Resilience levels, associated factors, and their correlation with serum neurotransmitter levels in patients with gastric cancer

Abstract

BACKGROUND

Although the pathogenesis and management of gastric cancer (GC) have made significant progress, patient prognosis remains unsatisfactory. Patients’ psychological well-being should also be prioritized in addition to their physical health.

AIM

To investigate resilience among GC patients, identify determinants, and examine its association with serum neurotransmitters (NTs).

METHODS

We recruited 141 GC cases (research group) and 120 healthy individuals (control group). Surveys were conducted for all participants, encompassing the Connor-Davidson Resilience Scale (for resilience assessment), the Medical Coping Modes Questionnaire (for coping strategy evaluation), the General Self-Efficacy Scale (for self-efficacy quantification), and the Self-Rating Anxiety Scale/Self-Rating Depression Scale (for emotional distress measurement). Analyses were then conducted to identify inter-group differences in serum NTs, to pinpoint correlations between NTs and resilience (via Spearman’s test), and to determine resilience-associated predictors (using multivariate analysis).

RESULTS

The group scored 65.44 ± 6.97 (mean) on the global Connor-Davidson Resilience Scale (tenacity: 34.70 ± 5.32, self-improvement: 21.13 ± 3.91, optimism: 99.61 ± 1.40). Regarding coping styles, the confrontation, avoidance, and resignation dimension scores were 17.45 ± 1.56, 17.22 ± 1.47, and 10.01 ± 1.08, respectively. The mean self-efficacy score (General Self-Efficacy Scale) was 27.00 ± 3.74. GC cases exhibited reduced serum dopamine, 5-hydroxytryptamine, and norepinephrine than controls (P < 0.05). As to resilience-associated predictors, males, higher education, and greater per capita monthly income were all independently linked to higher resilience, while elevated anxiety/depressive symptoms and advanced-stage cancer showed an inverse correlation with resilience.

CONCLUSION

Reduced resilience and serum NTs, with the two being strongly correlated, are common in GC patients. Clinically, targeted psychological support is critical, particularly for those at-risk populations (e.g., females, lower socioeconomic status, limited education).

Key Words: Gastric cancer; Resilience level; Self-efficacy; Serum neurotransmitters; Psychological healthy

Core Tip: Being a prevalent malignancy, gastric cancer (GC) poses a great threat to patients’ physical and mental health. Despite the presence of extensive research on resilience’s psychological impact, insufficient evidence is available regarding its determinants in GC, with limited theoretical and variable inclusion frameworks. This investigation clarifies the variation in neurotransmitters between GC patients and healthy controls to elucidate how altered neurotransmitter levels influence patients’ resilience, while also identifying resilience-related determinants.

INTRODUCTION

Being a commonly seen malignancy, gastric cancer (GC) poses grave threats to physical and mental health[1]. Thanks to advancements in preventive strategies, GC prevalence and mortality have shown declines in recent years[2]. The sufferers not only experience physical manifestations but also endure psychological comorbidities that profoundly compromise their mental well-being[3]. Positive psychology has reshaped the traditional “trauma-stress-maladjustment” paradigm. Moving beyond conventional negative emotion-focused diagrams, the current research on psychological states of oncology patients is shifting to coping strategies, adaptability, and resilience[4]. Of these, resilience is defined as the ability of a person to recover from difficulties and to actively adjust their state of mind when facing major adversities[5]. GC patients usually exhibit lower resilience than the general population[6]. By adopting effective coping styles and strong social support, their psychological and spiritual well-being as well as resilience can be enhanced, ultimately improving survival and well-being[7].

Past evidence has attributed adverse mood in oncology patients to chemotherapy-induced toxicities. With advancing clinical research, however, dysregulated neurotransmitter (NT) activity has been increasingly recognized to more substantially influence patient prognoses[8]. However, there is scant research on resilience among GC patients, with little theoretical knowledge, insufficient exploration of influencing factors, and fewer correlation analyses linking NT expression. By profiling NTs in GC cases and healthy individuals, this study correlates NTs with resilience, while identifying resilience-associated determinants, so as to pave the way for optimized psychological interventions.

MATERIALS AND METHODS

Research population

After screening (see the criteria detailed below), we enrolled GC patients during their hospitalization in our hospital (January 2021 to January 2024). Eligibility requirements: (1) A GC diagnosis confirmed clinically and histologically; (2) Clear thinking, competent communication, and accurate comprehension of survey content; (3) Adults (≥ 18 years); (4) Life expectancy > 6 months; and (5) Case data completeness. Exclusion grounds: (1) Fatal comorbidities; (2) Trauma or significant life-altering events within the recent 6 months; (3) Cognitive/communication impairments; (4) Inflammatory or medically unstable patients; (5) Severe complications; (6) Psychiatric disorders; or (7) Case record defects. The controls were 120 healthy individuals presenting during the same timeframe, with their hematological parameters collected. We enrolled 141 GC patients (male/female 74/67, mean age 51.46 ± 10.79 years, mean body mass index 22.24 ± 3.03 kg/m²); comorbidities were diabetes in 35 cases and hypertension in 41. For controls, there were 68 males and 52 females aged 50.69 ± 10.26 years on average, with a mean body mass index of 22.74 ± 3.54 kg/m²; 23 had diabetes and 27 had hypertension. Comparability was indicated by the absence of statistical inter-group differences in baseline characteristics (P > 0.05).

Investigation tools

Data collection: (1) Demographic data (e.g., age, sex, education, marital status, employment status, monthly income, living conditions, medical expense coverage) were sourced from electronic health records; (2) The oncological characteristics documented covered disease stage, treatment modality, time since diagnosis, and metastatic status; and (3) We further gathered information on biochemical indices. Following venous blood sampling, enzyme-linked immunosorbent assay quantified serum NTs - dopamine (DA), 5-hydroxytryptamine (5-HT) and norepinephrine (NE). Enzyme-linked immunosorbent assay kits were procured from Nanjing Jiancheng Institute of Bioengineering Co., LTD. (China) with lot numbers: DA (H170-1-1), 5-HT (H104-1-1), and NE (H096-1-1).

Survey scales: (1) Resilience: Employing the 25-item Connor-Davidson Resilience Scale, resilience was assessed from tenacity, self-improvement, and optimism domains. Each item was rated on a five-point Likert scale (0 = “not true at all” to 4 = “true nearly always”). The total score (0-100) correlates positively with resilience. The scale’s favorable reliability and validity are supported by Cronbach’s α = 0.892; (2) Depression/anxiety: Psychological distress evaluation utilized the Self-Rating Depression Scale (SDS)/Self-Rating Anxiety Scale (SAS). The presence of depression and anxiety is indicated by a cutoff of ≥ 53 (SDS) and ≥ 50 (SAS), based on Chinese norms. Higher scores suggest greater severity; (3) Coping styles: For coping strategy assessment, the 20-item Medical Coping Modes Questionnaire was used. With items scored 1 point to 4 points, confrontation (8 items; score range: 8-32 points), avoidance (7 items; 7-28 points), and resignation (5 items; 5-20 points) dimensions were assessed. The questionnaire exhibited good reliability (α = 0.825); and (4) Self-efficacy: The General Self-Efficacy Scale evaluated self-efficacy through 10 items scored 1-4 (1 = completely incorrect; 2 = not quite correct; 3 = almost correct; and 4 = completely correct; range: 10-40). Scores are proportional to self-efficacy and confidence in challenge coping. The scale demonstrated strong reliability (α = 0.816).

Survey methods: All eligible patients underwent a questionnaire survey. Trained researchers used a uniform language to guide participants to fill out the questionnaire. The survey was conducted when the patient was free and mentally alert, usually after the patient’s afternoon nap at 14:00 or at 18:00 post-dinner. Researchers assisted individuals with reading difficulties in completing the survey, with suggestive language strictly prohibited. The questionnaire was expected to be completed within 30-40 minutes. For quality control, it could be completed over 1 day to 3 days during the patient’s hospital stay. All questionnaires were distributed and collected in person, with their completeness verified immediately. 145 of the 166 distributed questionnaires were recovered (87.3% response rate). 141 questionnaires were finally analyzed (84.9% effective response rate) after excluding 4 with invalid responses.

Statistical analysis

This study utilized SPSS 25.0 to analyze the obtained data. Measurements are reported using mean ± SD. For pairwise group comparisons, the Student’s t-test was applied, whereas one-way analysis of variance served to evaluate multi-group differences. Count data were reported in percentages, with the χ² test applied for comparison. To identify predictors independently influence resilience, variables significant in univariate analysis underwent further multivariate logistic regression analysis. Pearson’s rank correlation evaluated associations. The threshold for statistical significance was P < 0.05 (two-tailed, α = 0.05).

RESULTS

Resilience and mental health scores

Among patients with GC (n = 141), the overall resilience score was 65.44 ± 6.97, with subscale scores of 34.70 ± 5.32 (self-improvement), 21.13 ± 3.91 (tenacity), and 9.61 ± 1.40 (optimism). Mean SAS and SDS scores were 46.26 ± 5.25 and 47.26 ± 6.25, respectively. 40 (28.4%) and 37 (26.2%) patients were found to present clinically significant anxiety (SAS ≥ 50) and depression (SDS ≥ 53), respectively (Table 1).

Table 1 Resilience, anxiety, and depression assessments.

Categories	Minimum	Maximum	mean ± SD
Total resilience score	47	83	65.44 ± 6.97
Tenacity subscale	22	48	34.70 ± 5.32
Self-improvement subscale	11	29	21.13 ± 3.91
Optimism subscale	5	13	9.61 ± 1.40
SAS	35	58	46.26 ± 5.25
SDS	27	64	47.26 ± 6.25

SAS: Self-Rating Anxiety Scale; SDS: Self-Rating Depression Scale.

Coping style and self-efficacy scores

Coping style scores for patients with GC were as follows: 17.45 ± 1.56 (confrontation), 17.22 ± 1.47 (avoidance), and 10.01 ± 1.08 (resignation). This indicates dominant confrontation and avoidance strategies instead of resignation when handling disease-related challenges. The mean (General Self-Efficacy Scale) score was 27.00 ± 3.74 (Table 2).

Table 2 Coping style and self-efficacy scores.

Categories	Minimum	Maximum	mean ± SD
Medical coping style
Confrontation	12	20	17.45 ± 1.56
Avoidance	14	21	17.22 ± 1.47
Resignation	6	12	10.01 ± 1.08
Total self-efficacy score	16	36	27.00 ± 3.74

Serum NT levels

Serum analysis revealed significantly lower concentrations of DA, 5-HT, and NE in GC cases than in healthy controls (P < 0.05; Table 3).

Table 3 Serum neurotransmitter levels, mean ± SD.

Categories	DA (ng/L)	5-HT (μg/L)	NE (ng/L)
Healthy controls (n = 120)	66.94 ± 7.42	0.89 ± 0.11	40.87 ± 5.44
Gastric cancer patients (n = 141)	38.65 ± 4.98	0.62 ± 0.09	28.43 ± 3.04
t	36.614	21.807	23.229
P value	< 0.0001	< 0.0001	< 0.0001

DA: Dopamine; 5-HT: 5-hydroxytryptamine; NE: Neurotransmitter.

Correlations between various resilience dimensions and NT levels

Correlation analysis among the 141 patients with GC revealed significant positive correlations between NT levels (DA, 5-HT, NE) and total resilience scores (P < 0.05) and its subdimensions of tenacity and self-improvement (P < 0.05). However, optimism was not significantly correlated with NT concentrations (P > 0.05; Table 4).

Table 4 Correlations between various resilience dimensions and neurotransmitter levels.

Characteristic	Resilience score		Tenacity		Self-improvement		Optimism
	r	P value	r	P value	r	P value	r	P value
DA	0.439	< 0.0001	0.393	< 0.0001	0.267	0.001	-0.053	0.535
5-HT	0.525	< 0.0001	0.499	< 0.0001	0.223	< 0.0001	0.094	0.267
NE	0.576	< 0.0001	0.472	< 0.0001	0.373	< 0.0001	0.035	0.683

DA: Dopamine; 5-HT: 5-hydroxytryptamine; NE: Neurotransmitter.

Influence of sociodemographic variables on resilience

Resilience levels differed significantly by sex, education level, monthly income, and mental health status (anxiety/depression; P < 0.05). Conversely, age, marital status, employment status, living situation, and medical expense coverage had no significant effect (P > 0.05; Table 5).

Table 5 Resilience-associated socio-demographic variables (univariate assessment), mean ± SD.

Characteristic	Frequency (n = 141)	Resilience score	t/F	P value
Sex			5.170	< 0.0001
Male	74	68.09 ± 6.39
Female	67	62.51 ± 6.43
Age			0.329	0.720
≤ 45	39	64.72 ± 6.99
46-59	48	65.50 ± 5.98
≥ 60	54	65.91 ± 7.82
Marital status			0.610	0.545
Single	32	65.28 ± 7.47
Married	61	64.84 ± 7.52
Divorced/widowed	48	66.31 ± 5.88
Educational level			27.71	< 0.0001
Junior high school or below	30	59.10 ± 5.11
Senior high school/technical secondary school	69	65.64 ± 6.88
Junior college/university	42	69.64 ± 4.62
Employment status			0.111	0.895
Employed	73	65.68 ± 6.61
Retired	42	65.05 ± 7.46
Unemployed	26	65.38 ± 7.39
Monthly income			47.01	< 0.0001
< 3000	34	57.26 ± 4.30
3000-5000	56	66.73 ± 5.72
5001-10000	29	67.81 ± 4.12
> 10000	22	72.25 ± 4.41
Living situation			0.970	0.382
Alone	60	65.35 ± 6.53
With spouse	50	64.66 ± 7.61
With family	31	66.87 ± 6.74
Payment mode of medical expenses			0.653	0.515
Medical insurance	89	65.15 ± 6.94
Self-funded	52	65.94 ± 7.07
Anxiety			10.56	< 0.0001
Yes	40	58.08 ± 5.61
No	101	68.36 ± 5.07
Depression			10.15	< 0.0001
Yes	37	57.84 ± 5.50
No	104	68.14 ± 5.23

Influence of disease-related factors on resilience

Resilience levels varied significantly by tumor stage and treatment modality (P < 0.05), whereas disease duration and lymph node metastasis showed no significant association (P > 0.05; Table 6).

Table 6 Univariate predictors (disease-related) of resilience, mean ± SD.

Characteristic	Frequency	Resilience score	t/F	P value
Tumor staging			0.382	< 0.0001
I	21	73.19 ± 4.84
II	33	65.45 ± 2.85
III	71	65.20 ± 6.79
IV	16	56.31 ± 4.06
Course of disease (months)			0.041	0.125
< 10	23	62.26 ± 8.73
10-19	55	66.00 ± 6.46
20-30	36	66.19 ± 7.04
> 30	27	66.00 ± 5.76
Lymph node metastasis			0.626	0.532
Yes	77	65.10 ± 7.19
No	64	65.84 ± 6.74
Treatment modality			0.494	< 0.0001
Chemotherapy + radiotherapy	36	59.54 ± 5.36
Surgery + radiotherapy/chemotherapy	49	71.89 ± 4.01
Surgery + radiotherapy + chemotherapy	33	67.41 ± 3.94
Others	23	65.43 ± 6.72

Multivariate analysis of resilience in patients with GC

Variables significant in univariate analysis were included in a multivariate regression model. Independent predictors of resilience included sex, education, per capita monthly income, psychological state (anxiety/depression), and cancer stage, accounting for 72.7% of variance. Positive predictors were male sex, higher education, and greater income, while higher anxiety, depression, and advanced cancer stage correlated with reduced resilience (Table 7).

Table 7 Multiple linear regression analysis results of resilience determinants in gastric cancer.

Variable	Assignment	Regression coefficient	SE	Standardized regression coefficient	t	P value	95%CI	Collinear statistics
								Capacity	VIF
Constant		64.144	1.332		48.152	0.000	61.509-66.778
Sex	0 = female, 1 = male	2.031	0.662	0.146	3.070	0.003	0.722-3.339	0.863	1.159
Educational level	0 = junior high school or below, 1 = senior high school/technical secondary school, 2 = junior college/university	1.690	0.501	0.173	3.369	0.001	0.698-2.682	0.744	1.345
Per capita monthly income	0 ≤ 3000, 1 = 3000-5000, 2 = 5000-10000, 3 ≥ 10000	1.973	0.383	0.276	5.155	0.000	1.216-2.731	0.680	1.471
Anxiety	0 = no, 1 = yes	-2.955	0.952	-0.192	-3.104	0.002	-4.838 to -1.072	0.511	1.957
Depression	0 = no, 1 = yes	-4.316	0.869	-0.273	-4.969	0.000	-6.034 to -2.598	0.645	1.551
Tumor staging	0 = I, 1 = II, 2 = III, 3 = IV	-1.437	0.417	-0.181	-3.443	0.001	-2.262 to -0.611	0.704	1.421
Treatment modality	0 = other, 1 = chemotherapy + radiotherapy, 2 = surgery + radiotherapy/chemotherapy, 3 = surgery + radiotherapy + chemotherapy	0.132	0.344	0.019	0.385	0.701	-0.547 to -0.812	0.775	1.290

CI: Confidence interval; VIF: Variance inflation factor.

DISCUSSION

Although medical advances have extended survival of patients with GC, repeated treatments and disease recurrence continue to impair physical and psychological well-being, significantly reducing quality of life and causing profound psychological distress[9]. Resilience describes one’s adaptation and bounces back from trauma, adversity, stress, etc.[10]. For oncology patients, higher resilience means greater emotional stability, reduced anxiety and depression, enhanced quality of life, and better physical health status[11]. Rosenberg et al[12] further demonstrated decreased psychological distress, enhanced quality of life, and fewer physical impairments among cancer sufferers with higher resilience.

Our findings reveal a relatively low resilience level among GC cases, with a mean resilience score of 65.44 ± 6.97 (tenacity: 34.70 ± 5.32, self-improvement: 21.13 ± 3.91, optimism: 9.61 ± 1.40). China has witnessed an ongoing increase in cancer incidence. However, due to medical advances, survival rates are continuously rising and life expectancy is steadily extending. From this perspective, cancer is increasingly becoming a chronic condition[13]. Consequently, long-term physiological, psychological, familial, and social stressors are common in cancer sufferers. Over time, these stressors may exceed patients’ adaptive capacity, resulting in anxiety (n = 40 in our group) and depression (n = 37) that adversely impact quality of life and outcomes. Being disease-specific, medical coping strategies deliver more applicable guidance than general coping mechanisms[14]. In our group, higher reliance on confrontation and avoidance strategies was found, evidenced by 20-item Medical Coping Modes Questionnaire subscale scores (confrontation: 17.45 ± 1.56, avoidance: 17.22 ± 1.47, resignation: 10.01 ± 1.08). Medical coping styles (confrontation, avoidance, and resignation), with their effects differing across populations, are significant predictors of resilience[15]. Regarding self-efficacy (an individual’s confidence in successfully performing specific tasks), the mean score was 27.00 ± 3.74. In GC treatment, stronger self-efficacy is often indicative of greater control over their therapeutic course, fostering more adaptive coping with disease-related challenges[16].

Through NT profiling, we found marked lower DA, 5-HT, and NE in GC cases vs controls, as well as a positive correlation of these biomarkers with resilience. As classical monoamine NTs[17], DA, 5-HT, and NE are synthesized in sympathetic postganglionic neurons and intracerebral adrenergic terminals. In addition to modulating peripheral physiological functions, DA may also exert anti-tumor efficacy[18]. The deficiency of 5-HT and NE, key emotion regulators, heightens emotional reactivity and induces depression[19,20]. Adverse mood, prevalent among cancer sufferers, leads to treatment adherence reduction and clinical outcome worsening, further lowering resilience. Stress orchestrates physiological responses by modulating the sympathetic nervous system, neuroendocrine signaling, and behavior. Activated hypothalamic-pituitary-adrenal axis plus suppressed hypothalamic-pituitary-gonadal axis, sympathetic nervous system, and dopaminergic and serotonergic systems are subsequently induced, altering NT contents[21,22]. Therefore, psychological stress severity exerts a direct influence on serum NTs levels. The identified resilience determinants in GC cases included sex, education, monthly income, anxiety/depression, and tumor stage. Male gender, education, and income correlated positively with resilience, whereas anxiety/depression and tumor staging showed an inverse association with resilience scores. These results echo previous research findings. Female patients are believed to experience greater psychological stress, potentially reducing resilience[23]. However, some studies report inconclusive results regarding sex, marital status, and socioeconomic status[24]. Education is a robust predictor. Literature has linked higher education to greater adaptability, easier access to health information[25], and more proactive health management. Yilmaz et al[26] similarly identified education as a key resilience factor in gynecological cancers. Financial stress is also critical, as cancer treatment-induced substantial costs impose heavy economic burdens. This is particularly true for low-income patients who are struggling with medical expenses and income disruption, increasing the risk of developing emotional distress. Depression is markedly more prevalent in hospitalized GC cases than in cases suffering from other chronic diseases or healthy controls[27]. This can undermine treatment effectiveness while provoking anxiety, fear of recurrence, and persistent psychological distress, potentially shortening survival and forming a vicious circle. Consequently, emotional regulation is essential in cancer management. Interestingly, resilience varied significantly among patients with distinct therapeutic combinations, though treatment modality was excluded by multivariate analysis as an independent predictor. Surgically-treated patients with radiotherapy/chemotherapy exhibited higher resilience, possibly due to enhanced confidence in recovery following surgery, though adjunct therapy-induced adverse effects may heighten psychological stress.

Several limitations should be noted: (1) The relatively small sample size may restrict generalizability; and (2) The absence of treatment status-based stratification, as well as single NT profiling, limits causal inference regarding their connection with psychological states. Therefore, validation analyses by adopting larger, rigorously designed protocols that incorporate different treatment phases and longitudinal monitoring are warranted.

CONCLUSION

GC sufferers exhibit moderate resilience levels. Their significantly reduced monoamine NT expression appears to adversely affect resilience. Key determinants include sex, education, monthly income, and psychological distress. Hence, incorporating psychotherapeutic and psychological interventions into comprehensive GC care is crucial for both resilience and outcome enhancement.