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Boström, A. D., Andersson, P., Jamshidi, E., Wilczek, A., Nilsonne, Å., Rask-Andersen, M., . . . Jokinen, J. (2023). Accelerated epigenetic aging in women with emotionally unstable personality disorder and a history of suicide attempts. Translational Psychiatry, 13(1), Article ID 66.
Open this publication in new window or tab >>Accelerated epigenetic aging in women with emotionally unstable personality disorder and a history of suicide attempts
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2023 (English)In: Translational Psychiatry, E-ISSN 2158-3188, Vol. 13, no 1, article id 66Article in journal (Refereed) Published
Abstract [en]

Emotional unstable personality disorder (EUPD; previously borderline personality disorder, BPD) is associated with excess natural-cause mortality, comorbid medical conditions, poor health habits and stress related epigenomic alterations. Previous studies demonstrated that GrimAge – a state-of-the-art epigenetic age (EA) estimator – strongly predicts mortality risk and physiological dysregulation. Herein, we utilize the GrimAge algorithm to investigate whether women with EUPD and a history of recent suicide attempts exhibit EA acceleration (EAA) in comparison to healthy controls. Genome-wide methylation patterns were measured using the Illumina Infinum Methylation Epic BeadChip in whole blood from 97 EUPD patients and 32 healthy controls. The control group was significantly older (p < 0.0001) and reported lesser exposure to violent behavior in both youth and adulthood (p < 0.0001). Groups were otherwise comparable regarding gender, BMI, or tobacco usage (p > 0.05). EA estimator DNAmGrimAge exceeded chronological age by 8.8 and 2.3 years in the EUPD and control group, respectively. Similarly, EAA marker AgeAccelGrim was substantially higher in EUPD subjects when compared to controls, in both univariate and multivariate analyzes (p < 0.00001). Tobacco usage conferred substantial within-group effects on the EA-chronological age difference, i.e., 10.74 years (SD = 4.19) compared to 6.00 years (SD = 3.10) in the non-user EUPD group (p < 0.00001). Notably, past alcohol and substance abuse, use of psychotropic medications, global assessment of functioning, self-reported exposure to violent behavior in youth and adulthood, later completed suicide (N = 8) and age at first suicide attempt did not predict EAA in the EUPD group (p > 0.05). These results underscore the importance of addressing medical health conditions along with low-cost preventative interventions aimed at improving somatic health outcomes in EUPD, such as efforts to support cessation of tobacco use. The independency of GrimAge to other EA algorithms in this group of severely impaired EUPD patients, suggest it may have unique characteristics to evaluate risk of adverse health outcomes in context of psychiatric disorders.

Place, publisher, year, edition, pages
Nature Publishing Group, 2023
National Category
Psychiatry
Identifiers
urn:nbn:se:umu:diva-205493 (URN)10.1038/s41398-023-02369-7 (DOI)000936883100002 ()36813766 (PubMedID)2-s2.0-85148746069 (Scopus ID)
Funder
Swedish Research CouncilUmeå UniversityRegion VästerbottenRegion Stockholm
Available from: 2023-03-14 Created: 2023-03-14 Last updated: 2024-01-22Bibliographically approved
Pahnke, J., Jansson-Fröjmark, M., Andersson, G., Bjureberg, J., Jokinen, J., Bohman, B. & Lundgren, T. (2023). Acceptance and commitment therapy for autistic adults: a randomized controlled pilot study in a psychiatric outpatient setting. Autism, 27(5), 1461-1476
Open this publication in new window or tab >>Acceptance and commitment therapy for autistic adults: a randomized controlled pilot study in a psychiatric outpatient setting
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2023 (English)In: Autism, ISSN 1362-3613, E-ISSN 1461-7005, Vol. 27, no 5, p. 1461-1476Article in journal (Refereed) Published
Abstract [en]

Autistic adults are at risk of stress-related psychiatric disorders and reduced life quality due to social, cognitive, and perceptual challenges. Mental health interventions adapted to autistic adults are scarce. Acceptance and commitment therapy has preliminarily indicated health benefits in autistic adults, although it has not been robustly evaluated. Overall, 39 adults (21 males; 21–72 years) with autism spectrum disorder and normal intellectual ability (IQ M = 108.5; SD = 13.5) were randomized to 14 weeks of adapted acceptance and commitment therapy group treatment (NeuroACT) or treatment as usual. The intervention was feasible. Perceived stress and quality of life (primary outcomes), alongside psychological inflexibility, cognitive fusion, cognitive and behavioral avoidance, and autistic mannerism were statistically significantly improved in NeuroACT compared with treatment as usual (d = 0.70–0.90). Clinically significant changes in perceived stress and quality of life were in favor of NeuroACT. Between-group altered depression, anxiety, sleep problems, one quality of life measure, functional impairment, social aspects of autism, and executive difficulties were statistically non-significant. Dropout was slightly higher in NeuroACT. NeuroACT may be a promising treatment for autistic adults with co-existing stress and reduced quality of life. More extensive studies are warranted to evaluate NeuroACT further. 

Place, publisher, year, edition, pages
Sage Publications, 2023
Keywords
acceptance and commitment therapy, anxiety, autism, cognitive defusion, depression, interventions—psychosocial/behavioral, mindfulness, psychological flexibility, quality of life, stress
National Category
Psychiatry Applied Psychology
Identifiers
urn:nbn:se:umu:diva-202003 (URN)10.1177/13623613221140749 (DOI)000896879700001 ()36510817 (PubMedID)2-s2.0-85144189525 (Scopus ID)
Funder
Stiftelsen Söderström - Königska sjukhemmet
Available from: 2022-12-29 Created: 2022-12-29 Last updated: 2023-09-27Bibliographically approved
Andersson, P., Jamshidi, E., Ekman, C.-J., Tedroff, K., Björkander, J., Sjögren, M., . . . Boström, A. D. (2023). Anorexia nervosa with comorbid severe depression: a systematic scoping review of brain stimulation treatments. Journal of ECT, 39(4), 227-234
Open this publication in new window or tab >>Anorexia nervosa with comorbid severe depression: a systematic scoping review of brain stimulation treatments
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2023 (English)In: Journal of ECT, ISSN 1095-0680, E-ISSN 1533-4112, Vol. 39, no 4, p. 227-234Article in journal (Refereed) Published
Abstract [en]

Major depressive disorder (MDD) is highly prevalent in individuals with anorexia nervosa (AN) and is a predictor of greater clinical severity. However, there is a limited amount of evidence supporting the use of psychotropic medications for its management. A systematic scoping review was conducted to assess the current literature on brain stimulation treatments for AN with comorbid MDD, with a specific focus on MDD treatment response and weight restoration. This review was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, and the PubMed, PsycInfo, and MEDLINE databases were searched until July 2022 using specific key words related to AN and brain stimulation treatments. A total of 373 citations were identified, and 49 treatment studies that met the inclusion criteria were included in the review. The initial evidence suggests that electroconvulsive therapy, repetitive transcranial magnetic stimulation, and deep-brain stimulation may be effective in managing comorbid MDD in AN. Emerging evidence suggests that transcranial direct current stimulation may have a positive effect on body mass index in individuals with severe to extreme AN. However, there is a need for the development of better measurement techniques for assessing the severity of depression in the context of AN. Controlled trials that are adequately designed to account for these limitations are highly warranted for deep-brain stimulation, electroconvulsive therapy, and repetitive transcranial magnetic stimulation and hold promise for providing clinically meaningful results.

Place, publisher, year, edition, pages
Lippincott Williams & Wilkins, 2023
Keywords
DBS, ECT, inpatients, MDD, severe anorexia nervosa, treatment guidelines
National Category
Psychiatry
Identifiers
urn:nbn:se:umu:diva-218470 (URN)10.1097/YCT.0000000000000922 (DOI)37053429 (PubMedID)2-s2.0-85178497245 (Scopus ID)
Funder
Region StockholmSwedish Research CouncilRegion Västerbotten
Available from: 2023-12-20 Created: 2023-12-20 Last updated: 2024-01-22Bibliographically approved
Andersson, P., Jokinen, J., Jarbin, H., Lundberg, J. & Desai Boström, A. E. (2023). Association of Bipolar Disorder Diagnosis With Suicide Mortality Rates in Adolescents in Sweden. JAMA psychiatry, 80(8), 796-802
Open this publication in new window or tab >>Association of Bipolar Disorder Diagnosis With Suicide Mortality Rates in Adolescents in Sweden
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2023 (English)In: JAMA psychiatry, ISSN 2168-6238, E-ISSN 2168-622X, Vol. 80, no 8, p. 796-802Article in journal (Refereed) Published
Abstract [en]

Importance: The association of early diagnosis and management of bipolar disorder with adolescent suicide mortality (ASM) is unknown.

Objective: To assess regional associations between ASM and bipolar disorder diagnosis frequencies.

Design, Setting, and Participants: This cross-sectional study investigated the association between annual regional ASM and bipolar disorder diagnosis rates in Swedish adolescents aged 15 to 19 years in January 1, 2008, through December 31, 2021. Aggregated data without exclusions reported at the regional level encompassed 585 suicide deaths, constituting 588 unique observations (ie, 21 regions, 14 years, 2 sexes).

Exposures: Bipolar disorder diagnosis frequencies and lithium dispensation rates were designated as fixed-effects variables (interaction term in the case of males). An interaction term between psychiatric care affiliation rates and the proportion of psychiatric visits to inpatient and outpatient clinics constituted independent fixed-effects variables. Region and year comprised random intercept effect modifiers. Variables were population adjusted and corrected for heterogeneity in reporting standards.

Main Outcomes and Measures: The main outcomes were sex-stratified, regional, and annual ASM rates in adolescents aged 15 to 19 years per 100 000 inhabitants as analyzed using generalized linear mixed-effects models.

Results: Female adolescents were diagnosed with bipolar disorder almost 3 times more often than male adolescents (mean [SD], 149.0 [19.6] vs 55.3 [6.1] per 100 000 inhabitants, respectively). Median regional prevalence rates of bipolar disorder varied over the national median by a factor of 0.46 to 2.61 and 0.00 to 1.82 in females and males, respectively. Bipolar disorder diagnosis rates were inversely associated with male ASM (β = -0.00429; SE, 0.002; 95% CI, -0.0081 to -0.0004; P = .03) independent of lithium treatment and psychiatric care affiliation rates. This association was replicated by β-binomial models of a dichotomized quartile 4 ASM variable (odds ratio, 0.630; 95% CI, 0.457-0.869; P = .005), and both models were robust after adjusting for annual regional diagnosis rates of major depressive disorder and schizophrenia. No such association was observed in females.

Conclusions and Relevance: In this cross-sectional study, lower suicide death rates in adolescent males was robustly associated with regional diagnosis rates of bipolar disorder at an estimated magnitude of approximately 4.7% of the mean national suicide death rate. The associations could be due to treatment efficacy, early diagnosis and management, or other factors not accounted for.

Place, publisher, year, edition, pages
American Medical Association (AMA), 2023
National Category
Psychiatry
Identifiers
urn:nbn:se:umu:diva-212739 (URN)10.1001/jamapsychiatry.2023.1390 (DOI)000995698100006 ()37223908 (PubMedID)2-s2.0-85166393689 (Scopus ID)
Funder
Swedish Research Council, 2020-01183
Available from: 2023-08-14 Created: 2023-08-14 Last updated: 2023-08-14Bibliographically approved
Boström, A. D., Jamshidi, E., Manu, D.-M., Kular, L., Schiöth, H. B., Åsberg, M. & Jokinen, J. (2023). Epigenetic changes in the CYP2D6 gene are related to severity of suicide attempt: A cross-sectional study of suicide attempters. Journal of Psychiatric Research, 160, 217-224
Open this publication in new window or tab >>Epigenetic changes in the CYP2D6 gene are related to severity of suicide attempt: A cross-sectional study of suicide attempters
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2023 (English)In: Journal of Psychiatric Research, ISSN 0022-3956, E-ISSN 1879-1379, Vol. 160, p. 217-224Article in journal (Refereed) Published
Abstract [en]

Background: The ability to accurately estimate risk of suicide deaths on an individual level remains elusive.

Methods: This study reports on a case-control study set-up from a well-characterized cohort of 88 predominantly female suicide attempters (SA), stratified into low- (n = 57) and high-risk groups (n = 31) based on reports of later death by suicide, as well as degree of intent-to-die and lethality of SA method. We perform an unbiased analysis of 12,930 whole-blood derived CpG-sites (Illumina Infinium EPIC BeadChip) previously demonstrated to be more conciliable with brain-derived variations. The candidate site was validated by pyrosequencing. External replication was performed in (1) relation to age at index suicide attempt in 97 women with emotionally unstable personality disorder (whole-blood) and (2) death by suicide in a mixed group of 183 prefrontal-cortex (PFC) derived samples who died by suicide or from non-psychiatric etiologies.

Results: CYP2D6-coupled CpG-site cg07016288 was hypomethylated in severe suicidal behavior (p < 10E-06). Results were validated by pyrosequencing (p < 0.01). Replication analyses demonstrate hypomethylation of cg07016288 in relation to age at index SA in females (p < 0.05) and hypermethylation in PFC of male suicide completers (p < 0.05). Limitations: Genotyping of CYP2D6 was not performed and CpG-site associations to gene expression were not explored.

Conclusions: CYP2D6-coupled epigenetic markers are hypomethylated in females in dependency of features known to confer increased risk of suicide deaths and hypermethylated in PFC of male suicide completers. Further elucidating the role of CYP2D6 in severe suicidality or suicide deaths hold promise to deduce clinically meaningful results.

Place, publisher, year, edition, pages
Elsevier, 2023
Keywords
cg07016288, CYP2D6, DNA methylation, Psychiatry, Suicide, Suicide prevention
National Category
Psychiatry
Identifiers
urn:nbn:se:umu:diva-205637 (URN)10.1016/j.jpsychires.2023.02.025 (DOI)000949417500001 ()2-s2.0-85149250745 (Scopus ID)
Funder
Swedish Research Council, 5454Swedish Research Council, K2009-61P-21304-04-4Swedish Research Council, K2009-61X-21305-01-1Umeå UniversityRegion VästerbottenThe Swedish Brain Foundation
Available from: 2023-03-14 Created: 2023-03-14 Last updated: 2024-01-22Bibliographically approved
Jamshidi, E., Boström, A. D., Wilczek, A., Nilsonne, Å., Åsberg, M. & Jokinen, J. (2023). Increased methylation of brain-derived neurotrophic factor (BDNF) is related to emotionally unstable personality disorder and severity of suicide attempt in women. Cells, 12(3), Article ID 350.
Open this publication in new window or tab >>Increased methylation of brain-derived neurotrophic factor (BDNF) is related to emotionally unstable personality disorder and severity of suicide attempt in women
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2023 (English)In: Cells, E-ISSN 2073-4409, Vol. 12, no 3, article id 350Article in journal (Refereed) Published
Abstract [en]

Brain-derived neurotrophic factor (BDNF) has previously been associated with the pathogenesis of both emotionally unstable personality disorder (EUPD) and suicidal behavior. No study has yet investigated BDNF-associated epigenetic alterations in a group of severely impaired EUPD and suicidal patients. The discovery cohort consisted of 97 women with emotionally unstable personality disorder (EUPD) with at least two serious suicide attempts (SAs) and 32 healthy female controls. The genome-wide methylation pattern was measured by the Illumina EPIC BeadChip and analyzed by robust linear regression models to investigate mean BDNF methylation levels in a targeted analysis conditioned upon severity of suicide attempt. The validation cohort encompassed 60 female suicide attempters, stratified into low- (n = 45) and high-risk groups (n = 15) based on degree of intent-to-die and lethality of SA method, and occurrence of death-by-suicide at follow-up. Mean BDNF methylation levels exhibited increased methylation in relation to EUPD (p = 0.0159, percentage mean group difference ~3.8%). Similarly, this locus was confirmed as higher-methylated in an independent cohort of females with severe suicidal behavior (p = 0.0300). Results were independent of age and BMI. This is the first study to reveal emerging evidence of epigenetic dysregulation of BDNF with dependence on features known to confer increased risk of suicide deaths (lethality of suicide-attempt method and presence of EUPD diagnosis with history of recent SAs). Further studies investigating epigenetic and genetic effects of BDNF on severe suicidal behavior and EUPD are needed to further elucidate the role of epigenetic regulatory mechanisms and neurotrophic factors in relation to suicide and EUPD, and hold potential to result in novel treatment methods.

Keywords
BDNF, borderline personality disorder, BPD, brain-derived neurotrophic factor, DNA Methylation, emotionally unstable personality disorder, EUPD, suicide
National Category
Psychiatry
Identifiers
urn:nbn:se:umu:diva-205002 (URN)10.3390/cells12030350 (DOI)000933813900001 ()2-s2.0-85147858487 (Scopus ID)
Funder
Swedish Research Council, K2009-61P-21304-04-4Region Stockholm, ALF, FoUI-954107Region Västerbotten, ALF, RV-967864
Available from: 2023-03-01 Created: 2023-03-01 Last updated: 2024-01-22Bibliographically approved
Andersson, P., Lundberg, J., Jarbin, H., Jokinen, J. & Boström, A. D. (2023). Inverse association of anti-inflammatory prescription fills and suicide-related mortality in young adults: Evidence from a nationwide study of Swedish regions, 2006–2021. Brain, Behavior, and Immunity - Health, 31, Article ID 100665.
Open this publication in new window or tab >>Inverse association of anti-inflammatory prescription fills and suicide-related mortality in young adults: Evidence from a nationwide study of Swedish regions, 2006–2021
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2023 (English)In: Brain, Behavior, and Immunity - Health, E-ISSN 2666-3546, Vol. 31, article id 100665Article in journal (Refereed) Published
Abstract [en]

Background: This cross-sectional study examined nationwide real-world associations between anti-inflammatory agent fills and suicide-related death rates in 20–24-year-olds across the 21 Swedish regions during 2006–2021.

Methods: Nationwide Swedish registers were used to compare regional year-wise suicide-related mortality (SRM) and dispensations for anti-inflammatory agents (ATC-code: M01) in 20–24-year-olds. Dispensations for paracetamol (ATC-code: N02BE01) was applied as a control variable. Associations between regional year-wise SRM and dispensation rates were analyzed by sex-stratified zero-inflated generalized linear mixed effect models (GLMM). Dispensation rates of paracetamol and inflammatory agents were designated as independent fixed effects variables, and year and region constituted random-intercept effects.

Results: Acetic acid derivatives and related substances (M01AB) and propionic acid derivates (M01A3) accounted for ∼71% of measured dispensation fills for anti-inflammatory agents. Diclofenac fills constituted ∼98% of the former category, whereas dispensations for Ibuprofen (∼21%), Naproxen (∼62%) and Ketoprofen (∼13%) constituted the most prescribed agents in the latter category. Regional yearly dispensation rates of anti-inflammatory agents in 20–24-year-old females were inversely associated with female SRM (β = −0.095, p = 0.0393, 95% CI -0.186, −0.005) – independent of paracetamol rates, which were unassociated to SRM (p = 0.2094). Results were confirmed in validation analyses for anti-inflammatory agents (OR = 0.7232, p = 0.0354, 95% CI [OR] 0.5347, 0.9781). No association was demonstrated in males (p = 0.833).

Conclusion: Anti-inflammatory agent dispensation rates were independently associated to lower suicide-related death rates in female 20-24-year-olds. This adds to growing evidence implicating inflammatory processes in mental disorders, warranting trials focusing on the suicide preventative potential of anti-inflammatories in young adults.

Place, publisher, year, edition, pages
Elsevier, 2023
National Category
Public Health, Global Health, Social Medicine and Epidemiology
Identifiers
urn:nbn:se:umu:diva-212066 (URN)10.1016/j.bbih.2023.100665 (DOI)2-s2.0-85163971630 (Scopus ID)
Funder
Swedish Research Council, 2020-01183
Available from: 2023-07-18 Created: 2023-07-18 Last updated: 2024-01-22Bibliographically approved
Andersson, P., Jamshidi, E., Ekman, C.-J., Tedroff, K., Björkander, J., Sjögren, M., . . . Boström, A. D. (2023). Mapping length of inpatient treatment duration and year-wise relapse rates in eating disordered populations in a well-defined Western-European healthcare region across 1998–2020. International Journal of Methods in Psychiatric Research, 32(4), Article ID e1960.
Open this publication in new window or tab >>Mapping length of inpatient treatment duration and year-wise relapse rates in eating disordered populations in a well-defined Western-European healthcare region across 1998–2020
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2023 (English)In: International Journal of Methods in Psychiatric Research, ISSN 1049-8931, E-ISSN 1557-0657, Vol. 32, no 4, article id e1960Article in journal (Refereed) Published
Abstract [en]

Objectives: Updated international guideline recommendations for AN inpatient care rely on expert opinions/observational evidence and promote extended inpatient stays, warranting investigation using higher-level ecological evidence.

Methods: The study was conducted according to Guidelines for Accurate and Transparent Health Estimates Reporting (GATHER). Data encompassing 13,885 ED inpatients (5336 adolescents and 8549 adults) was retrieved from Swedish public health registries. Variables analyzed included (1) ED inpatient care opportunities, (2) unique number of ED inpatients and (3) mean length of ED-related inpatient stays in age groups 15–19 and 20–88+, across 1998–2020.

Results: Mean length of inpatient stays was inversely correlated to relapse to ED-related inpatient care within the same year (p < 0.001, R-squaredadj = 0.5216 and p < 0.00001, R-squaredadj = 0.5090, in the 15–19 and 20–88+ age groups, respectively), independent of number of ED inpatients treated within a year in both age groups. Extending mean adolescent inpatient duration from 35 to 45 days was associated with a ∼30% reduction in the year-wise relapse rate.

Conclusions: Mean length of ED-related inpatient treatment stays was associated with reduced relapses to inpatient care within the same year, which could be interpreted as support for recommendations to include a stabilization phase in inpatient ED treatment.

Place, publisher, year, edition, pages
John Wiley & Sons, 2023
Keywords
ecological evidence, inpatients, severe anorexia nervosa, treatment guidelines, weight restoration
National Category
Psychiatry
Identifiers
urn:nbn:se:umu:diva-204758 (URN)10.1002/mpr.1960 (DOI)000919218700001 ()36710656 (PubMedID)2-s2.0-85147386766 (Scopus ID)
Funder
Swedish Research Council, 2020–01183
Available from: 2023-02-21 Created: 2023-02-21 Last updated: 2024-01-22Bibliographically approved
Sokolov, A. V., Manu, D.-M., Nordberg, D. O. T., Boström, A. D., Jokinen, J. & Schiöth, H. B. (2023). Methylation in MAD1L1 is associated with the severity of suicide attempt and phenotypes of depression. Clinical Epigenetics, 15(1), Article ID 1.
Open this publication in new window or tab >>Methylation in MAD1L1 is associated with the severity of suicide attempt and phenotypes of depression
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2023 (English)In: Clinical Epigenetics, E-ISSN 1868-7083, Vol. 15, no 1, article id 1Article in journal (Refereed) Published
Abstract [en]

Depression is a multifactorial disorder representing a significant public health burden. Previous studies have linked multiple single nucleotide polymorphisms with depressive phenotypes and suicidal behavior. MAD1L1 is a mitosis metaphase checkpoint protein that has been linked to depression in GWAS. Using a longitudinal EWAS approach in an adolescent cohort at two time points (n = 216 and n = 154), we identified differentially methylated sites that were associated with depression-related genetic variants in MAD1L1. Three methylation loci (cg02825527, cg18302629, and cg19624444) were consistently hypomethylated in the minor allele carriers, being cross-dependent on several SNPs. We further investigated whether DNA methylation at these CpGs is associated with depressive psychiatric phenotypes in independent cohorts. The first site (cg02825527) was hypomethylated in blood (exp(β) = 84.521, p value ~ 0.003) in participants with severe suicide attempts (n = 88). The same locus showed increased methylation in glial cells (exp(β) = 0.041, p value ~ 0.004) in the validation cohort, involving 29 depressed patients and 29 controls, and showed a trend for association with suicide (n = 40, p value ~ 0.089) and trend for association with depression treatment (n = 377, p value ~ 0.075). The second CpG (cg18302629) was significantly hypomethylated in depressed participants (exp(β) = 56.374, p value ~ 0.023) in glial cells, but did not show associations in the discovery cohorts. The last methylation site (cg19624444) was hypomethylated in the whole blood of severe suicide attempters; however, this association was at the borderline for statistical significance (p value ~ 0.061). This locus, however, showed a strong association with depression treatment in the validation cohort (exp(β) = 2.237, p value ~ 0.003) with 377 participants. The direction of associations between psychiatric phenotypes appeared to be different in the whole blood in comparison with brain samples for cg02825527 and cg19624444. The association analysis between methylation at cg18302629 and cg19624444 and MAD1L1 transcript levels in CD14+ cells shows a potential link between methylation at these CpGs and MAD1L1 expression. This study suggests evidence that methylation at MAD1L1 is important for psychiatric health as supported by several independent cohorts.

Place, publisher, year, edition, pages
BioMed Central (BMC), 2023
Keywords
Depression, DNA methylation, MAD1L1, Suicide
National Category
Psychiatry Medical Genetics
Identifiers
urn:nbn:se:umu:diva-202575 (URN)10.1186/s13148-022-01394-5 (DOI)000908834800002 ()36600305 (PubMedID)2-s2.0-85145533765 (Scopus ID)
Funder
The Swedish Brain FoundationSwedish Research Council, K2009-61P-21304-04-4Swedish Research Council, K200961X-21305-01-1Region Västerbotten, VLL-582221Region Stockholm, SLL-20150269
Available from: 2023-01-12 Created: 2023-01-12 Last updated: 2024-01-22Bibliographically approved
Boström, A. D., Andersson, P., Rask-Andersen, M., Jarbin, H., Lundberg, J. & Jokinen, J. (2023). Regional clozapine, ECT and lithium usage inversely associated with excess suicide rates in male adolescents. Nature Communications, 14(1), Article ID 1281.
Open this publication in new window or tab >>Regional clozapine, ECT and lithium usage inversely associated with excess suicide rates in male adolescents
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2023 (English)In: Nature Communications, E-ISSN 2041-1723, Vol. 14, no 1, article id 1281Article in journal (Refereed) Published
Abstract [en]

Advanced psychiatric treatments remain uncertain in preventing suicide among adolescents. Across the 21 Swedish regions, using nationwide registers between 2016-2020, we found negative correlation between adolescent excess suicide mortality (AESM) and regional frequencies of clozapine, ECT, and lithium (CEL) usage among adolescents (β = -0.613, p = 0.0003, 95% CI: -0.338, -0.889) and males (β = -0.404, p = 0.009, 95% CI: -0.130, -0.678). No correlation was found among females (p = 0.197). Highest CEL usage among male adolescents was seen in regions with lowest quartile (Q1) AESM (W = 74, p = 0.012). Regional CEL treatment frequency in 15-19-year-olds was related to lower AESM in males, reflecting potential treatment efficacy, treatment compliance or better-quality mental health care. Suicide prevention may benefit from early recognition and CEL treatment for severe mental illness in male adolescents. The results indicate association but further research, using independent samples and both prospective and observational methodologies, is needed to confirm causality.

Place, publisher, year, edition, pages
Nature Publishing Group, 2023
National Category
Psychiatry
Identifiers
urn:nbn:se:umu:diva-206021 (URN)10.1038/s41467-023-36973-4 (DOI)36918566 (PubMedID)2-s2.0-85150306127 (Scopus ID)
Funder
Swedish Research Council, 2020-01183
Available from: 2023-03-28 Created: 2023-03-28 Last updated: 2024-01-22Bibliographically approved
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ORCID iD: ORCID iD iconorcid.org/0000-0001-6766-7983

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