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Objective: There is an accumulation of stressful life events prior to the first mood episode, but the impact of previous severe life events on psychopathology in patients with bipolar disorder (BD) is not well studied. We aimed to examine the number of recent and lifetime life events in patients with newly diagnosed BD, their unaffected relatives (UR), and healthy controls (HC) as well as the impact of severe lifetime life events on the early course of BD. Methods: We compared the number of recent and lifetime life events in 398 patients with newly diagnosed BD, 109 UR, and 214 HC. We subsequently dichotomized the patients with BD by >2 lifetime life events to investigate the associations of severe lifetime life events with clinical characteristics and affective symptoms. Results: Patients with newly diagnosed BD reported significantly more life events in the last 12 months and lifetime before compared with UR and HC. Patients who reported >2 lifetime life events (n = 160) compared with patients with 0–2 life events (n = 238) had a significantly longer diagnostic delay (9.5 years ± 8.2 vs. 6.2 years ± 6.9), presented with more anxiety and depressive symptoms and had at least one previous suicide attempt (30.6% vs. 15.6%) and one previous admission (51.3% vs. 36.6%). Conclusion: The experience of severe lifetime life events seems to impact the early course in BD in terms of longer diagnostic delay, more severe psychopathology including more admissions and a more than doubled risk for previous suicide attempts. [ABSTRACT FROM AUTHOR]

Background. Childhood maltreatment is an established risk factor for incident unipolar disorder and bipolar disorder. It is separately observed that affective disorders (AD) are also associated with higher nucleoside damage by oxidation. Childhood maltreatment may induce higher levels of nucleoside damage by oxidation and thus contribute to the development of AD; however, this relation is only sparsely investigated. Methods. In total, 860 participants (468 patients with AD, 151 unaffected first-degree relatives, and 241 healthy control persons) completed the Childhood Trauma Questionnaire (CTQ). The association between CTQ scores and markers of systemic DNA and RNA damage by oxidation as measured by urinary excretion of 8-oxo-7,8-dihydro-20 -deoxyguanosine (8-oxodG) and 8- oxo-7,8-dihydroguanosine (8-oxoGuo) levels, respectively, was investigated. Results. In multiple regression models adjusted for sex- and age, 8-oxodG and 8-oxoGuo levels were found to be higher in individuals who had experienced more childhood maltreatment. These associations persisted in models additionally adjusted for body mass index, alcohol, and current smoking status. Emotional abuse, sexual abuse, and emotional neglect were principally responsible for the foregoing associations. Conclusions. Our findings of an association between childhood maltreatment and oxidative stress markers suggest that childhood maltreatment overall, notably emotional abuse and emotional neglect, is associated with enhanced systemic damage to DNA and RNA in adulthood. Further, individuals with AD reported a higher prevalence of childhood maltreatment, which may induce higher levels of nucleoside damage by oxidation in adulthood, possibly leading to increased risk of developing AD. Longitudinal studies are needed to clarify this relationship further. [ABSTRACT FROM AUTHOR]

Background: Patients with bipolar disorder (BD) experience persistent impairments in both affective and non-affective cognitive function, which is associated with a worse course of illness and poor functional outcomes. Nevertheless, the temporal progression of cognitive dysfunction in BD remains unclear and the identification of objective endophenotypes can inform the aetiology of BD. Methods: The present study is a cross-sectional investigation of cognitive baseline data from the longitudinal Bipolar Illness Onset-study. One hundred seventy-two remitted patients newly diagnosed with BD, 52 of their unaffected relatives (UR), and 110 healthy controls (HC) were compared on a large battery of behavioural cognitive tasks tapping into non-affective (i.e. neurocognitive) and affective (i.e. emotion processing and regulation) cognition. Results: Relative to HCs, patients with BD exhibited global neurocognitive deficits (ps < 0.001), as well as aberrant emotion processing and regulation (ps ⩽ 0.011); including decreased emotional reactivity to positive social scenarios, impaired ability to down-regulate positive emotion, as well as a specific deficit in the ability to recognise surprised facial expressions. Their URs also showed a trend towards difficulties identifying surprised faces (p = 0.075). No other differences in cognitive function were found for URs compared to HCs. Conclusions: Neurocognitive deficits and impairments within emotion processing and regulation may be illness-related deficits of BD that present after illness-onset, whereas processing of emotional faces may represent an early risk marker of BD. However, longitudinal studies are needed to examine the association between cognitive impairments and illness progression in BD. [ABSTRACT FROM AUTHOR]

Objectives: Bipolar disorder is associated with a decreased life expectancy of 8–12 years. Cardiovascular disease is the leading cause of excess mortality. For the first time, we investigated the Framingham 30-year risk score of cardiovascular disease in patients with newly diagnosed/first-episode bipolar disorder, their unaffected first-degree relatives and healthy individuals. Methods: In a cross-sectional study, we compared the Framingham 30-year risk score of cardiovascular disease in 221 patients with newly diagnosed/first-episode bipolar disorder, 50 of their unaffected first-degree relatives and 119 healthy age- and sex-matched individuals with no personal or first-degree family history of affective disorder. Among patients with bipolar disorder, we further investigated medication- and illness-related variables associated with cardiovascular risk. Results: The 30-year risk of cardiovascular disease was 98.5% higher in patients with bipolar disorder (p = 0.017) and 85.4% higher in unaffected first-degree relatives (p = 0.042) compared with healthy individuals in models adjusted for age and sex. When categorizing participants in low cardiovascular risk without considering age and sex distribution among participants, 81% of patients were at low risk, versus 92% of unaffected relatives and 89% of healthy individuals. Of the patients 209 (94.6%) were diagnosed within the preceding 2 years. Smoking was more prevalent among patients with bipolar disorder (45.2%) and their unaffected first-degree relatives (20.4%) compared with healthy individuals (12.8%). Similarly, dyslipidemia was more common among patients with bipolar disorder compared with healthy individuals. Treatment with psychotropic medication with metabolic adverse effects was associated with higher 30-year cardiovascular disease risk score, whereas we did not find illness-related variables associated with cardiovascular risk among patients with bipolar disorder. Conclusion: We found an enhanced cardiovascular disease risk score in patients with newly diagnosed bipolar disorder and their unaffected first-degree relatives, which points to a need for specific primary preventive interventions against smoking and dyslipidemia in these populations. [ABSTRACT FROM AUTHOR]

Background: Around 40% of patients with bipolar disorder (BD) additionally have anxiety disorder. The prevalence of anxiety in patients with newly diagnosed BD and their first-degree relatives (UR) has not been investigated.ObjectiveTo investigate (1) the prevalence of a comorbid anxiety diagnosis in patients with newly diagnosed BD and their UR, (2) sociodemographic and clinical differences between patients with and without a comorbid anxiety diagnosis and (3) the association between smartphone-based patient-reported anxiety and observer-based ratings of anxiety and functioning, respectively., Methods: We recruited 372 patients with BD and 116 of their UR. Daily smartphone-based data were provided from 125 patients. SCAN was used to assess comorbid anxiety diagnoses., Findings: In patients with BD, the prevalence of a comorbid anxiety disorder was 11.3% (N=42) and 10.3% and 5.9% in partial and full remission, respectively. In UR, the prevalence was 6.9%. Patients with a comorbid anxiety disorder had longer illness duration (p=0.016) and higher number of affective episodes (p=0.011). Smartphone-based patient-reported anxiety symptoms were associated with ratings of anxiety and impaired functioning (p<0.001)., Limitations: The SCAN interviews to diagnose comorbid anxiety disorder were carried out regardless of the participants' mood state.Clinical implicationsThe lower prevalence of anxiety in newly diagnosed BD than in later stages of BD indicates that anxiety increases with progression of BD. Comorbid anxiety seems associated with poorer clinical outcomes and functioning and smartphones are clinically useful for monitoring anxiety symptoms., Trial Registration Number: ClinicalTrials.gov Registry (NCT02888262)., Competing Interests: Competing interests: HLK, KSOS, IS, RNJ and MF-J declare no competing interests. LVK, SS and KC have within recent 3 years been a consultant for Lundbeck. MV has within the last 3 years been a consultant for Lundbeck, Sunovion and Janssen. JEB and MF are cofounders and shareholders of Monsenso A/S., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

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.)

Introduction: Women often develop malignant mesothelioma (MM) without occupational asbestos exposure. Northern Jutland has a high prevalence of MM due to previously high occupational exposures to asbestos. The aim of this study was to elucidate a possible domestic exposure to asbestos through first-degree relatives in women who develop MM., Material and Methods: This was a retrospective study in women with MM of the pleura. A total of 30 women were diagnosed with and treated for MM in Northern Jutland from 1996 to 2012. In all, 24 women were included. Demographic data, subtype of MM, time from first hospital contact to diagnosis, survival and information on occupational and domestic exposure to asbestos were obtained from hospital records., Results: A total of 12.5% of the study population were primarily exposed to asbestos. 46% had domestic exposure to asbestos through their husbands or sons. The median age of the study population was 66.5 years. In all, 75% suffered from the epitheloid subtype, 12.5% from the biphasic and 8.4% from the sarcomatoid subtype. Time from first hospital contact to diagnosis was one month and the median survival time was 12 months. The 1- and 5- year-survival were 58% and 0%, respectively., Conclusion: Nearly 50% of the women affected by MM have been domestically exposed to asbestos through first-degree relatives., Funding: not relevant., Trial Registration: not relevant.