We appreciate Drs Treuer and Karagianis interest in our work and their underscoring yet again the apparent complexity and multidisciplinary nature of the weight gain problems in patients with schizophrenia. The assertion that these problems may arise due to increases in ghrelin secretion from the stomach produced by the second-generation antipsychotic agents (SGAs) is however undermined by the following considerations: (a) preponderance of the studies reporting no or inverse relationship between plasma ghrelin levels and SGAs-induced weight gain (Togo et al, 2004; Palik et al, 2005; Theisen et al, 2005; Sporn et al, 2005; Hosojima et al, 2006); (b) the lack of reported evidence on ghrelin alterations in drug-free patients who are also prone for glucoregulatory abnormalities and for obesity; and (c) undetermined (primary vs secondary) mechanisms of the SGAs ghrelin effects. We have discussed the inconclusive ghrelin findings in the text (page 15) and in the tabulated format (Elman et al, 2006).

Nonetheless the letter by Drs Treuer and Karagianis raises an important question concerning reciprocity between central nervous system and gastrointestinal (GI) pathologies, the entity addressed by the discipline of neurogastroenterology. Indeed, embryonically, the central and the enteric nervous systems are derived from the same neural crest tissue and are subsequently linked via the vagus nerve. Furthermore, the GI tract is abundant with the same hormones and neurotransmitters that are mediating reward and homeostatic processes in the brain; to name a few, cholecystokinin, insulin, opiates, gamma-aminobutyric acid, dopamine, serotonin, glutamate, and norepinephrine. The GI concentrations of these chemicals are comparable to or are even exceed those in the brain (Gershon, 1998). Hence, it is in the realm of possible that the same prenatal lesion driving the development of schizophrenia neuropathology (Weinberger, 1987) may also result in corresponding alterations of the GI system, including impaired regulatory mechanisms of ghrelin secretion. Such a concept could gain indirect support from high prevalence of celiac disease in schizophrenic patients and their first-degree relatives (Eaton et al, 2004, 2006). In more general terms, the dynamic view of the brain–periphery interactions, rather than an either/or approach to the ailments afflicting both domains may provide heuristic value to clinical neuroscience and bring us closer to solving the mind–body mystery.

In sum, although available clinical evidence renders elevated ghrelin an unlikely cause of weight gain during SGAs therapy, further research in this area is warranted.