Microstructural white matter changes are correlated with the stage of psychiatric illness.

Microstructural white matter changes have been reported in the brains of patients across a range of psychiatric disorders. Evidence now demonstrates significant overlap in these regions in patients with affective and psychotic disorders, thus raising the possibility that these conditions share common neurobiological processes. If affective and psychotic disorders share these disruptions, it is unclear whether they occur early in the course or develop gradually with persistence or recurrence of illness. Utilisation of a clinical staging model, as an adjunct to traditional diagnostic practice, is a viable mechanism for measuring illness progression. It is particularly relevant in young people presenting early in their illness course. It also provides a suitable framework for determining the timing of emergent brain alterations, including disruptions of white matter tracts. Using diffusion tensor imaging, we investigated the integrity of white matter tracts in 74 patients with sub-syndromal psychiatric symptoms as well as in 69 patients diagnosed with established psychosis or affective disorder and contrasted these findings with those of 39 healthy controls. A significant disruption in white matter integrity was found in the left anterior corona radiata and in particular the anterior thalamic radiation for both the patients groups when separately contrasted with healthy controls. Our results suggest that patients with sub-syndromal symptoms exhibit discernable early white matter changes when compared with healthy control subjects and more significant disruptions are associated with clinical evidence of illness progression.

In vivo glutathione levels in young persons with bipolar disorder: a magnetic resonance spectroscopy study.

Oxidative stress has recently been reported to assume a significant role in the pathophysiology of bipolar disorder. Several studies have demonstrated the replenishment of glutathione (GSH) diminishes oxidative cellular damage and ameliorates depressive symptoms in this disorder. Whilst the mechanism by which GSH exerts any clinical effect is unknown it has been proposed that it involves the bolstering of antioxidant defences by increasing the bioavailability of GSH, which in turn reverses clinical symptoms of depression. Such a proposal is predicated on the implicit assumption that GSH is diminished in these patients prior to GSH supplementation. However hitherto no study has reported in vivo measures of GSH in patients with bipolar disorder. Using magnetic resonance spectroscopy we obtained in vivo measures of GSH in young people with bipolar disorder and contrasted these with matched healthy controls. Young people with bipolar disorder were found to have no diminution in baseline GSH concentration and, furthermore, no significant correlations were found between GSH and clinical scores of depression or mania. The results do not support the hypothesis that oxidative stress is involved in the primary pathophysiology of bipolar disorder.

Distinct neurometabolic profiles are evident in the anterior cingulate of young people with major psychiatric disorders.

Currently, there are no validated neurobiological methods for distinguishing different pathophysiological pathways in young patients presenting in the early phases of major psychiatric disorders. Hence, treatments are delivered simply on the basis of their possible effects on nonspecific symptom constructs such as depression, cognitive change or psychotic symptoms. In this study, the ratios (relative to creatine) of key metabolites (N-acetyl aspartate, myoinositol, glutamate and glutathione) were measured with proton magnetic resonance spectroscopy ((1)H-MRS) within the anterior cingulate cortex of 88 young persons presenting with major mood or psychotic symptoms. We derived empirically (using a cluster analytical technique) three subgroups of subjects on the basis of their patterns of in vivo brain biochemistry. The three subgroups were distinguished (from each other) by all the four metabolites, in particular, glutathione and glutamate. By contrast, the groups could not be distinguished by differences in terms of other demographic, functional or clinical measures. We propose that this (1)H-MRS-based subclassification system could be used as the basis for much more specific tests of novel intervention strategies (notably, antioxidant and glutamatergic therapies) early in the course of major psychiatric disorders.