The role of the stress hormone prolactin and sex differences in early psychosis

In the last 20 years, a huge effort has been made to implement and apply the principles of early diagnosis and treatment, already well established in other branches of medicine, to the field of psychotic disorders. The goal of research on early detection was and still is to prospectively identify people at-risk of developing full-blown psychosis. However, until now it is still not possible to predict transition to psychosis with adequate accuracy. Therefore, the prospective Fruherkennung von Psychosen (Fepsy) study aims at improving early detection of psychosis via a multilevel assessment containing a systematic assessment of psychopathological symptoms, a neuropsychological examination, blood sampling, electroencephalography (EEG) and magnetic resonance imaging (MRI). The present dissertation addresses the role of the hormone prolactin in emerging psychosis on one hand and on the other hand aims to elucidate whether there are any sex differences in emerging psychosis specifically regarding the hormone prolactin, cognitive functioning and the correlation of self- and observer-ratings of psychopathology. In the first publication, the role of the hormone prolactin in early psychosis is discussed whereas the topic of possible sex differences is covered by all of the publications included in this dissertation (1, 2 and 3). The first study validates literature by providing further evidence for frequent hyperprolactinemia in emerging psychosis and that it can even be observed in antipsychotic-naive patients (>30%). Hence, prolactin is not necessarily elevated as a side effect of antipsychotics but can also be a pre-existing condition probably in relation with the function of prolactin as stress hormone. Furthermore, all three publications which are included in this dissertation consider the aspect of sex differences, which may help to elucidate pathogenic mechanisms underlying psychosis that are specific to women or men. The first study demonstrated higher prolactin levels in women even after correction for the normal biological variation in prolactin levels between the sexes, which potentially provides an indication for a sex dependant stress reaction regarding the hormone prolactin. The results of our second study suggest that sex differences in cognitive functioning in patients are not different from those seen in healthy controls (HC). Specifically, the female advantage in verbal learning and memory, which has frequently been found in HC seems to be equally present in patients with an at-risk mental state (ARMS) for psychosis as well as in patients with a first episode psychosis (FEP). The third study shows that the associations of self- and observer-ratings of psychopathology were rather low and generally not different for men and women. Therefore, the results imply that self-rating scales cannot be a substitute for the more time-consuming observer-rating scales neither for men nor for women. In summary, prolactin plays a possible role in emerging psychosis in relation with its function as stress hormone and stress reactivity seems to be enhanced in women. Overall, there were few sex differences which could have been shown in the second and third study. Regarding sex differences in cognitive functioning (publication 2), they resemble those of the general population and were not different between HC and patients (ARMS, FEP).