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Journal of Psychiatry & Neuroscience :... 2024The interplay between state- and trait-related disruptions in structural networks remains unclear in bipolar disorder (BD), but graph theory can offer insights into...
BACKGROUND
The interplay between state- and trait-related disruptions in structural networks remains unclear in bipolar disorder (BD), but graph theory can offer insights into global and local network changes. We sought to use diffusion-tensor imaging (DTI) and graph theory approaches to analyze structural topological properties across distinct mood states and identify high-risk individuals by examining state- and trait-related impairments in BD.
METHODS
We studied changes in white matter network among patients with BD and healthy controls, exploring relationships with clinical variables. Secondary analysis involved comparing patients with BD with unaffected people at high genetic risk for BD.
RESULTS
We included 152 patients with BD, including 52 with depressive BD (DBD), 64 with euthymic BD (EBD) and 36 with manic BD (MBD); we also included 75 healthy controls. Secondary analyses involved 27 unaffected people at high genetic risk for BD. Patients with DBD and MBD exhibited significantly lower global efficiencies than those with EBD and healthy controls, with patients with DBD showing the lowest global efficiencies. In addition, patients with DBD displayed impaired local efficiency and normalized clustering coefficient (γ). At a global level, γ correlated negatively with depression and anxiety. Compared with healthy controls, and across mood states, patients with BD showed abnormal shortest path lengths in the frontolimbic circuit, a trend mirrored among those at high genetic risk for BD.
LIMITATIONS
Considerations include medication effects, absence of recorded BD episode counts and the cross-sectional nature of the study.
CONCLUSION
Mood-specific whole-brain network metrics could serve as potential biomarkers in BD for transitions between mood states. Moreover, these findings contribute to evidence of trait-related frontolimbic circuit irregularities, shedding light on underlying pathophysiological mechanisms in BD.
Topics: Humans; Bipolar Disorder; Cross-Sectional Studies; Brain; White Matter; Diffusion Tensor Imaging; Magnetic Resonance Imaging
PubMed: 38238036
DOI: 10.1503/jpn.230069 -
Nature Medicine Feb 2024Disruption in reciprocal connectivity between the right anterior insula and the left dorsolateral prefrontal cortex is associated with depression and may be a target for... (Randomized Controlled Trial)
Randomized Controlled Trial
Disruption in reciprocal connectivity between the right anterior insula and the left dorsolateral prefrontal cortex is associated with depression and may be a target for neuromodulation. In a five-center, parallel, double-blind, randomized controlled trial we personalized resting-state functional magnetic resonance imaging neuronavigated connectivity-guided intermittent theta burst stimulation (cgiTBS) at a site based on effective connectivity from the right anterior insula to the left dorsolateral prefrontal cortex. We tested its efficacy in reducing the primary outcome depression symptoms measured by the GRID Hamilton Depression Rating Scale 17-item over 8, 16 and 26 weeks, compared with structural magnetic resonance imaging (MRI) neuronavigated repetitive transcranial magnetic stimulation (rTMS) delivered at the standard stimulation site (F3) in patients with 'treatment-resistant depression'. Participants were randomly assigned to 20 sessions over 4-6 weeks of either cgiTBS (n = 128) or rTMS (n = 127) with resting-state functional MRI at baseline and 16 weeks. Persistent decreases in depressive symptoms were seen over 26 weeks, with no differences between arms on the primary outcome GRID Hamilton Depression Rating Scale 17-item score (intention-to-treat adjusted mean, -0.31, 95% confidence interval (CI) -1.87, 1.24, P = 0.689). Two serious adverse events were possibly related to TMS (mania and psychosis). MRI-neuronavigated cgiTBS and rTMS were equally effective in patients with treatment-resistant depression over 26 weeks (trial registration no. ISRCTN19674644).
Topics: Humans; Double-Blind Method; Magnetic Resonance Imaging; Prefrontal Cortex; Transcranial Magnetic Stimulation; Treatment Outcome; Depressive Disorder, Treatment-Resistant
PubMed: 38228914
DOI: 10.1038/s41591-023-02764-z -
Journal of Affective Disorders Apr 2024Investigation on specific biomarkers for diagnostic or prognostic usage in mental diseases and especially bipolar disorder BD seems to be one outstanding field in...
INTRODUCTION
Investigation on specific biomarkers for diagnostic or prognostic usage in mental diseases and especially bipolar disorder BD seems to be one outstanding field in current research. Serum neurofilament light (sNfL), a marker for neuro-axonal injury, is increased in various acute and chronic neurological disorders, but also neuro-psychiatric conditions, including affective disorders. The aim of our study was to determine a potential relation between a neuron-specific marker like sNfL and different clinical states of BD.
METHODS
In the current investigation, 51 patients with BD and 35 HC were included. Mood ratings with the Hamilton depression scale (HAMD) and the Young mania rating scale (YMRS) have been included. Illness duration was defined as the period from the time of diagnosis out of self-report and medical records. sNFL was quantified by a commercial ultrasensitive single molecule array (Simoa).
RESULTS
There was a significant positive correlation between the number of manic episodes in the past and sNfL, controlled for age and duration of illness. (R = 0.49, p = 0.03) Depressive episodes were not associated to sNfL values. (R = 0.311, p = n.s.) Patients with >3 years of illness duration showed significantly higher levels of sNfL (M18.59; SD 11.89) than patients with shorter illness duration (M = 12.38, p = 0.03) and HC (M = 11.35, p = 0.02). Patients with <3 years of illness and HC did not differ significantly in sNfL levels.
DISCUSSION
Interestingly, individuals with BD and HC did not differ in sNFL levels in general. Nevertheless, looking at the BD cohort more specifically, we found that individuals with BD with longer duration of illness (>3 years) had higher levels of sNfL than those with an illness duration below 3 years. Our results confirm previous reports on the relation of neuro-axonal injury as evidenced by sNfL and illness specific variables in bipolar disorder. Further studies are needed to clarify if sNfL may predict the disease course and/or indicated response to treatment regimes.
Topics: Humans; Bipolar Disorder; Intermediate Filaments; Mood Disorders; Psychotic Disorders; Prognosis; Biomarkers
PubMed: 38215991
DOI: 10.1016/j.jad.2024.01.088 -
Translational Psychiatry Jan 2024Nearly a quarter of bipolar disorder (BD) patients were misdiagnosed as major depressive disorder (MDD) patients, which cannot be corrected until mania/hypomania...
Nearly a quarter of bipolar disorder (BD) patients were misdiagnosed as major depressive disorder (MDD) patients, which cannot be corrected until mania/hypomania develops. It is important to recognize these obstacles so that the appropriate treatment can be initiated. Thus, we sought to distinguish patients with BD from MDD, especially to identify misdiagnosed BD before mania/hypomania, and further explore potential trait features that allow accurate differential diagnosis independent of state matters. Functional magnetic resonance imaging scans were performed at baseline on 92 MDD patients and 48 BD patients. The MDD patients were then followed up for more than two years. After follow-up, 23 patients transformed into BD (tBD), and 69 patients whose diagnoses remained unchanged were eligible for unipolar depression (UD). A support vector machine classifier was trained on the amygdala-based functional connectivity (FC) of 48 BD and 50 UD patients using a novel region-based feature selection. Then, the classifier was tested on the dataset, encompassing tBD and the remaining UD. It performed well for known BD and UD and can also distinguish tBD from UD with an accuracy of 81%, sensitivity of 82.6%, specificity of 79%, and AUC of 74.6%, respectively. Feature selection results revealed that ten regions within the cortico-limbic neural circuit contributed most to classification. Furthermore, in the FC comparisons among diseases, BD and tBD shared almost overlapped FC patterns in the cortico-limbic neural circuit, and both of them presented pronounced differences in most regions within the circuit compared with UD. The FC values of the most discriminating brain regions had no prominent correlations with the severity of depression, anxiety, and mania/hypomania (FDR correction). It suggests that BD possesses some trait features in the cortico-limbic neural circuit, rendering it dichotomized by the classifier based on known-diagnosis data.
Topics: Humans; Bipolar Disorder; Mania; Depressive Disorder, Major; Magnetic Resonance Imaging; Follow-Up Studies; Support Vector Machine; Mood Disorders
PubMed: 38191549
DOI: 10.1038/s41398-023-02703-z -
MedRxiv : the Preprint Server For... Dec 2023Understanding the mechanisms of major depressive disorder (MDD) improvement is a key challenge to determine effective personalized treatments.
IMPORTANCE
Understanding the mechanisms of major depressive disorder (MDD) improvement is a key challenge to determine effective personalized treatments.
OBJECTIVE
To perform a secondary analysis quantifying neural-to-symptom relationships in MDD as a function of antidepressant treatment.
DESIGN
Double blind randomized controlled trial.
SETTING
Multicenter.
PARTICIPANTS
Patients with early onset recurrent depression from the public Establishing Moderators and Biosignatures of Antidepressant Response in Clinical Care (EMBARC) study.
INTERVENTIONS
Either sertraline or placebo during 8 weeks (stage 1), and according to response a second line of treatment for 8 additional weeks (stage 2).
MAIN OUTCOMES AND MEASURES
To identify a data-driven pattern of symptom variations during these two stages, we performed a Principal Component Analysis (PCA) on the variations of individual items of four clinical scales measuring depression, anxiety, suicidal ideas and manic-like symptoms, resulting in a univariate measure of clinical improvement. We then investigated how initial clinical and neural factors predicted this measure during stage 1. To do so, we extracted resting-state global brain connectivity (GBC) at baseline at the individual level using a whole-brain functional network parcellation. In turn, we computed a linear model for each brain parcel with individual data-driven clinical improvement scores during stage 1 for each group.
RESULTS
192 patients (127 women), age 37.7 years old (standard deviation: 13.5), were included. The first PC (PC1) capturing 20% of clinical variation was similar across treatment groups at stage 1 and stage 2, suggesting a reproducible pattern of symptom improvement. PC1 patients' scores significantly differed according to treatment during stage 1, whereas no difference of response was evidenced between groups with the Clinical Global Impressions (CGI). Baseline GBC correlated to stage 1 PC1 scores in the sertraline, but not in the placebo group.
CONCLUSIONS AND RELEVANCE
Using data-driven reduction of symptoms scales, we identified a common profile of symptom improvement across placebo and sertraline. However, the neural patterns of baseline that mapped onto symptom improvement distinguished between treatment and placebo. Our results underscore that mapping from data-driven symptom improvement onto neural circuits is vital to detect treatment-responsive neural profiles that may aid in optimal patient selection for future trials.
PubMed: 38168378
DOI: 10.1101/2023.12.15.23300019 -
Journal of Affective Disorders Mar 2024It is estimated that up to 50 % of people with bipolar disorder (BD) also have comorbid post-traumatic stress disorder (PTSD). However, little is known about the...
BACKGROUND
It is estimated that up to 50 % of people with bipolar disorder (BD) also have comorbid post-traumatic stress disorder (PTSD). However, little is known about the presentation and treatment of people with this comorbidity.
METHODS
Data from 577 individuals diagnosed with bipolar disorder participating in the Heinz C. Prechter Longitudinal Study of BD were explored at baseline, year two and four. Three trauma groups were created: (i) one trauma (n = 75), (ii) multiple traumas (n = 417), and comorbid PTSD (n = 85). Measures of depression, mania, sleep, number of hospitalisations, suicide attempts, and medication use were analysed using regression modelling to determine differences between the three trauma groups.
RESULTS
There was an increase in depression, mania, and sleep scores and a higher number of hospitalisations in participants with comorbid PTSD compared to those experiencing one trauma. Additionally, increased mania and depression scores were reported in participants experiencing multiple traumas compared to those with one trauma. There was no difference in medication use between those who experienced one trauma compared to those with comorbid PTSD.
LIMITATIONS
The trauma groups may include confounding with more participants experiencing PTSD than reported in this study due to screening processes. Additionally, the severity of trauma was not recorded, therefore number of traumas was utilised as a proxy.
CONCLUSION
Comorbid BD and PTSD is associated with worse symptom scores compared to participants reporting one trauma. Clinical implications include the addition of trauma-informed care to clinical settings to identify PTSD to provide appropriate treatments.
Topics: Humans; Stress Disorders, Post-Traumatic; Bipolar Disorder; Longitudinal Studies; Mania; Comorbidity; Multiple Trauma
PubMed: 38163569
DOI: 10.1016/j.jad.2023.12.058 -
Journal of Affective Disorders Mar 2024Inflammation and immunological alterations, such as T-cell and cytokine changes, are implicated in bipolar disorder (BD), with some evidence linking them to brain...
BACKGROUND
Inflammation and immunological alterations, such as T-cell and cytokine changes, are implicated in bipolar disorder (BD), with some evidence linking them to brain structural changes (e.g., cortical thickness (CT), gray matter (GM) volume and white matter (WM) microstructure). However, the connection between specific peripheral cell types, such as T-cells, and neuroimaging in BD remains scarcely investigated.
AIMS OF THE STUDY
This study aims to explore the link between T-cell immunophenotype and neuroradiological findings in BD.
METHODS
Our study investigated 43 type I BD subjects (22 depressive, 21 manic) and 26 healthy controls (HC), analyzing T lymphocyte immunophenotype and employing neuroimaging to assess CT for GM and fractional anisotropy (FA) for WM.
RESULTS
In lymphocyte populations, BD patients exhibited elevated CD4+ and CD4+ central memory (T) cells frequencies, but lower CD8+ effector memory (T) and terminal effector memory (T) cells. Neuroimaging analysis revealed reduced CT in multiple brain regions in BD patients; and significant negative correlations between CD4 + T levels and CT of precuneus and fusiform gyrus. Tract-based spatial statistics (TBSS) analysis showed widespread alteration in WM microstructure in BD patients, with negative and positive correlations respectively between FA and radial diffusivity (RD) and CD4 + T. Additionally, positive and negative correlations were found respectively between FA and RD and the CD8 + T and CD8 + T subsets.
CONCLUSIONS
Our research revealed distinct T lymphocyte changes and brain structure alterations in BD, underscoring possible immune-brain interactions, warranting further study and therapeutic exploration.
Topics: Humans; Bipolar Disorder; White Matter; Diffusion Tensor Imaging; T-Lymphocytes; Brain; Anisotropy
PubMed: 38154587
DOI: 10.1016/j.jad.2023.12.054 -
Proceedings of the SIGCHI Conference on... Apr 2023We examine the feasibility of using accelerometer data exclusively collected during typing on a custom smartphone keyboard to study whether typing dynamics are...
Smartphone-derived Virtual Keyboard Dynamics Coupled with Accelerometer Data as a Window into Understanding Brain Health: Smartphone Keyboard and Accelerometer as Window into Brain Health.
We examine the feasibility of using accelerometer data exclusively collected during typing on a custom smartphone keyboard to study whether typing dynamics are associated with daily variations in mood and cognition. As part of an ongoing digital mental health study involving mood disorders, we collected data from a well-characterized clinical sample (N = 85) and classified accelerometer data per typing session into orientation (upright vs. not) and motion (active vs. not). The mood disorder group showed lower cognitive performance despite mild symptoms (depression/mania). There were also diurnal pattern differences with respect to cognitive performance: individuals with higher cognitive performance typed faster and were less sensitive to time of day. They also exhibited more well-defined diurnal patterns in smartphone keyboard usage: they engaged with the keyboard more during the day and tapered their usage more at night compared to those with lower cognitive performance, suggesting a healthier usage of their phone.
PubMed: 38115842
DOI: 10.1145/3544548.3580906 -
Annals of Medicine 2023Chronotherapeutic interventions for bipolar depression and mania are promising interventions associated with rapid response and benign side effect profiles. Filtering of...
INTRODUCTION
Chronotherapeutic interventions for bipolar depression and mania are promising interventions associated with rapid response and benign side effect profiles. Filtering of biologically active short wavelength (blue) light by orange tinted eyewear has been shown to induce antimanic and sleep promoting effects in inpatient mania. We here describe a study protocol assessing acute and long-term stabilizing effects of blue blocking (BB) glasses in outpatient treatment of bipolar disorder.
PATIENTS AND METHODS
A total of 150 outpatients with bipolar disorder and current symptoms of (hypo)-mania will be randomized 1:1 to wear glasses with either high (99%) (intervention group) or low (15%) (control group) filtration of short wavelength light (<500 nm). Following a baseline assessment including ratings of manic and depressive symptoms, sleep questionnaires, pupillometric evaluation and 48-h actigraphy, participants will wear the glasses from 6 PM to 8 AM for 7 consecutive days. The primary outcome is the between group difference in change in Young Mania Rating Scale scores after 7 days of intervention (day 9). Following the initial treatment period, the long-term stabilizing effects on mood and sleep will be explored in a 3-month treatment paradigm, where the period of BB treatment is tailored to the current symptomatology using a 14-h antimanic schedule during (hypo-) manic episodes (BB glasses or dark bedroom from 6 PM to 8 AM) and a 2-h maintenance schedule (BB glasses on two hours prior to bedtime/dark bedroom) during euthymic and depressive states.The assessments will be repeated at follow-up visits after 1 and 3 months. Throughout the 3-month study period, participants will perform continuous daily self-monitoring of mood, sleep and activity in a smartphone-based app. Secondary outcomes include between-group differences in actigraphic sleep parameters on day 9 and in day-to-day instability in mood, sleep and activity, general functioning and objective sleep markers (actigraphy) at weeks 5 and 15.
TRIAL REGISTRATION
The trial will be registered at www.clinicaltrials.gov prior to initiation and has not yet received a trial reference.
ADMINISTRATIVE INFORMATION
The current paper is based on protocol version 1.0_31.07.23. : Lars Vedel Kessing.
Topics: Humans; Bipolar Disorder; Antimanic Agents; Mania; Sleep; Ambulatory Care; Randomized Controlled Trials as Topic
PubMed: 38109922
DOI: 10.1080/07853890.2023.2292250