear, and risk indicators for intergenerational transmission remain undocumented. We aimed to assess this association, considering the child's developmental period at the time of parents' attempted suicide, and the parental relation. METHODS: Using a prospective cohort design, nationwide population data were linked to the Psychiatric Central Register and National Patient Register for all individuals aged 10 years or older living in Denmark between 1980 and 2016. We assessed incidence rate ratios (IRRs) and cumulative hazards for children's first SA. RESULTS: In a cohort of 4 419 651 children, 163 056 (3.7%) had experienced a parental SA. An SA was recorded among 6996 (4.3%) of the exposed children as opposed to 70112 (1.6%) in unexposed individuals. Higher rates were noted when a parental SA occurred during early childhood (0 ⩽ age < 2) [IRR, 4.7; 95% confidence interval (CI) 4.2-5.4] v. late childhood (6 ⩽ age < 13) (IRR, 3.6; 95% CI 3.4-3.8) when compared to those unexposed. Children exposed prior to age 2 had the highest rates of all sub-groups when reaching age 13-17 (IRR, 6.5; 95% CI 6.0-7.1) and 18-25 years (IRR, 6.8; 95% CI 6.2-7.4). Maternal SA (IRR, 3.4; 95% CI 3.2-3.5) was associated with higher rates than paternal (IRR, 2.8; 95% CI 2.7-2.9). CONCLUSION: Parental SA was associated with children's own SA. Exposure during early developmental stages was associated with the highest rates. Early preventive efforts are warranted as is monitoring of suicide risk in the children from age 13.

Adult-Life Alcohol Consumption and Age-Related Cognitive Decline from Early Adulthood to Late Midlife.

AIMS: Alcohol consumption is a modifiable and plausible risk factor for age-related cognitive decline but more longitudinal studies investigating the association are needed. Our aims were to estimate associations of adult-life alcohol consumption and consumption patterns with age-related cognitive decline. METHODS: We investigated the associations of self-reported adult-life weekly alcohol consumption and weekly extreme binge drinking (≥10 units on the same occasion) with changes in test scores on an identical validated test of intelligence completed in early adulthood and late midlife in 2498 Danish men from the Lifestyle and Cognition Follow-up study 2015. Analyses were adjusted for year of birth, retest interval, baseline IQ, education and smoking. RESULTS: Men with adult-life alcohol consumption of more than 28 units/week had a larger decline in IQ scores from early adulthood to late midlife than men consuming 1-14 units/week (B29-35units/week = -3.6; P < 0.001). Likewise, a 1-year increase in weekly extreme binge drinking was associated with a 0.12-point decline in IQ scores (P < 0.001). Weekly extreme binge drinking explained more variance in IQ changes than average weekly consumption. In analyses including mutual adjustment of weekly extreme binge drinking and average weekly alcohol consumption, the estimated IQ decline associated with extreme binge drinking was largely unaffected, whereas the association with weekly alcohol consumption became non-significant. CONCLUSIONS: Adult-life heavy alcohol consumption and extreme binge drinking appear to be associated with larger cognitive decline in men. Moreover, extreme binge drinking may be more important than weekly alcohol consumption in relation to cognitive decline.

Childhood dyspraxia predicts adult-onset nonaffective-psychosis-spectrum disorder.

Several neurological variables have been investigated as premorbid biomarkers of vulnerability for schizophrenia and other related disorders. The current study examined whether childhood dyspraxia predicted later adult nonaffective-psychosis-spectrum disorders. From a standardized neurological examination performed with children (aged 10-13) at genetic high risk of schizophrenia and controls, several measures of dyspraxia were used to create a scale composed of face/head dyspraxia, oral articulation, ideomotor dyspraxia (clumsiness), and dressing dyspraxia (n = 244). Multinomial logistic regression showed higher scores on the dyspraxia scale predict nonaffective-psychosis-spectrum disorders relative to other psychiatric disorders and no mental illness outcomes, even after controlling for genetic risk, χ2 (4, 244) = 18.61, p < .001. Findings that symptoms of dyspraxia in childhood (reflecting abnormalities spanning functionally distinct brain networks) specifically predict adult nonaffective-psychosis-spectrum disorders are consistent with a theory of abnormal connectivity, and they highlight a marked early-stage vulnerability in the pathophysiology of nonaffective-psychosis-spectrum disorders.

An association between autumn birth and clozapine treatment in patients with schizophrenia: a population-based analysis.

BACKGROUND: Numerous studies on seasonality of birth and schizophrenia risk have been published but it is uncertain whether, among those with schizophrenia, refractory illness exhibits any predilection for birth month. We hypothesized and examined whether a season of birth effect was present in patients with schizophrenia with a history of clozapine treatment. METHOD: Using record linkage with Danish registers, we examined patients with schizophrenia born between 1950 and 1970, and between 1995 and 2009 and Cox regression analysis was used to examine season of birth in relation to history of clozapine treatment. RESULTS: In a study population corresponding to 60,062 person-years from 5328 individuals with schizophrenia of which 1223 (23%) received at least one clozapine prescription, birth in the autumn (September-November) was associated with clozapine treatment (HR = 1.24; 95% CI 1.07-1.46) when compared with birth in the spring (March-May). CONCLUSION: Although replication studies are needed, this is the first evidence from a nationwide study suggesting a possible season-associated risk of clozapine treatment in schizophrenia. The reasons for this relationship remain to be further investigated but might be partially explained by early exposures such as winter flu season and low vitamin D levels.

The association between birth weight, ponderal index, psychotropic medication, and type 2 diabetes in individuals with severe mental illness.

BACKGROUND: Impaired fetal growth may increase vulnerability towards metabolic disturbances associated with some medications. We examined whether birth weight and ponderal index modify the association between psychotropic medication and type 2 diabetes among young adults with severe psychiatric diagnosis. METHODS: A total of 36,957 individuals born in Denmark between 1973 and 1983 with a diagnosis of schizophrenia, bipolar disorder, or depression were followed from first diagnosis until 2018. Cox proportional hazard models were applied to analyse risk of type 2 diabetes with use of psychotropic medications and interactions between psychotropic medication and birth weight and ponderal index, respectively. RESULTS: During follow-up, 1575 (4.2%) individuals received a diagnosis of type 2 diabetes. Use of antipsychotic, mood stabilizing and antidepressant medications were associated with higher hazard ratios (HRs) of type 2 diabetes (HRantipsychotics 1.68 [95%CI 1.49-1.90]; HRmood stabilizing medication 1.41 [95%CI 1.25-1.59]; HRantidepressants 2.00 [95%CI 1.68-2.37]), as were a birth weight below 2500 g (HR 1.13 [95%CI 1.01-1.28]), and high ponderal index (HR 1.26 [95%CI 1.11-1.43]). The highest rates of type 2 diabetes for each psychotropic medication category were found in medication users with low birth weight or high ponderal index. However, neither birth weight nor ponderal index significantly modified the association between psychotropic medication and diabetes risk. CONCLUSION: Psychotropic medication use, birth weight, and ponderal index were risk factors for type 2 diabetes in patients with severe mental illness, but neither birth weight nor ponderal index modified the association between psychotropic medication and type 2 diabetes.

The contribution of parental alcohol use disorders and other psychiatric illness to the risk of alcohol use disorders in the offspring.

BACKGROUND: Few population-based studies have investigated associations between parental history of alcoholism and the risk of alcoholism in offspring. The aim was to investigate in a large cohort the risk of alcohol use disorders (AUD) in the offspring of parents with or without AUD and with or without hospitalization for other psychiatric disorder (OPD). METHODS: Longitudinal birth cohort study included 7,177 men and women born in Copenhagen between October 1959 and December 1961. Cases of AUD were identified in 3 Danish health registers and cases of OPD in the Danish Psychiatric Central Register. Offspring registration with AUD was analyzed in relation to parental registration with AUD and OPD. Covariates were offspring gender and parental social status. RESULTS: Both maternal and paternal registration with AUD significantly predicted offspring risk of AUD (odds ratios 1.96; 95% CI 1.42 to 2.71 and 1.99; 95% CI 1.54 to 2.68, respectively). The association between maternal, but not paternal, OPD and offspring AUD was also significant (odds ratios 1.46; 95% CI 1.15 to 1.86 and 1.26; 95% CI 0.95 to 1.66, respectively). Other predictors were male gender and parental social status. A significant interaction was observed between paternal AUD and offspring gender on offspring AUD, and stratified analyses showed particularly strong associations of both paternal and maternal AUD with offspring AUD in female cohort members. CONCLUSIONS: Parental AUD was associated with an increased risk of offspring AUD independent of other significant predictors, such as gender, parental social status, and parental psychiatric hospitalization with other diagnoses. Furthermore, this association appeared to be stronger among female than male offspring. The results suggest that inherited factors related to alcoholism are at least as important in determining the risk of alcoholism among daughters as among sons.

A prospective study of smoking in young women and risk of later psychiatric hospitalization.

BACKGROUND: It is not known whether smoking is a risk factor for mental disorders. AIMS: To investigate the prospective associations between cigarette smoking in pregnant women and a range of psychiatric hospital diagnoses. METHOD: Using data from the Copenhagen Perinatal Cohort, we followed a cohort of 7926 young women from 1959-61 to 2007, linking data on cigarette smoking with psychiatric admission diagnoses obtained from the Danish Psychiatric Central Register. The women were interviewed by a physician in 1959-61 when data was obtained on smoking and other health related variables. With adjustment for age, social class and psychopharmacological treatment at baseline, the effects of smoking on the risk of (hierarchically ordered) major categories of mental disorders were examined. RESULTS: Significant positive associations were observed between number of cigarettes smoked and schizophrenia spectrum disorder, substance use-related disorder, a broad category of other non-psychotic disorders, and any psychiatric registration. For affective spectrum disorders, there was a significant, but non-linear association. CONCLUSION: Number of cigarettes smoked in young adulthood significantly predicted a range of psychiatric admission diagnoses and, for most diagnostic categories, evidence of a dose-response relationship was observed.

Preventing repetition of attempted suicide--II. The Amager project, a randomized controlled trial.

Repetition after attempted suicide is high but only few effect studies have been carried out. The Baerum Model from Norway offers practical and affordable intervention for those not being offered psychiatric treatment. During a period from 2005-2007, all attempted suicide patients except those with major psychiatric diagnoses (schizophrenia, bipolar disorder, severe/psychotic depression), were offered participation. The intervention group received the OPAC programme (outreach, problem solving, adherence, continuity) and the control group received treatment as usual (TAU). The intervention period was 6 months. After this intervention period, all patients were followed passively for an extra 6 months. The design was an intent-to-treat one. The outcomes were: 1) repetition of attempted suicide or suicide, and 2) total number of suicidal acts. A total of 200 patients were offered participation, 67 refused. Of the 133 participants, 69 were randomized to the OPAC programme and 64 to the (non-intervention) control group. Four in each group dropped out after initial participation. There was a significant lower proportion who repeated a suicide attempt the intervention group (proportion 8.7%) than in the control group (proportion 21.9%) and the number of repetitive acts was also significant lower (eight repetitions in the intervention group vs. 22 in the control group). In conclusion, our findings suggest a protective effect of the OPAC programme on the proportion who repeated a suicide attempt and on the total number of repetitions during the follow-up.

Lifetime psychiatric hospital diagnoses among 8,412 Danish men registered in an outpatient alcohol clinic.

OBJECTIVE: To describe the prevalence of lifetime psychiatric hospital diagnoses among men registered in an outpatient alcohol clinic and compare the prevalence with matched controls. To assess temporality of alcohol use disorder (AUD) diagnoses and another psychiatric hospital diagnosis and examine the prevalence of lifetime psychiatric hospital diagnoses according to this temporal order. METHODS: The study included 8,412 Danish men registered in an outpatient alcohol clinic, and 8,412 unregistered controls from the Danish Conscription Database matched on birth date, lifespan, intelligence and draft board district. Information on first outpatient AUD treatment was retrieved from the Copenhagen Alcohol Cohort. Information on lifetime psychiatric hospital diagnoses was retrieved from national Danish psychiatric registers and based on the International Classification of Diseases the 8th and 10th Revisions. Prevalence estimates of lifetime psychiatric hospital diagnoses were compared with odds ratios (OR) between men registered in an outpatient alcohol clinic and the control population. RESULTS: Among men registered in an outpatient alcohol clinic, 66.6% had a lifetime psychiatric hospital diagnosis. In total, 8.6% had neuroses and anxiety disorders, while 25.3% had personality disorders. The OR of a lifetime psychiatric hospital diagnosis was 9.77 (95%CI: 8.87-10.75) when comparing men registered in an outpatient alcohol clinic with the control population. Among men with a lifetime psychiatric hospital diagnosis, 42.8% was registered with another psychiatric hospital diagnosis before registration with an AUD diagnosis. CONCLUSION: Among men with a lifetime psychiatric hospital diagnosis, AUD is rarely diagnosed without psychiatric comorbidity at first-time admissions to psychiatric hospital departments.

Young adult predictors of alcohol dependence to age 53: a 44-year prospective cohort study of Danish men.

AIMS: To examine if (1) there is a positive association between drinking volume in young men and life-time risk of alcohol dependence (AD) and (2) there are other associations between young adulthood factors and life-time risk of AD. DESIGN: Prospective cohort study of sons of fathers with alcohol use disorder (AUD) and matched low-risk controls without paternal AUD. Setting and participants A total of 204 men, who were assessed at baseline in 1979 at age 19-20 years, were followed through record linkage with Danish registers and consecutive psychiatric interviews at the ages of 33, 43 and 53 years. MEASUREMENTS: AD diagnoses were interview-based according to the Diagnostic and Statistical Manual of Mental Disorders, 3rd edition, or made by treating clinicians according to the International Classification of Diseases (ICD) revision 8 (ICD-8) until 1993 and revision 10 (ICD-10) from 1994.We estimated odds ratios (ORs) with 95% confidence intervals (CI) for the development of AD after adjustment for confounders including smoking, social status and paternal AUD. FINDINGS: The following variables from the examination at age 19-20 independently predicted life-time AD: alcohol consumption > 21 beverages/week versus 0-21 [odds ratio (OR) = 2.46, 95% confidence interval (CI) = 1.22-4.97], police contact (OR = 2.60, 95% CI = 1.28-5.28) and institutionalization related to the individual (OR = 2.90, 95% CI = 1.39-6.02). Compared with < 1 beverages/week, the risk for AD did not increase significantly for drinking volume categories: 1-7, 8-14 or 15-21 beverages/week. CONCLUSION: Independently of other risk factors in young adulthood, young Danish men's risk for life-time alcohol dependence appears to be predicted by a drinking volume at age 19-20 years exceeding 21 beverages per week.

Premorbid IQ and adult schizophrenia spectrum disorder: verbal Performance subtests.

The present prospective high-risk study examined associations between childhood scores on five Wechsler Intelligence Scale for Children (WISC) subtests (vocabulary, similarities, block design, object assembly, and mazes) and later development of schizophrenia spectrum disorders (SSD). The sample comprised 244 high-risk or control children who were administered the WISC subtests at age 10 to 13 years in 1972. Adult psychiatric data were gathered from psychiatric interviews in 1992-93 and from the Danish Psychiatric Central Register in 2007. Thirty-two participants had developed SSD, 79 other psychiatric disorders (OPD), and 133 had no diagnosis (ND). The SSD group obtained lower scores than the ND group on all subtests and IQs, but when adjusted for sex and parental social status only significantly lower scores on similarities, object assembly, mazes, and total IQ. Compared with the ND group, the OPD group obtained significantly lower scores on similarities, vocabulary, verbal IQ, and total IQ. The only significant difference between the SSD and OPD groups was on object assembly (OPD performed at the level of ND). The results suggest a premorbid deficit in general intelligence in individuals who later develop SSD. The results for the OPD group support recent studies demonstrating that premorbid IQ deficits may characterize a wide range of psychiatric disorders.

Family structure and alcohol use disorder: a register-based cohort study among offspring with and without parental alcohol use disorder.

AIMS: To assess whether parental alcohol use disorder (AUD) is associated with higher risks of living in a non-intact family and assess whether non-intact family structure is associated with higher risks of AUD in the offspring. DESIGN: Prospective cohort study. SETTING: Danish nation-wide registries. PARTICIPANTS: A total of 9948 parental AUD offspring and 98 136 reference offspring from the Danish population. MEASUREMENTS: Family structure assessed at birth and at each birthday until age 15 as intact or non-intact (with mother only, father only or neither parent); years lived in an intact family defined as total number of years lived with both parents from birth until the 15th birthday; AUD defined as registration in medical, treatment and cause of death registries. Data were analyzed by Cox regression. FINDINGS: At birth, 30.9% [95% confidence interval (CI) = 29.1-32.6] of parental AUD offspring and 10.7% (95% CI = 10.3-11.0) of reference offspring lived in a non-intact family. At age 15, the numbers were 84.6% (95% CI = 83.9-85.3) and 38.4% (95% CI = 38.1-38.7). Parental AUD was associated with a higher risk of offspring AUD [hazard ratio (HR) = 1.88, 95% CI = 1.74-2.02]. Offspring were at lower risk of AUD if they lived 15 years in an intact family compared with offspring who never lived in an intact family (HR = 0.67, 95% CI = 0.52-0.87 for those with parental AUD, and HR = 0.53, 95% CI = 0.48-0.59 for those whose parents did not have AUD). Findings were inconclusive as to whether or not an association was present between family structure and AUD among offspring with parental AUD and reference offspring. CONCLUSIONS: The prevalence of non-intact family structure appears to be higher in offspring of parents with alcohol use disorder (AUD) than among offspring from the general population. Parental AUD appears to be associated with increased risk of offspring AUD, and non-intact family structure appears to be associated with increased risk of offspring AUD regardless of parental AUD.

Association between prenatal exposure to bacterial infection and risk of schizophrenia.

Recent research suggests that prenatal exposure to nonviral infection may be associated with increased risk of schizophrenia, and we hypothesized an association between maternal bacterial infection during pregnancy and elevated offspring risk of schizophrenia. Data on maternal infections from the Copenhagen Perinatal Cohort were linked with the Danish National Psychiatric Register. Offspring cases of narrowly defined schizophrenia (International Classification of Diseases, Eighth Revision [ICD-8]) and more broadly defined schizophrenia (ICD-8 and ICD-10) were identified before the ages of 32-34 and 45-47 years, respectively. The effect of prenatal exposure to bacterial infections was adjusted for prenatal exposure to analgesics and parental social status. In a risk set of 7941 individuals, 85 cases (1.1%) of ICD-8 schizophrenia were identified by the age of 32-34 years and 153 cases (1.9%) of more broadly defined schizophrenia by the age of 45-47 years. First-trimester exposure conferred an elevated risk of ICD-8 schizophrenia (odds ratio 2.53; 95% confidence interval [CI] 1.07-5.96) and also of broadly defined schizophrenia (odds ratio 2.14; 95% CI 1.06-4.31). Second-trimester exposure also conferred a significantly elevated risk of schizophrenia but only in unadjusted analyses. These findings suggest a relationship between maternal bacterial infection in pregnancy and offspring risk of schizophrenia, and this effect was somewhat stronger for ICD-8 schizophrenia with earlier onset. Post hoc analyses showed that upper respiratory tract and gonococcal infections were associated with elevated risk of the disease. An association between risk of schizophrenia and prenatal exposure to bacterial infections might be mediated through transplacental passage of maternally produced cytokines in response to bacterial infections.

Suicide and mental illness in parents and risk of suicide in offspring: a birth cohort study.

BACKGROUND: A family history of completed suicide and psychiatric illness has been identified as risk factors for suicide. AIMS: To examine the risk of offspring suicide in relation to parental history of suicide and other parental risk factors. METHOD: The study population consisted of 7,177 adult offspring born 1959-1961 and their parents from the Copenhagen Perinatal Cohort. Cohort members and their parents who had committed suicide were identified in the Danish Causes of Death Registry (follow-up until December 31, 2005), while information on psychiatric hospitalisation history was obtained from the Danish Psychiatric Central Research Register. RESULTS: Forty-eight cohort members, 77 mothers and 133 fathers had committed suicide during the follow-up. Independent of parental psychiatric illness and social status, parental suicide significantly increased suicide risk in offspring (hazard ratio 4.40 with 95% CI 1.81-10.69). A stronger effect of parental suicide was observed in offspring without a history of psychiatric hospitalisation. CONCLUSION: Parental history of suicide is a risk factor for suicide in offspring, but primarily in offspring without psychiatric hospitalisation.

Polygenic risk for psychiatric disorder and singleness in patients with severe mental illness and controls.

We aimed to investigate whether the polygenic risk score (PRS) for schizophrenia influences time in couple relationships for patients with severe mental illness and controls. We combined the nationwide Danish registers with genetic information from dried neonatal blood spots. We included 2,599 individuals with schizophrenia, 1,446 with bipolar disorder, 20,315 with depression, and 6,963 controls. PRS for schizophrenia, depression, and bipolar disorder were estimated using data from the Psychiatric Genetics Consortium and analyzed both as a scale-predictor and as highest versus other deciles. The main outcome was number of days in couple relationships. Patients with schizophrenia had markedly fewer days/year in couple relationships: 64 (95% CI; 61-69) than patients with depression: 119 (95% CI; 117-121), bipolar disorder: 103 (95% CI 97-110), and controls: 136 (95% CI 133-139). PRS for schizophrenia was associated with fewer days in couple relationships in patients with schizophrenia (scale-PRS: IRR = 0.95 (0.93-0.97)) or depression (highest decile: IRR = 0.93 (0.87-0.98)). PRS for bipolar disorder (as scale) was also associated with fewer days in couple relationships in patients with depression (IRR = 0.99 (0.99-1.00)) or bipolar disorder (IRR = 0.96 (0.94-0.99)) and controls (IRR = 0.99 (0.97-1.00), and IRR = 0.89 (0.81-0.98) for the highest decile). Due to the number of statistical tests, however, it cannot be concluded definitely that some of these may not be spurious findings. In conclusion, our findings implicate high genetic loading for schizophrenia as a predisposing factor to singleness in patients with schizophrenia or depression, and genetic loading for bipolar disorder a similar predisposing factor in patients with depression, bipolar disorder or controls.

Association between prior somatic disease and 5-year relapse risk among 11,856 incident patients with schizophrenia.

BACKGROUND: Somatic diseases have been associated with an increased risk for subsequent schizophrenia; however, it is unknown whether prior somatic diseases negatively affect early treatment outcomes after a first-time schizophrenia diagnosis. METHODS: We included all individuals born in Denmark after January 1st, 1977 and first-time diagnosed with schizophrenia between January 1st, 1996 and December 31st, 2015. We identified all life-time somatic hospital contacts and all prescriptions within the year before the first-time schizophrenia diagnosis and followed patients for up to five years regarding risk for schizophrenia (re)-hospitalization (relapse). We performed Cox regression analyses calculating hazard rate ratios (HRR) including 95%-confidence intervals (CI) and adjusted for relevant confounders. RESULTS: We followed a total of 11,856 patients with a first-time schizophrenia diagnosis (58.7% male, mean age 23.1 (SD = 4.7) years) for 39,033 person-years, whereof 5506 (46.4%) had relapse with schizophrenia re-hospitalization during 5-year of follow-up. Somatic hospital contacts ever before (95.4%; HRR = 1.30; 95%-CI = 1.07-1.59), and specifically during the year before schizophrenia diagnosis (42.5%; HRR = 1.36; 95%-CI = 1.11-1.66) were associated with an increased risk of schizophrenia relapse as were a greater number of prior somatic hospital contacts (p < 0.001). Individuals with up to four different prescriptions for somatic medications showed a trend towards a slightly lower risk of relapse. CONCLUSION: Somatic diseases and health seeking patterns might have an impact on the course of schizophrenia, where severe somatic comorbidity, specifically during the year before first-time schizophrenia diagnosis, seem to negatively affect early treatment course, whereas previous somatic medication use may indicate a better compliance and help-seeking behavior.

Associations between education and age-related cognitive changes from early adulthood to late midlife.

The aims of the study were to explore general trends and individual differences in cognitive changes from early adulthood to late midlife and to investigate associations between education and cognitive changes. We used data from the Lifestyle and Cognition Follow-Up Study 2015 on 1,543 Danish men born in 1950-1961. Test scores on the 78-item intelligence test used by the Danish conscription authorities, Børge Priens Prøve (BPP), completed at draft board examination (baseline, mean age = 20 years) and at follow-up (mean age = 61 years) were used to measure cognitive changes. The mean change in BPP scores was -2.94 (SD = 5.57), and a retest correlation of 0.81 between the baseline and follow-up BPP scores was observed. In spite of the substantial retest correlations, the 8.3% of the sample with statistically reliable change had a mean decline in BPP scores of -13.41 (SD = 2.56). In latent change score models adjusted for year of birth and retest interval, more years of education was associated with larger decline in BPP scores, but the association was reversed when further adjusting for baseline BPP scores. Moreover, significant interactions indicated that more years of education was associated with less cognitive decline in men with relatively low or average BPP scores at baseline, whereas no influence of education was found in men with high baseline scores. Hence, more years of education may compensate for low or average intelligence by increasing cognitive reserve in these individuals or by influencing mediating lifestyle and occupational factors. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Exploring Comorbidity Within Mental Disorders Among a Danish National Population.

Importance: Individuals with mental disorders often develop comorbidity over time. Past studies of comorbidity have often restricted analyses to a subset of disorders and few studies have provided absolute risks of later comorbidity. Objectives: To undertake a comprehensive study of comorbidity within mental disorders, by providing temporally ordered age- and sex-specific pairwise estimates between the major groups of mental disorders, and to develop an interactive website to visualize all results and guide future research and clinical practice. Design, Setting, and Participants: This population-based cohort study included all individuals born in Denmark between January 1, 1900, and December 31, 2015, and living in the country between January 1, 2000, and December 31, 2016. The analyses were conducted between June 2017 and May 2018. Main Outcomes and Measures: Danish health registers were used to identify mental disorders, which were examined within the broad 10-level International Statistical Classification of Diseases and Related Health Problems, 10th Revision, subchapter groups (eg, codes F00-F09 and F10-F19). For each temporally ordered pair of disorders, overall and lagged hazard ratios and 95% CIs were calculated using Cox proportional hazards regression models. Absolute risks were estimated using competing risks survival analyses. Estimates for each sex were generated. Results: A total of 5 940 778 persons were included in this study (2 958 293 men and 2 982 485 women; mean [SD] age at beginning of follow-up, 32.1 [25.4] years). They were followed up for 83.9 million person-years. All mental disorders were associated with an increased risk of all other mental disorders when adjusting for sex, age, and calendar time (hazard ratios ranging from 2.0 [95% CI, 1.7-2.4] for prior intellectual disabilities and later eating disorders to 48.6 [95% CI, 46.6-50.7] for prior developmental disorders and later intellectual disabilities). The hazard ratios were temporally patterned, with higher estimates during the first year after the onset of the first disorder, but with persistently elevated rates during the entire observation period. Some disorders were associated with substantial absolute risks of developing specific later disorders (eg, 30.6% [95% CI, 29.3%-32.0%] of men and 38.4% [95% CI, 37.5%-39.4%] of women with a diagnosis of mood disorders before age 20 years developed neurotic disorders within the following 5 years). Conclusions and Relevance: Comorbidity within mental disorders is pervasive, and the risk persists over time. This study provides disorder-, sex-, and age-specific relative and absolute risks of the comorbidity of mental disorders. Web-based interactive data visualization tools are provided for clinical utility.