RESUMO
BACKGROUND: Affective states influence the sympathetic nervous system, inducing variations in electrodermal activity (EDA), however, EDA association with bipolar disorder (BD) remains uncertain in real-world settings due to confounders like physical activity and temperature. We analysed EDA separately during sleep and wakefulness due to varying confounders and potential differences in mood state discrimination capacities. METHODS: We monitored EDA from 102 participants with BD including 35 manic, 29 depressive, 38 euthymic patients, and 38 healthy controls (HC), for 48 h. Fifteen EDA features were inferred by mixed-effect models for repeated measures considering sleep state, group and covariates. RESULTS: Thirteen EDA feature models were significantly influenced by sleep state, notably including phasic peaks (p < 0.001). During wakefulness, phasic peaks showed different values for mania (M [SD] = 6.49 [5.74, 7.23]), euthymia (5.89 [4.83, 6.94]), HC (3.04 [1.65, 4.42]), and depression (3.00 [2.07, 3.92]). Four phasic features during wakefulness better discriminated between HC and mania or euthymia, and between depression and euthymia or mania, compared to sleep. Mixed symptoms, average skin temperature, and anticholinergic medication affected the models, while sex and age did not. CONCLUSION: EDA measured from awake recordings better distinguished between BD states than sleep recordings, when controlled by confounders.
RESUMO
BACKGROUND: Bipolar disorder is highly prevalent and consists of biphasic recurrent mood episodes of mania and depression, which translate into altered mood, sleep and activity alongside their physiological expressions. AIMS: The IdenTifying dIgital bioMarkers of illnEss activity and treatment response in BipolAr diSordEr with a novel wearable device (TIMEBASE) project aims to identify digital biomarkers of illness activity and treatment response in bipolar disorder. METHOD: We designed a longitudinal observational study including 84 individuals. Group A comprises people with acute episode of mania (n = 12), depression (n = 12 with bipolar disorder and n = 12 with major depressive disorder (MDD)) and bipolar disorder with mixed features (n = 12). Physiological data will be recorded during 48 h with a research-grade wearable (Empatica E4) across four consecutive time points (acute, response, remission and episode recovery). Group B comprises 12 people with euthymic bipolar disorder and 12 with MDD, and group C comprises 12 healthy controls who will be recorded cross-sectionally. Psychopathological symptoms, disease severity, functioning and physical activity will be assessed with standardised psychometric scales. Physiological data will include acceleration, temperature, blood volume pulse, heart rate and electrodermal activity. Machine learning models will be developed to link physiological data to illness activity and treatment response. Generalisation performance will be tested in data from unseen patients. RESULTS: Recruitment is ongoing. CONCLUSIONS: This project should contribute to understanding the pathophysiology of affective disorders. The potential digital biomarkers of illness activity and treatment response in bipolar disorder could be implemented in a real-world clinical setting for clinical monitoring and identification of prodromal symptoms. This would allow early intervention and prevention of affective relapses, as well as personalisation of treatment.
RESUMO
BACKGROUND: Depressive and manic episodes within bipolar disorder (BD) and major depressive disorder (MDD) involve altered mood, sleep, and activity, alongside physiological alterations wearables can capture. OBJECTIVE: Firstly, we explored whether physiological wearable data could predict (aim 1) the severity of an acute affective episode at the intra-individual level and (aim 2) the polarity of an acute affective episode and euthymia among different individuals. Secondarily, we explored which physiological data were related to prior predictions, generalization across patients, and associations between affective symptoms and physiological data. METHODS: We conducted a prospective exploratory observational study including patients with BD and MDD on acute affective episodes (manic, depressed, and mixed) whose physiological data were recorded using a research-grade wearable (Empatica E4) across 3 consecutive time points (acute, response, and remission of episode). Euthymic patients and healthy controls were recorded during a single session (approximately 48 h). Manic and depressive symptoms were assessed using standardized psychometric scales. Physiological wearable data included the following channels: acceleration (ACC), skin temperature, blood volume pulse, heart rate (HR), and electrodermal activity (EDA). Invalid physiological data were removed using a rule-based filter, and channels were time aligned at 1-second time units and segmented at window lengths of 32 seconds, as best-performing parameters. We developed deep learning predictive models, assessed the channels' individual contribution using permutation feature importance analysis, and computed physiological data to psychometric scales' items normalized mutual information (NMI). We present a novel, fully automated method for the preprocessing and analysis of physiological data from a research-grade wearable device, including a viable supervised learning pipeline for time-series analyses. RESULTS: Overall, 35 sessions (1512 hours) from 12 patients (manic, depressed, mixed, and euthymic) and 7 healthy controls (mean age 39.7, SD 12.6 years; 6/19, 32% female) were analyzed. The severity of mood episodes was predicted with moderate (62%-85%) accuracies (aim 1), and their polarity with moderate (70%) accuracy (aim 2). The most relevant features for the former tasks were ACC, EDA, and HR. There was a fair agreement in feature importance across classification tasks (Kendall W=0.383). Generalization of the former models on unseen patients was of overall low accuracy, except for the intra-individual models. ACC was associated with "increased motor activity" (NMI>0.55), "insomnia" (NMI=0.6), and "motor inhibition" (NMI=0.75). EDA was associated with "aggressive behavior" (NMI=1.0) and "psychic anxiety" (NMI=0.52). CONCLUSIONS: Physiological data from wearables show potential to identify mood episodes and specific symptoms of mania and depression quantitatively, both in BD and MDD. Motor activity and stress-related physiological data (EDA and HR) stand out as potential digital biomarkers for predicting mania and depression, respectively. These findings represent a promising pathway toward personalized psychiatry, in which physiological wearable data could allow the early identification and intervention of mood episodes.