Search

Background: Patients with psychiatric disorders have increased all-cause mortality compared with the general population. Previous research has shown that there is a fourfold increased risk of sudden cardiac death (SCD) among the young., Objective: To investigate the incidence of SCD in patients with psychiatric disorders aged 18-90 years in the Danish population by systematically reviewing all deaths in 1 year., Methods: We examined all deaths in Denmark among residents aged 18-90 years in 2010 by reviewing death certificates and autopsy reports. All deaths were categorised as non-SCD or SCD based on the available information. Psychiatric disorder was defined according to International Classification of Diseases, 10th revision criteria or by redemption of a prescription for psychotropic medication within 1 year., Results: Of 4.3 million residents in 2010, we observed 45 703 deaths, of which 6002 were due to SCD. Overall, the incidence rate ratio of SCD was 1.79-6.45 times higher among patients with psychiatric disorders than in the general population and was age dependent (p<0.001 across all age groups). When adjusting for age, sex and comorbidities, psychiatric disorders were independently associated with SCD, with a HR of 2.31 (2.19 to 2.43, p<0.001), and HR was highest among patients with schizophrenic disorders, with a HR of 4.51 (3.95 to 5.16, p <0.001). Furthermore, 18-year-old patients with a psychiatric disorder had an expected 10-year excess loss of life. Patients aged 18-40 with a psychiatric disorder had 13% of excess life years lost caused by SCD., Conclusion: In this study, the rate of SCD in patients with psychiatric disorders is higher across all age groups than in the general population. Having a psychiatric disorder is independently associated with SCD. Patients with schizophrenic disease had the highest rates of SCD. Life expectancy for an 18-year old with a psychiatric disorder is estimated to be 10 years shorter in comparison with those without this disorder., Competing Interests: Competing interests: LVKe has within the preceding three years been a consultant for Teva and Lundbeck. LVKø has received speaker’s honorarium from AstraZeneca, Boehringer, Novartis and Novo Nordisk. JT-H is a consultant for Johnson and Johnson, Microport, Boston, Cytokinetics and Leo Pharma, and has received funding from John and Birthe Family foundation. The remaining authors declare no conflicts of interests., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Accumulating data support the association between increased inflammation and bipolar disorder (BD), and preliminary data suggest that augmentation with low-dose aspirin (LDA) may protect against the onset and deterioration of BD via anti-inflammatory pathways. The A-bipolar randomised controlled trial (RCT) aims to investigate whether adding LDA to standard treatment improves day-to-day mood instability (MI) in BD., Methods and Analysis: A two-arm, triple-blind, parallel-group, superiority RCT including 250 patients with newly diagnosed BD treated at the Copenhagen Affective Disorder Clinic, Denmark. Participants are randomised 1:1 to either 150 mg of acetylsalicylic acid daily (LDA) or a placebo for six months in addition to their regular treatment. Mood instability, calculated from daily smartphone-based mood evaluations, is the primary outcome measure due to its internal validity as a real-life measure for patients and external validity as it reflects patients' illness severity and functioning. Analyses will be conducted as intention-to-treat analyses using a linear mixed model including time (categorical) and the time-treatment interaction as fixed effects and with an unstructured covariance pattern to account for repeated measurements on each study participant. The trial is Good Clinical Practice monitored., Ethics and Dissemination: The Danish Research Ethics Committee (H-21014515) and the data agency, Capital Region of Copenhagen (P-2021-576) approved the trial. Results will be published in peer-reviewed journals., Trial Registration Number: NCT05035316., Competing Interests: Competing interests: CFB, MF-J, KWM, JLF and KC have no competing interests to declare. JZ has within the last 3 years received honoraria from Lundbeck Pharma A/S. LVK has within the preceding 3 years been a consultant for Lundbeck and Teva. MV has within the last 3 years served as consultant for Lundbeck and Janssen/Cilag., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: It is unclear whether treatment early after onset in bipolar disorder may improve the long-term illness course. The early intervention in affective disorders (EIA) randomised controlled trial found that 2-years treatment in a specialised mood disorder clinic combining evidence-based pharmacological treatment with group psychoeducation improved clinical outcomes compared with standard treatment in patients with bipolar disorder discharged after their 1st, 2nd, or 3rd hospital admission. We aimed to assess the 16 years long-term outcomes after randomisation of the participants in the EIA trial., Methods: Data were obtained by linking nation-wide Danish population-based registers. All 158 participants of the EIA trial (Trial Registration Number NCT00253071) were followed from time of randomisation (2005-2009) to end of study (31 December 2021). The primary outcome was risk of psychiatric readmission. Secondary outcomes were total admissions and costs, medication use, intentional self-harm or suicide attempt or suicide, and socio-economic measures., Results: The absolute mean risk of psychiatric readmission was 49.3% in the intervention group and 59.8% in the control group, with no statistically significant difference between the groups (b = -0.10, 95% CI: -0.26 to 0.047, p = 0.18). Compared with the control group, patients in the intervention group had numerically fewer total admission days (mean (SD) 44 (77) versus 62 (109)), lower total cost of psychiatric hospital admissions and hospital-based outpatient visits (mean (SD) 22,001 (36793) euros versus 29,822 (52671) euros) and higher use of lithium and antipsychotics, but the differences were not statistically significant. Fewer patients in the intervention group had an event of intentional self-harm or suicide attempt or suicide during follow-up (OR 0.25, 95% CI: 0.15-0.40, p < 0.001) compared with the control group and more patients in the intervention group used antiepileptics (OR 2.21, 95% CI: 1.08-4.60, p = 0.031)., Conclusion: Analyses of very long-term outcomes of the EIA trial may potentially indicate a beneficial effect of the intervention at the long term but were likely underpowered to detect a more subtle effect and for most outcomes the differences between groups were not statistically significant., (© 2024 The Author(s). Acta Psychiatrica Scandinavica published by John Wiley & Sons Ltd.)

Bipolar disorder (BD) is often accompanied by persistent cognitive impairment. However, screening for cognitive impairment in the clinic is challenged by a lack of consensus on screening procedures. This study assesses cognitive impairment prevalence and screening feasibility in alignment with the International Society for Bipolar Disorder Targeting Cognition Task Force recommendations. Between January 2022 and May 2023, 136 newly diagnosed BD outpatients were assessed with the Screen for Cognitive Impairment in Psychiatry after 15-20 months of specialised care at the Copenhagen Affective Disorder Clinic. Cognitive impairment patterns and associations with cognitive complaints, perceived stress, and functioning were examined. Most screened patients (73 %) achieved full or partial remission, with 51 % being cognitively normal, 38 % showing global impairments, and 11 % displaying selective impairments. Among remitted patients, 56 % were cognitively normal, while 31 % and 13 % exhibited global or selective impairments, respectively. Both objectively impaired patient groups reported more subjective cognitive difficulties than those who were cognitively normal. The globally impaired group also demonstrated poorer functioning, more depressive symptoms and lower quality of life than cognitively normal patients. Across all patients, lower cognitive performance correlated with more cognitive complaints, lower functioning, lower quality of life, and more depressive symptoms. Cognitive screenings were relatively easily implementable, involving only a 1.5 h session including mood ratings, feedback and cognitive strategy discussion. The study highlights the clinical relevance and feasibility of cognitive screenings in BD patients, emphasizing the need for tailored interventions given frequent cognitive impairment in clinically stable individuals., Competing Interests: Declaration of competing interest KWM reports having received consultancy fees from Lundbeck, Angelini, Gideon Richter and Janssen-Cilag in the past three years. LVK reports having received consultancy fees from Lundbeck and Teva in the past three years. JM, TR, JLB, ZKO, LH and report no conflicts of interest., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Bipolar disorder is associated with increased rates of many physical disorders, but the effects of medication are unclear. We systematically investigated the associations between sustained use of first line maintenance agents, lithium versus lamotrigine and valproate, and the risk of physical disorders using a nation-wide population-based target trial emulation covering the entire 5.9 million inhabitants in Denmark. We identified two cohorts. Cohort 1: patients with a diagnosis of bipolar disorder prior to first purchase (N = 12.607). Cohort 2: all 156.678 adult patients who had their first ever purchase (since 1995) of either lithium, lamotrigine or valproate between 1997 and 2021 regardless of diagnosis. Main analyses investigated the effect of sustained exposure defined as exposure for all consecutive 6-months periods during a 10-year follow-up. Outcomes included a diagnosis of incident stroke, arteriosclerosis, angina pectoris, myocardial infarction, diabetes mellitus, myxedema, osteoporosis, dementia, Parkinson's disease, chronic kidney disease and cancer (including subtypes). In both Cohorts 1 and 2, there were no systematic statistically significant differences in associations between sustained use of lithium versus lamotrigine and valproate, respectively, and any physical disorder, including subtypes of disorders, except myxedema, for which exposure to lithium increased the absolute risk of myxedema with 7-10 % compared with lamotrigine or valproate. In conclusion, these analyses emulating a target trial of "real world" observational register-based data show that lithium does not increase the risk of developing any kind of physical disorders, except myxedema, which may be a result of detection bias., Competing Interests: Declaration of competing interest Lars Vedel Kessing has the last three years been a consultant for Lundbeck and Teva. Christian Torp-Pedersen report grants for studies from Bayer and Novo Nordisk not related to current study. Michael Berk: Grant/Research Support: MRFF, NHMRC, Congressionally Directed Medical Research Programs (CDMRP) USA, AEDRTC Australian Eating Disorders Research and Translation Centre, Patient-Centered Outcomes Research Institute (PCORI), Baszucki Brain Research Fund, Danmarks Frie Forskningsfond. Psykiatrisk Center Kobenhavn, Stanley Medical Research Institute, Victorian Government Department of Jobs, Precincts and Regions, Wellcome Trust, Victorian Medical Research Acceleration Fund, Controversias Psiquiatria Barcelona, CRE, Victorian COVID-19 Research Fund, Consultancies: Lundbeck, Sandoz, Servier, Medisquire, HealthEd, ANZJP, EPA, Janssen, Medplan, RANZCP, Abbott India, ASCP, International Society of Bipolar Disorder, Precision Psychiatry, Penn State College of Medicine, Shanghai Mental Health Centre. (Last 3 years) – all unrelated to this work. Mark Bech Knudsen and Helene Charlotte Wiese Rytgaard report no financial disclosure and competing interests., (Copyright © 2024 Elsevier B.V. and ECNP. All rights reserved.)

Background: Evidence-based use of antidepressant medications is of major clinical importance. We aimed to uncover precription patterns in a large cohort of patients with unipolar depression., Material and Methods: Using Danish nationwide registers, we identified individuals with a first-time hospital diagnosis of unipolar depression between January 1st, 2001, and December 31st, 2016. Redemeed prescriptions of antidepressants from five years before to five years after diagnosis were retreived. Lithium and relevant antipsychotics were included. Data were analyzed with descriptive statistics including sunburst plots. Cox regressions were used to rank the risk of treatment failure according to antidepressant category and depression severity, as measured by hazard ratios of drug shift., Results: The full study population consisted of 113,175 individuals. Selective Serotonin Reuptake Inhibitors was the predominantly prescribed first-line group, both before (55.4%) and after (47.7%) diagnosis and across depression severities. Changes of treatment strategy were frequent; 60.8%, 33.7%, and 17.1% reached a second, third, and fourth treatment trial after the hospital diagnosis, respectively. More than half of patients continued their pre-diagnosis antidepressant after diagnosis. The risk of change of treatment strategy was generally lower in mild-moderate depression and higher in severe depression, with tricyclic antidepressants carrying the highest risk in the former and the lowest risks in the latter. Overall, prescribing were often not in accordance with guidelines., Conclusion: These findings uncover a potential for improving the clinical care for patients with unipolar depression through optimization of the use of marketed antidepressants., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Importance: Few studies have estimated the lifetime incidence of mental health disorders and the association with socioeconomic functioning., Objective: To investigate whether the lifetime incidence of treated mental health disorders is substantially higher than previously reported and estimate associations with long-term socioeconomic difficulties., Design, Setting, and Participants: This nationwide population-based register linkage study includes a randomly selected sample of 1.5 million individuals from the population of Denmark from 1995 to 2018. Data were analyzed from May 2022 to March 2023., Main Outcomes and Measures: Lifetime incidence of any treated mental health disorder in the general population was estimated from birth to age 100 years taking into account the competing risk of all-cause death and associations with socioeconomic functioning. Register measures were (1) from hospitals, a diagnosis of any mental health disorder at an inpatient/outpatient hospital contact; (2) from hospitals and prescription statistics, any mental health disorder/psychotropic prescription, including a hospital-contact diagnosis, or any psychotropic medication prescribed by physicians, including general practitioners or private psychiatrists; and (3) socioeconomic functioning as indicated by highest educational achievement, employment, income, residential status, and marital status., Results: Among a sample of 462 864 individuals with any mental health disorder, the median (IQR) age was 36.6 years (21.0-53.6 years), 233 747 (50.5%) were male, and 229 117 (49.5%) were female. Of these, 112 641 were registered with a hospital-contact mental health disorder diagnosis and 422 080 with a prescription of psychotropic medication. The cumulative incidence of a hospital-contact mental health disorder diagnosis was 29.0% (95% CI, 28.8-29.1), 31.8% (95% CI, 31.6-32.0) for females, and 26.1% (95% CI, 25.9-26.3) for males. When also considering psychotropic prescriptions, the cumulative incidence of any mental health disorder/psychotropic prescription was 82.6% (95% CI, 82.4-82.6), 87.5% (95% CI, 87.4-87.7) for females, and 76.7% (95% CI, 76.5-76.8) for males. Socioeconomic difficulties were associated with mental health disorder/psychotropic prescriptions, including lower income (hazard ratio [HR], 1.55; 95% CI, 1.53-1.56), increased unemployment or disability benefit (HR, 2.50; 95% CI, 2.47-2.53), and a greater likelihood of living alone (HR, 1.78; 95% CI, 1.76-1.80) and being unmarried (HR, 2.02; 95% CI, 2.01-2.04) during long-term follow-up. These rates were confirmed in 4 sensitivity analyses with the lowest being 74.8% (95% CI, 74.7-75.0) (1) by using varying exclusion periods, (2) by excluding prescriptions of anxiolytics and quetiapine that may be used for off-label indications, (3) by defining any mental health disorder/psychotropic prescription as any hospital-contact mental health disorder diagnosis or any psychotropic medication prescribed at least 2 times, and (4) by excluding individuals with somatic diagnoses for which psychotropics may be prescribed off-label., Conclusions and Relevance: This registry study of data from a large representative sample of the Danish population showed that the majority of individuals either received a diagnosis of a mental health disorder or were prescribed psychotropic medication during their lifetime, which was associated with subsequent socioeconomic difficulties. These findings may help change our understanding of normalcy and mental illness, reduce stigmatization, and further prompt rethinking the primary prevention of mental illness and future mental health clinical resources.

Objective: Patients with bipolar disorder and schizophrenia are at high cardiovascular risk; yet, the risk of out-of-hospital cardiac arrest (OHCA) compared with the general population remains scarcely investigated., Methods: We conducted a nested case-control study using Cox regression to assess the association of bipolar disorder and schizophrenia with the HRs of OHCA of presumed cardiac cause (2001-2015). Reported are the HRs with 95% CIs overall and in subgroups defined by established cardiac disease, cardiovascular risk factors and psychotropic drugs., Results: We included 35 017 OHCA cases and 175 085 age-matched and sex-matched controls (median age 72 years and 66.9% male). Patients with bipolar disorder or schizophrenia had overall higher rates of OHCA compared with the general population: HR 2.74 (95% CI 2.41 to 3.13) and 4.49 (95% CI 4.00 to 5.10), respectively. The association persisted in patients with both cardiac disease and cardiovascular risk factors at baseline (bipolar disorder HR 2.14 (95% CI 1.72 to 2.66), schizophrenia 2.84 (95% CI 2.20 to 3.67)) and among patients without known risk factors (bipolar disorder HR 2.14 (95% CI 1.09 to 4.21), schizophrenia HR 5.16 (95% CI 3.17 to 8.39)). The results were confirmed in subanalyses only including OHCAs presenting with shockable rhythm or receiving an autopsy. Antipsychotics-but not antidepressants, lithium or antiepileptics (the last two only tested in bipolar disorder)-increased OHCA hazard compared with no use in both disorders., Conclusions: Patients with bipolar disorder or schizophrenia have a higher rate of OHCA compared with the general population. Cardiac disease, cardiovascular risk factors and antipsychotics represent important underlying mechanisms., Competing Interests: Competing interests: CP reported receiving speaking fees from Lundbeck Pharma A/S and research grants from the Danish Heart Foundation and Eva and Henry Frænkel Memorial Foundation. LVK received speaking fees from Lundbeck Pharma A/S during recent 3 years. CB reported receiving speaking fees from Bayer A/S during recent 3 years. All remaining authors have declared no conflicts of interest., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Background Affective disorders (AD) have been associated with a higher prevalence of the gut Flavonifractor genus and a lower abundance of the gut Christensenellaceae family. Objective and methods By pooling two independent study samples of patients with AD (n = 176), their unaffected first-degree relatives (n = 70) and healthy controls (n = 101) we aimed to replicate and extend our prior findings of differential Flavonifractor prevalence and Christensenellaceae abundance when comparing patients with AD and healthy controls. The gut microbiota was profiled using 16S rRNA gene amplicon sequencing. Results The pattern of higher prevalence of Flavonifractor and lower Centered Log-Ratio (CLR) abundance of Christensenellaceae was associated with AD. In generalized linear models the CLR abundance of Christensenellaceae was lower in patients with AD (p = 0.024), and in smokers (p = 1.9*10 -4 ), and inversely associated with increasing waist circumference (p = 0.031). The prevalence of Flavonifractor was higher in patients with AD (p = 0.033) and in smokers (p = 0.036). No impact of psychotropic medication was found. The CLR abundance of Christensenellaceae (p = 0.041), but not the prevalence of Flavonifractor (p = 0.20) could distinguish non-smoking patients with AD from non-smoking healthy controls, whereas no such associations were found in smokers. Unaffected relatives neither differed from patients with AD nor from healthy controls. Conclusion Compared with findings in healthy controls, AD was associated with a significantly lower CLR abundance of the health-linked Christensenellaceae and a significantly higher prevalence of Flavonifractor; findings that are associated with enhanced oxidative stress and systemic low-grade inflammation. If our observations are validated in future independent studies, they support the notion that parts of aberrant gut microbiota are shared by AD and states of dysmetabolism., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Depressive episodes experienced in unipolar (UD) and bipolar (BD) disorders are characterized by anhedonia and have been associated with abnormalities in reward processes related to reward valuation and error prediction. It remains however unclear whether these deficits are associated with familial vulnerability to mood disorders., Methods: In a functional magnetic resonance imaging study, we evaluated differences in the expected value (EV) and reward prediction error (RPE) signals in ventral striatum (VS) and prefrontal cortex between three groups of monozygotic twins: affected twins in remission for either UD or BD (n = 53), their high-risk unaffected co-twins (n = 34), and low-risk twins with no family history of mood disorders (n = 25)., Results: Compared to low-risk twins, affected twins showed lower EV signal bilaterally in the frontal poles and lower RPE signal bilaterally in the VS, left frontal pole and superior frontal gyrus. The high-risk group did not show a significant change in the EV or RPE signals in frontostriatal regions, yet both reward signals were consistently lower compared with low-risk twins in all regions where the affected twins showed significant reductions., Conclusion: Our findings strengthen the notion that reduced valuation of expected rewards and reduced error-dependent reward learning may underpin core symptom of depression such as loss of interest in rewarding activities. The trend reduction in reward-related signals in unaffected co-twins warrants further investigation of this effect in larger samples and prospective follow-up to confirm possible association with increased familial vulnerability to mood disorders.

Objective: Psychiatric disorders have been associated with unfavourable outcome following respiratory infections. Whether this also applies to coronavirus disease 2019 (COVID-19) has been scarcely investigated., Methods: Using the Danish administrative databases, we identified all patients with a positive real-time reverse transcription-polymerase chain reaction test for COVID-19 in Denmark up to and including 2 January 2021. Multivariable cox regression was used to calculate 30-day absolute risk and average risk ratio (ARR) for the composite end point of death from any cause and severe COVID-19 associated with psychiatric disorders, defined using both hospital diagnoses and redemption of psychotropic drugs., Results: We included 144,321 patients with COVID-19. Compared with patients without psychiatric disorders, the standardized ARR of the composite outcome was significantly increased for patients with severe mental illness including schizophrenia spectrum disorders 2.43 (95% confidence interval [CI], 1.79-3.07), bipolar disorder 2.11 (95% CI, 1.25-2.97), unipolar depression 1.70 (95% CI, 1.38-2.02), and for patients who redeemed psychotropic drugs 1.70 (95% CI, 1.48-1.92). No association was found for patients with other psychiatric disorders 1.13 (95% CI, 0.86-1.38). Similar results were seen with the outcomes of death or severe COVID-19. Among the different psychiatric subgroups, patients with schizophrenia spectrum disorders had the highest 30-day absolute risk for the composite outcome 3.1% (95% CI, 2.3-3.9%), death 1.2% (95% CI, 0.4-2.0%) and severe COVID-19 2.7% (95% CI, 1.9-3.6%)., Conclusion: Schizophrenia spectrum disorders, bipolar disorder, unipolar depression and psychotropic drug redemption are associated with unfavourable outcomes in patients with COVID-19., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Recent evidence suggests that neurocognitive impairments in remitted patients with bipolar disorder (BD) are heterogeneous. Our study aims to replicate recent findings of neurocognitive subgroups, and further explore whether these are related to impairments in affective cognition, in a large sample of remitted patients recently diagnosed with BD and their unaffected relatives compared to healthy controls (HCs)., Methods: Hierarchal cluster analysis was conducted using neurocognitive data from remitted patients with BD (n = 158). Relatives of patients with BD (n = 52) were categorised into groups consistent with their affected relative's cluster assignment. The neurocognitive clusters of patients with BD and relatives, respectively, were compared with HCs (n = 110) in neurocognition and affective cognition (i.e. emotion processing and regulation)., Results: Three discrete neurocognitive clusters were identified in patients with BD: a globally impaired (23.4%), a selectively impaired (31.0%) and a cognitively intact cluster (45.6%). The neurocognitive subgroups differed in affective cognition, with patients categorised as globally impaired exhibited most impairments in facial expression recognition and emotion regulation in social scenarios. First-degree relatives of cognitively impaired patients displayed impaired facial expression recognition but no impairments in non-emotional cognition., Conclusions: In a clinical sample of remitted patients recently diagnosed with BD 54.4% had either global or selective cognitive impairment, replicating results of previous studies in patients with longer illness duration. The results suggest that patterns of neurocognition are associated with differential impairments in affective cognition. Aberrant affective cognition in relatives of patients categorised as neurocognitively impaired indicates an inherited risk for BD.

Objective: Diabetes is associated with an increased risk of depression. Some antidiabetes agents, specifically metformin and pioglitazone, have been suggested to have beneficial effects on depression, but associations between antidiabetes drugs and depression have not been systematically investigated., Research Design and Methods: We combined four Danish population-based registers to investigate whether the 20 most widely used orally administered antidiabetes drugs were associated with an altered risk of incident depression. Analyses of insulin were included for comparisons. All persons in Denmark in 2005 were included in the study and followed until 2015. Two different outcome measures of incident depression were included: 1 ) a diagnosis of depressive disorder at a psychiatric hospital as an inpatient or outpatient and 2 ) a combined measure of a diagnosis of depression or use of antidepressants. Data were analyzed using Cox regression models., Results: A total of 360,205 individuals using orally administered antidiabetes drugs and 64,582 using insulin at any time during the study period were included in the analyses. Continued use of metformin and combinations of drugs including metformin were associated with decreased rates of incident depression. Pioglitazone was not associated with a decreased rate of incident depression. No other antidiabetes drugs or insulin showed significant associations with depression., Conclusions: Real-life population-based data suggest a positive effect of metformin on depression rates. This evidence should be used in guiding prescriptions for patients with type 2 diabetes who are at risk for developing depression, including those with prior depression or anxiety and patients with a family history of depression., (© 2020 by the American Diabetes Association.)

Objectives: (1) To investigate daily smartphone-based self-reported and automatically generated sleep measurements, respectively, against validated rating scales; (2) to investigate if daily smartphone-based self-reported sleep measurements reflected automatically generated sleep measurements and (3) to investigate the differences in smartphone-based sleep measurements between patients with bipolar disorder (BD), unaffected first-degree relatives (UR) and healthy control individuals (HC)., Methods: We included 203 patients with BD, 54 UR and 109 HC in this study. To investigate whether smartphone-based sleep calculated from self-reported bedtime, wake-up time and screen on/off time reflected validated rating scales, we used the Pittsburgh Sleep Quality Index (PSQI) and sleep items on the Hamilton Depression Rating Scale 17-item (HAMD-17) and the Young Mania Rating Scale (YMRS)., Findings: (1) Self-reported smartphone-based sleep was associated with the PSQI and sleep items of the HAMD and the YMRS. (2) Automatically generated smartphone-based sleep measurements were associated with daily self-reports of hours slept between 12:00 midnight and 06:00. (3) According to smartphone-based sleep, patients with BD slept less between 12:00 midnight and 06:00, with more interruption and daily variability compared with HC. However, differences in automatically generated smartphone-based sleep were not statistically significant., Conclusion: Smartphone-based data may represent measurements of sleep patterns that discriminate between patients with BD and HC and potentially between UR and HC., Clinical Implication: Detecting sleep disturbances and daily variability in sleep duration using smartphones may be helpful for both patients and clinicians for monitoring illness activity., Trial Registration Number: clinicaltrials.gov (NCT02888262)., Competing Interests: Competing interests: LVK and MV has been a consultant for Lundbeck within recent 3 years. JEB and MF are co-founders and shareholders of Monsenso ApS., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Hypertension, cardiovascular diseases, and cerebrovascular diseases are associated with an increased risk of depression, but it remains unclear whether treatment with antihypertensive agents decreases or increases this risk. The effects of individual drugs are also unknown. We used Danish population-based registers to systematically investigate whether the 41 most used individual antihypertensive drugs were associated with an altered risk of incident depression. Analyses of diuretics were included for comparisons. Participants were included in the study in January 2005 and followed until December 2015. Two different outcome measures were included: (1) a diagnosis of depressive disorder at a psychiatric hospital as an inpatient or outpatient and (2) a combined measure of a diagnosis of depression or use of antidepressants. Continued use of classes of angiotensin agents, calcium antagonists, and β-blockers was associated with significantly decreased rates of depression, whereas diuretic use was not. Individual drugs associated with decreased depression included 2 of 16 angiotensin agents: enalapril and ramipril; 3 of 10 calcium antagonists: amlodipine, verapamil, and verapamil combinations; and 4 of 15 β-blockers: propranolol, atenolol, bisoprolol, and carvedilol. No drug was associated with an increased risk of depression. In conclusion, real-life population-based data suggest a positive effect of continued use of 9 individual antihypertensive agents. This evidence should be used in guiding prescriptions for patients at risk of developing depression including those with prior depression or anxiety and patients with a family history of depression.

Background: Metabolic syndrome (MetS) is associated with reduced life expectancy in patients with affective disorders, however, whether MetS also plays a role before the onset of affective disorder is unknown. We aimed to investigate whether MetS, inflammatory markers or oxidative stress act as risk factors for affective disorders, and whether MetS is associated with increased inflammation and oxidative stress., Methods: We conducted a high-risk study including 204 monozygotic (MZ) twins with unipolar or bipolar disorder in remission or partial remission (affected), their unaffected co-twins (high-risk) and twins with no personal or family history of affective disorder (low-risk). Metabolic Syndrome was ascertained according to the International Diabetes Federation (IDF) criteria. Inflammatory markers and markers of oxidative stress were analyzed from fasting blood and urine samples, respectively., Results: The affected and the high-risk group had a significantly higher prevalence of MetS compared to the low-risk group (20% v. 15% v. 2.5%, p = 0.0006), even after adjusting for sex, age, smoking and alcohol consumption. No differences in inflammatory and oxidative markers were seen between the three groups. Further, MetS was associated with alterations in inflammatory markers, and oxidative stress was modestly correlated with inflammation., Conclusion: Metabolic syndrome is associated with low-grade inflammation and may act as a risk factor and a trait marker for affective disorders. If confirmed in longitudinal studies, this suggests the importance of early intervention and preventive approaches targeted towards unhealthy lifestyle factors that may contribute to later psychopathology.

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.)., (Copyright © 2020 Massachusetts Medical Society.)

Background: Recently, the MONARCA I randomized controlled trial (RCT) was the first to investigate the effect of smartphone-based monitoring in bipolar disorder (BD). Findings suggested that smartphone-based monitoring sustained depressive but reduced manic symptoms. The present RCT investigated the effect of a new smartphone-based system on the severity of depressive and manic symptoms in BD., Methods: Randomized controlled single-blind parallel-group trial. Patients with BD, previously treated at The Copenhagen Clinic for Affective Disorder, Denmark and currently treated at community psychiatric centres, private psychiatrists or GPs were randomized to the use of a smartphone-based system or to standard treatment for 9 months. Primary outcomes: differences in depressive and manic symptoms between the groups., Results: A total of 129 patients with BD (ICD-10) were included. Intention-to-treat analyses showed no statistically significant effect of smartphone-based monitoring on depressive (B = 0.61, 95% CI -0.77 to 2.00, p = 0.38) and manic (B = -0.25, 95% CI -1.1 to 0.59, p = 0.56) symptoms. The intervention group reported higher quality of life and lower perceived stress compared with the control group. In sub-analyses, the intervention group had higher risk of depressive episodes, but lower risk of manic episodes compared with the control group., Conclusions: There was no effect of smartphone-based monitoring. In patient-reported outcomes, patients in the intervention group reported improved quality of life and reduced perceived stress. Patients in the intervention group had higher risk of depressive episodes and reduced risk of manic episodes. Despite the widespread use and excitement of electronic monitoring, few studies have investigated possible effects. Further studies are needed.

Aims: To investigate whether the recent improvements in pre-hospital cardiac arrest-management and survival following out-of-hospital cardiac arrest (OHCA) also apply to OHCA patients with psychiatric disorders., Methods: We identified all adult Danish patients with OHCA of presumed cardiac cause, 2001-2015. Psychiatric disorders were defined by hospital diagnoses up to 10 years before OHCA and analyzed as one group as well as divided into five subgroups (schizophrenia-spectrum disorders, bipolar disorder, depression, substance-induced mental disorders, other psychiatric disorders). Association between psychiatric disorders and pre-hospital OHCA-characteristics and 30-day survival were assessed by multiple logistic regression., Results: Of 27,523 OHCA-patients, 4772 (17.3%) had a psychiatric diagnosis. Patients with psychiatric disorders had lower odds of 30-day survival (0.37 95% confidence interval 0.32-0.43) compared with other OHCA-patients. Likewise, they had lower odds of witnessed status (0.75 CI 0.70-0.80), bystander cardiopulmonary resuscitation (CPR) (0.77 CI 0.72-0.83), shockable heart rhythm (0.37 95% CI, 0.33-0.40), and return of spontaneous circulation (ROSC) at hospital arrival (0.66 CI 0.59-0.72). Similar results were seen in all five psychiatric subgroups. The difference in 30-day survival between patients with and without psychiatric disorders increased in recent years: from 8.4% (CI 7.0-10.0%) in 2006 to 13.9% (CI 12.4-15.4%) in 2015 and from 7.0% (4.3-10.8%) in 2006 to 7.0% (CI 4.5-9.7%) in 2015, respectively., Conclusion: Patients with psychiatric disorders have lower survival following OHCA compared to non-psychiatric patients and the gap between the two groups has widened over time., (Copyright © 2019. Published by Elsevier B.V.)

Background Healthcare disparities for psychiatric patients are common. Whether these inequalities apply to postresuscitation management in out-of-hospital cardiac arrest (OHCA) is unknown. We investigated differences in in-hospital cardiovascular procedures following OHCA between patients with and without psychiatric disorders. Methods and Results Using the Danish nationwide registries, we identified patients admitted to the hospital following OHCA of presumed cardiac cause (2001-2015). Psychiatric disorders were identified using hospital diagnoses or redeemed prescriptions for psychotropic drugs. We calculated age- and sex-standardized incidence rates and incidence rate ratios (IRRs) of cardiovascular procedures during post-OHCA admission in patients with and without psychiatric disorders. Differences in 30-day and 1-year survival were assessed by multivariable logistic regression in the overall population and among 2-day survivors who received acute coronary angiography (CAG). We included 7288 hospitalized patients who had experienced an OHCA: 1661 (22.8%) had a psychiatric disorder. Compared with patients without psychiatric disorders, patients with psychiatric disorders had lower standardized incidence rates for acute CAG (≤1 day post-OHCA) (IRR, 0.51; 95% CI, 0.45-0.57), subacute CAG (2-30 days post-OHCA) (IRR, 0.40; 95% CI, 0.30-0.52), and implantable cardioverter-defibrillator implantation (IRR, 0.67; 95% CI, 0.48-0.95). Conversely, we did not detect differences in coronary revascularization among patients undergoing CAG (IRR, 1.11; 95% CI, 0.94-1.30). Patients with psychiatric disorders had lower survival even among 2-day survivors who received acute CAG: (odds ratio of 30-day survival, 0.68; 95% CI, 0.52-0.91; and 1-year survival, 0.66; 95% CI, 0.50-0.88). Conclusions Psychiatric patients had a lower probability of receiving post-OHCA CAG and implantable cardioverter-defibrillator implantation compared with nonpsychiatric patients but the same probability of coronary revascularization among patients undergoing CAG. However, their survival was lower irrespective of angiographic procedures.

Objective: Drug repurposing is an increasingly promising idea in many fields of medicine. We systematically used Danish nation-wide population-based registers to investigate whether continued use of non-aspirin non-steroidal anti-inflammatory drugs (NSAIDs), low-dose aspirin, high-dose aspirin, statins, allopurinol, and angiotensin agents decrease the rate of incident mania/bipolar disorder., Methods: A nation-wide population-based longitudinal study using Poisson regression analyses including all persons in Denmark who purchased the exposure medication of interest and a random sample of 30% of the Danish population. The follow-up period comprised a 10 years period from 2005 to 2015. Two different outcome measures were included, (1) a diagnosis of mania/bipolar disorder at a psychiatric hospital contact as inpatient or outpatient and (2) a combined measure of a diagnosis of mania/bipolar disorder or initiation of lithium use., Results: A total of 1,605,365 subjects were exposed to one of the six drugs of interest during the exposure period from 2005 to 2015, median age 57 years [quartiles: 43;69], and female proportion of 53.1%. Continued use of low-dose aspirin, statins, and angiotensin agents were associated with decreased rates of incident mania/bipolar disorder on both outcome measures. Continued uses of non-aspirin NSAIDs as well as high-dose aspirin were associated with an increased rate of incident bipolar disorder. There were no statistically significant associations for allopurinol., Conclusions: The study supports the potential of agents acting on inflammation and the stress response system in bipolar disorder and illustrates that population-based registers can be used to systematically identify drugs with repurposing potentials., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objective: To (i) validate patient-evaluated mixed symptoms and irritability measured using smartphones against clinical evaluations; (ii) investigate associations between mixed symptoms and irritability with stress, quality of life and functioning, respectively, in patients with bipolar disorder., Methods: A total of 84 patients with bipolar disorder used a smartphone-based system for daily evaluation of mixed symptoms and irritability for nine months. Clinically evaluated symptoms, stress, quality of life and clinically rated functioning were collected multiple times during follow-up., Results: Patients presented mild affective symptoms. Patient-reported mixed symptoms and irritability correlated with clinical evaluations. In analyses including confounding factors there was a statistically significant association between both mixed symptoms and irritability and stress (P < 0.0001) and between irritability and both quality of life and functioning (P < 0.0001) respectively. There was no association between mixed mood and both quality of life and functioning., Conclusion: Mixed symptoms and irritability can be validly self-reported using smartphones in patients with bipolar disorder. Mixed symptoms and irritability are associated with increased stress even during full or partial remission. Irritability is associated with decreased quality of life and functioning. The findings emphasize the clinical importance of identifying inter-episodic symptoms including irritability pointing towards smartphones as a valid tool., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

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.

Background: Increasing attention deficit hyperactivity disorder (ADHD) incidence has been proposed to be caused by factors influencing microbiota in early life. We investigated the potential causality between ADHD and two surrogate markers for changes in children's microbiota: birth delivery mode and early childhood antibiotic use., Method: This population-based, prospective cohort study linked nationwide registers of data for native Danish singleton live births in Denmark from 1997 to 2010. Exposure variables were delivery mode and antibiotic use during the first 2 years of life. The main outcome measure was ADHD diagnosis or redeemed ADHD medication prescriptions. For statistical analysis, we used both advanced sibling models and a more traditional approach., Results: We included 671,592 children, followed from their second birthday in the period 1999-2014 for 7,300,522 person-years. ADHD was diagnosed in 17,971. In total, 17.5% were born by cesarean delivery, and 72% received antibiotic treatment within their first 2 years of life. In the adjusted between-within sibling survival model, mode of delivery or antibiotics had no effect on ADHD when compared with vaginal delivery or no antibiotic treatment as hazard ratios were 1.09 (95% confidence interval 0.97-1.24) for intrapartum cesarean, 1.03 (0.91-1.16) for prelabor cesarean, 0.98 (0.90-1.07) for penicillin, and 0.99 (0.92-1.06) for broader spectrum antibiotics. In a sibling-stratified Cox regression, intrapartum cesarean was associated with increased ADHD risk, but other exposures were not. In a descriptive, nonstratified Cox model, we found increased risk for ADHD for all exposures., Conclusions: Detailed family confounder control using the superior between-within model indicates that cesarean delivery or use of antibiotics during the first 2 years of life does not increase ADHD risk. Therefore, our study suggests that changes in children's microbiota related to cesarean delivery or antibiotic use, do not cause ADHD., (© 2018 Association for Child and Adolescent Mental Health.)

Objective: Affective disorders seem associated with aberrant intestinal microbiota but whether this pattern also occurs in individuals at increased heritable risk is unknown. We investigated associations between gut microbiota profiles and affective disorders by comparing monozygotic (MZ) twins concordant (affected twins with unipolar or bipolar disorder in remission) and discordant to affective disorders (high-risk) with MZ twins without affective disorders (low-risk)., Methods: Stool samples were collected from 128 MZ twins and the microbiome was profiled using 16S rDNA sequencing of the V3-V4 region., Results: Affected twins had a lower diversity and an absence of a specific operational taxonomical unit (OTU) in comparison with low-risk twins. The high-risk twins exhibited the same pattern although the lower diversity was only at a trend level. The OTU belonged to the family Christensenellaceae. The findings were not explained by lifestyle factors (smoking, alcohol consumption, body mass index, or psychotropic medication)., Conclusion: Affected twins in remission and high-risk twins presented aberrant gut microbiota with depletion of a specific OTU. If replicated, this reduced relative sequence absence may together with the globally altered microbiota composition act as a vulnerability marker by accentuating the effect of gene-environment interactions in individuals genetically disposed for an affective disorder., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Hypotheses concerning adverse effects of changes in microbiota have received much recent attention, but unobserved confounding makes them difficult to test. We investigated whether surrogate markers for potential adverse microbiota change in infancy affected autism risk, addressing unobserved confounding using a sibling study design., Methods: This is a population-based, prospective cohort study including all singleton live births in Denmark from 1997 to 2010. The exposure variables were cesarean delivery and antibiotic use in the first 2 years of life. The outcome was a subsequent autism diagnosis. We used the between- and within-sibling model and compared it with sibling-stratified Cox models and simpler standard Cox models that ignored sibship., Results: Of our study population including 671,606 children, who were followed for up to 15 years (7,341,133 person-years), 72% received antibiotics, 17.5% were delivered by cesarean, and 1.2% (8,267) developed autism. The standard Cox models predicted that both cesarean (compared with vaginal) delivery and antibiotics increased the risk of autism. In the sibling-stratified Cox model, only broader spectrum antibiotics were associated with increased risk of autism: hazard ratio (HR) = 1.16 (95% confidence interval = 1.01, 1.36). The between-within model estimated no exposure effects: intrapartum cesarean HR = 1.06 (0.89, 1.26); prelabor cesarean HR = 0.97 (0.83, 1.15); exclusively penicillin HR = 1.05 (0.93, 1.18); and broader spectrum antibiotics HR = 1.05 (0.95, 1.16)., Conclusions: The between-within model rendered more precise estimates than sibling-stratified Cox models, and we believe that it also provided more valid estimates. Results from these preferred models do not support a causal relation between antibiotic treatment during infancy, cesarean delivery, and autism. See video abstract at, http://links.lww.com/EDE/B432.

Objective: To investigate whether continued use of non-aspirin NSAID, low-dose aspirin, high-dose aspirin, statins, allopurinol and angiotensin agents decreases the rate of incident depression using Danish nationwide population-based registers., Methods: All persons in Denmark who purchased the exposure medications of interest between 1995 and 2015 and a random sample of 30% of the Danish population was included in the study. Two different outcome measures were included, (i) a diagnosis of depressive disorder at a psychiatric hospital as in-patient or out-patient and (ii) a combined measure of a diagnosis of depression or use of antidepressants., Results: A total of 1 576 253 subjects were exposed to one of the six drugs of interest during the exposure period from 2005 to 2015. Continued use of low-dose aspirin, statins, allopurinol and angiotensin agents was associated with a decreased rate of incident depression according to both outcome measures. Continued uses of non-aspirin NSAIDs as well as high-dose aspirin were associated with an increased rate of incident depression., Conclusion: The findings support the potential of agents acting on inflammation and the stress response system in depression as well as the potential of population-based registers to systematically identify drugs with repurposing potential., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objective: An aberrant gut microbiota may be associated with a broad spectrum of diseases including mental illness. The gut microbiota is scarcely studied in bipolar disorder (BD). We examined the gut microbiota composition in patients with newly diagnosed BD, their unaffected first-degree relatives and healthy individuals., Methods: Stool samples were collected from 113 patients with BD, 39 unaffected first-degree relatives and 77 healthy individuals and the microbiota was profiled using 16S rRNA gene amplicon sequencing., Results: The gut microbiota community membership of patients with BD differed from that of healthy individuals (R 2  = 1.0%, P = 0.008), whereas the community membership of unaffected first-degree relatives did not. Flavonifractor was present in 61% of patients with BD, 42% of their unaffected relatives and 39% of healthy individuals. Presence of Flavonifractor was associated with an odds ratio of 2.9 (95%CI: 1.6-5.2, P = 5.8 × 10 -4 , Q = 0.036) for having BD. When excluding smokers, presence of Flavonifractor was associated with an odds ratio of 2.3 (95%CI: 1.1-5.3, P = 0.019) for having BD. However, when considering the subsample of non-smokers only, BD and presence of Flavonifractor were no longer associated when adjusted for all possible tests at genus level (Q = 0.6). Presence of Flavonifractor in patients with BD was associated with smoking and female sex, but not with age, waist circumference, exercise level, high-sensitive C-reactive protein, current affective state, subtype of BD, illness duration or psychotropic medication, respectively., Conclusion: Flavonifractor, a bacterial genus that may induce oxidative stress and inflammation in its host, was associated with BD. Higher prevalence of smoking among patients with BD contributed to our findings, and it cannot be excluded that findings are influenced by residual confounding., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Cognitive impairment is present in bipolar disorder (BD) during the acute and remitted phases and hampers functional recovery. However, there is currently no clinically available treatment with direct and lasting effects on cognitive impairment in BD. We will examine the effect of a novel form of cognitive remediation, action-based cognitive remediation (ABCR), on cognitive impairment in patients with BD, and explore the neural substrates of potential treatment efficacy on cognition., Methods/design: The trial has a randomized, controlled, parallel-group design. In total, 58 patients with BD in full or partial remission aged 18-55 years with objective cognitive impairment will be recruited. Participants are randomized to 10 weeks of ABCR or a control group. Assessments encompassing neuropsychological testing and mood ratings, and questionnaires on subjective cognitive complaints, psychosocial functioning, and quality of life are carried out at baseline, after 2 weeks of treatment, after the end of treatment, and at a six-month-follow-up after treatment completion. Functional magnetic resonance imaging scans are performed at baseline and 2 weeks into treatment. The primary outcome is a cognitive composite score spanning verbal memory, attention, and executive function. Two complete data sets for 52 patients will provide a power of 80% to detect a clinically relevant between-group difference on the primary outcome. Behavioral data will be analyzed using mixed models in SPSS while MRI data will be analyzed with the FMRIB Expert Analysis Tool (FEAT). Early treatment-related changes in neural activity from baseline to week 2 will be investigated for the dorsal prefrontal cortex and hippocampus as the regions of interest and with an exploratory whole-brain analysis., Discussion: The results will provide insight into whether ABCR has beneficial effects on cognition and functioning in remitted patients with BD. The results will also provide insight into early changes in neural activity associated with improvement of cognition, which can aid future treatment development., Trial Registration: Clinicaltrials.gov , NCT03295305 . Registered on 26 September 2017.

Background: Electroconvulsive therapy (ECT) is the most effective treatment for severe depression, but its use is impeded by its cognitive side effects. Novel treatments that can counteract these side effects may therefore improve current treatment strategies for depression. The present randomized trial investigates (1) whether short-term add-on treatment with erythropoietin (EPO) can reduce the cognitive side -effects of ECT and (2) whether such effects are long-lasting. Further, structural and functional magnetic resonance imaging (MRI) will be used to explore the neural underpinnings of such beneficial effects of EPO. Finally, the trial examines whether potential protective effects of EPO on cognition are accompanied by changes in markers of oxidative stress, inflammation, and neuroplasticity., Methods/design: The trial has a double-blind, randomized, placebo-controlled, parallel group design. Patients with unipolar or bipolar disorder with current moderate to severe depression referred to ECT (N = 52) are randomized to receive four high-dose infusions of EPO (40,000 IU/ml) or placebo (saline). The first EPO/saline infusion is administered within 24 h before the first ECT. The following three infusions are administered at weekly intervals immediately after ECT sessions 1, 4, and 7. Cognition assessments are conducted at baseline, after the final EPO/saline infusion (3 days after eight ECT sessions), and at a 3 months follow-up after ECT treatment completion. The neuronal substrates for potential cognitive benefits of EPO are investigated with structural and functional MRI after the final EPO/saline infusion. The primary outcome is change from baseline to after EPO treatment (3 days after eight ECT sessions) in a cognitive composite score spanning attention, psychomotor speed, and executive functions. With a sample size of N = 52 (n = 26 per group), we have ≥ 80% power to detect a clinically relevant between-group difference in the primary outcome measure at an alpha level of 5% (two-sided test). Behavioral, mood, and blood-biomarker data will be analyzed using repeated measures analysis of covariance. Functional MRI data will be preprocessed and analyzed using the FMRIB Software Library., Discussion: If EPO is found to reduce the cognitive side effects of ECT, this could have important implications for future treatment strategies for depression and for the scientific understanding of the neurobiological etiology of cognitive dysfunction in patients treated with ECT., Trial Registration: ClinicalTrials.gov, NCT03339596 . Registered on 10 November 2017.

Objective: The purpose of this study was to assess the relative risk of suicide attempt and suicide in users of hormonal contraception., Method: The authors assessed associations between hormonal contraceptive use and suicide attempt and suicide in a nationwide prospective cohort study of all women in Denmark who had no psychiatric diagnoses, antidepressant use, or hormonal contraceptive use before age 15 and who turned 15 during the study period, which extended from 1996 through 2013. Nationwide registers provided individually updated information about use of hormonal contraception, suicide attempt, suicide, and potential confounding variables. Psychiatric diagnoses or antidepressant use during the study period were considered potential mediators between hormonal contraceptive use and risk of suicide attempt. Adjusted hazard ratios for suicide attempt and suicide were estimated for users of hormonal contraception as compared with those who never used hormonal contraception., Results: Among nearly half a million women followed on average for 8.3 years (3.9 million person-years) with a mean age of 21 years, 6,999 first suicide attempts and 71 suicides were identified. Compared with women who never used hormonal contraceptives, the relative risk among current and recent users was 1.97 (95% CI=1.85-2.10) for suicide attempt and 3.08 (95% CI=1.34-7.08) for suicide. Risk estimates for suicide attempt were 1.91 (95% CI=1.79-2.03) for oral combined products, 2.29 (95% CI=1.77-2.95) for oral progestin-only products, 2.58 (95% CI=2.06-3.22) for vaginal ring, and 3.28 (95% CI=2.08-5.16) for patch. The association between hormonal contraceptive use and a first suicide attempt peaked after 2 months of use., Conclusions: Use of hormonal contraception was positively associated with subsequent suicide attempt and suicide. Adolescent women experienced the highest relative risk.

Background: In long-term follow-up studies on depression, the Eysenck Neuroticism Scale (ENS) at the score level of dysthymia has been found to be valid at predicting poor outcome., Aims: The ENS dysthymia level was compared with the Beck Depression Inventory (BDI) level to predict the prevalence of depressive symptoms at the 5-year follow-up of patients initially diagnosed with first episode depression using the Hamilton Depression Scale (HAM-D) to express depressive symptoms., Methods: A total of 301 in- or outpatients aged 18-70 years with a recent single depressive episode were assessed by ENS, BDI, and HAM-D from 2005-2007. At 5-year follow-up from 2011-2013, the participants were re-assessed by HAM-D. The HAM-D was used to measure depressive symptoms at the 5-year follow-up. The Mokken analysis was used to indicate scalability of the BDI and ENS., Results: A total of 185 participants were available for the psychometric analysis of the ESN and BDI, and the scalability was found acceptable. In total, 99 patients were available for the predictive analysis. Both the ENS and the BDI were significantly associated with depressive symptoms (HAM-D17 ≥ 8) at the 5-year follow-up (p < 0.05)., Conclusion: Dysthymia as measured by the two self-rating scales ENS and BDI can be considered part of a 'double depression' in patients with first episode depression, implying an existence of depressive symptoms at the 5-year follow-up., Clinical Implications: Evaluation of dysthymia or neuroticism is important to perform, even in patients with first episode depression, in order to identify 'double depression'.

Background: Healthy first-degree relatives of patients with affective disorders are at increased risk for affective disorders and express discrete structural and functional abnormalities in the brain reward system. However, value-based decision making is not well understood in these at-risk individuals., Methods: We investigated healthy monozygotic and dizygotic twins with or without a co-twin history of affective disorders (high-risk and low-risk groups, respectively) using functional MRI during a gambling task. We assessed group differences in activity related to gambling risk over the entire brain., Results: We included 30 monozygotic and 37 dizygotic twins in our analysis. Neural activity in the anterior insula and ventral striatum increased linearly with the amount of gambling risk in the entire cohort. Individual neuroticism scores were positively correlated with the neural response in the ventral striatum to increasing gambling risk and negatively correlated with individual risk-taking behaviour. Compared with low-risk twins, the high-risk twins showed a bilateral reduction of risk-related activity in the middle insula extending into the temporal cortex with increasing gambling risk. Post hoc analyses revealed that this effect was strongest in dizygotic twins., Limitations: The relatively old average age of the mono- and dizygotic twin cohort (49.2 yr) may indicate an increased resilience to affective disorders. The size of the monozygotic high-risk group was relatively small (n = 13)., Conclusion: The reduced processing of risk magnitude in the middle insula may indicate a deficient integration of exteroceptive information related to risk-related cues with interoceptive states in individuals at familial risk for affective disorders. Impaired risk processing might contribute to increased vulnerability to affective disorders.

Objectives: A recent alarming finding suggested an increased risk of renal tumors among long-term lithium users. The objectives of the present study were to estimate rates of renal and upper urinary tract tumors (RUT), malignant and benign, among individuals exposed to successive prescriptions for lithium, anticonvulsants, and other psychotropic agents used for bipolar disorder, and among unexposed individuals., Methods: This was a nationwide, population-based longitudinal study including time-specific data from all individuals exposed to lithium (n = 24,272) or anticonvulsants (n = 386,255), all individuals with a diagnosis of bipolar disorder (n = 9,651), and a randomly selected sample of 1,500,000 from the Danish population. The study period was from 1995 to 2012, inclusive. Outcomes were hazard rate ratios (HR) for RUT in three groups: (i) combined malignant and benign, (ii) malignant, and (iii) benign. Analyses were adjusted for the number of prescriptions for lithium/anticonvulsants, antipsychotic agents, antidepressants, and use of all other types of medication; age; gender; employment status; calendar year; and a diagnosis of bipolar disorder., Results: Continued treatment with lithium was not associated with increased rates of RUT [adjusted HR malignant or benign: 0.67-1.18, p (trend) = 0.70; adjusted HR malignant: 0.61-1.34, p (trend) = 0.90; adjusted HR benign: 0.74-1.18, p (trend) = 0.70]. Similarly, continued treatment with anticonvulsants was not associated with increased rates of RUT [adjusted HR malignant or benign: 0.97-1.18, p (trend) = 0.10; adjusted HR malignant: 0.82-1.15, p (trend) = 0.80; adjusted HR benign: 0.94-1.36, p (trend) = 0.20]. The associations were confirmed among the 9,651 patients with a diagnosis of bipolar disorder., Conclusions: Treatment with lithium is not associated with increased rates of RUT., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Importance: Lithium is the main mood stabilizing drug for bipolar disorder. However, it is controversial whether long-term maintenance treatment with lithium or other drugs for bipolar disorder causes chronic kidney disease (CKD)., Objective: To compare rates of CKD and in particular rates of end-stage CKD among individuals exposed to successive prescriptions of lithium, anticonvulsants, or other drugs used for bipolar disorder., Design, Setting, and Participants: This is a Danish nationwide population-based study of 2 cohorts. Cohort 1 comprised a randomly selected sample of 1.5 million individuals among all persons who were registered in Denmark on January 1, 1995, all patients with a diagnosis of a single manic episode or bipolar disorder between January 1, 1994, and December 31, 2012 (n =10,591), and all patients exposed to either lithium (n = 26,731) or anticonvulsants (n=420,959). Cohort 2 included the subgroup of 10,591 patients diagnosed as having bipolar disorder., Main Outcomes and Measures: Possible CKD, definite CKD, and end-stage CKD (defined as long-term dialysis or renal transplantation)., Results: A total of 14,727 (0.8%), 18,762 (1.0%), and 3407 (0.2%) in cohort 1 and 278 (2.6%), 319 (3.0%), and 62 (0.6%) in cohort 2 were diagnosed as having possible, definite, or end-stage CKD, respectively. Based on the total sample and not considering diagnoses, use of lithium was associated with an increased rate of definite CKD (0 prescriptions: hazard ratio [HR] = 1.09, 95% CI, 0.81-1.45; ≥60 prescriptions: HR = 3.65, 95% CI, 2.64-5.05; P for trend < .001) and possible CKD (0 prescriptions: HR = 1.01, 95% CI, 0.79-1.30; ≥60 prescriptions: HR = 2.88, 95% CI, 2.17-3.81; P for trend < .001), whereas use of anticonvulsants, antipsychotics, or antidepressants was not. Neither use of lithium nor use of any other drug class was associated with increasing rates of end-stage CKD. In patients with bipolar disorder, use of lithium was associated with an increased rate of definite CKD (1-2 prescriptions: HR = 0.89, 95% CI, 0.39-2.06; ≥60 prescriptions: HR = 2.54, 95% CI, 1.81-3.57; P for trend < .001) or possible CKD (1-2 prescriptions: HR = 1.26, 95% CI, 0.65-2.43; ≥60 prescriptions, HR = 2.48, 95% CI, 1.80-3.42; P for trend < .001), as was use of anticonvulsants (definite CKD, 1-2 prescriptions: HR = 1.23, 95% CI, 0.76-1.99; ≥60 prescriptions, HR = 2.30, 95% CI, 1.53-3.44; P for trend < .001; possible CKD, 1-2 prescriptions: HR = 1.11, 95% CI, 0.70-1.76; ≥60 prescriptions: HR = 1.97, 95% CI, 1.34-2.90; P for trend < .001). There was no such association with antipsychotics or antidepressants. Also in patients with bipolar disorder, use of lithium was not significantly associated with an increased rate of end-stage CKD, whereas use of anticonvulsants was (1-2 prescriptions, HR = 0 [95% CI, 0.00-infinity]; 30-39 prescriptions: HR = 3.23, 95% CI, 1.26-8.27; ≥60 prescriptions: HR = 2.06, 95% CI, 0.82-5.16; P for trend = .002)., Conclusions and Relevance: Maintenance treatment with lithium or anticonvulsants as practiced in modern care is associated with an increased rate of CKD. However, use of lithium is not associated with an increased rate of end-stage CKD. The associations between use of medication and CKD may at least partly be attributed to bias.

The main objective of the study was to find combinations of genetic variants significantly associated with bipolar disorder. In a previous study of bipolar disorder, combinations of three single nucleotide polymorphism (SNP) genotypes taken from 803 SNPs were analyzed, and four clusters of combinations were found to be significantly associated with bipolar disorder. In the present study, combinations of four SNP genotypes taken from the same 803 SNPs were analyzed, and one cluster of combinations was found to be significantly associated with bipolar disorder. Combinations from the new cluster and from the four previous clusters were identified in the genomes of 209 of the 607 patients in the study whereas none of the 1355 control participants had any of these combinations in their genome.

Background: Negative cognitive bias and aberrant neural processing of emotional faces are trait-marks of depression. Yet it is unclear whether these changes constitute an endophenotype for depression and are also present in healthy individuals with hereditary risk for depression., Method: Thirty healthy, never-depressed monozygotic (MZ) twins with a co-twin history of depression (high risk group: n = 13) or without co-twin history of depression (low-risk group: n = 17) were enrolled in a functional magnetic resonance imaging (fMRI) study. During fMRI, participants viewed fearful and happy faces while performing a gender discrimination task. After the scan, they were given a faces dot-probe task, a facial expression recognition task and questionnaires assessing mood, personality traits and coping strategies., Results: High-risk twins showed increased neural response to happy and fearful faces in dorsal anterior cingulate cortex (ACC), dorsomedial prefrontal cortex (dmPFC), pre-supplementary motor area and occipito-parietal regions compared to low-risk twins. They also displayed stronger negative coupling between amygdala and pregenual ACC, dmPFC and temporo-parietal regions during emotional face processing. These task-related changes in neural responses in high-risk twins were accompanied by impaired gender discrimination performance during face processing. They also displayed increased attention vigilance for fearful faces and were slower at recognizing facial expressions relative to low-risk controls. These effects occurred in the absence of differences between groups in mood, subjective state or coping., Conclusions: Different neural response and functional connectivity within fronto-limbic and occipito-parietal regions during emotional face processing and enhanced fear vigilance may be key endophenotypes for depression.

Purpose: To investigate the risk for first depression, assessed as incident hospital contacts for depression and incident use of antidepressants, among women with breast cancer., Patients and Methods: Danish national registries were used to identify 1,997,669 women with no diagnosis of cancer or a major psychiatric disorder. This cohort was followed from 1998 to 2011 for a diagnosis of breast cancer and for the two outcomes, hospital contact for depression and redeemed prescriptions for antidepressants. Rate ratios for incident hospital contacts for depression and incident use of antidepressants were estimated with Poisson regression models. Multivariable Cox regression was used to evaluate factors associated with the two outcomes among patients with breast cancer., Results: We identified 44,494 women with breast cancer. In the first year after diagnosis, the rate ratio for a hospital contact for depression was 1.70 (95% CI 1.41 to 2.05) and that for use of antidepressants was 3.09 (95% CI 2.95 to 3.22); these rate ratios were significantly increased after 3 and 8 years, respectively. Comorbidity, node-positive disease, older age, basic and vocational educational levels, and living alone were associated with use of antidepressants., Conclusion: Women with breast cancer are at long-term increased risk for first depression, including both severe episodes leading to hospital contact and use of antidepressants. Clinicians should be aware that the risk is highest in women with comorbid conditions, node-positive disease, and age of 70 years or more. We found no clear association between type of surgery or adjuvant treatment and risk for depression., (© 2014 by American Society of Clinical Oncology.)

Objectives: Inflammation is involved in the pathogenesis of depression. A few cross-sectional population-based studies have found that depression is associated with increased levels of inflammatory markers. Soluble urokinase plasminogen activation receptor (suPAR) is known to be a stable marker for inflammation. We investigated the bidirectional association between suPAR levels and use of antidepressants., Methods: suPAR level was measured in 9305 blood donors and analysed in relation to 5-years follow-up data on purchase of antidepressants and hospital diagnoses of depression from a nationwide Danish register., Results: For men and women without prior use of antidepressants we found a significantly higher risk for incident use of antidepressants with higher suPAR values. For men, the risk of first use of antidepressants increased by 72% from the 1st to the 4th quartile (HR = 1.72, 95% CI: 1.11-2.69). For women, it increased by 108% from the 1st to the 4th quartile (HR = 2.08, 95% CI: 1.45-2.98). Previous use of antidepressants was also significantly associated with higher suPAR levels (p = 0.002)., Conclusions: High suPAR levels are associated with an increased risk for both previous and future use of antidepressants in healthy men and women. High suPAR are also associated with increased risk for a hospital diagnosis of depression.

Background: No study has investigated when preventive treatment with lithium should be initiated in bipolar disorder., Aims: To compare response rates among patients with bipolar disorder starting treatment with lithium early v. late., Method: Nationwide registers were used to identify all patients with a diagnosis of bipolar disorder in psychiatric hospital settings who were prescribed lithium during the period 1995-2012 in Denmark (n = 4714). Lithium responders were defined as patients who, following a stabilisation lithium start-up period of 6 months, continued lithium monotherapy without being admitted to hospital. Early v. late intervention was defined in two ways: (a) start of lithium following first contact; and (b) start of lithium following a diagnosis of a single manic/mixed episode., Results: Regardless of the definition used, patients who started lithium early had significantly decreased rates of non-response to lithium compared with the rate for patients starting lithium later (adjusted analyses: first v. later contact: P<0.0001; hazard ratio (HR) = 0.87, 95% CI 0.76-0.91; single manic/mixed episode v. bipolar disorder: P<0.0001; HR = 0.75, 95% CI 0.67-0.84)., Conclusions: Starting lithium treatment early following first psychiatric contact or a single manic/mixed episode is associated with increased probability of lithium response., (Royal College of Psychiatrists.)

The prevalence of depression is not clearly established, but estimated to 3-4% in a Danish questionnaire study. Lifetime's prevalences of 12-17% are reported in other community samples. In the current diagnostic system depression is defined categorically and operationally. It has been argued, that these diagnostic criteria represent an oversimplification, which has blurred the concept of depression. We suggest a greater emphasis on the depressed mood as the core symptom of depression, which may increase the specificity of the diagnosis. Furthermore, basic principles for the treatment of depression are presented.

Purpose: Previous studies suggest that religious practice can have a positive effect on mental health, but may also have potential for harm. In Denmark, unique possibilities are available for studying the influence of religious practice on mental health: Denmark is characterized as a secular society and it is possible to follow members of religious societies in nationwide registers. In this study, we follow a cohort of Danish Seventh-day Adventists (SDA) and Baptists in a nationwide psychiatry register and compare the incidence in this cohort with the general population., Methods: We followed a cohort of 5,614 SDA and 3,663 Baptists in the Danish Psychiatric Central Register, which contained information on psychiatric hospitalizations from 1970 to 2009. Psychiatric disease incidence in the cohort was compared with that in the general Danish population as standardized incidence ratios and within-cohort comparisons were made with a Cox model., Results: The cohort had decreased incidence of abuse disorders compared to the general population. Furthermore, among Baptists, decreased incidence of unipolar disorders among men and decreased incidence of schizophrenia among women were observed. Surprisingly, we observed an increased incidence rate of unipolar disorder among women., Conclusions: In this nationwide cohort study with 40 years of follow-up, we observed increased incidence rates of unipolar disorders among women and decreased rates of alcohol- and drug-related psychiatric disorders compared to the general Danish population. We have no mechanistic explanation for the increased incidence of unipolar disorders among women, but discuss several hypotheses that could explain this observation.

Objective: To investigate whether measures of cognitive function can predict onset of affective disorder in individuals at heritable risk., Method: In a high-risk study, 234 healthy monozygotic and dizygotic twins with and without a co-twin history of affective disorder (high- and low-risk twins, respectively) were identified through nationwide registers and assessed at baseline using the Schedules for Clinical Assessment in Neuropsychiatry, the 17-item Hamilton Depression Rating Scale (HDRS), and the cognitive tests Trail Making Test Parts A and B, the Stroop test, and the Cambridge Cognitive Examination-Revised (CAMCOR). Participants were followed longitudinally at 6-month intervals for up to 9 years and finally reassessed with a personal interview to obtain information on whether they had developed psychiatric illness. The study was conducted between 2003 and 2012., Results: 36 participants (15.4%) developed psychiatric disorder, mainly affective and anxiety disorders (31 diagnoses) (ICD-10). Onset was predicted by decreased executive function as reflected by performance on the Trail Making Test A - B (hazard ratio [HR] = 1.02; 95% CI, 1.00-1.03) when adjusted for sex, age, years of education and HDRS score at baseline. Reduced global cognitive function as indicated by a lower CAMCOR score at baseline showed a trend toward an association with subsequent illness onset (P = .08). With regard to the 5 CAMCOR subscales, lower scores on attention (HR = 0.71; 95%, CI, 0.54-0.94) and language (HR = 0.76; 95% CI, 0.58-0.99) were significantly associated with subsequent illness onset., Conclusions: Among healthy individuals at heritable risk for affective disorder, discrete cognitive deficits, especially within executive function and attention, seem to predict subsequent onset of affective illness., (© Copyright 2013 Physicians Postgraduate Press, Inc.)

Rationale: Use of antidepressants during pregnancy has been associated with an increased rate of children small for gestational age (SGA), but it is unclear whether this is due to an effect of the underlying depressive disorder., Objectives: This study aimed to investigate the effect of antidepressants on SGA in a nationwide sample and to separate the effect of exposure to antidepressants in utero from the effect of maternal depression., Methods: A register study was conducted on all pregnant women in Denmark from 1996 to 2006 linking nationwide individualized data from the Medical Birth Register, the Psychiatric Central Register, and a prescription database. The rate of SGA (birth weight below the 10 percentile at given gestational week) was investigated for children exposed in utero to antidepressants or to a maternal psychiatric diagnosis of depression compared to children not prenatally exposed to antidepressants or maternal diagnosis., Results: A total of 673,853 pregnancies were included in the study of which 35.737 women had a diagnosis of depression and/or used antidepressants before end of pregnancy. Antidepressant use during pregnancy was weakly associated with SGA (hazard ratios (HR) = 1.19; 95 % confidence interval (CI), 1.11-1.28), whereas a psychiatric diagnosis before or during pregnancy was not (HR = 1.02; 95 % CI, 0.92-1.13). The association for use during pregnancy was found for selective serotonin reuptake inhibitors and newer antidepressants, but not for older antidepressants., Conclusions: The use of antidepressants during pregnancy slightly increases the rate of SGA. The association seems unrelated to the underlying maternal depressive disorder.

Background: Postoperative cognitive dysfunction (POCD) is a common complication in elderly patients after major surgery. An association between POCD and the development of dementia has been suspected. In this study, we assessed if POCD was a risk factor for the occurrence of dementia., Methods: Danish patients enrolled between November 1994 and October 2000 in the two International Studies of Postoperative Cognitive Dysfunction (ISPOCD 1 and 2) were followed until July 1, 2011. Cognitive performance was assessed at three time points: before operation, at 1 week, and 3 months after surgery, using a neuropsychological test battery. The time of (first) occurrence of dementia after surgery was assessed using the National Patient Register and the Psychiatric Central Research Register. Recorded dementia diagnoses (ICD-8 and ICD-10) were: Alzheimer's disease, vascular dementia, frontotemporal dementia, or dementia without specification. The risk of dementia according to POCD was assessed in the Cox regression models., Results: A total of 686 patients with a median age of 67 [inter-quartile range (IQR) 61-74] yr were followed for a median of 11.1 (IQR 5.2-12.6) yr. Only 32 patients developed dementia during follow-up. The hazard ratio (95% CI) for any dementia diagnoses in patients with POCD at 1 week (n=118) and POCD at 3 months (n=57) after surgery compared with those without POCD was 1.16 (0.48-2.78), P=0.74, and 1.50 (0.51-4.44); P=0.47, respectively., Conclusions: POCD was not significantly associated with registered dementia over a median follow-up of 11 yr.

Background: Assortative mating has been demonstrated in mental disorders but the extent of cohabitation between patients with clinically diagnosed psychiatric disease has been poorly explored. Method We conducted a register-based study of all Danes between 18 and 70 years of age in a 13-year observational period, linking data on individuals' contacts with psychiatric services with data on individuals' cohabitation status. Two different Poisson regression analyses were performed: the first comparing the rates of commencing cohabitation with a psychiatric patient between individuals, depending on whether the individuals themselves had, or did not have, a psychiatric diagnosis; the second comparing the incidence rates of psychiatric diagnoses for individuals cohabitating with psychiatric patients with the similar rates for individuals living with unaffected cohabitants., Results: In total, 159 929 (5.0%) out of 3 204 633 individuals were given a psychiatric diagnosis during the study period. Diagnosed individuals had an overall rate ratio (RR) of commencing cohabitation with a psychiatric patient of 1.95 [95% confidence interval (CI) 1.90-2.00] for women and 1.65 (95% CI 1.61-1.69) for men, when compared with unaffected individuals. The overall RR of receiving a psychiatric diagnosis while cohabitating with a psychiatric patient was 2.40 (95% CI 2.31-2.49) for women and 2.91 (95% CI 2.81-3.01) for men, when compared with those cohabitating with unaffected individuals. Individuals with schizophrenia and men with bipolar disorder had the highest RR of commencing cohabitation with a cohabitant with a similar diagnosis., Conclusions: Cohabitation among individuals with severe psychiatric disorders is increased. This has implications for research and for the clinical management of patients.

Background: Little is known about whether treatment in a specialised out-patient mood disorder clinic improves long-term prognosis for patients discharged from initial psychiatric hospital admissions for bipolar disorder., Aims: To assess the effect of treatment in a specialised out-patient mood disorder clinic v. standard decentralised psychiatric treatment among patients discharged from one of their first three psychiatric hospital admissions for bipolar disorder., Method: Patients discharged from their first, second or third hospital admission with a single manic episode or bipolar disorder were randomised to treatment in a specialised out-patient mood disorder clinic or standard care (ClinicalTrials.gov: NCT00253071). The primary outcome measure was readmission to hospital, which was obtained from the Danish Psychiatric Central Register., Results: A total of 158 patients with mania/bipolar disorder were included. The rate of readmission to hospital was significantly decreased for patients treated in the mood disorder clinic compared with standard treatment (unadjusted hazard ratio 0.60, 95% CI 0.37-0.97, P = 0.034). Patients treated in the mood disorder clinic more often used a mood stabiliser or an antipsychotic and satisfaction with treatment was more prevalent than among patients who received standard care., Conclusions: Treatment in a specialised mood disorder clinic early in the course of bipolar disorder substantially reduces readmission to a psychiatric hospital and increases satisfaction with care.

Purpose: To investigate whether normal tension glaucoma (NTG) is associated with increased risk of developing dementia/Alzheimer disease (AD)., Methods: A total of 69 patients with NTG were identified in the case note files in the Glaucoma Clinic, University Hospital of Copenhagen (Rigshospitalet), Denmark from 1980 to 2001. The rate of a subsequent diagnosis of dementia as recorded in nationwide health care registers from 1980 to 2005 was estimated and compared with the rate for the general population [standard mortality rate (SMR) = observed number of cases of dementia/expected number of cases of dementia]., Results: The 69 patients had a median age of 64 years (quartiles 57 and 73) at the time of the diagnosis, and the average follow-up period was 12.7 years. The SMR(dementia) was 0.20 (95% CI 0.01-1.11). No patient developed AD., Conclusion: Normal tension glaucoma was not associated with an increased risk of developing dementia/AD., (© 2011 The Authors. Acta Ophthalmologica © 2011 Acta Ophthalmologica Scandinavica Foundation.)

Background: Patients with unipolar depressive disorder may present with cognitive deficits in the remitted state, and the aim of the present study was to investigate whether cognitive deficits within specific cognitive domains are present., Method: Via the Danish registers (Civil Person Register, Danish Psychiatric Register) we identified individuals between 40 and 80 years of age with a diagnosis of unipolar disorder at their first discharge from a psychiatric hospital, and a gender- and age-matched control group. Particular emphasis was placed on assuring that patients were in a remitted state. Cognitive function was assessed with a broad range of neuropsychological tests., Results: A total of 88 patients and 50 controls were included in the study. In multiple linear regression analyses with simultaneous adjustment for age, gender, education level, premorbid IQ, and residual depressive symptoms, a diagnosis of unipolar disorder predicted lower performance on the Trail Making Test, the Symbol Digit Modalities Test, and on the Stroop test., Conclusion: Cognitive deficits are present in patients with unipolar disorder in the remitted state. The deficits seem to reside more within the cognitive domain of attention than within other domains, and may be characterized by impairment of processing speed and cognitive flexibility.