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

Abstract

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.

Structural Brain Imaging Studies Offer Clues about the Effects of the Shared Genetic Etiology among Neuropsychiatric Disorders

“…The high sMRI correlation between SCZ and BD is consistent with prior reports of sMRI similarities between the two disorders (26). Moreover, a large body of literature reports substantial etiologic overlap between the two disorders (27)(28)(29)(30)(31). Because of such data, the SCZ and BD have been described as sharing a continuum of etiology leading to psychotic (32), neurophysiological (32) and neurocognitive (33) symptoms.…”

“…The ENPACT study (33) showed shared fronto-temporo-occipital grey matter volume deficits in the right hemisphere of two disorders. A systematic review of associations between functional MRI activity and polygenic risk for SCZ and BD (27) reported that genetic load for these disorders affects taskrelated recruitment of predominantly frontal lobe brain regions.…”

Schizophrenia Polygenic Risk and Brain Structural Changes in Methamphetamine-Associated Psychosis in a South African Population

“…As the knowledge and evidence of imaging genetics increases, more nuanced structural and functional brain measures are being studied. For example, measures of brain connectivity and of task-dependent recruitment of multiple brain regions may be associated with genetic variation in psychosis ( Ranlund et al, 2017 ; Dezhina et al, 2019 ; Cao et al, 2020 ). Added to this, advanced methodological approaches integrating environmental exposures, gene-gene interactions, and epigenetics from a variety of ancestral cohorts, are needed to fully appreciate missing heritability ( Mufford et al, 2017 ; Alnæs et al, 2019 ).…”

Adjunct ketamine treatment effects on treatment-resistant depressive symptoms in chronic treatment-resistant schizophrenia patients are short-term and disassociated from regional homogeneity changes in key brain regions – a pilot study

“…Atypical brain activity findings have been reported for both schizophrenia [28][29][30] and major depressive disorder [31][32][33]. Interestingly, some similarities have been identified between schizophrenia-and major depressive disorder-related brain alteration patterns, particularly in regional homogeneity (ReHo) data, which represent local temporal homogeneity of regional blood oxygen level-dependent signals and can be used to assess resting-state neural activity [34][35][36][37][38][39].…”