Katherine E. Burdick’s research while affiliated with Harvard Medical School and other places

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Publications (280)


A critical role of philanthropic support in paving the way to precision medicine for bipolar disorder
  • Article

February 2025

Biological Psychiatry

Daniel L. Pham

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Emily G. Baxi

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Kelsey M. Barcomb

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[...]

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Cara M. Altimus


Fig. 1. Critic loss value
Fig. 2. Off-policy evaluation (OPE) results showing the impact of the learned policy on each patient's number of mood episodes. The average improvement across all patients is 15.7 %.
Fig. 3. 3D plot for policy comparison for a representative patient during the 9 periods. The number on each axis indicates the extent of change, where 0 = no change, 1 = small change, 2 = medium change, and 3 = large change compared with the previous period (see also footnote 1).
Fig. 4. The Decision Tree structure
Fig. 6. Pairwise relationships among features (age, age of onset, and duration) across clusters identified using K-means clustering. Diagonal histograms show the distribution of each feature within clusters, while scatterplots illustrate interactions between feature pairs.
A multi-agent reinforcement learning algorithm for personalized recommendations in bipolar disorder
  • Preprint
  • File available

December 2024

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12 Reads

This study introduces a novel multi-agent reinforcement learning (MARL) algorithm designed for identifying and optimizing personalized recommendations in bipolar disorder. The algorithm leverages longitudinal offline data from wearables to recommend self-care strategies tailored to individual patients. We focus on self-care strategies involving physical activity (measured by steps), sleep duration, and bedtime consistency, aiming to reduce the periods of mood exacerbations. Findings suggest that following our algorithm's self-care recommendations could significantly reduce periods of elevated mood symptoms, resulting in improved overall well-being. In addition, the algorithm offers important clinical insights for treating bipolar patients, and shows promising theoretical properties showcasing its potential for use in other chronic diseases. Significance statement Our multi-agent reinforcement learning algorithm provides an innovative approach to personalizing self-care recommendations for bipolar disorder patients. By integrating longitudinal data from wearable devices and self-reports, the algorithm dynamically tailors self-care recommendations to individual patient's profiles. Findings suggest that the self-care recommendations generated by our algorithm could reduce the occurrence of clinically significant mood symptoms. The algorithm, therefore, has the potential to guide behavior changes that might have the biggest impact on patients' symptoms, allowing them to better manage their chronic disease.

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Digital phenotyping in bipolar disorder: Using longitudinal Fitbit data and personalized machine learning to predict mood symptomatology

October 2024

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59 Reads

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3 Citations

Acta Psychiatrica Scandinavica

Background Effective treatment of bipolar disorder (BD) requires prompt response to mood episodes. Preliminary studies suggest that predictions based on passive sensor data from personal digital devices can accurately detect mood episodes (e.g., between routine care appointments), but studies to date do not use methods designed for broad application. This study evaluated whether a novel, personalized machine learning approach, trained entirely on passive Fitbit data, with limited data filtering could accurately detect mood symptomatology in BD patients. Methods We analyzed data from 54 adults with BD, who wore Fitbits and completed bi‐weekly self‐report measures for 9 months. We applied machine learning (ML) models to Fitbit data aggregated over two‐week observation windows to detect occurrences of depressive and (hypo)manic symptomatology, which were defined as two‐week windows with scores above established clinical cutoffs for the Patient Health Questionnaire‐8 (PHQ‐8) and Altman Self‐Rating Mania Scale (ASRM) respectively. Results As hypothesized, among several ML algorithms, Binary Mixed Model (BiMM) forest achieved the highest area under the receiver operating curve (ROC‐AUC) in the validation process. In the testing set, the ROC‐AUC was 86.0% for depression and 85.2% for (hypo)mania. Using optimized thresholds calculated with Youden's J statistic, predictive accuracy was 80.1% for depression (sensitivity of 71.2% and specificity of 85.6%) and 89.1% for (hypo)mania (sensitivity of 80.0% and specificity of 90.1%). Conclusion We achieved sound performance in detecting mood symptomatology in BD patients using methods designed for broad application. Findings expand upon evidence that Fitbit data can produce accurate mood symptomatology predictions. Additionally, to the best of our knowledge, this represents the first application of BiMM forest for mood symptomatology prediction. Overall, results move the field a step toward personalized algorithms suitable for the full population of patients, rather than only those with high compliance, access to specialized devices, or willingness to share invasive data.



Perceived loneliness and social support in bipolar disorder: relation to suicidal ideation and attempts

March 2024

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43 Reads

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1 Citation

International Journal of Bipolar Disorders

Background The suicide rate in bipolar disorder (BD) is among the highest across all psychiatric disorders. Identifying modifiable variables that relate to suicidal thoughts and behaviors (STBs) in BD may inform prevention strategies. Social connectedness is a modifiable variable found to relate to STBs in the general population, but differences exist across subgroups of the general population and findings specifically in BD have been equivocal. We aimed to clarify how perceived social connectedness relates to STBs in BD. Method 146 adults (86 BD, 60 healthy controls) completed clinical interviews (Hamilton Depression Rating Scale; Structured Clinical Interview for DSM-5) and self-report measures of loneliness (UCLA Loneliness Scale) and social support (Interpersonal Support Evaluation List). Analyses explored differences in indicators of social connectedness (loneliness and social support) between BD participants and healthy controls, and explored relationships between STBs (lifetime suicide attempts and current suicidal ideation) and indicators of social connectedness in BD participants. Results BD participants reported significantly higher loneliness and lower social support than healthy controls. In BD participants, perceived social support was significantly related to both ever having attempted suicide and number of lifetime attempts. Interestingly, perceived loneliness, but not social support, was significantly associated with current suicidal ideation. Conclusions Findings expand the evidence base supporting a relationship between perceived social connectedness and STBs in BD. They suggest that this modifiable variable could be a fruitful treatment target for preventing STBs in BD.


Efficacy and safety of established and off-label ADHD drug therapies for cognitive impairment or attention-deficit hyperactivity disorder symptoms in bipolar disorder: A systematic review by the ISBD Targeting Cognition Task Force

March 2024

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156 Reads

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3 Citations

Bipolar Disorders

Background Abnormalities in dopamine and norepinephrine signaling are implicated in cognitive impairments in bipolar disorder (BD) and attention-deficit hyperactivity disorder (ADHD). This systematic review by the ISBD Targeting Cognition Task Force therefore aimed to investigate the possible benefits on cognition and/or ADHD symptoms and safety of established and off-label ADHD therapies in BD. Methods We included studies of ADHD medications in BD patients, which involved cognitive and/or safety measures. We followed the procedures of the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) 2020 statement. Searches were conducted on PubMed, Embase and PsycINFO from inception until June 2023. Two authors reviewed the studies independently using the Revised Cochrane Collaboration's Risk of Bias tool for Randomized trials. Results Seventeen studies were identified (N = 2136), investigating armodafinil (k = 4, N = 1581), methylphenidate (k = 4, N = 84), bupropion (k = 4, n = 249), clonidine (k = 1, n = 70), lisdexamphetamine (k = 1, n = 25), mixed amphetamine salts (k = 1, n = 30), or modafinil (k = 2, n = 97). Three studies investigated cognition, four ADHD symptoms, and 10 the safety. Three studies found treatment-related ADHD symptom reduction: two involved methylphenidate and one amphetamine salts. One study found a trend towards pro-cognitive effects of modafinil on some cognitive domains. No increased risk of (hypo)mania was observed. Five studies had low risk of bias, eleven a moderate risk, and one a serious risk of bias. Conclusions Methylphenidate or mixed amphetamine salts may improve ADHD symptoms in BD. However, there is limited evidence regarding the effectiveness on cognition. The medications produced no increased mania risk when used alongside mood stabilizers. Further robust studies are needed to assess cognition in BD patients receiving psychostimulant treatment alongside mood stabilizers.



Change in Neurocognitive Functioning in Patients with Treatment-Resistant Depression with Serial Intravenous Ketamine Infusions: The Bio-K Multicenter Trial

February 2024

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39 Reads

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6 Citations

Psychiatry Research

This nonrandomized, multicenter, open-label clinical trial explored the impact of intravenous (IV) ketamine on cognitive function in adults (n = 74) with treatment-resistant depression (TRD). Patients received three IV ketamine infusions during the acute phase and, if remitted, four additional infusions in the continuation phase (Mayo site). Cognitive assessments using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) were conducted at baseline, end of the acute phase, and end of the continuation phase (Mayo site). Results showed a significant 53 % (39/74) remission rate in depression symptoms after the acute phase. In adjusted models, baseline language domain score was associated with a higher odd of remission (Odds Ratio, 1.09, 95 % CI = 1.03–1.17, p = 0.004) and greater improvement in MADRS at the end of the acute phase (β =-0.97; 95 % CI, -1.74 to -0.20; P = 0.02). The likelihood of remission was not significantly associated with baseline immediate or delayed memory, visuospatial/constructional, or attention scores. In the continuation phase, improvements in immediate and delayed memory and attention persisted, with additional gains in visuospatial and language domains. Limitations included an open-label design, potential practice effects, and ongoing psychotropic medication use. Overall, the study suggests cognitive improvement, not deterioration, associated with serial IV ketamine administrations for TRD. These findings encourage future studies with larger sample sizes and longer follow-up periods to examine any potential for deleterious effect with recurrent ketamine use for TRD.


Citations (65)


... Past studies have primarily focused on predicting depression and anxiety on average using assessments like PHQ-9 or GAD-7, respectively, but these measures estimate average levels over typically one or more weeks in a retrospective fashion 18,19 . One such study used data from 10k participants' FitBit data to predict these measures with relative accuracy 19 . ...

Reference:

Passive sensing with psyche: utilizing data from wearable technology to predict emotion states
Digital phenotyping in bipolar disorder: Using longitudinal Fitbit data and personalized machine learning to predict mood symptomatology
  • Citing Article
  • October 2024

Acta Psychiatrica Scandinavica

... This approach is further supported by a growing body of evidence showing that transdiagnostic cognitive behavioural therapy is not only as effective as disorder-specific therapy but also superior to waitlist and treatment-as-usual approaches in addressing emotional disorders (Schaeuffele et al. 2024). Furthermore, repetitive negative thinking and sleep disturbances are associated with several clinically significant outcomes, including suicidal behaviour, reduced quality of life and impaired social and global functioning (Adamis et al. 2024;Caudle et al. 2024;L. M. Harris et al. 2020;Kallestad et al. 2012), highlighting their potential as transdiagnostic treatment targets. ...

Predictors of psychosocial impairment in a transdiagnostic sample: Unique effects of repetitive negative thinking
  • Citing Article
  • August 2024

Journal of Affective Disorders

... The associations between higher genetic propensity to depression, bipolar and anxiety and poorer social connections typically aligns with the phenotypic literature. Individuals with higher phenotypic depressive symptoms tend to have high loneliness and strain in their connections and low perceived social support (Ali et al., 2022;Dahlberg et al., 2021;Turner et al., 2022), as do individuals with bipolar disorder (Eidelman et al., 2012;Koenders et al., 2015;Pike et al., 2024). Individuals with phenotypic anxiety also typically have poorer social connections (e.g., more conflict in their relationships) (Leach & Butterworth, 2020). ...

Perceived loneliness and social support in bipolar disorder: relation to suicidal ideation and attempts

International Journal of Bipolar Disorders

... However, four studies observed findings that contradict this conclusion [133][134][135][136]. Shiroma et al., (2020) found a correlation between better pre-treatment complex working memory and greater improvement in MADRS scores after five IV ketamine infusions (F 1,49 = 7.66, p < 0.01) [133]. ...

Change in Neurocognitive Functioning in Patients with Treatment-Resistant Depression with Serial Intravenous Ketamine Infusions: The Bio-K Multicenter Trial
  • Citing Article
  • February 2024

Psychiatry Research

... It is already known that cognitive disfunction and mood disorders are more prevalent in patients with systemic mastocytosis [12]. The prevalence varies greatly from 7% up to 70%, mostly due to different tools used for cognitive evaluation. ...

Cognitive Impairment and Depression in Mastocytosis: A Synthesis of the Literature

Current Allergy and Asthma Reports

... However, concerns remain. Studies, including Lipschitz et al. (2023), have raised serious concerns regarding modafinil's potential to exacerbate manic symptoms and disrupt sleep patterns in BD patients, particularly in those prone to mood cycling (Lipschitz et al., 2023). The emergence of S-CE-123, a selective dopamine reuptake inhibitor and structural analog of modafinil, offers a more refined approach to cognitive enhancement. ...

Modafinil’s effects on cognition and sleep quality in affectively-stable patients with bipolar disorder: a pilot study

... Thus, engagement often focuses on the extent to which an individual makes productive use of a tool in their daily life [180,214]. While many individuals are eager to try out new DMH tools, they often lack the sustained engagement needed to support learning and applying new skills and perspectives [126,145]. As such, the benefits of DMH tools that require prolonged use often remain unrealized relative to their potential [16,61]. ...

The Engagement Problem: a Review of Engagement with Digital Mental Health Interventions and Recommendations for a Path Forward

Current Treatment Options in Psychiatry

... 5 Despite the robust evidence base, lithium prescriptions remain disappointingly low, while the use of antidepressants and antipsychotics continues to increase. 6 The use of antidepressants in bipolar disorder remains particularly controversial, yet prescription rates continue to increase. 2003 data 7 show no significant difference in the occurrence of mood episodes between short-term and long-term use of adjunctive antidepressants with mood stabilisers or antipsychotics. ...

Patterns of pharmacotherapy for bipolar disorder: A GBC survey

Bipolar Disorders

... iPSCs derived from patients with bipolar disorder have been utilized to better understand the cellular behaviors and differential gene expression between lithium responders (LR) and nonresponders (NR) [3,28,29]. This research has generated novel insights into the molecular mechanisms of mood stabilizer function with focal adhesion, oxidative phosphorylation, and spliceosome modifications being implicated in therapeutic response. ...

Focal adhesion is associated with lithium response in bipolar disorder: evidence from a network-based multi-omics analysis

Molecular Psychiatry

... The Schizophrenia Exome Sequencing Meta-analysis (SCHEMA) study has confirmed association with ultra-rare variants at 10 genes [19]. This and other studies indicate an excess burden of rare protein truncating variants in schizophrenia cases compared to controls, evident across diverse human ancestries [20], and suggesting that there are many more ultra-rare variants to be found. Corvin and colleagues [21] conducted a family study using WGS of 35 individuals across 6 pedigrees that revealed deleterious missense variants in three genes (ATP2B2, SLC25A28, GSK3A) that co-segregated with disease status in three of the six pedigrees. ...

Schizophrenia risk conferred by rare protein-truncating variants is conserved across diverse human populations

Nature Genetics