Augustus John Rush

• M.D.
• Professor Emeritus at Duke-NUS Medical School

Acylcarnitines (ACs) are involved in bioenergetics processes that may play a role in the pathophysiology of depression. Previous genomic evidence identified four ACs potentially linked to depression risk. We carried forward these ACs and tested the association of their circulating levels with Major Depressive Disorder (MDD) diagnosis, overall depre...

Objective Bile acids may contribute to pathophysiologic markers of Alzheimer’s disease, including disruptions of the executive control network (ECN) and the default mode network (DMN). Cognitive dysfunction is common in major depressive disorder (MDD), but whether bile acids impact these networks in MDD patients is unknown. Methods Resting state f...

Background The 9-item Concise Health Risk Tracking – Self-Report (CHRT-SR 9 ) is a widely used patient-reported outcome measure of suicidal risk. The goal of this article is to provide an evidence-based interpretation of the CHRT-SR 9 total score in terms of four clinically actionable categories of suicidal risk (none, mild, moderate, and severe)....

Major Depressive Disorder (MDD) is a common, frequently chronic condition characterized by substantial molecular alterations and pathway dysregulations. Single metabolite and targeted metabolomics platforms have revealed several metabolic alterations in depression, including energy metabolism, neurotransmission, and lipid metabolism. More comprehen...

Metabolomics provides powerful tools that can inform about heterogeneity in disease and response to treatments. In this study, we employed an electrochemistry-based targeted metabolomics platform to assess the metabolic effects of three randomly-assigned treatments: escitalopram, duloxetine, and Cognitive Behavior Therapy (CBT) in 163 treatment-nai...

Purpose Major depressive disorder (MDD) is a leading cause of disability worldwide. An accurate assessment of depressive symptomology is crucial for clinical management and research. This study assessed the convergent validity, reliability, and total scale score interconversion across the 9-item Patient Health Questionnaire (PHQ-9) self-report, the...

Background The prevalence and associated overdose death rates from opioid use disorder (OUD) have dramatically increased in the last decade. Despite more available treatments than 20 years ago, treatment access and high discontinuation rates are challenges, as are personalized medication dosing and making timely treatment changes when treatments fa...

Background: Acylcarnitines (ACs) are involved in bioenergetics processes that may play a role in the pathophysiology of depression. Studies linking AC levels to depression are few and provide mixed findings. We examined the association of circulating ACs levels with Major Depressive Disorder (MDD) diagnosis, overall depression severity and specific...

Background Major depressive disorder (MDD) is common worldwide and can be highly disabling. People with MDD face many barriers to treatment and may not experience full symptom relief even when treated. Therefore, new treatment modalities are needed for MDD. Digital therapeutics (DTx) may provide people with MDD an additional treatment option. Obje...

BACKGROUND Major depressive disorder (MDD) is common worldwide and can be highly disabling. People with MDD face many barriers to treatment and may not experience full symptom relief even when treated. Therefore, new treatment modalities are needed for MDD. Digital therapeutics (DTx) may provide people with MDD an additional treatment option. OBJE...

Background Profiling patients on a proposed ‘immunometabolic depression’ (IMD) dimension, described as a cluster of atypical depressive symptoms related to energy regulation and immunometabolic dysregulations, may optimise personalised treatment. AimsTo test the hypothesis that baseline IMD features predict poorer treatment outcomes with antidepres...

Objective: To evaluate psychometrically and provide crosswalks between 3 self-report measures of depressive symptomatology in youth in psychiatric care settings. Ratings included the Patient Health Questionnaire for Adolescents (PHQ-A), a widely used 9-item self-report; the 16-item Quick Inventory of Depressive Symptomatology-Self-Report (QIDS-SR16...

Objective Characteristics of difficult-to-treat depression (DTD), including infrequent symptom remission and poor durability of benefit, compel reconsideration of the outcome metrics historically used to gauge the effectiveness of antidepressant interventions. Methods Self-report and clinician assessments of depression symptom severity were obtain...

Background Major depressive disorder (MDD) contributes to suicide risk. Treating MDD effectively is considered a key suicide prevention intervention. Yet many patients with MDD do not respond to their initial medication and require a ‘next-step’. The relationship between next-step treatments and suicidal thoughts and behaviors is uncharted. Method...

Major Depressive Disorder (MDD) is an often-chronic condition with substantial molecular alterations and pathway dysregulations involved. Single metabolite, pathway and targeted metabolomics platforms have indeed revealed several metabolic alterations in depression including energy metabolism, neurotransmission and lipid metabolism. More comprehens...

Scurvy is often considered to be a historical disease that once affected sailors, and so its modern-day prevalence is underestimated. Scurvy can present in various ways, such as with mucocutaneous and/or hematological symptoms in classic scurvy or with isolated psychiatric symptoms in neuropsychiatric scurvy. We describe two patient presentations o...

This report examines the predictive capabilities of two scales of suicidality in high-risk adolescents. Charts of adolescents with severe suicidality participating in an intensive outpatient program were reviewed. Self-report data from the 9-item Concise Health Risk Tracking Self-Report (CHRT-SR9) and clinician-completed data from the Columbia Suic...

Objective The current study aimed to evaluate the psychometric features of the Quick Inventory of Depressive Symptomatology, Adolescent version (QIDS-A17) and the clinician-rated Children’s Depression Rating Scale-Revised (CDRS-R). Methods Altogether, 103 outpatients (8 to 17 years) completed the self-report QIDS-A17-SR. Clinician interviews of ad...

Purpose Life engagement encompasses concepts such as life fulfillment, well-being, and participation in meaningful activities, encompassing cognitive, physical, social, and emotional dimensions. Patients with MDD experience impaired functioning across multiple domains of life engagement and have ranked concepts related to life engagement and fulfil...

Intentional foreign body ingestions (FBIs) are commonly seen in adult patients with intellectual disabilities, substance use, severe psychiatric conditions, or external motivations, but these cases are rarely reported in the psychiatric literature. We present the case of a patient with an extensive history of FBIs and suicide attempts and a multitu...

Purpose To evaluate the psychometric properties of a 9-item Concise Health Risk Tracking Self-Report (or CHRT-SR9) to assess suicidal risk in adult primary care outpatients. Methods Overall, 369 adults completed the original 14-item version of CHRT-SR at baseline and within 4 months thereafter, from which the CHRT-SR9 was extracted using multigrou...

Background: This study evaluated the psychometric properties of the 9-item Concise Health Risk Tracking Self-Report (CHRT-SR9), a measure of suicidality, in adolescent psychiatric outpatients. Methods: Altogether, 933 depressed or suicidal adolescents (12-20 years of age), receiving treatment at psychiatric outpatient clinics in Texas, completed...

Background: In difficult-to-treat depression (DTD) the outcome metrics historically used to evaluate treatment effectiveness may be suboptimal. Metrics based on remission status and on single end-point (SEP) assessment may be problematic given infrequent symptom remission, temporal instability, and poor durability of benefit in DTD. Methods: Sel...

Background: To address the clinical heterogeneity of Major Depressive Disorder (MDD), this investigation determined whether resting state functional magnetic resonance imaging (fMRI) could be deployed to identify circuit based homogeneous subgroups, and whether subgroups identified show differential treatment outcomes. Methods: Pretreatment rest...

Background: Artificial intelligence is currently being used to facilitate early disease detection, better understand disease progression, optimize medication/treatment dosages, and uncover promising novel treatments and potential outcomes. Methods: Utilizing the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) dataset, we built a...

Objectives: This observational retrospective real-world study examined changes in healthcare resource utilization (HCRU) pre- and post-initiation of aripiprazole once-monthly (AOM 400) in patients with schizophrenia or bipolar I disorder. Methods: Electronic health record-derived, de-identified data from the NeuroBlu Database (2013-2020) were used...

Background: Psilocybin is being studied for use in treatment-resistant depression. Methods: In this phase 2 double-blind trial, we randomly assigned adults with treatment-resistant depression to receive a single dose of a proprietary, synthetic formulation of psilocybin at a dose of 25 mg, 10 mg, or 1 mg (control), along with psychological suppo...

Objectives The Concise Health Risk Tracking Self‐Report (CHRT‐SR) assesses the risk of suicidal behavior. We report its psychometric properties in a representative sample of adolescent outpatients. Methods A sample (n = 657) of adolescents (<18 years of age) in primary or psychiatric care completed the 14‐item version of CHRT‐SR at both baseline a...

Subjective responses to psychoactive drugs have served as intriguing windows into consciousness as well as useful predictors. Subjective reactions to psychedelic molecules are particularly interesting given how they covary with subsequent improvements associated with psychedelic-assisted treatments. Although links between subjective reactions and d...

Heroin-induced toxic leukoencephalopathy (TLE) is an uncommon condition that presents with nonspecific and variable neuropsychiatric findings. It may result in satisfactory recovery or death. Traditionally referred to as “chasing the dragon” syndrome and associated with inhalation of pyrolyzed heroin, recent publications have reported forms of the...

Introduction EHRs contain a rich source of real-world data that can support evidence generation to better understand mental disorders and improve treatment outcomes. However, EHR datasets are complex and include unstructured free text data that are time consuming to manually review and analyse. We present NeuroBlu, a secure, cloud-based analytic to...

Background The gut microbiome may play a role in the pathogenesis of neuropsychiatric diseases including major depressive disorder (MDD). Bile acids (BAs) are steroid acids that are synthesized in the liver from cholesterol and further processed by gut-bacterial enzymes, thus requiring both human and gut microbiome enzymatic processes in their meta...

Background: Many patients with major depressive disorder (MDD) who experience no meaningful benefit (NMB) from antidepressive treatment go undetected. However, there is a lack of consensus on the definition of NMB from antidepressants. Methods: Equipercentile linking was used to identify a threshold for percent change in 17-item Hamilton Depressio...

Pediatric Quality of Life Enjoyment and Satisfaction Questionnaire is a brief 15-item self-report measure of quality of life and life satisfaction originally developed for clinical populations (6 to 17 years old). The current paper examines the initial factor structure proposed by the developers and underlying psychometric properties of the measure...

Purpose: NeuroBlu is a real-world data (RWD) repository that contains deidentified electronic health record (EHR) data from US mental healthcare providers operating the MindLinc EHR system. NeuroBlu enables users to perform statistical analysis through a secure web-based interface. Structured data are available for sociodemographic characteristics,...

Background The gut microbiome may play a role in the pathogenesis of neuropsychiatric diseases including major depressive disorder (MDD). Bile acids (BAs) are steroid acids that are synthesized in the liver from cholesterol and further processed by gut-bacterial enzymes, thus requiring both human and gut microbiome enzymatic processes in their meta...

Background Altered metabolism of acylcarnitines – transporting fatty acids to mitochondria – may link cellular energy dysfunction to depression. We examined the potential causal role of acylcarnitine metabolism in depression by leveraging genomics and Mendelian randomization. Methods Summary statistics were obtained from large GWAS: the Fenland St...

Purpose: Evaluate the psychometric properties of the 5-item Very Quick Inventory of Depressive Symptomatology self-report and clinician-rated versions (VQIDS-SR5/VQIDS-C5), compare their relative performance, create crosswalks between their total scores and other accepted depressive symptom ratings, and define clinically relevant depressive sympto...

Background Major depressive disorder (MDD) is a highly heterogenous disease, both in terms of clinical profiles and pathobiological alterations. Recently, immunometabolic dysregulations were shown to be correlated with atypical, energy-related symptoms but less so with the Melancholic or Anxious distress symptom dimensions of depression in The Neth...

Approximately one-third of individuals in a major depressive episode will not achieve sustained remission despite multiple, well-delivered treatments. These patients experience prolonged suffering and disproportionately utilize mental and general health care resources. The recently proposed clinical heuristic of ‘difficult-to-treat depression’ (DTD...

Background Altered metabolism of acylcarnitines – transporting fatty acids to mitochondria – may link cellular energy dysfunction to depression. We examined the potential causal role of acylcarnitine metabolism in depression by leveraging genomics and Mendelian randomization. Methods Summary statistics were obtained from large GWAS: the Fenland St...

Several magnetic resonance imaging (MRI) studies have reported reduction in anterior cingulate cortex (ACC) volume in individuals with major depressive disorder (MDD). However, some MRI studies did not find significant ACC volumetric changes in MDD, and sample sizes were generally small. This cross-sectional structural MRI study examined the relati...

Purpose To describe attrition patterns of opioid use disorder (OUD) patients treated with buprenorphine (BUP) and to assess how clinical, sociodemographic, or BUP medication dosing features are associated with attrition. Patients and Methods Electronic health records of adults (16+ year-olds) with OUD treated with BUP from 23 different substance u...

It is unknown whether indoles, metabolites of tryptophan that are derived entirely from bacterial metabolism in the gut, are associated with symptoms of depression and anxiety. Serum samples (baseline, 12 weeks) were drawn from participants (n = 196) randomized to treatment with cognitive behavioral therapy (CBT), escitalopram, or duloxetine for ma...

Morbidity and mortality from opioid use disorders (OUD) and other substance use disorders (SUD) is a major public health crisis, yet there are few medications to treat them. There is an urgency to accelerate SUD medication development. We present an integrated drug repurposing strategy that combines computational prediction, clinical corroboration...

Background: Major depressive disorder (MDD) is a highly heterogenous disease, both in terms of clinical profiles and pathobiological alterations. Recently, immunometabolic dysregulations were shown to be correlated with atypical, energy-related symptoms but less so with the Melancholic or Anxious distress symptom dimensions of depression in The Net...

Side effects to antidepressant medications are common and can impact the prognosis of successful treatment outcome in people with major depressive disorder (MDD). However, few studies have investigated the severity of side effects over the course of treatment and their association with treatment outcome. Here we assessed the severity of side effect...

Objective To develop clinically meaningful improvement thresholds in both the 17-item and the 6-item Hamilton Rating Scale for Depression (HRSD) total scores in depressed outpatients. Methods The post-hoc analysis included all adult outpatients with non-psychotic major depressive disorder in the STAR*D trial who entered and exited the first treatm...

Selective serotonin reuptake inhibitors (SSRIs) are the first-line treatment for major depressive disorder (MDD), yet their mechanisms of action are not fully understood and their therapeutic benefit varies among individuals. We used a targeted metabolomics approach utilizing a panel of 180 metabolites to gain insights into mechanisms of action and...

Measurement-based care (MBC) involves the systematic use of standardized measurements to inform treatment decisions. MBC can enhance clinical decision-making and quality of care by prompting personalized changes in treatment based on measured patient outcomes. MBC can also promote more precise communications between patients and clinicians around i...

Background : While childhood maltreatment (CMT) is associated with higher rates of chronicity and recurrence in depression, whether CMT results in poorer outcomes with antidepressant medication remains unclear. Methods : We performed secondary analyses with data from the large, representative, multisite trial Combining Medications to Enhance Depre...

Using pre-treatment biomarkers to guide patients to the preferred antidepressant medication treatment could be a promising approach to enhance its current modest response and remission rates. This open-label prospective study assessed the feasibility of using such pre-treatment biomarkers, by using previously identified EEG features (paroxysmal act...

Heterogeneity in the clinical presentation of major depressive disorder and response to antidepressants limits clinicians’ ability to accurately predict a specific patient’s eventual response to therapy. Validated depressive symptom profiles may be an important tool for identifying poor outcomes early in the course of treatment. To derive these sym...

Background The use of naltrexone plus bupropion to treat methamphetamine use disorder has not been well studied. Methods We conducted this multisite, double-blind, two-stage, placebo-controlled trial with the use of a sequential parallel comparison design to evaluate the efficacy and safety of extended-release injectable naltrexone (380 mg every 3...

Psychiatric practice routinely uses semistructured and/or unstructured free text to record the behavior and mental state of patients. Many of these data are unstructured, lack standardization, and are difficult to use for analysis. Thus, it is difficult to quantitatively analyze a patient’s illness trajectory over time and his or her responsiveness...

Purpose The Vagus Nerve Stimulation (VNS) Therapy System has been studied for more than 20 years in patients with severe, treatment-resistant, chronic mood disorder, i.e., difficult-to-treat depression (DTD). This review distills some of the implications of this research for future therapeutic trials in this population. Methods A narrative review...

Background It is unknown whether indoles, metabolites of tryptophan that are derived entirely from bacterial metabolism in the gut, are associated with symptoms of depression and anxiety. Methods Serum samples (baseline, 12 weeks) were drawn from participants (n=196) randomized to treatment with cognitive behavioral therapy (CBT), escitalopram, or...

Objective : To identify data-driven subgroups in Major Depressive Disorder (MDD) in order to elucidate underlying neural correlates and determine if these subgroups have utility in predicting response to antidepressant versus placebo. Methods : Using 27 clinical measures at baseline of Establishing Moderators and Biosignatures of Antidepressant Re...

Objective To use the Clinical Global Impression–Severity (CGI‐S) scale to estimate clinically meaningful and clinically substantial changes as measured using the Montgomery‐Åsberg Depression Rating Scale (MADRS), the Sheehan Disability Scale (SDS), and the Patient Health Questionnaire‐9 (PHQ‐9) in patients with treatment‐resistant depression (TRD)....

Introduction Resilience is a factor in how youth respond to adversity. The 88-item Adolescent Resilience Questionnaire is a comprehensive, multi-dimensional self-report measure of resilience developed with Australian youth. Methods Using a cross-sectional adolescent population (n = 3,222), confirmatory factor analysis was conducted to replicate th...

In 2008 the National Institutes of Health established the Research, Condition and Disease Categorization Database (RCDC) that reports the amount spent by NIH institutes for each disease. Its goal is to allow the public “to know how the NIH spends their tax dollars,” but it has been little used. The RCDC for 2018 was used to assess 428 schizophrenia...