Alexithymia in oncologic disease: Association with cancer invasion and hemoglobin levels

Abstract

BACKGROUND

The literature suggests that alexithymia is the result of individual differences and/or biological mechanisms. Both individual differences and disease mechanisms may play a role among individuals with medical or surgical conditions. The relative weight of clinical and individual differences factors related to alexithymia has not been studied in patients with cancer. The purpose of this study was to examine the extent to which individual differences in perceived stress and biological markers of illness severity are associated with alexithymia among patients with cancer.

METHODS

Treated oncologic outpatients (N = 37) were assessed using the 20-item Toronto Alexithymia Scale and Perceived Stress Scale. Alexithymia was examined in relation to perceived stress, tumor staging, and hemoglobin levels.

RESULTS

Among the patients studied, 34.2% endorsed the established cutoff score (≥61) for alexithymia. Higher alexithymia scores were found in patients with more advanced stages of cancer invasion. Alexithymia correlated directly with perceived stress and indirectly with hemoglobin levels. Hemoglobin levels and cancer invasion significantly correlated with alexithymia when controlling for perceived stress.

CONCLUSIONS

A significant component of alexithymia in cancer patients may be construed as acquired. But awareness of health status influencing perceived stress might partially mediate the role of cancer invasion and hemoglobin on alexithymia.

INTRODUCTION

Individuals with limited introspective capacity and a cognitive style characterized by difficulty expressing emotions and distinguishing between emotions and bodily sensations are commonly identified as alexithymic.¹ Alexithymia is associated with psychiatric disorders including substance,² somatoform,³ panic,⁴ posttraumatic stress,⁵ and eating disorders⁶; and with medical illnesses, such as gastrointestinal dysmotility,⁷ hypertension,⁸ and inflammatory bowel syndrome.⁹ Alexithymia is a stable personality trait (ie, primary alexithymia)¹⁰ but also can be acquired or secondary. Mechanisms for acquired alexithymia may be brain damage,¹¹ age-related gray matter reduction in the anterior cingulate cortex (ACC),¹² or dysfunction in the interhemispheric transfer of information (eg, resection of the corpus callosum).^13,14

Malignancies have been associated with elevated levels of alexithymia.¹⁵ Whereas identifying risk factors for alexithymia in oncologic illness may help in targeting medical interventions and may ultimately lead to improved quality of life,¹⁶ research in this area has been scant. The present study represents an initial step in identifying potential risk factors for alexithymia in cancer patients. It was posited that alexithymia in oncologic disease may have primary (related to individual differences)¹⁰ and/or secondary (acquired or biological) mechanisms.^11,17 As an individual difference factor, the choice fell on stress because stress is perceived differently depending on the personality of the individual,¹⁸ and the degree to which stress is perceived is considered a heritable psychological factor.¹⁹ In addition, the trying life conditions of individuals with cancer invariably result in a wide range of stress responses, limiting foreseeable floor and ceiling effects on the perceived stress measure.

As biological factors, anemia and degree of cancer invasion were chosen because they are clear indicators of illness severity.²⁰ In addition, almost all individuals with cancer will develop some degree of anemia, with up to 80% of patients experiencing serious hemoglobin reduction.^21-23

This study examined the extent to which alexithymia among cancer patients is associated with psychological (ie, perceived stress) and/or biological (ie, anemia and tumor staging) factors.

METHODS

From March 2007 to June 2007, cognitively intact out-patients (N = 37; 20 women) with solid and hematologic malignancies were enrolled from the oncology services of the Cannizzaro and Ferrarotto Hospitals in Catania, Italy, based solely on their willingness to participate in the study and their ability to consent according to the Declaration of Helsinki. Malignancy type, staging, and hemoglobin levels were extracted from the medical record at the time of alexithymia assessment. Alexithymia was measured using the Italian version of the Toronto Alexithymia Scale (TAS-20).²⁴ The TAS-20 is a well-validated, widely used scale that measures alexithymia.²⁵ Cutoff scores are as follows: ≤50, no alexithymia; 51 to 60, borderline alexithymia; and ≥61, alexithymia.²⁵ Severity of depression was measured using the Italian version of the Beck Depression Inventory-II (BDI-II), with scores as follows: 0 to 13, minimal depression; 14 to 19, mild depression; 20 to 28, moderate depression; and 29 to 63, severe depression.^26,27

Perceived stress was measured using the 10-item Perceived Stress Scale (PSS),²⁸ a widely used instrument that measures stress perception for the previous month. Response options are assessed using a 5-level Likert scale (0, never to 4, very often). PSS scores range from 0 to 40, with higher scores indicating greater stress. Moreover, each patient was assigned a cancer stage according to the TNM classification, which considers size and extent of tumor (T), involvement of lymph nodes (N), and presence of metastasis (M).

Data analysis

The effects of sex and cancer type on alexithymia, perceived stress, and hemoglobin levels were examined for descriptive purposes using ranks (data were not normally distributed), and t and F statistics. Hypothesis testing (ie, associations of alexithymia with hemoglobin level and perceived stress) was carried out using ranks, correlation, and regression techniques. One-way analysis of variance (ANOVA) was used to examine the effect of illness staging on ranked alexithymia scores and hemoglobin levels. Least square differences (LSD) were examined to report post hoc significant differences when the omnibus model was significant. All analyses were carried out using the Statistical Package for the Social Sciences (SPSS) version 17.0.1.

RESULTS

The patients’ age range was 32 to 75 years (mean age, 59.8; SD = 10.2). Most patients (84.2%) were married, 15.8% were single or widowed; the mean education was 10.9 years (SD = 4.8); and employment was as follows: 5.3%, primary sector; 13.2%, secondary sector; 39.5%, tertiary sector; and 26.3%, retired. According to the BDI-II cutoff scores, 4 participants (10.8%) had moderate depression, and 14 (37.8%) had severe depression. Patient malignancies were as follows: 13, gastroenteric; 10, breast; 6, urogenital; 5, hematologic; and 3, pulmonary. Proportions of patients by TNM staging were as follows: stage I, 5.4%; stage II, 43.2%; stage III, 37.8%; and stage IV, 13.5%. Patients with hematologic cancer were at stage II (80%) or III (20%); patients with gastroenteric cancer were at stage II (31%), stage III (46%), or stage IV (23%); patients with breast cancer were at stage I (20%), stage II (40%), stage III (20%), or stage IV (20%); patients with urogenital cancer were at stage II (80%) or stage III (20%); and all pulmonary cancer patients were at stage III.

Prevalence of alexithymia (TAS-20 ≥61) was 34.2%. Mean alexithymia score was 55.3 (SD = 9.7; range, 40 to 79). For women, the mean score was 54.4 (SD = 11.5) and for men it was 56.5 (SD = 7.4) (t = .63; df = 36; P > .5). Mean perceived stress was 21.6 (SD = 6.0), with men showing a mean of 21.5 (SD = 5.5) and women showing 21.7 (SD = 6.5) (t = –.11; df = 36; P > .4). Hemoglobin mean values were 10.7 mg/dL (SD = 1.8; range, 8 to 14 mg/dL). Mean values for men (11.1 mg/dL; SD = 1.9) were not different from mean values for women (10.3 mg/dL; SD = 1.6) (t = 1.4; df = 36; P > .2).

Effects of malignancy type on alexithymia, perceived stress, and hemoglobin levels were examined for descriptive purposes (TABLE 1). A significant effect of cancer type on alexithymia was found (F[4,32] = 3.6; P < .02), while the effect on perceived stress just failed to meet significance (F[4,32] = 2.6; P = .051) and there was no significant effect of cancer type on hemoglobin level (F[4,32) = .8; P > .4). Patients with breast cancer had the lowest alexithymia scores, whereas patients with lung cancer had the highest alexithymia scores (TABLE 1). Patients with hematologic (LSD = 12.2; P < .03) and lung malignancies (LSD = 22; P = .001) showed significantly higher alexithymia compared with patients with breast cancer. No other differences were found to be statistically significant.

TABLE 1.

Alexithymia, perceived stress, and hemoglobin levels by malignancy type

Cancer type	n	TASa		PSSb		Hemoglobinc
		Mean	SD	Mean	SD	Mean	SD
Hematologic	5	60.4	10.8	26.4	6.58	9.80	2.05
Gastroenteric	13	56.0	8.6	21.8	6.72	10.62	1.94
Genitourinary	6	55.5	5.8	19.2	2.99	11.17	1.83
Breast	10	48.5	10.2	19.6	5.87	11.20	1.55
Lungs	3	66.3	1.5	25.3	2.52	9.67	2.08
TOTAL	37	55.35	9.78	21.46	6.00	10.68	1.83

^aANOVA for TAS: F(4,32) = 3.6; P < .02.

^bANOVA for PSS: F(4,32) = 2.6; P = .051.

^cANOVA for hemoglobin level: F(4,32) = .8; P > .4.

Post hoc analyses: Patients with hematologic malignancies (LSD = 12.2; P < .03) and lung malignancies (LSD = 22; P = .001) showed significantly higher alexithymia compared with patients with breast cancer.

ANOVA: analysis of variance; LSD: least squares difference; PSS: Perceived Stress Scale; SD: standard deviation; TAS: Toronto Alexithymia Scale.

The influence of stage of tissue invasion on alexithymia, perceived stress, and hemoglobin levels are shown in TABLE 2. The effect of cancer invasion on alexithymia was statistically significant (F[3,33] = 5.8; P = .002) and showed that alexithymia scores were higher with greater tissue invasion (see TABLE 2 for details on post hoc analyses). The effect of cancer staging on perceived stress also was significant (F[3,33] = 3.5; P = .025) (see TABLE 2 for details on post hoc analyses). The effect of cancer staging on hemoglobin level just failed to reach statistical significance (F[3,33] = 2.7; P = .063). When patients with hematologic cancer (n = 5) were excluded from the analysis, the effect of cancer staging on hemoglobin level became statistically significant (F[3,28] = 3.5; P = .028), confirming that stage of cancer invasion and anemia are related indices of illness severity.

TABLE 2.

Alexithymia, perceived stress, and hemoglobin levels by cancer staging

Cancer stage	n	TASa		PSSb		Hemoglobinc
		Mean	SD	Mean	SD	Mean	SD
I	2	44.0	0	10.50	0.71	10.50	.71
II	16	50.9	2.3	21.31	5.03	11.56	1.82
III	14	59.0	1.9	20.17	5.89	9.86	1.56
IV	5	63.6	4.2	26.20	5.72	10.20	1.92
TOTAL	37	55.35	9.78	21.66	6.05	10.68	1.83

^aANOVA for TAS: F(3,33) = 5.8; P = .002.

^bANOVA for PSS: F(3,33) = 3.5; P = .025.

^cANOVA for hemoglobin level: F(3,33) = 2.7; P = .063.

Post hoc analyses for TAS showed significant differences between stages I and III (LSD = 18; P < .02) and I and IV (LSD = 21.6; P <.01), and between stages II and III (LSD = 10.1; P < .006) and IV (LSD = 13.3; P <.01). No significant differences were found between stages I and II (LSD = 8.3; P > .2) or between III and IV (LSD = 3.1; P >.5).

Post hoc analyses for PSS showed significant differences between stages I and III (LSD = 17.6; P < .03) and I and IV (LSD = 25.7; P < .005) and between stages II and IV (LSD = 10.9; P < .04). No significant difference was found between stages I and II (LSD = 14.8; P = .055) or between III and IV (LSD = 8.0; P =.13).

ANOVA: analysis of variance; LSD: least squares difference; PSS: Perceived Stress Scale; SD: standard deviation; TAS: Toronto Alexithymia Scale.

Hemoglobin level inversely correlated with alexithymia (r = −.51; P = .001) and with perceived stress (r = −.42; P = .005), which directly correlated with alexithymia (r = .52; P = .001). When patients with hematologic cancer were excluded, correlations between hemoglobin levels and alexithymia remained essentially the same (r = −.49; P = .004; n = 32) as well as the association between alexithymia and perceived stress (r = .50; P = .003; n = 32), but the correlation between hemoglobin level and perceived stress was no longer significant (r = −.27; P > .1; n = 32). These 2 sets of analyses indicate that lower hemoglobin levels predicted severity of alexithymia, which was also associated with perception of stress, but in nonhematologic oncologic disease, perceived stress was not predicted by anemia.

Perceived stress, cancer staging, and hemoglobin level were then examined in a regression model predicting alexithymia. The model showed an overall r = .70 (R² = .49) (F[3,33] = 10.6; P < .0001). Standardized beta for perceived stress was .25 (t[1,36] = 1.7; P > .10), while for cancer staging it was .37 (t[1,36] = 2.6; P < .02), and for hemoglobin it was –.29 (t[1,36] = –2.05; P < .05). Perceived stress, hemoglobin, and cancer staging were also entered independently in the hierarchical model. In this case, the R² for perceived stress was .29 (F[1,35] = 14.4; P = .001), whereas the R² changed to .38 after hemoglobin (F[1,34] = 5.1; P < .05) was entered, and to .49 (F[1,33] = 6.9; P < .02) after cancer staging was entered. The order in which the independent variables were entered did not affect the results. In summary, perceived stress, cancer invasion, and hemoglobin level together accounted for about 50% of the variance in alexithymia. Hemoglobin level and cancer staging were significant predictors of alexithymia, independent of perceived stress.

DISCUSSION

The present study found a 34.2% prevalence of alexithymia in cancer patients. This is consistent with the 36.4% prevalence found in women with breast cancer¹⁵ and is about 8-fold greater than in the general population of Italy (4.5%).⁹ There is broad consensus that alexithymia may stem from individual developmental differences,¹⁰ age-related brain changes,¹² or medical or surgical disease.¹⁷ In this sample of cancer patients, psychological factors (ie, stress perception) accounted for about 30% of the variance in alexithymia. Hemoglobin level and degree of cancer invasion were independently associated with alexithymia, and each accounted for an additional 10% of the variance. In addition, cancer invasion and lower levels of hemoglobin were associated with greater perceived stress. When patients with hematologic cancer were excluded from the analysis, the association of low hemoglobin levels with perceived stress was no longer significant. These findings confirm that overall health status has significant implications on psychological well-being. We do not know how many patients were fully aware of their survival prognosis based on their cancer progression, which raises the possibility that illness severity and perceived stress were at least in part associated because of the patients’ knowledge of their prognosis.

Some limitations should be acknowledged before further discussion of the findings in this study. The sample size was limited, and enrollment was notably influenced by patients’ willingness to take part in the study. These findings—including the association between cancer type and alexithymia—will need replication with a larger, randomly selected sample of patients. In addition, the sample size limited the number of possible analyses. Only the TAS-20 total score, and not the 3 factors—difficulty identifying emotions, difficulty describing emotions, and externally oriented thinking—was examined, and no analyses were conducted to explore the association of alexithymia and its factors with depressive symptoms. This association has been examined extensively in the literature, showing that overlap and independence of the 2 constructs exist.^29,30

Similarly, the number of psychological illness severity factors was limited. A different set of illness severity predictors may have yielded different results. No longitudinal measures of alexithymia were available, allowing a definite causal association with biological or psychological factors. In this regard, contrary to the implications of the results of the present study, relative stability of alexithymia in cancer has been reported.³¹ In that study, stability of alexithymia was suggested based on an initial evaluation carried out the day before surgery and another evaluation attained 6 months after surgery; no measures of illness severity were reported at the initial or follow-up evaluations.³¹ A longitudinal design with assessment of alexithymia before onset of the malignancy may resolve this question.

In addition, the findings in the present study may not generalize to childhood malignancies, as 5-year cancer survivors (diagnosed before age 19) showed no significant differences in alexithymia compared with healthy comparisons, and no indication of medical severity—not including hemoglobin levels—was found to be associated with alexithymia.³²

The relationship between alexithymia and cancer is complex and bidirectional. By altering the expression of immune function, alexithymia may have a role in the etiology of cancer.³³ Levels of IL-1β, IL-2, and IL-4 and T_H1/T_H2 lymphocytes (IL-2/IL-10) and CD4:CD8 ratios, as well as CD4, are decreased in women with alexithymia.³⁴ This may in part be the indirect result of elevated steroid response to stress as a function of alexithymia.³⁵ T_H1 lymphocytes induce the proliferation of lymphocytes, CD8⁺, and natural killer cells and therefore may have an important role in stimulating cell-mediated defense against cancerous cells. On the other hand, alexithymia may be a psychological consequence of stress and suffering,³⁶ common especially in advanced stages of tissue invasion. The present study has shown that in addition to these psychological mechanisms, cancer may play a significant role in alexithymia by altering the normal somatic physiology, through both invasion of healthy tissue and anemia.

The ACC, a cerebral structure involved in the mechanisms of alexithymia,^12,37-39 is among the brain regions most vulnerable to hypoxic injury.⁴⁰ In humans, the ACC shows early functional decline,⁴¹ perhaps due to vascular vulnerability.⁴² Decline in function and structure of the ACC has been considered a mechanism for the greater degree of alexithymia observed in older age.¹² Therefore, a potential mechanism by which hemoglobin is associated with alexithymia is a reduction of oxygen transport to the brain and, specifically, to the anterior cingulate.^12,42 The corpus callosum also has been posited as a brain structure involved in alexithymia.^43,44 This important route of interhemispheric communication also is vulnerable to low oxygen, as hypobaric hypoxia affects the morphologic and functional maturation of the corpus callosum in rats during postnatal development.⁴⁵

The findings of the present study confirm the well-established and general notion that lower hemoglobin levels are associated with impaired psychological functioning.⁴⁶ It is noteworthy that correction of low hemoglobin levels with iron therapy improves cognitive performance in otherwise healthy adults.⁴⁷ The hypothesis that treatment of anemia improves alexithymia warrants empirical testing. Improvement of alexithymia with relatively simple interventions aimed at reducing anemia may alleviate the negative effects of alexithymia on immune response.

In summary, patients with cancer in the present study showed greatly elevated rates of alexithymia in relation with rates in the general population.⁹ Alexithymia was associated with progression of cancer invasion. Alexithymia correlated directly with perceived stress and indirectly with hemoglobin levels. Hemoglobin levels and cancer invasion significantly correlated with alexithymia when controlling for perceived stress. Perceived stress, strongly influenced by personality, was associated with cancer invasion but less definitively with lower levels of hemoglobin. These findings suggest that alexithymia in cancer patients can be viewed as partly acquired and potentially amenable to improvement with treatment of the underlying medical condition.