Association of Ptosis with Mental Health Conditions in Adults from a Large United States Research Database Open Access

Blepharoptosis (ptosis), a condition characterized by drooping of the upper eyelid, may impact mental health due to both functional and cosmetic impairments. Although commonly associated with aging, ptosis can be congenital or acquired, and can be further classified by its underlying cause, which include myogenic, neurogenic, mechanical, traumatic, or aponeurotic etiologies. [1]. Ptosis can result from a range of etiologies – myogenic, neurogenic, mechanical, traumatic, or aponeurotic. Neurogenic causes, such as cranial nerve III palsy, suggest involvement of central motor pathways, some of which overlap with neuropsychiatric circuits. Myogenic ptosis may also relate to systemic or inherited neuromuscular disorders, which have known psychiatric comorbidities. These mechanisms warrant further investigation into neuroinflammatory and neuromotor links between ptosis and mental illness. Regardless of etiology, it can impact quality of life. By partially obstructing the visual field, ptosis can lead to impaired vision, fatigue, compensatory head tilting and brow elevation, and amblyopia in congenital or pediatric cases [1]. Ptosis also has cosmetic implications as eyelid drooping of one or both upper eyelids can result in an asymmetrical or unsatisfactory appearance of the eyes. This study cast a wide net across psychiatric conditions to evaluate not only those linked with psychosocial distress (e.g., anxiety and depression), but also conditions that share potential neurobiological or motor pathway overlap with ptosis, such as schizophrenia and bipolar disorder.

These ocular and cosmetic complications highlight the significant effect of ptosis on quality of life, and studies have found ptosis to be associated with mental health issues [2, 3]. For example, adult patients with ptosis reported greater anxiety, depression, and distress about appearance than the general population [2]. Mental illness was also significantly more common in a cohort of children with congenital ptosis than without ptosis [3]. However, larger adult population studies evaluating the relationship between the clinical diagnoses of ptosis and mental illness do not exist in the current literature. Thus, this study investigated the association of ptosis with mental health disorders using the National Institutes of Health’s All of Us Research Program, a public research database aimed at enhancing precision medicine by aggregating health-related data from over one million Americans, with a particular focus on including populations traditionally underrepresented in biomedical research [4, 5].

This cross-sectional study used data from the National Institutes of Health’s All of Us Research Program. The study utilized de-identified data from the NIH’s All of Us Research Program, which collects electronic health records, surveys, and physical measurements from over one million diverse participants across the US the program emphasizes inclusion of underrepresented populations. Clinical diagnoses were derived using ICD-10-CM codes documented in EHRs. Data were collected between 2018 and 2023 from a network of academic medical centers and partner institutions. The study included all adults (aged ≥18 years) with ptosis diagnosis and a 1:1 propensity score-matched controls (using R version 4.2.1). We included all adults aged 18 or older with a ptosis diagnosis code. Controls were matched using propensity scoring on age, sex, race, education, and income (Table 1). Mental health conditions and ptosis were identified using SNOMED clinical terms and OMOP CDM Concept IDs from the All of Us Research program. The full list of codes is provided in online supplementary Table A (for all online suppl. material, see https://doi.org/10.1159/000546894).

Matching was performed on participants’ age, sex, race, highest education, and family income level. The prevalence of anxiety, depression, bipolar, schizophrenia spectrum, and substance use and addiction disorders among adults with ptosis were compared with their matched controls. After matching, logistic regression was used to further adjust for health-related covariates including BMI, elevated blood pressure, and blood glucose. Propensity score matching was selected to reduce confounding due to demographic and socioeconomic differences. This approach creates comparable groups and approximates randomization in observational data. The study was approved by the IRB at Weill Cornell Medicine (Protocol #24-05027490). Informed consent was waived for this analysis of de-identified data.

Descriptive statistics were summarized using means (SD) for continuous variables and frequencies (%) for categorical variables. Chi-square and t tests were used for comparisons. Logistic regression adjusted for BMI, blood pressure, and glucose. Missing data were minimal and assumed to be missing at random; no imputation was performed.

This study included 4,411 adults with ptosis and 4,411 propensity score-matched controls. Individuals with ptosis had significantly higher prevalence of anxiety, depression, bipolar, schizophrenia spectrum, and substance use/addictive disorders (46.8%, 44.9%, 5.8%, 1.8%, and 23.4%, respectively) compared to their matched controls (28.9%, 27.8%, 3.6%, 1.1%, and 17.0%, respectively). The prevalence of any mental health condition was significantly higher than controls (63.4% vs. 44.8%, p < 0.001). Further adjustment revealed that adults with ptosis had higher odds of any mental health condition compared to individuals without ptosis (aOR: 1.92, 95% CI, 1.76–2.10). Likewise, ptosis was associated with significantly greater odds for every mental health condition analyzed.

Table 2 shows that patients with ptosis had significantly higher prevalence across all mental health conditions studied. The largest differences were observed in anxiety (46.8% vs. 28.9%) and depression (44.9% vs. 27.8%). Notably, even lower prevalence disorders like bipolar disorder and schizophrenia spectrum disorders showed significant differences, suggesting a consistent pattern. Adjusted odds ratios ranged from 1.39 (substance use) to 1.92 (anxiety), reinforcing the robustness of the association.

This study found that mental health conditions were more common in adults with ptosis than in those without ptosis. This was true for all psychiatric illnesses analyzed, which included anxiety, depression, bipolar, schizophrenia spectrum, substance use disorders, and addiction disorders. The associations were significant even when matching for age, sex, race, education, and income, and adjusting for other lifestyle and health conditions. This indicates that ptosis may be an independent risk factor for a wide range of mental health disorders.

Beyond psychosocial burden, future research should investigate whether underlying neurologic or immunologic mechanisms might link ptosis and psychiatric disorders. Neurogenic ptosis in particular may share common pathways with motor disturbances observed in schizophrenia or bipolar mania. Exploring inflammatory markers, structural neuroimaging, and genotype-phenotype correlations in ptosis patients could yield novel insights.

Prior literature has reported similar findings. In a retrospective cohort study of 81 children with congenital ptosis, 31 (38%) were diagnosed with a DSM-V mental illness, and those with ptosis were 2.5 times more likely to develop a mental illness than controls [3]. The consistency with our study, which had a larger sample size and focused on adults, highlights the impact of ptosis on mental health. Other studies have proposed appearance as a possible mechanism for this effect. In a survey-based study, 61 adults with ptosis reported greater anxiety, depression, and distress about appearance than the general population [2]. Moreover, reviewers rated preoperative photographs of patients with ptosis more negatively than postoperative photographs regarding all 11 characteristics analyzed, including intelligence, happiness, trustworthiness, and mental illness [6]. Thus, both personal appearance concerns and negative perceptions from others represent potential psychosocial stressors and causes of the increased mental illness risk for individuals with ptosis.

This study has several limitations. This study may be subject to Berkson’s bias, wherein individuals with ptosis may have more frequent health care encounters, increasing the likelihood of being diagnosed with psychiatric conditions. Although many potential confounding variables were accounted for through matching and logistic regression, this cross-sectional study cannot prove a causal relationship between ptosis and mental illnesses. It also does not shed light on the potential mechanism and modifiers of ptosis’ association with psychiatric disorders. Specifically, because ptosis diagnoses were not broken down by etiology, age of onset, severity, or other factors, our study is unable to further stratify risk of mental illness. It remains unknown whether a patient recently diagnosed with aponeurotic ptosis is at the same increased risk for mental illness as a patient living with congenital ptosis their whole life. Additionally, diagnoses of both ptosis and mental health disorders were identified using diagnostic codes, which are susceptible to coding errors. Diagnostic codes can be not only inaccurate, but also susceptible to the confounder of health care access. Compared to those without ptosis, patients diagnosed with ptosis likely have more contact with health care providers, which increase their overall likelihood of being diagnosed with a mental health condition. This serves as a possible explanation for the results of this study, as ptosis was associated with every psychiatric illness analyzed. Future work should include sensitivity analyses using unrelated medical diagnoses (e.g., GI disorders) to evaluate the extent of generalized diagnostic exposure contributing to the association. Future studies should incorporate simulation-based sensitivity analyses to assess the robustness of findings under varying assumptions of health care utilization and diagnostic frequency.

The relationship between ptosis and psychiatric disorders must be further explored with future research. Longitudinal cohort studies, tracking the mental health of patients with ptosis and controlling for health care access, will clarify the role of ptosis in this apparent association. Additional large population studies that contain details regarding ptosis severity, etiology, age of onset, duration, and treatment, will reveal potential modifiers of the relationship with psychiatric conditions. This will help stratify patients with ptosis by their risk for mental illness, inform the use of mental illness screening tools by health care providers, and ultimately improve the care of patients with ptosis.

This study utilized data from a large publicly available database containing de-identified information. The need for informed consent was waived by the Institutional Review Board (IRB) of NewYork-Presbyterian Weill Cornell Medicine. The study was reviewed and approved by the IRB of NewYork-Presbyterian Weill Cornell Medicine (Protocol # 24-05027490). The research was conducted in accordance with ethical principles outlined in the World Medical Association Declaration of Helsinki, ensuring the integrity, safety, and confidentiality of participant data.

The authors have no financial disclosures to report. The authors have no conflicts of interest to declare.

There is no funding source to report for this project.

Jaffer Shah, BS: conceptualization, data curation, formal analysis, investigation, methodology, validation, and writing. Matthew Lin, BS: data curation, formal analysis, investigation, methodology, validation, and writing. Gabriella Schmuter, MD: methodology, writing, validation, review, and editing. Kyle D. Kovacs, MD: investigation, validation, writing, review, and editing. Kyle J. Godfrey, MD: investigation, validation, writing, review, and editing.

The data that support the findings of this study are openly available at https://www.researchallofus.org.