SP 4

Transdiagnostic neurocognitive biomarkers for the major psychoses

Subproject 4 (SP4) of the research consortium IntegraMent investigates the neurogenetic causes, differences, and similarities of the three major psychiatric disease groups schizophrenia, bipolar disorder, and unipolar (depressive) affective disorder.

The aim of SP4 is to identify brain characteristics that show association with these illnesses and their complex genetic causes.

„Imaging Genetics“ is an approach used to identify intermediate phenotypes. This should determine intermediate phenotypes that mediate the pathogenesis between risk genes and psychiatric illness (Walter H, Meyer-Lindenberg A, Heinz A (2014) Imaging Genetics. In: Gruber O, Falkai P (eds.) Systemische Neurowissenschaften in der Psychiatrie. Methoden und Anwendungen in der Praxis. Kohlhammer, Stuttgart, pp. 308-326.).

Using „Imaging Genetics“, i.e. the combination of brain imaging and standardized genetic investigations, the influence of risk genes on the structure and function of the brain is investigated in order to improve understanding of the underlying disease mechanisms. The hereby identified brain features are termed intermediate phenotypes, since in disease development, they lie between the genotype (the genetic characteristics of the individual) and the clinical phenotype (the observable characteristics of the illness).

Transdiagnostic approach to the investigation of similarities and differences.

Similarities and differences between the diagnostic groups are also investigated. In particular, diverse statistical methods are applied to identify diagnostic and predictive markers. This “transdiagnostic approach” is based on the observation that a strict differentiation between the three illness groups is often difficult, since psychotic and affective disorders often overlap or blend in terms of their symptoms and mechanisms, and are likely to be part of a disease spectrum. It therefore seems reasonable to use long-term neurobiological mechanisms as the basis for improved disease classification, diagnostics, and therapy, rather than symptoms alone.

Staged-approach to the investigation of neurobiological risk- and disease features. This identifies neurological mechanisms that are associated with the extent of disease risk.

The „staged-approach” is also used to investigate how brain characteristics differ between different risk/disease states. The required comparisons with groups of healthy control persons and the non-affected first degree relatives of patients is enabled by the availability of large datasets from our previous study, “MooDS - Neurogenetic risk mechanisms of affective disorders and schizophrenia.”

Imaging investigations of brain structure and function (using magnetic resonance imaging, MRI), genetic analyses, as well as neuropsychological- and psychological testing are conducted.

SP4 makes a substantial contribution to the overall aim of the Consortium through its investigation of the effect of genetic markers on basal cognitive function in three patient samples and one control cohort, the collection of functional and structural MRI-data, and the advancement of data analysis in collaboration with the other SPs. Joint data analyses are performed in close collaboration with SP1 and SP10. We also cooperate with SP1 in the integration of pathway based information, e.g. from protein-protein interaction networks (SP8), into the analysis of imaging data.

In collaboration with the other subprojects SP4 aims to continue to develop computational models and statistical methods which can be applied to MRI data in order to detect underlying neural processes, and thus contribute to an improved understanding of the functional changes that occur in psychiatric illness.

Keywords: schizophrenia; depression; bipolar disorder; neuroimaging; imaging genetics; transdiagnostic biomarkers; vulnerability; risk mechanisms; genetics