Alcohol use and mismatch negativity in young patients with psychotic disorder

Clinical Research Unit, Brain and Mind Research Institute, University of Sydney, Sydney, Australia.
Neuroreport (Impact Factor: 1.52). 12/2011; 22(17):918-22. DOI: 10.1097/WNR.0b013e32834cdc3f
Source: PubMed


Mismatch negativity (MMN) is a neurophysiological indicator of the brain's ability to extract relevant information from an irrelevant background. MMN has been described as a reliable biomarker of schizophrenia and more recently it has found to be impaired in the early stages of psychosis. In addition, drugs (including alcohol) that block glutamate's N-methyl-D-aspartate receptor have been shown to reduce MMN. This study aims to determine whether risky alcohol consumption in young patients with psychotic disorder further impacts or changes their MMN response. Patients with high-alcohol use were found to show reduced temporal MMN amplitudes compared with patients with low-alcohol use and controls. In contrast, early psychosis patients with low-alcohol use showed reduced fronto-central MMN amplitudes compared with controls; whereas patients with high-alcohol use showed an intermediate response at these sites. Correlational analysis revealed distinct patterns of association between MMN and alcohol use in patients with early psychosis compared with controls. This study shows that early psychosis outpatients who engaged in risky drinking have decreased temporal MMN amplitudes, compared with their peers. This may reflect an additive effect of N-methyl-D-aspartate receptor hypofunction and high-alcohol consumption.

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    • "Sixty young outpatients (see details below) underwent a baseline clinical, neuropsychological and neurophysiological assessment and consented to being contacted in the future (i.e. after at least 12 months had elapsed) for follow-up assessments as part of our longitudinal neurobiological study (Hermens et al., 2011; Lee et al., 2013; Scott et al., 2013). As described in our previous neurophysiological studies (Chitty et al., 2011; Hermens et al., 2010; Kaur et al., 2011; Kaur et al., 2012a; Kaur et al., 2012b; Pesa et al., 2012), patients were recruited from specialised referral services for the assessment and early intervention of mental health problems (Scott et al., 2009; Scott et al., 2012). Twenty-two per cent (13/60) of the patients assessed at baseline could not be contacted at follow-up, for the following reasons: changed contact details (n = 8) or, did not respond to phone calls or emails (n = 5). "
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    ABSTRACT: Background: Impaired mismatch negativity (MMN) is a robust finding in schizophrenia and, more recently, similar impairments have been reported in other psychotic- and affective-disorders (including at early stages of illness). Although cross-sectional studies have been numerous, there are few longitudinal studies that have explored the predictive value of this event-related potential in relation to clinical/functional outcomes. This study assessed changes in MMN (and the concomitant P3a) amplitude over time and aimed to determine the longitudinal relationship between MMN/P3a and functional outcomes in patients recruited during the early stage of a schizophrenia- or affective-spectrum disorder. Methods: Sixty young patients with schizophrenia- and affective-spectrum disorders and 30 healthy controls underwent clinical, neuropsychological and neurophysiological assessment at baseline. Thirty-one patients returned for clinical and neuropsychological follow-up 12-30months later, with 28 of these patients also repeating neurophysiological assessment. On both occasions, MMN/P3a was elicited using a two-tone passive auditory paradigm with duration deviants. Results: Compared with controls, patients showed significantly impaired temporal MMN amplitudes and trend-level deficits in central MMN/P3a amplitudes at baseline. There were no significant differences for MMN measures between the diagnostic groups, whilst the schizophrenia-spectrum group showed reduced P3a amplitudes compared to those with affective-spectrum disorders. For those patients who returned for follow-up, reduced temporal MMN amplitude at baseline was significantly associated with greater levels of occupational disability, and showed trend-level associations with general and social disability at follow-up. Paired t-tests revealed that MMN amplitudes recorded at the central-midline site were significantly reduced in patients over time. Interestingly, those patients who did not return for follow-up showed reduced frontal MMN and fronto-central P3a amplitudes compared to their peers who did return for repeat assessment. Conclusions: This study provides some evidence of the predictive utility of MMN at the early stages of schizophrenia- and affective-spectrum disorders and demonstrated that MMN impairments in such patients may worsen over time. Specifically, we found that young patients with the most impaired MMN amplitudes at baseline showed the most severe levels of disability at follow-up. Furthermore, in the subset of patients with repeat neurophysiological testing, central MMN was further impaired suggestive of neurodegenerative effects. MMN may serve as a neurophysiological biomarker to more accurately predict functional outcomes and prognosis, particularly at the early stages of illness.
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    ABSTRACT: Cannabis use is prevalent among the early psychosis (EP) population. The event-related potentials, mismatch negativity (MMN) and P3a are reduced in EP. Cannabinoids have been shown to modulate N-methyl-D-aspartate receptors which are involved in MMN generation. This study is the first to investigate the effects of cannabis use on MMN/P3a in EP. EP was defined as a history of psychosis or psychotic symptoms with no progression to date to chronic schizophrenia. Twenty-two EP patients with cannabis use (EP + CANN), 22 non-cannabis-using EP patients (EP-CANN) and 21 healthy controls participated in this study. MMN/P3a was elicited using a two-tone, auditory paradigm with 8% duration deviants. As expected, EP-CANN showed marked reductions in MMN/P3a amplitudes compared to controls. However, EP + CANN showed evidence of a different pattern of neurophysiological expression of MMN/P3a compared to non-using patients, most notably in terms of delayed frontal MMN/P3a latencies. This study provides further evidence that MMN/P3a deficits are present during early psychosis and suggests that this biomarker may have utility in differentiating substance- from non-substance-related psychoses.
    Psychopharmacology 03/2012; 222(3):507-18. DOI:10.1007/s00213-012-2676-2 · 3.88 Impact Factor

  • Cortex 02/2013; 49(4). DOI:10.1016/j.cortex.2013.02.007 · 5.13 Impact Factor
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