Therapeutic signposts: using biomarkers to guide better treatment of schizophrenia and other psychotic disorders

Abstract

We propose that various measures of brain structure or function, gene expression and proteomic technologies can be used to guide better treatment of schizophrenia and other psychotic disorders. These measures are not used to establish a specific diagnosis. Their purpose is to predict variations in underlying illness activity that predict severity, course of clinical illness, or other morbidity. We propose a new instrument that uses a composite scoring system of systemic biomarkers of illness‐related changes in health status: the Brain and Mind Research Institute Biomarker Index. This may permit comparison of biological dysfunction among patients who are at similar points in their illness or have similar clinical features. A specific example of the use of a novel positron emission tomography marker of progressive brain disease in patients with schizophrenia is described.

Mismatch negativity (MMN) reduction in schizophrenia—Impaired prediction-error generation, estimation or salience?

“…Certainly this supports the use of MMN as a useful functional index of the effects of the proposed later-onset lesion but it is worth asking whether we can use this knowledge to design more sensitive measures of deficit and whether MMN can tell us anything more about the underlying vulnerability to the process for which the end point is grey matter loss. Preliminary data reported by Banati and Hickie (2009) note that reduced MMN size is significantly correlated with up regulation of peripheral benzodiazepine binding sites. This up regulation, indexed by (R)-PK11195, is a purported quantification of the brain's immune response to presumed disease activity.…”

The Immune System, Cytokines, and Biomarkers in Autism Spectrum Disorder

“…Additional applications of biomarkers have been proposed, such as use as a diagnostic tool for the identification of those patients with a disease or abnormal condition, and for the prediction and monitoring of the clinical response to an intervention. Specifically, with respect to using biomarkers to guide better treatment of schizophrenia and other psychotic disorders, Banati and Hickie have proposed clinically useful properties of biomarkers, including diagnostically non-specific, quantitative, longitudinal, plausibly linked to underlying pathophysiology, and predictive of risk of impairment [79]. They also highlight the clinical importance of the role of biomarkers in guiding treatment selection, and demonstrating a correlation between active interventions and the short-term clinical response.…”

The maturation of mismatch negativity networks in normal adolescence

“…MMN has been used to give clinical information for a multitude of medical conditions (Näätänen et al, 2012). It has been used to index excitability in epilepsy (Miyajima et al, 2011) and schizophrenia (Banati and Hickie, 2009), level of consciousness in coma (Naccache et al, 2005) and persistent vegetative states (Wijnen et al, 2007). Advanced analysis of MMN using dynamic causal modelling (DCM) has been performed on patients in a vegetative state showing impaired top-down modulation (Boly et al, 2011).…”