Publications

Objective: Whilst dopaminergic dysfunction remains a necessary component involved in the pathogenesis of schizophrenia, our current pharmacological armoury of dopamine antagonists does little to control the negative symptoms of schizophrenia. This suggests other pathological processes must be implicated. This paper aims to elaborate on such theories. Methods: Data for this review were sourced from the electronic database PUBMED, and was not limited by language or date of publication. Results: It has been suggested that multiple ‘hits’ may be required to unveil the clinical syndrome in susceptible individuals. Such hits potentially first occur in utero, leading to neuronal disruption, epigenetic changes and the establishment of an abnormal inflammatory response. The development of schizophrenia may therefore potentially be viewed as a neuroprogressive response to these early stressors, driven on by changes in tryptophan catabolite (TRYCAT) metabolism, reactive oxygen species handling and N-methyl d-aspartate (NMDA) circuitry. Given the potential for such progression over time, it is prudent to explore the new treatment strategies which may be implemented before such changes become established. Conclusions: Outside of the dopaminergic model, the potential pathogenesis of schizophrenia has yet to be fully elucidated, but common themes include neuropil shrinkage, the development of abnormal neuronal circuitry, and a chronic inflammatory state which further disrupts neuronal function. Whilst some early non-dopaminergic treatments show promise, none have yet to be fully studied in appropriately structured randomized controlled trials and they remain little more than potential attractive targets.

We report the case of a VIPoma diagnosed in a 15-year-old teenager who experienced profuse secretory diarrhea associated with hypokalemia, metabolic acidosis and high plasma levels of vasoactive intestinal peptide (VIP) and pancreatic polypeptide (PP). Angiography showed an abnormal mass in the head of the pancreas. Before surgery, subcutaneous injections (100 micrograms every 8 hours) of the long-acting somatostatin analogue octreotide or SMS 201-995, were administered in order to stabilize the clinical status of the patient and to reduce the intravenous administration of fluid and electrolytes. This treatment resulted in prompt relief of the symptoms and in a partial decrease of the plasma levels of VIP and PP. At subsequent laparotomy, there was a tumour localized in the head of the pancreas, which was completely removed by Whipple resection. The immunohistochemical staining revealed the presence of VIP and PP inside the tumour cells. Two years after surgical resection, the patient is healthy without clinical or laboratory evidence of recurrence.