Specific Disorders Research Articles

The neural connectome of suicidality in adults with mood and anxiety disorders

Although suicide risk is a major public health issue, attempts to understand the neural basis of suicidality have been limited by small sample sizes and a focus on specific psychiatric disorders. This sample comprised 579 participants, of whom 428 had a psychiatric disorder (depression, anxiety or stress-related disorder) and 151 were non-psychiatric controls. All participants underwent structured clinical interviews, including an assessment of suicidality in the past month, and completed a functional magnetic resonance imaging scan. There were 238 (41.1%) participants who met criteria for suicidality and 341 (58.9%) were non-suicidal. Task-derived functional connectivity was calculated for 436 brain regions, comprising 8 intrinsic connectivity networks. Participants who were suicidal had decreased connectivity in a network of 143 connections across 86 brain regions. This pattern was characterized primarily by decreased connectivity within the visual, somatomotor and salience networks, between these networks, and also with the default mode and limbic networks. By adopting a transdiagnostic approach with a very large sample of individuals with mood disorders, anxiety and stress and non-psychiatric participants, this study highlights the hypoconnectivity that characterizes suicidality and points to altered connectivity within and between key networks involved in emotional, sensory and cognitive processes that are implicated in suicidal risk.

Exploring the role of genetic factors in personality disorders among women with heroin dependence

Heroin dependence is a severe psychiatric issue that often coexists with mood disorders and personality disorders, which further compound the complexity and severity of the dependence. The utilization of genetic factors in predicting psychiatric disorders has made notable advancements. We enrolled female patients diagnosed with heroin dependence (n = 263) and assessed individuals with paranoid personality disorder, depressive personality disorder, antisocial personality disorder, and schizoid personality disorder based on the DSM-IV criteria. Our objective was to examine the single nucleotide polymorphisms (SNPs; rs174696, rs174699, rs4680, rs4818, rs737866, rs933271, rs12953076b, and rs44458044b) and their association with personality. We discovered a significant association of antisocial personality disorder with rs1544325, rs4680, and rs4818 (P < 0.05). Additionally, hallucinogen use was associated with rs3792738 (P < 0.05), rs10062367 (P < 0.05), and rs1875999 (P < 0.01). However, we did not observe a relationship between the SNPs and schizoid personality disorder, paranoid personality disorder, or depressive personality disorder. Heroin dependence is linked to specific personality disorders, particularly antisocial personality disorder. The influence of genetic factors could have a significant impact on the emergence of personality alterations linked to the consumption of heroin.

Evaluation of primary markers of inflammation and the systemic inflammation index in specific learning disabilities.

Aim: Specific learning disorder (SLD) is a term that refers to reading, writing and arithmetic difficulties. The neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR) and systemic inflammation index (SII) are affordable and accessible inflammatory biomarkers. This research aims to evaluate the relationship between NLR, PLR, SII and SLD to determine whether inflammation contributes to pathogenesis.Methods: This study included 90 SLD-diagnosed patients and 90 age-, sex- and ethnicity-matched healthy controls. Blood cell counts and NLR, PLR and SII values were obtained from medical records and compared between the two groups.Results: The NLR, PLR and SII were significantly higher (p=0.029, p=0.033 and p=0.018 respectively) and lymphocyte counts were significantly lower (p=0.041) in the SLD group. WISC-R total scores decreased with age in the SLD group (-1.988 coefficient, Beta=-0.247ß, p=0.041). Multivariate logistic regression analysis revealed that the SII was the only parameter independently associated with the diagnosis of SLD (Beta=0.003, p=0.023).Conclusion: Inflammation might play a role in SLD etiopathogenesis. NLR, PLR and SII may be potential biomarkers for SLD in children. Further research may lead to early diagnosis and additional anti-inflammatory pharmacological therapies for SLDs.

Initial development of a digitally based comprehensive child mental health questionnaire.

The present report describes the item development and initial validation of a comprehensive child mental health questionnaire through a series of four studies. To maximize clinical utility, the questionnaire was developed to directly reflect Diagnostic and Statistical Manual of Mental Disorders, fifth edition psychiatric criteria and diagnoses, cover all mental health conditions that present in youth, and capitalize on the benefits of digital administration, particularly tiered branching logic. Study 1 describes the item generation and development of a tiered item structure. Study 2 established internal consistency and discriminant validity in a representative community sample of 1,000 youth aged 7-17 and a parent. Study 3 examined the acceptability of the questionnaire's content and structure to families and made indicated text revisions. Finally, Study 4 cross validated the internal consistency and tiered structure of a revised version of the questionnaire in a second representative normative sample of 1,000 parent and child dyads. The four studies resulted in a questionnaire consisting of one general mental health question (parent-report only), 16 items (for both parent and child) on a diagnostic category checklist, and 40 scales with screener and follow-up items reflecting DSM-5 criteria for specific disorders (371 parent items and 326 child items). The data support the potential of the questionnaire to efficiently assess the breadth of youth psychiatric symptoms efficiently. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Advances in the Differentiation of hiPSCs into Cerebellar Neuronal Cells.

The cerebellum has historically been primarily associated with the regulation of precise motor functions. However, recent findings suggest that it also plays a pivotal role in the development of advanced cognitive functions, including learning, memory, and emotion regulation. Pathological changes in the cerebellum, whether congenital hereditary or acquired degenerative, can result in a diverse spectrum of disorders, ranging from genetic spinocerebellar ataxias to psychiatric conditions such as autism, and schizophrenia. While studies in animal models have significantly contributed to our understanding of the genetic networks governing cerebellar development, it is important to note that the human cerebellum follows a protracted developmental timeline compared to the neocortex. Consequently, employing animal models to uncover human-specific molecular events in cerebellar development presents significant challenges. The emergence of human induced pluripotent stem cells (hiPSCs) has provided an invaluable tool for creating human-based culture systems, enabling the modeling and analysis of cerebellar physiology and pathology. hiPSCs and their differentiated progenies can be derived from patients with specific disorders or carrying distinct genetic variants. Importantly, they preserve the unique genetic signatures of the individuals from whom they originate, allowing for the elucidation of human-specific molecular and cellular processes involved in cerebellar development and related disorders. This review focuses on the technical advancements in the utilization of hiPSCs for the generation of both 2D cerebellar neuronal cells and 3D cerebellar organoids.

An observational study of the causes of an isolated elevated alkaline phosphatase level of unclear etiology

BackgroundSerum alkaline phosphatase (ALP) is a commonly obtained laboratory test, but its diagnostic specificity is limited because it is found in multiple tissues. We investigated patients with isolated, elevated, ALP levels without an obvious etiology at presentation to determine the frequency of different causes of an isolated elevated ALP. MethodsThis was a retrospective, cohort study of adults (age >18 years old) from January 1st, 2013, to June 30th, 2020 in both the in- and outpatient setting at the Medical University of South Carolina. 260 patients with an isolated, elevated ALP of unknown etiology (patients with known biliary obstruction, underlying parenchymal liver disease, or pregnancy were excluded) were included. A secondary outcome was mean survival time from the ALP result. ResultsThe most common cause of ALP elevation was due to underlying malignancy (147, 57%), with 61 patients having infiltrative intrahepatic malignancy, 52 patients having bony metastasis, and 34 patients having both hepatic and bone metastasis. Bone disease (75, 29%), unsuspected parenchymal liver disease (18, 7%), non-malignant infiltrative liver disease (7, 2%), and other disorders (13, 5%) accounted for the remainder of the cohort. Notably, 123 of 260 (47%) patients died within an average of 58 months after identification of isolated, elevated ALP. ConclusionsAn isolated, elevated ALP of unclear etiology is associated with several very specific and important disorders, in particular metastatic intrahepatic malignancy - and is uncommonly associated with primary parenchymal liver disease. Providers should be aware of the potential clinical significance of an elevated ALP.

Mediation-adjusted multivariable Mendelian randomisation study identified novel metabolites related to mental health

BackgroundFrom the pathway perspective, metabolites have the potential to improve knowledge about the aetiology of psychiatric diseases. Previous studies suggested a link between specific blood metabolites and mental disorders, but...

Refining criteria for a neurodevelopmental sub-phenotype of bipolar disorders: a FondaMental Advanced Centers of Expertise for Bipolar Disorders study

Bipolar disorder (BD) is a complex and heterogeneous psychiatric disorder. Neurodevelopmental factors were suggested to contribute to the etiology of BD, yet a specific neurodevelopmental phenotype of the disorder remains unidentified. Our objective was to define and characterize a neurodevelopmental phenotype (NDP) in BD and validate its associations with clinical outcomes, polygenic risk scores (PGS), and treatment responses. We analyzed the FACE-BD cohort of 4,468 BD patients, a validation cohort of 101 BD patients, and two independent replication datasets of 274 and 89 BD patients. Using factor analyses, we identified a set of criteria for defining NDP. We next developed a scoring system for NDP-load and assessed its association with prognosis, neurological soft signs, polygenic risk scores for neurodevelopmental disorders, and responses to treatment using multiple regressions, adjusted for age and sex with bootstrap replications. Our study established a NDP in BD consisting of nine clinical features: advanced paternal age, advanced maternal age, childhood maltreatment, attention deficit hyperactivity disorder (ADHD), early onset of BD, early onset of substance use disorders, early onset of anxiety disorders, early onset of eating disorders, specific learning disorders. Patients with higher NDP-load showed a worse prognosis and increased neurological soft signs. Notably, these individuals exhibited a poorer response to lithium treatment. Furthermore, a significant positive correlation was observed between the NDP-load and PGS for ADHD suggesting potential overlapping genetic factors or pathophysiological mechanisms between BD and ADHD. The proposed NDP constitutes a promising clinical tool for patient stratification in BD.

A Document Analysis on the Use of Assistive Technology in School-Based Instruction for Children with Specific Learning Disorders in Cameroon and Canada

This study explored the use of assistive technology (AT) in the school-based instruction of children with specific learning disorders (SLDs) in Cameroon and Canada using a content-analysis, qualitative research design. Eight documents met inclusion criteria and were analyzed, leading to a comparison of both countries. Three themes are reported on: availability of AT, policies and legislation, and financial assistance. The results of the study show that AT is available for use in both countries and that there are policies and legislation in both countries to control access to and provision of AT. Also, there is financial assistance provided to help fund AT needs for children with SLD. Implications and a number of recommendations are offered, including providing AT to children with SLD; increasing funding and financial support for the provision of AT; training children with SLD, teachers, and family members in the use of AT; and enacting national AT legislation.

Exploring the intersection of polygenic risk scores and prenatal alcohol exposure: Unraveling the mental health equation.

Prenatal alcohol exposure poses significant risks to offspring mental health. However, the interplay between genetic predispositions to mental health disorders and prenatal alcohol exposure remains incompletely understood, limiting our ability to develop effective interventions for these conditions. Data from the Adolescent Brain and Cognitive Development (ABCD) Study were analyzed to explore associations between polygenic risk scores (PRS) for mental disorders and maternal alcohol consumption during pregnancy. Logistic regression and structural equation modeling were utilized to assess these relationships. Maternal alcohol consumption after pregnancy awareness was significantly associated with an increased genetic risk for specific mental health disorders, particularly bipolar disorder in offspring. The relationship between maternal alcohol consumption and mental health outcomes was influenced by polygenic risk scores, with both externalizing and internalizing problems being affected. Our findings highlight the specific interaction between increased genetic risk for bipolar disorder and prenatal alcohol exposure in shaping offspring mental health outcomes. The significant associations we observed underscore the importance of considering both polygenic risk scores and prenatal alcohol exposure when assessing mental health risks in children. These insights emphasize the need for targeted interventions that address both genetic predispositions and environmental exposures to better understand and mitigate the impact on offspring mental health.

Role of MRI in Diagnosis of Rapidly Progressive Cognitive Impairment- A Case Of Sporadic Creutzfeldt Jakob Disease (sCJD)

Abstract Background The role of neuroimaging in dementia extends beyond its traditional role of excluding neurosurgical lesions. Radiological findings may support the diagnosis of specific neurodegenerative disorders and aid differentiation from other neurodegenerative conditions e.g. CJD1. sCJD is a fatal neurodegenerative disease, which typically presents with neuropsychiatric symptoms, myoclonus, cerebellar and pyramidal/extrapyramidal symptoms. The diagnosis often is quite difficult, requiring high degree of suspicion, advanced neuroimaging and biochemical markers. Confirmation is only possible via brain biopsy. The condition can result in rapidly progressive dementia/neurocognitive decline and death, usually within a year from onset. Methods We report a case of a rapidly progressive dementia in a 79-year-old male who was diagnosed with probable sCJD, after having an MRI which picked up suspicious characteristic findings leading to the eventual diagnosis confirmation via further workup. The patient presented with acute rapid progressive forgetfulness and functional decline of 2 weeks with initial workup unyielding. Results A contrast MRI Brain eventually showed focal increased T2 and flair signals in the right parafalcine and parietal cortex demonstrating mild fluid restriction without any focal contrast enhancement, a pattern highly suspicious for sCJD. A CSF sample subsequently revealed RT-QulC positivity confirming the diagnosis. The patient eventually passed away despite ward-based care after 4 weeks of admission due to rapid neurological decline. A brain biopsy was not deemed feasible given patient’s condition. Conclusion The case highlights a relatively atypical symptomology of sCJD and, highlights the role of MRI imaging in assessment and diagnosis of dementias and specifically in sCJD. Increasing use of advanced neuroimaging may aid in diagnosis of specific/rare causes of rapidly progressive dementias. Reference Vitali, P., Maccagnano, E., Caverzasi, E., Henry, R.G., Haman, A., Torres-Chae, C., Johnson, D.Y., Miller, B.L. and Geschwind, M.D., 2011. Diffusion-weighted MRI hyperintensity patterns differentiate CJD from other rapid dementias. Neurology, 76(20), pp. 1711-1719.

Changes in Child Psychiatry Presentations in the Second Wave of Coronavirus Disease 2019 Pandemic Compared to the Pre-pandemic Period and the First Wave: A Follow-up Study.

It is to examine how child psychiatry admissions, diagnosis and treatment trends in the second wave (September-December 2020/SD20) of the coronavirus disease 2019 (COVID-19) pandemic change compared to the pre-pandemic (SD19) and the first wave (March-June 2020/MJ20). Our study was planned as a multicenter, retrospective cross-sectional. Data were obtained from hospital computer systems databases. All patients admitted to the child psychiatry clinic on SD19 and SD20 constituted the study sample. In total, 5244 admissions were assessed. Of the admissions, 1459 were repeat exams, and 3785 were cases. 50.9% (n = 1927) of the cases came in SD19 and 49.1% (n = 1858) in SD20. In 2019, 37% (n = 825) of cases were girls, compared to 41.6% (n = 646) in 2020 (P = .004). The mean age of those who came in 2019 was 9.61 ± 4.08; The mean age of those who came in 2020 was 10.15 ± 5.38 (P = .002). In 2020, oppositional defiant conduct disorder, major depressive disorder, social anxiety disorder, obsessive-compulsive disorder, sleep-wake disorder, and dysthymia were significantly higher, while specific learning disorders, separation anxiety disorder, and intellectual disability were found to be lower. The decrease in second-wave admissions is less than in the first wave. In the second wave, externalizing and internalizing problems have increased. Drug therapy was prioritized. Postponing admissions was less in the second wave.

A Study on the Effects of Memory Training and Speech Processing Intervention on Children's Working Memory and Speech Skills: Based on the Perspective of Brain and Cognitive Science

The present study examined the effect of phonological processing and working memory intervention on the verbal working memory and phonological skills of children with Specific reading disorders. Ten participants between 7 to 10 years of age who met ICD 10 criteria for specific reading disorders, were assigned to an experimental group, or a control group. Intelligence screening was done using the Colored Progressive Matrices. Pre - test and post - test measures were the Test of Memory for Children (TOMC) and Informal Reading Assessment (IRA). The intervention group received 30 sessions of phonological processing intervention and working memory intervention. The control group received no intervention. Post - test assessments included TOMC and IRA. Participants who had received the intervention showed more improvement than controls. The majority of the participants in the experimental group performed higher post - intervention.

Association of air pollutants with psychiatric disorders: a two-sample Mendelian randomization

BackgroundThe link between air pollution and increased risk of psychiatric disorders has been growing in evidence. However, the causal relationship between air pollution and psychiatric disorders remains poorly understood. MethodsSingle-nucleotide polymorphisms associated with air pollutants (including NOx, NO2, PM2.5, PM2.5–10, and PM10) from the UK Biobank were used as instrumental variables. Summary-level data for psychiatric disorders (major depressive disorder, anxiety, bipolar disorder, schizophrenia, post-traumatic stress disorder, attention deficit hyperactivity disorder, autism spectrum disorder, anorexia nervosa, and obsessive-compulsive disorder) were procured from the Psychiatric Genomics Consortium and FinnGen consortium. Two-sample Mendelian randomization (MR) analysis was conducted to analyze the causal associations. ResultsThe MR analysis revealed significant associations between certain air pollutants and specific types of psychiatric disorders. The inverse-variance weighted model of preliminary analysis indicated that genetically predicted NO2 was associated with increased risks of major depressive disorder (odds ratio [OR]: 1.13, 95 % confidence intervals [CI]: 1.00–1.28, P = 0.041), bipolar disorder (OR: 1.26, 95 % CI: 1.00–1.58, P = 0.0497), schizophrenia (OR: 1.57, 95 % CI: 1.23–2.00, P < 0.001), attention deficit hyperactivity disorder (OR: 1.61, 95 % CI: 1.25–2.09, P < 0.001) and autism spectrum disorder (OR: 1.39, 95 % CI: 1.01–1.91, P = 0.044). Genetically predicted PM2.5 showed a positive association with the risk of major depressive disorder (OR: 1.21, 95 % CI: 1.06–1.39, P = 0.006), bipolar disorder (OR: 1.32, 95 % CI: 1.03–1.69, P = 0.030) and attention deficit hyperactivity disorder (OR: 1.57, 95 % CI: 1.16–2.12, P = 0.004). In addition, our results also indicated that NOx (OR: 1.64, 95 % CI: 1.21–2.21, P = 0.0012) and PM10 (OR: 1.70, 95 % CI: 1.23–2.36, P = 0.0014) could increase the risk of attention deficit hyperactivity disorder. ConclusionsThe MR analysis provides evidence for the causality of different air pollutants on specific psychiatric disorders, underscoring the importance of mitigating air pollution to reduce the risk of psychiatric disorders.

Hypertensive Disorders of Pregnancy: A Window into Breastfeeding Outcomes in Varied Healthcare Systems

Varied hospital systems demonstrate diverse and often very different approaches to patient care. This may best be analyzed by looking at specific disorders and outcomes in a population with these disorders. As one such lens, hypertensive disorders of pregnancy (HDPs) continue to pose a severe health risk for mothers and infants, and breastfeeding outcomes play a crucial role in determining long-term maternal and fetal health. This pilot study investigated breastfeeding outcomes in two hospitals, as representatives for differing healthcare systems, among patients diagnosed with HDPs. Data were collected for 12 months at two hospitals, one private and one military, on 729 patients diagnosed with HDPs. Data were analyzed for infant maturity at birth and breastfeeding outcomes. Most participants (83.2%) stated their intention to breastfeed for the first six months of life. By hospital discharge, only 56% (p = 0.0001) of the private hospital participants were breastfeeding compared to 65% of the military hospital participants. In addition, while 69% of infants were born before term, more infants were born before term at the private hospital (71%) than at the military hospital (65%), with 37% (private) and 42% (military) of preterm infants breastfeeding at hospital discharge. Significant differences existed between these two hospital systems in the number of those initiating breastfeeding and breastfeeding at hospital discharge. The military hospital was more successful in assisting these high-risk women in meeting their breastfeeding intentions. Changes in hospital practices, such as metrics and incentivization, focusing on breastfeeding support, could improve the rate of breastfeeding at hospital discharge and impact long-term health outcomes.

The role of ATP citrate lyase in myelin formation and maintenance.

Formation of myelin by Schwann cells is tightly coupled to peripheral nervous system development and is important for neuronal function and long-term maintenance. Perturbation of myelin causes a number of specific disorders that are among the most prevalent diseases affecting the nervous system. Schwann cells synthesize myelin lipids de novo rather than relying on uptake of circulating lipids, yet one unresolved matter is how acetyl CoA, a central metabolite in lipid formation is generated during myelin formation and maintenance. Recent studies have shown that glucose-derived acetyl CoA itself is not required for myelination. However, the importance of mitochondrially-derived acetyl CoA has never been tested for myelination in vivo. Therefore, we have developed a Schwann cell-specific knockout of the ATP citrate lyase (Acly) gene to determine the importance of mitochondrial metabolism to supply acetyl CoA in nerve development. Intriguingly, the ACLY pathway is important for myelin maintenance rather than myelin formation. In addition, ACLY is required to maintain expression of a myelin-associated gene program and to inhibit activation of the latent Schwann cell injury program.

Phosphodiesterases: Evolving Concepts and Implications for Human Therapeutics.

Phosphodiesterases (PDEs) are a superfamily of enzymes that hydrolyze cyclic nucleotides. While the 11 PDE subfamilies share common features, key differences confer signaling specificity. The differences include substrate selectivity, enzymatic activity regulation, tissue expression, and subcellular localization. Selective inhibitors of each subfamily have elucidated the protean role of PDEs on normal cell function. PDEs are also linked to diseases, some of which affect the immune, cardiac, and vascular systems. Selective PDE inhibitors are clinically used to treat these specific disorders. Ongoing preclinical studies and clinical trials are likely to lead to the approval of additional PDE-targeting drugs for therapy in human disease. In this review, we discuss the structure and function of PDEs and examine current and evolving therapeutic uses of PDE inhibitors, highlighting their mechanisms and innovative applications that could further leverage this crucial family of enzymes in clinical settings.

Predicting Mental Health Hospitalizations Among First Nations Adults in Residential Treatment

Indigenous peoples in Canada experience disproportionately higher rates of hospitalization for mental health and substance use concerns than non-Indigenous populations. Ambulatory care sensitive conditions are community-level markers of mental illness which can theoretically be managed through community-based health services, and therefore should not require urgent care services. Previous mental health related ambulatory sensitive conditions have included psychotic and mood disorders; however, limited research has explored these relationships of increased hospitalization among specific health disorders with Indigenous populations. This study analyzed predictors of prior mental health hospitalizations among a predominately First Nations population seeking residential treatment for substance use. We hypothesized that increased co-morbid mental health concerns would predict increased hospitalizations for mental health concerns, and this relationship would be moderated by higher Adverse Childhood Experience (ACE) scores. Logistic regression showed that for every increase in each reported mental health concern, the odds of prior hospitalization was 1.6 times higher among this sample, although ACEs did not moderate this relationship. Participants with depressive, anxiety-related, psychotic, and personality-related disorders reported proportionally more hospitalization. Although study results suggest ACEs are not a useful predictor of hospitalization, their presence has previously shown to exacerbate co-morbid concerns, and thus, may influence prior hospitalization history indirectly. Further research can explore relationships between exposure to childhood trauma and hospitalization, particularly in consideration of access to tertiary mental health services.

The effect of individual differences on Pavlovian conditioning in specific Internet-use disorders

The I-PACE model suggests that Internet-use disorders result from the interplay of individual vulnerabilities and cognitive and affective processes. As in substance use disorders, Pavlovian conditioning processes are attributed a key role. However, and despite progress in identifying individual vulnerabilities, factors influencing appetitive conditioning remain poorly understood. We therefore conducted a Pavlovian conditioning experiment in which individuals with risky as well as non-problematic use of either gaming or buying-shopping applications learned to associate different abstract stimuli with either gaming or buying-shopping. Regression analyses were used to identify individual characteristics influencing awareness of the experimental contingencies, speed of acquisition of awareness and the magnitude of the conditioned emotional responses regarding pleasantness and arousal ratings of the stimuli. Results demonstrated successful Pavlovian conditioning and an attentional bias towards reward-predicting cues. Awareness of the experimental contingencies was linked solely to cognitive abilities, while the speed of acquisition of awareness and the magnitude of conditioned responses was influenced by specific personality characteristics, experiences of compensation from using the application and severity of problematic use. Importantly, certain characteristics specifically predicted the magnitude of the conditioned response towards gaming, while others specifically predicted the response towards buying-shopping, highlighting differing vulnerabilities. These findings underscore the importance of targeted interventions and prevention strategies tailored to these specific vulnerability factors. Further implications and limitations are discussed.

Educational differences in years lived with disability due to mental and substance use disorders: a cohort study using nationwide Norwegian and Danish registries

BackgroundFindings from the Global Burden of Disease (GBD) study have shown that the burden of mental and substance use disorders is considerable, and unevenly distributed across demographic groups in the population. However, there is a lack of knowledge on how this burden differs by socioeconomic position. The aim of this study was to examine educational differences in years lived with disability (YLDs) from mental and substance use disorders among males and females in two high-income countries, taking comorbidity with other diseases into account.MethodsThe study included all registered residents in Denmark and Norway from 2011 to 2021. Diagnostic information was retrieved from records in the Norwegian National Patient Registry (NPR) and the Danish Psychiatric Central Research Register (PCRR) and used as proxy measures for disorder prevalence. Demographical and educational information was taken from administrative registries. The YLD is a measure of the non-fatal health loss in the population and was calculated by multiplying the duration of a disorder with a disability weight (DW), scaled between 0 and 1. Information on remission and DWs were retrieved from the GBD study and other sources, and disorder specific DWs were averaged by severity levels and adjusted for comorbidity.ResultsEducational gradients in YLD rates were found for mental and substance disorders overall, and for most of the specific disorders. The educational gradient was more pronounced for schizophrenia, intellectual disability and substance use disorders than for eating, anxiety, and affective disorders. Both higher YLD rates, and a larger attributed proportion of the total YLDs, were found for schizophrenia, intellectual disability, and substance use disorders in the groups with low versus high education. YLD rates for eating, anxiety, and affective disorders were more equal across educational levels, but constituted a smaller proportion of the total YLDs among the groups with low versus the groups with high educational level.ConclusionMost of the disease burden related to mental and substance use disorders falls on those with the fewest years of education. This should be taken into consideration when public health targets aimed at improving mental health and reducing social inequalities in health are developed and implemented.