Mismatch negativity is a breakthrough biomarker for understanding and treating psychotic disorders

Abstract Background Prognostic heterogeneity in early psychosis patients yields significant difficulties in determining the degree and duration of early intervention; this heterogeneity highlights the need for prognostic biomarkers. Although mismatch negativity (MMN) has been widely studied across early phases of psychotic disorders, its potential as a common prognostic biomarker in early periods, such as clinical high risk (CHR) for psychosis and first-episode psychosis (FEP), has not been fully studied. Methods A total of 104 FEP patients, 102 CHR individuals, and 107 healthy controls (HCs) participated in baseline MMN recording. Clinical outcomes were assessed; 17 FEP patients were treatment resistant, 73 FEP patients were nonresistant, 56 CHR individuals were nonremitters (15 transitioned to a psychotic disorder), and 22 CHR subjects were remitters. Baseline MMN amplitudes were compared across clinical outcome groups and tested for utility prognostic biomarkers using binary logistic regression. Results MMN amplitudes were greatest in HCs, intermediate in CHR subjects, and smallest in FEP patients. In the clinical outcome groups, MMN amplitudes were reduced from the baseline in both FEP and CHR patients with poor prognostic trajectories. Reduced baseline MMN amplitudes were a significant predictor of later treatment resistance in FEP patients [Exp(β) = 2.100, 95% confidence interval (CI) 1.104–3.993, p = 0.024] and nonremission in CHR individuals [Exp(β) = 1.898, 95% CI 1.065–3.374, p = 0.030]. Conclusions These findings suggest that MMN could be used as a common prognostic biomarker across early psychosis periods, which will aid clinical decisions for early intervention.

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Supplemental Material for Associations of Mismatch Negativity With Psychotic Symptoms and Functioning Transdiagnostically Across Psychotic Disorders

Journal of Abnormal Psychology ◽

10.1037/abn0000506.supp ◽

2020 ◽

Keyword(s):

Mismatch Negativity ◽

Psychotic Disorders ◽

Psychotic Symptoms

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Auditory Mismatch Negativity Under Predictive Coding Framework and Its Role in Psychotic Disorders

Frontiers in Psychiatry ◽

10.3389/fpsyt.2020.557932 ◽

2020 ◽

Vol 11 ◽

Author(s):

Chun Yuen Fong ◽

Wai Him Crystal Law ◽

Takanori Uka ◽

Shinsuke Koike

Keyword(s):

Mismatch Negativity ◽

Psychotic Disorders ◽

Predictive Coding

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F200. Relationships Between Mismatch Negativity and Transdiagnostic Symptoms Across Psychotic Disorders

Biological Psychiatry ◽

10.1016/j.biopsych.2018.02.814 ◽

2018 ◽

Vol 83 (9) ◽

pp. S316-S317

Author(s):

Kayla Donaldson ◽

Roman Kotov ◽

Keisha Novak ◽

Greg Perlman ◽

Daniel Foti ◽

...

Keyword(s):

Mismatch Negativity ◽

Psychotic Disorders

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MMN amplitude in first-degree relatives of psychotic disorders: Links with cognition and schizotypy

10.31234/osf.io/uka3t ◽

2020 ◽

Author(s):

Kayla R. Donaldson ◽

Emmett M. Larsen ◽

Katherine Jonas ◽

Sara Tramazzo ◽

Greg Perlman ◽

...

Keyword(s):

Mismatch Negativity ◽

Healthy Subjects ◽

Psychotic Disorders ◽

Clinical Symptoms ◽

Cognitive Impairments ◽

Familial Risk ◽

First Degree Relatives ◽

Per Se ◽

Meta Analyses ◽

Schizotypal Symptoms

Background: Mismatch negativity (MMN) amplitude is reliably reduced in psychotic disorders. While several studies have examined this effect in first-degree relatives of individuals with schizophrenia, few have sought to quantify deficits in relatives of individuals with other psychotic disorders. While some studies conclude that, compared to healthy subjects, first-degree relatives of schizophrenia show reduced MMN, others contradict this finding, a discrepancy which extends to two recent meta-analyses. Furthermore, though MMN is often shown to be associated with cognitive impairments and clinical symptoms in psychotic disorders, to our knowledge no studies have sought to examine these relationships in studies of first-degree relatives. Method: The present study sought to clarify the extent of MMN amplitude reductions in a large sample of siblings of individuals with diverse psychotic disorders (n=65), compared to cases with psychosis (n=220) and never psychotic comparison subjects (n=252). We further examined associations of MMN amplitude with cognition and schizotypal symptoms across these groups. Results: We found that MMN amplitude was intact in siblings compared to cases with psychosis. MMN amplitude was associated with cognition and schizotypal symptoms dimensionally across levels of familial risk. Conclusions: The present results imply that MMN amplitude reductions emerge as a result of, or in conjunction with, clinical features associated with psychosis. Such findings carry important implications for the utility of MMN amplitude as an indicator of inherited risk, and suggest that this component may be best conceptualized as a marker for clinical symptoms and cognitive impairments, rather than risk for psychosis per se.

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Features of Duration Mismatch Negativity Around the Onset of Overt Psychotic Disorders: A Longitudinal Study

Cerebral Cortex ◽

10.1093/cercor/bhaa364 ◽

2020 ◽

Author(s):

Takahiro Tateno ◽

Yuko Higuchi ◽

Suguru Nakajima ◽

Daiki Sasabayashi ◽

Mihoko Nakamura ◽

...

Keyword(s):

At Risk ◽

Mental State ◽

Mismatch Negativity ◽

Psychotic Disorders ◽

Transition Period ◽

Oddball Paradigm ◽

Auditory Oddball ◽

Not At Risk ◽

At Risk Mental State

Abstract Reduced amplitude of duration mismatch negativity (dMMN) has been reported in psychotic disorders and at-risk mental state (ARMS); however, few longitudinal MMN studies have examined the amplitude changes during the course of psychosis. We compared dMMN amplitude between ARMS individuals with later psychosis onset and those without, and we longitudinally examined potential dMMN changes around psychosis onset. Thirty-nine ARMS subjects and 22 healthy controls participated in this study. Of the 39 ARMS subjects, 11 transitioned to psychosis (at-risk mental state with later psychosis onset [ARMS-P]) during follow-up and 28 did not (at-risk mental state without later psychosis onset [ARMS-NP]). dMMN was measured twice using an auditory oddball paradigm with a mean interval of 2 years. Follow-up dMMN data were available for all but four ARMS-P subjects. dMMN amplitude at baseline was smaller in ARMS-P subjects compared with control and ARMS-NP subjects. Additionally, ARMS-P subjects displayed a longitudinal decline in dMMN amplitude, which was not present in control and ARMS-P subjects. We also observed a progressive decline in dMMN amplitude during the transition period, suggesting dynamic brain changes associated with the psychosis onset. Our findings implicate dMMN amplitude as a biological predictor of future psychosis onset in high-risk individuals, which may be used for early detection and intervention of psychosis.

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Psychosocial Risks and Management for Children and Adolescents With 22q11.2 Deletion Syndrome

Perspectives of the ASHA Special Interest Groups ◽

10.1044/2019_pers-sig5-2019-0002 ◽

2019 ◽

Vol 4 (4) ◽

pp. 633-640 ◽

Cited By ~ 1

Author(s):

Canice E. Crerand ◽

Ari N. Rabkin

Keyword(s):

Cognitive Abilities ◽

Psychotic Disorders ◽

Developmental Stages ◽

Early Adulthood ◽

22Q11.2 Deletion Syndrome ◽

Deletion Syndrome ◽

22Q11.2 Deletion ◽

Psychosocial Risks ◽

Empirically Supported ◽

Specific Education

Purpose This article reviews the psychosocial risks associated with 22q11.2 deletion syndrome, a relatively common genetic condition associated with a range of physical and psychiatric problems. Risks associated with developmental stages from infancy through adolescence and early adulthood are described, including developmental, learning, and intellectual disabilities as well as psychiatric disorders including anxiety, mood, and psychotic disorders. Other risks related to coping with health problems and related treatments are also detailed for both affected individuals and their families. Conclusion The article ends with strategies for addressing psychosocial risks including provision of condition-specific education, enhancement of social support, routine assessment of cognitive abilities, regular mental health screening, and referrals for empirically supported psychiatric and psychological treatments.

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Assessing Mental and Behavioral Disorder Impairment: Overview of Sixth Edition Approaches

Guides Newsletter ◽

10.1001/amaguidesnewsletters.2008.novdec01 ◽

2008 ◽

Vol 13 (6) ◽

pp. 1-7

Author(s):

Norma Leclair ◽

Steve Leclair ◽

Robert Barth

Keyword(s):

Mental Disorders ◽

Behavioral Disorders ◽

Psychotic Disorders ◽

Behavioral Disorder ◽

Behavioral Impairment ◽

Central Nervous System Damage ◽

Brain Functioning ◽

Sixth Edition ◽

Diagnostic And Statistical Manual ◽

Mental And Behavioral Disorders

Abstract Chapter 14, Mental and Behavioral Disorders, in the AMA Guides to the Evaluation of Permanent Impairment (AMA Guides), Sixth Edition, defines a process for assessing permanent impairment, including providing numeric ratings, for persons with specific mental and behavioral disorders. These mental disorders are limited to mood disorders, anxiety disorders, and psychotic disorders, and this chapter focuses on the evaluation of brain functioning and its effects on behavior in the absence of evident traumatic or disease-related objective central nervous system damage. This article poses and answers questions about the sixth edition. For example, this is the first since the second edition (1984) that provides a numeric impairment rating, and this edition establishes a standard, uniform template to translate human trauma or disease into a percentage of whole person impairment. Persons who conduct independent mental and behavioral evaluation using this chapter should be trained in psychiatry or psychology; other users should be experienced in psychiatric or psychological evaluations and should have expertise in the diagnosis and treatment of mental and behavioral disorders. The critical first step in determining a mental or behavioral impairment rating is to document the existence of a definitive diagnosis based on the current edition of the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders. The article also enumerates the psychiatric disorders that are considered ratable in the sixth edition, addresses use of the sixth edition during independent medical evaluations, and answers additional questions.

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