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Results for “comorbidity”

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PubMed2025

Comorbidity alters the genetic relationship between anxiety disorders and major depression.

BACKGROUND: Comorbid anxiety disorders (ANX) and major depression (MD) have worse clinical outcomes than either disorder alone. Analysis of genomic data based on comorbidity status may reveal more precise biological pathways and causal relationships with potential clinical implications. We investigated the genetic relationship between ANX and MD with and without mutual comorbidity. METHODS: We leveraged data from UK Biobank to perform disorder-specific genome-wide association studies (GWAS) of ANX-only (n=189,422) and MD-only (n=194,339) and generate polygenic risk scores (PRS). The Norwegian Mother, Father, and Child Cohort (MoBa, n = 130,992) served to test the associations of PRS with diagnoses. MD and ANX GWAS, including comorbidities (MD-comorbid and ANX-comorbid), were used for comparison. Genetic correlations were compared by comorbidity status, and Mendelian randomization was employed to assess causal relationships. RESULTS: The MD-only PRS showed a stronger association with MD-only compared to ANX-only cases (Z=3.74; Padjusted=0.002); however, MD-comorbid PRS did not show a significant difference (Z=2.71; Padjusted=0.08). The genetic correlation between ANX-only and MD-only was 0.53, lower than between ANX-comorbid and MD-comorbid (0.90). ANX-only showed a causal relationship with MD-only (Padjusted=0.015), but not vice versa, and contrasted the bidirectional causal relationship (Padjusted=2.9e-12, and Padjusted=9.3e-06) when comorbidity was included. Gene sets of MD-comorbid, ANX-comorbid, and MD-only, but not of ANX-only, were enriched for immune regulation pathways such as interleukin production. CONCLUSIONS: ANX and MD show more distinct genetics when comorbid cases are excluded, and ANX may be causal for MD. Disorder-specific genetic studies help uncover more relevant biological mechanisms and guide tailored clinical interventions.

Journal Article↗

PubMed2026

Apoptosis protein markers in comorbid type 2 diabetes mellitus and depression; relationships with cognitive performance, incident dementia, and white matter hyperintensities.

Type 2 diabetes mellitus (T2DM) and major depressive disorder (MDD) are reciprocal risk factors, and both elevate dementia risk. Dysregulation of programmed cell death is implicated in T2DM, MDD, and neurodegeneration, but proteomic markers of apoptosis have yet to be studied as dementia predictors in people with T2DM and/or MDD. This study examines apoptosis markers in comorbid T2DM and MDD, and their associations with cognitive, dementia, and neuroimaging outcomes. The retrospective sample (n = 15,765) consisted of UK Biobank participants (MDD only n = 1230; T2DM only n = 3644; comorbid T2DM + MDD n = 721). Individuals with T2DM + MDD comorbidity had poorer cognitive performance, and a higher 15-year dementia incidence (HR = 4.44, 95% CI = [3.23,6.11]). Among 60 apoptosis-related proteins identified by Kyoto Encyclopedia of Genes and Genomes pathway enrichment, 41 were significantly up-regulated in comorbid T2DM + MDD relative to controls, and 4 were higher in the comorbid group than both T2DM alone and MDD alone. Tumor necrosis factor ligand superfamily member 10 (TNFSF10), growth arrest and DNA damage-inducible protein GADD45 beta, tumor necrosis factor ligand superfamily member 6, and RAC-gamma serine/threonine-protein kinase were associated with dementia risk. Nine proteins (e.g. apoptosis-inducing factor 1, mitochondrial, caspase-2, mitogen-activated protein kinase kinase kinase 5, TNFSF10), were associated with white matter hyperintensity volumes in comorbid T2DM + MDD after FDR correction, but none were associated with cognitive performance, atrophy, or white matter microstructural changes. These findings identify peripheral apoptosis markers that were further elevated in comorbid T2DM + MDD compared to either alone, pointing to an important pathophysiological element underlying adverse outcomes in the context of mood and metabolic comorbidity.

Humans↗

PubMed1992

Comorbidity among anxiety disorders: implications for treatment and DSM-IV.

Research on comorbidity among psychological disorders is relatively new. Yet, comorbidity data have fundamental significance for classification and treatment. This significance is particularly apparent in the anxiety disorders, which, prior to DSM-III-R, were subsumed under disorders considered more significant (e.g., psychotic and depressive disorders). After considering definitional, methodological, and theoretical issues of comorbidity, data on comorbidity among the anxiety disorders are reviewed as well as data on comorbidity of anxiety disorders with the depressive, personality, and substance use disorders. Treatment implications are presented with preliminary data on the effects of psychosocial treatment of panic disorder on co-morbid generalized anxiety disorder. Implications of comorbidity for research on the nature of psychopathology and the ultimate integration of dimensional and categorical features in our nosology are considered.

Anxiety Disorders↗

PubMed2026

Plasma Proteomic Profiling of Comorbid and Noncomorbid COVID-19 Patients in ICU.

Type 2 Diabetes (T2D) and hypertension (HTN) are common comorbidities in severe COVID-19, yet their specific impact on proteomic recovery remains unclear. This study analyzed plasma protein signatures of critical COVID-19 patients with and without these comorbidities (COVID-only group [COG] and COVID comorbid group [CTHG]) on the first and last days of ICU stay. Proteomic analysis revealed a systemic shift characterized by upregulated immune responses and downregulated metabolic processes at admission across all patients. Survival was fundamentally defined by the restoration of homeostasis; liver-derived proteins─including LPA, TTR, and AHSG─were initially suppressed but rebounded significantly in survivors. This homeostatic recovery was impaired in CTHG compared to COG, with CTHG survivors showing attenuated recovery of metabolic markers. Distinct mortality-associated signatures also emerged between groups. COG nonsurvivors exhibited liver failure and severe hemolysis marked by persistent suppression of haptoglobin (HP). In contrast, CTHG mortality was driven by lipid metabolism dysregulation, with CD5L and APOA2 levels dropping specifically in comorbid nonsurvivors, often accompanied by a paradoxical elevation in APOA4─likely reflecting impaired renal clearance rather than restored lipid homeostasis. These findings indicate that preexisting T2D and HTN hinder physiological resolution of metabolic and lipid dysregulation, providing proteomic evidence for distinct mortality risks associated with failure to restore metabolic homeostasis in comorbid COVID-19 patients.

Humans↗

PubMed1992

Comorbidity in mania at first hospitalization.

Comorbidity was studied in 41 manic and mixed-state bipolar patients at first hospitalization. The lifetime prevalence of comorbidity was high; 21 subjects (51.2%) had at least one other psychiatric diagnosis (N = 16, 39.0%) or medical disorder (N = 9, 22.0%). Nine subjects had multiple comorbid diagnoses. Women were 2.7 times more likely to have a comorbid diagnosis. The presence of comorbidity was not associated with differences in outcome measures.

Adult↗

PubMed1992

Age-related psychiatric comorbidities and level of functioning in alcoholic veterans seeking outpatient treatment.

The relationship of age and of level of adaptive functioning to comorbidity of mental disorders among alcoholics was studied in a survey of all alcoholics seeking outpatient mental health treatment in the Veterans Affairs mental health care system during a one-month period in 1986 (N = 22,463). More than half of the alcoholic outpatients had one or more comorbid psychiatric diagnoses. Rates for comorbid substance abuse disorders, posttraumatic stress disorder, schizophrenia, and personality disorders peaked in younger alcoholics and then decreased with age. Age-related increases were observed for major depression, anxiety disorders, and organic brain syndrome or dementia. DSM-III axis V ratings of poor to grossly impaired functioning were consistent across age groups. More than half of alcoholics with a comorbid psychiatric disorder were rated as severely impaired, compared with less than a third of those with no comorbid mental disorder.

Activities of Daily Living↗

PubMed1992

Patient selection to peritoneal dialysis versus hemodialysis according to comorbid conditions.

An historical prospective sample of 2,420 non-diabetic and 1,738 diabetic Medicare patients incident from 1986-87 was analyzed for the selection of patients to peritoneal dialysis (PD) and hemodialysis (HD) according to comorbid factors. Data measuring the degree of comorbidity, describing the major diagnosis leading to end-stage renal disease (ESRD), and reporting other sociodemographic factors for incident ESRD patients were collected in a special study of the USRDS. Patients selected to PD were more likely to be white (greater mortality risk), diabetic (greater mortality risk), and younger (lower mortality risk) than patients assigned to HD. Estimates of the overall level of comorbidity with adjustment for race, gender, diabetes, and age provided evidence of a reduced total count of comorbid factors for PD compared to HD, particularly among diabetic patients under 60 years of age (p < 0.01). Assessment of selected risk factors, with adjustment for age and diabetes, indicated that patients selected to PD were not at greater comorbid risk according to cardiovascular factors but demonstrated a 20 percent increase in the likelihood of peripheral vascular disease (p = 0.02).

Cardiovascular Diseases↗

PubMed1992

Comorbid conditions and correlations with mortality risk among 3,399 incident hemodialysis patients.

The percent distribution of selected comorbid conditions from a national sample of 3,399 Medicare patients starting maintenance hemodialysis in 1986-87 is described. Using the Cox proportional hazards model, the relative mortality risk (RR) was assessed for comorbid conditions at time of ESRD while adjusting for the other comorbid and demographic covariates. Coronary artery disease and congestive heart failure, each present in 41 percent of patients, were associated with RR of 1.22 and 1.26 respectively (p < 0.0005 each). Fifty percent of patients had a serum albumin concentration at onset of ESRD of less than 3.5 gm/dl, and an increased risk of dying. Additionally, patients recorded as undernourished had an elevated risk (RR = 1.34, without adjustment for serum albumin, p < 0.0001). Other factors associated with a statistically significant increased mortality risk (p < 0.005) included older age, diabetes as cause of ESRD (particularly if insulin dependent), history of neoplasm, active smoker, and relatively low serum creatinine concentration. By describing the magnitude of risk associated with comorbid conditions, this study emphasizes the need for preventive efforts during the pre-ESRD stages of renal impairment. Studies are needed to document whether improvement in serum albumin or other comorbid factors before ESRD leads to reduction in mortality risk for ESRD patients.

Comorbidity↗

PubMed2025

Clinical impact of obsessive-compulsive disorder comorbidity in bipolar disorder: a systematic review and meta-analysis.

BACKGROUND: Bipolar disorder (BD) is commonly comorbid with other psychiatric conditions, such as obsessive-compulsive disorder (OCD). Despite increasing interest in this comorbidity, quantitative data on its clinical characteristics remain limited. This systematic review and meta-analysis aimed to evaluate the clinical impact of OCD comorbidity in BD by comparing individuals with BD and OCD (BD-OCD) to those with BD without OCD. METHODS: We systematically searched the PubMed/MEDLINE, Scopus, PsycINFO, and Web of Science databases up to April 15, 2024. Meta-analyses were conducted to compare BD-OCD and BD without OCD groups across multiple clinical domains. RESULTS: From 11,959 initial records screened, 26 studies were included in the qualitative synthesis, with 22 eligible for meta-analysis. Individuals with BD-OCD showed higher odds of experiencing chronic mood episodes (OR = 9.42; 95%CI = 2.23, 39.9), rapid cycling (OR = 1.92; 95%CI = 1.04, 3.53), comorbid eating disorders (OR = 3.37; 95%CI = 1.99, 5.7), panic disorder (OR = 3.3; 95%CI = 2.11, 5.2), substance use disorders (OR = 1.39; 95%CI = 1.02, 1.89), and lifetime suicide attempts (OR = 1.85; 95%CI = 1.21, 2.84). Additionally, they presented earlier onset of BD (SMD = -0.27; 95%CI = -0.52, -0.01) and reduced functioning (SMD = -0.42; 95%CI = -0.59, -0.24). Most data were derived from adult populations, limiting the evidence available for children and adolescents. CONCLUSIONS: BD-OCD presents a more severe and complex clinical profile, requiring specialized assessment and integrated treatment approaches. Identifying these features may support earlier recognition and inform personalized interventions for this population.

Humans↗

PubMedDate not supplied

Treatment implications of comorbid psychopathology in American Indians and Alaska Natives.

This paper discusses treatment implications of comorbid psychopathology in the context of American Indian and Alaska Native culture and in the context of the Indian Health Service's Mental Health and Alcohol and Substance Abuse Program Branches. Treatment of comorbidity in this population is a particularly difficult problem due to numerous barriers to treatment and a poorly defined treatment system. As in other clinical populations, these patients are high utilizers of the limited treatment services available, but may not receive the type of treatment they need. After describing the extent of comorbidity in this population, we present an historical perspective of mental illness that provides an Indian's view of why we are where we are today in treating these problems. Next, we discuss Western and traditional treatment implications for comorbidity among adults and adolescents. Finally, we suggest directions for future research in this area.

Alaska↗

PubMed2026

Genetic architecture of endometriosis: risk factors, comorbidities and clinical implications.

BACKGROUND: In 1999, Dr Susan Treloar and colleagues conducted a landmark twin study in Australia and reported their estimate of 51% for the heritability of endometriosis. This important result led several groups to begin mapping genetic factors contributing to increased endometriosis risk. Despite early challenges, advances in genome-wide association studies (GWAS) have identified multiple genetic risk factors and some target genes implicated in follow-up studies on genetic regulation of transcription. Access to large publicly available genetic datasets and analysis with endometriosis GWAS results is also providing new opportunities to answer important questions about comorbid conditions associated with endometriosis and their implications for clinical practice. OBJECTIVE AND RATIONALE: The objective of the review is to summarize the last 25 years of genetic studies in endometriosis, outline contributions to our understanding of the disease, and suggest future directions to accelerate biological insights from genetic studies to improve clinical outcomes. SEARCH METHODS: A comprehensive review of scientific literature on the genetics of endometriosis was conducted through searches in PubMed and Google Scholar up to June 2026. Search terms included "endometriosis AND (genetics OR GWAS OR genetic risk factors)", For studies addressing the functional characterization of genetic risk loci, additional searches employed the terms "endometriosis AND (genotype-phenotype associations OR colocalization OR eQTL OR mQTL OR multi omics methods)". To identify studies examining shared genetic risk between endometriosis and comorbid conditions, the search strategy included "endometriosis AND (genetic correlation OR colocalization OR Mendelian randomisation)". Publications reporting discoveries related to genetic risk factors for endometriosis and studies interpreting their biological and clinical significance were critically evaluated, and 144 publications were discussed in the review. OUTCOMES: Discovery of genetic risk factors started slowly and has accelerated in recent years with developments in technology and international collaborations to combine data and increase statistical power. GWAS have mapped 80 genetic risk factors that implicate gene regulation of hormonal targets, development of the reproductive tract, regulation of cell proliferation, and regulation of epithelial cell differentiation. In common with most other complex diseases, effects of individual common genetic risk factors are small. However, several examples demonstrate that small effect sizes are not a good predictor for the impact of drugs developed against genetically validated targets. Genetic risk factors implicate five genes regulating gonadotrophin release and oestrogen action, the major target pathway of current drugs for treatment of endometriosis demonstrating proof-of-principal for biologically meaningful results. Genetic correlation and Mendelian Randomization studies highlight important causal relationships between endometriosis and comorbid conditions including a possible role for testosterone during development and shared genetic risk factors for gynaecological, gastrointestinal, pain, psychiatric, and inflammatory conditions. Understanding causal relationships between endometriosis and related conditions will aid clinical management and more personalized treatments. WIDER IMPLICATIONS: Genetic studies provide novel insights into endometriosis pathogenesis and associations with related comorbid conditions. Genetic factors modifying gene regulation and disease risk likely act in specific cell types, and access to datasets from genetically informed cell-based models, single-cell and spatial omics data are needed to accelerate progress. Future studies should address critical questions of heterogeneity and disease subtypes, expand the search for genetic risk factors to non-European populations, evaluate the role of rare and structural variants, and better integrate data from functional, genomics, genetics, and clinical studies to reduce diagnostic delay, develop novel treatment strategies, and translate discoveries into personalized management strategies for affected individuals. REGISTRATION NUMBER: N/A.

comorbid conditions↗

PubMed1992

Psychiatric comorbidity in treatment-seeking anorexics and bulimics.

Current and lifetime psychiatric diagnoses were compared in 229 female patients seeking treatment for current episodes of anorexia nervosa (N = 41), bulimia nervosa (N = 98) and mixed anorexia nervosa and Schizophrenia-Lifetime Version, which was modified to include a section for DSM-III-R eating disorders, the Longitudinal Interval Follow-up Evaluation, and the Structured Interview for DSM-III Personality Disorders. Seventy-three percent of the anorexia nervosa subjects, 60% of the bulimia nervosa subjects, and 82% of the mixed anorexia nervosa and bulimia nervosa subjects had a current comorbid Axis I diagnosis. Major depression was the most commonly diagnosed comorbid disorder. Low rates of alcohol and substances abuse disorder were diagnosed, and personality disorder occurred in a minority of the sample. The subjects with mixed disorder manifested a higher lifetime prevalence of kleptomania than either the anorexics or the bulimics. High levels of comorbidity were noted across the eating disorder samples. Mixed disorder subjects manifested the most comorbid psychopathology and especially warrant further study.

Adolescent↗

PubMed1992

Patterns of affective comorbidity in a clinical population of dually diagnosed adolescent substance abusers.

Patterns of affective comorbidity with substance abuse are examined in a sample of 156 adolescent psychiatric inpatients, ages 13 to 18 years old. Affective disorders, including adjustment disorder with depressed mood, were observed in 51.3% of patients. A total of 30.7% of patients had comorbid major depression. In both males and females, secondary major depressive disorder was more common than its primary form. In this population, the primary-secondary paradigm did not predict either acute remission for depressive symptoms or distinct family history of comorbid disorders. Consistent with previous studies of adults, significantly more females had comorbid affective disorder and significantly more males had conduct disorder.

Adolescent↗

PubMed2026

Assessing the comorbidity between asthma and depression through polygenic risk scoring and time-to-event models.

BACKGROUND: Patients with asthma have an increased risk of developing depression, affecting their quality of life. To date, the processes contributing to this comorbidity remain unclear. METHODS: We integrated two large genome-wide association studies (88,486 patients with asthma and 447,859 controls; 412,024 patients with depression and 1,587,577 controls) with cross-sectional and longitudinal information available from the All of Us Research Program (N = 87,167) through polygenic risk scoring (PRS), Cox proportional-hazards models, one-sample Mendelian randomization (MR), and gene-set and drug-repurposing analyses. RESULTS: We observed that depression PRS was associated with increased asthma risk (hazard ratio, HR = 1.13, 95% CI = 1.09-1.17), also when accounting for comorbidity status (HR = 1.08, 95% CI = 1.04-1.12). Conversely, the effect of asthma PRS was null after accounting for comorbidity status. One-sample MR analysis showed an effect of depression genetic liability on asthma, ranging from beta = 0.36 ± 0.03 when considering a linear relationship to beta = 3.21 ± 0.31 when considering possible nonlinear relationships. Conversely, the effect of asthma genetic risk on depression was null after accounting for potential confounders. The gene-set analyses showed that asthma and depression polygenic risks share biological processes, molecular functions, and cellular components related to the immune system and the lung-brain axis. CONCLUSIONS: Genetic predisposition contributes to asthma-depression comorbidity through direct effects and shared pathogenic processes. These findings highlight the potential to develop targeted interventions to prevent and treat the co-occurrence of respiratory and neuropsychiatric disorders.

Comorbidity↗

PubMed1992

Introduction to special section: comorbidity and treatment implications.

This article initiates the special section on comorbidity and treatment implications. The presence of comorbidity is recognized, the multiple meanings of comorbidity are mentioned, and an invitation for much-needed research on comorbidity and related treatment is extended.

Comorbidity↗

PubMed2026

Phenotyping strategies for chronic overlapping pain conditions and internalizing disorders in Veterans: Prevalence, comorbidity, and latent structure as evidence for construct validity.

Chronic overlapping pain conditions (COPCs), internalizing (INT) disorders, and opioid use disorder (OUD) are common, comorbid, and difficult to phenotype at scale. Electronic health record (EHR) studies commonly define cases using Any Code (AC; ≥1 ICD-9/10 code) and Multiple Code (MC; ≥1 inpatient or ≥2 outpatient codes) phenotyping strategies, but it is unclear whether these thresholds change only case numbers or also the clinical relationships among conditions. This cross-sectional study included approximately 950,000 Million Veteran Program participants with ≥2 visits. AC and MC phenotypes for 17 conditions spanning COPCs, INT, and OUD were compared in prevalence, case characteristics, comorbidity, and latent structure. Random-thinning analysis compared AC-MC differences to case reduction alone. Construct validity was evaluated through correspondence with expected patterns of association and latent organization. Back pain (AC=58.1%; MC=48.1%), major depressive disorder (41.5%; 36.2%), and post-traumatic stress disorder (32.6%; 29.1%) were most prevalent. MC excluded 33.5% of AC cases on average, and MC cases had greater healthcare utilization, diagnostic burden, opioid exposure, and psychiatric medication use than AC-only cases. The observed mean absolute correlation change (mean |Δr|=0.014) was smaller than in all 1000 random-thinning replicates. Both strategies supported a correlated, four-factor model consistent with "Anxious Misery," "Fear," "Diffuse Pain," and "Head Pain" (AC: CFI=0.987, RMSEA=0.015; MC: CFI=0.987, RMSEA=0.014). The MC strategy reduced prevalence and altered case composition but maintained the expected comorbidity and latent organization patterns among conditions. Findings provide evidence of phenotype construct validity and inform selection of EHR phenotyping strategies for epidemiological and genomic research. PERSPECTIVE: Commonly used EHR phenotyping strategies tested in nearly one million Veterans produce broadly similar latent organization across comorbid and prevalent chronic overlapping pain conditions, internalizing disorders, and opioid use disorder. Findings support construct validity and clarify trade-offs involving case inclusion, recorded burden, and healthcare observation in large-scale research.

Chronic overlapping pain conditions↗

PubMed2026

Unsupervised characterization of 100,272 EHR patients identifies high-risk groups and comorbidities linked to premature aging.

Electronic health records (EHRs) contain extensive multidimensional patient data, presenting challenges for the discovery of novel and meaningful clinical patterns. Unsupervised clustering of high-dimensional clinical data holds great potential for identifying novel clinical patterns. Here, we performed unsupervised clustering and characterized 100,272 patients in the Electronic Medical Records and GEnomics (eMERGE) Network. We identified 70 clusters defined by distinct comorbidity patterns. Meanwhile, age and sex are also strongly associated with patient stratification, influencing phenotype prevalence and onset time. Notably, phenotype onset time accurately predicted chronological age and was significantly associated with overall mortality risk. Besides age and sex, we assessed the contribution of genetic variation to phenotype development and observed evidence of cross-phenotype associations influencing cluster membership and comorbidity patterns. However, the role of genetics recedes during aging. We also identified several high-risk clusters with elevated Charlson Comorbidity Index (CCI) scores and validated these findings in an independent cohort. Further analysis of these clusters revealed phenotypes linked to premature aging and highlighted a survival selection among older participants in observational studies. Overall, this study enables phenome-wide unsupervised patient stratification for multimorbidity discovery in largely unannotated clinical data, offering valuable insights into patient stratification, comorbidity analysis, aging, and health outcomes.

Journal Article↗

PubMed1992

Comorbidity and functional status in older women with breast cancer: implications for screening, treatment, and prognosis.

This is a review of research on the effects of comorbidity and functional status on breast cancer diagnosis, treatment, and prognosis in older women. The objective is to summarize results from recent studies and recommend directions for future research (a) to develop more precise guidelines for breast cancer screening, and (b) to identify and eliminate barriers preventing the attainment of those guidelines. Research is needed to determine more clearly how comorbidity and functioning affect screening practices and stage of disease at diagnosis. There is evidence that comorbidity explains, in part, why older women receive less invasive therapy. It is unknown, however, whether these treatment decisions improve quality or duration of survival. Although it is evident that comorbidity and disability adversely affect survival, research is needed to examine the etiology, course, and effects of specific combinations of conditions. Final recommendations include using the Established Populations for Epidemiologic Studies of the Elderly (EPESE) and the Surveillance, Epidemiology, and End Results (SEER) programs to address a number of these questions.

Aged↗