BackgroundAnxiety and depression are common, debilitating and costly. These disorders are influenced by multiple risk factors, from genes to psychological vulnerabilities and environmental stressors, but research is hampered by a lack of sufficiently large comprehensive studies. We are recruiting 40,000 individuals with lifetime depression or anxiety and broad assessment of risks to facilitate future research.MethodsThe Genetic Links to Anxiety and Depression (GLAD) Study (www.gladstudy.org.uk) recruits individuals with depression or anxiety into the NIHR Mental Health BioResource. Participants invited to join the study (via media campaigns) provide demographic, environmental and genetic data, and consent for medical record linkage and recontact.ResultsOnline recruitment was effective; 42,531 participants consented and 27,776 completed the questionnaire by end of July 2019. Participants’ questionnaire data identified very high rates of recurrent depression, severe anxiety, and comorbidity. Participants reported high rates of treatment receipt. The age profile of the sample is biased toward young adults, with higher recruitment of females and the more educated, especially at younger ages.DiscussionThis paper describes the study methodology and descriptive data for GLAD, which represents a large, recontactable resource that will enable future research into risks, outcomes, and treatment for anxiety and depression.

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Background: The COVID-19 pandemic is a novel population-level stressor. As such, it is important to examine pandemic-related changes in mental health and to identify which individuals are at greatest risk of worsening symptoms.Methods: Online questionnaires were administered to 34,465 individuals in the UK, recruited from existing cohorts or via social media. Around one third (n = 12,718) with prior diagnoses of depression or anxiety completed pre-pandemic mental health assessments, allowing prospective investigation of symptom change. We examined changes in depression, anxiety and PTSD symptoms using prospective, retrospective and global ratings of change assessments. We also examined the effect of key risk factors on changes in symptoms. Research in contextEvidence before this study We conducted a literature search (PubMed, Scopus) with the terms "mental*" or "psychiatr*" and "covid*" or "coronavirus" published before 8th February 2021. This resulted in 4,573 unique references, but only 15 longitudinal studies examining changes in symptoms of mental health conditions from before to during the COVID-19 pandemic. Results to date are mixed. Some studies found increases in mental distress, some found increases in either depression or anxiety, and others saw no observable change in symptoms.Examining individual-level risk factors, heightened vulnerability to worsening mental health during the pandemic has been demonstrated among young people, females, individuals with lower incomes/financial problems and among health care or key workers. Only one previous study used a large sample with prior mental health diagnoses to examine changes in anxiety and depression. This study showed that having a prior mental health diagnosis was associated with higher levels of perceived worsening of mental health but, when examining actual prospectively measured symptoms, a prior mental health diagnosis was actually associated with a lower likelihood of symptom worsening, compared to no prior diagnosis. This discrepancy across measures requires further investigation in order to understand the nature of changing mental health during the COVID-19 pandemic. Added value of this studyThis study prospectively examined changes in symptoms of depression, anxiety and PTSD in a large UK-based sample of individuals with prior depression or anxiety. Analyses were supplemented with data from additional cohorts to examine individual difference risk factors with greater statistical power. Inclusion of both prospectively measured and retrospectively estimated changes in symptoms, as well as ratings of perceived change in mental health, allowed closer examination of discrepancies in subjective experience versus actual objective change in symptoms.people who are students or are unemployed. Additionally, discrepancies in estimated symptom change across prospective and retrospective measures highlight the importance of using prospectively collected data to examine longitudinal changes.

Background: Anxiety and depression are common, debilitating and costly. These disorders are influenced by multiple risk factors, from genes to psychological vulnerabilities and environmental stressors but research is hampered by a lack of sufficiently large comprehensive studies. We are recruiting 40,000 individuals with lifetime depression or anxiety, with broad assessment of risks to facilitate future research. Methods: The Genetic Links to Anxiety and Depression (GLAD) Study (www.gladstudy.org.uk) recruits individuals with depression or anxiety into the NIHR Mental Health BioResource. Participants invited to join the study (via media campaigns) provide demographic, environmental and genetic data, and consent for medical record linkage and recontact. Results: Online recruitment was effective; 41,892 consented and 26,877 participants completed the questionnaire by July 2019. Participants' questionnaire data identified very high rates recurrent depression, severe anxiety and comorbidity. Participants reported high rates of treatment receipt. The age profile of sample is biased toward young adults, with higher recruitment of females and the better educated, especially at younger ages. Discussion: This paper describes the study methodology and descriptive data for GLAD, which represents a large, recontactable resource that will enable future research into risks, outcomes and treatment for anxiety and depression.

Objective: The disruption caused by the COVID-19 pandemic has been associated with poor mental health, including increases in eating disorders and self-harm symptoms. We investigated risk and protective factors for the new onset of these symptoms during the pandemic. Method: Data were from the COVID-19 Psychiatry and Neurological Genetics study and the Repeated Assessment of Mental health in Pandemics Study (n = 36,715).Exposures were socio-demographic characteristics, lifetime psychiatric disorder, and COVID-related variables, including SARS-CoV-2 infection/illness with COVID-19.We identified four subsamples of participants without pre-pandemic experience of our outcomes: binge eating (n = 24,211), low weight (n = 24,364), suicidal and/or

Background: Generalized anxiety and depression are extremely prevalent and debilitating. There is evidence for age and sex variability in symptoms of depression, but despite comorbidity it is unclear whether this extends to anxiety symptomatology. Studies using questionnaire sum scores typically fail to address this phenotypic complexity. Method: We conducted exploratory and confirmatory factor analyses on Generalized Anxiety Disorder (GAD-7) and Patient Health Questionnaire (PHQ-9) items to identify latent factors of anxiety and depression in participants from the Genetic Links to Anxiety and Depression Study (N = 35,637; 16-93 years). We assessed ageand sex-related variability in latent factors and individual symptoms using multiple logistic regression. Results: Four factors of mood, worry, motor, and somatic symptoms were identified (comparative fit index [CFI] = 0.99, Tucker-Lewis Index [TLI] = 0.99, root mean square error of approximation [RMSEA] = 0.07, standardized root mean square residuals [SRMR] = 0.04). Symptoms of irritability (odds ratio [OR] = 0.81) were most strongly associated with younger age, and sleep change (OR = 1.14) with older age.Males were more likely to report mood and motor symptoms (p < .001) and females to report somatic symptoms (p < .001). Conclusion:Significant age and sex variability suggest that classic diagnostic criteria reflect the presentation most commonly seen in younger males. This study provides avenues for diagnostic adaptation and factor-specific interventions.

Background: The COVID-19 pandemic is a novel population-level stressor. As such, it is important to examine pandemic-related changes in mental health and to identify which individuals are at greatest risk of worsening symptoms.Methods: Online questionnaires were administered to 34,465 individuals in the UK, recruited from existing cohorts or via social media. Around one third (n = 12,718) with prior diagnoses of depression or anxiety completed pre-pandemic mental health assessments, allowing prospective investigation of symptom change. We examined changes in depression, anxiety and PTSD symptoms using prospective, retrospective and global ratings of change assessments. We also examined the effect of key risk factors on changes in symptoms.Outcomes: Prospective analyses showed small decreases in depression (PHQ-9: - .43 points) and anxiety symptoms (GAD-7: -.33 points), and increases in PTSD symptoms (PCL-6: .22 points). Conversely, retrospective analyses demonstrated large significant increases in depression (2.40 points) and anxiety symptoms (1.97 points) and 55% reported worsening mental health since the beginning of the pandemic on a global change rating. Using both prospective and retrospective symptom measures, regression analyses demonstrated that worsening depression, anxiety and PTSD symptoms were associated with i) prior mental health diagnoses, ii) female gender; iii) young age, and iv) unemployed or student status.Interpretation: We highlight the effect of prior mental health diagnoses on worsening mental health during the pandemic and confirm previously-reported sociodemographic risk factors. Discrepancies between prospective and retrospective measures of changes in mental health may be related to recall bias underestimating prior symptom severity.

Background Reported trauma is associated with differences in the course and outcomes of depression and anxiety. However, no research has explored the association between reported trauma and patterns of clinically relevant symptoms of both depression and anxiety. Methods We used network analysis to investigate associations between reported trauma and depression and anxiety symptom interactions in affected individuals from the Genetic Links to Anxiety and Depression (GLAD) Study (n = 17720), and population volunteers from the UK Biobank (n = 11120). Participants with current moderate symptoms of depression or anxiety were grouped into reporters and non-reporters of lifetime trauma. Networks of 16 depression and anxiety symptoms in the two groups were compared using the network comparison test. Results In the GLAD Study, networks of reporters and non-reporters of lifetime trauma did not differ on any metric. In the UK Biobank, the symptom network of reporters had significantly greater density (7.80) than the network of non-reporters (7.05). Limitations The data collected in the GLAD Study and the UK Biobank are self-reported with validated or semi-validated questionnaires. Conclusions Reported lifetime trauma was associated with stronger interactions between symptoms of depression and anxiety in population volunteers. Differences between reporters and non-reporters may not be observed in individuals with severe depression and/or anxiety due to limited variance in the presentation of disorder.