Schizophrenia research

Schizophrenia is a heterogeneous disease strongly influenced by genetic disposition. A large variety of candidate genes has been identified. However, each gene only explains a small proportion of the genetic risk. For this reason, stable markers, so called endophenotypes, are of primary interest.

In the last decade, we have developed an endophenotype based on visual masking, which is called the shine-through effect and we have extensively studied its characteristics. This test has a much higher sensitivity and specificity to “detect” schizophrenia than most other perceptual and cognitive paradigms (Key Publications: Herzog, Kopmann et al., 2004; Chkonia et al., 2010). Most importantly, not only schizophrenic patients show strong performance deficits but also their unaffected relatives and even unaffected people scoring high in cognitive disorganization (Cappe et al., 2012; Favrod et al., 2017) and 22q11 patients (Tomescu et al., 2015). This is crucial for an endophenotype because endopheotypes are aimed to reveal the genetic risk to suffer from disease. Our genetic analysis pointed to abnormalities in the cholinergic system, which correlated well with deficits in our visual masking paradigm (Bakanidze et al., 2013).

Based on these findings, we have developed a model that relates visual deficits to abnormally weak enhancement of target processing. We propose that vision is largely intact in the patients under normal instances. However, when stimuli are of low contrast or only briefly presented, they usually go unnoticed in both controls and patients. Only when these stimuli become behaviorally relevant and need to be enhanced, the enhancement deficits of the patients, which we relate to abnormalities in the cholinergic system, become obvious (Key Publication: Herzog et al., 2013). We propose that similar enhancement deficits can explain other symptoms of the patients, such as thought disorder, which can be viewed as an abnormality of staying focused. In line with this hypothesis, we also found that healthy students scoring high in cognitive disorganization show masking deficits, but to a much lesser degree than patients. In addition, we found that both patients and high scoring students show diminished EEG responses, which again supports the enhancement deficit hypothesis (Key Publication: Plomp et al., 2013). Depressive patients do not show masking deficits but EEG abnormalities (Favrod et al., 2019).

It is important to publish not only significant results, i.e., where patients are abnormal to controls, but also null results, i.e., where patients are not impaired, to avoid the impression that all aspects of all domains are abnormal in the patients. For example, non-retinotopic illusion processing and body ownership are intact (Lauffs et al., 2016; Grzeczkowski et al., 2018; Shaqiri et al., 2018).

Publications

Review
Theory
Endophenotype
Genetics
EEG
Schizotypy & 22q11
Visual processing
Intact processing in schizophrenia