Neuroendocrine studies in suicide attempters and in hypersexual disorder

Early life adversity is associated with increased risk of high psychiatric disease, suicidal behavior as well as risky sexual behavior in adulthood. Altered functioning of several neurobiological systems, like the serotonergic system and the hypothalamic-pituitary-adrenal axis associated with suicidal behavior, may stem from both genetic and developmental causes. Adversity in early life has developmental effects on these systems that persist into adulthood. Other neuroendocrine systems such as oxytocin regulating social behavior and DHEA-S with multiple biological actions might also be implicated in suicidal behavior. Hypersexual disorder includes features of impulsivity, addiction, sexual desire deregulation and some aspects of hypersexual behavior are also associated with more suicidality. Neurobiological alterations in patients with hypersexual disorder are for the moment largely unknown. The aim of this PhD project was to investigate neuroendocrine systems with focus on HPA axis, Oxytocin and DHEAS in suicide attempters and in patients with Hypersexual Disorder. Focus was on early life adversity and violent behavior in relation to neuroendocrine biomarkers. Studies I-III: The clinical cohort consists of 28 medication free suicide attempters and 19 healthy volunteers who participated in this cross sectional and longitudinal study. CSF and plasma basal levels of oxytocin, cortisol, DHEA-S and CSF 5-HIAA levels were assessed. Suicide intent, depressive symptoms, interpersonal violence in childhood an adult life as well as childhood emotional climate were assessed with psychometric rating scales. All patients were followed up for cause of death. Results: Suicide attempters showed a trend for lower CSF oxytocin levels compared to healthy volunteers, CSF and plasma oxytocin was significantly negatively related to suicide intent especially in men and showed a trend for negative correlation with lifetime violent behavior. Revictimized suicide attempters had lower plasma oxytocin and a more negative childhood emotional climate compared to non revictimized suicide attempters. Higher CSF and plasma cortisol levels were also present in suicide attempters compared to healthy volunteers, whereas CSF DHEA-S levels were higher in male suicide attempters and CSF 5-HIAA levels lower in female suicide attempters respectively. CSF cortisol/DHEAS ratio was inversely correlated with exposure to interpersonal violence as a child adjusted for age, gender and depression severity in a regression analysis. In suicide prediction, suicide victims tended to have low CSF 5-HIAA and high CSF cortisol and suicide victims that were abused in childhood had higher CSF cortisol compared to suicide victims with low exposure to interpersonal violence as a child. Oxytocin or DHEA-S levels did not differ in suicide victims compared to survivors. Study IV: The study includes 67 male patients with hypersexual disorder and 39 healthy male volunteers. Basal morning plasma levels of cortisol and ACTH were assessed and the dexamethasone (0.5 mg) suppression test was performed with cortisol and ACTH measured post dexamethasone administration. Multiple psychometric rating scales were used for assessing sexual behavior, depressive symptoms and early life adversity. Results: Men with hypersexual disorder had higher DST-ACTH levels and were more often DST non-suppressors compared to healthy volunteers. Men with hypersexual disorder reported more depressive symptoms and early life adversity than healthy volunteers. Early life adversity and hypersexual behavior were negatively correlated with HPA axis measures in patients. In the regression analyses the diagnosis of hypersexual disorder was significantly associated with both DST non-suppression and higher plasma DST-ACTH even when adjusted for childhood trauma. Conclusion: Early life adversity, interpersonal violence and suicide intent are risk factors for suicide and oxytocin by modulating prosocial behaviors might thus be protective in individuals with high suicide risk. The role of DHEA-S in suicidal behavior is proposed to be through the effects of early life adversity and its implication to the allostatic load while other possible mechanisms cannot be excluded. The study on male patients with hypersexual disorder reports for the first time HPA axis dysregulation. LIST OF SCIENTIFIC PAPERS I. Jokinen J, Chatzittofis A, Hellström C, Nordström P, Uvnäs-Moberg K, Åsberg M. Low CSF oxytocin reflects high intent in suicide attempters. Psychoneuroendocrinology. 2012;37:482-490. II. Chatzittofis A, Nordström P, Hellström C, Arver S, Åsberg M, Jokinen J. CSF 5-HIAA, Cortisol and DHEAS levels in Suicide Attempters. European Neuropsychopharmacology. 2013;23(10):1280-1287. III. Chatzittofis A, Nordström P, Uvnäs-Moberg K, Åsberg M, Jokinen J. CSF and plasma oxytocin levels in suicide attempters, the role of childhood trauma and revictimization. Neuro Endocrinology Letters. 2014; 35(3):213-217. IV. Chatzittofis A, Arver S, Öberg K, Hallberg J, Nordström P, Jokinen J. HPA axis dysregulation in patients with hypersexual disorder. Psychoneuroendocrinology. 2016; 63:247-253. CONTENTS