Electrophysiological Deficits in Schizophrenia: Models and Mechanisms

Abstract

Schizophrenia a complex neuropsychiatric diso rder, is characterized by core impairments including positive symptoms (hallucinations, delusions), negative symptoms (blunted affect, alogia, social deficits, anhedonia, avo lition), as well as persistent neurocognitive deficits (memory, concentration, and learni ng). Positive symptoms usually show good response to currently approved medications, all of which act exclusively by blocking D2 receptors. Alternatively, the negative and ne urocognitive symptoms respond poorly to D2 antagonists, and therefore persist even in tr eated patients. Developing new therapies to target treatment-resistant symptoms requires identification of neural endophenotypes associated with these deficits (Braff and Li ght, 2005). Additionally , neurophysiological biomarkers may be objective indices of prominen t features in schizophrenia patients such as cognitive dysfunction (Javitt et al., 2008). Th e brain processes underlying neurocognitive symptoms can be investigated using various neurophysiological meas ures such as event related potentials (ERP) and electroencephalography (EEG). Event-related potentials and EEG oscillations represent coordinated neuronal activity and are thought to be a means to assess fundamental mechanisms of memory, attention, learning, and other cognitive functions. Consequently, these measures are lik ely to be an appropriate biomarker for brain abnormalities in schizophrenia. As such, grea t effort has been made to link particular electrophysiological features with rele vant aspects of schi zophrenia including psychopathology, clinical outcome, genetics, and pharmacology. First, we will introduce the re ader to the human EEG by giving an overview of the different components, highlighting each co mponent’s clinical relevance, as well as addressing its limitations. Subsequently, we highlight the char acteristics of ERPs of schizophrenia. In the second part of the review, current preclinical models (i.e., transgenic, pharmacological, and environmental approaches) of EEG abnormalit ies in schizophrenia will be discussed. We then discuss potential requir ements of future model and methods in order to provide further insight into the pathophysiologic al disease mechanism and thus allow the development and evaluation of new treatments.