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  1. Dodd S, Fish R, Gorst S, Hall D, Jacobsen P, Kirkham J, et al.
    HRB Open Res, 2021;4:45.
    PMID: 34368618 DOI: 10.12688/hrbopenres.13139.3
    Background: The COMET Initiative promotes the development and use of 'core outcome sets' (COS), agreed standardised sets of outcomes that should be measured and reported in all studies in a particular clinical condition. COS are determined by consensus amongst key stakeholders, including health professionals, policymakers and patients, ensuring that the priorities and expertise of these representatives inform the choice of the most important outcomes to measure for a given condition. There is increased recognition of the need to integrate COS across the healthcare system and with existing regulatory apparatus, to ensure that outcomes being recorded are those of key relevance to important stakeholders. The aim of this study is to assess the degree of concordance between outcomes recommended in COS for research and in guidance provided by two key regulators: US Food and Drug Administration (FDA) and the European Medicines Agency (EMA). Methods: COS for research published during 2015-2019 with patient involvement and covering drug or device interventions will be compared against relevant regulatory guidelines, matched by condition. Guidance documents matching in scope (relating to intervention and population) to a COS for research will be scrutinised to identify all suggested outcomes for comparison against the core outcomes in the corresponding COS. Discussion: This study will identify variation between outcomes suggested in FDA and EMA regulatory guidance relative to outcomes included in published COS for research, thus demonstrating the degree of representation of COS in regulatory guidance and vice versa. We will share the study findings (in particular, highlighting any lack of concordance between COS and regulatory guidance overall or for particular disease areas) and will invite feedback from FDA and EMA; we will seek to highlight where findings support the recommendations towards using well-developed COS or will make recommendations to COS developers on outcomes of importance to these key regulators.
  2. Saldanha IJ, Dodd S, Fish R, Gorst SL, Hall DA, Jacobsen P, et al.
    BMJ Med, 2022;1(1):e000233.
    PMID: 36936602 DOI: 10.1136/bmjmed-2022-000233
    OBJECTIVE: To compare the outcomes in published core outcome sets with the outcomes recommended in corresponding guidance documents from the European Medicines Agency (EMA) and US Food and Drug Administration (FDA), matched by health condition.

    DESIGN: Cross sectional analysis.

    SETTING: US and Europe.

    POPULATION: Sample of core outcome sets related to drugs, devices, and gene therapy that involved patients in the consensus process, published between 1 January 2015 and 31 December 2019; and corresponding EMA and FDA guidance documents.

    MAIN OUTCOME MEASURES: The extent of matches between outcomes included within core outcome sets and those recommended in corresponding EMA and FDA guidance documents were assessed. Matches were considered to be general (ie, non-specific) or specific (ie, exact). General matches were assessed to determine whether the core outcome set or guidance document outcome was narrower.

    RESULTS: Relevant guidance documents were found for for 38 (39%) of 98 eligible published core outcome sets. Among outcomes in core outcome sets, medians of 70% (interquartile range 48-86%) and 52% (33-77%) were matches with outcomes recommended in EMA and FDA documents, respectively. Medians of 46% (27-68%) and 26% (18-46%) were specific matches with outcomes in EMA and FDA documents, respectively. When outcomes were generally matched, the outcomes from core outcome sets were more frequently narrower than the regulatory outcomes (83% and 75% for EMA and FDA, respectively).

    CONCLUSION: Greater adoption of, and reference to, core outcome sets in regulatory guidance documents can encourage clinical trialists, especially those in industry, to measure and report consistent and agreed outcomes and improve the quality of guidance. Given the overlap between outcomes in core outcome sets and regulatory guidance, and given that most core outcome sets now involve patients in the consensus process, these sets could serve as a useful resource for regulators when recommending outcomes for studies evaluating regulated products. Developers are encouraged to appraise recommended outcomes in salient regulatory documents when planning a core outcome set.

  3. Bauer M, Glenn T, Alda M, Andreassen OA, Angelopoulos E, Ardau R, et al.
    Eur. Psychiatry, 2015 Jan;30(1):99-105.
    PMID: 25498240 DOI: 10.1016/j.eurpsy.2014.10.005
    PURPOSE: Two common approaches to identify subgroups of patients with bipolar disorder are clustering methodology (mixture analysis) based on the age of onset, and a birth cohort analysis. This study investigates if a birth cohort effect will influence the results of clustering on the age of onset, using a large, international database.

    METHODS: The database includes 4037 patients with a diagnosis of bipolar I disorder, previously collected at 36 collection sites in 23 countries. Generalized estimating equations (GEE) were used to adjust the data for country median age, and in some models, birth cohort. Model-based clustering (mixture analysis) was then performed on the age of onset data using the residuals. Clinical variables in subgroups were compared.

    RESULTS: There was a strong birth cohort effect. Without adjusting for the birth cohort, three subgroups were found by clustering. After adjusting for the birth cohort or when considering only those born after 1959, two subgroups were found. With results of either two or three subgroups, the youngest subgroup was more likely to have a family history of mood disorders and a first episode with depressed polarity. However, without adjusting for birth cohort (three subgroups), family history and polarity of the first episode could not be distinguished between the middle and oldest subgroups.

    CONCLUSION: These results using international data confirm prior findings using single country data, that there are subgroups of bipolar I disorder based on the age of onset, and that there is a birth cohort effect. Including the birth cohort adjustment altered the number and characteristics of subgroups detected when clustering by age of onset. Further investigation is needed to determine if combining both approaches will identify subgroups that are more useful for research.

  4. Bauer M, Glenn T, Alda M, Andreassen OA, Angelopoulos E, Ardau R, et al.
    J Affect Disord, 2014;167:104-11.
    PMID: 24953482 DOI: 10.1016/j.jad.2014.05.032
    The onset of bipolar disorder is influenced by the interaction of genetic and environmental factors. We previously found that a large increase in sunlight in springtime was associated with a lower age of onset. This study extends this analysis with more collection sites at diverse locations, and includes family history and polarity of first episode.
  5. Bauer M, Glenn T, Alda M, Andreassen OA, Angelopoulos E, Ardau R, et al.
    J Psychiatr Res, 2015 May;64:1-8.
    PMID: 25862378 DOI: 10.1016/j.jpsychires.2015.03.013
    Environmental conditions early in life may imprint the circadian system and influence response to environmental signals later in life. We previously determined that a large springtime increase in solar insolation at the onset location was associated with a younger age of onset of bipolar disorder, especially with a family history of mood disorders. This study investigated whether the hours of daylight at the birth location affected this association.
  6. Conell J, Bauer R, Glenn T, Alda M, Ardau R, Baune BT, et al.
    Int J Bipolar Disord, 2016 Dec;4(1):17.
    PMID: 27552813 DOI: 10.1186/s40345-016-0058-0
    BACKGROUND: Information seeking is an important coping mechanism for dealing with chronic illness. Despite a growing number of mental health websites, there is little understanding of how patients with bipolar disorder use the Internet to seek information.

    METHODS: A 39 question, paper-based, anonymous survey, translated into 12 languages, was completed by 1222 patients in 17 countries as a convenience sample between March 2014 and January 2016. All patients had a diagnosis of bipolar disorder from a psychiatrist. Data were analyzed using descriptive statistics and generalized estimating equations to account for correlated data.

    RESULTS: 976 (81 % of 1212 valid responses) of the patients used the Internet, and of these 750 (77 %) looked for information on bipolar disorder. When looking online for information, 89 % used a computer rather than a smartphone, and 79 % started with a general search engine. The primary reasons for searching were drug side effects (51 %), to learn anonymously (43 %), and for help coping (39 %). About 1/3 rated their search skills as expert, and 2/3 as basic or intermediate. 59 % preferred a website on mental illness and 33 % preferred Wikipedia. Only 20 % read or participated in online support groups. Most patients (62 %) searched a couple times a year. Online information seeking helped about 2/3 to cope (41 % of the entire sample). About 2/3 did not discuss Internet findings with their doctor.

    CONCLUSION: Online information seeking helps many patients to cope although alternative information sources remain important. Most patients do not discuss Internet findings with their doctor, and concern remains about the quality of online information especially related to prescription drugs. Patients may not rate search skills accurately, and may not understand limitations of online privacy. More patient education about online information searching is needed and physicians should recommend a few high quality websites.

  7. Bauer M, Glenn T, Alda M, Aleksandrovich MA, Andreassen OA, Angelopoulos E, et al.
    Acta Psychiatr Scand, 2017 Dec;136(6):571-582.
    PMID: 28722128 DOI: 10.1111/acps.12772
    OBJECTIVE: To confirm prior findings that the larger the maximum monthly increase in solar insolation in springtime, the younger the age of onset of bipolar disorder.

    METHOD: Data were collected from 5536 patients at 50 sites in 32 countries on six continents. Onset occurred at 456 locations in 57 countries. Variables included solar insolation, birth-cohort, family history, polarity of first episode and country physician density.

    RESULTS: There was a significant, inverse association between the maximum monthly increase in solar insolation at the onset location, and the age of onset. This effect was reduced in those without a family history of mood disorders and with a first episode of mania rather than depression. The maximum monthly increase occurred in springtime. The youngest birth-cohort had the youngest age of onset. All prior relationships were confirmed using both the entire sample, and only the youngest birth-cohort (all estimated coefficients P < 0.001).

    CONCLUSION: A large increase in springtime solar insolation may impact the onset of bipolar disorder, especially with a family history of mood disorders. Recent societal changes that affect light exposure (LED lighting, mobile devices backlit with LEDs) may influence adaptability to a springtime circadian challenge.

  8. Bauer R, Glenn T, Strejilevich S, Conell J, Alda M, Ardau R, et al.
    Int J Bipolar Disord, 2018 Sep 04;6(1):20.
    PMID: 30178112 DOI: 10.1186/s40345-018-0127-7
    BACKGROUND: The world population is aging and the number of older adults with bipolar disorder is increasing. Digital technologies are viewed as a framework to improve care of older adults with bipolar disorder. This analysis quantifies Internet use by older adults with bipolar disorder as part of a larger survey project about information seeking.

    METHODS: A paper-based survey about information seeking by patients with bipolar disorder was developed and translated into 12 languages. The survey was anonymous and completed between March 2014 and January 2016 by 1222 patients in 17 countries. All patients were diagnosed by a psychiatrist. General estimating equations were used to account for correlated data.

    RESULTS: Overall, 47% of older adults (age 60 years or older) used the Internet versus 87% of younger adults (less than 60 years). More education and having symptoms that interfered with regular activities increased the odds of using the Internet, while being age 60 years or older decreased the odds. Data from 187 older adults and 1021 younger adults were included in the analysis excluding missing values.

    CONCLUSIONS: Older adults with bipolar disorder use the Internet much less frequently than younger adults. Many older adults do not use the Internet, and technology tools are suitable for some but not all older adults. As more health services are only available online, and more digital tools are developed, there is concern about growing health disparities based on age. Mental health experts should participate in determining the appropriate role for digital tools for older adults with bipolar disorder.

  9. Bauer R, Conell J, Glenn T, Alda M, Ardau R, Baune BT, et al.
    Psychiatry Res, 2016 08 30;242:388-394.
    PMID: 27391371 DOI: 10.1016/j.psychres.2016.05.055
    There is considerable international interest in online education of patients with bipolar disorder, yet little understanding of how patients use the Internet and other sources to seek information. 1171 patients with a diagnosis of bipolar disorder in 17 countries completed a paper-based, anonymous survey. 81% of the patients used the Internet, a percentage similar to the general public. Older age, less education, and challenges in country telecommunications infrastructure and demographics decreased the odds of using the Internet. About 78% of the Internet users looked online for information on bipolar disorder or 63% of the total sample. More years of education in relation to the country mean, and feeling very confident about managing life decreased the odds of seeking information on bipolar disorder online, while having attended support groups increased the odds. Patients who looked online for information on bipolar disorder consulted medical professionals plus a mean of 2.3 other information sources such as books, physician handouts, and others with bipolar disorder. Patients not using the Internet consulted medical professionals plus a mean of 1.6 other information sources. The percentage of patients with bipolar disorder who use the Internet is about the same as the general public. Other information sources remain important.
  10. Bauer R, Conell J, Glenn T, Alda M, Ardau R, Baune BT, et al.
    Nord J Psychiatry, 2017 Aug;71(6):473-476.
    PMID: 28696841 DOI: 10.1080/08039488.2017.1334819
    BACKGROUND: Peer support is an established component of recovery from bipolar disorder, and online support groups may offer opportunities to expand the use of peer support at the patient's convenience. Prior research in bipolar disorder has reported value from online support groups.

    AIMS: To understand the use of online support groups by patients with bipolar disorder as part of a larger project about information seeking.

    METHODS: The results are based on a one-time, paper-based anonymous survey about information seeking by patients with bipolar disorder, which was translated into 12 languages. The survey was completed between March 2014 and January 2016 and included questions on the use of online support groups. All patients were diagnosed by a psychiatrist. Analysis included descriptive statistics and general estimating equations to account for correlated data.

    RESULTS AND CONCLUSIONS: The survey was completed by 1222 patients in 17 countries. The patients used the Internet at a percentage similar to the general public. Of the Internet users who looked online for information about bipolar disorder, only 21.0% read or participated in support groups, chats, or forums for bipolar disorder (12.8% of the total sample). Given the benefits reported in prior research, clarification of the role of online support groups in bipolar disorder is needed. With only a minority of patients using online support groups, there are analytical challenges for future studies.

  11. Bauer M, Glenn T, Alda M, Andreassen OA, Angelopoulos E, Ardau R, et al.
    J Psychiatr Res, 2019 06;113:1-9.
    PMID: 30878786 DOI: 10.1016/j.jpsychires.2019.03.001
    In many international studies, rates of completed suicide and suicide attempts have a seasonal pattern that peaks in spring or summer. This exploratory study investigated the association between solar insolation and a history of suicide attempt in patients with bipolar I disorder. Solar insolation is the amount of electromagnetic energy from the Sun striking a surface area on Earth. Data were collected previously from 5536 patients with bipolar I disorder at 50 collection sites in 32 countries at a wide range of latitudes in both hemispheres. Suicide related data were available for 3365 patients from 310 onset locations in 51 countries. 1047 (31.1%) had a history of suicide attempt. There was a significant inverse association between a history of suicide attempt and the ratio of mean winter solar insolation/mean summer solar insolation. This ratio is smallest near the poles where the winter insolation is very small compared to the summer insolation. This ratio is largest near the equator where there is relatively little variation in the insolation over the year. Other variables in the model that were positively associated with suicide attempt were being female, a history of alcohol or substance abuse, and being in a younger birth cohort. Living in a country with a state-sponsored religion decreased the association. (All estimated coefficients p 
  12. Bauer M, Glenn T, Achtyes ED, Alda M, Agaoglu E, Altınbaş K, et al.
    Int J Bipolar Disord, 2021 Sep 01;9(1):26.
    PMID: 34467430 DOI: 10.1186/s40345-021-00231-7
    BACKGROUND: Bipolar disorder is associated with circadian disruption and a high risk of suicidal behavior. In a previous exploratory study of patients with bipolar I disorder, we found that a history of suicide attempts was associated with differences between winter and summer levels of solar insolation. The purpose of this study was to confirm this finding using international data from 42% more collection sites and 25% more countries.

    METHODS: Data analyzed were from 71 prior and new collection sites in 40 countries at a wide range of latitudes. The analysis included 4876 patients with bipolar I disorder, 45% more data than previously analyzed. Of the patients, 1496 (30.7%) had a history of suicide attempt. Solar insolation data, the amount of the sun's electromagnetic energy striking the surface of the earth, was obtained for each onset location (479 locations in 64 countries).

    RESULTS: This analysis confirmed the results of the exploratory study with the same best model and slightly better statistical significance. There was a significant inverse association between a history of suicide attempts and the ratio of mean winter insolation to mean summer insolation (mean winter insolation/mean summer insolation). This ratio is largest near the equator which has little change in solar insolation over the year, and smallest near the poles where the winter insolation is very small compared to the summer insolation. Other variables in the model associated with an increased risk of suicide attempts were a history of alcohol or substance abuse, female gender, and younger birth cohort. The winter/summer insolation ratio was also replaced with the ratio of minimum mean monthly insolation to the maximum mean monthly insolation to accommodate insolation patterns in the tropics, and nearly identical results were found. All estimated coefficients were significant at p 

  13. Bauer M, Glenn T, Achtyes ED, Alda M, Agaoglu E, Altınbaş K, et al.
    Int J Bipolar Disord, 2023 Jun 22;11(1):22.
    PMID: 37347392 DOI: 10.1186/s40345-023-00303-w
    BACKGROUND: Sunlight contains ultraviolet B (UVB) radiation that triggers the production of vitamin D by skin. Vitamin D has widespread effects on brain function in both developing and adult brains. However, many people live at latitudes (about > 40 N or S) that do not receive enough UVB in winter to produce vitamin D. This exploratory study investigated the association between the age of onset of bipolar I disorder and the threshold for UVB sufficient for vitamin D production in a large global sample.

    METHODS: Data for 6972 patients with bipolar I disorder were obtained at 75 collection sites in 41 countries in both hemispheres. The best model to assess the relation between the threshold for UVB sufficient for vitamin D production and age of onset included 1 or more months below the threshold, family history of mood disorders, and birth cohort. All coefficients estimated at P ≤ 0.001.

    RESULTS: The 6972 patients had an onset in 582 locations in 70 countries, with a mean age of onset of 25.6 years. Of the onset locations, 34.0% had at least 1 month below the threshold for UVB sufficient for vitamin D production. The age of onset at locations with 1 or more months of less than or equal to the threshold for UVB was 1.66 years younger.

    CONCLUSION: UVB and vitamin D may have an important influence on the development of bipolar disorder. Study limitations included a lack of data on patient vitamin D levels, lifestyles, or supplement use. More study of the impacts of UVB and vitamin D in bipolar disorder is needed to evaluate this supposition.

  14. N Fountoulakis K, N Karakatsoulis G, Abraham S, Adorjan K, Ahmed HU, Alarcón RD, et al.
    Soc Psychiatry Psychiatr Epidemiol, 2023 Sep;58(9):1387-1410.
    PMID: 36867224 DOI: 10.1007/s00127-023-02438-8
    INTRODUCTION: The current study aimed to investigate the rates of anxiety, clinical depression, and suicidality and their changes in health professionals during the COVID-19 outbreak.

    MATERIALS AND METHODS: The data came from the larger COMET-G study. The study sample includes 12,792 health professionals from 40 countries (62.40% women aged 39.76 ± 11.70; 36.81% men aged 35.91 ± 11.00 and 0.78% non-binary gender aged 35.15 ± 13.03). Distress and clinical depression were identified with the use of a previously developed cut-off and algorithm, respectively.

    STATISTICAL ANALYSIS: Descriptive statistics were calculated. Chi-square tests, multiple forward stepwise linear regression analyses, and Factorial Analysis of Variance (ANOVA) tested relations among variables.

    RESULTS: Clinical depression was detected in 13.16% with male doctors and 'non-binary genders' having the lowest rates (7.89 and 5.88% respectively) and 'non-binary gender' nurses and administrative staff had the highest (37.50%); distress was present in 15.19%. A significant percentage reported a deterioration in mental state, family dynamics, and everyday lifestyle. Persons with a history of mental disorders had higher rates of current depression (24.64% vs. 9.62%; p 

  15. Fountoulakis KN, Karakatsoulis GN, Abraham S, Adorjan K, Ahmed HU, Alarcón RD, et al.
    CNS Spectr, 2024 Apr;29(2):126-149.
    PMID: 38269574 DOI: 10.1017/S1092852924000026
    BACKGROUND: The prevalence of medical illnesses is high among patients with psychiatric disorders. The current study aimed to investigate multi-comorbidity in patients with psychiatric disorders in comparison to the general population. Secondary aims were to investigate factors associated with metabolic syndrome and treatment appropriateness of mental disorders.

    METHODS: The sample included 54,826 subjects (64.73% females; 34.15% males; 1.11% nonbinary gender) from 40 countries (COMET-G study). The analysis was based on the registration of previous history that could serve as a fair approximation for the lifetime prevalence of various medical conditions.

    RESULTS: About 24.5% reported a history of somatic and 26.14% of mental disorders. Mental disorders were by far the most prevalent group of medical conditions. Comorbidity of any somatic with any mental disorder was reported by 8.21%. One-third to almost two-thirds of somatic patients were also suffering from a mental disorder depending on the severity and multicomorbidity. Bipolar and psychotic patients and to a lesser extent depressives, manifested an earlier (15-20 years) manifestation of somatic multicomorbidity, severe disability, and probably earlier death. The overwhelming majority of patients with mental disorders were not receiving treatment or were being treated in a way that was not recommended. Antipsychotics and antidepressants were not related to the development of metabolic syndrome.

    CONCLUSIONS: The finding that one-third to almost two-thirds of somatic patients also suffered from a mental disorder strongly suggests that psychiatry is the field with the most trans-specialty and interdisciplinary value and application points to the importance of teaching psychiatry and mental health in medical schools and also to the need for more technocratically oriented training of psychiatric residents.

  16. Bauer M, Glenn T, Achtyes ED, Alda M, Agaoglu E, Altınbaş K, et al.
    J Psychosom Res, 2022 Sep;160:110982.
    PMID: 35932492 DOI: 10.1016/j.jpsychores.2022.110982
    OBJECTIVE: Circadian rhythm disruption is commonly observed in bipolar disorder (BD). Daylight is the most powerful signal to entrain the human circadian clock system. This exploratory study investigated if solar insolation at the onset location was associated with the polarity of the first episode of BD I. Solar insolation is the amount of electromagnetic energy from the Sun striking a surface area of the Earth.

    METHODS: Data from 7488 patients with BD I were collected at 75 sites in 42 countries. The first episode occurred at 591 onset locations in 67 countries at a wide range of latitudes in both hemispheres. Solar insolation values were obtained for every onset location, and the ratio of the minimum mean monthly insolation to the maximum mean monthly insolation was calculated. This ratio is largest near the equator (with little change in solar insolation over the year), and smallest near the poles (where winter insolation is very small compared to summer insolation). This ratio also applies to tropical locations which may have a cloudy wet and clear dry season, rather than winter and summer.

    RESULTS: The larger the change in solar insolation throughout the year (smaller the ratio between the minimum monthly and maximum monthly values), the greater the likelihood the first episode polarity was depression. Other associated variables were being female and increasing percentage of gross domestic product spent on country health expenditures. (All coefficients: P ≤ 0.001).

    CONCLUSION: Increased awareness and research into circadian dysfunction throughout the course of BD is warranted.

  17. Fountoulakis KN, Vrublevska J, Abraham S, Adorjan K, Ahmed HU, Alarcón RD, et al.
    J Affect Disord, 2024 May 01;352:536-551.
    PMID: 38382816 DOI: 10.1016/j.jad.2024.02.050
    BACKGROUND: The COVID-19 pandemic has brought significant mental health challenges, particularly for vulnerable populations, including non-binary gender individuals. The COMET international study aimed to investigate specific risk factors for clinical depression or distress during the pandemic, also in these special populations.

    METHODS: Chi-square tests were used for initial screening to select only those variables which would show an initial significance. Risk Ratios (RR) were calculated, and a Multiple Backward Stepwise Linear Regression Analysis (MBSLRA) was followed with those variables given significant results at screening and with the presence of distress or depression or the lack of both of them.

    RESULTS: The most important risk factors for depression were female (RR = 1.59-5.49) and non-binary gender (RR = 1.56-7.41), unemployment (RR = 1.41-6.57), not working during lockdowns (RR = 1.43-5.79), bad general health (RR = 2.74-9.98), chronic somatic disorder (RR = 1.22-5.57), history of mental disorders (depression RR = 2.31-9.47; suicide attempt RR = 2.33-9.75; psychosis RR = 2.14-10.08; Bipolar disorder RR = 2.75-12.86), smoking status (RR = 1.15-5.31) and substance use (RR = 1.77-8.01). The risk factors for distress or depression that survived MBSLRA were younger age, being widowed, living alone, bad general health, being a carer, chronic somatic disorder, not working during lockdowns, being single, self-reported history of depression, bipolar disorder, self-harm, suicide attempts and of other mental disorders, smoking, alcohol, and substance use.

    CONCLUSIONS: Targeted preventive interventions are crucial to safeguard the mental health of vulnerable groups, emphasizing the importance of diverse samples in future research.

    LIMITATIONS: Online data collection may have resulted in the underrepresentation of certain population groups.

  18. Fountoulakis KN, Karakatsoulis G, Abraham S, Adorjan K, Ahmed HU, Alarcón RD, et al.
    Eur Neuropsychopharmacol, 2022 Jan;54:21-40.
    PMID: 34758422 DOI: 10.1016/j.euroneuro.2021.10.004
    INTRODUCTION: There are few published empirical data on the effects of COVID-19 on mental health, and until now, there is no large international study.

    MATERIAL AND METHODS: During the COVID-19 pandemic, an online questionnaire gathered data from 55,589 participants from 40 countries (64.85% females aged 35.80 ± 13.61; 34.05% males aged 34.90±13.29 and 1.10% other aged 31.64±13.15). Distress and probable depression were identified with the use of a previously developed cut-off and algorithm respectively.

    STATISTICAL ANALYSIS: Descriptive statistics were calculated. Chi-square tests, multiple forward stepwise linear regression analyses and Factorial Analysis of Variance (ANOVA) tested relations among variables.

    RESULTS: Probable depression was detected in 17.80% and distress in 16.71%. A significant percentage reported a deterioration in mental state, family dynamics and everyday lifestyle. Persons with a history of mental disorders had higher rates of current depression (31.82% vs. 13.07%). At least half of participants were accepting (at least to a moderate degree) a non-bizarre conspiracy. The highest Relative Risk (RR) to develop depression was associated with history of Bipolar disorder and self-harm/attempts (RR = 5.88). Suicidality was not increased in persons without a history of any mental disorder. Based on these results a model was developed.

    CONCLUSIONS: The final model revealed multiple vulnerabilities and an interplay leading from simple anxiety to probable depression and suicidality through distress. This could be of practical utility since many of these factors are modifiable. Future research and interventions should specifically focus on them.

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