Decoupled but Intertwined Association Between Dissociation and Depression: The Impact of Sleep and Gastrointestinal Symptoms
Article information
Abstract
Objective
Whether dissociation and depression are distinct constructs remains controversial. The aim of this study was to explore the interrelations and associated factors between them.
Methods
This study included inpatients with major depressive disorder (MDD) and bipolar disorder with major depressive episode (BD). Clinical rating scales were used to measure levels of depression, dissociation, and psychotic symptoms. Generalized estimating equations were used to estimate interrelations between dissociation and related factors over time, including depression. Moreover, the impacts of individual items of the Hamilton Depression Rating Scale (HAMD) on dissociation were evaluated after multiple adjustments.
Results
A total of 91 participants were included into the analysis, of whom 59 had MDD and 32 had BD. After standardized treatment, levels of depression and psychotic symptoms significantly decreased, whereas the level of dissociation did not. However, the level of dissociation significantly decreased in the high-dissociation group, and this was positively associated with the change in depression and psychotic symptoms. Female sex and comorbidity with borderline personality disorder were also positively correlated with dissociation. Among items of the HAMD, insomnia and gastrointestinal symptoms contributed to the association between depression and dissociation.
Conclusion
We identified a decoupled but intertwined relationship between dissociation and depression. Clinicians should be aware of this comorbidity and provide timely interventions for dissociation during clinical practice.
INTRODUCTION
Dissociation, a disruption in the usually integrated functions of attention, autobiographical memory, perception of the environment and self, and sense of identity, is a psychiatric dysfunction that can lead to severe socio-occupational dysfunction [1]. It affects approximately 20% of psychiatric inpatients and 18% of outpatients according to research from different nations [2-4]. The poly-symptomatic presentation of dissociation increases the difficulty of diagnosis and raises debate about the psychopathology [5]. The characteristic poly-symptomatic manifestation of dissociation has led to two opposing views toward dissociation. One view argues that dissociation is a distinct cluster of psychopathologies, and that the poly-symptomatic presentation is an associated feature of dissociative disorder [6]. For instance, evidence-based behavioral interventions for borderline personality disorder (BPD) do not work in patients comorbid with dissociation, indicating the unique psychopathology of dissociation [7]. Alternatively, dissociation may be an epiphenomenon secondary to another disorder due to the intertwined relationship between them. A previous study explored the association between dissociation and other mental illnesses such as posttraumatic stress disorder (PTSD) and anxiety, and found that such complicated etiologies may be clinically challenging [8]. Patients with mental illness who experience dissociation are often associated with undesirable outcomes, complicated symptom profile [9], predominant disability [10], and poor prognosis [11] Consequently, understanding the etiology and function of dissociation is crucial for clinical practice.
Some emerging studies have discussed the association between dissociation and a number of psychopathologies including schizophrenia, BPD, conversion disorder, psychotic symptoms, eating disorders, and substance abuse [12-14]. In addition, a previous large-scale community study examined the relationship between dissociation and depression [15]. Depression is a common comorbidity of dissociation [16], and up to 70% of patients with depression also have a dissociative disorder [2,17]. Etiologically, both dissociative symptoms and major depressive disorder (MDD) might be strongly associated with higher alexithymia levels [18,19]. This association between dissociation and depression led us to consider whether dissociation is an epiphenomenon of depression or a distinct psychopathology from depression. Dissociation has been reported to negatively affect treatment for BPD [6], and also to hinder treatment efficacy in patients with anxiety or depression [20]. In addition to these differences in treatment efficacy, the diversity of symptomology between dissociative depression and non-dissociative depression should also be considered. Individuals with dissociative depression tend to have more depressive symptoms and interpersonal distress than those with non-dissociative depression [21]. However, previous studies have demonstrated high comorbidity and a strong association between depression and dissociation [2,17]. Therefore, direct evidence that dissociation is unique rather than secondary to depression remains to be elucidated.
The above findings indicate that several gaps in the literatures remain. First, whether the level of dissociation will decrease with improvements in depression after standardized treatment, and whether this can reflect the interaction between depression and dissociation. We hypothesized that if dissociation is an epiphenomenon during depression, it is possible that the level of dissociation would follow the severity of depression. State dissociation would be a feature of patients with more severe initial depression, and it may then decrease after improvements in depression. Alternatively, if the remission of depression could not improve state dissociation, dissociation should not be ascribed to depression. Second, the impacts of individual components of depression on dissociation have also yet to be explored. These components include items from the Hamilton Depression Rating Scale (HAMD) [22], such as depressed mood, guilt, or insomnia. Exploring the impacts of these components may lead to a better understanding of the detailed etiologies for the association between dissociation and depression. Therefore, we designed this treatment outcome study of MDD and bipolar disorder with major depressive episode (BD) with the aim of examining changes in state dissociation in relation to the remission of state depression. In addition, we also evaluated the factors associated with changes in the level of dissociation, including level of depression, psychotic symptoms, and other demographic factors. Moreover, we evaluated the impacts of individual components of depression derived from the HAMD on changes in dissociation.
METHODS
Ethics
This study derived data from the Investigations on interpersonal adversity, psychiatric status, and socio-cognitive function (IAPS) project, which aimed to investigate the interactions between interpersonal adversity, psychiatric status, level of dissociation, and socio-cognitive functions [13]. The IAPS project recruited healthy controls and inpatients with MDD, BD with depressive episodes, and schizophrenia. The recruited inpatients were assessed with two phases of examinations. Phase 1 assessments were conducted at the first week of admission. Self-reported measures of psychopathology and childhood interpersonal adversity, neurocognitive test, and clinical interview schedules were recorded. In addition, phase 2 assessments were the same as in phase 1, and they were conducted during the last week of admission or 6 weeks after the admission. Assessment of healthy controls were conducted only in Phase 1. This research was approved by the Institutional Review Board of Kai-Syuan Psychiatric Hospital (KSPH-2014-34 and KSPH-2017-04) and conducted according to the current revision of the Declaration of Helsinki and national legal requirements (Human Subjects Research Act, Taiwan). All participants signed written informed consent after a detailed explanation of the study procedures.
Participants and procedures
Details of the IAPS project have been published elsewhere [13,23,24]. In this study, we included data of newly admitted patients with the acute onset of MDD and BD at Kaohsiung Municipal Kai-Syuan Psychiatric Hospital, Taiwan, from December 30, 2014 to December 21, 2016. The inclusion criteria of patients were: 1) admission due to MDD or BD following the Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV-TR or DSM-5 diagnostic criteria through interviews by psychiatrists; 2) age between 20 and 50 years; and 3) a native speaker of Mandarin Chinese. Patients were not eligible for this study if they: 1) had been diagnosed as ketamine use disorder, or 2) exhibited intellectual disability so that they could not understand the purpose of the IAPS project or follow orders of the researchers to complete the tests. Intellectual disability was diagnosed from boarded psychiatrists and was recorded in the medical record. We excluded them in the initial screen. The recruited patients were assessed with two series of examinations. The baseline assessments were conducted during the first week of admission, and the follow-up assessments were conducted during the last week of admission or 6 weeks after admission. During the admission, the patients were treated with standardized treatment for MDD or BD by psychiatrists.
Outcome measures
Positive and Negative Syndrome Scale
We used the Positive and Negative Syndrome Scale (PANSS) to measure the severity of psychotic symptoms, negative symptoms and general psychopathology [22]. The PANSS is a clinical interview scale composed of 30 questions, with each question being scored on a Likert scale from 1 to 7. The Chinese-Mandarin version of the PANSS has been shown to have acceptable reliability and validity [25], and this version was used in our study. Only positive symptoms of the PANSS (PANSSP) including 7 items were used in this study, indicating the presence of psychotic symptoms (e.g., hallucinations or delusions). Other items were excluded to fit the aim of our study. A higher total PANSS-P score indicates more severe psychotic symptoms.
HAMD
The HAMD was used to assess the severity of depression [26]. The HAMD is a clinical interview scale composed of 17 items, with a total score from 0 to 52. A higher total HAMD score indicates more severe depression. In this study, we used the total HAMD score to examine the association between changes in depression severity and dissociation. If a significant association was identified, we further entered individual items of the HAMD into the analysis to explore their predictive effect on the change in dissociation scores. These items were as follows: item-1 (depressed mood), item-2 (feeling of guilt), item-3 (suicide), item-4 (insomnia: early in the night), item-5 (insomnia: middle of the night), item-6 (insomnia: early hours in the morning; late insomnia), item-7 (work and activities), item-8 (retardation), item-9 (agitation), item-10 (anxiety psychological), item-11 (anxiety somatic), item-12 (somatic symptoms gastrointestinal), item-13 (general somatic symptoms), item-14 (genital symptoms), item-15 (hypochondriasis), item-16 (loss of weight), and item-17 (insight).
Clinician-Administered Dissociative States Scale
We applied the Clinician-Administered Dissociative States Scale (CADSS) to estimate the state of dissociation in this study. The CADSS is a 27-item scale with 19 subject-rated items and 8 items scored by an observer. It is scored using a Likert scale from 0 to 4, and it has been shown to be reliable and valid [27]. In this study, total subject-rated CADSS scores were used to measure the severity of dissociation. To ensure the reliability of the rating scales in the IAPS project, the PANSS, HAMD, and CADSS were conducted by three welltrained psychiatrists, with intra-class correlation coefficients of at least 0.9.
Demographic information
Demographic data at baseline were collected, including the patients’ sex, age, educational level (recorded in years), comorbidity with illegal substance use (yes or no), comorbidity with PTSD (yes or no), and comorbidity with BPD (yes or no). The defined daily dose (DDD) of antidepressants [28], antipsychotics [29], and benzodiazepine [30,31] were also recorded to adjust for the confounding effect of medications in the analysis. In addition, intelligence quotient (IQ) scores assessed during follow-up were included to assess cognitive function after remission of major depressive episodes. The IQ score was entered into the analysis to adjust for the confounding effect of cognitive function between variables, and measured using the Wechsler Adult Intelligence Scale, fourth edition [32].
Statistical analysis
Descriptive statistics were applied to summarize the clinical characteristics at baseline. The patients were divided into MDD and BD groups, and the two groups were compared. Pearson’s χ2 test was used to compare categorical variables, and the independent t-test was used for continuous variables. To estimate the differences in the PANSS-P, CADSS, and HAMD, we used the independent t-test to compare scores between baseline and follow-up. Moreover, we analyzed differences in the changes in PANSS-P, CADSS, and HAMD scores between the high-dissociation group and the low-dissociation group. Since no previous study has defined the cut-off point of the CADSS to differentiate high and low levels of dissociation, we used the mean score (14.82) as the cut-off point. The independent t-test was used to compare baseline and follow-up scores between the high- and low-dissociation groups.
To estimate the factors associated with changes in CADSS scores over time, generalized estimating equations (GEEs) with a first-order autoregressive working correlation structure [33] were used; these GEEs were also used to estimate the interrelation between depression and dissociation. If changes in HAMD scores were associated with changes in CADSS scores over time, GEEs were used again to identify the predictive effect of each item of the HAMD (17 items) on the change in CADSS scores. To reduce the confounding effect, each item of the HAMD in the analysis was adjusted for multiple characteristics, including sex, comorbidities (PTSD, BPD, and substance abuse), age, level of education, IQ scores, DDD (antidepressants, antipsychotics, and benzodiazepine), and severity of psychotic symptoms. All tests were two-tailed, and statistical significance was set at p<0.05. All data were processed using SPSS version 23.0 for Windows (IBM Corp.).
RESULTS
Regarding participants with MDD or BD, 389 of inpatients were initially screened. In total, 298 of them were excluded due to refusal at initial screen (n=252), exhibition of intellectual disability (n=14), ketamine use (n=27), and dropout at phase 2 (n=5). Finally, 91 of patients were entered into the analysis, of whom 59 were diagnosed with MDD and 32 with BD. The mean age of all patients was 40.59±7.50 years, and 64 patients (70.3%) were female. Comparisons of the demographic characteristics and rating scores (PANSS-P, HAMD, and CADSS) between the patients with MDD or BD are summarized in Supplementary Table 1. There were no significant differences between the two groups except for DDD of antidepressants (MDD: 1.21±0.65 vs. BD: 0.65±0.5, p<0.001) and antipsychotics (MDD: 0.28±0.48 vs. BD: 0.76±0.59, p<0.001). In addition, there was no significant difference in IQ scores at follow-up between the two groups (MDD: 86.32±17.18 vs. BD: 82.69±16.41, p=0.33).
Table 1 shows the differences in scores between baseline and follow-up. For all participants, the HAMD and PANSS-P scores were significantly lower at follow-up than those at baseline (baseline vs. follow-up: 24.45±5.34 vs. 13.96±6.74, p< 0.001; and 11.97±3.80 vs. 9.98±3.61, p<0.001). This indicated decreases in the severity of depression and psychotic symptoms after standardized treatment. However, the difference in CADSS score between baseline and follow-up did not reach statistical significance (14.82±16.66 vs. 13.56±16.23, p=0.148). The low-dissociation group demonstrated a similar pattern to the overall cohort, in that the depression (22.24±3.83 vs. 12.22±6.04, p<0.001) and psychotic symptom (10.93±3.14 vs. 9.37±2.89, p<0.001) scores significantly decreased, but dissociation did not (4.80±4.62 vs. 5.76±6.91, p=0.119). However, the depression (28.16±5.78 vs. 17.16±6.87, p<0.001), psychotic symptom (13.88±4.20 vs. 11.09±4.48, p<0.001), and dissociation (33.31±14.88 vs. 27.94±18.61, p=0.013) scores all significantly decreased in the high-dissociation group.
Difference of scores in depression, psychotic symptoms, and dissociation between baseline and follow-up
Table 2 demonstrates the results of GEEs examining the factors associated with changes in CADSS scores over time for all participants. We found that female sex (estimate: 8.24, 95% confidence interval [CI]: 3.56–12.93, p=0.004) and comorbidity with BPD (estimate: 10.04, 95% CI: 1.16–18.91, p=0.027) were associated with increases in CADSS score. Comorbidity with PTSD (estimate: 7.4, 95% CI: -0.1–14.9, p=0.053) demonstrated a similar but insignificant trend. In addition, PANSS-P (estimate: 0.54, 95% CI: 0.07–1.01, p=0.025) and HAMD (estimate: 0.19, 95% CI: 0.05–0.34, p=0.008) also reached statistical significance. These results indicated positive correlations between the change in dissociation and the studied predictors (depression and psychotic symptoms). Furthermore, Table 3 presents the associations between changes in the scores of individual items of the HAMD and changes in CADSS scores. After adjusting for sex, comorbidities (PTSD, BPD, and illegal substance abuse), age, level of education, IQ scores, and PANSS-P scores, the results showed that changes in middle insomnia (estimate: 2.31, 95% CI: 0.61–4.02, p=0.008) and gastrointestinal symptom (estimate: 3.62, 95% CI: 1.08– 6.16, p=0.005) scores were positively associated with change in CADSS scores. In contrast, the change in late insomnia (estimate: -2.09, 95% CI: -4.15– -0.03, p=0.046) score was nega-tively associated with the change in CADSS score. Several insignificant trends were also identified, including that the changes in early insomnia (estimate: 1.71, 95% CI: -0.14–3.55, p=0.069) and anxiety somatic symptom (estimate: 2.26, 95% CI: -0.01–4.53, p=0.051) scores were insignificantly and positively associated with the change in CADSS score.
Predictors over time on the total scores of CADSS using generalized estimating equation
DISCUSSION
Summarized findings
This study comprehensively explores the association between dissociation and depression across symptomology. We found differences in the changes of the severity of depression, psychotic symptoms, and dissociation over time, and the severity of depression and psychotic symptoms significantly decreased at follow-up. However, although the level of dissociation did not significantly decrease in the overall cohort or lowdissociation group, it did significantly decrease in the highdissociation group. In addition, we identified that the change in the level of dissociation was positively associated with the change in the level of depression. Moreover, the change in psychotic symptoms demonstrated a similar pattern to the level of depression. Females and those who were comorbid with PTSD or BPD were also associated with an increased level of dissociation. After multiple adjustments, more severe levels of middle insomnia and gastrointestinal symptoms were associated with an increased level of dissociation. Early insomnia and anxiety somatic symptoms demonstrated similar but insignificant trends. However, a decreased level of late insomnia was associated with an increased level of dissociation, indicating that those who had a lower level of late insomnia may have had a higher level of dissociation.
Decoupling dissociation from depression
We found some controversial but interesting findings for the association between depression and dissociation. The level of depression significantly decreased after standardized treatment, but the level of dissociation did not. This may indicate that dissociation is etiologically different from depression, since standardized treatment for depression was not as effective for dissociation. Some studies have also demonstrated that comorbidity with dissociation may interfere with the treatment efficacy of mental illnesses such as BPD or anxiety [6,20]. This is consistent with our findings that dissociation may be a unique psychopathology that compromises the treatment efficacy of other mental illnesses. Intriguingly, GEE analysis showed that the change in depression was positively correlated with the change in dissociation, and that this correlation may be due to the associated symptoms of depression. We found that the significant predictors of dissociation were insomnia and gastrointestinal symptoms, but not depressed mood. Taken together, we hypothesize that the association between depression and dissociation may be due to insomnia or gastrointestinal symptoms, but not the core symptom of MDD (depressed mood) [34]. This may also reflect an etiological difference between dissociation and depression. Nevertheless, further studies are needed to better clarify the complicated etiologies behind dissociation.
Impact of sleep and gastrointestinal symptoms
Sleep disturbance, including early and middle insomnia, was positively associated with dissociation. Several studies have discussed the impact of sleep disturbance on dissociation, and poor sleep quality and sleepiness have been reported to increase the odds of having dissociative experiences [35]. Another study demonstrated that sleep experiences could explain most variance in the severity of dissociation compared with other factors such as impulsivity or negative affect [36]. Moreover, other research found that unusual dreaming and sleepiness were related to dissociative experiences [37,38]. The finding that late insomnia was negatively correlated with dissociation is unexpected. One previous study reported a negative association between time spent awake during the night and level of dissociation [39], which is comparable to our results. On the other hand, we also found a positive association between dissociation and gastrointestinal upset, including items of gastrointestinal symptoms and anxiety somatic symptoms with subscales of gastrointestinal complaints. A previous meta-analysis indicated a strong link between dissociation and somatic symptom disorder [40]. However, only one study has specifically discussed gastrointestinal symptoms. The authors demonstrated the impact of dissociation on irritable bowel syndrome, and concluded that it may be a long-term coping pattern related to past sexual trauma, emotional distress, alcoholism, and physical disability [40]. Further studies focusing on the association between dissociation and late insomnia or gastrointestinal symptoms may be helpful to clarify the phenomenological characteristics.
Other factors associated with changes in dissociation
We found a positive correlation between dissociation and psychotic symptoms. A previous epidemiological study in the general population demonstrated that dissociation was related to psychotic experiences [8], and another study also reported that a state of dissociation could significantly predict the later occurrence of auditory hallucinations [41]. Our previous work also exhibited this relationship among patients with MDD and BD [13]. In addition, we found that comorbidity with BPD was associated with dissociation. Several studies have comprehensively discussed this association, and it may be related to the socio-cognitive model [42,43]. The socio-cognitive model is an open, dynamic, multidimensional perspective that can accommodate a wide range of social, cultural, and cognitive variables [44]. The socio-cognitive model is thought to contribute to the way that individuals with dissociation express their experiences, such as emotional instability, identity problems, and impulsive behavior, which is associated with BPD [45]. On the other hand, PTSD has been positively correlated with dissociation, which may be explained by the traumatic model of dissociation. According to this model, using dissociation as a defensive strategy to cope with unbearable, overwhelming experiences during a potentially traumatizing event can allegedly compartmentalize experiences and memories in a discrete personality for patients with dissociative disorder [5]. Regarding the impact of gender differences on the change in dissociation, we found that the female participants were positively associated with dissociation. Epidemiological research on children with a history of psychological trauma reported that female children showed a higher level of dissociation symptoms than males [46], and this may echo our results.
Limitations
There are several limitations to this study. First, the IAPS project did not recruit elderly patients to minimize the confounding effect of recall bias from self-reported questionnaires which were used in other studies. Second, this is a naturalistic observation study, and the recruited participants were treated by various teams. Therefore, the treatment plan of the participants was individualized according to the clinical status and the judgment of their clinical teams rather than standardized. However, we adjusted for the confounding effect of psychotropic medications through their DDD, and this may have minimized this effect.
Conclusions
In conclusion, our results demonstrated a decoupled but intertwined relationship between dissociation and depression. Dissociation should not be considered an epiphenomena of depression, while their symptomology is partially correlated. This correlation may result from the impact of sleep disturbance and gastrointestinal symptoms. In addition, female sex, psychotic symptoms, and comorbidity of BPD were independent factors associated with changes in dissociation. Due to the unique psychopathology of dissociation, the clinical implication of this study is the important and urgent need to develop specific treatment for dissociation, as psychotherapy and psychopharmacological treatment for dissociative disorder are still insufficient [5]. Empirically trauma-specific psychotherapy or some psychotropic medications (e.g., opioid antagonists; paroxetine) may be potentially beneficial in reducing dissociative symptoms [47]. Effective interventions for dissociation may help clinicians to adjust treatment strategies for depression when approaching patients with this comorbidity. Regarding the potential research targets, the link between dissociation and late insomnia or gastrointestinal symptoms among patients with depression deserves further investigation on the clinical symptomology or biomedical etiologies. Moreover, it may extend to other clinical or non-clinical individuals to explore if these factors (sleep problems or gastrointestinal symptoms) are independent from depression. Further studies with well-controlled comparisons and a larger prospective cohort are necessary to explore the precise link and even causality between dissociation and depression.
Supplementary Materials
The Supplement is available with this article at https://doi.org/10.30773/pi.2024.0076.
Demographic characteristics at baseline comparing patients with major depressive disorder or bipolar depression
Notes
Availability of Data and Material
The data sets used and/or analyzed during the present study are available from the corresponding author on reasonable request to Dian-Jeng Li (edcrfvm45@hotmail.com).
Conflicts of Interest
The authors have no potential conflicts of interest to disclose.
Author Contributions
Conceptualization: Yung-Chi Hsieh, Li-Shiu Chou, Dian-Jeng Li. Data curation: Li-Shiu Chou, Chui-De Chiu. Formal analysis: Yung-Chi Hsieh, Ching-Hua Lin, Dian-Jeng Li. Funding acquisition: Li-Shiu Chou. Investigation: Yung-Chi Hsieh, Li-Shiu Chou, Chui-De Chiu. Methodology: Yung-Chi Hsieh, Chui-De Chiu, Dian-Jeng Li. Project administration: Dian-Jeng Li. Writing—original draft: Yung-Chi Hsieh. Writing—review & editing: Dian-Jeng Li.
Funding Statement
This study was supported by a grant from Kaohsiung Municipal Kai-Syuan Psychiatric Hospital (104-01).
Acknowledgments
The authors appreciate the assistance of the staff at the Kaohsiung Municipal Kai-Syuan Psychiatric Hospital. All authors are responsible for the content and writing of the paper.