Background
In DSM-5 activity is a core criterion for diagnosing hypomania and mania. However, there are no guidelines for quantifying changes in activity. The objectives of the study were (1) to ...investigate daily smartphone-based self-reported and automatically-generated activity, respectively, against validated measurements of activity; (2) to validate daily smartphone-based self-reported activity and automatically-generated activity against each other; (3) to investigate differences in daily self-reported and automatically-generated smartphone-based activity between patients with bipolar disorder (BD), unaffected relatives (UR) and healthy control individuals (HC).
Methods
A total of 203 patients with BD, 54 UR, and 109 HC were included. On a smartphone-based app, the participants daily reported their activity level on a scale from −3 to + 3. Additionally, participants owning an android smartphone provided automatically-generated data, including step counts, screen on/off logs, and call- and text-logs. Smartphone-based activity was validated against an activity questionnaire the International Physical Activity Questionnaire (IPAQ) and activity items on observer-based rating scales of depression using the Hamilton Depression Rating scale (HAMD), mania using Young Mania Rating scale (YMRS) and functioning using the Functional Assessment Short Test (FAST). In these analyses, we calculated averages of smartphone-based activity measurements reported in the period corresponding to the days assessed by the questionnaires and rating scales.
Results
(1) Smartphone-based self-reported activity was a valid measure according to scores on the IPAQ and activity items on the HAMD and YMRS, and was associated with FAST scores, whereas the majority of automatically-generated smartphone-based activity measurements were not. (2) Daily smartphone-based self-reported and automatically-generated activity correlated with each other with nearly all measurements. (3) Patients with BD had decreased daily self-reported activity compared with HC. Patients with BD had decreased physical (number of steps) and social activity (more missed calls) but a longer call duration compared with HC. UR also had decreased physical activity compared with HC but did not differ on daily self-reported activity or social activity.
Conclusion
Daily self-reported activity measured via smartphone represents overall activity and correlates with measurements of automatically generated smartphone-based activity. Detecting activity levels using smartphones may be clinically helpful in diagnosis and illness monitoring in patients with bipolar disorder.
Trial registration
clinicaltrials.gov NCT02888262
Background
Voice features have been suggested as objective markers of bipolar disorder (BD).
Aims
To investigate whether voice features from naturalistic phone calls could discriminate between (1) ...BD, unaffected first-degree relatives (UR) and healthy control individuals (HC); (2) affective states within BD.
Methods
Voice features were collected daily during naturalistic phone calls for up to 972 days. A total of 121 patients with BD, 21 UR and 38 HC were included. A total of 107.033 voice data entries were collected BD (n = 78.733), UR (n = 8004), and HC (n = 20.296). Daily, patients evaluated symptoms using a smartphone-based system. Affective states were defined according to these evaluations. Data were analyzed using random forest machine learning algorithms.
Results
Compared to HC, BD was classified with a sensitivity of 0.79 (SD 0.11)/AUC = 0.76 (SD 0.11) and UR with a sensitivity of 0.53 (SD 0.21)/AUC of 0.72 (SD 0.12). Within BD, compared to euthymia, mania was classified with a specificity of 0.75 (SD 0.16)/AUC = 0.66 (SD 0.11). Compared to euthymia, depression was classified with a specificity of 0.70 (SD 0.16)/AUC = 0.66 (SD 0.12). In all models the user dependent models outperformed the user independent models. Models combining increased mood, increased activity and insomnia compared to periods without performed best with a specificity of 0.78 (SD 0.16)/AUC = 0.67 (SD 0.11).
Conclusions
Voice features from naturalistic phone calls may represent a supplementary objective marker discriminating BD from HC and a state marker within BD.
Abstract
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-2′-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 Although numerous studies have dealt with changes in blood brain-derived neurotrophic factor (BDNF), methodological issues about BDNF measurements have only been incompletely resolved. We ...validated BDNF ELISA with respect to accuracy, reproducibility and the effect of storage and repeated freezing cycles on BDNF concentrations. Additionally, the effect of demographic characteristics in healthy subjects on BDNF was verified. Whole blood and serum was collected from 206 healthy subjects and a subgroup was genotyped for BDNF Val66Met polymorphism. The effect of age, gender, BDNF genotype and thrombocyte count on whole blood BDNF was assessed. The BDNF ELISA measurement was accurate, 91.6 ± 3.0%, and showed high reproducibility, whereas inter-assay and intra-subject variations were modest, 8.4 ± 5.2% and 17.5 ± 14.1%, respectively. Storage of whole blood samples at 4 °C significantly decreased BDNF concentration, while repeated freezing cycles and storage at −20 °C was without any effect. Storage at −20 °C of serum, but not whole blood, was associated with a significant decrease in BDNF concentration. Women had significantly higher whole blood BDNF concentrations than men (18.6 ± 1.3 ng/ml versus 16.5 ± 1.4 ng/ml), and showed a right-skewed BDNF concentration distribution. No association between whole blood BDNF concentrations and thrombocyte count, age, or BDNF genotype was found. In conclusion, the BDNF ELISA assay determines whole blood BDNF accurately and with high reproducibility. Female gender is associated with higher whole blood BDNF concentrations whereas age, thrombocyte count and BDNF Val66Met polymorphism were un-associated.
Abstract
Enhanced oxidative stress-generated nucleoside damage may contribute to the increased cardiovascular disease mortality in patients with bipolar disorder (BD) but the association has never ...been investigated. We investigated the associations between oxidative stress-generated damage to DNA (8-oxodG) and RNA (8-oxoGuo), respectively, and three measures reflecting cardiovascular risk; namely, the Framingham 30-year risk score of cardiovascular diseases, the metabolic syndrome, and the insulin resistance index in 360 patients newly diagnosed with BD, 102 of their unaffected relatives (UR) and 197 healthy control individuals (HC). In sex- and age-adjusted models, the 30-year cardiovascular risk score increased by 20.8% (CI = 7.4–35.9%,
p
= 0.002) for every one nM/mM creatinine increase in 8-oxoGuo and by 15.6% (95% CI = 5.8–26.4%,
p
= 0.001) for every one nM/mM creatinine increase in 8-oxodG, respectively. Further, insulin resistance index increased by 24.1% (95% CI = 6.7–43%,
p
= 0.005) when 8-oxoGuo increased one nM/mM creatinine. The associations between cardiovascular measures and oxidative nucleoside damage were more pronounced in patients with BD compared with UR, and HC. Metabolic syndrome was not associated with nucleoside damage. Overall, higher oxidative stress-generated nucleoside damage was associated with a higher cardiovascular risk score and a higher degree of insulin resistance index, and having BD impacted the associations. Further, within patients, treatment with psychotropics seemed to enhance the associations between 30-year CVD risk score and insulin resistance index, respectively, and oxidatively stress-generated nucleoside damage. Our findings support enhanced oxidative stress-generated nucleoside damage as a putative pathophysiological mechanism that may mediate the higher cardiovascular risk observed in patients with BD already at the time of diagnosis.
To validate the ICD-10 diagnosis of a single depressive episode as used in daily clinical psychiatric practice and as recorded in the Danish Psychiatric Central Research Register.
Patients discharged ...with a diagnosis of a single depressive episode were consecutively sampled from the register and diagnosed according to an interview using the Schedules for Clinical Assessment in Neuropsychiatry (SCAN).
A total of 75.4% of 399 patients with a register diagnosis of a single depressive episode also got this diagnosis according to the SCAN interview (82.8% for severe type of a single depression, 76.0% for moderate type of a single depression and 65.2% for mild type of a single depression).
The ICD-10 diagnosis of a single depressive episode can be used in daily clinical practice with sufficient precision. The validity of the diagnosis is highest for severe and moderate type of depression and decreases for mild depression.
Abstract Background Abnormalities in psychomotor activity are a central and essential feature of affective disorder. Studies measuring differences in psychomotor activity between unipolar and bipolar ...disorder show divergent results and none have used a combined heart rate and movement monitor for measuring activity during free-living conditions. Objective To compare objectively measured psychomotor activity in patients with unipolar and bipolar disorder in a remitted or mild/moderate depressive state. Further, both groups were compared to a healthy control group. Methods A cross-sectional study of outpatients suffering from unipolar (n = 20) and bipolar (n = 18) disorder and healthy controls (n = 31), aged 18–60 years. For three consecutive days a combined acceleration (m/s2 ) and heart rate (beats per minute) monitoring was used in conjunction with a step test to estimate activity energy expenditure (J/min/kg) as measures of psychomotor activity and physical fitness. Results Overall score on Hamilton-17 items ranged between 0 and 22. Patients had higher sleeping heart rate (p < 0.001), lower fitness (p = 0.02), lower acceleration (p = 0.004), and lower activity energy expenditure (p = 0.004) compared to controls. Comparing unipolar and bipolar patients and adjusting for differences in Hamilton-17 revealed lower acceleration (p = 0.01) and activity energy expenditure in bipolar patients (p = 0.02); the difference was most prominent in the morning. Conclusions Electronic monitoring of psychomotor activity may be a promising additional tool in the distinction between unipolar and bipolar affective disorder when patients present in a remitted or depressive state.
IntroductionClozapine and olanzapine are some of the most effective antipsychotics, but both are associated with weight gain and relevant metabolic disturbances, including pre-diabetes and diabetes. ...Non-pharmacological/behavioural interventions have had limited effects counteracting these adverse effects. Semaglutide, a glucagon-like peptide 1 receptor agonist, is approved for the treatment of type 2 diabetes and obesity. We will investigate the long-term effects of add-on treatment with semaglutide once a week versus placebo once a week on the metabolic status in pre-diabetic (glycated haemoglobin A1c (HbA1c) 35–47 mmol/mol (5.4%–6.4%) and diabetic (HbA1c 48–57 mmol/mol (6.5%–7.4%)) patients diagnosed with a schizophrenia spectrum disorder who initiated clozapine or olanzapine treatment within the last 60 months.Methods and analysisThis is a 26-week, double-blinded, randomised, placebo-controlled trial. Altogether, 104 patients diagnosed with a schizophrenia spectrum disorder, aged 18–65 years, with pre-diabetes or diabetes will be randomised to injections of 1.0 mg semaglutide once a week or placebo for 26 weeks. The primary endpoint is change from baseline in HbA1c. Secondary endpoints include changes in body weight, hip and waist circumference and plasma levels of insulin, glucagon, glucose, and C-peptide, insulin sensitivity, beta cell function, hepatic function, fibrosis-4 score, lipid profile, incretin hormones, bone markers, body composition, bone density, proteomic analyses and oxidative stress markers. Together with alcohol, tobacco and drug use, potential effects on the reward value of a sweet–fat stimulus, psychopathology, level of activity and quality of life will also be assessed.Ethics and disseminationThis study is approved by the Danish Medicines Agency and the regional scientific ethics committee of the Capital Region of Denmark (committee C, #H-20019008) and will be carried out in accordance with International Council for Harmonisation Good Clinical Practice guidelines and the Helsinki Declaration. The results will be disseminated through peer-review publications and conference presentations.Trial registration numberNCT04892199.
: Lipids influence brain function and mental health. Understanding the role of apolipoproteins in affective disorders could provide valuable insights and potentially pave the way for novel ...therapeutic approaches.
We examined the apolipoprotein E genotype and ApoE-levels, lipid profiles, and the correlation with cognition in 204 monozygotic (MZ) twins with unipolar or bipolar disorder in remission or partial remission (affected, AT), their unaffected co-twins (high-risk, HR), and twins with no personal or family history of affective disorder (low-risk, LR).
The APOE genotype was not associated with affective disorders. No significant group differences in ApoE levels were found between the three risk groups. Post hoc analysis group-wise comparisons showed higher ApoE levels in the AT than HR twins and in the concordant AT twin pairs relative to the discordant twin pairs. Within the discordant twin pairs, higher ApoE levels were observed in the affected twins (AT = 39.4 mg/L vs. HR = 36.8 mg/L,
= 0.037).
The present study could benefit from a larger sample size. We did not assess dietary habits.
The results did not support our main hypothesis. However, exploratory post hoc analysis suggests a role for plasma ApoE and triglycerides in affective disorders. Future research is needed.
Objective
The Cortisol Awakening Response (CAR) measured as the transient increase in cortisol levels following morning awakening appears to be a distinct feature of the HPA axis. Patients with ...bipolar disorder (BD) experience daily stress, mood instability (MI) and studies have shown disrupted HPA-axis dynamics. Aims: to evaluate (1) patient-evaluated stress against the CAR, (2) associations between the CAR and mood symptoms, and (3) the effect of smartphone-based treatment on the CAR.
Methods
Patients with BD (n = 67) were randomized to the use of daily smartphone-based monitoring (the intervention group) or to the control group for six months. Clinically rated symptoms according to the Hamilton Depression Rating Scale 17-items (HDRS), the Young Mania Rating Scale (YMRS), patient-evaluated perceived stress using Cohen’s Perceived Stress Scale (PSS) and salivary awakening cortisol samples used for measuring the CAR were collected at baseline, after three and six months. In the intervention group, smartphone-based data on stress and MI were rated daily during the entire study period.
Results
Smartphone-based patient-evaluated stress (
B: 134.14, 95% CI: 1.35; 266.92, p
=
0.048
) and MI (
B: 430.23, 95% CI: 52.41; 808.04, p
=
0.026
) mapped onto increased CAR. No statistically significant associations between the CAR and patient-evaluated PSS or the HDRS and the YMRS, respectively were found. There was no statistically significant effect of smartphone-based treatment on the CAR.
Conclusion
Our data, of preliminary character, found smartphone-based patient-evaluations of stress and mood instability as read outs that reflect CAR dynamics. Smartphone-supported clinical care did not in itself appear to disturb CAR dynamics.
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