Abstract
Inter-relationships ordinarily exist between mRNA expression of GABAA subunits in the frontopolar cortex (FPC) of individuals that had died suddenly from causes other than suicide. However, these correlations were largely absent in persons that had died by suicide. In the present investigation, these findings were extended by examining GABAA receptor expression patterns (of controls and depressed individuals that died by suicide) in the orbital frontal cortex (OFC), hippocampus, amygdala. locus coeruleus (LC) and paraventricular nucleus (PVN), all of which have been implicated in either depression, anxiety or stress responsivity. Using QPCR analysis, we found that in controls the inter-relations between GABAA subunits varied across brain regions, being high in the hippocampus and amygdala, intermediate in the LC, and low in the OFC and PVN. The GABAA subunit inter-relations were markedly different in persons that died by suicide, being reduced in hippocampus and amygdala, stable in the LC, but more coordinated in the OFC and to some extent in the PVN. It seems that altered brain region-specific inhibitory signaling, stemming from altered GABAA subunit coordination, are associated with depression/suicide. Although, it is unknown whether GABAA subunit re-organization was specifically tied to depression, suicide, or the accompanying distress, these data show that the coordinated expression of this transcriptome does vary depending on brain region and is plastic.
Highlights
Major depressive disorder (MDD) is a complex psychiatric illness that likely involves genetic, neurochemical and experiential factors (Caspi et al, 2003; Kendler et al, 2005; Millan, 2006)
Inter-relationships ordinarily exist between mRNA expression of GABAA subunits in the frontopolar cortex (FPC) of individuals that had died suddenly from causes other than suicide. These correlations were largely absent in persons that had died by suicide. These findings were extended by examining GABAA receptor expression patterns in the orbital frontal cortex (OFC), hippocampus, amygdala. locus coeruleus (LC) and paraventricular nucleus (PVN), all of which have been implicated in either depression, anxiety or stress responsivity
Using QPCR analysis, we found that in controls the inter-relations between GABAA subunits varied across brain regions, being high in the hippocampus and amygdala, intermediate in the LC, and low in the OFC and PVN.The GABAA subunit inter-relations were markedly different in persons that died by suicide, being reduced in hippocampus and amygdala, stable in the LC, but more coordinated in the OFC and to some extent in the PVN
Summary
Major depressive disorder (MDD) is a complex psychiatric illness that likely involves genetic, neurochemical and experiential factors (Caspi et al, 2003; Kendler et al, 2005; Millan, 2006). Considerable evidence has pointed to a role for serotonergic processes in subserving MDD (Maes and Meltzer, 1995; Pineyro and Blier, 1999), several other neurochemical mechanisms have been implicated in this disorder These have included growth factors, such as brain-derived neurotrophic factor (BDNF) (Duman and Monteggia, 2006; Shaltiel et al, 2007), corticotropin releasing hormone (CRH) and other peptides, including neuromedin B and somatostatin (Nemeroff, 1996; Reul and Holsboer, 2002; Merali et al, 2004, 2006). GABAA receptors are present in virtually all neurons of the central nervous systems, and play a fundamental role in controlling brain excitability (Fritschy and Brunig, 2003) These receptors are constructed of pentameric protein complexes (subunits) derived from a repertoire (cassette) of 21 different proteins/ genes. It was suggested that changes of the expression of GABAA receptor subunits might influence the timing of neuronal firing patterns, which ostensibly could have functional consequences associated with psychopathology
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
