Pub Date : 2026-01-21DOI: 10.1016/s2215-0366(25)00247-0
Alexandra M Schuster, Nisreen A Alwan, Felicity Callard, Eric Yu Hai Chen, Simon Gilbody, Bronwyn M Graham, Stephani L Hatch, Edgar Jones, Ayana Jordan, Martin Knapp, Carlos López-Jaramillo, Ethel Nakimuli-Mpungu, Soumitra Pathare, Kerry J Ressler, Simon Wessely, Lawrence A White, Peter B Jones
{"title":"The implications of the COVID-19 pandemic for clinical mental health care","authors":"Alexandra M Schuster, Nisreen A Alwan, Felicity Callard, Eric Yu Hai Chen, Simon Gilbody, Bronwyn M Graham, Stephani L Hatch, Edgar Jones, Ayana Jordan, Martin Knapp, Carlos López-Jaramillo, Ethel Nakimuli-Mpungu, Soumitra Pathare, Kerry J Ressler, Simon Wessely, Lawrence A White, Peter B Jones","doi":"10.1016/s2215-0366(25)00247-0","DOIUrl":"https://doi.org/10.1016/s2215-0366(25)00247-0","url":null,"abstract":"","PeriodicalId":48784,"journal":{"name":"Lancet Psychiatry","volume":"31 1","pages":""},"PeriodicalIF":64.3,"publicationDate":"2026-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146014335","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-14DOI: 10.1016/s2215-0366(25)00338-4
Sasson Zemach,Joseph Zohar,Christoph U Correll,Stephen M Stahl,Filippo Drago,Guy M Goodwin,Hans-Jurgen Moller,Hiroyuki Uchida,Spyridon Siafis,Marlene Santos,Pierre Blier
In this Personal View, we introduce the concept of different dosage different pharmacology (DDDP), which describes how certain psychotropic medications have distinct therapeutic effects at low and high doses due to differing neurobiological mechanisms. Using the Neuroscience-based Nomenclature (NbN) framework, which classifies drugs by pharmacology and modes of action, we identified ten agents demonstrating DDDP in a comprehensive expert-based consensus process: amisulpride, amitriptyline, aripiprazole, brexpiprazole, cariprazine, doxepin, mirtazapine, quetiapine, risperidone, and trazodone. These medications show clearly demarcated dose-dependent effects, with changes in pharmacological action. For example, some drugs show anxiolytic or hypnotic effects at low doses (via histamine H1 or noradrenergic α1 antagonism) and antidepressant effects at high doses (via reuptake inhibition of serotonin or norepinephrine). Understanding these differences supports more rational prescribing (eg, increasing dopamine partial agonist doses beyond the optimal range might reduce efficacy). DDDP, within the NbN framework, offers a neuroscience-based approach to more precise psychopharmacology.
{"title":"Dose-dependent pharmacological mechanisms within the Neuroscience-based Nomenclature: a new concept to facilitate neuroscience-based prescribing.","authors":"Sasson Zemach,Joseph Zohar,Christoph U Correll,Stephen M Stahl,Filippo Drago,Guy M Goodwin,Hans-Jurgen Moller,Hiroyuki Uchida,Spyridon Siafis,Marlene Santos,Pierre Blier","doi":"10.1016/s2215-0366(25)00338-4","DOIUrl":"https://doi.org/10.1016/s2215-0366(25)00338-4","url":null,"abstract":"In this Personal View, we introduce the concept of different dosage different pharmacology (DDDP), which describes how certain psychotropic medications have distinct therapeutic effects at low and high doses due to differing neurobiological mechanisms. Using the Neuroscience-based Nomenclature (NbN) framework, which classifies drugs by pharmacology and modes of action, we identified ten agents demonstrating DDDP in a comprehensive expert-based consensus process: amisulpride, amitriptyline, aripiprazole, brexpiprazole, cariprazine, doxepin, mirtazapine, quetiapine, risperidone, and trazodone. These medications show clearly demarcated dose-dependent effects, with changes in pharmacological action. For example, some drugs show anxiolytic or hypnotic effects at low doses (via histamine H1 or noradrenergic α1 antagonism) and antidepressant effects at high doses (via reuptake inhibition of serotonin or norepinephrine). Understanding these differences supports more rational prescribing (eg, increasing dopamine partial agonist doses beyond the optimal range might reduce efficacy). DDDP, within the NbN framework, offers a neuroscience-based approach to more precise psychopharmacology.","PeriodicalId":48784,"journal":{"name":"Lancet Psychiatry","volume":"36 1","pages":""},"PeriodicalIF":64.3,"publicationDate":"2026-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145993044","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-12DOI: 10.1016/s2215-0366(25)00341-4
Rosa Ritunnano, Jeannette Littlemore, Barnaby Nelson, Clara S Humpston, Matthew R Broome
<h3>Background</h3>Delusions in psychosis involve complex and dynamic experiential, affective, cognitive, behavioural, and interpersonal alterations. Their pattern of emergence during the early stages of illness remains poorly understood and the origin of their thematic content unclear. Phenomenological accounts have emphasised alterations of selfhood and reality experience in delusion formation but have not considered the role of life events and other contextual factors in the development of these disturbances. This study aimed to investigate the relationship between self-experience and the lived world in first-episode psychosis by situating the phenomenological analysis of delusions in the context of the person's life narrative.<h3>Methods</h3>In this qualitatively driven study, we recruited individuals with lived experience of delusions receiving care from three Early Intervention in Psychosis (EIP) teams in the UK. People with lived experience were involved in the development of the study design and protocol. Inclusion criteria were that the individual was being treated within an EIP service; past or current experience of clinically significant delusions, assessed by the attending psychiatrist to be at least of moderate severity; aged between 18 and 65 years; and willing and able to give informed consent and able to undertake interviews in English. Exclusion criteria included presence of a psychotic disorder solely related to substance intoxication or withdrawal. We used a novel multi-perspectival design to investigate delusions across three analytical standpoints: standard clinical psychopathology (third person), phenomenological psychopathology (a top-down approach to eliciting first-person data), and narrative inquiry (a bottom-up approach to eliciting first-person data). Delusion content was classified based on the definitions provided by the Scale for the Assessment of Positive Symptoms. Participants completed standardised psychometric scales, a narrative interview (ad-hoc Life Story Interview), and a phenomenological (Examination of Anomalous World Experience [EAWE]) interview. Findings were integrated through meta-inference across analytical frameworks.<h3>Findings</h3>Between Jan 4, 2023, and June 14, 2023, 33 interview sessions were completed with ten adults with first-episode psychosis and lived experience of delusions (three men, six women, and one person who was non-binary; median age 24·5 years [IQR 14·8]; eight White, two White and Black Caribbean). The three most common delusion themes were: persecutory (ten [100%]), reference (nine [90%]), and grandiose or religious (nine [90%]). No theme occurred in isolation. The phenomenological component of the analysis revealed a global, qualitative shift in the subjective experience of the lived world, with total EAWE scores ranging from 13 to 48 (mean 26·5 [SD 10·85]). The first narrative theme highlighted the role of early and repeated negative interpersonal emotions (especially shame)
{"title":"Delusion as embodied emotion: a qualitatively driven, multimethod study of first-episode psychosis in the UK","authors":"Rosa Ritunnano, Jeannette Littlemore, Barnaby Nelson, Clara S Humpston, Matthew R Broome","doi":"10.1016/s2215-0366(25)00341-4","DOIUrl":"https://doi.org/10.1016/s2215-0366(25)00341-4","url":null,"abstract":"<h3>Background</h3>Delusions in psychosis involve complex and dynamic experiential, affective, cognitive, behavioural, and interpersonal alterations. Their pattern of emergence during the early stages of illness remains poorly understood and the origin of their thematic content unclear. Phenomenological accounts have emphasised alterations of selfhood and reality experience in delusion formation but have not considered the role of life events and other contextual factors in the development of these disturbances. This study aimed to investigate the relationship between self-experience and the lived world in first-episode psychosis by situating the phenomenological analysis of delusions in the context of the person's life narrative.<h3>Methods</h3>In this qualitatively driven study, we recruited individuals with lived experience of delusions receiving care from three Early Intervention in Psychosis (EIP) teams in the UK. People with lived experience were involved in the development of the study design and protocol. Inclusion criteria were that the individual was being treated within an EIP service; past or current experience of clinically significant delusions, assessed by the attending psychiatrist to be at least of moderate severity; aged between 18 and 65 years; and willing and able to give informed consent and able to undertake interviews in English. Exclusion criteria included presence of a psychotic disorder solely related to substance intoxication or withdrawal. We used a novel multi-perspectival design to investigate delusions across three analytical standpoints: standard clinical psychopathology (third person), phenomenological psychopathology (a top-down approach to eliciting first-person data), and narrative inquiry (a bottom-up approach to eliciting first-person data). Delusion content was classified based on the definitions provided by the Scale for the Assessment of Positive Symptoms. Participants completed standardised psychometric scales, a narrative interview (ad-hoc Life Story Interview), and a phenomenological (Examination of Anomalous World Experience [EAWE]) interview. Findings were integrated through meta-inference across analytical frameworks.<h3>Findings</h3>Between Jan 4, 2023, and June 14, 2023, 33 interview sessions were completed with ten adults with first-episode psychosis and lived experience of delusions (three men, six women, and one person who was non-binary; median age 24·5 years [IQR 14·8]; eight White, two White and Black Caribbean). The three most common delusion themes were: persecutory (ten [100%]), reference (nine [90%]), and grandiose or religious (nine [90%]). No theme occurred in isolation. The phenomenological component of the analysis revealed a global, qualitative shift in the subjective experience of the lived world, with total EAWE scores ranging from 13 to 48 (mean 26·5 [SD 10·85]). The first narrative theme highlighted the role of early and repeated negative interpersonal emotions (especially shame)","PeriodicalId":48784,"journal":{"name":"Lancet Psychiatry","volume":"120 1","pages":""},"PeriodicalIF":64.3,"publicationDate":"2026-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145955017","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-06DOI: 10.1016/s2215-0366(25)00393-1
Jennifer Hall,Ledia Lazeri,Joao Breda,Natasha Azzopardi-Muscat
{"title":"Applying a quality lens to strengthening WHO European region child and youth mental health services.","authors":"Jennifer Hall,Ledia Lazeri,Joao Breda,Natasha Azzopardi-Muscat","doi":"10.1016/s2215-0366(25)00393-1","DOIUrl":"https://doi.org/10.1016/s2215-0366(25)00393-1","url":null,"abstract":"","PeriodicalId":48784,"journal":{"name":"Lancet Psychiatry","volume":"3 1","pages":""},"PeriodicalIF":64.3,"publicationDate":"2026-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145937683","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-05DOI: 10.1016/s2215-0366(25)00332-3
Elias Wagner, Mikkel Højlund, Jess G Fiedorowicz, René Ernst Nielsen, Søren Dinesen Østergaard, Anne Høye, Ina H Heiberg, Laura Poddighe, Marco Delogu, Richard I G Holt, Christoph U Correll, Samuele Cortese, Andre F Carvalho, Laurent Boyer, Elena Dragioti, Ebba Du Rietz, Joseph Firth, Paolo Fusar-Poli, Catharina A Hartman, Henrik Larsson, Riccardo De Giorgi, Kelli Lehto, Peter Lindgren, Mirko Manchia, Merete Nordentoft, Karolina Skonieczna-Żydecka, Areti-Angeliki Veroniki, Wolfgang Marx, Mattia Campana, Matin Mortazavi, Alkomiet Hasan, Brendon Stubbs, Heidi Taipale, Davy Vancampfort, Eduard Vieta, Marco Solmi
<h3>Background</h3>People with mental disorders have an increased risk of diabetes, yet conflicting evidence exists regarding the quality of diabetes care they receive. To address this evidence gap, we conducted a systematic review and meta-analysis to assess and compare diabetes quality of care in people with diabetes with mental disorders versus people with diabetes without mental disorders.<h3>Methods</h3>In this systematic review and random-effects meta-analysis, we searched Scopus, Embase, MEDLINE, and PsycINFO for cohort and case-control studies published between database inception and Feb 8, 2025. We estimated summary odds ratios (ORs) for diabetes quality of care indicators in individuals with any mental disorder versus without mental disorders to investigate the association between the presence of a mental disorder and diabetes quality of care indicators, including overall diabetes monitoring and treatment. Studies were excluded if it was not possible to generate pooled quantitative data. The primary outcome was a binary composite measure of diabetes quality of care, meaning the percentage of people receiving any diabetes monitoring and treatment (ie, urine albumin-creatinine ratio test, HbA<sub>1c</sub> test, blood pressure measured, foot surveillance, serum creatinine test, serum cholesterol test, BMI recorded, smoking status recorded, retinal monitoring). Secondary outcomes were study-specific diabetes quality of care individual indicators matched to the nine NICE diabetes monitoring indicators and specific diabetes interventions and anti-diabetes medications. We analysed primary and secondary outcomes according to any mental disorder and to specific diagnostic subgroups. Study quality was evaluated using the Newcastle–Ottawa Scale (NOS).<h3>Findings</h3>Data from 49 studies (42 cohort and seven case-control) were included, comprising 5 503 712 individuals with diabetes, of whom 838 366 (15·2%) had a diagnosed mental disorder (defined using ICD-9 or ICD-10 criteria in 40 studies). Sex was reported in 35 of 49 studies, comprising 4 250 666 individuals, 1 956 506 (46·0%) of whom were female and 2 294 160 (54·0%) were male. The mean age was 61·4 years (SD 8·7; range 47–82 years). 38 studies reported on various mental disorders, 21 on mood disorders spectrum, 21 on major depressive disorder, 20 on schizophrenia, 11 on bipolar disorder, 11 on substance use disorder spectrum, including alcohol use disorder, six on dementia, five on anxiety disorder spectrum, and one on personality disorder spectrum. Most studies were high quality and spanned Asia, North America, Europe, and Australasia. Significant negative associations were observed between having any mental disorder and the likelihood of receiving any recommended diabetes monitoring (29 studies, OR=0·81 [95% CI 0·70–0·94], p=0·0049). Negative associations were also observed for HbA<sub>1c</sub> measurement (24 studies, 0·81 [0·68–0·97], p=0·024), retinal screening (21 studies, 0·77 [0·63–
{"title":"Disparities in diabetes treatment and monitoring for people with and without mental disorders: a systematic review and meta-analysis","authors":"Elias Wagner, Mikkel Højlund, Jess G Fiedorowicz, René Ernst Nielsen, Søren Dinesen Østergaard, Anne Høye, Ina H Heiberg, Laura Poddighe, Marco Delogu, Richard I G Holt, Christoph U Correll, Samuele Cortese, Andre F Carvalho, Laurent Boyer, Elena Dragioti, Ebba Du Rietz, Joseph Firth, Paolo Fusar-Poli, Catharina A Hartman, Henrik Larsson, Riccardo De Giorgi, Kelli Lehto, Peter Lindgren, Mirko Manchia, Merete Nordentoft, Karolina Skonieczna-Żydecka, Areti-Angeliki Veroniki, Wolfgang Marx, Mattia Campana, Matin Mortazavi, Alkomiet Hasan, Brendon Stubbs, Heidi Taipale, Davy Vancampfort, Eduard Vieta, Marco Solmi","doi":"10.1016/s2215-0366(25)00332-3","DOIUrl":"https://doi.org/10.1016/s2215-0366(25)00332-3","url":null,"abstract":"<h3>Background</h3>People with mental disorders have an increased risk of diabetes, yet conflicting evidence exists regarding the quality of diabetes care they receive. To address this evidence gap, we conducted a systematic review and meta-analysis to assess and compare diabetes quality of care in people with diabetes with mental disorders versus people with diabetes without mental disorders.<h3>Methods</h3>In this systematic review and random-effects meta-analysis, we searched Scopus, Embase, MEDLINE, and PsycINFO for cohort and case-control studies published between database inception and Feb 8, 2025. We estimated summary odds ratios (ORs) for diabetes quality of care indicators in individuals with any mental disorder versus without mental disorders to investigate the association between the presence of a mental disorder and diabetes quality of care indicators, including overall diabetes monitoring and treatment. Studies were excluded if it was not possible to generate pooled quantitative data. The primary outcome was a binary composite measure of diabetes quality of care, meaning the percentage of people receiving any diabetes monitoring and treatment (ie, urine albumin-creatinine ratio test, HbA<sub>1c</sub> test, blood pressure measured, foot surveillance, serum creatinine test, serum cholesterol test, BMI recorded, smoking status recorded, retinal monitoring). Secondary outcomes were study-specific diabetes quality of care individual indicators matched to the nine NICE diabetes monitoring indicators and specific diabetes interventions and anti-diabetes medications. We analysed primary and secondary outcomes according to any mental disorder and to specific diagnostic subgroups. Study quality was evaluated using the Newcastle–Ottawa Scale (NOS).<h3>Findings</h3>Data from 49 studies (42 cohort and seven case-control) were included, comprising 5 503 712 individuals with diabetes, of whom 838 366 (15·2%) had a diagnosed mental disorder (defined using ICD-9 or ICD-10 criteria in 40 studies). Sex was reported in 35 of 49 studies, comprising 4 250 666 individuals, 1 956 506 (46·0%) of whom were female and 2 294 160 (54·0%) were male. The mean age was 61·4 years (SD 8·7; range 47–82 years). 38 studies reported on various mental disorders, 21 on mood disorders spectrum, 21 on major depressive disorder, 20 on schizophrenia, 11 on bipolar disorder, 11 on substance use disorder spectrum, including alcohol use disorder, six on dementia, five on anxiety disorder spectrum, and one on personality disorder spectrum. Most studies were high quality and spanned Asia, North America, Europe, and Australasia. Significant negative associations were observed between having any mental disorder and the likelihood of receiving any recommended diabetes monitoring (29 studies, OR=0·81 [95% CI 0·70–0·94], p=0·0049). Negative associations were also observed for HbA<sub>1c</sub> measurement (24 studies, 0·81 [0·68–0·97], p=0·024), retinal screening (21 studies, 0·77 [0·63–","PeriodicalId":48784,"journal":{"name":"Lancet Psychiatry","volume":"30 1","pages":""},"PeriodicalIF":64.3,"publicationDate":"2026-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145903344","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-01DOI: 10.1016/s2215-0366(25)00368-2
Mud,Karim Sultan,Sophie Leighton
{"title":"An introduction to the artist Mud.","authors":" Mud,Karim Sultan,Sophie Leighton","doi":"10.1016/s2215-0366(25)00368-2","DOIUrl":"https://doi.org/10.1016/s2215-0366(25)00368-2","url":null,"abstract":"","PeriodicalId":48784,"journal":{"name":"Lancet Psychiatry","volume":"15 1","pages":"12"},"PeriodicalIF":64.3,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145732777","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-17DOI: 10.1016/s2215-0366(25)00365-7
Apurva Parikh, Laura J Fochtmann
{"title":"Assessing adolescents' use of artificial intelligence in psychiatric practice","authors":"Apurva Parikh, Laura J Fochtmann","doi":"10.1016/s2215-0366(25)00365-7","DOIUrl":"https://doi.org/10.1016/s2215-0366(25)00365-7","url":null,"abstract":"","PeriodicalId":48784,"journal":{"name":"Lancet Psychiatry","volume":"108 1","pages":""},"PeriodicalIF":64.3,"publicationDate":"2025-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145784637","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-15DOI: 10.1016/s2215-0366(25)00389-x
Beatriz Pozuelo Moyano, Christoph Mueller, Robert Stewart
{"title":"Beyond a single diagnosis: disentangling midlife depressive symptoms as predictors of dementia","authors":"Beatriz Pozuelo Moyano, Christoph Mueller, Robert Stewart","doi":"10.1016/s2215-0366(25)00389-x","DOIUrl":"https://doi.org/10.1016/s2215-0366(25)00389-x","url":null,"abstract":"","PeriodicalId":48784,"journal":{"name":"Lancet Psychiatry","volume":"56 1","pages":""},"PeriodicalIF":64.3,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145760430","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-15DOI: 10.1016/s2215-0366(25)00331-1
Philipp Frank, Archana Singh-Manoux, Jaana Pentti, G David Batty, Andrew Sommerlad, Andrew Steptoe, Gill Livingston, Robert Howard, Mika Kivimäki
<h3>Background</h3>Midlife depression has been associated with an increased risk of dementia, but it remains unclear whether this risk is attributable to specific symptoms. We aimed to identify the midlife depressive symptoms most strongly linked to subsequent dementia and to ascertain whether these associations were independent of established dementia risk factors.<h3>Methods</h3>In this prospective, observational cohort study based on the UK Whitehall II study, participants (aged 35–55 years at study inception [1985–88]) were eligible for analysis if they had complete depression data and successful linkage to national health records; individuals with prevalent dementia at baseline were excluded. In 1997–99, the baseline for this analysis, participants underwent a clinical examination and completed the 30-item version of the General Health Questionnaire (GHQ-30, a validated screening instrument for detecting clinically significant psychiatric distress in the general population). Threshold-level depression was defined as a GHQ-30 score of 5 or higher. The primary outcome was incident dementia, ascertained via linkage to UK National Health Service (NHS) Hospital Episode Statistics for inpatient admissions, the Mental Health Services Data Set, or the NHS Central Registry for mortality from April 24, 1997, to March 1, 2023. Analyses were conducted using a series of multivariable-adjusted Cox proportional hazards regression models. Hazard ratios (HRs) and accompanying 95% CIs were adjusted for age, sex, and ethnicity in the basic model. People with lived experience were not involved in the study design or writing process.<h3>Findings</h3>Of 6511 participants in the Whitehall II study who completed the GHQ-30 between April 24, 1997, and Jan 8, 1999, 5811 were eligible for this analysis. The mean age of participants was 55·7 years (SD 6·0; range 45–69); 1646 (28·3%) participants were women, 4165 (71·7%) were men, 5356 (92·2%) reported their ethnicity as White, and 455 (7·8%) reported their ethnicity as non-White. During a mean follow-up of 22·6 years (SD 5·0), 586 participants (10·1%) developed dementia. Six depressive symptoms emerged as robust midlife indicators of increased dementia risk: “Losing confidence in myself” (HR 1·51, 95% CI 1·16–1·96), “Not able to face up to problems” (1·49, 1·09–2·04), “Not feeling warmth and affection for others” (1·44, 1·06–1·95), “Nervous and strung-up all the time” (1·34, 1·03–1·72), “Not satisfied with the way tasks are carried out” (1·33, 1·05–1·69), and “Difficulties concentrating” (1·29, 1·01–1·65). Associations were independent of established dementia risk factors, including <em>APOE</em>ε4 status, cardiometabolic conditions, and lifestyle factors. In individuals younger than 60 years at baseline, the six symptoms fully accounted for the association between midlife depression and dementia risk.<h3>Interpretation</h3>A distinct set of midlife depressive symptoms was associated with an increased risk of dementia,
{"title":"Specific midlife depressive symptoms and long-term dementia risk: a 23-year UK prospective cohort study","authors":"Philipp Frank, Archana Singh-Manoux, Jaana Pentti, G David Batty, Andrew Sommerlad, Andrew Steptoe, Gill Livingston, Robert Howard, Mika Kivimäki","doi":"10.1016/s2215-0366(25)00331-1","DOIUrl":"https://doi.org/10.1016/s2215-0366(25)00331-1","url":null,"abstract":"<h3>Background</h3>Midlife depression has been associated with an increased risk of dementia, but it remains unclear whether this risk is attributable to specific symptoms. We aimed to identify the midlife depressive symptoms most strongly linked to subsequent dementia and to ascertain whether these associations were independent of established dementia risk factors.<h3>Methods</h3>In this prospective, observational cohort study based on the UK Whitehall II study, participants (aged 35–55 years at study inception [1985–88]) were eligible for analysis if they had complete depression data and successful linkage to national health records; individuals with prevalent dementia at baseline were excluded. In 1997–99, the baseline for this analysis, participants underwent a clinical examination and completed the 30-item version of the General Health Questionnaire (GHQ-30, a validated screening instrument for detecting clinically significant psychiatric distress in the general population). Threshold-level depression was defined as a GHQ-30 score of 5 or higher. The primary outcome was incident dementia, ascertained via linkage to UK National Health Service (NHS) Hospital Episode Statistics for inpatient admissions, the Mental Health Services Data Set, or the NHS Central Registry for mortality from April 24, 1997, to March 1, 2023. Analyses were conducted using a series of multivariable-adjusted Cox proportional hazards regression models. Hazard ratios (HRs) and accompanying 95% CIs were adjusted for age, sex, and ethnicity in the basic model. People with lived experience were not involved in the study design or writing process.<h3>Findings</h3>Of 6511 participants in the Whitehall II study who completed the GHQ-30 between April 24, 1997, and Jan 8, 1999, 5811 were eligible for this analysis. The mean age of participants was 55·7 years (SD 6·0; range 45–69); 1646 (28·3%) participants were women, 4165 (71·7%) were men, 5356 (92·2%) reported their ethnicity as White, and 455 (7·8%) reported their ethnicity as non-White. During a mean follow-up of 22·6 years (SD 5·0), 586 participants (10·1%) developed dementia. Six depressive symptoms emerged as robust midlife indicators of increased dementia risk: “Losing confidence in myself” (HR 1·51, 95% CI 1·16–1·96), “Not able to face up to problems” (1·49, 1·09–2·04), “Not feeling warmth and affection for others” (1·44, 1·06–1·95), “Nervous and strung-up all the time” (1·34, 1·03–1·72), “Not satisfied with the way tasks are carried out” (1·33, 1·05–1·69), and “Difficulties concentrating” (1·29, 1·01–1·65). Associations were independent of established dementia risk factors, including <em>APOE</em>ε4 status, cardiometabolic conditions, and lifestyle factors. In individuals younger than 60 years at baseline, the six symptoms fully accounted for the association between midlife depression and dementia risk.<h3>Interpretation</h3>A distinct set of midlife depressive symptoms was associated with an increased risk of dementia,","PeriodicalId":48784,"journal":{"name":"Lancet Psychiatry","volume":"16 1","pages":""},"PeriodicalIF":64.3,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145760275","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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