Effect that the t(1;11) translocation and mental disorders have on glutamate and NAA levels in the prefrontal lobe, as measured by MRS

1H-Magnetic Resonance Spectroscopy (MRS) is a MRI paradigm that allows the levels of specific metabolites to be estimated in vivo [1]. This means that insights into the biochemical changes associated with a rare genetic change that raises the risk of mental disorders, and the impact of having a mental disorder, can potentially be made. In this study the levels of glutamate and N-acetyl-aspartate (NAA) were measured at 3T field strength in three separate voxels: right dorsolateral prefrontal cortex (DLPFC), left DLPFC and the anterior cingulate cortex (ACC). This thesis reports that members of a family that carry a unique t(1;11)(q42.2;q14) translocation that affects DISC1 have a substantially raised risk of developing a range of mental disorders, including bipolar affective disorder, schizophrenia and depression. A genetic change that leads to an increase in the susceptibility to a range of mental disorders is in line with other genetic studies that have been recently reported [2, 3]. The translocation was associated with a significant reduction in right DLPFC glutamate (mean difference= -2.11, CI= -0.24: -3.98, p=0.029) and left DLPFC NAA (mean difference= -1.97, CI= -0.34: -3.61, p=0.020). Changes in these metabolites offer some support to studies in cells and rodents trying to understand the impact of the t(1;11) translocation. More specifically the results offer support to studies that have linked alterations in DISC1’s molecular biology to changes in glutamate receptors and mitochondrial function [4-6]. The results need to be interpreted with some caution due to the small sample size and the lack of a significant effect in the bilateral DLPFCs. People with a major mental disorder were also found to have significantly lower levels of glutamate in the left DLPFC (F=3.16, p=0.047). When compared to controls the reductions were significant in the people with a diagnosis of schizophrenia (mean difference= -0.86, CI= -0.19: -1.51, p=0.012), but not in people with bipolar affective disorder. Glutamate levels were significantly correlated with negative symptoms in people with schizophrenia (SANS r= -0.44, CI= -0.07: - 0.70, p= 0.024). The effect of experiencing depressive symptoms was also evaluated due to support for a link in previous studies [7, 8]. Whist the participants were not recruited due their experience of depressive symptoms, metabolite levels were found to be significantly associated with depressive symptoms in all participants with a mental disorder (all three voxels, both NAA and glutamate p