Gene expression in the frontopolar cortex in schizophrenia
Medina AM, Waselus M, Krolewski DM, Barchas JD, Schatzberg AF, Myers RM, Akil H, Watson SJ Jr
Society for Neuroscience. 2018.
The Frontopolar cortex is one of the least studied areas of the human brain. Cytoarchitectonical studies catalogue it as Brodmann area 10, and functional imaging research suggest a role for this area in attentional control. In addition, it might also be involved in dynamically adjusting the contribution of internal and external information to moment–to-moment cognition.
Disturbances in the ability to discern between the information coming from external vs internal sources might be important in the context of disorders involving deficits in reality monitoring, as is the case in schizophrenia. Functional imaging studies have reported that schizophrenic patients show deficits in rostral prefrontal cortex activation, and it has been suggested that this might be related to patients’ deficits in reality monitoring. However, the underlining cellular dysfunctions that may be associated with these disturbances have not yet been studied.
In this study, we aim to analyze the differences in gene expression within the frontopolar cortex between postmortem brain tissue obtained from normal controls and schizophrenic subjects.
Materials and methods: Human brain blocks from the frontopolar cortex of 24 Schizophrenic subjects and 27 controls were obtained from the Brain Donor Program at the University of California, Irvine by agreement with the Pritzker Neuropsychiatric Consortium. The subjects included in the schizophrenic group met diagnostic criteria from the Diagnostics and Statistical Manual of Mental Disorders (DSM-V). In the control group there was no evidence of psychiatric or neurological disorders. Variables accounted for include gender, age and postmortem interval. All subjects used in the study had tissue pH above 6.5 and agonal factor scores (AFS) of zero. Fresh frozen blocks of tissue averaging 500 mg were dissected from the frontopolar region of each subject and processed for RNA extraction to be used for gene expression studies.
Results: Initial test RNA extractions from the fresh frozen tissue rendered adequate RIN values (average 8.1) and RNA content (average 590 ng/uL). Based on our previous results we will focus on reporting the effect of schizophrenia on the astrocytic network of the Frontopolar cortex and will describe gene expression patterns associated with glial activity in schizophrenic subjects compared to normal controls.