Endophenotype | EPFL Graph Search

In genetic epidemiology, endophenotype (or intermediate phenotype) is a term used to separate behavioral symptoms into more stable phenotypes with a clear genetic connection. By seeing the EP notion as a special case of a larger collection of multivariate genetic models, which may be fitted using currently accessible methodology, it is possible to maximize its valuable potential lessons for etiological study in psychiatric disorders. The concept was coined by Bernard John and Kenneth R. Lewis in a 1966 paper attempting to explain the geographic distribution of grasshoppers. They claimed that the particular geographic distribution could not be explained by the obvious and external "exophenotype" of the grasshoppers, but instead must be explained by their microscopic and internal "endophenotype". The endophenotype idea represents the influence of two important conceptual currents in biology and psychology research. An adequate technology would be required to perceive the endophenotype, w

Visual backward masking deficits in schizotypy are observed in late but not early onset nicotine smokers

Géraldine Beaud, Michael Herzog, Christine Mohr, Guillaume Sierro

Visual backward masking (VBM) is a potential endophenotype for schizophrenia. Relative VBM deficits were also observed in high as compared to low scorers in one schizotypal subdimension (cognitive disorganisation, CogDis; Cappe et al., 2012). VBM deficits may be related to dysfunctions of the nicotinergic ACh system. Interestingly, nicotine consumption is initiated earlier and higher in people within the schizophrenia spectrum. Here, we investigated whether chronic nicotine consumption relates to the link between VBM deficits and high CogDis scores. We tested 12 early onset smokers (≤ 15 years), 19 late onset smokers (>15 years) and 17 non-smokers. Participants completed the VBM task and the short version of the O-LIFE questionnaire. Indeed, impairments in VBM correlated with increasing CogDis scores in the late smokers and non-smokers, but we found the inverse relationship for early smokers. The other schizotypy dimensions (positive, negative) were unrelated to VBM performance. Hence, our findings support a nicotinic mediation of VBM performance and point to self-medications effects.

2014

(Visual) Endophenotypes in schizophrenia research

Ophélie Gladys Favrod, Michael Herzog, Albulena Jashari-Shaqiri, Maya Roinishvili

Objective: Schizophrenia is a heterogeneous disease strongly influenced by genetic disposition. However, genetic studies have shown that each single nucleotide polymorphism (SNP) contributes very little to the disease. For this reason, endophenotypes, located in between the genetic and clinical level, have become of great interest. Due to its heterogeneity, schizophrenia is likely not caused by one abnormality. Here, we asked the question to what extent deficits in various endophenotypes tap into the same deficits of schizophrenia. Methods: We tested schizophrenia patients, their relatives, and controls with a battery of perceptual and cognitive tests, such as visual backward masking, out of body experience, the Wisconsin Card Sorting Test (WCST), verbal fluency, and the continous performance task (CPT). Results: First, we found that visual backward masking is an extremely sensitive endophenotype of schizophrenia. Deficits are specific to the psychosis spectrum and not evident in depressive patients and abstinent alcoholics. As expected from an endophenotype, not only the patients but also their siblings show clear performance deficits, as well as adolescents with psychosis. Both genetic analysis and EEG recordings point to deficiencies in the cholinergic system. We then compared performance in visual backward masking with other tests. Surprisingly, performance in most tests did not correlate with each other. Conclusions: Our results suggest that each endophenotype is sensitive to different abnormal mechanisms. Schizophrenia is much more complex than previously thought. Heterogeneity can be best attacked by the combined investigation of sensitive endophenotypes.

2019

Electrophysiological correlates of visual backward masking in the schizophrenia continuum

Ophélie Gladys Favrod

In visual backward masking (VBM), a target is followed by a mask. Over the past decade, a VBM task, called the Shine-Through paradigm (ST), has been shown to be a very sensitive endophenotype of schizophrenia. In the present thesis, the electrophysiological correlates (EEG) of this endophenotype are investigated. Patients with schizophrenia show strongly reduced amplitudes of the Global Field Power (GFP, standard deviation across all electrodes of the EEG) 200 ms after target onset. Here, I show, first, that patients with first episode psychosis also have masking deficits and that the associated EEG amplitudes are between those of controls and patients with schizophrenia. In detail, when the task is challenging the neural correlates are similar to patients with schizophrenia and when the task is easy the neural correlates are similar to controls. This result suggests that patients with first episode psychosis are in an intermediate state where the disease is not fully developed yet. In addition, the neural signature is stable over at least one year meaning that the fully developed deficits must occur over durations longer than one year. Second, I show that healthy participants with high schizotypal traits, in particular scoring high in the cognitive disorganization dimension, also have GFP amplitude reductions 200 ms after target onset compared to participants with low schizotypal traits. Quantitatively, the difference between high and low scoring participants is much smaller than between patients and controls. Nonetheless, the result shows that deficits are qualitatively similar along the schizophrenia continuum even in a non-clinical population. Third, patients with 22q11 deletions syndrome, who also suffer from psychosis in 30% of the cases, do not show masking deficits. Deficits were expected but potentially because of high co-morbidity with other disorders, I did not find the same neural signature. Fourth, patients with major depressive disorder are not impaired in the ST, however, their neural correlates are lower compared to controls, though not as low as schizophrenia patients. This is surprising given the good behavioral performance. Despite the GFP reduction, the neural signature of depressive patients differs from the one of schizophrenia patients. They do not show the amplitude increment as a function of task difficulty seen in controls, siblings of patients with schizophrenia, and patients with schizophrenia. Finally, I describe preliminary results from on-going studies on healthy aging, autism and bipolarity. The objective is to make all populations fit in a unified framework.

EPFL2019