EXPERIMENTAL AND CLINICAL TRANSPLANTATION

Objectives: The aim of the present study was to investigate suicidal ideation and dissociative experiences and to predict demographic and clinical risk factors during isolation periods in patients undergoing hematopoietic stem cell transplant.

Materials and Methods: Our study included 61 consecutive stem cell recipients (29 autologous, 32 allogeneic). Patients were evaluated with the Suicidal Ideation Scale, Dissociative Experiences Scale, Hamilton Depression Scale, Hamilton Anxiety Scale, and State Trait Anxiety Inventory.

Results: The transplant procedure did not influence the Dissociative Experiences or Suicidal Ideation Scales (P > .05). However, patients had higher anxiety and depression levels at time of discharge (P < .001). Suicidal ideation scores were correlated with higher Hamilton Depression Scale, State Trait Anxiety Inventory, and Dissociative Experiences Scale scores on admission (P < .05), with the latter 2 scores also higher at the time of discharge in patients who received radiotherapy prior to transplant (P < .05).

Conclusions: Suicidal ideation and dissociative experiences, which may emerge because of complex and traumatic processes, should be considered by clinicians. Social and psychological support should be provided for patients undergoing hematopoietic stem cell transplant.

Key words : Anxiety, Depression, Risk factors, Psychological support

Hematopoietic stem cell transplant (HSCT) is a complex, challenging, and risky procedure. It can be difficult to identify an appropriate stem cell donor, drug toxicities may develop, and immunosuppressive drugs are required for prevention of graft-versus-host disease (GVHD).¹ In many patients who undergo HSCT, these factors may lead to mental health problems during the isolation period when contact with the outside world and family and also physical activity are restricted.

Earlier studies have shown that high levels of psychological stress can develop before, after, and during HSCT.^2-5 Depression, anxiety, mood disorders, depersonalization, brief psychotic disorders, and delirium have been reported in patients isolated during HSCT.^6-9 Risk factors for suicide include depression, hopelessness, being elderly (> 65 years of age), male biological sex, and having newly diagnosed cancer; however, studies on HSCT-related suicidal ideation and interventions have been mainly limited to case reports.^10,11

Cancer patients have suicide rates that are double the rate shown in the general population. Although the incidence of suicidal ideation with cancer patients has been reported to be 11% in Turkish populations, the incidence in different cultural populations have ranged from 0.8% to 71.4% globally.^12,13 Suicide rates are reported to be lower in eastern societies (except Japan) than in western societies. According to data from the World Health Organization, the lowest suicide rates are in Eastern Mediterranean countries.¹⁴ According to the European Group for Blood and Marrow Transplantation, the absolute excess risk of suicide after HSCT is 10.91 higher than in the European general population for 100 000 deaths.¹⁵

Hopelessness and loneliness can play important roles in development of depression and suicidal thoughts in cancer patients. In Turkish culture, social, spiritual, religious, and family support are of great importance for coping with this condition. The Turkish population is generally conformist and collectivist and follow strict customs. Most Turkish people value family intimacy and family cohesiveness. The strong tradition in Turkish culture for respecting and protecting family members and a “family first” ideology may motivate family members to help to maintain and improve the health of family members.^16,17

Dissociative experiences accompanying personality disorders, including posttraumatic stress disorder, conversion disorder, substance use disorder, and obsessive-compulsive disorder, have been shown to occur in 8.3% of the general population and in 31.5% of cancer patients.^18-20 Dissociative complaints (depersonalization, derealization, inability to remember a significant part of the traumatic event, lethargy, lack of awareness of ones surroundings) may develop with or without other mental pathologies. Dissociative experiences are important in terms of emotional expression in oncology patients, who experience trauma due to expectation anxiety and future anxiety.²¹

Despite the presence of studies on psychiatric problems in cancer patients, a limited number of studies are available on patients with hematologic malignancies. To the best of our knowledge, no prospective investigations are available in the literature on suicidal ideation and dissociative experiences during the isolation period in patients undergoing HSCT. The aim of the present study was to investigate the level of suicidal ideation and dissociative experiences and the predictive demographic and clinical risk factors during isolation periods in patients undergoing HSCT.

Materials and Methods

Participants and procedures
This prospective, single-center study included 61 consecutive patients (29 [47.5%] autologous, 32 [52.5%] allogeneic) who were between 18 and 60 years old. Patients had undergone HSCT between January 2015 and January 2018. Patient and disease-related data were obtained from forms created to evaluate transplant patients. These forms fulfilled the criteria of the Joint Accreditation Committee: International Society for Cellular Therapy and the European Group for Blood and Marrow Transplantation (JACIE) accreditation criteria for the Nucleus electronic data management system (version 9.3.39; Monad Software Co., Ankara, Turkey).²² Eligibility criteria included undergoing HSCT due to hematologic malignancies like acute leukemia, lymphoma, and multiple myeloma, as well as some benign diseases that could result in premature mortality like aplastic anemia and sickle cell disease. Expectations from treatment outcomes were approximated according to data from the Center for International Blood and Marrow Transplant Research.²³

Patients recommended for HSCT by the transplant council were given standardized verbal and written information.²⁴ The information procedure included the expectations from and difficulties of the treatment. Written informed consent was obtained from all patients prior to study enrollment.

The patients were evaluated by a psychiatrist at admission. Those who did not have a psychiatric disorder according to Structured Clinical Interview for DSM-IV Clinical Version were given a questionnaire to obtain their sociodemographic characteristics and were asked to fill out the Hamilton Depression Scale (HAM-D), Hamilton Anxiety Scale (HAM-A), Suicidal Ideation Scale (SIS), Dissociative Experiences Scale (DES), and State Trait Anxiety Inventory (STAI-I and STAI-II) questionnaires. During the transplant procedure, patients received a conditioning regimen according to the transplant type in a standard room and were taken to the isolation room 1 day before the peripheral stem cell infusion. The period beginning from this day until discharge was defined as “the isolation period.” Isolation rooms, which were monitored continuously by a camera (24 h/day),were equipped with telephone, television, and internet access. Portable computers, play stations, and mobile phones were also allowed. In accordance with the hygiene rules, companions were not allowed in the rooms especially during neutropenic periods. The patients could receive one visit per day, and the visitors could see them behind a glass door. A caregiver was allowed to stay in the room with the patient only when the patient could not manage the daily care routines without aid. Routine rounds were performed by physicians twice daily and additionally when needed. Minimum duration of the isolation period was 30 days.

The HAM-A and HAM-D scales were also filled out by the psychiatrist working for the transplant center, and self-reported scales were filled out again by patients on the day of discharge. Patients who had a psychotic disorder, mental retardation, bipolar disorder, personality disorder, alcohol or substance abuse, a severe physical disorder (renal failure, heart failure, diabetes mellitus, seizures), or history of a previous head trauma during childhood and patients who experienced severe complications like GVHD during isolation period were excluded from the study. Four patients who had been diagnosed with a psychiatric disorder and 9 patients who had a severe physical disorder were excluded from the study. Five patients who did not agree to participate, 3 patients who were illiterate, and 9 patients who did not fill out the data collection form on the day of discharge were also excluded.

The study was approved by the Baskent University Institutional Review Board (Project no: KA 13/114).

Instruments
Suicidal Ideation Scale
The SIS was developed by Linehan and Nielsen, with Turkish validity and reliability tests conducted by Dilbaz and associates.^25,26 This self-assessment scale, which is composed of 17 “yes-no” items scored as 0 or 1, evaluates the presence and severity of suicidal ideation. The overall score can range from 0 to 17, with higher scores indicating higher potential of suicidal ideation. A statistical or clinical cut-off score was not specified for SIS according to the Turkish reliability and validity study.

Dissociative Experiences Scale
The DES is a self-assessment scale used for screening dissociative experiences and disorders and measuring their severity. This scale may be applied to psychiatric patients, individuals who have experienced traumatic events, and to the general population for screening. It is composed of 28 questions scored between 0 and 100 with 10-point intervals. The overall score is divided by 28; a mean score of 30 or above indicates the likelihood of a dissociative disorder. The scale was developed by Bernstein and Putnam in 1986, and Turkish validity and reliability studies were conducted by Yargıc and colleagues.^27,28

Structured Clinical Interview for DSM-IV (SCID I) This structured clinical interview is used to diagnose the presence of Axis I psychiatric disorders. It was adapted for DSM-IV-TR by First and associates.²⁹ Turkish validity and reliability tests were done by Ozkurkcugil and colleagues.³⁰

Hamilton Depression Scale
The HAM-D questionnaire was developed to measure depression levels and changes in severity of depression.³¹ Acceptable levels of validity and reliability for the Turkish version used in this study have been established. The scale is composed of 17 questions on the level of depression and changes in severity of depression.³²

Hamilton Anxiety Scale
The HAM-A, developed in 1959, is used to determine anxiety level and distribution of experiences.³³This scale is composed of 14 items, with each item scored between 0 and 4. A score of 0 to 5 indicates no anxiety, a score of 6 to 14 indicates minor anxiety (mild-moderate), and a score of 15 and above indicates major anxiety (severe). Reliability and validity for the Turkish version have been established.³⁴

State Trait Anxiety Inventory
The STAI-I and STAI-II self-reported questionnaires were developed by Spielberg and associates for detection of state and trait anxiety levels.³⁵ These questionnaires are composed of 2 separate scales of 40 items. The state anxiety scale aims at defining the participant’s feelings at a certain time and under certain conditions. The trait anxiety scale requires the participant to describe how he/she usually feels. Turkish validity and reliability tests were conducted by Oner and Le Compte.³⁶

Statistical analyses
Statistical analyses were done with the SPSS software program (version 17.0; SPSS Inc., Chicago, IL, USA). Normality distribution of numerical data was tested with the Shapiro-Wilk and Kolmogorov-Smirnov tests and presented as median with minimum and maximum values. Comparisons were done with Wilcoxon test in dependent groups and Mann-Whitney U test and Kruskal-Wallis test for independent groups. Categorical variables are presented as numbers and percentages. Spearman correlation coefficient was used for assessment of associations between scales. A P level of .05 was determined as the significance level in all tests.

Sociodemographic data
Of total patients, 60.7% were men, 77% were married, 57.4% were employed, 42.6% were unemployed, 37.7% had 12 years or more of education, 9.8% had history of psychiatric treatment, 14.8% had history of smoking, 8.2% reported alcohol use, and 1.6% had history of substance use.

Characteristics related to hematopoietic stem cell transplant
Patient characteristics related to HSCT are shown in Table 1.

Comparisons of scale scores
Our results showed that both the DES and SIS scores remained constant after transplant. Anxiety and depression levels were found to be higher at discharge according to the HAM-A and HAM-D scale scores, with differences being statistically significant (P < .001). However, differences between admission and discharge scores for DES, STAI-I, STAI-II, and SIS were not significant (P > .05) (Table 2).

Factors related to the Suicidal Ideation Scale during isolation
Suicidal ideation scores were correlated with higher STAI-II (P = .001), HAM-D (P = .003), and DES (P = .001) scores at admission. Suicidal ideation scores were correlated with higher scores of DES (P = .003) and STAI-II (P < .001) and were higher at discharge in patients who received radiotherapy (P = .035) prior to transplant (Table 3).

To the best of our knowledge, this is the first study investigating suicidal ideation, dissociative experiences, and predictive risk factors during the HSCT isolation period. In this study, we found that anxiety and depression levels increased during the isolation period in patients receiving HSCT; however, no statistically significant differences in suicidal ideation and dissociative experiences were detected when scores at admission versus at discharge were compared.

Previous studies have revealed that anxiety and depression levels are high during the isolation period, which is consistent with our results.^4,5,37 Studies on psychopathologies that emerge during isolation have reported psychiatric findings in 38% to 44% of patients, with anxiety, depression, and adjustment disorders being the most common pathologies.^6,8,9,38,39

Although anxiety has been reported to decrease during the isolation period compared with levels shown at the beginning of isolation, some studies have reported that depression increases during hospitalization and decreases at the end of isolation. Anxiety and depression levels have also been shown to be high during hospitalization but decreased during the isolation period.^38,40-42 Here, we found that anxiety and depression levels were higher at the end of the isolation period, which is in contrast to that previously reported. This could be because of several factors, including anxiety over cultural stigmatization, fear of disease recurrence and emergence of complications or infections after discharge, worries about adaptation to normal daily life after discharge from hospitalization, and lack of social support.

In contrast to expected results, although rates of depression increased at the end of the isolation period, the extent of suicidal ideation did not change. This may be associated with the absence of major complications (such as GVHD), undergoing HSCT for the first time, a positive belief that HSCT would be curative, a low incidence of previous psychiatric disease, being employed, low alcohol and substance use, adequate knowledge about HSCT, good social support, and the presence of only minor depression as revealed by HAM-D scores. Spirituality, fatalism, and cultural factors may also affect the general behavior of patients and the better health-seeking and coping strategies in cancer patients. According to Islamic belief, suicide attempt or suicidal ideation is forbidden as it is thought to be an obstacle in reaching God. Muslims believe that the sufferings and disasters of the world will be rewarded by God in the Hereafter. This is stated in the Holy Qur'an, in Bakara and Hadid surahs. The Turkish family structure has been suggested to be another important factor in low suicidal ideation among patients. All family members support, respect, and protect each other, regardless of whether they are a part of the nuclear or the extended family. The ideology of family first may influence this support.^16,17

In our study, suicide-related factors included trait anxiety, high-level of depression, and dissociative experiences before isolation; having radiotherapy before HSCT; and having high-level trait anxiety during isolation. Thus far, studies investigating suicidal ideation-related risk factors have been limited to case reports. In a study of 3 patients from Molassiotis and Morris, depression, psychosis, chronic course of the disease, an abnormal metabolic condition with poor physical condition, poor family support, poor prognosis, drug-related central nervous system toxicity, sleepiness, steroid use, acute organic brain syndrome, substance/alcohol abstinence syndrome, male biological sex, and advanced age were reported to be predisposing factors for suicide.¹¹ A comprehensive comparison could not be made with the literature due to lack of studies.

Despite being the first such prospective study in the literature, this study has some limitations. First, the findings cannot be generalized to the general population due to the small sample size and being conducted at a single center. Second, different conditioning regimens were used due to heterogeneous hematologic disease groups.

Conclusions and implications for research
Cancer diagnosis and undergoing chemotherapy, radiotherapy, and HSCT treatment (which involve many invasive procedures) can be traumatic for the patient. The need for isolation during bone marrow transplant may exert several effects on mental status. Our study is unique in its nature as it investigated suicidal ideation, dissociative experiences, and related factors in a prospective manner.

Our study suggested that patients with high-level trait anxiety and depression levels, who were greatly affected by the traumatic consequences of the disease, who exhibited dissociative experiences, and who had undergone radiotherapy may be at risk of suicidal ideation during the isolation period. Therefore, suicidal ideation and dissociative experiences that may be triggered by traumatic processes should be considered by clinicians, and social and psychological support should be provided. Further studies with larger sample sizes and more homogenous disease groups are required.

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