A study recently published in the Journal of Psychiatric Research examined the relationship between insomnia, early life stressors, and the clinical manifestations of bipolar disorder. Below, lead author Laura Palagini, MD, PhD, explains what researchers found and clinical implications of the results.
Q: What led you and your colleagues to look into the role of insomnia symptoms in the clinical manifestations of BD?
A: Insomnia likely plays a triggering role in the onset and maintenance of BDs, as it may dysregulate the systems involved in mood and emotion regulation, including stress and inflammatory systems and circadian rhythms. Not only are circadian sleep alterations frequent in BD, as it has been shown in the last few years, but insomnia symptoms may be a factor in BDs across their entire course. As many as 80-100% of people suffer from it during the depressive episode, 30-35% experience it during manic and mixed episodes, and 45-55% do during the inter-episodic phase. Moreover, insomnia symptoms are considered a risk factor for BDs, increasing the risk of new onset mood episodes as well as relapse or recurrence of the disorder, while also being one of the most frequent residual symptoms. In addition, insomnia has been related to BD severity, emotional hyperreactivity or impulsivity, and increased suicidality.
Recently, targeting insomnia has been demonstrated to favorably impact the trajectory of mood disorders. Insomnia might be a potentially modifiable early marker in BDs, so a deeper understanding of its mechanism might be useful for both early diagnosis and in improving treatment strategies.
Early life stressors have also been demonstrated to alter sleep regulation, including both circadian sleep and homeostatic processes, in turn leading to lifelong/later-life sleep disturbances including insomnia. It has been hypothesized that sleep disruption related to early life stressors might contribute to the development pathways towards BDs in adult life through the epigenetic reprogramming of stress and inflammatory systems.
Despite these recent hypotheses, while some studies have evaluated the effect of early life stress on sleep quality in BDs, little is known about the associations between the exposure to early life stressors, insomnia symptoms, and the clinical manifestations of BDs. Within this framework, identifying insomnia symptoms as a target for therapeutic intervention in BDs should be an important translational consideration for the lifelong effects of early life stress on this condition.
Q: Please briefly describe your study method and key findings.
A: A consecutive series of inpatients hospitalized at the psychiatric ward of the Azienda Ospedaliero-Universitaria Pisana (AUOP, University of Pisa, Italy) were included in the study. Inclusion criteria were: participants 1) with a current diagnosis of major depressive episode with or without mixed features in the context of BD-I or BD-II 2) who were between 18 and 65 years of age and 3) who provided informed consent to participate in the study.
The exclusion criteria were: 1) a current or lifetime diagnosis of substance use disorder, 2) a current depressive episode with psychotic features, 3) other subtypes of BDs (ie, not otherwise specified), 4) a cognitive impairment, as assessed with the Mini-Mental State Evaluation with a cut-off score <24.
The current study was a cross-sectional observational study as a part of an ongoing main research plan aimed at characterizing insomnia and chronobiological rhythms in several types of mood disorders.
All participants were evaluated with a set of questionnaires including the Structured Clinical Interview for DSM-5 (SCID-5) to assess the presence of current or lifetime psychiatric diagnoses, the Italian version of the Early Trauma Inventory Self Report-Short Form (ETISR-SF) to assess early life stress, the Beck Hopelessness Scale (BHS) to evaluate hopelessness, the Scale for Suicide Ideation (SSI) to evaluate suicidal ideation and preparatory behaviors, and the Insomnia Severity Index to evaluate insomnia symptoms. In previous studies, a score of ≥8 has been used as a cut-off threshold for clinically significant insomnia symptoms.
The Beck Depression Inventory-II (BDI-II) was used to evaluate depressive symptoms, mixed features were diagnosed using the SCID-5, and hypomanic/manic symptoms were clinically evaluated with the Young Mania Rating Scale (YMRS). All the participants also completed clinical report forms that included current pharmacological treatments. We conducted regression and mediation analyses.
Our study suggests that:
1) BD patients in a depressive phase with clinically significant insomnia met a greater severity not only of depressive symptoms and suicidal risk, but also of early life stressors and the cognitive part of hopelessness, compared with patients without insomnia
2) insomnia symptoms could predict mood symptoms, suicidal ideation and plans, and the cognitive component of hopelessness
3) insomnia symptoms might mediate the effect of early life stressors on mood symptoms, hopelessness, and suicidal ideation and behaviors.
Taken together, these findings may have clinical implications for systematic screening of insomnia dimension and for prevention and early intervention with appropriate therapeutic strategies for insomnia. In particular, targeting insomnia symptoms may potentially modify the clinical features of BD in response to early life stressful events.
Q: How can mental health clinicians use your findings to improve patient care?
A: Together, these findings may have clinical implications for systematic screening of insomnia dimension and for prevention and early intervention strategies with appropriate therapeutic strategies for insomnia. In particular, targeting insomnia symptoms may potentially modify the clinical features of BD in response to early life stressful events.
Q: Are you conducting any follow-up research in this area, and are there any other studies you feel are needed?
A: Longitudinal studies are needed with larger samples of patients and other types of mood disorders with psychotic symptoms, anxiety or other features of BDs, but also patients who attempted suicide to better examine the direction of risk and be able to generalize these findings.
Q: Is there anything else pertaining to this topic that you would like to add?
A: Insomnia symptoms should be easily addressed in clinical practice with 1-2 questions. Insomnia treatment should be considered as a treatment to prevent BD relapse and recurrence and to prevent suicide and the effect of early life stress on BD.
Palagini L, Bastien CH, Marazziti D, Ellis JG, Riemann D. The key role of insomnia and sleep loss in the dysregulation of multiple systems involved in mood disorders: a proposed model. Journal of Sleep Research. 2019;28:e12841.
Palagini L, Domschke K, Benedetti F, Foster RG, Wulff K, Riemann D. Developmental pathways towards mood disorders in adult life: is there a role for sleep disturbances? Journal of Affective Disorders. 2019; 243:121-132.
Palagini L, Cipollone G, Masci I, et al. Insomnia symptoms predict emotional dysregulation, impulsivity and suicidality in depressive bipolar II patients with mixed features. Comprehensive Psychiatry. 2019;89: 46-51.
Palagini L, Miniati M, Caruso D, Association between affective temperaments and mood features in bipolar disorder II: the role of insomnia and chronobiological rhythms desynchronization. Journal of Affective Disorders. 2020;266:263-272.
Palagini L, Manni R, Aguglia E, et al. Expert opinions and consensus recommendations for the evaluation and management of insomnia in clinical practice: joint statements of five Italian scientific societies. Frontiers in Psychiatry. 2020;11:558.
Palagini L, Miniati M, Marazziti D, Sharma V, Riemann D. Association among early life stress, mood features, hopelessness and suicidal risk in bipolar disorder: The potential contribution of insomnia symptoms. Journal of Psychiatric Research. 2021;135:52-59.
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Laura Palagini, MD, PhD, is Medical Assistant Psychiatrist and Associate Professor of Psychiatry at the Psychiatric Clinic, University Hospital Azienda Ospedaliero Universitaria Pisana (AUOP), Department of Clinical and Experimental Medicine, University of Pisa, Italy. She is the coordinator of the sleep disorders outpatient clinic and the pregnancy center for psychiatric disorders in the psychiatric clinic. She is also a member of the board of the Italian Association of Sleep Medicine (2015-2021), a member of the committee for the World Sleep Association’s World Sleep Day, the European Insomnia Network, European CBT-I Academy, and European Sleep Research Society, and an Associate Editor of the Journal of Sleep Research.