Abstract
BackgroundWe 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.MethodsEighty 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.ResultsThree 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.ConclusionsThese 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.
Highlights
A major topic of debate in psychiatric research is whether categorical diagnoses represent distinct disorders or, if they are better represented as a continuum of psychiatric illness [1,2,3]
Similar associations have been found between P3a amplitudes and cognitive or psychosocial functioning [21,22] suggesting that the mismatch negativity (MMN)/P3a complex may be a marker of the fundamental sensory processes that underlie higher-order functions
We have demonstrated that the MMN/P3a complex in early affectivespectrum disorders is impaired as in early schizophreniaspectrum disorders
Summary
A major topic of debate in psychiatric research is whether categorical diagnoses (e.g. depressive disorder, bipolar disorder and schizophrenia) represent distinct disorders (in terms of their underlying neurobiology) or, if they are better represented as a continuum of psychiatric illness [1,2,3]. MMN is thought to reflect NMDA receptor mediated neurotransmission and impaired MMN is likely to reflect glutamatergic dysfunction [36,37], whereas variations in the amplitude of P3a are thought to be primarily modulated by dopaminergic changes [38,39] Both of these neurotransmitters have been shown to be dysregulated across several psychiatric disorders, making them ideal for exploration in this cohort. We have recently shown that the event-related potential biomarkers, mismatch negativity (MMN) and P3a, are 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
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