Toward an Extended Definition of Major Depressive Disorder Symptomatology: Digital Assessment and Cross-validation Study.

BACKGROUND: Diagnosing major depressive disorder (MDD) is challenging, with diagnostic manuals failing to capture the wide range of clinical symptoms that are endorsed by individuals with this condition. OBJECTIVE: This study aims to provide evidence for an extended definition of MDD symptomatology. METHODS: Symptom data were collected via a digital assessment developed for a delta study. Random forest classification with nested cross-validation was used to distinguish between individuals with MDD and those with subthreshold symptomatology of the disorder using disorder-specific symptoms and transdiagnostic symptoms. The diagnostic performance of the Patient Health Questionnaire-9 was also examined. RESULTS: A depression-specific model demonstrated good predictive performance when distinguishing between individuals with MDD (n=64) and those with subthreshold depression (n=140) (area under the receiver operating characteristic curve=0.89; sensitivity=82.4%; specificity=81.3%; accuracy=81.6%). The inclusion of transdiagnostic symptoms of psychopathology, including symptoms of depression, generalized anxiety disorder, insomnia, emotional instability, and panic disorder, significantly improved the model performance (area under the receiver operating characteristic curve=0.95; sensitivity=86.5%; specificity=90.8%; accuracy=89.5%). The Patient Health Questionnaire-9 was excellent at identifying MDD but overdiagnosed the condition (sensitivity=92.2%; specificity=54.3%; accuracy=66.2%). CONCLUSIONS: Our findings are in line with the notion that current diagnostic practices may present an overly narrow conception of mental health. Furthermore, our study provides proof-of-concept support for the clinical utility of a digital assessment to inform clinical decision-making in the evaluation of MDD

The Delta Study - Prevalence and characteristics of mood disorders in 924 individuals with low mood: Results of the of the World Health Organization Composite International Diagnostic Interview (CIDI).

OBJECTIVES: The Delta Study was undertaken to improve the diagnosis of mood disorders in individuals presenting with low mood. The current study aimed to estimate the prevalence and explore the characteristics of mood disorders in participants of the Delta Study, and discuss their implications for clinical practice. METHODS: Individuals with low mood (Patients Health Questionnaire-9 score ≥5) and either no previous mood disorder diagnosis (baseline low mood group, n = 429), a recent (≤5 years) clinical diagnosis of MDD (baseline MDD group, n = 441) or a previous clinical diagnosis of BD (established BD group, n = 54), were recruited online. Self-reported demographic and clinical data were collected through an extensive online mental health questionnaire and mood disorder diagnoses were determined with the World Health Organization Composite International Diagnostic Interview (CIDI). RESULTS: The prevalence of BD and MDD in the baseline low mood group was 24% and 36%, respectively. The prevalence of BD among individuals with a recent diagnosis of MDD was 31%. Participants with BD in both baseline low mood and baseline MDD groups were characterized by a younger age at onset of the first low mood episode, more severe depressive symptoms and lower wellbeing, relative to the MDD or low mood groups. Approximately half the individuals with BD diagnosed as MDD (49%) had experienced (hypo)manic symptoms prior to being diagnosed with MDD. CONCLUSIONS: The current results confirm high under- and misdiagnosis rates of mood disorders in individuals presenting with low mood, potentially leading to worsening of symptoms and decreased well-being, and indicate the need for improved mental health triage in primary care

A machine learning algorithm to differentiate bipolar disorder from major depressive disorder using an online mental health questionnaire and blood biomarker data.

The vast personal and economic burden of mood disorders is largely caused by their under- and misdiagnosis, which is associated with ineffective treatment and worsening of outcomes. Here, we aimed to develop a diagnostic algorithm, based on an online questionnaire and blood biomarker data, to reduce the misdiagnosis of bipolar disorder (BD) as major depressive disorder (MDD). Individuals with depressive symptoms (Patient Health Questionnaire-9 score ≥5) aged 18-45 years were recruited online. After completing a purpose-built online mental health questionnaire, eligible participants provided dried blood spot samples for biomarker analysis and underwent the World Health Organization World Mental Health Composite International Diagnostic Interview via telephone, to establish their mental health diagnosis. Extreme Gradient Boosting and nested cross-validation were used to train and validate diagnostic models differentiating BD from MDD in participants who self-reported a current MDD diagnosis. Mean test area under the receiver operating characteristic curve (AUROC) for separating participants with BD diagnosed as MDD (N = 126) from those with correct MDD diagnosis (N = 187) was 0.92 (95% CI: 0.86-0.97). Core predictors included elevated mood, grandiosity, talkativeness, recklessness and risky behaviour. Additional validation in participants with no previous mood disorder diagnosis showed AUROCs of 0.89 (0.86-0.91) and 0.90 (0.87-0.91) for separating newly diagnosed BD (N = 98) from MDD (N = 112) and subclinical low mood (N = 120), respectively. Validation in participants with a previous diagnosis of BD (N = 45) demonstrated sensitivity of 0.86 (0.57-0.96). The diagnostic algorithm accurately identified patients with BD in various clinical scenarios, and could help expedite accurate clinical diagnosis and treatment of BD

A machine learning algorithm to differentiate bipolar disorder from major depressive disorder using an online mental health questionnaire and blood biomarker data

The vast personal and economic burden of mood disorders is largely caused by their under- and misdiagnosis, which is associated with ineffective treatment and worsening of outcomes. Here, we aimed to develop a diagnostic algorithm, based on an online questionnaire and blood biomarker data, to reduce the misdiagnosis of bipolar disorder (BD) as major depressive disorder (MDD). Individuals with depressive symptoms (Patient Health Questionnaire-9 score >= 5) aged 18-45 years were recruited online. After completing a purpose-built online mental health questionnaire, eligible participants provided dried blood spot samples for biomarker analysis and underwent the World Health Organization World Mental Health Composite International Diagnostic Interview via telephone, to establish their mental health diagnosis. Extreme Gradient Boosting and nested cross-validation were used to train and validate diagnostic models differentiating BD from MDD in participants who self-reported a current MDD diagnosis. Mean test area under the receiver operating characteristic curve (AUROC) for separating participants with BD diagnosed as MDD (N = 126) from those with correct MDD diagnosis (N = 187) was 0.92 (95% CI: 0.86-0.97). Core predictors included elevated mood, grandiosity, talkativeness, recklessness and risky behaviour. Additional validation in participants with no previous mood disorder diagnosis showed AUROCs of 0.89 (0.86-0.91) and 0.90 (0.87-0.91) for separating newly diagnosed BD (N = 98) from MDD (N = 112) and subclinical low mood (N = 120), respectively. Validation in participants with a previous diagnosis of BD (N = 45) demonstrated sensitivity of 0.86 (0.57-0.96). The diagnostic algorithm accurately identified patients with BD in various clinical scenarios, and could help expedite accurate clinical diagnosis and treatment of BD

A machine learning algorithm to differentiate bipolar disorder from major depressive disorder using an online mental health questionnaire and blood biomarker data.

The vast personal and economic burden of mood disorders is largely caused by their under- and misdiagnosis, which is associated with ineffective treatment and worsening of outcomes. Here, we aimed to develop a diagnostic algorithm, based on an online questionnaire and blood biomarker data, to reduce the misdiagnosis of bipolar disorder (BD) as major depressive disorder (MDD). Individuals with depressive symptoms (Patient Health Questionnaire-9 score ≥5) aged 18-45 years were recruited online. After completing a purpose-built online mental health questionnaire, eligible participants provided dried blood spot samples for biomarker analysis and underwent the World Health Organization World Mental Health Composite International Diagnostic Interview via telephone, to establish their mental health diagnosis. Extreme Gradient Boosting and nested cross-validation were used to train and validate diagnostic models differentiating BD from MDD in participants who self-reported a current MDD diagnosis. Mean test area under the receiver operating characteristic curve (AUROC) for separating participants with BD diagnosed as MDD (N = 126) from those with correct MDD diagnosis (N = 187) was 0.92 (95% CI: 0.86-0.97). Core predictors included elevated mood, grandiosity, talkativeness, recklessness and risky behaviour. Additional validation in participants with no previous mood disorder diagnosis showed AUROCs of 0.89 (0.86-0.91) and 0.90 (0.87-0.91) for separating newly diagnosed BD (N = 98) from MDD (N = 112) and subclinical low mood (N = 120), respectively. Validation in participants with a previous diagnosis of BD (N = 45) demonstrated sensitivity of 0.86 (0.57-0.96). The diagnostic algorithm accurately identified patients with BD in various clinical scenarios, and could help expedite accurate clinical diagnosis and treatment of BD

The Delta Study – Prevalence and characteristics of mood disorders in 924 individuals with low mood: Results of the of the World Health Organization Composite International Diagnostic Interview (CIDI)

Abstract Objectives The Delta Study was undertaken to improve the diagnosis of mood disorders in individuals presenting with low mood. The current study aimed to estimate the prevalence and explore the characteristics of mood disorders in participants of the Delta Study, and discuss their implications for clinical practice. Methods Individuals with low mood (Patients Health Questionnaire‐9 score ≥5) and either no previous mood disorder diagnosis (baseline low mood group, n = 429), a recent (≤5 years) clinical diagnosis of MDD (baseline MDD group, n = 441) or a previous clinical diagnosis of BD (established BD group, n = 54), were recruited online. Self‐reported demographic and clinical data were collected through an extensive online mental health questionnaire and mood disorder diagnoses were determined with the World Health Organization Composite International Diagnostic Interview (CIDI). Results The prevalence of BD and MDD in the baseline low mood group was 24% and 36%, respectively. The prevalence of BD among individuals with a recent diagnosis of MDD was 31%. Participants with BD in both baseline low mood and baseline MDD groups were characterized by a younger age at onset of the first low mood episode, more severe depressive symptoms and lower wellbeing, relative to the MDD or low mood groups. Approximately half the individuals with BD diagnosed as MDD (49%) had experienced (hypo)manic symptoms prior to being diagnosed with MDD. Conclusions The current results confirm high under‐ and misdiagnosis rates of mood disorders in individuals presenting with low mood, potentially leading to worsening of symptoms and decreased well‐being, and indicate the need for improved mental health triage in primary care

Metabolomic Biomarker Signatures for Bipolar and Unipolar Depression.

IMPORTANCE: Bipolar disorder (BD) is frequently misdiagnosed as major depressive disorder (MDD) because of overlapping symptoms and the lack of objective diagnostic tools. OBJECTIVE: To identify a reproducible metabolomic biomarker signature in patient dried blood spots (DBSs) that differentiates BD from MDD during depressive episodes and assess its added value when combined with self-reported patient information. DESIGN, SETTING, AND PARTICIPANTS: This diagnostic analysis used samples and data from the Delta study, conducted in the UK between April 27, 2018, and February 6, 2020. The primary objective was to identify BD in patients with a recent (within the past 5 years) diagnosis of MDD and current depressive symptoms (Patient Health Questionnaire-9 score of 5 or more). Participants were recruited online through voluntary response sampling. The analysis was carried out between February 2022 and July 2023. MAIN OUTCOMES AND MEASURES: Patient data were collected using a purpose-built online questionnaire (n = 635 questions). DBS metabolites (n = 630) were analyzed using a targeted mass spectrometry-based platform. Mood disorder diagnoses were established using the Composite International Diagnostic Interview. RESULTS: Of 241 patients in the discovery cohort, 170 (70.5%) were female; 67 (27.8%) were subsequently diagnosed with BD and 174 (72.2%) were confirmed as having MDD; and the mean (SD) age was 28.1 (7.1) years. Of 30 participants in the validation cohort, 16 (53%) were female; 9 (30%) were diagnosed with BD and 21 (70%) with MDD; and the mean (SD) age was 25.4 (6.3) years. DBS metabolite levels were assessed in 241 patients with depressive symptoms with a recent diagnosis of MDD, of whom 67 were subsequently diagnosed with BD by the Composite International Diagnostic Interview and 174 were confirmed as having MDD. The identified 17-biomarker panel provided a mean (SD) cross-validated area under the receiver operating characteristic curve (AUROC) of 0.71 (SD, 0.12; P < .001), with ceramide d18:0/24:1 emerging as the strongest biomarker. Combining biomarker data with patient-reported information significantly enhanced diagnostic performance of models based on extensive demographic data, PHQ-9 scores, and the outcomes from the Mood Disorder Questionnaire. The identified biomarkers were correlated primarily with lifetime manic symptoms and were validated in a separate group of patients who received a new clinical diagnosis of MDD (n = 21) or BD (n = 9) during the study's 1-year follow-up period, with a mean (SD) AUROC of 0.73 (0.06; P < .001). CONCLUSIONS AND RELEVANCE: This study provides a proof of concept for developing an accessible biomarker test to facilitate the differential diagnosis of BD and MDD and highlights the potential involvement of ceramides in the pathophysiological mechanisms of mood disorders.This work was supported by Stanley Medical Research Institute (grant number 07R-1888) and Psyomics Ltd

A Combined Digital and Biomarker Diagnostic Aid for Mood Disorders (the Delta Trial): Protocol for an Observational Study

Background: Mood disorders affect hundreds of millions of people worldwide, imposing a substantial medical and economic burden. Existing diagnostic methods for mood disorders often result in a delay until accurate diagnosis, exacerbating the challenges of these disorders. Advances in digital tools for psychiatry and understanding the biological basis of mood disorders offer the potential for novel diagnostic methods that facilitate early and accurate diagnosis of patients