The Indirect Effect of Depression between Nightmares and Well-Being in Lebanese Patients with Schizophrenia

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Background
Schizophrenia is one of the most severe mental disorders when it comes to its detrimental efects on various psychosocial areas and the overall quality of life of the patient [1]. Because schizophrenia causes misery and incapacity, the majority of attention has been focused on understanding and mitigating its negative efects on daily life functioning, with a rising focus on broad positive variables such as life satisfaction and subjective well-being [2]. Well-being has been widely acknowledged to entail both functioning effectively and feeling well [3]. Terefore, it is important to note that sufering from mental disorders does not imply poor well-being, and the lack of psychopathology does not guarantee a productive lifestyle [4]. Promoting well-being, on the other hand, can greatly aid recovery and improve the patient's quality of life and illness prognosis [5]. Terefore, it is important to study factors that may afect the well-being of patients diagnosed with schizophrenia for better functioning and recovery. A variety of psychological and biological factors, such as long-term environmental infuences and ongoing stressors, general cognitive abilities and personality traits, exposure to transiently traumatic life events, mental health interventions, and coping, afect the functioning and well-being of schizophrenia patients [6]. Trauma and posttraumatic stress disorder (PTSD), which are commonly prevalent among individuals with schizophrenia [7], are linked to personal well-being, which can be optimized following PTSD treatment [8]. However, the diagnosis of depression is likely the one most closely associated with a lack of well-being [4]. Patients with mental disorders, particularly those with schizophrenia, commonly experience depression [9]. Comorbid depressive symptoms, estimated in 30-75% of schizophrenia patients [10], have been linked to worse long-term functioning [11] and a lower level of life quality and well-being [12]. Te World Health Organization has reported that schizophrenia is the fourth most prominent cause of disability globally [13]. Individuals with schizophrenia who also sufer from depression experience a substantial level of disability [14], which impairs their ability to manage their mental and physical health, leading to a vicious cycle of deteriorating disability [15]. Moreover, it has been discovered that depression plays a partial mediator role in the connection between the severity of schizophrenia and disability [16]. Given the magnitude of negative symptoms, the impairments in functioning and well-being, and the risk of suicidality, schizophrenia patients with depressive symptoms should be monitored closely [17]. Tis occurrence of depressive symptoms in schizophrenia may be caused by overlapping risk factors, thereby having an impact on these patients' general well-being.
Early diagnosis and treatment of comorbid depression are essential to improving functioning in schizophrenia; therefore, assessing the components that contribute to their depressive symptoms is critical [18]. Besides demographic and psychosocial factors [19], sleep disorders and nightmares could also be implicated in the clinical course of psychiatric disorders and are very commonly associated with increased psychological distress [20]. Nightmares, in particular, can lead to depression, which may indirectly increase the risk of suicide [21,22]. Terefore, it is essential to address nightmares in the context of schizophrenia since they are associated with hopelessness [23], depression [24], and suicidal ideations and behaviors [25]. Depression may be linked to an increased risk of suicide attributable to recurring and terrifying nightmares [26] typically relating to negative self-image [27]. Secondly, schizophrenia patients experience nightmares more frequently than the normal population. Tis can worsen daytime psychotic symptoms and impair their day-to-day functioning [28], which demands serious attention due to its implications for the patient's overall well-being. Dream anxiety, which refers to distressing experiences during frightening dreams or nightmares, plays a signifcant intermediary role in the link between sleep disruption and suicide attempts [29]. Te presence and frequency of nightmares have been shown to be associated with an increased risk of suicide [30].
Since the start of the COVID-19 pandemic, there has been an increase in the frequency of dreams and nightmares, and dream content has been linked to an increase in the symptoms of mental disorders [31]. Te prevalence and severity of nightmares were linked to higher levels of anxiety, depersonalization, hallucinogenic experiences, and paranoia in the general population [32]. Regularly experiencing nightmares has been associated with other sleep difculties, particularly insomnia, and mental health concerns, notably depressive symptoms, as well as reduced overall quality of life [33,34]. However, the relationship between nightmares, depressive symptoms, and well-being in patients diagnosed with schizophrenia is poorly known. Because nightmares seem to be associated with depression in schizophrenia, detecting them early in therapeutic practice might be critical to ensuring efective avoidance of the development of depressive symptomatology and for designing efective psychosocial intervention strategies. Terefore, examining wellbeing and its associated psychological variables among schizophrenia patients is most valuable and benefcial for interventions. Previous fndings revealed that improvements in PTSD and depression symptoms were independent predictors of personal well-being over time [8], whereas other studies have found a link between well-being and depression [35][36][37]. Since sleep disturbances and the occurrence of nightmares were linked to higher levels of suicidal ideation as well as more symptoms of depression, it is important to study the possible pathway that links nightmares to well-being through depression. Hence, in this study, the aim was to examine the indirect efect of depression between nightmares and well-being in a Lebanese sample of patients with schizophrenia. We hypothesize that depression has an indirect efect in the association between nightmares and well-being: among patients with schizophrenia, more nightmares would be correlated with lower well-being, mediated by higher depression.

Study Design.
Tis monocentric cross-sectional study, conducted in July 2022, enrolled patients with chronic schizophrenia disorder diagnosed by a psychiatrist (according to the Diagnostic and Statistical Manual, Fifth Edition, DSM-5 criteria) and admitted to the "Psychiatric Hospital of the Cross," one of the largest psychiatric hospitals in the Middle East where psychiatric patients receive the necessary treatment, handling, or support. Inclusion criteria were as follows: participants had to be 18 years old or older, have a documented and confrmed schizophrenia diagnosis, and have a competent linguistic and educational level in Arabic to complete and consent to the questionnaire. As for exclusion criteria, we have performed psychiatric examinations according to DSM-5 and excluded patients with alcohol and substance use disorder, learning disabilities, or dementia.
A total of 148 patients were included in this study after the exclusion of patients who were diagnosed with schizoafective disorder, and those who were for any reason not available for the questionnaire: on a holiday or assigned to extracurricular activities outside the foors (not present on the foor during the data collection), or patients who refused or were unable to fnish the entire questionnaire ( Figure 1).

Minimal Sample Size Calculation.
A minimal sample of 125 was deemed necessary using the formula suggested by Fritz and MacKinnon [38] to estimate the sample size: 26 for medium efect size, L � 7.85 for an α error of 5% and power β � 80%, and k � 8 variables to be entered in the model.

Data Collection and Measurement.
Data were collected from each participant through face-to-face personal interviews after obtaining their oral consent. Tese interviews were conducted by trained third year medical (MED3) students; each student participated in two training sessions to explain and understand the research objectives and interview questions. Additionally, each student was requested to complete two practice runs to demonstrate their questioning approach to the patients.

Questionnaire.
Te questionnaire used was prepared in Arabic, Lebanon's native language, and required around 10 to 15 minutes for completion. In the frst section, the age, main diagnosis, and patient ID were collected from the medical fles available at the hospital. In the second part of the questionnaire, fve diferent scales were incorporated.

Nightmare Measure.
Patients were asked to indicate how many nightmares they estimated experiencing during the past 2 weeks (14 nights). If a participant had at least one nightmare, they were asked to choose their worst nightmare and rate it on a 7-point Likert scale for intensity, vividness, and distress, as well as whether it was recurring (yes or no). Retrospective nightmare logs measuring up to 1 month in the past are known to yield similar results to prospective measures [39].

Calgary Depression Scale for Schizophrenia. Te
Calgary Depression Scale for Schizophrenia (CDSS) is a nine-item, clinician-rated outcome measure used to assess depression in patients sufering from schizophrenia. It consists of nine items, including eight questions and one observation item, that measure various aspects of depression such as hopelessness, guilt, and suicidal thoughts. Te score ranges from 0 to 27, with higher scores indicating more severe depression. It is the frst depression scale developed specifcally for adults with schizophrenia spectrum disorder. Previous studies demonstrated good interrater validity and reliability of the questionnaire [40]. Te Arabic version of the CDSS was validated in the Arab population and showed high internal consistency with Cronbach's alpha of 0.82 [41] (Cronbach's alpha in this study � 0.78).

PTSD Checklist for DSM-5 (PCL-5).
Te Posttraumatic Stress Disorder Checklist (PCL-5) is a 20-item self-report measure that assesses the presence and severity of PTSD symptoms; the questions on the PCL-5 correspond with DSM-5 diagnosis criteria. Te PCL-5 has a variety of purposes, including quantifying and monitoring symptoms over time, screening individuals for PTSD, and assisting in making a provisional diagnosis of PTSD. Respondents are required to indicate how much they have been disturbed by symptoms during the previous month. Respondents rate how much they have been afected by each symptom in the past month on a scale from 0 to 4. A total score can be calculated by adding up the scores for each item, with higher scores indicating more severe symptoms [42]. Te PCL-5 has been shown to have strong reliability and validity (α � 0.94 to

Te Digit Span Subtest.
Tis questionnaire is a subtest from the third edition of the Wechsler Memory Scale [46]. Te WMS is a test that assesses verbal and fgurative memory, memory for signifcant and abstract information, and immediate and delayed recall. Te digit span subtest reliably estimates the working memory of each participant using a consistent score. Tis subtest consists of the forward and backward tests. Te subject is prompted to recall the numerals in the order in which they were presented in the forward version of the test. In contrast, the subject is encouraged to recall the stimuli in the reverse order in which they were delivered in the backward form of the digit span test. Te internal inconsistency reliability has been originally reported at 0.93 [47]. In this study, the digit span subtest holds a high reliability coefcient of 0.81 for the backward scale and 0.86 for the forward scale.

Results
A total of 148 patients were enrolled in the study (mean age � 54.53; SD � 13.10; 66.2% males). One-third (34.5%) experienced nightmares in the last 2 weeks, with 49% of them experiencing recurrent nightmares (Table 1). Tables 2 and 3. Higher well-being scores were seen in males compared to females. Higher depression and higher PTSD were signifcantly associated with lower wellbeing.

Mediation Analysis.
In the frst model adjusted over sex, depression fully mediated the association between the presence of nightmares and well-being; the presence of nightmares was signifcantly associated with more depression, whereas higher depression was signifcantly associated with lower well-being. It is noteworthy that the presence of nightmares was not directly associated with wellbeing (Table 4; Figure 2). When adjusting over all variables in the second model, the mediation efect of depression between the presence of nightmares and well-being was not signifcant anymore. Finally, since this is a cross-sectional study with the occurrence of symptoms/events not known through time, we thought about evaluating the indirect efect of nightmares between depression and well-being; the results showed that the presence of nightmares did not have an indirect efect in the association between depression and well-being (beta � 0.015; 95% CI −0.01; 0.06; p � 0.192).

Discussion
An evaluation of depression's mediating efect is necessary to comprehend the unclear relationship between nightmares and well-being. According to this study, depression mediates the negative association between nightmares and well-being. Previous studies focused on low subjective well-being as a predictor of depressive symptoms [51]. However, this study takes well-being as the dependent variable with the other variables as predictors. According to earlier research, depressed people have a persistently pessimistic view and a propensity to misattribute unpleasant occurrences and experiences to internal causes [52], which may impair how well they assess their own well-being. Concerning schizophrenia patients, in particular, several studies have found that individuals with schizophrenia who also have comorbid depression experience a lower quality of life compared to those who do not have depression [53][54][55]. Less depressive symptoms and a higher quality of life in schizophrenia patients can indicate an earlier recovery and improved wellbeing [56]. Our results demonstrate how co-occurring depressive symptoms in schizophrenia patients signifcantly impact their well-being, leading to unfavorable outcomes.

Te Mediating Efect of Depression between Nightmares
and Well-Being. While higher depression was signifcantly associated with lower well-being, the presence of nightmares was signifcantly associated with more depression, even when adjusted over sex. Nightmares are common in people sufering from psychosis [57] and have been linked to worsening daytime and nocturnal impairment [58]. In our sample, a third of schizophrenia patients reported having nightmares recently, with around half of them experiencing recurrent nightmares. Tese frequent nightmares correlated with the presence of more depressive symptoms, per previous studies showing that depression was more common among patients experiencing nightmares [22,59]. Te mediating role of depressive symptoms in the association between nightmares and suicide risk was already studied [22,60], but its role as a mediator in the association between nightmares and well-being in schizophrenia patients had never been studied before. Prior research indicates that nightmares were related to suicidal ideation, but this link became insignifcant after controlling for the severity of PTSD, depression, and anxiety symptoms. Notably, only the severity of depressive symptoms remained signifcantly associated with suicidal ideation [22]. In our study, the occurrence of nightmares was not directly related to well-being, but it was associated with higher depression, which, in turn, was associated with worse well-being. As a result, depression played a role in mediating this negative relationship. Tis can be explained by the fact that the relation between our daily life experiences and dreams are reciprocal; daily life experiences can be put into efect in our dreams but also, the content of dreams may afect our life when being awake. [61]. Terefore, dreams can impact our lived reality heavily and may cause distress when they are unpleasant. Furthermore, dream assessment can be utilized to determine the quality of the preceding or upcoming day since the distress experienced during the day carries over to the night and vice versa. Tere is a proven association between nightmare frequency and the general level of psychopathology, mood and anxiety disorders, and other sleep disorders [62]. Both psychache and dream anxiety have full mediator roles in the relationship between sleep disturbance and suicide attempts [29]. Research also suggests that the severity of the psychiatric disorder is more closely related to the distress associated with nightmares [63] than to their frequency [64]. Nightmares have been shown to be a major predictor of depressive symptoms and suicidal ideation [65]. Tey cause great sufering to the person experiencing them and must be addressed seriously due to their close association with suicidal behavior [66]. Previous studies support the association between nightmares and both depressive disorder and schizophrenia symptoms [57,58]. Consequently, depressive symptoms in schizophrenia have many negative repercussions on the patients, including a higher risk of suicide, a worse prognosis, and personal sufering [67][68][69], all of which implicate lower levels of well-being. However, when adjusted over all variables, we lost the mediating efect, suggesting that other variables may be infuencing the indirect efect found. At this stage, we do not have  Perspectives in Psychiatric Care enough evidence to make a conclusion about the presence or absence of a mediating efect. Future studies are needed to consolidate or refute those results. Sleep problems and common mental disorders have a reciprocal relationship, where each can worsen the other, and it is important to address both to achieve the best results for patients [70]. Terefore, we evaluated as well the indirect efect between depression and well-being since this is a cross-sectional study with the occurrence of events not known through time. However, we found that nightmares did not have an indirect efect on the association between depression and well-being. Tis fnding is consistent with previous research suggesting that nightmares may be a symptom of depression rather than a distinct contributor to poor mental health outcomes or suicide [59]. Future research could use longitudinal designs to better understand the temporal relationships between depression, nightmares, and well-being. Additionally, incorporating measures of other factors that may impact the relationship between depression, nightmares, and well-being, such as sleep quality or trauma exposure, could provide a more nuanced understanding of these complex associations.

Clinical Implications
Clinical healthcare professionals treating people with mental illnesses have shifted their focus from treating symptoms alone to focusing on overall functional improvement [71]. Since wellbeing is afected directly by depression and indirectly by nightmares, interventions targeting both problems may provide signifcant functional therapeutic benefts in schizophrenia patients. As a result, putting more emphasis on the distress associated with frequent nightmares, which are rarely addressed in therapy, may have a signifcant clinical efect on reducing the risk of depression. Additionally, if nightmares can be treated efectively, this may help patients feel less distress from their psychotic symptoms throughout the day, which will improve their quality of life and well-being.

Limitations
First, the results of this cross-sectional study refect correlational associations among the variables, making it difcult to establish causation. Tis could be prevented in future studies by replicating the study longitudinally. Second, the scales are subjectively reported by the patients sufering from mental illness, which could lead to information bias, and not all of the scales are validated in Arabic. Tird, not all the factors (physical, psychological, and social such as cognitive impairment or afective blunting or residual positive symptoms) that may be associated with well-being were taken into consideration, predisposing us to a residual confounding bias.

Conclusion
Our fndings demonstrate that nightmares lead to lower well-being in schizophrenia patients, with depression serving as a mediating factor in this association. As a result, the outcomes of this research may represent a frst step towards emphasizing the importance of addressing patients' distressing dreams during therapy in order to alleviate their depressive symptoms, which in turn promotes improved well-being. We support further investigation into nightmares as a potential indirect causal component of decreased well-being in schizophrenia to improve the quality of life and general subjective well-being among schizophrenia patients.

Data Availability
Te datasets generated and/or analysed during the current study are not publicly available due to restrictions from the Ethics Committee but are available from the corresponding author on reasonable request.

Ethical Approval
Te Psychiatric Hospital of the Cross Ethics Committee approved the study protocol (HPC-017-2022). All methods were carried out in accordance with relevant guidelines and regulations.

Consent
Written informed consent was obtained from each participant.

Disclosure
Tis paper is submitted on behalf of the Psychiatric Hospital of the Cross research committee: Marouan Zoghbi, Chadia Haddad, Dory Hachem, Oussama Dahdouh, Gisele Kazour, and Waad Bsaibes.

Conflicts of Interest
Te authors have no conficts of interest to report.

Authors' Contributions
Georges Haddad, Sahar Obeid and Souheil Hallit are last coauthors. SO, SH, and GH conceived and designed the survey. SH was involved in the statistical analysis and data interpretation. DM wrote the manuscript. JEA and SHe assisted in the writing. MT, CT, and KR were involved in the data collection. All authors have read the manuscript, critically revised it for intellectual content, and approved the fnal version.