Functional connectivity measures as schizophrenia intermediate phenotypes: advances, limitations, and future directions

•We review current findings of intermediate connectivity phenotypes for schizophrenia.•We outline functional connectivity methods used for intermediate phenotype studies.•We discuss current limitations and future directions for intermediate connectivity phenotype studies in schizophrenia research.

The search for quantifiable biological mediators of genetic risk or 'intermediate phenotypes' is an essential strategy in psychiatric neuroscience and a useful tool for exploring the complex relationships between genes, neural circuits and behaviors. In recent years, the examination of connectivity-based intermediate phenotypes has gained increasing popularity in the study of schizophrenia, a brain disorder that manifests in early adulthood and disturbs a wide range of neural network functions. To date, several potential connectivity phenotypes have been identified that link neuroimaging measures of neural circuit interaction to genetic susceptibility for schizophrenia. This paper briefly reviews recent advances, current limitations and future directions in the search for functional connectivity intermediate phenotypes for schizophrenia across different cognitive domains.