1. INTRODUCTION During last decades much evidence has been accumulated concerning the neuroendocrine aetiopathological basis of schizophrenia. Recently research has been shifted towards the prodromal phase of psychosis. During last decades much evidence has been accumulated concerning the neuroendocrine aetiopathological basis of schizophrenia. Recently research has been shifted towards the prodromal phase of psychosis. A SYSTEMATIC REVIEW OF NEUROENDOCRINE MECHANISMS IN AT RISK FOR PSYCHOSIS SUBJECTS AND RELATED PSYCHOPATHOLOGICAL IMPLICATIONS E Karanikas 1, S Archontidou 1, D Antoniadis 2, G Garyfallos 2 1 424 General Military Hospital, Psychiatric clinic, Thessaloniki, Greece 2 Aristotle University, 2 nd Psychiatric Department, Thessaloniki, Greece

2. Hypothesis The current review is the first one with systematic design aiming to delineate the hypothesis of circulating cortisol’s abnormalities and the potential association with psychopathological parameters in At Risk for Psychosis, (ARP), subjects. A SYSTEMATIC REVIEW OF NEUROENDOCRINE MECHANISMS IN AT RISK FOR PSYCHOSIS SUBJECTS AND RELATED PSYCHOPATHOLOGICAL IMPLICATIONS E Karanikas 1, S Archontidou 1, D Antoniadis 2, G Garyfallos 2 1 424 General Military Hospital, Psychiatric clinic, Thessaloniki, Greece 2 Aristotle University, 2 nd Psychiatric Department, Thessaloniki, Greece

3. Methods This systematic review was conducted with the aid of the Internet search machines of medical data. We used keywords or phrases such as ‘‘relatives/UHR/ARMS/ risk’’ in combination with, ‘‘stress/HPA axis/cortisol’’ and ‘‘psychosis” and “psychopathology” for the search A SYSTEMATIC REVIEW OF NEUROENDOCRINE MECHANISMS IN AT RISK FOR PSYCHOSIS SUBJECTS AND RELATED PSYCHOPATHOLOGICAL IMPLICATIONS E Karanikas 1, S Archontidou 1, D Antoniadis 2, G Garyfallos 2 1 424 General Military Hospital, Psychiatric clinic, Thessaloniki, Greece 2 Aristotle University, 2 nd Psychiatric Department, Thessaloniki, Greece

4. Results We sorted out 15 studies. We sorted out 15 studies. i)5 studies conducted on At Genetic Risk for Psychosis, (AGRP), subjects as being first degree relatives of psychotic patients and the rest referred to At Clinical Risk for Psychosis, (ACRP), subjects as per the Scale Of Prodromal Symptom Miller’s criteria or the Comprehensive Assessment for At Risk Mental State, Young’s criteria. One of the most consistent findings was increased cortisol levels in saliva. ii)The findings of cortisol in blood samples were minimal and less consistent. iii)The studies with longitudinal design, though with divergent results, hinted towards upregulation of total cortisol secretion prior to conversion to psychosis. iv)The studies regarding the evaluation of cortisol’s reactivity after application of either metabolic stressors or psychosocial ones exhibited no differentiation compared with the healthy control group or divergent results respectively. The hypothesized relation of psychotic symptomatology with cortisol in ARP subjects was not confirmed by the majority of the studies. On the contrary, the anxiety parameter and stress intolerance index both showed significant association with cortisol A SYSTEMATIC REVIEW OF NEUROENDOCRINE MECHANISMS IN AT RISK FOR PSYCHOSIS SUBJECTS AND RELATED PSYCHOPATHOLOGICAL IMPLICATIONS E Karanikas 1, S Archontidou 1, D Antoniadis 2, G Garyfallos 2 1 424 General Military Hospital, Psychiatric clinic, Thessaloniki, Greece 2 Aristotle University, 2 nd Psychiatric Department, Thessaloniki, Greece

5. Discussion/ Conclusion The literature related to the cortisol levels’ evaluation at prodrome is hitherto minimal. Although the evidence favor cortisol’s participation in the pathophysiology of psychosis the exact cause effect sequence and the intertwining of cortisol with psychopathology are unclear A SYSTEMATIC REVIEW OF NEUROENDOCRINE MECHANISMS IN AT RISK FOR PSYCHOSIS SUBJECTS AND RELATED PSYCHOPATHOLOGICAL IMPLICATIONS E Karanikas 1, S Archontidou 1, D Antoniadis 2, G Garyfallos 2 1 424 General Military Hospital, Psychiatric clinic, Thessaloniki, Greece 2 Aristotle University, 2 nd Psychiatric Department, Thessaloniki, Greece

6. References 1. Corcoran CM, Smith C, McLaughlin D, auther A, Malaspina D, Cornblatt B.(2012). HPA axis function and symptoms in adolescents at clinical high risk for schizophrenia. Schizophr Res135:170-174 2. Thompson KN, Philips LJ, Komesaroff P, Yuen HP, Wood SJ, Pantelis C, Velakoulis D, Yung AR, McGorry PD. (2007) Stress and HPA axis functioning in young people at ultra high risk for psychosis. J Psychiatr Res. 41:561-569 A SYSTEMATIC REVIEW OF NEUROENDOCRINE MECHANISMS IN AT RISK FOR PSYCHOSIS SUBJECTS AND RELATED PSYCHOPATHOLOGICAL IMPLICATIONS E Karanikas 1, S Archontidou 1, D Antoniadis 2, G Garyfallos 2 1 424 General Military Hospital, Psychiatric clinic, Thessaloniki, Greece 2 Aristotle University, 2 nd Psychiatric Department, Thessaloniki, Greece