Carsten Hjorthøj

Years of potential life lost and life expectancy in schizophrenia: a systematic review and meta-analysis

BACKGROUNDnSeveral studies and meta-analyses have shown that mortality in people with schizophrenia is higher than that in the general population but have used relative measures, such as standardised mortality ratios. We did a systematic review and meta-analysis to estimate years of potential life lost and life expectancy in schizophrenia, which are more direct, absolute measures of increased mortality.nnnMETHODSnWe searched MEDLINE, PsycINFO, Embase, Cinahl, and Web of Science for published studies on years of potential life lost and life expectancy in schizophrenia. Data from individual studies were combined in meta-analyses as weighted averages. We did subgroup analyses for sex, geographical region, timing of publication, and risk of bias (estimated with the Newcastle-Ottawa Scale).nnnFINDINGSnWe identified 11 studies in 13 publications covering all inhabited continents except South America (Africa n=1, Asia n=1, Australia n=1, Europe n=7, and North America n=3) that involved up to 247u2008603 patients. Schizophrenia was associated with a weighted average of 14·5 years of potential life lost (95% CI 11·2-17·8), and was higher for men than women (15·9, 13·8-18·0 vs 13·6, 11·4-15·8). Loss was least in the Asian study and greatest in Africa. The overall weighted average life expectancy was 64·7 years (95% CI 61·1-71·3), and was lower for men than women (59·9 years, 95% CI 55·5-64·3 vs 67·6 years, 63·1-72·1). Life expectancy was lowest in Asia and Africa. Timing of publication and risk of bias had little effect on results.nnnINTERPRETATIONnThe effects of schizophrenia on years potential life lost and life expectancy seem to be substantial and not to have lessened over time. Development and implementation of interventions and initiatives to reduce this mortality gap are urgently needed.nnnFUNDINGnNone.

Association between alcohol and substance use disorders and all-cause and cause-specific mortality in schizophrenia, bipolar disorder, and unipolar depression: a nationwide, prospective, register-based study

BACKGROUNDnPeople with severe mental illness have both increased mortality and are more likely to have a substance use disorder. We assessed the association between mortality and lifetime substance use disorder in patients with schizophrenia, bipolar disorder, or unipolar depression.nnnMETHODSnIn this prospective, register-based cohort study, we obtained data for all people with schizophrenia, bipolar disorder, or unipolar depression born in Denmark in 1955 or later from linked nationwide registers. We obtained information about treatment for substance use disorders (categorised into treatment for alcohol, cannabis, or hard drug misuse), date of death, primary cause of death, and education level. We calculated hazard ratios (HRs) for all-cause mortality and subhazard ratios (SHRs) for cause-specific mortality associated with substance use disorder of alcohol, cannabis, or hard drugs. We calculated standardised mortality ratios (SMRs) to compare the mortality in the study populations to that of the background population.nnnFINDINGSnOur population included 41u2008470 people with schizophrenia, 11u2008739 people with bipolar disorder, and 88u2008270 people with depression. In schizophrenia, the SMR in those with lifetime substance use disorder was 8·46 (95% CI 8·14-8·79), compared with 3·63 (3·42-3·83) in those without. The respective SMRs in bipolar disorder were 6·47 (5·87-7·06) and 2·93 (2·56-3·29), and in depression were 6·08 (5·82-6·34) and 1·93 (1·82-2·05). In schizophrenia, all substance use disorders were significantly associated with increased risk of all-cause mortality, both individually (alcohol, HR 1·52 [95% CI 1·40-1·65], p<0·0001; cannabis, 1·24 [1·04-1·48], p=0·0174; hard drugs, 1·78 [1·56-2·04], p<0·0001) and when combined. In bipolar disorder or depression, only substance use disorders of alcohol (bipolar disorder, HR 1·52 [95% CI 1·27-1·81], p<0·0001; depression, 2·01 [1·86-2·18], p<0·0001) or hard drugs (bipolar disorder, 1·89 [1·34-2·66], p=0·0003; depression, 2·27 [1·98-2·60], p<0·0001) increased risk of all-cause mortality individually.nnnINTERPRETATIONnMortality in people with mental illness is far higher in individuals with substance use disorders than in those without, particularly in people who misuse alcohol and hard drugs. Mortality-reducing interventions should focus on patients with a dual diagnosis and seek to prevent or treat substance use disorders.nnnFUNDINGnThe Lundbeck Foundation.

From research to practice: how OPUS treatment was accepted and implemented throughout Denmark.

The early phases of psychosis have been hypothesized to constitute a critical period, a window of opportunity. At the same time, the early phases of psychosis are associated with increased risk of unwanted outcome, such as suicidal behaviour and social isolation. This was the background for the emergence of early intervention services, and in Denmark, the OPUS trial was initiated as part of that process.

Prevalence of substance use disorders in psychiatric patients: a nationwide Danish population-based study

PurposeThe present study established the national prevalence of substance use disorders (SUDs) among Danish psychiatric patients. Furthermore, patients with SUDs and those without SUDs were compared on a range of socio-demographic, clinical, and treatment characteristics.MethodsData were obtained from several Danish population-based registers. The study population was defined as all individuals with incidents of schizophrenia, schizotypal disorder, other psychoses, bipolar disorder, depression, anxiety, obsessive–compulsive disorder (OCD), post-traumatic stress disorder (PTSD), and personality disorders since 1969. The prevalence of SUDs was examined for the following psychoactive substances: alcohol, opioids, cannabis, sedatives, cocaine, psycho-stimulants and hallucinogens.ResultsA total of 463,003 patients were included in the analysis. The prevalence of any lifetime SUD was: 37xa0% for schizophrenia, 35xa0% for schizotypal disorder, 28xa0% for other psychoses, 32xa0% for bipolar disorder, 25xa0% for depression, 25xa0% for anxiety, 11xa0% for OCD, 17% for PTSD, and 46xa0% for personality disorders. Alcohol use disorder was the most dominating SUD in every psychiatric category (25xa0% of all included patients). Patients with SUDs were more often men, had fewer years of formal education, more often received disability pension and died due to unnatural causes.ConclusionsThe study was the most comprehensive of its kind so far to estimate the prevalence of SUDs in an unselected population-based cohort, and it revealed remarkably high prevalence among the psychiatric patients. The results should encourage continuous focus on possible comorbidity of psychiatric patients, as well as specialised and integrated treatment along with increased support of patients with comorbid disorders.

Ten-Year Follow-up of the OPUS Specialized Early Intervention Trial for Patients With a First Episode of Psychosis

INTRODUCTIONnSpecialized early intervention programs such as The Danish OPUS treatment are efficient in treating patients with a first episode of psychosis (FEP) at least after 2 and 5 years. Few studies have examined long-term outcomes of these interventions.nnnAIMnTo examine the effect of 2 years of OPUS vs treatment as usual (TAU) within an FEP cohort, 10 years after inclusion into the OPUS trial.nnnMETHODSnFrom 1998 to 2000, participants were randomized to OPUS or TAU. Ten years later, we conducted comprehensive interviews and performed register-based follow-up on all participants in national Danish registers. We analyzed participants according to the intention-to-treat principle.nnnRESULTSnOf the 547 participants included in the study, 347 (63.4%) took part in this follow-up. While there was evidence of a differential 10-year course in the development of negative symptoms, psychiatric bed days, and possibly psychotic symptoms in favor of OPUS treatment, differences were driven by effects at earlier follow-ups and had diminished over time. Statistically significant differences in the course of use of supported housing were present even after 8-10 years. There were no differences between OPUS and TAU regarding income, work-related outcomes, or marital status.nnnCONCLUSIONnMost of the positive short-term effects of the OPUS intervention had diminished or vanished at this long-term follow-up. We observed a clear tendency that OPUS treatment leads to fewer days in supported housing. There is a need for further studies investigating if extending the intervention will improve outcomes more markedly at long-term follow-ups.

Research Review: Do motor deficits during development represent an endophenotype for schizophrenia? A meta-analysis.

BACKGROUNDnEarly detection of schizophrenia risk is a critical goal in the field. Endophenotypes in children to relatives of affected individuals may contribute to this early detection. One of the lowest cost and longest theorized domains is motor development in children.nnnMETHODSnA meta-analysis was conducted comparing individuals ≤21 years old with affected first-degree relatives (FDR) with (1) individuals from unaffected families (controls), or (2) individuals with FDR having other psychiatric disorders. Studies were classified by motor outcome and separate meta-analyses were performed across six correlated domains, with available N varying by domain.nnnRESULTSnInclusion criteria were met by k = 23 independent studies with a total N = 18,582, and N across domains varying from 167 to 8619. The youth from affected families had delays in gross and fine motor development in infancy (k = 3, n = 167, Hedgesg = 0.644, confidence intervals (CI) = [0.328, 0.960], p < .001), walking milestones (k = 3, n = 608, g = 0.444, CI = [0.108, 0.780], p = .01), coordination (k = 8, n = 8619, g = 0.625, CI = [0.453, 0.797], p < .0001), and had more abnormal movements such as involuntary movements (k = 6, n = 8365, g = 0.291, CI = [0.041, 0.542], p = .02) compared with controls. However, not all effects survived correction for publication bias. Effects for neurological soft signs were small and not reliably different from zero (k = 4, n = 548, g = 0.238, CI = [-0.106, 0.583], p = .18). When comparing the FDR group to youth from families with other psychiatric disorders, the FDR group was distinguished by poorer gross and fine motor skills (k = 2, n = 275, g = 0.847, CI = [0.393, 1.300], p < .001).nnnCONCLUSIONSnMotor deficits during development likely represent an endophenotype for schizophrenia, although its specificity is limited in relation to other serious mental disorders. It holds promise as a low cost domain for early risk detection, although it will have to be combined with other indicators to achieve clinically usable prediction accuracy. Impaired coordination was the most robust result with a moderate effect size and lack of heterogeneity and publication bias.

Associations between substance use disorders and suicide or suicide attempts in people with mental illness: a Danish nation-wide, prospective, register-based study of patients diagnosed with schizophrenia, bipolar disorder, unipolar depression or personality disorder

AIMnTo estimate and test associations between substance use disorders (SUDs) and both completed suicides and suicide attempts in a population with severe mental illness.nnnDESIGNnRegister-based cohort study with adjusted Cox regression of substance use disorders as time-varying covariates.nnnSETTINGnDenmark.nnnPARTICIPANTSnPeople born in Denmark since 1955 with a diagnosis of schizophrenia (nxa0=xa035u2009625), bipolar disorder (nxa0=xa09279), depression (nxa0=xa072u2009530) or personality disorder (nxa0=xa063u2009958).nnnMEASUREMENTSnTreated SUDs of alcohol and illicit substances identified in treatment registers; suicide attempt identified in treatment registers; and completed suicides identified in the Cause of Death register. Covariates were sex and age at diagnosis.nnnFINDINGSnHaving any SUD was associated with at least a threefold increased risk of completed suicide when compared with those having no SUD. Alcohol misuse was associated with an increased risk of completed suicide in all populations with hazard ratios (HR) between 1.99 [95% confidence interval (CI)xa0=xa01.44-2.74] and 2.70 (95% CIxa0=xa02.40-3.04). Other illicit substances were associated with a two- to threefold risk increase of completed suicide in all populations except bipolar disorder, and cannabis was associated with increased risk of attempted suicide only in people with bipolar disorder (HRxa0=xa01.86, 95% CIxa0=xa01.15-2.99). Alcohol and other illicit substances each displayed strong associations with attempted suicide, HR ranging from 3.11 (95% CIxa0=xa02.95-3.27) to 3.38 (95% CIxa0=xa03.24-3.53) and 2.13 (95% CIxa0=xa02.03-2.24) to 2.27 (95% CIxa0=xa02.12-2.43), respectively. Cannabis was associated with suicide attempts only in people with schizophrenia (HRxa0=xa01.11, 95% CIxa0=xa01.03-1.19).nnnCONCLUSIONnSubstance use disorders are associated strongly with risk of completed suicides and suicide attempts in people with severe mental illness.

Antipsychotic medication and remission of psychotic symptoms 10 years after a first-episode psychosis

BACKGROUNDnSeveral national guidelines recommend continuous use of antipsychotic medication after a psychotic episode in order to minimize the risk of relapse. However some studies have identified a subgroup of patients who obtain remission of psychotic symptoms while not being on antipsychotic medication for a period of time. This study investigated the long-term outcome and characteristics of patients in remission of psychotic symptoms with no use of antipsychotic medication at the 10-year follow-up.nnnMETHODSnThe study was a cohort study including 496 patients diagnosed with schizophrenia spectrum disorders (ICD 10: F20 and F22-29). Patients were included in the Danish OPUS Trial and followed up 10years after inclusion, where patient data was collected on socio-demographic factors, psychopathology, level of functioning and medication.nnnFINDINGSn61% of the patients from the original cohort attended the 10-year follow up and 30% of these had remission of psychotic symptoms at the time of the 10-year follow up with no current use of antipsychotic medication. This outcome was associated with female gender, high GAF-F score, participation in the labour market and absence of substance abuse.nnnCONCLUSIONnOur results describe a subgroup of patients who obtained remission while not being on antipsychotic medication at the 10-year follow-up. The finding calls for further investigation on a more individualized approach to long-term treatment with antipsychotic medication.

Risk of psychiatric disorders in offspring of parents with a history of homelessness during childhood and adolescence in Denmark: a nationwide, register-based, cohort study

BACKGROUNDnChildren and adolescents from deprived backgrounds have high rates of psychiatric problems. Parental and social factors are crucial for childrens healthy and positive development, but whether psychiatric morbidity is associated with parental social marginalisation is unknown. We aimed to analyse the association between mothers and fathers history of homelessness and the offsprings risk of psychiatric disorders, including substance use disorder, during childhood and adolescence.nnnMETHODSnWe did a nationwide, register-based cohort study of 1u2008072u2008882 children and adolescents aged 0-16 years, who were living or born in Denmark between Jan 1, 1999, and Dec 31, 2015. Parental homelessness was the primary exposure, data on which were obtained from the Danish Homeless Register. The Danish Civil Registration System was used to extract the population and link offspring to parental information, and the outcome, psychiatric disorders in the offspring, was obtained from the Danish Psychiatric Central Research Register and the Danish National Patient Register. We analysed the association between parental history of homelessness and risk of psychiatric disorders in offspring by survival analysis using Poisson regression and incidence rate ratios (IRRs), adjusted for year and offspring characteristics, and additionally adjusted for parental factors (age at offsprings birth and parental psychiatric disorders).nnnFINDINGSn17u2008238 (2%) offspring had either one or two parents with a history of homelessness, and 56u2008330 (5%) children and adolescents were diagnosed with any psychiatric disorder during the study period. The incidence of any psychiatric disorder was 15·1 cases per 1000 person-years (95% CI 14·4-15·8) in offspring with at least one parent with a history of homelessness, compared with 6·0 per 1000 person-years (95% CI 6·0-6·1) in those whose parents had no such history (IRR 2·5 [95% CI 2·3-2·7] for mother homeless, 2·3 [2·2-2·5] for father homeless, and 2·8 [2·4-3·2] for both parents homeless, after adjustment for year and offspring characteristics). This risk remained elevated after additional adjustment for factors including parental psychiatric disorders. IRRs in offspring were increased for most specific psychiatric disorders, with the highest risk for attachment disorder when both parents had a history of homelessness (IRR 32·5 [95% CI 24·6-42·9]) and substance use disorder when only the mother had a history of homelessness (6·9 [4·9-9·7]). In offspring whose mothers had a history of both homelessness and a psychiatric disorder, 35·9% (95% CI 27·1-44·8) had been diagnosed with a psychiatric disorder by the age of 15 years.nnnINTERPRETATIONnParental homelessness was associated with an increased risk of psychiatric disorders in offspring during childhood and adolescence. These findings have important implications for public health and policy because they suggest a need for improvement in the support of socially marginalised families to help prevent psychiatric illness in offspring.nnnFUNDINGnUniversity of Copenhagen, The Lundbeck Foundation Initiative for Integrated Psychiatric Research (iPSYCH).

Association of Substance Use Disorders With Conversion From Schizotypal Disorder to Schizophrenia

Importance Understanding the role of substance use disorders in conversion from schizotypal disorder to schizophrenia may provide physicians and psychiatrists with important tools for prevention or early detection of schizophrenia. Objective To investigate whether substance use disorders, in particular cannabis use disorder, are associated with conversion to schizophrenia in individuals with schizotypal disorder. Design, Setting, and Participants This prospective cohort study included a population-based sample of all individuals born in Denmark from January 1, 1981, through August 10, 2014, with an incident diagnosis of schizotypal disorder and without a previous diagnosis of schizophrenia. Follow-up was completed on August 10, 2014, and data were analyzed from March 10, 2017, through February 15, 2018. Exposures Information on substance use disorders combined from 5 different registers. Main Outcomes and Measures Cox proportional hazards regression using time-varying information on substance use disorders and receipt of antipsychotics and adjusted for parental history of mental disorders, sex, birth year, and calendar year were used to estimate hazard ratios (HRs) and 95% CIs for conversion to schizophrenia. Results A total of 2539 participants with incident schizotypal disorder were identified (1448 men [57.0%] and 1091 women [43.0%]; mean [SD] age, 20.9 [4.4] years). After 2 years, 16.3% (95% CI, 14.8%-17.8%) experienced conversion to schizophrenia. After 20 years, the conversion rate was 33.1% (95% CI, 29.3%-37.3%) overall and 58.2% (95% CI, 44.8%-72.2%) among those with cannabis use disorders. In fully adjusted models, any substance use disorder was associated with conversion to schizophrenia (HR, 1.34; 95% CI, 1.11-1.63). When data were stratified by substance, cannabis use disorders (HR, 1.30; 95% CI, 1.01-1.68), amphetamine use disorders (HR, 1.90; 95% CI, 1.14-3.17), and opioid use disorders (HR, 2.74; 95% CI, 1.38-5.45) were associated with conversion to schizophrenia. These associations were not explained by concurrent use of antipsychotics, functional level before incident schizotypal disorder, or parental history of mental disorders. Conclusions and Relevance Substance use disorders, in particular cannabis, amphetamines, and opioids, may be associated with conversion from schizotypal disorder to schizophrenia. However, conversion rates are high even in those without substance use disorders, indicating a need for universal and substance-targeted prevention in individuals with schizotypal disorder.