Dissociative symptomatology includes a variety of processes and phenomena along a continuum from adaptive coping strategies to more pathological states (1). The 5th edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) defines dissociative symptoms as “a disruption of and/or discontinuity in the normal integration of consciousness, memory, identity, emotion, perception, body representation, motor control, and behavior,” and identifies five components of dissociation: depersonalization, derealization, amnesia, identity confusion, and identity alteration (2).

Two major theories have been proposed to explain the etiology of dissociative symptoms. The “trauma theory” considers dissociation as the coping strategy adopted to deal with severe anxiety symptoms associated with traumatic experiences (3–5). On the other hand, the “disrupted sleep theory” considers the distortion of cognitions, emotions, and sensations associated with prolonged sleep deprivation as the trigger for the experience of dissociative symptoms (6, 7).

Current evidence suggests that the assessment of dissociative symptoms could be useful in differentiating patients with BD from those with unipolar major depression during depressive episodes. It has been reported that patients with BD are more likely to report dissociative symptoms than those patients with unipolar depression (8). Moreover, dissociative symptoms may precede the onset of the disorder and could be a risk factor for the development of BD (9). Besides, dissociative symptoms are frequently associated with a worse prognosis and a greater number of mood fluctuations (10–14). Further, available data suggest that the presence of dissociative symptoms is considered a marker of poor treatment response in BD (15). Despite dissociative symptoms can have a potential impact on the psychopathological burden of patients with BD, only a few studies have assessed the relationship between dissociative and psychotic symptoms and treatment response to mood stabilizers.

The aims of the present study are to assess: (1) the relationship between the presence of dissociative symptoms and psychotic symptoms in patients with BD; (2) the clinical and socio-demographic characteristics more frequently associated with dissociative symptoms; and (3) the potential role of dissociative symptoms on the response to treatment with mood stabilizers.

The total sample consisted of 100 patients (55 BD-I and 45 BD-II), 50% males, mean age 46.5 ± 13.9 years. Table 1 illustrates the socio-demographic and clinical characteristics of participants according to their diagnosis. Almost half of patients were in a stable relationship, employed and had a positive history for psychiatric disorders. The mean age at onset was 27.30 ± 9.85 and the duration of illness was 19 ± 12.99 years. Significant differences emerged in clinical variables, BD features and ALDA score according to diagnosis. Only patients with BD-I reported psychotic symptoms (43/55); patients reported psychotic symptoms during manic (51%), depressive (9%), or both episodes (40%).

Table 2 includes the results of Spearman's correlations between DES-II and the clinical features of patients. Significant correlations emerge for all variables except age at onset of bipolar disorder. Successively a linear regression analysis was performed to determine the relationship between clinical variables and DES. Successively a linear regression analysis was performed to determine the relationship between clinical variables and DES. The results indicated that there was a significant effect of clinical variables on DES [F_{(3, 47)} = 39.880, p < 0.001, R² corrected = 0.713). The individual predictors were examined further and indicated that mixed features (t = 3.762, p < 0.001), psychotic symptoms (t = 4.932, p < 0.001 and previous suicide attempt (t = 3.928, p < 0.001) were significant predictors in the model (Table 3).

Finally, a significant negative association between DES and ALDA scores (t = −0.593; p < 0.001) emerged from the correlation analysis.

The main finding of our study is the presence of a stable correlation between dissociative symptoms psychotic symptom, mixed features, and previous suicides attempts in BD. Our study is the first to demonstrate that the occurrence of dissociative dimension is higher in BD type I, especially in those with psychotic features and in those who present a greater clinical severity (22–24). In our sample, 45% of patients developed psychotic symptoms, all of them with BD-I. Moreover, such correlation is related to clinical severity as shown by the higher DES-II total score in patients with a higher number of episodes, aggressive behaviors, seasonality, mixed features, and poor response to mood stabilizers (25). Possibly, as previously demonstrated for other mental disorders, dissociative symptoms are more expressed in patients with psychotic symptoms (26). According to Allen et al. (27), who developed the theory of “dissociative detachment,” dissociative phenomena “undermines the individual's grounding in the outer world,” rendering the individual susceptible to developing psychotic features. Additionally, other authors have highlighted the inverse relationship in which dissociation is a defense against the disorganization and acute distress generated by psychosis (28). Other possible mechanisms might be the early trauma exposure that predisposes to a higher psychopathological load among different psychiatric disorders, including BD (29, 30). However, we did not assess the impact of trauma in this study and therefore this explanation remains speculative.

In addition, mixed characteristics were associated with a higher DES-II total score. Mixed features are associated with a lack of response to mood stabilizers in BD and this could explain why patients with dissociative are refractory to treatment (31). Mixed features are often triggered by antidepressant therapy, and this feature appeared associated with greater dissociative symptomatology as demonstrated in our study.

Patients with a lifetime history of suicide attempts reported higher rates of dissociative symptoms and a higher DES-II total score. Suicide could represent an attempt to cope with dissociative symptoms or a last attempt to reach a dissociative state (32, 33). Thus, the link between dissociative symptoms and suicidal behaviors represent an interesting topic in order to improve the risk assessment and to develop models of intervention in patients with BD.

The significant correlation between DES and poor response to treatment with mood stabilizers emerged. We can explain it because clinical variables associated with dissociative symptoms are superimposable with those that predispose to refractoriness to drug treatment. In fact, this correlation gains further support from the significant correlations between clinical variables and dissociative symptoms that emerged from our study (i.e., the higher number of lifetime episodes, the seasonality, the antidepressant switch, the aggressive behavior, the anxious features, and the irregular course of illness) that are all predictive factors of poor response to treatment for patients with BD. So of poor response to treatment in patients with bipolar disorder (34).

The authors acknowledge some limits, the first being the cross-sectional design with a small sample size that narrows conclusions about the reverse causality. Surely, a longitudinal evaluation of dissociative symptoms would allow clarifying their association with clinical variables. Another limit is the backward clinical assessment of psychotic symptoms. The recall bias of incompleteness and imprecision of the patients' memories represents another limitation. Ultimately, patients completed the protocol while clinically stabilized so, assessing dissociative symptoms during the acute phase of the BD, although interesting was not possible. For all these reasons, the authors have planned follow-up assessments and including patients in the acute depressive, manic, or hypomanic episodes to counterbalance these limits.

Dissociative phenomena are closely related to the presence of psychotic symptoms, mixed features, and previous suicide attempts in BD, especially in BD-I. Given the close association between dissociative and psychotic symptoms, this association could represent a diagnostic indicator of BD-I. Therefore, we consider it extremely important to evaluate the presence of ongoing dissociation in BD to guide the clinician to plan the most appropriate treatment. Future studies should investigate in greater depth the causes underlying this association and the most appropriate therapeutic strategies to reduce the impact that these symptoms have on the course of BD.

The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.

The studies involving human participants were reviewed and approved by Regione Calabria, sezione Area Centro. The patients/participants provided their written informed consent to participate in this study.

LS: conceptualization. LS and ML: methodology. LS, ML, and CS-G: formal analysis. LS, EAC, and RF: investigation. EV and RF: data curation. LS, EAC, and ML: writing the original draft preparation. CS-G and PD: writing and review and editing. All authors read and approved the final manuscript.

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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