Publications by authors named "Enda Byrne"

Background: Genetic vulnerability to mental disorders has been associated with coronavirus disease-19 (COVID-19) outcomes. We explored whether polygenic risk scores (PRSs) for several mental disorders predicted poorer clinical and psychological COVID-19 outcomes in people with pre-existing depression.

Methods: Data from three assessments of the Australian Genetics of Depression Study ( = 4405; 52.

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Article Synopsis
  • The COVID-19 pandemic led to increased flexibility in sleep-wake schedules, significantly impacting sleep patterns, especially in individuals with a history of depression.
  • Before the pandemic, 70% of participants reported optimal sleep (6-8 hours), but this dropped to 49% during the pandemic, with many shifting to either short (<6 hours) or long sleep (>8 hours).
  • Factors like pre-pandemic mental health, insomnia, and stressful life events were linked to the shift to short sleep, while no significant predictors were found for those who moved to long sleep, suggesting the need for targeted interventions for affected individuals.
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  • - The study aimed to explore the genetic basis of major depressive disorder by analyzing symptoms across various clinical and community cohorts, acknowledging challenges like sample size differences and missing data patterns.
  • - Researchers performed genome-wide association studies using data from both diagnosed and undiagnosed participants, fitting models to understand the relationships between different depressive symptoms.
  • - Findings emphasized the relevance of symptom directionality (e.g., hypersomnia vs. insomnia) and the necessity of considering study design when analyzing genetic data related to depression.
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The concept of ultra-high risk for psychosis (UHR) has been at the forefront of psychiatric research for several decades, with the ultimate goal of preventing the onset of psychotic disorder in high-risk individuals. Orygen (Melbourne, Australia) has led a range of observational and intervention studies in this clinical population. These datasets have now been integrated into the UHR 1000+ cohort, consisting of a sample of 1,245 UHR individuals with a follow-up period ranging from 1 to 16.

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Melancholia has been proposed as a qualitatively distinct depressive subtype associated with a characteristic symptom profile (psychomotor retardation, profound anhedonia) and a better response to biological therapies. Existing work has suggested that individuals with melancholia are blunted in their display of positive emotions and differ in their neural response to emotionally evocative stimuli. Here, we unify these brain and behavioural findings amongst a carefully phenotyped group of seventy depressed participants, drawn from an established Australian database (the Australian Genetics of Depression Study) and further enriched for melancholia (high ratings of psychomotor retardation and anhedonia).

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  • * A genome-wide association meta-analysis of nearly 122,000 ANX cases revealed 58 significant genetic variants and 66 related genes, with many of these findings replicated in a larger independent sample.
  • * The findings indicate a substantial genetic overlap between ANX and other conditions like depression, emphasizing GABAergic signaling as a key mechanism, thereby enhancing our understanding of the genetic basis of ANX for future research.
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  • Obsessive-compulsive disorder (OCD) affects about 1% of people and has a strong genetic component, but previous studies have not fully explained its genetic causes or biological mechanisms.
  • A large genome-wide association study (GWAS) analyzed data from over 53,000 OCD cases and over 2 million control participants, identifying 30 significant genetic markers related to OCD and suggesting a 6.7% heritability from SNPs.
  • The research also found 249 candidate risk genes linked to OCD, particularly in specific brain regions, and showed genetic correlations with various psychiatric disorders, laying the groundwork for further studies and potential treatments.
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Introduction: Major depression (MD) is more common amongst women than men, and MD episodes have been associated with fluctuations in reproductive hormones amongst women. To investigate biological underpinnings of heterogeneity in MD, the associations between depression, stratified by sex and including perinatal depression (PND), and blood biomarkers, using UK Biobank (UKB) data, were evaluated, and extended to include the association of depression with biomarker polygenic scores (PGS), generated as proxy for each biomarker.

Method: Using female ( = 39,761) and male ( = 38,821) UKB participants, lifetime MD and PND were tested for association with 28 blood biomarkers.

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The dominant ('general') version of the diathesis-stress theory of depression views stressors and genetic vulnerability as independent risks. In the Australian Genetics of Depression Study (N = 14,146; 75% female), we tested whether polygenic scores (PGS) for major depression, bipolar disorder, schizophrenia, anxiety, ADHD, and neuroticism were associated with reported exposure to 32 childhood, past-year, lifetime, and accumulated stressful life events (SLEs). In false discovery rate-corrected models, the clearest PGS-SLE relationships were for the ADHD- and depression-PGSs, and to a lesser extent, the anxiety- and schizophrenia-PGSs.

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Background: Preliminary evidence suggests that evening chronotype is related to poorer efficacy of selective serotonin reuptake inhibitors. It is unknown whether this is specific to particular medications, self-rated chronotype, or efficacy.

Methods: In the Australian Genetics of Depression Study (n = 15,108; 75% women; 18-90 years; 68% with ≥1 other lifetime diagnosis), a survey recorded experiences with 10 antidepressants, and the reduced Morningness-Eveningness Questionnaire was used to estimate chronotype.

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Article Synopsis
  • - A new multi-ancestry genome-wide association study (GWAS) of major depression (MD) analyzed data from 88,316 cases and 902,757 controls, representing various ancestries including African, East Asian, South Asian, and Hispanic/Latin American.
  • - The study discovered 53 novel genetic loci significantly linked to MD, with fewer existing European ancestry loci proving relevant to other ancestry groups.
  • - A transcriptome-wide association study in this research identified 205 new genes associated with MD, highlighting the importance of diverse ancestry in genetic research for better understanding and finding relevant genes.
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Problematic alcohol use (PAU), a trait that combines alcohol use disorder and alcohol-related problems assessed with a questionnaire, is a leading cause of death and morbidity worldwide. Here we conducted a large cross-ancestry meta-analysis of PAU in 1,079,947 individuals (European, N = 903,147; African, N = 122,571; Latin American, N = 38,962; East Asian, N = 13,551; and South Asian, N = 1,716 ancestries). We observed a high degree of cross-ancestral similarity in the genetic architecture of PAU and identified 110 independent risk variants in within- and cross-ancestry analyses.

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Background: Multimodal modeling that combines biological and clinical data shows promise in predicting transition to psychosis in individuals who are at ultra-high risk. Individuals who transition to psychosis are known to have deficits at baseline in cognitive function and reductions in gray matter volume in multiple brain regions identified by magnetic resonance imaging.

Methods: In this study, we used Cox proportional hazards regression models to assess the additive predictive value of each modality-cognition, cortical structure information, and the neuroanatomical measure of brain age gap-to a previously developed clinical model using functioning and duration of symptoms prior to service entry as predictors in the Personal Assessment and Crisis Evaluation (PACE) 400 cohort.

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Background: Factors influencing antidepressant treatment discontinuation are poorly understood. In the present study, we aimed to estimate the prevalence of antidepressant treatment discontinuation and identify demographic characteristics, psychiatric comorbidities, and specific side effects associated with treatment discontinuation.

Methods: We leveraged data from the Australian Genetics of Depression Study (AGDS; N = 20,941) to perform a retrospective cohort study on antidepressant treatment discontinuation.

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Article Synopsis
  • The study focuses on postpartum depression (PPD), a hereditary form of major depressive disorder, using genome-wide association studies (GWAS) to explore its genetic basis across various populations.
  • It analyzed data from 18,770 PPD cases and 58,461 controls, finding no single-nucleotide polymorphisms (SNPs) that met genome-wide significance, though it highlighted significant genetic correlations with other mental health conditions.
  • The findings suggest that PPD is polygenic and heritable, potentially involving unique genetic factors despite its close relationship with major depressive disorder and implicate specific brain neurons associated with its treatment.
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Aim: To examine whether polygenic risk scores (PRS) for neuroticism, depression, bipolar disorder and schizophrenia are higher in individuals manifesting trans-diagnostic risk factors for the development of major mental disorders and whether PRS enhance prediction of early onset full-threshold disorders.

Methods: Using data from the Brisbane Longitudinal Twin Study, we examined individual PRS for neuroticism, depression, bipolar disorder and schizophrenia, recorded evidence of subthreshold syndromes and family history of mood and/or psychotic disorders and noted progression to trans-diagnostic clinical caseness (onset of major mental disorders) at follow-up. We undertook multivariate, receiver operating curve and logistic regression analyses that were adjusted for known variables of influence (age, twin status, and so on).

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Introduction: Sex steroid hormone fluctuations may underlie both reproductive disorders and sex differences in lifetime depression prevalence. Previous studies report high comorbidity among reproductive disorders and between reproductive disorders and depression. This study sought to assess the multivariate genetic architecture of reproductive disorders and their loading onto a common genetic factor and investigated whether this latent factor shares a common genetic architecture with female depression, including perinatal depression (PND).

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  • Major depressive disorder shows varied symptoms, and genetic analysis can help identify specific subtypes and clinical profiles.
  • Challenges in integrating symptom data arise from differences in sample sizes and patterns of missing data in clinical vs. community groups.
  • The study used genome-wide association studies to find that a model including unique symptom factors and accounting for missing data best represented the symptoms of depression, highlighting the need to consider symptom directionality and study design when analyzing genetic data.
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Background: Traumatic experiences are associated with increased risk for major depressive disorder (MDD). This study sought to determine the extent that trauma exposure, depression polygenic risk scores (PRS), and their interaction are associated with MDD and individual depression symptoms.

Methods: Data from 102,182 individuals from the large-scale UK Biobank population cohort was analysed.

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Problematic alcohol use (PAU) is a leading cause of death and disability worldwide. To improve our understanding of the genetics of PAU, we conducted a large cross-ancestry meta-analysis of PAU in 1,079,947 individuals. We observed a high degree of cross-ancestral similarity in the genetic architecture of PAU and identified 110 independent risk variants in within- and cross-ancestry analyses.

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Samples can be prone to ascertainment and attrition biases. The Australian Genetics of Depression Study is a large publicly recruited cohort (n = 20,689) established to increase the understanding of depression and antidepressant treatment response. This study investigates differences between participants who donated a saliva sample or agreed to linkage of their records compared to those who did not.

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Objectives: This study sought to evaluate the prevalence, timing of onset and duration of symptoms of depression in the perinatal period (PND) in women with depression, according to whether they had a history of depression prior to their first perinatal period. We further sought to identify biopsychosocial correlates of perinatal symptoms in women with depression.

Design And Setting: The Australian Genetics of Depression Study is an online case cohort study of the aetiology of depression.

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