Symptoms and signs of the initial prodrome of bipolar II disorder

Abstract

Bipolar disorder (BD) is a chronic and debilitating illness characterized by severe dysregulation of mood, energy, and activity that results in episodes of depression and (hypo)mania. Approximately 60% of patients with BD experience the onset before the end of their teens. Thus, people who develop BD are often afflicted during their most vulnerable and formative years. A delay in appropriate treatment may worsen the course and outcome of the disorder. Hence, early identification and treatment is important to improve prognosis. This thesis explores symptoms and signs and temporal aspects of the pre-onset phase (initial prodrome) of BD to investigate whether it might be possible to identify the development of BD before the onset of the illness based on clinical phenomena. The thesis comprises two projects: a literature review of the initial prodrome of BD and an original research study on the initial prodrome of bipolar II disorder (BD-II).<br><br>

In the literature review (paper I), systematic studies addressing symptoms, signs and temporal aspects of the initial prodrome of BD were reviewed in search of potential clinical targets for early intervention. We found that irritability/aggressiveness, sleep disturbances, depression and mania symptoms, hyperactivity, anxiety, and mood swings are common symptom clusters of the initial prodrome of BD. The symptoms are not sufficiently specific to reliably identify BD prospectively. No studies have explicitly investigated the initial prodrome of BD-II.<br><br>

To investigate the phenomenology of the initial prodrome of BD-II, we conducted an exploratory retrospective study using qualitative methodology supplemented by quantitative analyses. Choosing a qualitative design enabled us to pursue an in-depth exploration of an under-investigated field of research in a flexible and open fashion and to collect complex data that could be analyzed in numerous ways. Hence, we gave priority to the in-depth study of a limited sample (15 BD-II patients and 22 family member informants) to search for findings that could generate hypotheses, which could be tested on larger samples in future studies. A series of open-ended in-depth interviews covering the patients’ life course from birth to the time of the study was conducted with each patient and family members. Given our interest in exploring the prodromal phase of BD-II, the time period preceding the estimated time of full diagnosable onset (hypomania and major depression) was emphasized. With the exception of certain temporal aspects, the findings presented in this thesis refer to the time period from birth to the first major affective episode (FMAE) of BD-II.<br><br>

In paper II we present findings on clinically significant symptoms/behaviors, the temporal aspects of these symptoms including onset ages and time intervals, and how clinical features differ between two distinct subgroups that were identified based on prominent and enduring personal characteristics prior to the FMAE. The symptoms reported were organized into categories that mirrored the categories of the review except for the “hyperactivity” category. As in the review, we conclude that the symptoms appear to be too nonspecific to reliably predict BD-II prospectively. However, the patients in one of the identified subgroups appear to be relatively more identifiable prior to the FMAE. These patients experienced neurocognitive deficits and pronounced irritability and aggressiveness, and earlier onset of the FMAE, earlier prodromal symptom onset, and more symptoms compared to a subgroup that was described as very well-functioning. This subgroup may be of potential interest for early identification.<br><br>

In paper III and IV we speculate whether the assessment of symptom instances’ temporal and contextual characteristics may help identify clinical indicators with enhanced predictive power. If so, it is insufficient only to assess the types of symptoms of individuals at perceived risk of developing BD. A specific symptom may be a likely or unlikely early manifestation of a forthcoming BD depending on its’ constellation of temporal and contextual characteristics. Based on theoretical reasoning, we propose that symptom instances which are characterized as episodic or chronic and as exaggerated responses to life events or inexplicable, may be the most likely early manifestations of the FMAE of BD-II. Symptom instances that were characterized as temporary, and thus, did not persist from symptom onset to the onset of the FMAE, were regarded as unrelated to the subsequent BD-II. Symptom instances characterized as episodic or chronic and as normal responses to life events were regarded as possible early manifestations. Assuming that symptom instances that emerge late in the prodrome are more likely to be early manifestations of the disorder itself, our preliminary findings support the notion that symptom instances classified as likely early manifestations may be the relatively best clinical predictors of a forthcoming BD-II. We also found that the majority of the symptom instances categorized as mood swings and irritability/aggressiveness met the criteria as likely early manifestations, and thus, may be the most prominent predictors of the FMAE of BD-II.<br><br>

In sum, this thesis contributes to the knowledge of the initial prodrome of BD and is the first to explicitly investigate the initial prodrome of BD-II. Novel hypotheses about patient subgroups, intergroup differences, and symptom characteristics with enhanced predictive value are proposed. The hypotheses generated need to be tested in future studies.