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

Interpersonal violence, early life adversity, and suicidal behavior in hypersexual men

There are significant gaps in knowledge regarding the role of childhood adversity, interpersonal violence, and suicidal behavior in hypersexual disorder (HD). The aim of this study was to investigate interpersonal violence in hypersexual men compared with healthy volunteers and the experience of violence in relation to suicidal behavior. Methods This case–control study includes 67 male patients with HD and 40 healthy male volunteers. The Childhood Trauma Questionnaire – Short Form (CTQ-SF) and the Karolinska Interpersonal Violence Scale (KIVS) were used for assessing early life adversity and interpersonal violence in childhood and in adult life. Suicidal behavior (attempts and ideation) was assessed with the Mini-International Neuropsychiatric Interview (version 6.0) and the Montgomery–Åsberg Depression Rating Scale – Self-rating. Results Hypersexual men reported more exposure to violence in childhood and more violent behavior as adults compared with healthy volunteers. Suicide attempters (n = 8, 12%) reported higher KIVS total score, more used violence as a child, more exposure to violence as an adult as well as higher score on CTQ-SF subscale measuring sexual abuse (SA) compared with hypersexual men without suicide attempt. Discussion Hypersexuality was associated with interpersonal violence with higher total scores in patients with a history of suicide attempt. The KIVS subscale exposure to interpersonal violence as a child was validated using the CTQ-SF but can be complemented with questions focusing on SA for full assessment of early life adversity. Conclusion Childhood adversity is an important factor in HD and interpersonal violence might be related to suicidal behavior in hypersexual men

Cortisol levels and suicidal behavior: a meta-analysis

Suicide is a major cause of death worldwide, responsible for 1.5% of all mortality. The causes of suicidal behavior are not fully understood. Dysregulated hypothalamic-pituitary-adrenal (HPA) axis activity, as measured by cortisol levels, is one potential risk factor. This meta-analytic review aimed i) to estimate the strength and variability of the association between naturally fluctuating cortisol levels and suicidal behavior and ii) to identify moderators of this relationship. A systematic literature search identified 27 studies (N = 2226; 779 suicide attempters & 1447 non-attempters) that met the study eligibility criteria from a total of 417 unique records initially examined. Estimates of effect sizes (r) obtained from these studies were analysed using Comprehensive Meta-Analysis. In these analyses, we compared participants identified as having a past history of suicide attempt(s) to those with no such history. Study quality, mean age of sample and percentage of male participants were examined as potential moderators. Overall, there was no significant effect of suicide group on cortisol. However, significant associations between cortisol and suicide attempts were observed as a function of age. In studies where the mean age of the sample was below 40 years the association was positive (i.e., higher cortisol was associated with suicide attempts; r = .234, p < .001), and where the mean age was 40 or above the association was negative (i.e., lower cortisol was associated with suicide attempts; r = - .129, p < .001). These findings confirm that HPA axis activity, as indicated by age-dependent variations in cortisol levels, is associated with suicidal behavior. The challenge for theory and clinical practice is to explain the complete reversal of the association with age and to identify its clinical implications

Mental health and adherence to covid-19 protective behaviors among cancer patients during the covid-19 pandemic: An international, multinational cross-sectional study

A population-based cross-sectional study was conducted during the first COVID-19 wave, to examine the impact of COVID-19 on mental health using an anonymous online survey, enrolling 9565 individuals in 78 countries. The current sub-study examined the impact of the pandemic and the associated lockdown measures on the mental health, and protective behaviors of cancer patients in comparison to non-cancer participants. Furthermore, 264 participants from 30 different countries reported being cancer patients. The median age was 51.5 years, 79.9% were female, and 28% had breast cancer. Cancer participants reported higher self-efficacy to follow recommended national guidelines regarding COVID-19 protective behaviors compared to non-cancer participants (p < 0.01). They were less stressed (p < 0.01), more psychologically flexible (p < 0.01), and had higher levels of positive affect compared to non-cancer participants. Amongst cancer participants, the majority (80.3%) reported COVID-19, not their cancer, as their priority during the first wave of the pandemic and females reported higher levels of stress compared to males. In conclusion, cancer participants appeared to have handled the unpredictable nature of the first wave of the pandemic efficiently, with a positive attitude towards an unknown and otherwise frightening situation. Larger, cancer population specific and longitudinal studies are warranted to ensure adequate medical and psychological care for cancer patients

Mental health and adherence to covid-19 protective behaviors among cancer patients during the covid-19 pandemic: An international, multinational cross-sectional study

A population-based cross-sectional study was conducted during the first COVID-19 wave, to examine the impact of COVID-19 on mental health using an anonymous online survey, enrolling 9565 individuals in 78 countries. The current sub-study examined the impact of the pandemic and the associated lockdown measures on the mental health, and protective behaviors of cancer patients in comparison to non-cancer participants. Furthermore, 264 participants from 30 different countries reported being cancer patients. The median age was 51.5 years, 79.9% were female, and 28% had breast cancer. Cancer participants reported higher self-efficacy to follow recommended national guidelines regarding COVID-19 protective behaviors compared to non-cancer participants (p < 0.01). They were less stressed (p < 0.01), more psychologically flexible (p < 0.01), and had higher levels of positive affect compared to non-cancer participants. Amongst cancer participants, the majority (80.3%) reported COVID-19, not their cancer, as their priority during the first wave of the pandemic and females reported higher levels of stress compared to males. In conclusion, cancer participants appeared to have handled the unpredictable nature of the first wave of the pandemic efficiently, with a positive attitude towards an unknown and otherwise frightening situation. Larger, cancer population specific and longitudinal studies are warranted to ensure adequate medical and psychological care for cancer patients. © 2021 by the authors. Licensee MDPI, Basel, Switzerland

Depressive symptoms in higher education students during the COVID-19 pandemic: the role of containment measures

Background Students are a vulnerable group for the indirect impact of the COVID-19 pandemic, particularly their mental health. This paper examined the cross-national variation in students’ depressive symptoms and whether this can be related to the various protective measures implemented in response to the initial stage of the COVID-19 outbreak. Methods Student data stem from the COVID-19 International Student Well-being Study, covering 26 countries during the first wave of the COVID-19 pandemic. Country-level data on government responses to the COVID-19 pandemic were retrieved from the Oxford COVID-19 Tracker. Multilevel analyses were performed to estimate the impact of the containment and economic support measures on students’ depressive symptoms (n = 78 312). Results School and workplace closures, and stay-at-home restrictions were positively related to students’ depressive symptoms during the COVID-19 pandemic, while none of the economic support measures significantly related to depressive symptoms. Countries’ scores on the index of these containment measures explained 1.5% of the cross-national variation in students’ depressive symptoms (5.3%). This containment index’s effect was stable, even when controlling for the economic support index, students’ characteristics, and countries’ epidemiological context and economic conditions. Conclusions Our findings raise concerns about the potential adverse effects of existing containment measures (especially the closure of schools and workplaces and stay-at-home restrictions) on students’ mental health

The Role of Perceived Organizational Support in Mental Health of Healthcare Workers During the COVID-19 Pandemic: A Cross-Sectional Study

Background: Data support the link between the coronavirus disease 2019 (COVID-19) pandemic and mental distress in healthcare workers (HCWs). Although previous studies have documented the association between organizational policies and employees' psychological and mental status, there is still scant evidence regarding the effect of perceived organizational support (POS) on mental distress in HCWs during the pandemic. Aims: The present study aimed to assess the association between POS and mental distress in HCWs during the COVID-19 pandemic. The role of POS in stress, depressive and trauma symptoms in HCWs was investigated. Methods: This was an online cross-sectional study in 424 HCWs. Data were collected during the first wave of the pandemic, and included demographics, a 7-item questionnaire assessing POS, the “Patient Health Questionnaire” assessing depressive symptoms, the “Impact of Events Scale Revised,” measuring post-traumatic stress disorder (PTSD) symptoms and the “Perceived Stress Scale” assessing perceived stress. Results: The mean POS score was 3.33 [standard deviation:1.85; range 0–7]. Younger (p < 0.001), less experienced (p < 0.001), female (p = 0.002), and non-physician HCWs (p = 0.031) were more likely to report lower self-perceived organizational support than older, male, more experienced physicians. Self-perceived organizational support was significantly and negatively associated with and self-assessed intensity of stress, depressive and traumatic symptoms, after adjusting for putative confounders (p < 0.001). Discussion: Self-perceived organizational support was significantly associated with HCWs' self-assessed mental status during the pandemic. Organizational support and mental distress should be addressed simultaneously in HCWs during the COVID-19 pandemic to increase resilience among them

GWAS studies reveal a possible genetic link between cancer and suicide attempt

Inuit is the population with the highest incidence of suicide attempt and cancer in the world. Previous studies reported that people attempted suicide have a higher future risk for cancer. In view of these data, the largest available genome wide association studies (GWAS) for four major mental disorder groups were screened here for any common genes with all known cancer associated genes and oncogenes/tumor suppressor genes. A common genetic background came out only between suicide attempt and cancer (cancer associated genes analysis: RR = 1.64, p = 7.83 × 10−5; oncogenes/tumor suppressor genes analysis: RR = 2.55, p = 2.82 × 10−22), this supporting existing epidemiological data. Incidence/prevalence of both conditions was found to correlate with extreme cold geographical regions (adjusted R2 = 0.135, p = 3.00 × 10−4); this is not the case for other mental disorders. Our results show a possible genetic link between suicide attempt and cancer and a possible evolutionary connection of both diseases with extreme cold environments. These data are useful for future molecular studies or even for investigation of possible therapeutic protocols