Type and duration of subsyndromal symptoms in youth with bipolar I disorder prior to their first manic episode

Abstract

Objectives To systematically evaluate the prodrome to mania in youth. Methods New-onset/worsening symptoms/signs of ≥ moderate severity preceding first mania were systematically assessed in 52 youth (16.2 ± 2.8 years) with a research diagnosis of bipolar I disorder (BD-I). Youth and/or caregivers underwent semi-structured interviews, using the Bipolar Prodrome Symptom Scale–Retrospective. Results The mania prodrome was reported to start gradually in most youth (88.5%), with either slow (59.6%) or rapid (28.8%) deterioration, while a rapid-onset-and-deterioration prodrome was rare (11.5%). The manic prodrome, conservatively defined as requiring ≥ 3 symptoms, lasted 10.3 ± 14.4 months [95% confidence interval (CI): 6.3–14.4], being present for ≥ 4 months in 65.4% of subjects. Among prodromal symptoms reported in ≥ 50% of youth, three were subthreshold manic in nature (irritability: 61.5%, racing thoughts: 59.6%, increased energy/activity: 50.0%), two were non-specific (decreased school/work functioning: 65.4%, mood swings/lability: 57.7%), and one each was depressive (depressed mood: 53.8%) or subthreshold manic/depressive (inattention: 51.9%). A decreasing number of youth had ≥ 1 (84.6%), ≥ 2 (48.1%), or ≥ 3 (26.9%) specific subthreshold mania symptoms (i.e., elation, grandiosity, decreased need for sleep, racing thoughts, or hypersexuality), lasting 9.5 ± 14.9 months (95% CI: 5.0–14.0), 3.5 ± 3.5 months (95% CI: 2.0–4.9), and 3.0 ± 3.2 months (95% CI: 1.0–5.0) for ≥ 1, ≥ 2, or ≥ 3 specific symptoms, respectively. Conclusions In youth with BD-I, a relatively lengthy, predominantly slow-onset mania prodrome appears to be common, including subthreshold manic and depressive psychopathology symptoms. This suggests that early clinical identification and intervention may be feasible in bipolar disorder. Identifying biological markers associated with clinical symptoms of impending mania may help increase chances for early detection and prevention before full mania.

Challenges and developments in research of the early stages of bipolar disorder

“…28,29 Several studies have recognized mood lability, major depressive episodes, subsyndromal manic symptoms, a diagnosis of a bipolar spectrum disorder (such as cyclothymia or BD not otherwise specified), and mood-congruent psychotic symptoms as precursors of BD. [30][31][32] On the other hand, in clinical practice, identification of a symptomatic high-risk BD phase is complicated by the complex nature of dimensions of this disorder, by potentially different symptom presentations in children and adolescents, 5,21,33 and by the blurred lines between the prodrome and the disease itself. 34 Retrospective and prospective studies have revealed a pattern of putative prodromal symptoms, of which mood lability/mood swings/cyclothymic features, depressive mood, racing thoughts, irritability, and physical agitation are most commonly reported.…”

“…52 Most used either unstructured questionnaires or chart reviews, and failed to assess the onset pattern of the disorder and the symptom severity of the prodromal period, which limits validity. 5 Furthermore, it remains unclear which person (i.e., the patient, a parent, teacher, or peer) is most likely to first notice the prodromal symptoms. 5 Thus, studies that access information regarding prodromal symptoms only from the point of view of patients themselves may be less reliable.…”

“…5 Furthermore, it remains unclear which person (i.e., the patient, a parent, teacher, or peer) is most likely to first notice the prodromal symptoms. 5 Thus, studies that access information regarding prodromal symptoms only from the point of view of patients themselves may be less reliable. Finally, recall bias is another limitation that must be taken into account when analyzing findings on neurobiology derived from retrospective studies.…”

“…5 To date, only preliminary data about biomarkers in at-risk states are available. These indicate that individuals at high risk of developing BD may have higher levels of lipid peroxidation as compared with healthy controls and lower levels compared with young people with syndromal BD.…”

“…[1][2][3] Recently, a focus on prevention, including early detection and intervention, has begun to attract increasing attention, as such strategies have the potential to delay, lessen the severity, prevent progression, or even prevent full-blown BD. 4,5 The notion that BD is a condition that follows a reasonable, predictable course across stages was a key aspect in developing proposals for prevention and early intervention. 6 Indeed, there are consistent data suggesting that, at least for a large subgroup of patients, BD actually follows a progressive course, which can be observed both in clinical outcomes (such as functional impairment) and in neurobiological findings (such as structural brain damage).…”