Abraham Nunes

Abraham Nunes
Dalhousie University | Dal · Department of Psychiatry

MD PhD MBA FRCPC

About

49
Publications
10,422
Reads
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472
Citations
Introduction
My research falls broadly within the field of computational psychiatry, where I use both theory-driven and theory-free approaches to study the heterogeneity of psychopathology. My mathematical work on heterogeneity overlaps considerably with research in ecology (biodiversity), economics (wealth inequality), statistics (agreement measures), and statistical physics (generalized entropies).
Additional affiliations
July 2014 - present
Dalhousie University
Position
  • Medical Doctor
Education
September 2017 - May 2020
Dalhousie University
Field of study
  • Computer Science
September 2011 - April 2012
University of Alberta
Field of study
September 2009 - July 2014
University of Alberta
Field of study
  • Medicine

Publications

Publications (49)
Preprint
Full-text available
Bipolar disorder (BD) is a mood disorder involving recurring (hypo)manic and depressive episodes. The inherently temporal nature of BD has inspired its conceptualization using dynamical systems theory, which is a mathematical framework for understanding systems that evolve over time. In this paper we provide a critical review of dynamical systems m...
Article
Background Many individuals with eating disorders remain symptomatic after a course of psychotherapy and pharmacotherapy; therefore, the development of innovative treatments is essential. Method To learn more about the current evidence for treating eating disorders with stimulants, we searched for original articles and reviews published up to Apri...
Article
An improved understanding of genetic etiological heterogeneity in a psychiatric condition may help us (a) isolate a neurophysiological 'final common pathway' by identifying its upstream genetic origins and (b) facilitate characterization of the condition's phenotypic variation. This review aims to identify existing genetic heterogeneity measurement...
Article
Outpatient care (e.g., individual, group, or self‐help therapies) and day treatment programs (DTPs) are common and effective treatments for adults with eating disorders. Compared to outpatient care, DTPs have additional expenses and could have unintended iatrogenic effects (e.g., may create an overly protective environment that undermines self‐effi...
Article
Objective: This study examined the feasibility, safety, and potential efficacy of lisdexamfetamine (LDX) as a treatment for adults with bulimia nervosa (BN). Method: An open-label 8-week feasibility study was conducted in participants with BN. Enrollment rate, dropout rate, safety outcomes, and eating disorder symptom change were examined. Resu...
Article
Full-text available
Predicting lithium response prior to treatment could both expedite therapy and avoid exposure to side effects. Since lithium responsiveness may be heritable, its predictability based on genomic data is of interest. We thus evaluate the degree to which lithium response can be predicted with a machine learning (ML) approach using genomic data. Using...
Article
Full-text available
Predicting lithium response (LiR) in bipolar disorder (BD) may inform treatment planning, but phenotypic heterogeneity complicates discovery of genomic markers. We hypothesized that patients with “exemplary phenotypes”—those whose clinical features are reliably associated with LiR and non-response (LiNR)—are more genetically separable than those wi...
Article
Full-text available
Abstract This review summarizes the last decade of work by the ENIGMA (Enhancing NeuroImaging Genetics through Meta Analysis) Consortium, a global alliance of over 1400 scientists across 43 countries, studying the human brain in health and disease. Building on large-scale genetic studies that discovered the first robustly replicated genetic loci as...
Article
Full-text available
Heterogeneity is an important concept in psychiatric research and science more broadly. It negatively impacts effect size estimates under case–control paradigms, and it exposes important flaws in our existing categorical nosology. Yet, our field has no precise definition of heterogeneity proper. We tend to quantify heterogeneity by measuring associ...
Article
Full-text available
Normative modeling is an increasingly popular method for characterizing the ways in which clinical cohorts deviate from a reference population, with respect to one or more biological features. In this paper, we extend the normative modeling framework with an approach for measuring the amount of heterogeneity in a cohort. This heterogeneity measure...
Article
Full-text available
Bipolar disorders (BDs) are among the leading causes of morbidity and disability. Objective biological markers, such as those based on brain imaging, could aid in clinical management of BD. Machine learning (ML) brings neuroimaging analyses to individual subject level and may potentially allow for their diagnostic use. However, fair and optimal app...
Article
Full-text available
A system’s heterogeneity (diversity) is the effective size of its event space, and can be quantified using the Rényi family of indices (also known as Hill numbers in ecology or Hannah–Kay indices in economics), which are indexed by an elasticity parameter q≥0. Under these indices, the heterogeneity of a composite system (the γ-heterogeneity) is dec...
Article
Full-text available
MRI‐derived brain measures offer a link between genes, the environment and behavior and have been widely studied in bipolar disorder (BD). However, many neuroimaging studies of BD have been underpowered, leading to varied results and uncertainty regarding effects. The Enhancing Neuro Imaging Genetics through Meta‐Analysis (ENIGMA) Bipolar Disorder...
Preprint
Full-text available
This paper provides two arguments against the use of variance as a measure of heterogeneity. First, we show that variance does not satisfy the replication principle, which requires that if two random variables 1 and 2 have disjoint event spaces but equal heterogeneity ℎ, then a composite random variable˜, formed by pooling 1 and 2 , should have a h...
Preprint
Full-text available
Normative modeling is an increasingly popular method for characterizing the ways in which clinical cohorts deviate from a reference population, with respect to one or more biological features. In this paper, we extend the normative modeling framework with an approach for measuring the amount of heterogeneity in a cohort. This heterogeneity measure...
Preprint
Full-text available
Predicting lithium response (LiR) in bipolar disorder (BD) could expedite effective pharmacotherapy, but phenotypic heterogeneity of bipolar disorder has complicated the search for genomic markers. We thus sought to determine whether patients with "exemplary phenotypes"---those whose clinical features are reliably predictive of LiR and non-response...
Preprint
Full-text available
Heterogeneity is an important concept in psychiatric research and science more broadly. It negatively impacts effect size estimates under case-control paradigms, and it exposes important flaws in our existing categorical nosology. Yet, our field has no precise definition of heterogeneity proper. We tend to quantify heterogeneity by measuring associ...
Article
Background : Depressed patients with chronic and complex health issues commonly relapse; therefore, examining longer-term outcomes is an important consideration. For treatment resistant depression (TRD), the post-treatment efficacy of time-limited Intensive Short-Term Dynamic Psychotherapy (ISTDP) has been demonstrated but longer-term outcomes and...
Article
Full-text available
A discrete system’s heterogeneity is measured by the Rényi heterogeneity family of indices (also known as Hill numbers or Hannah–Kay indices), whose units are the numbers equivalent. Unfortunately, numbers equivalent heterogeneity measures for non-categorical data require a priori (A) categorical partitioning and (B) pairwise distance measurement o...
Preprint
Full-text available
A system's heterogeneity (\textit{diversity}) is the effective size of its event space, and can be quantified using the R\'enyi family of indices (also known as Hill numbers in ecology or Hannah-Kay indices in economics), which are indexed by an elasticity parameter $q \geq 0$. Under these indices, the heterogeneity of a composite system (the $\gam...
Article
Objective: To undertake a large-scale clinical study of predictors of lithium (Li) response in bipolar-I-disorder (BD-I) and apply contemporary multivariate approaches to account for inter-relationships between putative predictors. Methods: We used network analysis to estimate the number and strength of connections between potential predictors o...
Article
Full-text available
The Alda score is commonly used to quantify lithium responsiveness in bipolar disorder. Most often, this score is dichotomized into “responder” and “non-responder” categories, respectively. This practice is often criticized as inappropriate, since continuous variables are thought to invariably be “more informative” than their dichotomizations. We t...
Preprint
Full-text available
A discrete system's heterogeneity is measured by the R\'enyi heterogeneity family of indices (also known as Hill numbers or Hannah-Kay indices), whose units are known as the numbers equivalent, and whose scaling properties are consistent and intuitive. Unfortunately, numbers equivalent heterogeneity measures for non-categorical data require a prior...
Preprint
Full-text available
The Alda score is commonly used to quantify lithium responsiveness in bipolar disorder. Most often, this score is dichotomized into "responder" and "non-responder" categories, respectively. This practice is often criticized as inappropriate, since continuous variables are thought to invariably be "more informative" than their dichotomizations. We t...
Article
Objective: Promptly establishing maintenance therapy could reduce morbidity and mortality in patients with bipolar disorder. Using a machine learning approach, we sought to evaluate whether lithium responsiveness (LR) is predictable using clinical markers. Methods: Our data are the largest existing sample of direct interview-based clinical data...
Article
Machine learning (ML) is increasingly applied to bipolar disorders research, and one often encounters two questions about this approach (specifically the supervised form). The answers to these questions are relevant for the broader community to more critically appraise applied ML in psychiatry. This article is protected by copyright. All rights res...
Preprint
Full-text available
This review summarizes the last decade of work by the ENIGMA (Enhancing NeuroImaging Genetics throughMeta Analysis) Consortium, a global alliance of over 1,400 scientists across 43 countries, studying the humanbrain in health and disease. Building on large-scale genetic studies that discovered the first robustly replicatedgenetic loci associated wi...
Preprint
Full-text available
The relationship between clinical eating disorder symptom severity and balance of model-based (MB) and model-free (MF) control is unclear, and these traits' predictive capacity is untested in this population. In 25 healthy controls (HCs), 25 subjects with binge eating disorder (BED), and 25 subjects with bulimia nervosa (BN), we show an inverse rel...
Preprint
Full-text available
Mapping brain functions to their underlying neural substrates is a central goal of cognitive neuroscience. Functional magnetic resonance imaging (fMRI) has proven indispensable in this endeavour. Recently, there has been growing interest in tackling this problem by mapping semantic concepts onto brain regions using repositories of images and text f...
Preprint
Full-text available
Constrained optimization is often used to estimate the parameters of reinforcement learning models from human behavioural data. In this paper, we show that use of boundary constraints may artificially truncate parameter estimates, yielding worse performance than smooth penalty functions. View on arXiv: https://arxiv.org/abs/1803.09018
Article
Full-text available
Psychiatric neuroscience is increasingly aware of the need to define psychopathology in terms of abnormal neural computation. The central tool in this endeavour is the fitting of computational models to behavioural data. The most prominent example of this procedure is fitting reinforcement learning (RL) models to decision-making data collected from...
Conference Paper
Current evidence suggests that the brain uses multiple systems for instrumental control; these systems are known as \textit{model-based} and \textit{model-free}. The former predicts action-outcomes using an internal model of the agent's environment, while the latter learns to repeat previously rewarded actions. This paper proposes a neural architec...
Article
Background: Mechanical circulatory support (MCS) is an option for the treatment of medically intractable end-stage heart failure. MCS therapy, however, is resource intensive. Objective: The purpose of this report was to systematically review the MCS cost-effectiveness literature as it pertains to the treatment of adult patients in end-stage hear...
Article
Full-text available
Using Danish registry data, Kessing et al examined the relationship between lithium response and the timing of treatment (early v . delayed).[1][1] Early treatment was associated with an increased probability of lithium response. This is a clinically important finding, given the increasing emphasis
Article
Full-text available
Double aortic arch is a congenital anomaly that rarely presents in adults. We describe the case of a 69-year-old male who presented with a double aortic arch, right arch dominant, left arch patent, experiencing progressive dysphagia since childhood.
Article
Destination therapy with the HeartMate II left-ventricular assist device (Thoratec Corp, Pleasanton, CA) was undertaken in an adult patient with Down syndrome and end-stage heart failure. The patient was bridged to the HeartMate II with extracorporeal membrane oxygenation followed by the Levitronix CentriMag (Levitronix, Waltham, MA). HeartMate II...
Article
Full-text available
The purpose of this study was to compare the effects of sleep deprivation and rest on postural control. It was hypothesized that significant increases in COP deviations will occur after sleep deprivation. Methods. Four healthy adults (age= 21.50 years; mass= 68.93 kg) participated in two protocols involving sleep and sleep-deprivation. Within each...

Questions

Question (1)
Question
I.e. checklists such as what we would use in meta analyses for evaluating study quality, risk of bias, etc.

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Projects

Projects (3)
Project
Conceptual, mathematical, and applied work concerning the measurement of heterogeneity. On the applied side, a particular focus is placed on psychiatric research applications.
Project
Diagnostic and treatment prediction in bipolar disorder.
Project
To provide an easily accessible interface for methods to fit computational models to behavioural data. Install the PyPI release from terminal with "pip install fitr." Install the latest GitHub version with the following command: "pip install git+https://github.com/ComputationalPsychiatry/fitr.git" Tutorials can be found in the `examples` folder in our GitHub repo: https://github.com/ComputationalPsychiatry/fitr