Pub Date : 2024-05-10DOI: 10.1017/S0033291724001016
Eduard Vieta
The controversy on whether bipolar disorder is a neurodevelopmental versus a neuroprogressive illness is still around, despite some reductionistic claims that only one model is right. The current diagnostic classifications are not helpful to address this issue, and there is conflicting evidence in favor and against either model. In practice, though, understanding that many patients may show a progressive cognitive and functional decline which may be correlated with the number and severity of episodes may lead to better outcomes through early intervention strategies.
{"title":"Neuroprogression in bipolar disorder: why right is wrong.","authors":"Eduard Vieta","doi":"10.1017/S0033291724001016","DOIUrl":"https://doi.org/10.1017/S0033291724001016","url":null,"abstract":"<p><p>The controversy on whether bipolar disorder is a neurodevelopmental versus a neuroprogressive illness is still around, despite some reductionistic claims that only one model is right. The current diagnostic classifications are not helpful to address this issue, and there is conflicting evidence in favor and against either model. In practice, though, understanding that many patients may show a progressive cognitive and functional decline which may be correlated with the number and severity of episodes may lead to better outcomes through early intervention strategies.</p>","PeriodicalId":20891,"journal":{"name":"Psychological Medicine","volume":null,"pages":null},"PeriodicalIF":6.9,"publicationDate":"2024-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140899501","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-09DOI: 10.1017/S0033291724000746
R Effah, K Ioannidis, J E Grant, S R Chamberlain
Decision-making deficits, assessed cognitively, are often associated with mental health symptoms, however, this relationship is not fully understood. This paper explores the relationship between mental health disorders and decision-making, using the Cambridge Gambling Task (CGT). Our study investigated how decision-making varied across 20 different mental health conditions compared to controls in a sample of 572 young adults from the Minneapolis and Chicago metropolitan areas, using a computerized laboratory-based task. Almost all mental health conditions were associated with at least mild (i.e. at least small effect size) impairment in all three studied parameters of the CGT (risk adjustment, quality of decision-making and overall proportion of bet). Notably, binge eating disorder had the largest cognitive impairment and gambling disorder had moderate impairment. Post-traumatic stress disorder (PTSD) was associated with impaired decision-making while obsessive-compulsive disorder (OCD) and depression showed moderate impairment. Additionally, half of the disorders assessed had moderate to large impairment in risk adjustment.These findings suggest that mental health conditions may have a more complex cognitive profile than previously thought, and a better understanding of these impairments may aid in risk assessment and targeted clinical interventions. This study underscores the need for further research to determine the causal pathways between mental health conditions and cognition, as well as to better understand the day-to-day impact of such deficits.
{"title":"Exploring decision-making performance in young adults with mental health disorders: a comparative study using the Cambridge gambling task.","authors":"R Effah, K Ioannidis, J E Grant, S R Chamberlain","doi":"10.1017/S0033291724000746","DOIUrl":"https://doi.org/10.1017/S0033291724000746","url":null,"abstract":"<p><p>Decision-making deficits, assessed cognitively, are often associated with mental health symptoms, however, this relationship is not fully understood. This paper explores the relationship between mental health disorders and decision-making, using the Cambridge Gambling Task (CGT). Our study investigated how decision-making varied across 20 different mental health conditions compared to controls in a sample of 572 young adults from the Minneapolis and Chicago metropolitan areas, using a computerized laboratory-based task. Almost all mental health conditions were associated with at least mild (i.e. at least small effect size) impairment in all three studied parameters of the CGT (risk adjustment, quality of decision-making and overall proportion of bet). Notably, binge eating disorder had the largest cognitive impairment and gambling disorder had moderate impairment. Post-traumatic stress disorder (PTSD) was associated with impaired decision-making while obsessive-compulsive disorder (OCD) and depression showed moderate impairment. Additionally, half of the disorders assessed had moderate to large impairment in risk adjustment.These findings suggest that mental health conditions may have a more complex cognitive profile than previously thought, and a better understanding of these impairments may aid in risk assessment and targeted clinical interventions. This study underscores the need for further research to determine the causal pathways between mental health conditions and cognition, as well as to better understand the day-to-day impact of such deficits.</p>","PeriodicalId":20891,"journal":{"name":"Psychological Medicine","volume":null,"pages":null},"PeriodicalIF":6.9,"publicationDate":"2024-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140892396","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-09DOI: 10.1017/S0033291724001065
Kimmo Suokas, Maija Lindgren, Mika Gissler, Emmi Liukko, Laura Schildt, Raimo K R Salokangas, Päivi Rissanen, Tapio Gauffin, Petri Näätänen, Minna Holm, Jaana Suvisaari
Background: Timely outpatient follow-up and readmission after discharge are common quality indicators in psychiatric care, but their association varies in previous research. We aimed to examine whether the impact of outpatient follow-up and other factors on readmission risk evolves over time in people with non-affective psychotic disorder (NAP).
Methods: The Finnish Quality of Care Register includes all people diagnosed with NAP since January 2010. Here, we followed patients with a hospital discharge between 2017 and 2021 until readmission, death, or up to 365 days. Time of the first outpatient follow-up appointment, length of stay (LOS), number of previous hospitalizations, psychosis diagnosis, substance use disorder (SUD), residential status, economic activity, gender, age, year, and region were included. Follow-up time was divided into five periods: week 1, weeks 2-4, weeks 5-13, weeks 14-25, and weeks 26-52, and each period was analyzed separately with Cox regression.
Results: Of the 29 858 discharged individuals, 54.1% had an outpatient follow-up within a week. A total of 10 623 (35.6%) individuals were readmitted. Short LOS increased the readmission risk in the first four weeks, whereas lack of outpatient follow-up raised the risk (adjusted HRs between 1.15 (95% CI 1.04-1.26) and 1.53 (1.37-1.71) in weeks 5-52. The number of previous hospitalizations remained a consistent risk factor throughout the follow-up, while SUD increased risk after 4 weeks and living without family after 13 weeks.
Conclusions: Risk factors of readmission vary over time. These temporal patterns must be considered when developing outpatient treatment programs.
背景:及时的门诊随访和出院后的再入院是精神病治疗中常见的质量指标,但在以往的研究中它们之间的关系却各不相同。我们旨在研究门诊随访和其他因素对非情感性精神障碍(NAP)患者再入院风险的影响是否会随着时间的推移而变化:方法:芬兰医疗质量登记册包括了自2010年1月以来被诊断为非情感性精神障碍的所有患者。在此,我们对2017年至2021年期间出院的患者进行了跟踪调查,直至患者再次入院、死亡或最长365天。随访内容包括首次门诊随访时间、住院时间(LOS)、既往住院次数、精神病诊断、药物使用障碍(SUD)、居住状况、经济活动、性别、年龄、年份和地区。随访时间分为五个阶段:第1周、第2-4周、第5-13周、第14-25周和第26-52周,并对每个阶段分别进行了Cox回归分析:在 29 858 名出院者中,54.1% 在一周内进行了门诊随访。共有 10 623 人(35.6%)再次入院。住院时间短增加了前四周的再入院风险,而缺乏门诊随访则增加了第五至第五十二周的再入院风险(调整后的HRs介于1.15(95% CI 1.04-1.26)和1.53(1.37-1.71)之间)。在整个随访过程中,既往住院次数仍然是一个稳定的风险因素,而 SUD 在 4 周后会增加风险,13 周后无家人居住会增加风险:再次入院的风险因素随时间而变化。在制定门诊治疗计划时,必须考虑到这些时间模式。
{"title":"Factors contributing to readmission in patients with psychotic disorders, with a special reference to first follow-up visit in outpatient care.","authors":"Kimmo Suokas, Maija Lindgren, Mika Gissler, Emmi Liukko, Laura Schildt, Raimo K R Salokangas, Päivi Rissanen, Tapio Gauffin, Petri Näätänen, Minna Holm, Jaana Suvisaari","doi":"10.1017/S0033291724001065","DOIUrl":"https://doi.org/10.1017/S0033291724001065","url":null,"abstract":"<p><strong>Background: </strong>Timely outpatient follow-up and readmission after discharge are common quality indicators in psychiatric care, but their association varies in previous research. We aimed to examine whether the impact of outpatient follow-up and other factors on readmission risk evolves over time in people with non-affective psychotic disorder (NAP).</p><p><strong>Methods: </strong>The Finnish Quality of Care Register includes all people diagnosed with NAP since January 2010. Here, we followed patients with a hospital discharge between 2017 and 2021 until readmission, death, or up to 365 days. Time of the first outpatient follow-up appointment, length of stay (LOS), number of previous hospitalizations, psychosis diagnosis, substance use disorder (SUD), residential status, economic activity, gender, age, year, and region were included. Follow-up time was divided into five periods: week 1, weeks 2-4, weeks 5-13, weeks 14-25, and weeks 26-52, and each period was analyzed separately with Cox regression.</p><p><strong>Results: </strong>Of the 29 858 discharged individuals, 54.1% had an outpatient follow-up within a week. A total of 10 623 (35.6%) individuals were readmitted. Short LOS increased the readmission risk in the first four weeks, whereas lack of outpatient follow-up raised the risk (adjusted HRs between 1.15 (95% CI 1.04-1.26) and 1.53 (1.37-1.71) in weeks 5-52. The number of previous hospitalizations remained a consistent risk factor throughout the follow-up, while SUD increased risk after 4 weeks and living without family after 13 weeks.</p><p><strong>Conclusions: </strong>Risk factors of readmission vary over time. These temporal patterns must be considered when developing outpatient treatment programs.</p>","PeriodicalId":20891,"journal":{"name":"Psychological Medicine","volume":null,"pages":null},"PeriodicalIF":6.9,"publicationDate":"2024-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140892402","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-09DOI: 10.1017/S0033291724001156
Yi Dang, Bin Lu, Tamara Vanderwal, Francisco Xavier Castellanos, Chao-Gan Yan
Background: Major depressive disorder (MDD) is one of the most prevalent and disabling illnesses worldwide. Treatment of MDD typically relies on trial-and-error to find an effective approach. Identifying early response-related biomarkers that predict response to antidepressants would help clinicians to decide, as early as possible, whether a particular treatment might be suitable for a given patient.
Methods: Data were from the two-stage Establishing Moderators and Biosignatures of Antidepressant Response for Clinical Care (EMBARC) trial. A whole-brain, voxel-wise, mixed-effects model was applied to identify early-treatment cerebral blood flow (CBF) changes as biomarkers of treatment response. We examined changes in CBF measured with arterial spin labeling 1-week after initiating double-masked sertraline/placebo. We tested whether these early 1-week scans could be used to predict response observed after 8-weeks of treatment.
Results: Response to 8-week placebo treatment was associated with increased cerebral perfusion in temporal cortex and reduced cerebral perfusion in postcentral region captured at 1-week of treatment. Additionally, CBF response in these brain regions was significantly correlated with improvement in Hamilton Depression Rating Scale score in the placebo group. No significant associations were found for selective serotonin reuptake inhibitor treatment.
Conclusions: We conclude that early CBF responses to placebo administration in multiple brain regions represent candidate neural biomarkers of longer-term antidepressant effects.
{"title":"Early-treatment cerebral blood flow change as a predictive biomarker of antidepressant treatment response: evidence from the EMBARC clinical trial.","authors":"Yi Dang, Bin Lu, Tamara Vanderwal, Francisco Xavier Castellanos, Chao-Gan Yan","doi":"10.1017/S0033291724001156","DOIUrl":"https://doi.org/10.1017/S0033291724001156","url":null,"abstract":"<p><strong>Background: </strong>Major depressive disorder (MDD) is one of the most prevalent and disabling illnesses worldwide. Treatment of MDD typically relies on trial-and-error to find an effective approach. Identifying early response-related biomarkers that predict response to antidepressants would help clinicians to decide, as early as possible, whether a particular treatment might be suitable for a given patient.</p><p><strong>Methods: </strong>Data were from the two-stage Establishing Moderators and Biosignatures of Antidepressant Response for Clinical Care (EMBARC) trial. A whole-brain, voxel-wise, mixed-effects model was applied to identify early-treatment cerebral blood flow (CBF) changes as biomarkers of treatment response. We examined changes in CBF measured with arterial spin labeling 1-week after initiating double-masked sertraline/placebo. We tested whether these early 1-week scans could be used to predict response observed after 8-weeks of treatment.</p><p><strong>Results: </strong>Response to 8-week placebo treatment was associated with increased cerebral perfusion in temporal cortex and reduced cerebral perfusion in postcentral region captured at 1-week of treatment. Additionally, CBF response in these brain regions was significantly correlated with improvement in Hamilton Depression Rating Scale score in the placebo group. No significant associations were found for selective serotonin reuptake inhibitor treatment.</p><p><strong>Conclusions: </strong>We conclude that early CBF responses to placebo administration in multiple brain regions represent candidate neural biomarkers of longer-term antidepressant effects.</p>","PeriodicalId":20891,"journal":{"name":"Psychological Medicine","volume":null,"pages":null},"PeriodicalIF":6.9,"publicationDate":"2024-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140892376","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-09DOI: 10.1017/S0033291724000965
Jaehyuk Jung, Kyeong-Eun Lee, Seri Hong, Jae Bum Park, Inchul Jeong
Background: While unemployment is known to increase the risk of suicide, its cumulative effect remains underexplored. This study investigates how unemployment affects suicide mortality and whether the effect varies based on the number of unemployment spells using two years of nationwide data.
Methods: Using the data from the National Statistical Office and Employment Insurance Database for 2018 and 2019, we identified an average of 2365 cases of suicide over two years among 7.76 million workers aged 25-64 years who had been employed within one year before their suicide. The number of unemployment spells was counted using the employment history of the past five years. We calculated crude suicide mortality rates per 100 000 population, age- and sex- standardized mortality rates (SMRs), and proportionate mortality rates (PMRs) for suicide.
Results: Over the two years, the crude suicide rate was 30.0 per 100 000 among the general population and 30.5 among workers. Workers with no unemployment spells in the past five years had a significantly lower SMR (0.44; 0.42-0.46), while those with four or more unemployment spells had a significantly higher SMR (3.13; 2.92-3.35) than the general population. These findings were consistent across all sex and age groups. Additionally, workers with four or more unemployment spells had a significantly higher PMR than the general population.
Conclusion: The impact of unemployment on suicide mortality intensifies as the number of unemployment spells increases. These results underscore the necessity for additional social and psychological support along with economic assistance for individuals facing recurrent unemployment.
{"title":"Cumulative effect of unemployment on suicide mortality in South Korean workers (2018-2019).","authors":"Jaehyuk Jung, Kyeong-Eun Lee, Seri Hong, Jae Bum Park, Inchul Jeong","doi":"10.1017/S0033291724000965","DOIUrl":"https://doi.org/10.1017/S0033291724000965","url":null,"abstract":"<p><strong>Background: </strong>While unemployment is known to increase the risk of suicide, its cumulative effect remains underexplored. This study investigates how unemployment affects suicide mortality and whether the effect varies based on the number of unemployment spells using two years of nationwide data.</p><p><strong>Methods: </strong>Using the data from the National Statistical Office and Employment Insurance Database for 2018 and 2019, we identified an average of 2365 cases of suicide over two years among 7.76 million workers aged 25-64 years who had been employed within one year before their suicide. The number of unemployment spells was counted using the employment history of the past five years. We calculated crude suicide mortality rates per 100 000 population, age- and sex- standardized mortality rates (SMRs), and proportionate mortality rates (PMRs) for suicide.</p><p><strong>Results: </strong>Over the two years, the crude suicide rate was 30.0 per 100 000 among the general population and 30.5 among workers. Workers with no unemployment spells in the past five years had a significantly lower SMR (0.44; 0.42-0.46), while those with four or more unemployment spells had a significantly higher SMR (3.13; 2.92-3.35) than the general population. These findings were consistent across all sex and age groups. Additionally, workers with four or more unemployment spells had a significantly higher PMR than the general population.</p><p><strong>Conclusion: </strong>The impact of unemployment on suicide mortality intensifies as the number of unemployment spells increases. These results underscore the necessity for additional social and psychological support along with economic assistance for individuals facing recurrent unemployment.</p>","PeriodicalId":20891,"journal":{"name":"Psychological Medicine","volume":null,"pages":null},"PeriodicalIF":6.9,"publicationDate":"2024-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140892371","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-09DOI: 10.1017/S003329172400076X
Sarah E Paul, David A A Baranger, Emma C Johnson, Joshua J Jackson, Aaron J Gorelik, Alex P Miller, Alexander S Hatoum, Wesley K Thompson, Michael Strube, Danielle M Dick, Chella Kamarajan, John R Kramer, Martin H Plawecki, Grace Chan, Andrey P Anokhin, David B Chorlian, Sivan Kinreich, Jacquelyn L Meyers, Bernice Porjesz, Howard J Edenberg, Arpana Agrawal, Kathleen K Bucholz, Ryan Bogdan
Background: Although the link between alcohol involvement and behavioral phenotypes (e.g. impulsivity, negative affect, executive function [EF]) is well-established, the directionality of these associations, specificity to stages of alcohol involvement, and extent of shared genetic liability remain unclear. We estimate longitudinal associations between transitions among alcohol milestones, behavioral phenotypes, and indices of genetic risk.
Methods: Data came from the Collaborative Study on the Genetics of Alcoholism (n = 3681; ages 11-36). Alcohol transitions (first: drink, intoxication, alcohol use disorder [AUD] symptom, AUD diagnosis), internalizing, and externalizing phenotypes came from the Semi-Structured Assessment for the Genetics of Alcoholism. EF was measured with the Tower of London and Visual Span Tasks. Polygenic scores (PGS) were computed for alcohol-related and behavioral phenotypes. Cox models estimated associations among PGS, behavior, and alcohol milestones.
Results: Externalizing phenotypes (e.g. conduct disorder symptoms) were associated with future initiation and drinking problems (hazard ratio (HR)⩾1.16). Internalizing (e.g. social anxiety) was associated with hazards for progression from first drink to severe AUD (HR⩾1.55). Initiation and AUD were associated with increased hazards for later depressive symptoms and suicidal ideation (HR⩾1.38), and initiation was associated with increased hazards for future conduct symptoms (HR = 1.60). EF was not associated with alcohol transitions. Drinks per week PGS was linked with increased hazards for alcohol transitions (HR⩾1.06). Problematic alcohol use PGS increased hazards for suicidal ideation (HR = 1.20).
Conclusions: Behavioral markers of addiction vulnerability precede and follow alcohol transitions, highlighting dynamic, bidirectional relationships between behavior and emerging addiction.
背景:尽管酗酒与行为表型(如冲动、消极情绪、执行功能[EF])之间的联系已得到证实,但这些联系的方向性、酗酒阶段的特异性以及共同遗传责任的程度仍不清楚。我们估算了酗酒里程碑、行为表型和遗传风险指数之间的纵向关联:数据来自酗酒遗传学合作研究(n = 3681;年龄 11-36 岁)。酒精过渡(第一次:饮酒、醉酒、酒精使用障碍[AUD]症状、酒精使用障碍诊断)、内化和外化表型来自酗酒遗传学半结构化评估(Semi-Structured Assessment for the Genetics of Alcoholism)。EF通过伦敦塔和视觉跨度任务进行测量。计算了酒精相关表型和行为表型的多基因分数(PGS)。Cox 模型估计了 PGS、行为和酗酒里程碑之间的关联:结果:外化表型(如行为障碍症状)与未来开始酗酒和酗酒问题有关(危险比(HR)⩾1.16)。内化表型(如社交焦虑)与从首次酗酒发展到严重 AUD 的危险比相关(HR⩾1.55)。开始饮酒和 AUD 与日后抑郁症状和自杀意念的危险增加有关(HR⩾1.38),开始饮酒与日后行为症状的危险增加有关(HR = 1.60)。EF 与酒精过渡无关。每周饮酒量 PGS 与酒精过渡的危险性增加有关(HR⩾1.06)。有问题的饮酒 PGS 增加了自杀倾向的危险性(HR = 1.20):成瘾脆弱性的行为标记在酒精过渡之前和之后出现,突显了行为和新出现的成瘾之间的动态双向关系。
{"title":"Alcohol milestones and internalizing, externalizing, and executive function: longitudinal and polygenic score associations.","authors":"Sarah E Paul, David A A Baranger, Emma C Johnson, Joshua J Jackson, Aaron J Gorelik, Alex P Miller, Alexander S Hatoum, Wesley K Thompson, Michael Strube, Danielle M Dick, Chella Kamarajan, John R Kramer, Martin H Plawecki, Grace Chan, Andrey P Anokhin, David B Chorlian, Sivan Kinreich, Jacquelyn L Meyers, Bernice Porjesz, Howard J Edenberg, Arpana Agrawal, Kathleen K Bucholz, Ryan Bogdan","doi":"10.1017/S003329172400076X","DOIUrl":"10.1017/S003329172400076X","url":null,"abstract":"<p><strong>Background: </strong>Although the link between alcohol involvement and behavioral phenotypes (e.g. impulsivity, negative affect, executive function [EF]) is well-established, the directionality of these associations, specificity to stages of alcohol involvement, and extent of shared genetic liability remain unclear. We estimate longitudinal associations between transitions among alcohol milestones, behavioral phenotypes, and indices of genetic risk.</p><p><strong>Methods: </strong>Data came from the Collaborative Study on the Genetics of Alcoholism (<i>n</i> = 3681; ages 11-36). Alcohol transitions (first: drink, intoxication, alcohol use disorder [AUD] symptom, AUD diagnosis), internalizing, and externalizing phenotypes came from the Semi-Structured Assessment for the Genetics of Alcoholism. EF was measured with the Tower of London and Visual Span Tasks. Polygenic scores (PGS) were computed for alcohol-related and behavioral phenotypes. Cox models estimated associations among PGS, behavior, and alcohol milestones.</p><p><strong>Results: </strong>Externalizing phenotypes (e.g. conduct disorder symptoms) were associated with future initiation and drinking problems (hazard ratio (HR)⩾1.16). Internalizing (e.g. social anxiety) was associated with hazards for progression from first drink to severe AUD (HR⩾1.55). Initiation and AUD were associated with increased hazards for later depressive symptoms and suicidal ideation (HR⩾1.38), and initiation was associated with increased hazards for future conduct symptoms (HR = 1.60). EF was not associated with alcohol transitions. Drinks per week PGS was linked with increased hazards for alcohol transitions (HR⩾1.06). Problematic alcohol use PGS increased hazards for suicidal ideation (HR = 1.20).</p><p><strong>Conclusions: </strong>Behavioral markers of addiction vulnerability precede and follow alcohol transitions, highlighting dynamic, bidirectional relationships between behavior and emerging addiction.</p>","PeriodicalId":20891,"journal":{"name":"Psychological Medicine","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2024-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140892368","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-09DOI: 10.1017/S0033291724001004
J P Selten, M Di Forti, D Quattrone, P B Jones, H E Jongsma, C Gayer-Anderson, A Szöke, P M Llorca, C Arango, M Bernardo, J Sanjuan, J L Santos, M Arrojo, I Tarricone, D Berardi, A Lasalvia, S Tosato, C la Cascia, E Velthorst, E M A van der Ven, L de Haan, B P Rutten, J van Os, J B Kirkbride, C M Morgan, R M Murray, F Termorshuizen
Background: We examined whether cannabis use contributes to the increased risk of psychotic disorder for non-western minorities in Europe.
Methods: We used data from the EU-GEI study (collected at sites in Spain, Italy, France, the United Kingdom, and the Netherlands) on 825 first-episode patients and 1026 controls. We estimated the odds ratio (OR) of psychotic disorder for several groups of migrants compared with the local reference population, without and with adjustment for measures of cannabis use.
Results: The OR of psychotic disorder for non-western minorities, adjusted for age, sex, and recruitment area, was 1.80 (95% CI 1.39-2.33). Further adjustment of this OR for frequency of cannabis use had a minimal effect: OR = 1.81 (95% CI 1.38-2.37). The same applied to adjustment for frequency of use of high-potency cannabis. Likewise, adjustments of ORs for most sub-groups of non-western countries had a minimal effect. There were two exceptions. For the Black Caribbean group in London, after adjustment for frequency of use of high-potency cannabis the OR decreased from 2.45 (95% CI 1.25-4.79) to 1.61 (95% CI 0.74-3.51). Similarly, the OR for Surinamese and Dutch Antillean individuals in Amsterdam decreased after adjustment for daily use: from 2.57 (95% CI 1.07-6.15) to 1.67 (95% CI 0.62-4.53).
Conclusions: The contribution of cannabis use to the excess risk of psychotic disorder for non-western minorities was small. However, some evidence of an effect was found for people of Black Caribbean heritage in London and for those of Surinamese and Dutch Antillean heritage in Amsterdam.
背景:我们研究了使用大麻是否会增加欧洲非西方少数民族患精神病的风险:我们研究了吸食大麻是否会导致欧洲非西方少数民族患精神病的风险增加:我们使用了欧盟-欧洲精神病学研究所(EU-GEI)研究(在西班牙、意大利、法国、英国和荷兰的研究机构收集)中 825 名首次发病患者和 1026 名对照者的数据。我们估算了几组移民与当地参照人群相比患精神病的几率比例(OR),并对大麻使用情况进行了调整:结果:根据年龄、性别和招募地区进行调整后,非西方少数民族患精神病的几率比为 1.80(95% CI 1.39-2.33)。根据吸食大麻的频率对该OR进行进一步调整后,效果甚微:OR = 1.81 (95% CI 1.38-2.37)。对使用高浓度大麻频率的调整也是如此。同样,对大多数非西方国家分组的 OR 进行调整的效果也很小。但有两个例外。对于伦敦的加勒比黑人群体,在对吸食高浓度大麻的频率进行调整后,OR 从 2.45(95% CI 1.25-4.79)下降到 1.61(95% CI 0.74-3.51)。同样,阿姆斯特丹的苏里南人和荷属安的列斯人在调整每日使用量后,OR 值也有所下降:从 2.57(95% CI 1.07-6.15)降至 1.67(95% CI 0.62-4.53):使用大麻对非西方少数民族罹患精神病性障碍的超额风险影响很小。不过,有证据表明,伦敦的加勒比黑人以及阿姆斯特丹的苏里南人和荷属安的列斯人吸食大麻会产生影响。
{"title":"The contribution of cannabis use to the increased psychosis risk among minority ethnic groups in Europe.","authors":"J P Selten, M Di Forti, D Quattrone, P B Jones, H E Jongsma, C Gayer-Anderson, A Szöke, P M Llorca, C Arango, M Bernardo, J Sanjuan, J L Santos, M Arrojo, I Tarricone, D Berardi, A Lasalvia, S Tosato, C la Cascia, E Velthorst, E M A van der Ven, L de Haan, B P Rutten, J van Os, J B Kirkbride, C M Morgan, R M Murray, F Termorshuizen","doi":"10.1017/S0033291724001004","DOIUrl":"https://doi.org/10.1017/S0033291724001004","url":null,"abstract":"<p><strong>Background: </strong>We examined whether cannabis use contributes to the increased risk of psychotic disorder for non-western minorities in Europe.</p><p><strong>Methods: </strong>We used data from the EU-GEI study (collected at sites in Spain, Italy, France, the United Kingdom, and the Netherlands) on 825 first-episode patients and 1026 controls. We estimated the odds ratio (OR) of psychotic disorder for several groups of migrants compared with the local reference population, without and with adjustment for measures of cannabis use.</p><p><strong>Results: </strong>The OR of psychotic disorder for non-western minorities, adjusted for age, sex, and recruitment area, was 1.80 (95% CI 1.39-2.33). Further adjustment of this OR for frequency of cannabis use had a minimal effect: OR = 1.81 (95% CI 1.38-2.37). The same applied to adjustment for frequency of use of high-potency cannabis. Likewise, adjustments of ORs for most sub-groups of non-western countries had a minimal effect. There were two exceptions. For the Black Caribbean group in London, after adjustment for frequency of use of high-potency cannabis the OR decreased from 2.45 (95% CI 1.25-4.79) to 1.61 (95% CI 0.74-3.51). Similarly, the OR for Surinamese and Dutch Antillean individuals in Amsterdam decreased after adjustment for daily use: from 2.57 (95% CI 1.07-6.15) to 1.67 (95% CI 0.62-4.53).</p><p><strong>Conclusions: </strong>The contribution of cannabis use to the excess risk of psychotic disorder for non-western minorities was small. However, some evidence of an effect was found for people of Black Caribbean heritage in London and for those of Surinamese and Dutch Antillean heritage in Amsterdam.</p>","PeriodicalId":20891,"journal":{"name":"Psychological Medicine","volume":null,"pages":null},"PeriodicalIF":6.9,"publicationDate":"2024-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140892411","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: There is a clear demand for innovative therapeutics for bipolar disorder (BD).
Methods: We integrated the largest BD genome-wide association study (GWAS) dataset (NCase = 41 917, NControl = 371 549) with protein quantitative trait loci from brain, cerebrospinal fluid, and plasma. Using a range of integrative analyses, including Mendelian randomization (MR), Steiger filter analysis, Bayesian colocalization, and phenome-wide MR analysis, we prioritized novel drug targets for BD. Additionally, we incorporated data from the UK Biobank (NCase = 1064, NControl = 365 476) and the FinnGen study (NCase = 7006, NControl = 329 192) for robust biological validation.
Results: Through MR analysis, we found that in the brain, downregulation of DNM3, MCTP1, ABCB8 and elevation of DFNA5 and PDF were risk factors for BD. In cerebrospinal fluid, increased BD risk was associated with increased levels of FRZB, AGRP, and IL36A and decreased CTSF and LRP8. Plasma analysis revealed that decreased LMAN2L, CX3CL1, PI3, NCAM1, and TIMP4 correlated with increased BD risk, but ITIH1 did not. All these proteins passed Steiger filtering, and Bayesian colocalization confirmed that 12 proteins were colocalized with BD. Phenome-wide MR analysis revealed no significant side effects for potential drug targets, except for LRP8. External validation further underscored the concordance between the primary and validation cohorts, confirming MCTP1, DNM3, PDF, CTSF, AGRP, FRZB, LMAN2L, NCAM1, and TIMP4 are intriguing targets for BD.
Conclusions: Our study identified druggable proteins for BD, including MCTP1, DNM3, and PDF in the brain; CTSF, AGRP, and FRZB in cerebrospinal fluid; and LMAN2L, NCAM1, and TIMP4 in plasma, delineating promising avenues to development of novel therapies.
{"title":"Uncovering novel drug targets for bipolar disorder: a Mendelian randomization analysis of brain, cerebrospinal fluid, and plasma proteomes.","authors":"Tingting Jia, Tiancheng Liu, Shiyi Hu, Yongjun Li, Peixi Chen, Fengqin Qin, Yongji He, Feng Han, Chengcheng Zhang","doi":"10.1017/S0033291724001077","DOIUrl":"https://doi.org/10.1017/S0033291724001077","url":null,"abstract":"<p><strong>Background: </strong>There is a clear demand for innovative therapeutics for bipolar disorder (BD).</p><p><strong>Methods: </strong>We integrated the largest BD genome-wide association study (GWAS) dataset (<i>N</i><sub>Case</sub> = 41 917, <i>N</i><sub>Control</sub> = 371 549) with protein quantitative trait loci from brain, cerebrospinal fluid, and plasma. Using a range of integrative analyses, including Mendelian randomization (MR), Steiger filter analysis, Bayesian colocalization, and phenome-wide MR analysis, we prioritized novel drug targets for BD. Additionally, we incorporated data from the UK Biobank (<i>N</i><sub>Case</sub> = 1064, <i>N</i><sub>Control</sub> = 365 476) and the FinnGen study (<i>N</i><sub>Case</sub> = 7006, <i>N</i><sub>Control</sub> = 329 192) for robust biological validation.</p><p><strong>Results: </strong>Through MR analysis, we found that in the brain, downregulation of <i>DNM3</i>, <i>MCTP1</i>, <i>ABCB8</i> and elevation of <i>DFNA5</i> and <i>PDF</i> were risk factors for BD. In cerebrospinal fluid, increased BD risk was associated with increased levels of <i>FRZB</i>, <i>AGRP</i>, and <i>IL36A</i> and decreased <i>CTSF</i> and <i>LRP8</i>. Plasma analysis revealed that decreased <i>LMAN2L</i>, <i>CX3CL1</i>, <i>PI3</i>, <i>NCAM1</i>, and <i>TIMP4</i> correlated with increased BD risk, but <i>ITIH1</i> did not. All these proteins passed Steiger filtering, and Bayesian colocalization confirmed that 12 proteins were colocalized with BD. Phenome-wide MR analysis revealed no significant side effects for potential drug targets, except for <i>LRP8</i>. External validation further underscored the concordance between the primary and validation cohorts, confirming <i>MCTP1</i>, <i>DNM3</i>, <i>PDF</i>, <i>CTSF</i>, <i>AGRP</i>, <i>FRZB</i>, <i>LMAN2L</i>, <i>NCAM1</i>, and <i>TIMP4</i> are intriguing targets for BD.</p><p><strong>Conclusions: </strong>Our study identified druggable proteins for BD, including <i>MCTP1</i>, <i>DNM3</i>, and <i>PDF</i> in the brain; <i>CTSF</i>, <i>AGRP</i>, and <i>FRZB</i> in cerebrospinal fluid; and <i>LMAN2L</i>, <i>NCAM1</i>, and <i>TIMP4</i> in plasma, delineating promising avenues to development of novel therapies.</p>","PeriodicalId":20891,"journal":{"name":"Psychological Medicine","volume":null,"pages":null},"PeriodicalIF":6.9,"publicationDate":"2024-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140892343","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-09DOI: 10.1017/S0033291724000709
Hyun-Ho Yang, Kyu-Man Han, Aram Kim, Youbin Kang, Woo-Suk Tae, Mi-Ryung Han, Byung-Joo Ham
Background: Epigenetic modifications, such as DNA methylation, contribute to the pathophysiology of major depressive disorder (MDD). This study aimed to identify novel MDD-associated epigenetic loci using DNA methylation profiles and explore the correlations between epigenetic loci and cortical thickness changes in patients with MDD.
Methods: A total of 350 patients with MDD and 161 healthy controls (HCs) were included in the epigenome-wide association studies (EWAS). We analyzed methylation, copy number alteration (CNA), and gene network profiles in the MDD group. A total of 234 patients with MDD and 135 HCs were included in neuroimaging methylation analysis. Pearson's partial correlation analysis was used to estimate the correlation between cortical thickness of brain regions and DNA methylation levels of the loci.
Results: In total, 2018 differentially methylated probes (DMPs) and 351 differentially methylated regions (DMRs) were identified. DMP-related genes were enriched in two networks involved in the central nervous system. In neuroimaging analysis, patients with MDD showed cortical thinning in the prefrontal regions and cortical thickening in several occipital regions. Cortical thickness of the left ventrolateral prefrontal cortex (VLPFC, i.e. pars triangularis) was negatively correlated with eight DMPs associated with six genes (EML6, ZFP64, CLSTN3, KCNMA1, TAOK2, and NT5E).
Conclusion: Through combining DNA methylation and neuroimaging analyses, negative correlations were identified between the cortical thickness of the left VLPFC and DNA methylation levels of eight DMPs. Our findings could improve our understanding of the pathophysiology of MDD.
{"title":"Neuroimaging and epigenetic analysis reveal novel epigenetic loci in major depressive disorder.","authors":"Hyun-Ho Yang, Kyu-Man Han, Aram Kim, Youbin Kang, Woo-Suk Tae, Mi-Ryung Han, Byung-Joo Ham","doi":"10.1017/S0033291724000709","DOIUrl":"https://doi.org/10.1017/S0033291724000709","url":null,"abstract":"<p><strong>Background: </strong>Epigenetic modifications, such as DNA methylation, contribute to the pathophysiology of major depressive disorder (MDD). This study aimed to identify novel MDD-associated epigenetic loci using DNA methylation profiles and explore the correlations between epigenetic loci and cortical thickness changes in patients with MDD.</p><p><strong>Methods: </strong>A total of 350 patients with MDD and 161 healthy controls (HCs) were included in the epigenome-wide association studies (EWAS). We analyzed methylation, copy number alteration (CNA), and gene network profiles in the MDD group. A total of 234 patients with MDD and 135 HCs were included in neuroimaging methylation analysis. Pearson's partial correlation analysis was used to estimate the correlation between cortical thickness of brain regions and DNA methylation levels of the loci.</p><p><strong>Results: </strong>In total, 2018 differentially methylated probes (DMPs) and 351 differentially methylated regions (DMRs) were identified. DMP-related genes were enriched in two networks involved in the central nervous system. In neuroimaging analysis, patients with MDD showed cortical thinning in the prefrontal regions and cortical thickening in several occipital regions. Cortical thickness of the left ventrolateral prefrontal cortex (VLPFC, i.e. pars triangularis) was negatively correlated with eight DMPs associated with six genes (<i>EML6</i>, <i>ZFP64</i>, <i>CLSTN3</i>, <i>KCNMA1</i>, <i>TAOK2</i>, and <i>NT5E</i>).</p><p><strong>Conclusion: </strong>Through combining DNA methylation and neuroimaging analyses, negative correlations were identified between the cortical thickness of the left VLPFC and DNA methylation levels of eight DMPs. Our findings could improve our understanding of the pathophysiology of MDD.</p>","PeriodicalId":20891,"journal":{"name":"Psychological Medicine","volume":null,"pages":null},"PeriodicalIF":6.9,"publicationDate":"2024-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140892407","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-01Epub Date: 2023-11-15DOI: 10.1017/S003329172300329X
Margot P van de Weijer, Perline A Demange, Dirk H M Pelt, Meike Bartels, Michel G Nivard
Background: Extensive research has focused on the potential benefits of education on various mental and physical health outcomes. However, whether the associations reflect a causal effect is harder to establish.
Methods: To examine associations between educational duration and specific aspects of well-being, anxiety and mood disorders, and cardiovascular health in a sample of European Ancestry UK Biobank participants born in England and Wales, we apply four different causal inference methods (a natural policy experiment leveraging the minimum school-leaving age, a sibling-control design, Mendelian randomization [MR], and within-family MR), and assess if the methods converge on the same conclusion.
Results: A comparison of results across the four methods reveals that associations between educational duration and these outcomes appears predominantly to be the result of confounding or bias rather than a true causal effect of education on well-being and health outcomes. Although we do consistently find no associations between educational duration and happiness, family satisfaction, work satisfaction, meaning in life, anxiety, and bipolar disorder, we do not find consistent significant associations across all methods for the other phenotypes (health satisfaction, depression, financial satisfaction, friendship satisfaction, neuroticism, and cardiovascular outcomes).
Conclusions: We discuss inconsistencies in results across methods considering their respective limitations and biases, and additionally discuss the generalizability of our findings in light of the sample and phenotype limitations. Overall, this study strengthens the idea that triangulation across different methods is necessary to enhance our understanding of the causal consequences of educational duration.
{"title":"Disentangling potential causal effects of educational duration on well-being, and mental and physical health outcomes.","authors":"Margot P van de Weijer, Perline A Demange, Dirk H M Pelt, Meike Bartels, Michel G Nivard","doi":"10.1017/S003329172300329X","DOIUrl":"10.1017/S003329172300329X","url":null,"abstract":"<p><strong>Background: </strong>Extensive research has focused on the potential benefits of education on various mental and physical health outcomes. However, whether the associations reflect a causal effect is harder to establish.</p><p><strong>Methods: </strong>To examine associations between educational duration and specific aspects of well-being, anxiety and mood disorders, and cardiovascular health in a sample of European Ancestry UK Biobank participants born in England and Wales, we apply four different causal inference methods (a natural policy experiment leveraging the minimum school-leaving age, a sibling-control design, Mendelian randomization [MR], and within-family MR), and assess if the methods converge on the same conclusion.</p><p><strong>Results: </strong>A comparison of results across the four methods reveals that associations between educational duration and these outcomes appears predominantly to be the result of confounding or bias rather than a true causal effect of education on well-being and health outcomes. Although we do consistently find no associations between educational duration and happiness, family satisfaction, work satisfaction, meaning in life, anxiety, and bipolar disorder, we do not find consistent significant associations across all methods for the other phenotypes (health satisfaction, depression, financial satisfaction, friendship satisfaction, neuroticism, and cardiovascular outcomes).</p><p><strong>Conclusions: </strong>We discuss inconsistencies in results across methods considering their respective limitations and biases, and additionally discuss the generalizability of our findings in light of the sample and phenotype limitations. Overall, this study strengthens the idea that triangulation across different methods is necessary to enhance our understanding of the causal consequences of educational duration.</p>","PeriodicalId":20891,"journal":{"name":"Psychological Medicine","volume":null,"pages":null},"PeriodicalIF":6.9,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"107592127","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}