Mismatch negativity/P3a complex in young people with psychiatric disorders: a cluster analysis

PLoS One. 2012;7(12):e51871. doi: 10.1371/journal.pone.0051871. Epub 2012 Dec 14.

Abstract

Background: We have recently shown that the event-related potential biomarkers, mismatch negativity (MMN) and P3a, are similarly impaired in young patients with schizophrenia- and affective-spectrum psychoses as well as those with bipolar disorder. A data driven approach may help to further elucidate novel patterns of MMN/P3a amplitudes that characterise distinct subgroups in patients with emerging psychiatric disorders.

Methods: Eighty seven outpatients (16 to 30 years) were assessed: 19 diagnosed with a depressive disorder; 26 with a bipolar disorder; and 42 with a psychotic disorder. The MMN/P3a complex was elicited using a two-tone passive auditory oddball paradigm with duration deviant tones. Hierarchical cluster analysis utilising frontal, central and temporal neurophysiological variables was conducted.

Results: Three clusters were determined: the 'globally impaired' cluster (n = 53) displayed reduced frontal and temporal MMN as well as reduced central P3a amplitudes; the 'largest frontal MMN' cluster (n = 17) were distinguished by increased frontal MMN amplitudes and the 'largest temporal MMN' cluster (n = 17) was characterised by increases in temporal MMN only. Notably, 55% of those in the globally impaired cluster were diagnosed with schizophrenia-spectrum disorder, whereas the three patient subgroups were equally represented in the remaining two clusters. The three cluster-groups did not differ in their current symptomatology; however, the globally impaired cluster was the most neuropsychologically impaired, compared with controls.

Conclusions: These findings suggest that in emerging psychiatric disorders there are distinct MMN/P3a profiles of patient subgroups independent of current symptomatology. Schizophrenia-spectrum patients tended to show the most global impairments in this neurophysiological complex. Two other subgroups of patients were found to have neurophysiological profiles suggestive of quite different neurobiological (and hence, treatment) implications.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Biomarkers / analysis
  • Bipolar Disorder / physiopathology*
  • Bipolar Disorder / psychology
  • Cluster Analysis
  • Depressive Disorder / physiopathology*
  • Depressive Disorder / psychology
  • Event-Related Potentials, P300 / physiology*
  • Evoked Potentials, Auditory / physiology*
  • Female
  • Humans
  • Male
  • Neuropsychological Tests
  • Psychotic Disorders / physiopathology*
  • Psychotic Disorders / psychology
  • Reaction Time / physiology
  • Schizophrenia / physiopathology*
  • Young Adult

Substances

  • Biomarkers

Grants and funding

This work was funded by a National Health & Medical Research Council (NHMRC) program grant (No. 566529) and a NHMRC Australia Fellowship (No. 464914) awarded to IBH. SLN was funded by a NMHRC Clinical Research Fellowship (No. 464914). MK was supported by an NHRMC Postgraduate Scholarship. The funding bodies had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.