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

Prediction and prevention of suicide in patients with unipolar depression and anxiety

Epidemiological data suggest that between 59 and 87% of suicide victims suffered from major depression while up to 15% of these patients will eventually commit suicide. Male gender, previous suicide attempt(s), comorbid mental disorders, adverse life-situations, acute psycho-social stressors etc. also constitute robust risk factors. Anxiety and minor depression present with a low to moderate increase in suicide risk but anxiety-depression comorbidity increases this risk dramatically Contrary to the traditional psychoanalytic approach which considers suicide as a retrospective murder or an aggression turned in-wards, more recent studies suggest that the motivations to commit suicide may vary and are often too obscure. Neurobiological data suggest that low brain serotonin activity might play a key role along with the tryptophan hydroxylase gene. Social factors include social support networks, religion etc. It is proven that most suicide victims had asked for professional help just before committing suicide, however they were either not diagnosed (particularly males) or the treatment they received was inappropriate or inadequate. The conclusion is that promoting suicide prevention requires the improving of training and skills of both psychiatrists and many non-psychiatrists and especially GPs in recognizing and treating depression and anxiety. A shift of focus of attention is required in primary care to detect potentially suicidal patients presenting with psychological problems. The proper use of antidepressants, after a careful diagnostic evaluation, is important and recent studies suggest that successful acute and long-term antidepressant pharmacotherapy reduces suicide morbidity and mortality

Effects of Bisphenol-A and Other Endocrine Disruptors Compared With Abnormalities of Schizophrenia: An Endocrine-Disruption Theory of Schizophrenia

In recent years, numerous substances have been identified as so-called “endocrine disruptors” because exposure to them results in disruption of normal endocrine function with possible adverse health outcomes. The pathologic and behavioral abnormalities attributed to exposure to endocrine disruptors like bisphenol-A (BPA) have been studied in animals. Mental conditions ranging from cognitive impairment to autism have been linked to BPA exposure by more than one investigation. Concurrent with these developments in BPA research, schizophrenia research has continued to find evidence of possible endocrine or neuroendocrine involvement in the disease. Sufficient information now exists for a comparison of the neurotoxicological and behavioral pathology associated with exposure to BPA and other endocrine disruptors to the abnormalities observed in schizophrenia. This review summarizes these findings and proposes a theory of endocrine disruption, like that observed from BPA exposure, as a pathway of schizophrenia pathogenesis. The review shows similarities exist between the effects of exposure to BPA and other related chemicals with schizophrenia. These similarities can be observed in 11 broad categories of abnormality: physical development, brain anatomy, cellular anatomy, hormone function, neurotransmitters and receptors, proteins and factors, processes and substances, immunology, sexual development, social behaviors or physiological responses, and other behaviors. Some of these similarities are sexually dimorphic and support theories that sexual dimorphisms may be important to schizophrenia pathogenesis. Research recommendations for further elaboration of the theory are proposed

Plasma testosterone and dehydroepiandrosterone sulfate in male and female patients with dysthymic disorder

Background: Depressive symptomatology has been connected with an activation of the hypothalamus-pituitary-adrenal axis and, in several studies, with reduced androgen levels, while administration of androgens, usually in older subjects, may have positive effects on mood, both in males and females. Regarding dysthymic disorder (DD), low serum testosterone levels have been reported in older males, while information on younger male or on female patients is lacking. Methods: We assessed the serum levels of testosterone (T), dehydroepiandrosterone sulfate (DHEAS) and cortisol in male and female patients with DD, and compared them to the levels of sex and age matched controls. Eighteen male and 43 female patients in the age range of 22 to 71 years were studied and diagnosed according to the Scheduled Diagnostic Interview for DSM-IV axis I disorders (SCID). Depressive symptomatology was assessed using the Hamilton Depression Rating Scale. Subgroups with subjects below or over 50 years of age were also built and compared. Results: Serum T levels were lower than controls mainly in the subjects aged below 50 years, in both genders. More pronounced were reductions in DHEAS levels both in male and female patients, while cortisol levels were normal or reduced. T levels were positively correlated to both DHEAS and cortisol. The negative correlations of DHEAS and T to age were significant for all groups and subgroups, except in the group of male patients. Four male patients (22%) had T levels below 2.0 ng/ml. Conclusions: Male and female patients with DD aged below 50 years show reduced gonadal and adrenal androgen levels, and normal to low cortisol levels. These neuroendocrine characteristics differentiate DD from depression, and place this diagnostic group closer to posttraumatic stress disorder. (c) 2006 Elsevier B.V. All rights reserved

Neurochemical variables in subjects with adjustment disorder after suicide attempts

The investigation of biological correlates of suicidal behavior is important for identifying high-risk subjects. The objective of this study was to examine the neurochemical variables’ platelet MAO activity and urinary MHPG, 5HIAA and HVA, the main metabolites of noradrenaline, serotonin and dopamine, neurotransmitters that are considered to be involved in the pathophysiology of suicidal behavior, as well as plasma cortisol, in a group of subjects with adjustment disorder after a suicide attempt. Fifty-three patients, 42 females and 11 males, were included in the study and were compared to a group of 50 healthy controls, 25 females and 25 males. Platelet MAO activity was found to be significantly lower in both male and female patients compared to controls of the same sex (P &lt; 0.001 for both comparisons). 5HIAA and HVA were not different between patients and controls, but MHPG was significantly higher in the patients group (P = 0.008). Moreover, plasma levels of cortisol were significantly higher in the patients compared to the controls (P &lt; 0.001). Our results confirm the hypothesis of low platelet MAO activity as a biological characteristic of patients who attempt suicide. They also point to a possible parallel activation of the noradrenergic system. (C) 2000 Editions scientifiques et medicales Elsevier SAS

Biogenic amine turnover and serum cholesterol in suicide attempt

The investigation of biological correlates of suicidal behavior is important in searching for possible changes in neuronal systems activity related to that behavior, so that pharmacological interventions may be proposed, especially in high-risk subjects. In a sample of 111 subjects admitted in a general hospital after suicide attempt, we studied the turnover of neurotransmitters by measuring the urinary output of the main metabolites of serotonin, dopamine and noradrenaline (5-HIAA, HVA, MHPG respectively), as well as serum cholesterol, and compared them to those of a group of 62 healthy controls. Venous blood samples and urine samples were collected within 24 hours of admission. Psychiatric diagnosis was made according to DSM-IIIR criteria and assessment of suicide intent with Beck’s Suicidal Intent Scale (SIS). Fifty-four (54) subjects received the diagnosis of adjustment disorder, 25 of depression, 16 of schizophrenia and 16 of personality disorder. Fourteen subjects (14) had employed a violent mode of attempt. Urinary MHPG was found significantly higher in all diagnostic groups compared to controls. No difference was found concerning the excretion of HVA and 5-HIAA. Serum total cholesterol was found significantly lower both in violent and non-violent attempters compared to controls after correcting for age. No difference in serum cholesterol or MHPG was found between violent and non-violent attempts. Serum cholesterol and MHPG correlated negatively, while the correlations between cholesterol and 5-HIAA or HVA were not significant. Our results confirm previous reports of lower serum cholesterol in attempted suicide. They are also indicative of an increased noradrenaline turnover in subjects who attempt suicide, at least within 24 hours after the attempt. Whether this activation precedes or follows the attempt because of the specific stress, can not be answered at present

Gonadal axis hormones in psychiatric male patients after a suicide attempt

Epidemiological and clinical studies support the view that aggressive acts like suicidal and violent behaviors share a common substrate. Certain aspects of violence in males have been related to high testosterone levels, but the relation of testosterone to attempted suicide has not been studied until now. We estimated plasma levels of testosterone (T), LH, and FSH in 80 male subjects after a suicide attempt and in whom a psychiatric assessment was done during their hospitalization. Suicide intent was evaluated in 72 subjects. A group of 56 healthy males in the same age range served as control. As a group, attempters showed significantly lower T levels, marginally higher LH, and normal FSH compared to controls. The attempters who used violent methods (26 subjects) had T levels even lower than the non-violent (drug overdose) subgroup. Comparisons of T levels of subgroups according to the (main) drug ingested (analgesics, benzodiazepines, antidepressants, neuroleptics, or other drugs) did not reveal any significant drug effect. In relation to diagnosis, the lowest T levels were found in the subgroup with schizophrenia (29 subjects). The T levels of this subgroup were also significantly lower compared to those of a group of 31 male schizophrenic patients, hospitalized and treated with neuroleptics. If the influence of post-attempt stress and medical condition on plasma T could be ruled out, low plasma T may prove to be a biological predictor of attempt, at least in male schizophrenic patients. Nevertheless, the findings differentiate suicidal behavior from other aggressive/violent behaviors and do not support the notion that suicidal and aggressive behaviors are manifestations of the same impulse

Platelet MAO activity in patients with dysthymic disorder

The aim of the present study was to examine possible associations between platelet monoamine oxidase (MAO) activity and primary dysthymic disorder. For that purpose we estimated the enzyme activity in 58 patients (15 males and 43 females) selected according to DSM-III-R criteria and in 61 healthy controls (30 males and 31 females). Platelet MAO activities were found significantly lower in the female patients compared to female controls. Moreover, the enzyme activities were found to be even lower in the female patients who had attempted suicide. These differences did not exist in the male population. We could not find any associations of MAO activity to the age of the patients, the age of onset, the duration of dysthymia, or HAM-D and SCL-90R scores. Our findings are consistent with the hypothesis that platelet MAO activity is a trait-dependent indicator of vulnerability to dysthymic disorder and suicidality in our female population. (C) 1998 Elsevier Science Ireland Ltd