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Bipolar disorder in the balance

  • Brian J. LithgowEmail author
  • Zahra Moussavi
  • Caroline Gurvich
  • Jayashri Kulkarni
  • Jerome J. Maller
  • Paul B. Fitzgerald
Original Paper

Abstract

Bipolar disorder (BD) is a severe mood disorder that lacks established electrophysiological, neuroimaging or biological markers to assist with both diagnosis and monitoring disease severity. This study’s aim is to describe the potential of new neurophysiological features assistive in BD diagnosis and severity measurement utilizing the recording of electrical activity from the outer ear canal called Electrovestibulography (EVestG). From EVestG data sensory vestibulo-acoustic features were extracted from a single supine-vertical translation stimulus to distinguish 50 depressed and partly remitted/remitted bipolar disorder patients [18 symptomatic (BD-S, MADRS > 19), 32 reduced symptomatic (BD-R, MADRS ≤ 19)] and 31 age and gender matched healthy individuals (controls). Six features were extracted from the measured firing pattern interval histogram and the extracted shape of the average field potential response. Five of the six features had low but significant correlations (p < 0.05) with the MADRS assessment. Using leave-one-out-cross-validation, unbiased parametric and non-parametric classification routines resulted in 75–79%, 84–86%, 76–85% and 79–82% accuracy for separation of control from BD, BD-S and BD-R as well as BD-S from BD-R groups, respectively. The main limitation of this study was the inability to fully disentangle the impact of prescribed medication from the responses recorded. A mix of stationary and movement evoked EVestG features produced good discrimination between control and BD patients whether BD-S or BD-R. Moreover, BD-S and BD-R appear to have measurably different pathophysiological manifestations. The firing pattern features used were dissimilar to those observed in a prior major depressive disorder study.

Keywords

Bipolar disorder Depression Neurobiology Electrovestibulography Biological markers Vestibular 

Abbreviations

AD

Antidepressant medication

AMPA

a-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid

Background phase

1.5 s EVestG recording immediately prior to motion

BD

Bipolar disorder, (-S) symptomatic, (-R) reduced symptomatic (-R can be broken into (-M) mild and (-A) asymptomatic)

EVestG

Electrovestibulography

FP

Field potential

IH1, IH2

EVestG short interval features. Intervals were the time between detected FP’s

IH331, IH332

EVestG long interval features. Intervals were the time between each 33rd FP

LDA

Linear discriminant analysis

MADRS

Montgomery Asberg Depression Rating Scale

MDD

Major depressive disorder, (-S) symptomatic, (-R) reduced symptomatic

MS

Mood stabilizer medication

NDMA

N-methyl-d-aspartate

AP

Antipsychotic medication

NEER

Neural event extraction routine

NM

No-medication

NPC

Non-parametric classifier

Acceleration phase

1.5 s EVestG recording during the acceleration phase

Deceleration phase

1.5 s EVestG recording during the deceleration phase

Sh1, Sh2

EVestG shape features

Notes

Acknowledgements

We would like to thank all members of Monash Alfred Psychiatry Research Center who supported this research. Amber Garrett (a Ph.D. student) recorded many of the EVestG recordings. This work was supported by grants from the Australian Research Council and National Health and Medical Research Council. Neural Diagnostics Pty Ltd was the industry partner in this research. PF is supported by an NHMRC practitioner fellowship.

Author contributions

BL wrote the first draft and did main data analysis; ZM and PF were the major contributors to the data analysis and paper writing; BL, PF, JK and CG conceived the experiment(s). PF and JK examined and referred the patients. CG and JM contributed to patient assessments. All authors reviewed the manuscript.

Funding

Funding was provided by Australian Research Council (Grant no. LP0669420).

Compliance with ethical standards

Conflict of interest

BL owns < 0.5% of shares in Neural Diagnostics Pty Ltd. (ND) and acts as a part-time consultant for ND. PF is supported by a NHMRC Practitioner Fellowship (1078567). PF has received equipment for research from MagVenture A/S, Medtronic Ltd, Cervel Neurotech and Brainsway Ltd and funding for research from Neuronetics and Cervel Neurotech. He is on the scientific advisory board for Bionomics Ltd. ZM, CG, JM, JK report no financial interests or potential conflicts of interest.

Supplementary material

406_2018_935_MOESM1_ESM.docx (101 kb)
Supplementary material 1 (DOCX 100 KB)

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Monash Alfred Psychiatry Research CentreMonash University Central Clinical School and The Alfred HospitalMelbourneAustralia
  2. 2.Diagnostic and Neurosignal Processing Research Laboratory, Riverview Health CentreUniversity of ManitobaWinnipegCanada

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