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.
Bipolar disorder (BD) and unipolar disorder (UD) are associated with cognitive deficits and abnormal neural activity in a "cognitive control network." There is an increased prevalence of cognitive ...dysfunction in psychiatric patients' first-degree relatives, which constitutes a risk factor for psychiatric illness onset. However, there is no treatment with enduring pro-cognitive efficacy. We found preliminary evidence for beneficial effects of eight weekly doses of recombinant human erythropoietin (EPO) on cognition in BD in a recent randomized controlled trial (RCT). The present RCT consists of two sub-studies that extend our previous work by investigating important novel aspects: (1) the effects of 12 weekly doses of EPO on cognition in first-degree relatives of patients with BD, UD, or schizophrenia; and (2) the effects of extending the treatment schedule from 8 to 12 weeks in remitted patients with BD or UD; and (3) assessment of early treatment-associated neural activity changes that may predict cognitive improvement.
The trial comprises two parallel sub-studies with randomized, controlled, double-blinded, parallel group designs. First-degree relatives (sub-study 1; n = 52) and partially or fully remitted patients with BD or UD (sub-study 2; n = 52) with objectively verified cognitive dysfunction are randomized to receive weekly high-dose EPO (40,000 IU/mL) or placebo (saline) infusions for 12 weeks. Assessments of cognition and mood are conducted at baseline, after two weeks of treatment, after treatment completion, and at six-month follow-up. Functional magnetic resonance imaging (fMRI) is conducted at baseline and after two weeks of treatment. Psychosocial function is assessed at baseline, after treatment completion and six-month follow-up. The primary outcome is change in a cognitive composite score of attention, verbal memory, and executive functions. Statistical power of ≥ 80% is reached to detect a clinically relevant between-group difference by including 52 first-degree relatives and 52 patients with BD or UD, respectively. Behavioral data are analyzed with an intention-to-treat approach using mixed models. fMRI data are analyzed with the FMRIB Software Library.
If this trial reveals pro-cognitive effects of EPO, this may influence future treatment of mood disorders and/or preventive strategies in at-risk populations. The fMRI analyses may unravel key neurobiological targets for pro-cognitive treatment.
ClinicalTrials.gov , NCT03315897. Registered on 20 October 2017.
The COVID-19 pandemic has led to an increased psychological strain on public mental health and may impact behavioral, mental, and physical health, presumably with effects on patients with severe ...mental disorders. This study examines pandemic-related physical and mental health and (compensatory) behavioral changes, in patients with BD as compared to healthy control individuals.
Physical and mental health and self-reported changes in daily structure and behavior due to the pandemic were assessed using a self-constructed questionnaire and the brief symptom inventory (BSI) in Germany, Austria, and Denmark in individuals with BD and a healthy control group.
The present study included 118 individuals with BD and 215 healthy controls. Individuals with BD reported statistically significant higher physical risk burden, increased weight gain, more physical comorbidities, and a decrease in physical activity and they further reported higher rates of COVID-19 testing, had more worries concerning health, and experienced more anxiety but less social distancing.
The COVID-19 pandemic seems to have a greater impact on physical health in individuals with BD than in healthy controls. Individuals with BD appear to be having more difficulties compensating their behavior due to the pandemic which could amplify the effect of risk factors associated with poorer physical health. This highlights the necessity for optimizing and targeting the overall treatment of both mental and physical health in patients with BD during periods with far-reaching changes such as the COVID-19 pandemic.
Sampling issues and self-report forms, selectivity (missing elderly, and those lacking access or knowledge of technology).
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.
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.
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.
Clinicaltrials.gov , NCT03295305 . Registered on 26 September 2017.
The efficacy of antidepressant treatment is fair, but the efficacy is considerably lower in patients failing two or more trials underscoring the need for new treatment options. Our study evaluated ...the augmenting antidepressant effect of 8-weeks transcranial pulsed electromagnetic field (T-PEMF) therapy in patients with treatment-resistant depression.
A multicenter 8-week single-arm cohort study conducted by the Danish University Antidepressant Group.
In total, 58 participants (20 men and 38 women) with a moderate to severe depression as part of a depressive disorder according to ICD-10 who fulfilled criteria for treatment resistance were included, with 19 participants being nonresponders to electroconvulsive therapy during the current depressive episode. Fifty-two participants completed the study period. Scores on the Hamilton Depression Scale 17-items version (HAM-D17) decreased significantly from baseline (mean = 20.6, SD 4.0) to endpoint (mean = 12.6, SD 7.1; N = 58). At endpoint, utilizing a Last Observation Carried Forward analysis, 49 and 28% of those participants with, respectively, a nonchronic current episode (≤2 years; N = 33) and a chronic current episode (>2 years; N = 25) were responders, that is, achieved a reduction of 50% or more on the HAM-D17 scale. At endpoint, respectively, 30 and 16% obtained remission, defined as HAM-D17 ≤ 7. On the Hamilton Scale 6-item version (HAM-D6), respectively, 51 and 16% obtained remission, defined as HAM-D6 ≤ 4.
The findings indicate a potential beneficial role of T-PEMF therapy as an augmentation treatment to ongoing pharmacotherapy in treatment-resistant depression.
Background
Cognitive impairments in patients with bipolar disorder (BD) have been associated with reduced functioning. Aims: To investigate the association between (1) patient-evaluated cognitive ...function measured daily using smartphones and stress, quality of life and functioning, respectively, and (2) patient-evaluated cognitive function and objectively measured cognitive function with neuropsychological tests.
Methods
Data from two randomized controlled trials were combined. Patients with BD (N = 117) and healthy controls (HC) (N = 40) evaluated their cognitive function daily for six to nine months using a smartphone. Patients completed the objective cognition screening tool, the Screen for Cognitive Impairment in Psychiatry and were rated with the Functional Assessment Short Test. Raters were blinded to smartphone data. Participants completed the Perceived Stress Scale and the WHO Quality of Life questionnaires. Data was collected at multiple time points per participant. p-values below 0.0023 were considered statistically significant.
Results
Patient-evaluated cognitive function was statistically significant associated with perceived stress, quality of life and functioning, respectively (all p-values < 0.0001). There was no association between patient-evaluated cognitive function and objectively measured cognitive function (
B:0.0009, 95% CI 0.0017; 0.016, p
=
0.015
). Patients exhibited cognitive impairments in subjectively evaluated cognitive function in comparison with HC despite being in full or partly remission (
B:
−
0.36, 95% CI
−
0.039;
−
0.032, p
<
0.0001
).
Conclusion
The present association between patient-evaluated cognitive function on smartphones and perceived stress, quality of life and functional capacity suggests that smartphones can provide a valid tool to assess disability in remitted BD. Smartphone-based ratings of cognition could not provide insights into objective cognitive function.
Background
Mood instability in bipolar disorder is associated with a risk of relapse. This study investigated differences in mood instability between patients with bipolar disorder type I and type ...II, which previously has been sparingly investigated.
Methods
Patients with bipolar disorder type I (n = 53) and type II (n = 31) used a daily smartphone-based self-monitoring system for 9 months. Data in the present reflect 15.975 observations of daily collected smartphone-based data on patient-evaluated mood.
Results
In models adjusted for age, gender, illness duration and psychopharmacological treatment, patients with bipolar disorder type II experienced more mood instability during depression compared with patients with bipolar disorder type I (
B: 0.27, 95% CI 0.007; 0.53, p
=
0.044
), but lower intensity of manic symptoms. Patients with bipolar disorder type II did not experience lower mean mood or higher intensity of depressive symptoms compared with patients with bipolar disorder type I.
Conclusions
Compared to bipolar disorder type I, patients with bipolar disorder type II had higher mood instability for depression. Clinically it is of importance to identify these inter-episodic symptoms. Future studies investigating the effect of treatment on mood instability measures are warranted.
Trial registration
NCT02221336
Background
Individuals with mental health disorders have a higher risk of sexual problems impacting intimate relations and quality of life. For individuals with bipolar disorder (BD) the mood shifts ...might to a particular degree affect their sexual function with possible hypersexual interest during manic episodes and low sexual interest during depressive episodes. The diagnosis is often given in late adolescence, which may impact sexual identity and development. Only a few studies have looked at BD and sexual life, with no qualitative research on the topic.
We conducted a qualitative pilot study exploring sexuality in connection to mood swings in five participants with BD.
Results
Thematic content analysis revealed five themes: (1) sexual drive and impulses, (2) sexual behavior, (3) thoughts and feelings in relation to sexual issues, (4) intimate relationships, and (5) sexuality and identity. During manic episodes the participants described having a higher sexual drive, leading for some to more sexual interactions. During depressed episodes, the sexual drive in the three female participants was low, however, in the two men, rather than a reduced sexual drive, a more self-destructive way of engaging in sex prevailed. The sexual outgoing behavior during manic phases was described as joyful, with no feelings of shame connected to it. However, the shifts in sexual drive connected to mood shifts affected the participants’ relationships negatively. Further, all the participants described having outgoing sexual behavior in their youth.
Conclusions
Overall, changes in sexual drive may act as a trigger or early warning symptoms of new episodes, pinpointing the clinical relevance of addressing sexuality in individuals with BD. In general, sexual drive followed affective episodes. However, during depressive episodes sex could be, instead of reduced drive, associated with negative feelings.
All participants described having an outgoing sexual behavior in their youth before the onset of BD, which might be essential to consider if there is a clinical suspension of BD in an individual.
Background
Sleep disturbances are a central feature in bipolar disorder (BD) that often persist in remission and seem to be present also in unaffected first-degree relatives (UR) of patients with BD, ...presenting a possible risk factor for later onset of BD. However, it is unknown if these disturbances are associated with unhealthy life-style as reflected in low levels of physical activity. We investigated sleep disturbances and physical activity levels in patients with newly diagnosed BD in full or partial remission, their UR and healthy controls (HC).
Methods
Sleep patterns and physical activity were compared in 227 patients with newly diagnosed BD, 76 UR and 148 HC. The Pittsburgh Sleep Quality Index (PSQI) and the International Physical Activity Questionnaire (IPAQ) were used to assess sleep disturbances and physical activity, respectively.
Results
In sex- and age-adjusted analyses, patients with BD exhibited more sleep disturbances and lower physical activity compared with UR and HC, respectively. Unaffected relatives reported significantly longer sleep latency and a non-significant trend towards more overall sleep disturbances compared with HC.
Conclusions
Sleep disturbances and less physical activity are present in patients with newly diagnosed BD in partial or full remission. Individuals at familiar risk of BD reported longer sleep latency and similar physical activity compared with HC. Further prospective studies are needed to clarify whether these discrete sleep disturbances act as risk factor for later onset of BD and whether increased physical activity in high-risk individuals may act as a protective factor against development of psychiatric illness.
Objective
The prevalence of metabolic syndrome and insulin resistance is twice as high in patients with bipolar disorder compared with the general population, and possibly associated with a disabling ...illness trajectory of bipolar disorder, an increased risk of cardiovascular disease and premature death. Despite these detrimental effects, the prevalence of metabolic syndrome and insulin resistance in patients newly diagnosed with bipolar disorder and their unaffected first-degree relatives is largely unknown.
Methods
In a cross-sectional study of 206 patients with newly diagnosed bipolar disorder, 50 of their unaffected first-degree relatives and 109 healthy age- and sex-matched individuals, we compared the prevalence of metabolic syndrome and insulin resistance (HOMA-IR). In patients with bipolar disorder, we further investigated illness and medication variables associated with the metabolic syndrome and insulin resistance.
Results
Higher rates of metabolic syndrome (odds ratio = 3.529, 95% CI 1.378–9.041,
P
= 0.009) and levels of insulin resistance (B = 1.203, 95% CI 1.059–1.367,
P
= 0.005) were found in patients newly diagnosed with bipolar disorder, but not in their unaffected first-degree relatives compared with matched healthy individuals (data adjusted for sex and age). Most patients with bipolar disorder (94.7%) were diagnosed within the preceding 2 years, and the average illness duration, defined as time from first mood episode, was 10 years.
Conclusion
Our findings of elevated prevalence of metabolic syndrome and insulin resistance in patients with newly diagnosed bipolar disorder highlight the importance of screening for these conditions at an early stage to employ adequate and early care reducing the risk of cardiovascular disease and premature death.
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