Abstract
Introduction
A substantial proportion of patients with bipolar disorder experience daily subsyndromal mood swings, and the term “mood instability” reflecting the variability in mood seems ...associated with poor prognostic factors, including impaired functioning, and increased risk of hospitalization and relapse.
During the last decade, we have developed and tested a smartphone-based system for monitoring bipolar disorder. The present SmartBipolar randomized controlled trial (RCT) aims to investigate whether (1) daily smartphone-based outpatient monitoring and treatment
including
clinical feedback versus (2) daily smartphone-based monitoring
without
clinical feedback or (3) daily smartphone-based mood monitoring
only
improves mood instability and other clinically relevant patient-related outcomes in patients with bipolar disorder.
Methods and analysis
The SmartBipolar trial is a pragmatic randomized controlled parallel-group trial. Patients with bipolar disorder are invited to participate as part of their specialized outpatient treatment for patients with bipolar disorder in Mental Health Services in the Capital Region of Denmark. The included patients will be randomized to (1) daily smartphone-based monitoring and treatment
including
a clinical feedback loop (intervention group) or (2) daily smartphone-based monitoring
without
a clinical feedback loop (control group) or (3) daily smartphone-based mood monitoring only (control group). All patients receive specialized outpatient treatment for bipolar disorder in the Mental Health Services in the Capital Region of Denmark. The trial started in March 2021 and has currently included 150 patients. The outcomes are (1) mood instability (primary), (2) quality of life, self-rated depressive symptoms, self-rated manic symptoms, perceived stress, satisfaction with care, cumulated number and duration of psychiatric hospitalizations, and medication (secondary), and (3) smartphone-based measures per month of stress, anxiety, irritability, activity, and sleep as well as the percentage of days with presence of mixed mood, days with adherence to medication and adherence to smartphone-based self-monitoring. A total of 201 patients with bipolar disorder will be included in the SmartBipolar trial.
Ethics and dissemination
The SmartBipolar trial is funded by the Capital Region of Denmark and the Independent Research Fund Denmark. Ethical approval has been obtained from the Regional Ethical Committee in The Capital Region of Denmark (H-19067248) as well as data permission (journal number: P-2019–809). The results will be published in peer-reviewed academic journals, presented at scientific meetings, and disseminated to patients’ organizations and media outlets.
Trial registration
Trial registration number: NCT04230421. Date March 1, 2021. Version 1.
Background
DSM-IV states that criterion A for diagnosing hypomania/mania is mood change. The revised DSM-5 now states that increased energy or activity must be present alongside mood changes to ...diagnose hypomania/mania, thus raising energy/activity to criterion A. We set out to investigate how the change in criterion A affects the diagnosis of hypomanic/manic visits in patients with a newly diagnosed bipolar disorder.
Results
In this prospective cohort study, 373 patients were included (median age = 32; IQR, 27–40). Women constituted 66% (n = 245) of the cohort and 68% of the cohort (n = 253) met criteria for bipolar type II, the remaining patients were diagnosed bipolar type I. Median number of contributed visits was 2 per subject (IQR, 1–3) and median follow-up time was 3 years (IQR, 2–4). During follow-up, 127 patients had at least one visit with fulfilled DSM-IV criterion A. Applying DSM-5 criterion A reduced the number of patients experiencing a hypomanic/manic visit by 62% at baseline and by 50% during longitudinal follow-up, compared with DSM-IV criterion A. Fulfilling DSM-5 criterion A during follow-up was associated with higher modified young mania rating scale score (OR = 1.51, CL 1.34, 1.71, p < 0.0001) and increased number of visits contributed (OR = 1.86, CL 1.52, 2.29, p < 0.0001).
Conclusion
Applying the stricter DSM-5 criterion A in a cohort of newly diagnosed bipolar patients reduced the number of patients experiencing a hypomanic/manic visit substantially, and was associated with higher overall young mania rating scale scores, compared with DSM-IV criterion A. Consequently, fewer hypomanic/manic visits may be detected in newly diagnosed bipolar patients with applied DSM-5 criterion A, and the upcoming ICD-11, which may possibly result in longer diagnostic delay of BD as compared with the DSM-IV.
Background
Overall functioning is already impaired in patients newly diagnosed with bipolar disorder (BD) and, to a lesser degree, also in their unaffected first-degree relatives (UR). Further, ...aggregation of psychiatric disorders among the patients’ first-degree relatives seems to be associated with higher illness burden and poorer prognosis. However, whether this aggregation of psychiatric disorders among first-degree relatives, the familial load (FL), impacts overall functioning in patients newly diagnosed with BD and their UR remains unresolved.
Methods
In total, 388 patients newly diagnosed with BD, 144 of their UR and 201 healthy control individuals were included. Overall functioning was assessed using three different assessment methods: The interviewer based “Functioning Assessment Short Test” (FAST), the questionnaire “Work and Social Adjustment Scale” (WSAS) and six outcome measures covering the participants’ socio-economic status (SES); educational achievement, employment, work ability, relationship, cohabitation and marital status. Familial load of psychiatric disorder was assessed using the “Family History Research Diagnostic Criteria” interview. Associations between FL and overall functioning in patients and UR were investigated categorically using logistic and continuously in linear regression models.
Results
Contrasting with the hypotheses, the FL of psychiatric disorders was not associated with impaired overall functioning, neither in patients newly diagnosed with BD nor in their UR.
Conclusion
The findings indicate that impaired functioning in the early phase of BD is not associated with aggregation of psychiatric disorders among first-degree relatives. The observed functional impairment in patients newly diagnosed with BD seems driven by the personal impact of the disorder rather than the impact of having first-degree relatives with psychiatric disorders. Keywords: bipolar disorder, first-degree relatives, familial load of psychiatric disorders, functioning, socio-economic status.
Affective disorders have a long-term impact on psychiatric health and are caused by multiple interacting factors including familial risk, childhood adversity, life events and personality traits.
In ...this study, monozygotic twins (MZ) at familial risk (indexed by affective disorder in their co-twin; high-risk group), affected MZ twins (indexed by a diagnosis with affective disorder) and MZ twins with no family history of affective disorder (low-risk group) were identified through cross-linking of nation-wide Danish registers. In total, 204 MZ twins were included and psychopathology, personality traits and life adversity were evaluated by semi-structured interviews and questionnaires.
Affected MZ twins presented with more subclinical affective symptoms and were functionally impaired as evidenced by higher unemployment rates and reduced functional status. The affected and the high-risk groups reported more childhood adversity and had experienced more stressful life events than the low-risk group. A direct comparison within the discordant twin pairs showed that the high-risk twins presented fewer affective symptoms, better functional status, more extraversion and lower neuroticism scores than their affected co-twins although they had equal levels of life adversity as their affected co-twins.
These findings add to the evidence indicating that patients experience higher neuroticism, persistent subclinical symptoms and reduced socio-occupational function after affective episodes. Additionally, neuroticism and extraversion seem capable of moderating the sensitivity to exposure from the environment.
IntroductionDespite current available treatment patients with bipolar disorder often experience relapses and decreased overall functioning. Furthermore, patients with bipolar disorder are often not ...treated medically or psychologically according to guidelines and recommendations. A Clinical Academic Group is a new treatment initiative bringing together clinical services, research, education and training to offer care and treatment that is based on reliable evidence backed up by research. The present Clinical Academic Group for bipolar disorder (the CAG Bipolar) randomised controlled trial (RCT) aims for the first time to investigate whether specialised outpatient treatment in CAG Bipolar versus generalised community-based treatment improves patient outcomes and clinician’s satisfaction with care in patients with bipolar disorder.Methods and analysisThe CAG Bipolar trial is a pragmatic randomised controlled parallel-group trial undertaken in the Capital Region of Denmark covering a catchment area of 1.85 million people. Patients with bipolar disorder are invited to participate as part of their outpatient treatment in the Mental Health Services. The included patients will be randomised to (1) specialised outpatient treatment in the CAG Bipolar (intervention group) or (2) generalised community-based outpatient treatment (control group). The trial started 13 January 2020 and has currently included more than 600 patients. The outcomes are (1) psychiatric hospitalisations and cumulated number and duration of psychiatric hospitalisations (primary), and (2) self-rated depressive symptoms, self-rated manic symptoms, quality of life, perceived stress, satisfaction with care, use of medication and the clinicians’ satisfaction with their care (secondary). A total of 1000 patients with bipolar disorder will be included.Ethics and disseminationThe CAG Bipolar RCT is funded by the Capital Region of Denmark and ethical approval has been obtained from the Regional Ethical Committee in The Capital Region of Denmark (H-19067248). Results will be published in peer-reviewed academic journals, presented at scientific meetings and disseminated to patient organisations and media outlets.Trial registration numberNCT04229875.
Cognitive impairments in bipolar disorder (BD) such as memory deficits are associated with poor functional outcomes and it has been suggested that the brain-derived neurotrophic factor (BDNF) ...Val66Met polymorphism contributes to individual variability in memory function in BD. The current study investigated the relationship between the BDNF Val66Met polymorphism, neural activity during a picture-encoding task, and subsequent memory recall.
A total of 70 patients with BD grouped according to genotype ValVal or Met carriers (MetVal/MetMet) underwent fMRI while performing a picture-encoding task. Memory for the encoded pictures was tested with a subsequent free recall memory task.
There was no difference between the ValVal homozygotes and Met carriers in the involvement of hypothesized memory encoding regions i.e. hippocampus and dorsal prefrontal cortex (dPFC). However, an exploratory whole-brain analysis showed greater encoding-related lateral occipital cortex activity in Met carriers. Behaviorally, Met carriers also showed better free recall of the encoded pictures.
We found no effect of the BDNF genotype on encoding-related hippocampal and dPFC activity in BD, although Met carriers showed superior memory performance after the scan, which could be related to more efficient perceptual processing during encoding.
Background: Daily variation in mood and activity between and within affective episodes in bipolar disorder has become a field of increasing interest. The present exploratory study aimed to identify ...predictors of mood and activity instability in participants with bipolar disorder (BD). Methods: A total of 258 participants with newly diagnosed BD type I and II were included as part of a longitudinal study (the Bipolar Illness Onset study (BIO)). The participants completed daily smartphone-based mood and activity ratings for a median interquartile range (IQR) of 109 days 40;240 and 106 days 40;243, respectively. Clinical evaluations and questionnaires were collected at the baseline visit. Backwards stepwise regression analysis was employed to identify predictors. Results: Predictors of increased mood instability included childhood trauma (e.g., B = 0.006, 95 % CI 0.001;0.011, p = 0.031), increasing number of depressive episodes, antipsychotic medication, functional impairment, and impaired sleep quality. Predictors of increased activity instability included longer Illness duration, lower age at onset, number of depressive episodes, functional impairment, and impaired sleep quality (e.g., B = 0.089, 95 %CI=0.033;0.145, p = 0.002). Limitations: Risk of type 1 error due to the large number of analyses. Conclusions: Increasing number of prior depressive episodes, functional impairment, and poor sleep quality were consistent predictors of subsequent increased mood and activity instability. Childhood trauma was a predictor of increased mood instability only, whereas age of onset was a predictor of increased activity instability only.
Background:
Mental imagery abnormalities feature across affective disorders including bipolar disorder (BD) and unipolar depression (UD). Maladaptive emotional imagery has been proposed as a ...maintenance factor for affective symptomatology and a target for mechanism-driven psychological treatment developments. Where imagery abnormalities feature beyond acute affective episodes, further opportunities for innovation arise beyond treatments, such as for tertiary/relapse prevention (e.g., in remitted individuals) or primary prevention (e.g., in non-affected but at-risk individuals). The aim of our study was to investigate for the first time the presence of possible mental imagery abnormalities in affected individuals in remission and at-risk individuals for affective disorders using a familial risk design.
Methods:
A population-based cohort of monozygotic twins was recruited through linkage between the Danish national registries (
N
=204). Participants were grouped as: affected (remitted BD/UD;
n
= 115); high-risk (co-twin with history of BD/UD;
n
= 49), or low-risk (no co-twin history of BD/UD;
n
= 40). Twins completed mental imagery measures spanning key subjective domains (spontaneous imagery use and emotional imagery) and cognitive domains (imagery inspection and imagery manipulation).
Results:
Affected twins in remission reported enhanced emotional mental imagery compared to both low- and high-risk twins. This was characterized by greater impact of i) intrusive prospective imagery (Impact of Future Events Scale) and ii) deliberately-generated prospective imagery of negative scenarios (Prospective Imagery Task). There were no significant differences in these key measures between affected BD and UD twins in remission. Additionally, low- and high-risk twins did not significantly differ on these emotional imagery measures. There were also no significant differences between the three groups on non-emotional measures including spontaneous imagery use and cognitive stages of imagery.
Conclusions:
Abnormalities in emotional prospective imagery are present in monozygotic twins with affective disorders in remission—despite preserved cognitive stages of imagery—but absent in unaffected high-risk twins, and thus do not appear to index familial risk (i.e., unlikely to qualify as “endophenotypes”). Elevated emotional prospective imagery represents a promising treatment/prevention target in affective disorders.
Objectives:
The aim of the study was to evaluate the prevalence of and illness characteristics in adults with major depressive disorder (MDD) with anxious distress specifier (ADS) enrolled in the ...International Mood Disorders Collaborative Project, which is a collaborative research platform at the Mood Disorders Psychopharmacology Unit, University of Toronto, Canada and the Cleveland Clinic, Cleveland, Ohio, USA.
Methods:
Data from participants who met criteria for a current major depressive episode as part of MDD (n = 830) were included in this post hoc analysis. Diagnostic and Statistical Manual Version-5-defined ADS was operationalized as the presence of at least two out of three proxy items instead of two out of five specifiers.
Results:
A total of 464 individuals (i.e. 56%) met criteria for ADS. There were no between-group differences in sociodemographic variables (e.g. gender, employment, marital status). Greater severity of illness was observed in adults with ADS as evidenced by a higher number of hospitalizations, higher rates of suicidal ideation, greater depressive symptom severity, greater workplace impairment, decreased quality of life, and greater self-reported cognitive impairment.
Conclusions:
Our findings underscore the importance of evaluating ADS in adults with MDD as its presence identifies a subpopulation with greater illness-associated burden and hazards.
Abstract Unipolar depression is moderately heritable. It is unclear whether structural brain changes associated with unipolar depression are present in healthy persons at risk of the disorder. Here ...we investigated whether a genetic predisposition to unipolar depression is associated with structural brain changes. A priori, hippocampal volume reductions were hypothesized. Using a high-risk study design, magnetic resonance imaging brain scans were obtained from 59 healthy high-risk subjects having a co-twin with unipolar depression, and 53 healthy low-risk subjects without a first-degree family history of major psychiatric disorder. High-risk twins had smaller hippocampal volumes than low-risk twins ( p < 0.04). The finding was most pronounced in DZ twins. Groups did not differ on global brain tissue volumes or regional tissue volumes assessed in exploratory voxel-wise whole cerebrum analyses. In conclusion, hippocampal volume reduction may index a predisposition to develop depression and thus may be predictive of future onset of the disorder. Further studies are needed to elucidate the role of (shared) environmental and genetic factors.
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