A systematic review of associations between functional MRI activity and polygenic risk for schizophrenia and bipolar disorder

Genetic factors account for up to 80% of the liability for schizophrenia (SCZ) and bipolar disorder (BD). Genome-wide association studies have successfully identified several genes associated with increased risk for both disorders. This has allowed researchers to model the aggregate effect of genes associated with disease status and create a polygenic risk score (PGRS) for each individual. The interest in imaging genetics using PGRS has grown in recent years, with several studies now published. We have conducted a systematic review to examine the effects of PGRS of SCZ, BD and cross psychiatric disorders on brain function and connectivity using fMRI data. Results indicate that the effect of genetic load for SCZ and BD on brain function affects task-related recruitment, with frontal areas having a more prominent role, independent of task. Additionally, the results suggest that the polygenic architecture of psychotic disorders is not regionally confined but impacts on the task-dependent recruitment of multiple brain regions. Future imaging genetics studies with large samples, especially population studies, would be uniquely informative in mapping the spatial distribution of the genetic risk to psychiatric disorders on brain processes during various cognitive tasks and may lead to the discovery of biological pathways that could be crucial in mediating the link between genetic factors and alterations in brain networks

Computational models of schizophrenia and dopamine modulation in the prefrontal cortex

Computational neuroscience models can be used to understand the diminished stability and noisy neurodynamical behaviour of prefrontal cortex networks in schizophrenia. These neurodynamical properties can be captured by simulated neural networks with randomly spiking neurons that introduce noise into the system and produce trial-by-trial variation of postsynaptic potentials. Theoretical and experimental studies have aimed to understand schizophrenia in relation to noise and signal-to-noise ratio, which are promising concepts for understanding the symptoms that characterize this heterogeneous illness. Simulations of biologically realistic neural networks show how the functioning of NMDA (N-methyl-D-aspartate), GABA (g-aminobutyric acid) and dopamine receptors is connected to the concepts of noise and variability, and to related neurophysiological findings and clinical symptoms in schizophrenia