Neurophysiological biomarkers support bipolar-spectrum disorders within psychosis cluster

Neurophysiological biomarkers support bipolar-spectrum disorders within psychosis cluster

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J Psychiatry Neurosci 2012;37(4):313-21

Manreena Kaur, BSc (Hons); Robert A. Battisti, PhD; Jim Lagopoulos, PhD; Philip B. Ward, PhD; Ian B. Hickie, FRANZCP; Daniel F. Hermens, PhD

Kaur, Battisti, Lagopoulos, Hickie, Hermens — Clinical Research Unit, Brain & Mind Research Institute, University of Sydney, Sydney, Australia; Ward — School of Psychiatry, University of New South Wales, Sydney, and Schizophrenia Research Unit, South West Sydney Local Health Network, Liverpool Hospital, Liverpool, Australia


Background: Mismatch negativity (MMN) and P3a are event-related potentials that index deviance detection and the orienting response, respectively. We have previously shown that the MMN/P3a complex is impaired in patients with schizophrenia and affective spectrum psychoses, which suggests that it may index a common pathophysiology and argues against the purported specificity in schizo phrenia. Further research is warranted to determine whether patients with bipolar-spectrum disorders show similar impairments in these biomarkers.

Methods: We assessed patients aged 15–30 years with early schizophrenia-spectrum disorders (schizophrenia, schizoaffective disorder, schizophreniform disorder), early bipolar-spectrum disorders (bipolar I or II, with and without psychotic features) and healthy, matched controls. We acquired MMN/P3a amplitudes during a 2-tone, auditory paradigm with 8% duration deviants. Clinical, psychosocial and neuro psychological assessments were also undertaken.

Results: We included 20 patients with schizophrenia-spectrum disorders, 20 with bipolar-spectrum disorders and 20 controls in our study. Both patient groups showed significantly reduced frontocentral MMN and central P3a amplitudes. The schizophrenia-spectrum group had additional impairments in left temporal MMN and frontal P3a. Both patient groups performed worse than controls across psychosocial and clinical measures; however, only the schizophrenia-spectrum group performed significantly worse than controls for cognitive measures. Correlational analyses between patient groups revealed associations between frontocentral or left temporal MMN and psychiatric symptomatology or quality of life measures.

Limitations: Limitations to our study include the modest sample size and the lack of control with regards to the effects of other (i.e., nonantipsychotic) psychotropic medications.

Conclusion: Compared with patients in early stages of schizophrenia-spectrum disorders, those in the early stages of bipolar- spectrum disorders are similarly impaired in established biomarkers for schizophrenia. These findings support a shared diathesis model for psychotic and bipolar disorders. Furthermore, MMN/P3a may be a biomarker for a broader pathophysiology that overlaps traditional diagnostic clusters.

Submitted July 21, 2011; Revised Nov. 16, Dec. 14, 2011; Accepted Dec. 20, 2011.

Acknowledgements: This work was supported in part by the National Health and Medical Research Council (NHMRC) of Australia via a fellowship (ID 511921) and a program grant (ID 566529).

Competing interests: None declared for M. Kaur, R.A. Battisti, J. Lagopoulos and P.B. Ward. As above for I.B. Hickie and D.F. Hermens; their institution also receives grant support from the Mental Health & Drug & Alcohol Office, NSW Department of Health. I.B. Hickie declares board membership with Headspace, consulting for Bupa Australia, the National Council on Mental Healthy and Access to Allied Psychological Services.

Contributors: M. Kaur, I.B. Hickie and D.F. Hermens designed the study. M. Kaur, R.A. Battisti and D.F. Hermens acquired the data, which M. Kaur, R.A. Battisti, J. Lagopoulos, P.B. Ward and D.F. Hermens analyzed. M. Kaur and D.F. Hermens wrote the article. All authors reviewed the article and approved its publication.

DOI: 10.1503/jpn.110081

Correspondence to: M. Kaur, Clinical Research Unit, Brain & Mind Research Institute, University of Sydney, 100 Mallet St., Camperdown, NSW 2050, Australia;