Objective and biological markers in bipolar spectrum presentations

ABSTRACT

Introduction: Subthreshold presentations of bipolarity (BSPs) pose a diagnostic conundrum, in terms of whether they should be conceptualized and treated similarly as traditionally defined bipolar disorders (BD). While it has been argued that BSPs are on a pathophysiologic continuum with traditionally defined BDs, there has been limited examination of biological and objective markers in these presentations to validate this assertion.

Areas covered: The authors review studies examining genetic, neurobiological, cognitive and peripheral markers in BSPs, encompassing clinical and non-clinical populations with subthreshold hypo/manic symptoms. Results are placed in the context of previously identified markers in traditionally defined BDs.

Expert commentary: There have been few studies of objective and biological markers in subthreshold presentations of BD, and results are mixed. While abnormalities in brain structure/functioning, peripheral inflammatory, and cognitive markers have been reported, it is unclear whether these findings are specific to BD or indicative of broad affective pathology. However, some studies suggest that increased sensitivity to reward and positive stimuli are shared between subthreshold and traditionally defined BDs, and may represent a point of departure from unipolar major depression. Further examination of such markers may improve understanding of subthreshold bipolar presentations, and provide guidance in terms of therapeutic strategies.

KEYWORDS:

• Bipolar disorder
• bipolar spectrum disorders
• subthreshold bipolar disorder
• biomarker
• cognition
• inflammatory cytokine
• neuroimaging
• genetic

Article highlights

• Patients with subthreshold presentations of bipolar disorder have been proposed to form part of a ‘bipolar spectrum’ continuous with bipolar I (BDI) and bipolar II (BDII) disorders.

• This subset of patients share demographic and clinical similarities with BDI and II, lending support to the bipolar spectrum model and leading some to suggest that these presentations should be treated similarly to traditionally defined BD.

• However, there has thus far been limited examination of biological and objective markers in proposed bipolar spectrum presentations (BSPs).

• In this review of the literature, we find BSPs to be variably defined, with variable thresholds applied for symptom number/duration, and variable tools used to assess subthreshold presentations.

• In addition to the variability such heterogeneity introduces, studies specifically investigating genetic, neurobiological, peripheral or cognitive markers in BSPs have been sparse.

• Although abnormalities in brain structure/functioning, inflammatory/peripheral markers and cognition in BSPs are reported, results are inconsistent, and it is unclear whether these findings are specific to bipolar disorders versus indicative of broad affective dysfunction.

• Previous studies, however, have identified markers of increased sensitivity to reward and positive stimuli as potentially specific to BD, and some studies find evidence for similar markers in BSPs.

• Further investigation of markers of increased sensitivity to reward and positive stimuli in BSPs may help establish pathophysiologic continuity with BD, and guide in determining the most effective treatment strategy in these presentations.

• This box summarizes key points contained in the article.

Declaration of interest

L Yatham has been a member of advisory boards, received research grants, or been a speaker for Allergan, Alkermes, Astrazeneca, Bristol Myers Squibb, Dainippon Sumitomo Pharma, GSK, Janssen, Lilly, Otsuka, Pfizer, Servier, Sunovion and Teva. T Chakrabarty reports no financial disclosures. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or conflict with the subject matter or materials discussed in this manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.