Neurocognitive impairments and prefrontal brain functioning in individuals at risk for schizophrenia and bipolar disorder : a first step in search for potential biomarkers

Abstract

Summary Early recognition of schizophrenia and bipolar disorder has been a popular and important research topic in the last years. Even though the early symptoms of these disorders may emerge in adolescence, the disorders themselves usually remain un- or misdiagnosed for up to several years. Research has shown that this delay in treatment or a wrong treatment all together may have a negative impact on the course of a disorder. Therefore, several early recognition programs aim at identifying individuals at risk for schizophrenia and bipolar disorder before the disorders beome fully manifest. The early recognition programs are mostly based on assessment of various constellations of psychopathological symptoms. However, many of these symptoms, as well as other risk factors, are simultaneously predictive for many psychiatric disorders, making the early recognition processes difficult. Therefore, objectively measureable biological markers indicating the presence, absence or stage of a disorder are being searched for. Despite the intense research, no biomarker with sufficient sensitivity and specificity has been found until now. The aim of this dissertation was to investigate the frontal brain functioning in the individuals at risk for schizophrenia and bipolar disorder and through that contribute to the early recognition research. The data used in this dissertation were gathered within the framework of the Zurich Program for Sustainable Development of Mental Health Services (Zurcher Impulsprogramm zur nachhaltigen Entwicklung der Psychiatrie, ZInEP), subprojects 2 and 6. Subproject 2 (Early Recognition) aimed to identify individuals at risk for schizophrenia and bipolar disorder. Additionally to psychopathology assessment, neuropsychological testing has been conducted to find cognitive dysfunctions in the at-risk individuals. Subproject 6 aimed to identify neurophysiological abnormalities, which can be used as potential biomarkers for the at-risk state of schizophrenia and bipolar disorder. The studies presented in this work used the functional near-infrared spectroscopy (fNIRS) to measure the brain activation during two neuropsychological tasks. This method is particularly fitting for the early recognition research because it is relatively insensitive to movement and it is well suited for restless participants who may have problems during long monotonous i studies. Furthermore, it is inexpensive and easy to apply, which could facilitate investigating large study populations as well as transition to the clinical practice in the future. The prefrontal cortex (PFC) has been chosen as the region of interest in both studies presented here. Previous research has reported cognitive deficits as well as related deficits in PFC functioning in manifest schizophrenia and bipolar patients. Study 1 assessed emotional interference measured by the emotional Stroop task, whereas Study 2 used a well-established semantic…