The Bipolar Illness Onset study: research protocol for the BIO cohort study

Abstract

IntroductionBipolar disorder is an often disabling mental illness with a lifetime prevalence of 1%–2%, a high risk of recurrence of manic and depressive episodes, a lifelong elevated risk of suicide and a substantial heritability. The course of illness is frequently characterised by progressive shortening of interepisode intervals with each recurrence and increasing cognitive dysfunction in a subset of individuals with this condition. Clinically, diagnostic boundaries between bipolar disorder and other psychiatric disorders such as unipolar depression are unclear although pharmacological and psychological treatment strategies differ substantially. Patients with bipolar disorder are often misdiagnosed and the mean delay between onset and diagnosis is 5–10 years. Although the risk of relapse of depression and mania is high it is for most patients impossible to predict and consequently prevent upcoming episodes in an individual tailored way. The identification of objective biomarkers can both inform bipolar disorder diagnosis and provide biological targets for the development of new and personalised treatments. Accurate diagnosis of bipolar disorder in its early stages could help prevent the long-term detrimental effects of the illness.The present Bipolar Illness Onset study aims to identify (1) a composite blood-based biomarker, (2) a composite electronic smartphone-based biomarker and (3) a neurocognitive and neuroimaging-based signature for bipolar disorder.Methods and analysisThe study will include 300 patients with newly diagnosed/first-episode bipolar disorder, 200 of their healthy siblings or offspring and 100 healthy individuals without a family history of affective disorder. All participants will be followed longitudinally with repeated blood samples and other biological tissues, self-monitored and automatically generated smartphone data, neuropsychological tests and a subset of the cohort with neuroimaging during a 5 to 10-year study period.Ethics and disseminationThe study has been approved by the Local Ethical Committee (H-7-2014-007) and the data agency, Capital Region of Copenhagen (RHP-2015-023), and the findings will be widely disseminated at international conferences and meetings including conferences for the International Society for Bipolar Disorders and the World Federation of Societies for Biological Psychiatry and in scientific peer-reviewed papers.Trial registration numberNCT02888262.

Is smartphone‐based mood instability associated with stress, quality of life, and functioning in bipolar disorder?

“…Future studies investigating differences in mood instability between patients with bipolar disorder, healthy relatives at risk of bipolar disorder and healthy control individuals are ongoing and will provide more results regarding this matter. 22 The statistical analyses included illness duration as a possible confounding variable but did not include the number of pre- This will add to the opportunity to intervene early and potentially treat to prevent decreased functioning and potential relapse. Using mood instability to monitor and assess patients with bipolar disorder over time and to identify changes may provide new opportunities for early intervention, which has been shown to reduce the risk of rehospitalization.…”

Differentiating unipolar and bipolar depression: Contribution of the Rorschach test (Comprehensive System)

“…Furthermore, the fact that patients have had unipolar or bipolar disorder for many years significantly mitigates the concern that the unipolar group might include patients in whom the bipolar shift has not yet occurred, since the unipolar to bipolar conversion in most bipolar patients with depressive onset occurs within 5–10 years (Kessing et al, ). However, despite an average of 15.49 years, the illness duration was lower than 11 years for 17 (24%) unipolar patients and less than 5 for three (4%).…”

A multisystem composite biomarker as a preliminary diagnostic test in bipolar disorder

“…Further efforts in evaluating novel biomarkers involve replication in independent samples, prospective validation in prospective cohorts, evaluating of incremental added and clinical utility, among others . Building on our current efforts, we are presently undertaking a large cohort study, including relatives of patients with bipolar disorder, where we will investigate the potential for a composite biomarker as a marker of illness risk .…”

“…Further, for a composite biomarker to have clinical applicability, the use of tissues and laboratory methods that have potential to be integrated into a clinical setting should be considered. Along that line, in an ongoing cohort study involving patients with bipolar disorder, their healthy first‐generation relatives and healthy control individuals we are planning to combine markers from multiple and readily available tissues . In the current study, variable selection was entirely data driven and we investigated composite markers that would be sensitive to trait and state separately.…”