**12. References**

[1] Abel KM, Heatlie HF, Howard LM, Webb RT. Sex- and age-specific incidence of fractures in mental illness: a historical, population-based cohort study. J Clin Psychiatry. 2008;69:1398-403

4. **Can genetics help us predict individual responses to potentially prolactin-elevating antipsychotics?** Data allow us to predict which antipsychotics are more likely to elevate prolactin but not with any precision. Potentially any patient given any antipsychotic may have prolactin elevation ranging from small to large. In the future, one can imagine that genetics will better help us understand which patients are more at risk of adverse events associated with individual antipsychotics and also their likelihood of a clinical response. Genetic variation is likely to contribute substantially. Certainly this work is ongoing in the area of weight change with antipsychotic treatment and we can expect

5. **Can antipsychotic polypharmacy be a potential treatment option?** Aripiprazole is already cited as a potential treatment option as an additive treatment in the influential Maudsley guidelines (Taylor et al, 2009). With the increasing availability of generic antipsychotic options over the next decade one can envisage a greater degree of polypharmacy similarly designed to reduce or prevent specific adverse events. Prolactin is one area where at least five established antipsychotics are cited as not usually associated with hyperprolactinaemia (Taylor et al, 2009). Such experimental combinations have not been well researched to date and will require a solid trial base

6. **How important is the prolactin receptor in terms of cancer?** The prolactin signalling cascade may be important in the pathology of breast and prostate cancers. The antagonism of the prolactin receptor and its pathways may also be important. As we learn the molecular and genetic perspectives of the role of prolactin and its signalling pathways, we may learn more about any potential role of antipsychotic treatments and

Long-term antipsychotic treatment currently represents a usual outcome for patients with schizophrenia and bipolar disorder. Hyperprolactinaemia can be measured in between 33- 69% of patients in antipsychotic studies and many antipsychotics significantly elevate prolactin with no suggestion of any longer term decline in prolactin levels. Hyperprolactinaemia can no longer be regarded in any sense as a benign abnormality and it may have significant potential short- and potential longer term consequences. Whereas the short-term adverse events are more easily detectable, the potential longer term consequences may remain hidden and undetectable until a bone fracture or cancer emerges. Over the last 10 years, patients receiving biologics to treat rheumatoid arthritis have been entered into voluntary, long-term databases that have addressed, albeit in a naturalistic manner, incidence of potentially associated adverse events (cancers, reactivation of TB, serious infections). There is a need to formally determine the longer term harm of untreated hyperprolactinaemia in psychiatry. In addition, future research needs to focus on the risk-

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fractures in mental illness: a historical, population-based cohort study. J Clin

that pharmacogenetics may play a critical role (Reynolds, 2007).

before definitive conclusions can be drawn.

**11. Conclusion** 

**12. References** 

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**24** 

**Tolerance to Tick-Borne** 

Giuseppe Rubino and Ferruccio Petazzi

Elisa Pieragostini, Elena Ciani,

*University of Bari* 

*Italy* 

**Diseases in Sheep: Highlights of a Twenty-Year** 

The European landscape is characterised by a range of diverse farming systems. These relate not only to varied geographical environments and animal genetic resources, but also to different social and cultural contexts for farming and food production. This diversity is unique to Europe and, among the European countries, Italy is the home for a great variety of native breeds because of its complex orography and its long boot shape with very different climatic conditions from north to south. In the 1980's, two of us moved from northern Italy to Apulia and soon came to appreciate the differences between the biotic and abiotic features of northern environment and the Apulian one. One of the most impressive differences were the enzootic tick borne diseases (TBD) and the related responses of the animals. As a consequence, much of our professional life has been devoted to the challenges posed by the diseases and to the study of the genetic peculiarities of native breeds both *per* 

This report is a review of the results obtained in a 20-year experience investigating the haematological features and tolerance to tick-borne diseases in Mediterranean native sheep breeds - mainly Apulian native breeds - compared to exotic breeds under various experimental conditions. In the wake of William Thomson (Lord Kelvin), a pioneer in thermodynamics and electricity, who said in 1891 that when you can measure what you are speaking about, and express it in numbers, you know something about it, but when you cannot measure it, your knowledge is of a meager and unsatisfactory kind, the central concept or research theme that guided all our research efforts stems from the notion that direct measurement of disease phenotypes and/or physiological features such as the hematological pattern provides a direct assay for measuring disease changes and the attitude of a genetic pool in facing disease. The work is concerned with the following main

**1. Introduction** 

issues:

*se* and in terms of their tolerance to TBD.

Haematological pattern of Apulian native sheep breeds

Response to *Anaplasma ovis* infection in experimentally infected sheep.

 Breeds and tolerance to TBD in Apulia Response to experimental anaemia

**Experience in a Mediterranean Environment** 

