Correlation of anxiety and depression with sleep quality and post-traumatic growth in brain tumor patients and associated determinants

Abstract

BACKGROUND

Patients with brain tumors (BTs) are often accompanied by anxiety and depression, which are not conducive to improved clinical outcomes.

AIM

To investigate anxiety and depression in relation to sleep quality and post-traumatic growth (PTG) in patients with BTs and identified associated determinants.

METHODS

A total of 169 patients with BTs admitted between October 2022 and January 2025 were enrolled. Data on anxiety and depression (Hospital Anxiety and Depression Scale, HADS), sleep quality (Pittsburgh Sleep Quality Index, PSQI), and PTG was collected. Correlation analysis was conducted to evaluate associations between HADS subscales - HADS-Anxiety and HADS-Depression - and PSQI and PTG Inventory (PTGI) scores. Anxiety or depression-associated determinants were identified using univariate screening followed by binary logistic regression analysis.

RESULTS

Among the 169 patients with BTs, the prevalence of anxiety, depression, anxiety-depression comorbidity, and either anxiety or depression was 34.91%, 30.18%, 10.65%, and 54.44%, respectively. The four most PSQI dimensions were sleep latency, sleep duration, daytime dysfunction, and sleep quality. The mean PTGI score was 59.89 ± 8.83, with 47.93% of patients scoring < 60. The correlation analysis demonstrated positive correlations between HADS-Anxiety and HADS-Depression scores and PSQI, and negative correlations with PTGI. Regression analysis showed that age, educational level, PSQI, and PTGI independently influenced anxiety or depression in patients with BTs.

CONCLUSION

Anxiety and depression in patients with BTs are closely associated with sleep quality and PTG. Age ≥ 50 years, high school education, and PTGI ≥ 60 exert protective effects against anxiety or depression, whereas PSQI ≥ 11 independently increases the risk.

Key Words: Brain tumor; Anxiety; Depression; Sleep quality; Post-traumatic growth; Correlation analysis and determinants

Core Tip: This study reports the correlations between anxiety, depression, sleep quality, and post-traumatic growth (PTG) in patients with brain tumors (BTs) and identifies related influencing factors. The findings indicate that patients with BT commonly experience negative emotions such as anxiety and depression, accompanied by relatively severe sleep disorders and insufficient PTG. These negative emotional states are strongly associated with sleep quality and PTG. Factors, including age < 50 years, educational level below high school, PTG-inventory score < 60, and Pittsburgh Sleep Quality Index score ≥ 11, increases the likelihood of anxiety or depression in patients with BTs.

INTRODUCTION

Brain tumors (BTs) are heterogeneous, complex, and highly fatal, with a five-year survival rate of approximately 36%[1]. Radiation exposure, family history, and impaired immunity are closely associated with BT occurrence[2]. Primary BTs originate from intracranial tissues and are related to abnormal proliferation of brain cells, presenting as either benign or malignant tumors[3]. Statistics indicate that approximately 700000 individuals in the United States are diagnosed with primary BTs, primarily, including meningiomas, gliomas, and pituitary tumors, all of which variably compromise patient survival[4]. Anxiety and depression are common among patients with BTs, with reported prevalence rates of 10%-40% and 5%-50%, respectively[5]. These psychological conditions are associated with the physiological and psychological burden of tumor diagnosis, disease progression, repeated treatments, and recurrence. Moreover, chronic stress can further affect tumor microenvironment, immune function, and hormonal regulation, thereby promoting tumor progression[6].

More than 60% of patients with BTs experience sleep disorders, and nearly 20% suffer from insomnia, which not only delays wound healing but also contributes to emotional disturbances, increased complication risk, and poorer clinical outcomes[7]. Sleep disturbances may involve neuroinflammation, impaired hippocampal synaptic plasticity, and blood-brain barrier dysfunction, negatively affecting immune regulation and stress responses and increasing perioperative anxiety and depression risk[8].

Post-traumatic growth (PTG) refers to positive psychological changes that occur beyond baseline functioning following traumatic or stressful experiences. PTG may help patients actively cope with adversity, alleviate psychological stress, and restore mental health[9].

However, PTG in patients with primary BTs remain insufficiently studied, and analyses of its relationship with psychological characteristics are limited[10]. This study therefore examines anxiety and depression in relation to sleep quality and PTG in patients with BTs, aiming to address existing research gaps and provide evidence to inform clinical management.

MATERIALS AND METHODS

Case selection

Inclusion criteria: Diagnosis of BT confirmed via imaging and pathological examination[11]; age > 18 years; estimated survival < 6 months; clear consciousness and normal communication; first-time treatment recipient for the condition; normal cognitive function; and complete clinical data. Exclusion criteria: Severe cardiovascular or cerebrovascular disease, hypertension, or diabetes; immune diseases or coagulopathy; history of cranial repair or skull defects; visual, hearing, or cognitive impairment; presence of other malignancies; and history of epilepsy. Based on these criteria, 169 patients with BTs admitted to the First People’s Hospital of Changde City between October 2022 and January 2025 were enrolled. The criterion of estimated survival < 6 months was jointly determined by two or more senior neurosurgeons or oncologists, based on the Karnofsky Performance Status Scale score, tumor pathological type, molecular subtype, recurrence or distant metastasis status, and response to current standard treatments. This criterion was applied to ensure that patients had sufficient cognitive ability and physical strength to complete psychological assessments and to ensure data quality. In addition, it provided a relatively stable observation window for psychological processes such as PTG, while avoiding unnecessary research burden in terminally ill patients. The patient selection flowchart is shown in Figure 1.

Figure 1 Patient selection flowchart.

Investigation methods

A general data questionnaire, Hospital Anxiety and Depression Scale (HADS), Pittsburgh Sleep Quality Index (PSQI), and PTG Inventory (PTGI) were administered to patients. For participants unable to complete the questionnaires independently because of reading difficulties or physical impairment, trained personnel provided one-on-one assistance. To minimize measurement bias, outcome assessors and data analysts were blinded. All researchers involved in data collection received unified training to ensure consistent understanding of scale content, questioning procedures, and assistance standards. In addition, a dedicated individual conducted double verification and logical checks on the entered data, with any missing or abnormal values traced and corrected.

Data collection and outcome measurement

Negative emotions. Anxiety and depression were assessed using the HADS[12], which comprises two subscales: HADS-Anxiety (HADS-A) and HADS-Depression (HADS-D). Each subscale includes 7 items, totaling 14 items. Items are rated on a 4-point scale (0-3), with subscale scores of 0-21. Scores of 0-7 indicate no systems, 8-10 indicate suspected symptoms, and 11-21 indicate positive anxiety or depression.

Sleep quality: Sleep quality was assessed using the PSQI[13], which evaluates seven dimensions: Subjective sleep quality, sleep latency, sleep duration, sleep efficiency, sleep disorders, use of hypnotic medication, and daytime dysfunction. Each dimension is scored 0-3, totaling 21 points. Lower scores indicate better sleep quality.

PTG: PTG was evaluated using the 21-item PTGI[14], covering five domains: Relating to others (6 items), personal strength (5 items), appreciation of life (5 items), new possibilities (3 items), and spiritual change (2 items). Each item is rated from 0 (“not at all”) to 5 (“a very great degree”), a maximum total score of 105. PTGI scores were categorized as < 60 (low), 60-65 (moderate), and ≥ 66 (high), with higher scores indicating greater PTG.

Statistical analysis

Normality was assessed using the Shapiro-Wilk test. Measurement data conforming to a normal distribution were expressed as mean ± SD, with comparisons performed using the independent-sample t-test (between groups) and the paired t-test (pre- vs post-intervention). Non-normally distributed data were described as median [interquartile range, median (Q1, Q3)]. Categorical data were described as n (%) and compared using the χ² test. All analyses were conducted using SPSS 23.0. Correlations between HADS-A and HADS-D scores and PSQI and PTGI scores were examined using Spearman’s correlation or Pearson’s r coefficients. Univariate analysis followed by multivariate binary logistic regression was performed to identify determinants of anxiety or depression. Statistical significance was set at P < 0.05.

RESULTS

Anxiety and depression in patients with BTs

The HADS-A and HADS-D results are detailed in Table 1. Among the 169 patients, the mean HADS-A score was 9.00 (7.00, 12.00), with 65.68% exhibiting suspected or definite anxiety symptoms. The mean HADS-D score was 8.82 ± 3.64, with suspected or positive depression accounting for 63.91% of the cases. Further analysis revealed that more than half of the patients (54.44%) had obvious anxiety or depression (≥ 11 points on either subscale), while 10.65% exhibited significant anxiety-depression comorbidity. These findings indicate that emotional disorders are highly prevalent in patients with BTs and represent a core clinical concern.

Table 1 Anxiety and depression in brain tumor patients, n (%).

Categories	Score	Asymptomatic	Suspicious	Positive
		0-7 points	8-10 points	≥ 11 points
HADS-A (points)	9.00 (7.00, 12.00)	58 (34.32)	52 (30.77)	59 (34.91)
HADS-D (points), mean ± SD	8.82 ± 3.64	61 (36.09)	57 (33.73)	51 (30.18)

HADS-A: Hospital Anxiety and Depression Scale Anxiety; HADS-D: Hospital Anxiety and Depression Scale Depression.

Sleep quality of patients with BTs

Sleep quality assessed using the PSQI is presented in Table 2. Overall sleep quality was relatively poor, with a mean PSQI score of 9.00 (8.00, 11.00). Among the PSQI dimensions, sleep latency and insufficient sleep duration ranked highest, followed by daytime dysfunction and poor subjective sleep quality. In contrast, sleep efficiency, sleep disorders, and use of hypnotic medication exerted little influence. These results suggest that difficulty initiating asleep and shortened sleep duration are the primary factors underlying impaired sleep quality in this population.

Table 2 Sleep status of patients with brain tumors.

Categories	Score
Sleep latency (points)	1.00 (1.00, 2.00)
Sleep duration (points)	0.00 (0.00, 1.00)
Daytime dysfunction (points)	1.00 (1.00, 2.00)
Sleep quality (points)	1.00 (1.00, 2.00)
Sleep efficiency (points)	2.00 (1.00, 2.00)
Sleep disorders (points)	2.00 (1.00, 2.00)
Hypnotic drug use (points)	1.00 (1.00, 2.00)
PSQI (points)	9.00 (8.00, 11.00)

PSQI: Pittsburgh Sleep Quality Index.

PTG of patients with BTs

Table 3 presents the assessment of PTG based on the PTGI scale. The mean PTGI score was 59.89 ± 8.83 indicating marked inter-individual variability. Nearly half of the patients (47.93%) scored < 60, suggesting limited PTG, whereas approximately one quarter (25.44%) achieved relatively high PTG levels (PTGI ≥ 66). These findings highlight significant differences in psychological adaptation and growth following a BT diagnosis.

Table 3 Post-traumatic growth of brain tumor patients, mean ± SD.

Categories	Score
Relating to others (points)	18.23 ± 5.02
Personal strength (points)	14.43 ± 3.83
Appreciation of life (points)	14.73 ± 4.41
New possibilities (points)	7.00 (6.00, 9.00)
Spiritual change (points)	5.00 (4.00, 6.50)
PTGI (points)	59.89 ± 8.83
< 60	81 (47.93)
60-65	45 (26.63)
≥ 66	43 (25.44)

PTGI: Post-traumatic Growth Inventory.

Correlations of anxiety and depression with sleep quality and PTG

Pearson’s/Spearman’s correlation analysis (Table 4) showed that both anxiety (HADS-A) and depression (HADS-D) were moderately and positively correlated with PSQI scores and negatively correlated with PTGI scores. This suggests that greater emotional distress is associated with poorer sleep quality and lower levels of positive psychological growth.

Table 4 Correlation analysis results.

Categories	r, P value
HADS-A vs PSQI	r = 0.341, P < 0.001
HADS-A vs PTGI	r = -0.342, P < 0.001
HADS-D vs PSQI	r = 0.363, P < 0.001
HADS-D vs PTGI	r = -0.396, P < 0.001

HADS-A: Hospital Anxiety and Depression Scale Anxiety; HADS-D: Hospital Anxiety and Depression Scale Depression; PSQI: Pittsburgh Sleep Quality Index; PTGI: Post-traumatic Growth Inventory.

Determinants of anxiety or depression in patients with BTs

Univariate analysis of determinants associated with anxiety or depression is shown in Table 5. Age, educational level, marital status, and disease duration were significantly associated with the presence or absence of anxiety or depression (P < 0.05), whereas gender and tumor type were not (P > 0.05). Higher PSQI scores (worse sleep) and lower PTGI scores (lower growth levels) were also significantly correlated with anxiety or depression, suggesting a close relationship between psychosocial factors and emotional disorders.

Table 5 Univariate analysis of anxiety or depression in brain tumor patients, n (%).

Categories	n	Anxiety/depression (n = 92)	Non-anxiety nor depression (n = 77)	χ2	P value
Sex				0.343	0.558
Male	105	59 (64.13)	46 (59.74)
Female	64	33 (35.87)	31 (40.26)
Age (years)				6.651	0.010
< 50	95	60 (65.22)	35 (45.45)
≥ 50	74	32 (34.78)	42 (54.55)
Disease course (years)				5.608	0.018
< 2	93	43 (46.74)	50 (64.94)
≥ 2	76	49 (53.26)	27 (35.06)
Educational level				4.688	0.030
Below senior high school	79	50 (54.35)	29 (37.66)
Senior high school or above	90	42 (45.65)	48 (62.34)
Marital status				5.573	0.018
Married	87	55 (59.78)	32 (41.56)
Single	82	37 (40.22)	45 (58.44)
Tumor type				0.309	0.857
Meningoma	80	42 (45.65)	38 (49.35)
Glioma	51	28 (30.43)	23 (29.87)
Hypophysoma	38	22 (23.91)	16 (20.78)
PSQI (points)				5.831	0.016
< 11	123	60 (65.22)	63 (81.82)
≥ 11	46	32 (34.78)	14 (18.18)
PTGI (points)				12.546	< 0.001
< 60	80	55 (59.78)	25 (32.47)
≥ 60	89	37 (40.22)	52 (67.53)

PSQI: Pittsburgh Sleep Quality Index; PTGI: Post-traumatic Growth Inventory.

Multivariate logistic regression results are summarized in Table 6. Age [odds ratio (OR) = 0.347, 95% confidence interval (CI): 0.171-0.706], educational level (OR = 0.421, 95%CI: 0.208-0.852), PSQI score (OR = 2.763, 95%CI: 1.205-6.334), and PTGI score (OR = 0.257, 95%CI: 0.123-0.537) were identified as independent determinants of anxiety or depression in patients with BTs (P < 0.05), whereas disease duration and marital status were not independently associated (P > 0.05).

Table 6 Multivariate analysis of anxiety or depression in brain tumor patients.

Categories	B	SE	Wald	P value	OR	95%CI
Age (years)	-1.058	0.362	8.521	0.004	0.347	0.171-0.706
Disease course (years)	0.412	0.357	1.330	0.249	1.510	0.750-3.041
Educational level	-0.865	0.360	5.788	0.016	0.421	0.208-0.852
Marital status	-0.450	0.354	1.612	0.204	0.638	0.318-1.277
PSQI (points)	1.016	0.423	5.765	0.016	2.763	1.205-6.334
PTGI (points)	-1.358	0.376	13.083	< 0.001	0.257	0.123-0.537

CI: Confidence interval; OR: Odds ratio; PSQI: Pittsburgh Sleep Quality Index; PTGI: Post-traumatic Growth Inventory.

DISCUSSION

BTs pose varying degrees of negative threats to life expectancy and can occur across all age groups. However, current treatment options remain limited and are often accompanied by low response rates and inevitable drug resistance[15,16]. Previous research has shown that early diagnosis and intervention for emotional disorders can reduce symptom severity and duration, prevent recurrence, and improve overall functioning[17]. This present study confirms that patients with BT commonly experience anxiety/depression and sleep disorders, alongside relatively low levels of PTG. Moreover, sleep quality and PTG were significantly associated with negative emotional states.

In this cohort (n = 169), the prevalence of anxiety or depression reached 54.44%, with anxiety and depression rates of 34.91% and 30.18%, respectively. Liu and Zhan[18] reported anxiety and depression rates of 32.50% and 30.00%, respectively, in newly diagnosed glioma patients, while Ernster et al[19] observed a depression rate of 32.30% in primary BT patients, consistent with the present findings. Anxiety and depression in patients with BT may be related to oxidative stress-induced neuronal damage, neuroinflammation, and disruption of synaptic plasticity in the medial prefrontal cortex. In addition, the involvement of the cell tumor antigen p53-DNA-damage-inducible transcript 4-nuclear factor κB signaling axis has been suggested[20].

Second, the overall sleep quality of patients with BT was poor, with prolonged sleep latency and insufficient sleep duration identified as the most prominent problems. Willis et al[21] reported that 61.50% of primary BT patients experienced sleep disorders, including insomnia in 22.00%, which was associated with increased cancer-related fatigue and corticosteroid use. Sleep disturbances in BT patients may also be attributed to microglial activation mediated by topoisomerase 1, which can exacerbate hippocampal neuronal injury and behavioral abnormalities related to sleep deprivation[22]. PTG assessment showed a mean PTGI score of 59.89 ± 8.83, indicating generally low PTG levels. Similarly, Du et al[23] reported a low PTG level among young and middle-aged patients with primary BTs, with a mean PTGI score of 55.04 ± 7.86.

Correlation analyses demonstrated that anxiety and depression were positively associated with poorer sleep quality and negatively associated with PTG. These findings indicate that more severe negative emotions are accompanied by worse sleep quality and lower PTG in patients with BT. Mitterling et al[24] identified depressive symptoms as an independent contributor to poor sleep quality in adult glioma patients, indirectly supporting this association. King et al[25] further showed that primary BT patients with moderate to severe sleep disorders experienced more severe emotional disorders. Casellas-Grau et al[26] reported a negative correlation between depression/anxiety and PTG in tumor patients, consistent with our findings. A mouse experiment indicates that the activation of the NOD-like receptor pyrin domain-containing 3 inflammasome mediates the memory and emotional behavioral deficits induced by sleep deprivation, potentially via the transient receptor potential vanilloid subtype 1 channel, which may partially explain the potential associations between anxiety, depression, sleep quality, and PTG in patients with BT[27].

Multivariate regression analysis further identified age ≥ 50 years, high school education or above, and PTGI ≥ 60 as independent protective factors against anxiety or depression, whereas PSQI ≥ 11 was an independent risk factor. Older patients (age ≥ 50 years) may possess greater psychological maturity and coping flexibility, enabling them more adaptive responses to disease-related stressors. Higher educational attainment may reflect better cognitive function and information-seeking ability, facilitating more accurate illness perception and positive coping strategies. A PTGI score ≥ 60 indicates moderate or high PTG level, suggesting greater resilience when facing traumatic events. Conversely, a PSQI score ≥ 11 reflects severe sleep disorders, which can substantially deplete mental energy, aggravate cancer-related fatigue, and intensify psychological burden.

CONCLUSION

In summary, anxiety/depression and sleep disturbances are highly prevalent among patients with BT, who also tend to exhibit relatively low PTG level. Anxiety or depression in this population is closely related to sleep quality and PTG. Being aged 50 or older, having at least a high school education, and achieving a PTGI score ≥ 60 appear to protect against anxiety or depression, whereas a PSQI score ≥ 11 significantly increases the risk of anxiety or depression in these patients.