|Year : 2016 | Volume
| Issue : 4 | Page : 193-199
Cortisol level in depressed patients and its relation with suicidal risk and anhedonia
Samia Ahmed, Fatma Moussa, Akmal Moustafa, Doaa R Ayoub MD
Psychiatry Department, Kasr El Ainy Hospital, Cairo University, Cairo, Egypt
|Date of Submission||02-Mar-2016|
|Date of Acceptance||29-Sep-2016|
|Date of Web Publication||17-Mar-2017|
Doaa R Ayoub
Psychiatry Department, Kasr El Ainy Hospital, Cairo University, Cairo, 12311
Source of Support: None, Conflict of Interest: None
In recent times, there has been an increased interest in research related to anhedonia. Nevertheless, its linkage to major depressive disorders and underlying neurobiology are still not well understood. High levels of cortisol are associated with an increased risk for suicide as evidenced by several studies; however, others have not found this association between cortisol levels and suicidality.
The aim of this work was to examine whether there is an increased activity of the hypothalamic–pituitary–adrenal axis in major depressive disorder patients and to detect the presence of an association between the level of cortisol and thoughts of death and anhedonia in at-risk patients with major depressive disorder.
Settings and design
This case–control study that was conducted on 20 patients with major depressive disorder, diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders, 4th ed., text revision, in comparison with 20 controls.
Patients and methods
All patients were assessed using the Present State Examination 10th revision of the Schedules of Clinical Assessment in Neuropsychiatry, Snaith Hamilton Pleasure Scale, Beck’s Suicidal Ideation Scale, and Beck’s Depressive Inventory. Blood samples were collected to assess plasma cortisol level in the morning and evening.
Statistical calculations were carried out using SPSS, version 15.
There were increased levels of morning and evening cortisol in major depressive disorder patients. Thoughts of death were positively associated with elevated morning cortisol in depression. Anhedonia was associated with higher evening cortisol level in depressed patients in the studied sample.
There are relatively increased levels of morning and evening cortisol in major depressive disorder patients in comparison with controls; thoughts of death are positively associated with elevated morning and evening cortisol level.
Keywords: anhedonia, cortisol, hypothalamic–pituitary–adrenal axis, major depressive disorder, thoughts of death
|How to cite this article:|
Ahmed S, Moussa F, Moustafa A, Ayoub DR. Cortisol level in depressed patients and its relation with suicidal risk and anhedonia. Egypt J Neurol Psychiatry Neurosurg 2016;53:193-9
|How to cite this URL:|
Ahmed S, Moussa F, Moustafa A, Ayoub DR. Cortisol level in depressed patients and its relation with suicidal risk and anhedonia. Egypt J Neurol Psychiatry Neurosurg [serial online] 2016 [cited 2017 Oct 23];53:193-9. Available from: http://www.ejnpn.eg.net/text.asp?2016/53/4/193/202375
| Introduction|| |
Most investigators would agree that one of the important findings in biological psychiatry is the hyperactivity of the hypothalamic–pituitary–Adrenocortical (HPA) axis observed in a significant group of patients with major depression ,,.
Anhedonia, which is defined as the decreased capacity to experience pleasure, is a central feature of Diagnostic and Statistical Manual of Mental Disorders, 4th ed. (DSM-IV) unipolar major depressive disorder (MDD) .
Investigation on the relationship of the HPA axis and anhedonia was carried out by Bogdan and Pizzagalli , who reported that an acute stressor blunted reward responsiveness − specifically, participants’ ability to modulate behavior as a function of rewards. Using the same probabilistic reward task, participants with high levels of perceived life stress were characterized by decreased reward responsiveness .
McGirr et al.  stated that dysregulation of the HPA axis is hypothesized to play a role in increasing susceptibility to suicidal behavior.
High levels of cortisol were associated with increased suicidal risk , and nonsuppression in the dexamethasone test has also been associated with an increased risk for suicide in depressed patients ,.
However, other studies have not found an association between cortisol response to the dexamethasone suppression test (DST) and suicidality ,.
The aim of this work was to examine whether there is an increased activity of the HPA axis in major depressive disorder patients, and to detect the presence of an association between the level of plasma cortisol and thoughts of death and anhedonia in the studied sample.
| Patients and methods|| |
This study was conducted on a nonrandomized purposive sample of 20 patients with major depressive disorder diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders, 4th ed., text revision (DSM IV-TR) after approval of the ethical committee, in comparison to 20 controls. Patients were selected from the outpatient clinic of the Psychiatry Department, Kasr El Aini Hospital, Cairo University.
All patients in the study were asked to provide written informed consent before starting the assessment.
After the initial diagnosis, the morning cortisol sample was collected from the participants and they were given an appointment to come in the evening to collect the evening cortisol sample and carry out psychometric assessments.
Twenty individuals matched in age and sex who did not experience/or have a past history of any psychiatric disorders and did not have first-degree relatives with psychiatric disorder comprised the control group.
Inclusion criteria were as follows: both sexes; age between 19 and 50 years; having major depressive disorder of either mild, moderate, or severe degree, provided it is not an episode of depression in the course of bipolar disorder; and not receiving any medications, substance, and/or electroconvulsive therapy in the last 6 months.
Patients refusing to participate, those having bipolar disorder, those below 19 years or above 50 years of age, patients who did not complete the required tests, those with any medical disorder that may affect the cortisol level (e.g. Cushing’s syndrome, pheochromocytoma, etc.), substance abusers, pregnant women or women taking oral contraceptive pills, patients receiving corticosteroid therapy, those having any major chronic disabling disease (e.g. stroke, systemic lupus erythematosis, etc.), and women in their postpartum period due to the hormonal changes in this period were excluded from the study.
- Full psychiatric examination using Present State Examination 10th revision of the Schedules of Clinical Assessment in Neuropsychiatry (PSE-10): The study by Sabry  illustrated that the short Arabic version of the PSE is a reliable interview with adequate levels of internal consistency.
- General Medical Examination to detect and exclude any medical condition.
- Psychometric assessment:
- Snaith Hamilton Pleasure Scale (SHAPS) : The Arabic version was obtained from Thomas et al. .
- Beck’s Suicidal Ideation Scale : It consists of 19 items that evaluate three dimensions of suicide ideation: active suicidal desire, specific plans for suicide, and passive suicidal desire. The English version was used.
- Beck’s Depression Inventory : It assesses mood, cognitive, and somatic symptoms of depression; it consists of 21 items. The English version was used.
- Laboratory tests and specimen collection:
Blood samples were collected between 8 and 9 a.m. and between 8 and 9 p.m. from all participants to assess plasma cortisol level.
Blood was drawn into plain tubes, preserved freezed at −4°C and then separated for subsequent measurement of cortisol in serum with the IMMULITE and IMMULITE 1000 analyzers by Simens (Simens Medical Solutions Diagnostics: Los Angeles, California, USA). The volume of serum required was 10 µl. Reference ranges for cortisol vary from laboratory to laboratory but are usually within the following ranges for blood: 8–9 a.m., 5–38 µg/dl; and 8–9 p.m., 3–15 µg/dl .
Statistical methods and analysis
Collected data in this study were analyzed using the statistical package for the social sciences (SPSS, version 15; SPSS Inc., Chicago, Illinois, USA). Qualitative variables were described as number and percentages and quantitative variables as mean±SD.
The χ2-test of statistical significance was used for comparison between different groups, in which qualitative variables are expressed as percentages when comparing categorical data. An exact test was used instead when the expected frequency was less than 5.
A statistical test for comparison of numerical variables between the study groups was performed for independent samples when comparing two groups. P value was used to indicate the level of significance (P<0.05 was considered significant). Linear relationships were examined with Pearson’s correlation coefficient.
| Results|| |
The mean age of patients was 31.00±8.76 years, whereas the mean age of the control group was 32.50±11.19 years. Overall, 90% of the depressed patients were female, whereas women constituted 60% of the control group and70% of the depressed patients were married, compared with 75% in the control group.
In the sample of depressed patients, 30% of them had an acute onset of illness, 70% had subacute onset, and none of them had a gradual onset. As regards the course of the illness, 60% of the patients had a stationary course and 40% had a progressive course; duration of the psychiatric illness ranged between 1 and 15 months, with a mean of 14.00±6.94 months.
In all, 80% of the patients had no family history of psychiatric disorder, 5% had a family history of psychiatric illness similar to the patient, and 15% of them had a family history of psychiatric illness dissimilar to the patient.
Psychometric assessment tools
As shown in [Table 1], 16 patients had suicidal ideas, acts, or plans, whereas none of the patients in the control group had suicidal ideas, acts, or plans.
As shown in [Table 2], we found that none of the patients had mild depression, whereas 50% of the patients had moderate depression and 50% had severe depression; there was a statistically significant difference between the depressed patients studied as regards the degree of depression (P=0.000).
[Table 3] illustrates that there was no statistically significant difference between patients as regards suicide risk, as none of the patients had low suicide risk, 30% had moderate suicide risk, and 70% had high suicide risk.
From [Table 4], we can see that the mean for SHAPS score was 10.85±2.32.
As shown in [Table 5], there were relatively increased levels of morning and evening cortisol in major depressive disorder patients compared with the control group, but there was no statistically significant difference as regards cortisol level in the morning (P=0.075) nor serum cortisol in the evening (P=0.311) between patients and controls.
|Table 5 Serum cortisol level (in the morning and evening) in the study sample|
Click here to view
As shown in [Table 6], there was a significant positive correlation between SHAPS score and Beck’s Depressive Inventory score (r=0.597). P is significant if r is at least 0.32.
|Table 6 The correlation between Snaith Hamilton Pleasure Scale, Beck’s Depression Inventory, and serum cortisol level in the depression group|
Click here to view
Moreover, there was a significant positive correlation between SHAPS score and serum cortisol level in the evening (r=0.446).
As shown in [Table 7], there was a statistically positive correlation between Beck’s Suicidal Ideation Scale score and Beck’s Depression Inventory score (r=0.830).
|Table 7 The correlation between Beck’s Suicidal Ideation Scale, Beck’s Depression Inventory, serum cortisol level, and Snaith Hamilton Pleasure Scale in the depression group|
Click here to view
Moreover, there was a statistically positive correlation between Beck’s Suicidal Ideation Scale score and SHAPS score (r=0.799), suggesting a proportionate relationship between anhedonia and suicidal ideation in MDD.
However, there was no correlation between the suicidal ideation scale and serum cortisol levels in the morning or evening.
As shown in [Table 8], there was a positive correlation between suicidal thoughts and serum cortisol level both in the morning and evening (r=0.918 and 0.410, respectively) showing a statistically significant difference (P=0.003 and 0.024, respectively). There was a positive correlation between loss of interest and serum cortisol level in the evening (r=0.685) showing a statistically significant difference (P=0.024). There is a proportionate relationship between suicidal thoughts and cortisol level in MDD.
|Table 8 The correlation between specific symptoms of Beck’s Depression Inventory and serum cortisol level in the studied group|
Click here to view
| Discussion|| |
This work was intended to study whether there is an increased activity of the HPA axis in major depressive disorder patients as demonstrated by assessing serum cortisol levels in the morning and evening and to detect the presence of an association between the level of serum cortisol and thoughts of death and anhedonia in a sample of depressed patients.
The mean age of the studied group was 31.00±8.76 years; selection of middle-aged patients was intended to avoid the adolescence period with its possible endocrinal changes. Moreover, older patients (aged >50 years) were excluded to avoid the higher level of diurnal cortisol secretion that advanced age can be associated with, as collaborated by Wrosch et al. .
The years of formal education ranged between 0 and 17 years, with a mean of 10.30±6.35 years, whereas in controls the years of formal education were the highest ranging between 0 and 18 and the mean was 12.30±5.165. Decreased mean years of formal education in depression might be due to the effect of depressive illness and symptoms of depressed mood, sense of hopelessness and helplessness, and decreased concentration, which affects the academic achievement in depressed individuals, as considered by Hawton et al. .
The mean for SHAPS score was 10.85±2.32. Anhedonia is a clinical symptom in depression and it rates highly in making a diagnosis of this disorder. The DSM IV-TR describes a ‘lack of interest or pleasure’ as a main symptom in diagnosing MDD .
There are relatively increased levels of morning and evening cortisol in major depressive disorder patients compared with the control group, but no statistically significant difference was found. The mean for serum cortisol level in the morning was 18.15±10.74 g/dl and it was 8.03±4.29 μg/dl for serum cortisol level in the evening. This is higher than that in the control group, in which the mean was 10.15±9.8 μg/dl for serum cortisol level in the morning and 3.43±1.38 μg/dl for serum cortisol level in the evening.
The results of this work are in agreement with much of the literature studies reporting HPA hyperactivity in individuals with depression; higher plasma cortisol levels are reported in MDD ,,,,. In an even larger meta-analysis, Stetler and Miller  and Cubała and Landowski  showed evidence for higher cortisol levels. Further, this evidence illustrated that depressed individuals displayed increased cortisol levels due to HPA axis dysfunction.
Most patients with depression present with hypercortisolemia both in plasma and CSF, increased cortisol response to adrenocorticotropic hormone (ACTH), and a deficient feedback mechanism, reflected in an abnormal dexamethasone suppression test as well as by enlarged pituitary and adrenal glands ,.
We also found a significant positive correlation between SHAPS score and Beck’s Depressive Inventory score. This is in agreement with the study by Leventhal et al.  on depressed individuals; they also found that hedonic capacity had a negative correlation with depression severity. Furthermore, imaging studies enabled Gorwood  and Walter et al.  to integrate the clinical dimension of anhedonia into a functional framework related to altered brain function in MDD.
However, Schrader  found in a follow-up study over 1-year period that, although depression severity was significantly reduced, anhedonia scores remained constant. This provided support for the view that in chronic depression anhedonia may have trait-like properties, and that the propensity toward anhedonic responses may occur irrespective of the depression severity.
There was a significant positive correlation between loss of pleasure as a symptom and serum cortisol level in the evening (r=0.387, P=0.001); as the level of serum cortisol in the evening increased, anhedonia increased ([Table 8]).
Similarly, there was a positive correlation between SHAPS score and serum cortisol level in the evening in the depression group (r=0.446, P=0.049).
The cross-sectional design of our study restricts conclusions about the direction of causality between increased cortisol levels and anhedonia.
The diurnal pattern of cortisol secretion has been well characterized and is typified by higher morning levels that decrease throughout the day. Flattened cortisol slope − that is, an attenuated decrease throughout the day – has been found to be associated with vulnerability toward psychiatric disorders .
In contrast, greater self-reported negative affect has been found to be associated with higher diurnal cortisol levels  and flatter diurnal cortisol slopes. Although the exact effects of disrupted diurnal cortisol secretion have not been determined, it appears to signal a deviation of normal HPA axis function, which is associated with pathology and affective disturbance.
Von Zerssen et al.  further stated that the coincidence of the time course of depressed mood and cortisol excretion in the patients was interpreted as reflecting a temporal relationship between diurnal mood swings in depression and the cortisol rhythm.
Overall, 50% of patients in this work suffered from severe depression, which was found to be characterized by anhedonic features and is often associated with hypercortisolemia, as found by Gold and Chrousos .
People suffering from anhedonia in association with depression generally have a better mood in the morning and they get worse in the evenings . These findings were consistent with those of Grippo et al. , who suggested that there is an important communication between the peripheral and central nervous systems in depression and that HPA system hyperactivity is associated with anhedonia, and increased central nervous system cortisol levels may be related to the severity of this anhedonia.
In addition, in this work, the presence of a positive statistically significant correlation between Beck’s Depressive Inventory score and Beck’s Suicidal Ideation Scale was found. The finding that major depressive disorder emerged as significant risk factors for suicide is consistent with previous research on psychiatric patients, in which severe depression showed a high long-term risk for suicide ,.
Moreover, there was a positive statistically significant correlation between Beck’s Suicidal Ideation Scale score and SHAPS score (P=0.799, r=0.000), suggesting that anhedonia is a risk factor for suicide.
Similarly, Fawcett et al.  found a relationship between anhedonia and committing suicide within 1 year. Similar finding was reported by Xie et al. , who studied 40 depressed outpatients and found that anhedonia was linked to suicidal behavior; most suicidal patients described a lack of pleasure in their life as a major reason for becoming suicidal. A suicidal mindset is manifested as decreased experience to hedonia.
In this work, there was also a significant positive correlation between suicidal thoughts and serum cortisol level both in the morning and evening.
Furczyk et al.  emphasized that there is clear evidence that the activity of certain neurobiological systems has a role in the pathophysiology of suicidal behavior. This includes hyperactivity of the HPA axis.
A large amount of evidence linking HPA axis dysfunction to suicidality has been published to date as evidenced by elevated cortisol levels in depressed patients .
HPA axis hyperactivity in depressed individuals was associated with future completed suicide, as found in the studies conducted by ,,.
In contrast, several studies have reported findings indicating no difference in cortisol levels based on a history of suicide attempts, prospectively observed attempts, or completed suicides ,. Other studies have even demonstrated evidence of lower HPA axis activity in individuals with suicide attempts ,.
Inconsistencies in results may be due to the effects of several factors. Yerevanian et al.  found that nearly all of the prospective studies of DST-nonsuppression results and later suicide were limited to inpatients or did not separate inpatients from outpatients in their analysis. In addition, inconsistencies may be attributed to demographic differences, mood state, diagnosis, illness severity, diagnostic comorbidities, and the phase of illness during which the blood sample was taken. Earlier in MDD excessive secretion of ACTH by the pituitary was noticed, leading to excessive secretion of cortisol from the adrenal cortex. Later in the illness, downregulation of the system occurs most likely secondary to chronically high levels of CRF, which is produced in the paraventricular nucleus of the hypothalamus in response to psychosocial stress and activates the HPA axis. It binds to the pituitary gland to induce the release of ACTH, which in turn stimulates the release of cortisol from the adrenal gland .
Clearly, measures of HPA axis activity alone cannot completely explain the causes for such a complex behavior as suicide .
Strengths and limitations
Our patients received no psychiatric intervention (electroconvulsive therapy, antipsychotics, antidepressants, and/or mood stabilizer) in the past 6 months, to eliminate the effect of psychotropic drugs on cortisol level as a potential confounding factor. Moreover, we did not include any patient with comorbid substance abuse in the past 6 months.
The limitation of this study was the small sample size due to the difficulty to locate patients to whom inclusion criteria apply.
| Conclusion|| |
There are relatively increased levels of morning and evening cortisol in major depressive disorder patients compared with the control group, suggesting hyperactivity of the HPA axis. Thoughts of death are positively associated with elevated morning and evening cortisol level. Both anhedonia and suicide risk are high in MDD, and anhedonia predicts suicidal tendencies in depression; the higher the anhedonia, the higher the suicidal ideations. This supports its use as a symptom in assessing suicide risk if replicable in further studies with a larger study sample.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Nemeroff CB, Neigh GN. Neuroendocrinology. In: Gelder M, Andreasen NA, Lopez-Ibor JJ, Geddes JR, editors. New oxford textbook of psychiatry. 2nd ed. New York, NY: Oxford UniversityPress, 2009. 160–168.
Von Werne Baes C, de Carvalho Tofoli SM, Martins CMS, Juruena MF. Assessment of the hypothalamic–pituitary–adrenal axis activity: glucocorticoid receptor and mineralocorticoid receptor function in depression with early life stress – a systematic review. Acta Neuropsychiatr 2012; 24:4–15.
Von Werne Baes C, Martins CMS, de Carvalho Tofoli SM, Juruena MF. Early life stress in depressive patients: HPA axis response to GR and MR agonist. Front Psychiatry 2014; 5:2.
American Psychiatric Association. Diagnostic and statistical manual of mental disorders, text revision. 4th ed. Washington, DC: American Psychiatric Press; 2002.
Bogdan R, Pizzagalli DA. Acute stress reduces reward responsiveness: implications for depression. Biol Psychiatry 2006; 60:1147–1154.
Pizzagalli DA, Bogdan R, Ratner KG, Jahn AL. Increased perceived stress is associated with blunted hedonic capacity: potential implications for depression research. Behav Res Ther 2007; 45:2742–2753.
McGirr A, Diaconu G, Berlim MT. Dysregulation of the sympathetic nervous system, hypothalamic-pituitary-adrenal axis and executive function in individuals at risk for suicide. J Psychiatry Neurosci 2010; 35:399–408.
Guzmán PD, Rodríguez MJ, Alfonso AP. Relationship between levels of salivary cortisol with depression and suicidal ideation. Eur Psychiatry 2011; 26:1631.
Fountoulakis KN, Iacovides A, Fotiou F. Neurobiological and psychological correlates of suicidal attempts and thoughts of death in patients with major depression. Neuropsychobiology 2004; 49:42–52.
Jokinen J, Ouda J, Nordström P. Noradrenergic function and HPA axis dysregulation in suicidal behaviour. Psychoneuroendocrinology 2010; 35:1536–1542.
Pitchot W, Reggers J, Pinto E. Catecholamine and HPA axis dysfunction in depression: relationship with suicidal behavior. Neuropsychobiology 2003; 47:152–157.
Jokinen J, Carlborg A, Martensson B. DST non-suppression predicts suicide after attempted suicide. Psychiatry Res 2007; 150:297–303.
Sabry N. Inter-rater reliability of the short arabic form of the present state examination. Egypt J Psychiatry 2009; 29:45–54.
Snaith RP, Hamilton M, Morley S, Humayan A, Hargreaves D, Trigwell P. A scale for the assessment of hedonic tone the Snaith-Hamilton Pleasure Scale. Br J Psychiatry 1995; 167:99–103
Thomas J, Al Ali M, Al Hashmi A, Rodriguez A. Convergent validity and internal consistency of an Arabic Snaith Hamilton Pleasure Scale. Int Perspect Psychol Res Pract Consult 2012; 1:46–51.
Beck A, Kovacs M, Weissman A. Assessment of suicidal intention: the Scale for Suicide Ideation. J Consult Clin Psychol 1979; 47:343–352.
Beck AT, Ward CH, Mendelson M. An inventory for measuring depression. Arch Gen Psychiatry 1961; 4:561–571.
Foster L, Dunn R. Single antibody technique for radioimmunoassay of cortisol in unextracted serum or plasma. Clin Chem 1974; 20:365.
Wrosch C, Miller GE, Lupien S, Pruessner JC. Diurnal cortisol secretion and 2-year changes in older adults’ acute physical symptoms: the moderating roles of negative affect and sleep. Health Psychol 2008; 27:685–693.
Hawton K, Van Heeringen K, Taylor T. Suicide. Lancet 2009; 373:1372–1381
Der-Avakian A, Markou A. The neurobiology of anhedonia and other reward-related deficits. Trends Neurosci 2012; 35:68–77.
Brown RP, Stoll PM, Stokes PE, Frances A, Sweeney JA, Kocsis JH. Adrenocortical hyperactivity in depression: effects of agitation, delusions, melancholia, and other illness variables. Psychiatry Res 1987; 23:167.
Oquendo MA, Echavarria G, Galfalvy H, Grunebaum MF, Burke AB, Barrera A. Lower cortisol levels in depressed patients with comorbid post-traumatic stress disorder. Neuropsychopharmacology 2003; 28:591–598.
Muck-Seler D, Pivac N, Mustapic M, Crncevic Z, Jakovljevic M, Sagud M. Platelet serotonin and plasma prolactin and cortisol in healthy, depressed and schizophrenic women. Psychiatry Res 2004; 127:217–226.
Stetler C, Miller GE. Depression and hypothalamic-pituitary-adrenal activation: a quantitative summary of four decades of research. Psychosom Med 2011; 73:114–126.
Gold PW, Chrousos GP. Melancholic and atypical subtypes of depression represent distinct pathophysiological entities: CRH, neural circuits, and the diathesis for anxiety and depression. Mol Psychiatry 2013; 18:632–634.
Cubała WJ, Landowski J. C-reactive protein and cortisol in drug-naïve patients with short-illness-duration first episode major depressive disorder: possible role of cortisol immunomodulatory action at early stage of the disease. J Affect Disord 2014; 152–154:534–537
Van Heeringen K, Audenaert K, Van de WL, Verstraete A. Cortisol in violent suicidal behaviour: association with personality and monoaminergic activity. J Affect Disord 2003; 60:181–189.
Leventhal AM, Chasson GS, Tapia E, Miller EK, Pettit JW. Measuring hedonic capacity in depression: a psychometric analysis of three anhedonia scales. J Clin Psychol 2006; 62:1545–1558.
Gorwood P. Neurobiological mechanisms of anhedonia. Dialogues Clin Neurosci 2008; 10:291.
Walter M, Henning A, Grimm S, Schulte RF, Beck J, Dydak U, Northoff G. The relationship between aberrant neuronal activation in the pregenual anterior cingulate, altered glutamatergic metabolism, and anhedonia in major depression. Arch Gen Psychiatry 2009; 66:478–486.
Schrader GD. Does anhedonia correlate with depression severity in chronic depression?. Compr Psychiatry 1997; 38:260–263.
Putnam KM, Pizzagalli DA, Gooding DC, Kalin NH, Davidson RJ. Neural activity and diurnal variation of cortisol: evidence from brain electrical tomography analysis and relevance to anhedonia. Psychophysiology 2008; 45:886–895.
Jacobs N, Myin-Germeys I, Derom C, Delespaul P, van Os J, Nicolson NA. A momentary assessment study of the relationship between affective and adrenocortical stress responses in daily life. Biol Psychol 2007; 74:60–66.
Von Zerssen D, Doerr P, Emrich HM, Lund R, Pirke KM. Diurnal variation of mood and the cortisol rhythm in depression and normal states of mind. Eur Arch Psychiatry Neurol Sci 2007; 237:36–45.
Gold PW, Chrousos GP. Organization of the stress system and its dysregulation in melancholic and atypical depression: high vs low CRH/NE states. Mol Psychiatry 2002; 7:254–275.
Tomb DA Psychiatry. 7th ed. New York: Lippincott Williams & Wilkins; 2008. 44. USA.
Grippo AJ, Francis J, Beltz TG, Felder RB, Johnson AK. Neuroendocrine and cytokine profile of chronic mild stress-induced anhedonia. Physiol Behav 2005; 84:697–706.
Lépine JP, Briley M. The increasing burden of depression. Neuropsychiatr Dis Treat 2011; 7(Suppl 1):3–7.
Hawton K, Casañas I, Comabella C, Haw C, Saunders K. Risk factors for suicide in individuals with depression: a systematic review. J Affect Disord 2013; 147:17–28.
Fawcett J, Scheftner WA, Fogg L, Clark DC, Hedeker D, Gibbons R, Coryell W. Time-related predictors of suicide in major affective disorder. Am J Psychiatry 1990; 147:1189–1194.
Xie W, Li H, Luo X, Fu R, Ying X, Wang N et al.
Anhedonia and pain avoidance in the suicidal mind: behavioral evidence for motivational manifestations of suicidal ideation in patients with major depressive disorder. J Clin Psychol 2014; 70:681–692.
Furczyk K, Schutová B, Michel TM, Thome J, Büttner AM. The neurobiology of suicide − a review of post-mortem studies. J Mol Psychiatry 2013; 1:2.
Jokinen J, Nordström P. HPA axis hyperactivity as suicide predictor in elderly mood disorder inpatients. Psychoneuroendocrinology 2008; 33:1387–1393.
Dwivedi Y, Coryell W. Do serum cholesterol values and dst results comprise independent risk factors for suicide? [Chapter 7] In: Dwivedi Y, editor. The neurobiological basis of suicide. Boca Raton, FL: CRC Press/Taylor & Francis; 2012.
Chatzittofis A, Nordström P, Hellström C, Arver S, Åsberg M, Jokinen J. CSF5-HIAA, cortisol and DHEAS levels in suicide attempters. Eur Neuropsychopharmacol 2013; 23:1280–1287.
Duval F, Mokrani MC, Correa H, Bailey P, Valdebenito M, Monreal J et al.
Lack of effect of HPA axis hyperactivity on hormonal responses to d-fenfluramine in major depressed patients: implications for pathogenesis of suicidal behaviour. Psychoneuroendocrinology 2001; 26:521–537.
Pitchot W, Scantamburlo G, Pinto E, Hansenne M, Reggers J, Ansseau M, Legros JJ. Vasopressin-neurophysin and DST in major depression: relationship with suicidal behavior. J Psychiatr Res 2008; 42:684–688.
Pfennig A, Kunzel HE, Kern N, Ising M, Majer M, Fuchs B et al.
Hypothalamus-pituitary-adrenal system regulation and suicidal behavior in depression. Biol Psychiatry 2005; 57:336–342.
Lindqvist D, Isaksson A, Träskman-Bendz L, Brundin L. Salivary cortisol and suicidal behavior – a follow-up study. Psychoneuroendocrinology 2008; 33:1061–1068.
Yerevanian BI, Feusner JD, Koek RJ, Mintz J. The dexamethasone suppression test as a predictor of suicidal behavior in unipolar depression. J Affect Disorders 2004; 83:103–108.
Ozbolt LB, Nemeroff CB. HPA axis modulation in the treatment of mood disorders. Psychiatr Disord 2013; 21:149–157.
Coryell W, Young E, Carroll B. Hyperactivity of the hypothalamic-pituitary-adrenal axis and mortality in major depressive disorder. Psychiatry Res 2006; 142:99–104.
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7], [Table 8]