1. INTRODUCTION The stress diathesis hypothesis of psychosis is one of the most prevailing models of the aetiopathology of psychotic disorders. Cortisol is the most researched stress hormone yet its role in First Episode Psychosis,(FEP), has only recently been under investigation. A SYSTEMATIC REVIEW ON THE ROLE OF CORTISOL IN FIRST EPISODE OF PSYCHOSIS (FEP) AND RELATED PSYCHOPATHOLOGICAL IMPLICATIONS E Karanikas 1, D Antoniadis 2, T Serafeim 1, G Garyfallos 2 1 424 General Military Hospital, Psychiatric Clinic, Thessaloniki, Greece 2 Aristotle University, 2 nd Psychiatric Department, Thessaloniki, Greece

2. HYPOTHESIS Thus the aim of the present study is to systematically review the evidence concerning the hypothesis that cortisol might play a role in FEP and can be associated with psychopathology A SYSTEMATIC REVIEW ON THE ROLE OF CORTISOL IN FIRST EPISODE OF PSYCHOSIS (FEP) AND RELATED PSYCHOPATHOLOGICAL IMPLICATIONS E Karanikas 1, D Antoniadis 2, T Serafeim 1, G Garyfallos 2 1 424 General Military Hospital, Psychiatric Clinic, Thessaloniki, Greece 2 Aristotle University, 2 nd Psychiatric Department, Thessaloniki, Greece

3. METHODS We systematically searched the internet search machines for medical data using the following key words or phrases “FEP”, “psychosis”and ”cortisol”, “HPA axis” and “psychopathology” from 1990 up to 2013. A SYSTEMATIC REVIEW ON THE ROLE OF CORTISOL IN FIRST EPISODE OF PSYCHOSIS (FEP) AND RELATED PSYCHOPATHOLOGICAL IMPLICATIONS E Karanikas 1, D Antoniadis 2, T Serafeim 1, G Garyfallos 2 1 424 General Military Hospital, Psychiatric Clinic, Thessaloniki, Greece 2 Aristotle University, 2 nd Psychiatric Department, Thessaloniki, Greece

4. RESULTS RESULTS We sorted out 22 studies with 911 patients and 697 Healthy Controls,(HC). Higher cortisol levels in blood samples are consistently replicated. In contrast, the studies involving an estimation of cortisol levels in saliva at baseline as well as the ones evaluating Cortisol Awakening Response, (CAR), exhibited divergent results. Moreover, longitudinal studies favor the notion of upregulation of cortisol secretion in FEP and subsequent decrease of its levels after antipsychotic treatment. Regarding the more dynamic methods of evaluating cortisol’s reactivity after neuroendocrine or psychosocial stressors, again, the findings were minimal and divergent. In relation to the hypothesized cortisol’s association with psychotic symptomatology the evidence weighs towards no significant relation. Similarly, neither the affective parameters were significantly correlated with cortisol. A SYSTEMATIC REVIEW ON THE ROLE OF CORTISOL IN FIRST EPISODE OF PSYCHOSIS (FEP) AND RELATED PSYCHOPATHOLOGICAL IMPLICATIONS E Karanikas 1, D Antoniadis 2, T Serafeim 1, G Garyfallos 2 1 424 General Military Hospital, Psychiatric Clinic, Thessaloniki, Greece 2 Aristotle University, 2 nd Psychiatric Department, Thessaloniki, Greece

5. CONCLUSION/ CONCLUSION/DISCUSSION The literature related to basal cortisol levels in FEP is at a preliminary stage. Studies aiming to the evaluation of cortisol’s reactivity –fluctuation are even more minimal. Findings converge towards an elevation of cortisol secretion during FEP. The evidence suggests a role of cortisol in psychosis but the lack of specificity of the association of cortisol with psychopathological symptoms render this field of interplay obscure. Future research should be more focused on more pure diagnostic entities, clearly defined stages of the disorder and refined methods of hormonal measurement. A SYSTEMATIC REVIEW ON THE ROLE OF CORTISOL IN FIRST EPISODE OF PSYCHOSIS (FEP) AND RELATED PSYCHOPATHOLOGICAL IMPLICATIONS E Karanikas 1, D Antoniadis 2, T Serafeim 1, G Garyfallos 2 1 424 General Military Hospital, Psychiatric Clinic, Thessaloniki, Greece 2 Aristotle University, 2 nd Psychiatric Department, Thessaloniki, Greece

6. REFERENCES Borges S, Gayer-Anderson C, Mondelli V. (2013). A systematic review of the activity of the hypothalamic-pituitary-adrenal axis in first episode psychosis. Psychoneuroendocrinology. 38:603- 611 Bradley AJ, Dinan TG.(2010). A systematic review of hypothalamic-pituitary-adrenal axis function in schizophrenia:implications for mortality.J Psychopharmacol 24: 91-117 A SYSTEMATIC REVIEW ON THE ROLE OF CORTISOL IN FIRST EPISODE OF PSYCHOSIS (FEP) AND RELATED PSYCHOPATHOLOGICAL IMPLICATIONS E Karanikas 1, D Antoniadis 2, T Serafeim 1, G Garyfallos 2 1 424 General Military Hospital, Psychiatric Clinic, Thessaloniki, Greece 2 Aristotle University, 2 nd Psychiatric Department, Thessaloniki, Greece