| 1. |
- Andersson, Peter, et al.
(författare)
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Anorexia Nervosa With Comorbid Severe Depression : A Systematic Scoping Review of Brain Stimulation Treatments
- 2023
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Ingår i: Journal of ECT. - : Lippincott Williams & Wilkins. - 1095-0680 .- 1533-4112. ; 39:4, s. 227-234
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 2. |
- Andersson, Peter, et al.
(författare)
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Association of Bipolar Disorder Diagnosis With Suicide Mortality Rates in Adolescents in Sweden
- 2023
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Ingår i: JAMA psychiatry. - : American Medical Association (AMA). - 2168-6238 .- 2168-622X. ; 80:8, s. 796-802
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 3. |
- Andersson, Peter, et al.
(författare)
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Inverse association of anti-inflammatory prescription fills and suicide-related mortality in young adults : Evidence from a nationwide study of Swedish regions, 2006-2021
- 2023
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Ingår i: Brain, Behavior, and Immunity - Health. - : Elsevier. - 2666-3546. ; 31
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Tidskriftsartikel (refereegranskat)abstract
- 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 (& beta; = - 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.
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| 4. |
- Andersson, Peter, et al.
(författare)
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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
- 2023
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Ingår i: International Journal of Methods in Psychiatric Research. - : John Wiley & Sons. - 1049-8931 .- 1557-0657. ; 32:4
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 5. |
- Boström, Adrian Desai E., et al.
(författare)
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Accelerated epigenetic aging in women with emotionally unstable personality disorder and a history of suicide attempts
- 2023
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Ingår i: Translational Psychiatry. - : Nature Publishing Group. - 2158-3188. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 6. |
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| 7. |
- Boström, Adrian Desai E., et al.
(författare)
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Epigenetic changes in the CYP2D6 gene are related to severity of suicide attempt : A cross-sectional study of suicide attempters
- 2023
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Ingår i: Journal of Psychiatric Research. - : Elsevier. - 0022-3956 .- 1879-1379. ; 160, s. 217-224
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 8. |
- Boström, Adrian Desai E., et al.
(författare)
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HPA-axis dysregulation is not associated with accelerated epigenetic aging in patients with hypersexual disorder
- 2022
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Ingår i: Psychoneuroendocrinology. - : Elsevier. - 0306-4530 .- 1873-3360. ; 141
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundHypersexual disorder (HD) - a nonparaphilic sexual desire disorder with impulsivity component - was evaluated for inclusion as a diagnosis in the DSM-5 and the diagnosis compulsive sexual behavior disorder is included as an impulse control disorder in the ICD-11. Hypothalamic-pituitary-adrenal (HPA)-axis hyperactivity is believed to affect cellular senescence and has been implicated in HD. No previous study investigated HD or HPA-axis dysregulation in relation to measures of epigenetic age (EA) acceleration.MethodsThis study reports on a case-control study set-up from a well-characterized cohort, contrasting EA predictors in relation to 60 HD patients and 33 healthy volunteers (HV) and 19 mixed HD/HV exhibiting dexamethasone suppression test (DST) non-suppression to 73 mixed HD/HV DST controls. The genome-wide methylation pattern was measured in whole blood from 94 subjects using the Illumina Infinium Methylation EPIC BeadChip and preprocessed according to specialized protocols suitable for epigenetic age estimation. The online DNAm Age Calculator (https://dnamage.genetics.ucla.edu/) was implemented to retrieve various EA predictors, which were compared between the in-silico generated subgroups.ResultsQuality control analyses indicated strong correlations between the EA measure DNA methylation GrimAge (DNAm GrimAge – the EA clock most reliably associated with mortality risk) and chronological age in all sub-groups. The study was adequately powered to detect differences of 2.5 and 3.0 years in DNAm GrimAge minus age in relation to both HD and HPA-axis dysregulation, respectively. Baseline DNAm GrimAge exceeded chronological age by 2.8 years on average across all samples. No EA acceleration marker was associated with HD or DST suppression status (p > 0.05).ConclusionEA acceleration markers shown to be strongly predictive of physiological dysregulation and mortality-risk, are not related to HD or DST non-suppression status (measured after 0.5 mg dexamethasone). The independency of HPA-axis dysregulation to EA acceleration does not support the biological relevance of this dosage-regimen when applied to patients with HD. These findings do not support the notion of accelerated cellular senescence in HD. Studies stratifying DST non-suppressors according to established dosage-regimens in somatic settings are needed to fully elucidate the putative contribution of HPA-axis dysregulation to EA.
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| 9. |
- Boström, Adrian Desai E., et al.
(författare)
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Regional clozapine, ECT and lithium usage inversely associated with excess suicide rates in male adolescents
- 2023
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Ingår i: Nature Communications. - : Nature Publishing Group. - 2041-1723. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 10. |
- Chatzittofis, Andreas, et al.
(författare)
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HPA axis dysregulation is associated with differential methylation of CpG-sites in related genes
- 2021
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Ingår i: Scientific Reports. - : Springer Nature. - 2045-2322. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- DNA methylation shifts in Hypothalamic–pituitary–adrenal (HPA) axis related genes is reported in psychiatric disorders including hypersexual disorder. This study, comprising 20 dexamethasone suppression test (DST) non-suppressors and 73 controls, examined the association between the HPA axis dysregulation, shifts in DNA methylation of HPA axis related genes and importantly, gene expression. Individuals with cortisol level ≥ 138 nmol/l, after the low dose (0.5 mg) dexamethasone suppression test (DST) were classified as non-suppressors. Genome-wide methylation pattern, measured in whole blood using the EPIC BeadChip, investigated CpG sites located within 2000 bp of the transcriptional start site of key HPA axis genes, i.e.: CRH, CRHBP, CRHR-1, CRHR-2, FKBP5 and NR3C1. Regression models including DNA methylation M-values and the binary outcome (DST non-suppression status) were performed. Gene transcripts with an abundance of differentially methylated CpG sites were identified with binomial tests. Pearson correlations and robust linear regressions were performed between CpG methylation and gene expression in two independent cohorts. Six of 76 CpG sites were significantly hypermethylated in DST non-suppressors (nominal P < 0.05), associated with genes CRH, CRHR1, CRHR2, FKBP5 and NR3C1. NR3C1 transcript AJ877169 showed statistically significant abundance of probes differentially methylated by DST non-suppression status and correlated with DST cortisol levels. Further, methylation levels of cg07733851 and cg27122725 were positively correlated with gene expression levels of the NR3C1 gene. Methylation levels of cg08636224 (FKBP5) correlated with baseline cortisol and gene expression. Our findings revealed that DNA methylation shifts are involved in the altered mechanism of the HPA axis suggesting that new epigenetic targets should be considered behind psychiatric disorders.
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| 11. |
- Chatzittofis, Andreas, et al.
(författare)
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Neurochemical and Hormonal Contributors to Compulsive Sexual Behavior Disorder
- 2022
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Ingår i: Current Addiction Reports. - : Springer Berlin/Heidelberg. - 2196-2952. ; 9, s. 23-31
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Forskningsöversikt (refereegranskat)abstract
- Purpose of Review: Compulsive sexual behavior disorder has been recently included in the 11th revision of the International Classification of Diseases (ICD-11), and the possible contribution of neurochemical and hormonal factors have been reported. However, relatively little is known concerning the neurobiology underlying this disorder. The aim of this article is to review and discuss published findings in the area.Recent Findings: Evidence suggests that the neuroendocrine systems are involved in the pathophysiology of compulsive sexual behavior. The hypothalamus-pituitary adrenal axis, the hypothalamus-pituitary–gonadal axis, and the oxytocinergic system have been implicated.Summary: Further studies are needed to elucidate the exact involvement of neuroendocrine and hormonal systems in compulsive sexual behavior disorder. Prospective longitudinal studies are particularly needed, especially those considering co-occurring psychiatric disorders and obtaining hormonal assessments in experimental circumstances with appropriate control groups.
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| 12. |
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| 13. |
- Flanagan, John, et al.
(författare)
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High plasma oxytocin levels in men with hypersexual disorder
- 2022
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : Oxford University Press. - 0021-972X .- 1945-7197. ; 107:5, s. e1816-e1822
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Tidskriftsartikel (refereegranskat)abstract
- Context: Hypersexual disorder (HD) involves excessive, persistent sexual behaviors related to various mood states and the diagnosis compulsive sexual behavior disorder is included as an impulse control disorder in the 11th revision of the International Classification of Diseases. Although the neurobiology behind the disorder is not clear, some studies suggest dysregulated hypothalamic-pituitary-adrenal axis. Oxytocin acts as counterregulatory neuroendocrine hormone to cortisol and is also involved in sexual behavior.Objective: We hypothesized that oxytocin may play a role in the pathophysiology of HD with compensatory actions to cortisol.Design: Longitudinal.Setting: ANOVA clinic (Karolinska University Hospital).Patients or other participants: 64 males with HD and 38 age-matched healthy volunteers.Main Outcome Measures: Plasma oxytocin levels, measured with radioimmunoassay; Hypersexual Disorder Screening Inventory; and Hypersexual Disorder: Current Assessment Scale for assessing hypersexual symptoms.Interventions: A patient subgroup (n=30) completed the manual-based group-administered cognitive-behavioral therapy (CBT) program for HD, and posttreatment oxytocin levels were measured.Results: Hypersexual men (n=64) exhibited significantly higher oxytocin plasma levels (mean±SD: 31.0±9.9 pM) compared with healthy volunteers (16.9±3.9 pM; P<0.001). There were significant positive correlations between oxytocin levels and the rating scales measuring hypersexual behavior. Patients who completed CBT treatment (n=30) had a significant reduction of oxytocin plasma levels from pretreatment (30.5±10.1 pM) to posttreatment (20.2±8.0 pM; P<0.001).Conclusions: The results suggest that the hyperactive oxytocinergic system in hypersexual men may be a compensatory mechanism to attenuate hyperactive stress.
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| 14. |
- Jamshidi, Esmail, et al.
(författare)
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Increased methylation of brain-derived neurotrophic factor (BDNF) is related to emotionally unstable personality disorder and severity of suicide attempt in women
- 2023
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Ingår i: Cells. - : MDPI AG. - 2073-4409. ; 12:3
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 15. |
- Jokinen, Jussi, et al.
(författare)
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Accelerated epigenetic aging in suicide attempters uninfluenced by high intent-to-die and choice of lethal methods
- 2022
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Ingår i: Translational Psychiatry. - : Springer Nature. - 2158-3188. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Suicide attempts (SA) are associated with excess non-suicidal mortality, putatively mediated in part by premature cellular senescence. Epigenetic age (EA) estimators of biological age have been previously demonstrated to strongly predict physiological dysregulation and mortality risk. Herein, we investigate if violent SA with high intent-to-die is predictive of epigenetics-derived estimates of biological aging. The genome-wide methylation pattern was measured using the Illumina Infinium Methylation EPIC BeadChip in whole blood of 88 suicide attempters. Subjects were stratified into two groups based on the putative risk of later committed suicide (low- [n = 58] and high-risk [n = 30]) in dependency of SA method (violent or non-violent) and/or intent-to-die (high/low). Estimators of intrinsic and extrinsic EA acceleration, one marker optimized to predict physiological dysregulation (DNAmPhenoAge/AgeAccelPheno) and one optimized to predict lifespan (DNAmGrimAge/AgeAccelGrim) were investigated for associations to severity of SA, by univariate and multivariate analyses. The study was adequately powered to detect differences of 2.2 years in AgeAccelGrim in relation to SA severity. Baseline DNAmGrimAge exceeded chronological age by 7.3 years on average across all samples, conferring a mean 24.6% increase in relation to actual age. No individual EA acceleration marker was differentiated by suicidal risk group (p > 0.1). Thus, SA per se but not severity of SA is related to EA, implicating that excess non-suicidal mortality in SA is unrelated to risk of committed suicide. Preventative healthcare efforts aimed at curtailing excess mortality after SA may benefit from acting equally powerful to recognize somatic comorbidities irrespective of the severity inherent in the act itself.
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| 16. |
- Lundberg, Mathias, et al.
(författare)
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Challenges and opportunities in the diagnosis and treatment of early-onset psychosis : a case series from the youth affective disorders clinic in Stockholm, Sweden
- 2024
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Ingår i: Schizophrenia. - : Springer Nature. - 2754-6993. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- Early-onset psychosis is linked to adverse long-term outcomes, recurrent disease course, and prolonged periods of untreated illness; thus highlighting the urgency of improving early identification and intervention. This paper discusses three cases where initial emphasis on psychosocial treatments led to diagnostic and therapeutic delays: (1) a 15-year-old misdiagnosed with emotionally unstable personality disorder and autism, who improved on bipolar medication and antipsychotics; (2) another 15-year-old misdiagnosed with autism, who stabilized on lithium and antipsychotics, subsequently allowing for gender dysphoria evaluation; (3) a 9-year-old autistic boy incorrectly treated for ADHD, who recovered with appropriate antipsychotic treatment. These cases illuminate the vital importance of adhering to a diagnostic hierarchy, prioritizing diagnostic utility, and conducting longitudinal evaluations to facilitate early targeted treatment of psychotic symptoms in early-onset psychosis. Adherence to such strategies can minimize delays in managing early-onset psychosis and improve long-term prognoses.
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| 17. |
- Sokolov, Aleksandr V., et al.
(författare)
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Methylation in MAD1L1 is associated with the severity of suicide attempt and phenotypes of depression
- 2023
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Ingår i: Clinical Epigenetics. - : BioMed Central (BMC). - 1868-7083. ; 15:1
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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