Gliomas And Mental Health Issues

Overview

Approximately one-third of adults with cancer experience common mental health disorders alongside their primary malignancy. However, it is not well understood whether this prevalence is similar in patients with brain tumors or what factors contribute to the risk of psychiatric comorbidities in this group. In a multicenter study, patients with high-grade glioma were consecutively recruited from 13 neuro-oncology clinics and assessed using the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders (SCID) to diagnose common mental disorders. Predictors of psychiatric comorbidity were examined using binary logistic regression to identify potential influencing factors.

 

Introduction

Mental health disorders are a significant burden for patients and caregivers alike, irrespective of whether these disorders occur as primary conditions or as comorbidities with physical illnesses. This is particularly true in the context of cancer, where the profound existential challenges associated with a

 

life-threatening diagnosis and the physical changes from the disease can lead to substantial psychological distress. Studies have consistently demonstrated that approximately one-third of individuals with cancer experience common mental health disorders, such as depression and anxiety, alongside their malignancy. These conditions, while disruptive to emotional well-being and daily life, typically do not impair insight, distinguishing them from psychotic disorders.

The psychological impact of cancer is often intensified when the disease affects the brain. Brain tumors, especially high-grade gliomas, present unique challenges, as they compromise a vital organ integral to cognition, emotion, and overall bodily functions. Patients with brain tumors face not only the shock of diagnosis but also the cumulative toll of debilitating symptoms such as neurological deficits, fatigue, seizures, and cognitive impairment throughout their disease course. These factors contribute to an elevated risk of mental health disorders, transforming subclinical psychological issues into clinically significant conditions.

Despite these vulnerabilities, brain tumors are often underrepresented or subsumed within broader cancer categories in epidemiological research on mental health. Few studies have specifically examined the mental health of brain tumor patients, and those that do frequently rely on small sample sizes or focus narrowly on a single psychiatric condition, such as major depression or substance use disorders. Structured clinical interviews, which are considered the gold standard for diagnosing mental health disorders, have rarely been utilized in this context.

However, existing data provide critical insights. For example, major depression has been reported in 0–28% of brain tumor patients, and alcohol use disorders have been noted in 0–4%. Adjustment disorders (4–11%), generalized anxiety disorders (0–4%), and acute stress disorders (11–19%) have also been identified, though the reliability of these findings is limited by small study populations. Overall, the prevalence of any mental health disorder in brain tumor patients is estimated to range from 17% to 38%.

The scarcity of comprehensive, multicenter studies leaves a gap in understanding the true prevalence of mental health disorders in patients with high-grade gliomas. Furthermore, most existing research combines various types of brain tumors, such as meningiomas, glioblastomas, and astrocytomas, despite their differing clinical courses and psychological implications. As a result, precise prevalence estimates and a nuanced understanding of the psychiatric burden in high-grade glioma patients remain elusive.

In addition to prevalence, it is critical to understand the factors that increase the risk of mental health disorders in this population. Existing research on cancer patients, and specifically brain tumor patients, suggests several potential predictors. Gender differences are notable, with women more likely to experience general psychiatric disorders and men more prone to alcohol dependence. Younger age, unemployment, low income, living alone, reduced physical performance, fatigue, and cognitive impairments have also been associated with higher psychiatric comorbidity rates. Time since diagnosis appears to play a role as well, though the nature of this relationship—whether mental health issues worsen or improve over time—remains unclear.

Clinical variables, including tumor histology, grade, stage, location, laterality, and concurrent somatic diseases, have been investigated for their impact on mental health outcomes, but findings are inconsistent. Similarly, evidence on the influence of antineoplastic treatments, such as surgical resection, radiotherapy, and chemotherapy, has been inconclusive, with some studies suggesting no direct correlation between these treatments and psychiatric comorbidity in glioma patients.

Given these gaps, the current study seeks to provide more accurate and comprehensive estimates of the prevalence of common mental health disorders in adults with high-grade gliomas. Additionally, it aims to identify risk factors associated with psychiatric comorbidities, using gold-standard diagnostic methods and a multicenter approach to ensure robust and generalizable findings. This work is essential not only for improving clinical care but also for addressing the emotional and psychological needs of this vulnerable patient population.

 

Methods

Inclusion and Exclusion Criteria

Inclusion Criteria

The study employed a structured approach to ensure the selection of appropriate participants with high-grade gliomas. Eligible patients met the following criteria:

1. Age: Participants had to be 18 years or older at the time of enrollment, ensuring the inclusion of adult patients capable of providing legally valid consent.
2. Legal Competency: Only legally competent individuals were considered eligible. This required patients to demonstrate the capacity to understand the nature and implications of the study, including its procedures, risks, and benefits.
3. Histological Diagnosis: A confirmed histological diagnosis of high-grade glioma was mandatory. The eligible subtypes included glioblastoma (CNS WHO Grade 4), astrocytoma (CNS WHO Grade 3), oligodendroglioma (CNS WHO Grade 3), and other relevant high-grade gliomas.
4. Consent: Written informed consent was a non-negotiable prerequisite for participation. Patients were provided with detailed verbal and written information to ensure they were fully informed before agreeing to participate.
5. Clinical Setting: Enrollment was restricted to patients attending one of the 13 neuro-oncology clinics participating in the study. This ensured consistency in patient management and study procedures.
6. Physical and Cognitive Ability: Participants needed to be physically and cognitively capable of completing the study assessments, such as structured interviews and quality-of-life questionnaires.

Exclusion Criteria

To maintain the integrity of the data and the welfare of the participants, the study excluded individuals based on the following:

1. Lack of Consent: Any individual who declined participation or failed to provide written informed consent after being fully informed about the study was excluded.
2. Severe Medical Instability: Patients with medical conditions that rendered them too fragile or unstable for meaningful participation in the study were not eligible. This included individuals undergoing acute medical crises or those with rapidly deteriorating conditions.
3. Communication Barriers: Individuals unable to read, understand, or communicate in German were excluded. This criterion was essential to ensure the accurate completion of study instruments, such as interviews and questionnaires, which were conducted in German.
4. Inability to Complete Study Measures: Participants who, due to severe physical or cognitive impairment, were unable to complete the structured clinical interview (SCID) or other study tools were excluded to preserve data quality and participant welfare.
5. Concurrent Psychiatric or Medical Conditions: Individuals whose psychiatric or medical conditions, unrelated to high-grade glioma, would interfere with study participation were excluded. For example, patients with severe psychiatric disorders, such as untreated psychosis, or significant non-neurological comorbidities requiring immediate attention, were deemed ineligible.

Rationale for Criteria

The inclusion criteria were carefully designed to ensure that the study captured a representative sample of adults with high-grade gliomas while minimizing confounding variables. Meanwhile, the exclusion criteria safeguarded participant safety, ensured the feasibility of completing study assessments, and maintained the validity and reliability of the data. These parameters also ensured the efficient use of study resources while fostering the ethical conduct of research.

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Analysis

To assess potential selection bias, the researchers compared the age, gender, and tumor grades between participants and nonparticipants. Cognitive functioning and fatigue levels were then categorized based on the threshold for clinical importance (TCI) developed by Giesinger et al. The TCIs were derived from patient interviews, where participants evaluated how their EORTC QLQ-C30 scores reflected limitations in daily activities, reliance on assistance, and overall concerns. A cognitive functioning score below 75 indicated clinically significant problems, while a fatigue score above 39 suggested clinically meaningful fatigue.

The prevalence of common mental disorders was calculated across the entire sample and analyzed based on various predictor variables. The frequencies of individual mental disorders and the total number of psychiatric conditions were also determined.

Univariate and multivariate binary logistic regression analyses were conducted to identify potential predictors of psychiatric comorbidities (defined as having at least one common mental disorder) and to examine the factors associated with specific mental health conditions. These predictors were preselected based on existing literature and clinical expertise, avoiding any deliberate post hoc selection procedures. The same predictor set was applied across all mental health outcomes, without predefined hypotheses for disorders other than depression due to insufficient prior research. Consequently, p-values were not reported for effect estimates; only confidence intervals were presented.

Multicollinearity among predictor variables was checked beforehand using the variance inflation factor. All statistical analyses were conducted using STATA (Stata Statistical Software, Release 16; StataCorp LP), ensuring rigorous methodological standards.

 

Results

Participant Flow
During the study, 1,568 patients with glioma were screened across participating clinics. Of these, 1,387 met the eligibility criteria, with 763 consenting to participate. Among these, 702 agreed to undergo interviews, and 691 patients (50% of eligible participants; 91% of those who participated) completed the SCID-based diagnostic assessment. Nonparticipants, on average, were older by four years and were more frequently diagnosed with glioblastoma (67% compared to 61% among participants). Gender distribution showed no significant differences between participants and nonparticipants.

Sample Characteristics
The 691 participants interviewed had a mean age of 52 years (range: 19–86), with 57% being male. The most common diagnosis was glioblastoma (59%), followed by astrocytoma (25%) and oligodendroglioma (13%).

Frequency of Mental Disorders
A total of 217 patients (31%; 95% CI, 28%–35%) were diagnosed with at least one common mental disorder. The number of diagnoses per individual ranged from zero to four, with a mean of 1.2 diagnoses among affected patients. Diagnosed conditions included:

• Major depressive episode: 6%
• Persistent depressive disorder: 8%
• PTSD: 10%
• Generalized anxiety disorder: 7%
• Adjustment disorder: 4%
• Alcohol use disorder: 1%

Screening identified additional mental health conditions, raising the prevalence to 46%. These included panic disorder (10%), agoraphobia (5%), social phobia (3%), specific phobias (6%), insomnia (13%), hypersomnolence (17%), and non-alcohol substance use disorder (1%).

Predictors of Psychiatric Comorbidity
Logistic regression analysis revealed several predictors for the presence of mental disorders:

• Age: Patients younger than 50 years had 1.9 times the likelihood of developing a mental disorder compared to those aged 65 years or older (95% CI, 1.1–3.4; p = 0.04).
• Disease Status: Patients with stable disease were 1.7 times more likely to be diagnosed with a mental disorder than those in complete remission (95% CI, 1.1–2.8; p = 0.04).
• Income: Those with monthly equivalent incomes of €1000–€1499 had higher odds of psychiatric conditions compared to those earning ≥€1500 (OR, 1.7; 95% CI, 1.0–2.8; p = 0.04).
• Living Alone: Patients living alone faced increased odds of mental health issues (OR, 1.6; 95% CI, 1.0–2.6; p = 0.05).
• Fatigue and Cognitive Impairment: Poor quality of life due to fatigue (OR, 1.6; 95% CI, 1.1–2.4; p = 0.03) and self-reported cognitive dysfunction (OR, 2.3; 95% CI, 1.5–3.6; p < 0.01) were also significant predictors.

Minimal differences between univariate and multivariate analyses indicated low confounding effects.

Predictors of Specific Mental Disorders
Certain factors were uniquely associated with specific mental health conditions:

• Major Depressive Episode: More likely among those with Karnofsky scores ≤70 (OR, 4.2; 95% CI, 1.8–9.9), severe fatigue (OR, 10.1; 95% CI, 2.2–46.7), and impaired cognitive functioning (OR, 3.8; 95% CI, 1.1–13.8).
• Persistent Depressive Disorder: Linked to anaplastic astrocytoma (OR, 2.9; 95% CI, 1.4–6.1), somatic comorbidities (OR, 2.0; 95% CI, 1.1–3.7), lower income (OR, 2.2; 95% CI, 1.0–4.7), and cognitive impairment (OR, 2.1; 95% CI, 1.0–4.4).
• PTSD: More frequent in patients younger than 50 years (OR, 4.3; 95% CI, 1.6–12.1) but less common in those with recurrent disease (OR, 0.5; 95% CI, 0.2–1.0).
• Generalized Anxiety Disorder: More prevalent among women (OR, 1.8; 95% CI, 1.0–3.3).
• Adjustment Disorder: More common in patients with lower incomes (OR, 2.7; 95% CI, 1.1–7.0).

Due to the low number of cases (n = 8), a separate regression model for alcohol use disorder was not performed.

 

Conclusion

This study highlights the significant burden of psychiatric comorbidities among patients with glioma, affecting nearly one-third of those interviewed. Common mental disorders, such as depression, PTSD, and generalized anxiety, were prevalent, underscoring the critical need for routine mental health screening in neuro-oncology settings. Younger age, lower socioeconomic status, living alone, and poor quality of life indicators, including fatigue and cognitive impairment, emerged as key predictors of psychiatric conditions. Specific mental health diagnoses were also linked to disease severity, somatic comorbidities, and functional impairment, emphasizing the multifactorial nature of psychological distress in this population.

Targeted mental health interventions tailored to vulnerable subgroups, alongside comprehensive clinical care, could mitigate the psychological impact of glioma and improve overall patient well-being. Integrating psychosocial care into standard oncological treatment pathways is essential to address this unmet need effectively. Future research should explore longitudinal outcomes and the impact of early psychological interventions to optimize care strategies for this high-risk population.

 

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