Dexamethasone Suppression Test Nonsuppression Research Articles

Effect of intermittent theta-burst stimulation on the thyroid and adrenal systems in resistant depressed patients

IntroductionDisturbances in the hypothalamic-pituitary-thyroid (HPT) and hypothalamic-pituitary-adrenal (HPA) axes have been frequently reported in treatment resistant depressed patients (TRDs). So far, the effects of intermittent theta-burst stimulation (iTBS) treatment—a form of repetitive transcranial magnetic stimulation (rTMS) technique—on the activity of the HPT and HPA axes are poorly understood.ObjectivesThe present study aimed to evaluate the effects of iTBS sessions, applied to the left dorsolateral prefrontal cortex, in TRDs with abnormal chronobiological HPT functioning at baseline (BL) possibly associated with hypercortisolemia.MethodsThe ∆∆TSH test (i.e., the difference between the thyrotropin response to protirelin tests [∆TSH] performed at 8 AM and 11 PM on the same day) and the dexamethasone suppression test (DST) were performed in 12 TRDs and 14 healthy hospitalized control subjects (HCs). To be enrolled in this study, patients had to show at BL reduced ∆∆TSH values (i.e., < 2.5 mU/L) and a score of 18 or greater on the 17-item Hamilton Rating Scale for Depression (HAMD-17). Post-DST cortisol maximum (CORmax) serum level in excess of 120 nmol/L defined DST non-suppression (i.e., hypercortisolemia)—6 TRDs were DST non-suppressors at BL. After 10 and 20 iTBS sessions the ∆∆TSH test and the DST were repeated in all inpatients. A positive clinical response was defined by a final HAMD-17 score ≤ 8.ResultsCompared to HCs, ∆∆TSH values were lower in TRDs at BL (p < 0.00001), and remained reduced after 10 and 20 iTBS sessions (p < 0.001 and p < 0.02 respectively). Post-DST CORmax levels were higher in TRDs than in HCs at BL (p < 0.01), but were comparable to those of HCs after 10 and 20 iTBS sessions. Responders (n = 5) were characterized by 1) a normalization of their ∆∆TSH values after 20 iTBS sessions (whereas after 10 iTBS sessions ∆∆TSH values were still reduced compared to HCs [p < 0.05]), and 2) a normality of post-DST CORmax levels at BL—while after 10 and 20 iTBS sessions post-DST CORmax levels were decreased compared to HCs (p < 0.006 and p < 0.03 respectively). Non-responders (n = 7) showed 1) no significant change in their ∆∆TSH values which remained lower than those of HCs at each assessment (all p < 0.001), 2) while increased post-DST CORmax levels found at BL (p < 0.0008 vs. HCs) normalized from the 10th iTBS session.ConclusionsThe present pilot study suggests that successful iTBS treatment can restore the chronobiological activity of the HPT axis. Although iTBS may increase glucocorticoid receptor signaling, baseline hypercortisolemia could negatively impact subsequent response to iTBS treatment.Disclosure of InterestNone Declared

HPA-axis dysregulation is not associated with accelerated epigenetic aging in patients with hypersexual disorder

BackgroundHypersexual disorder (HD) - a nonparaphilic sexual desire disorder with impulsivity component - was evaluated for inclusion as a diagnosis in the DSM-5 and the diagnosis compulsive sexual behavior disorder is included as an impulse control disorder in the ICD-11. Hypothalamic-pituitary-adrenal (HPA)-axis hyperactivity is believed to affect cellular senescence and has been implicated in HD. No previous study investigated HD or HPA-axis dysregulation in relation to measures of epigenetic age (EA) acceleration. MethodsThis study reports on a case-control study set-up from a well-characterized cohort, contrasting EA predictors in relation to 60 HD patients and 33 healthy volunteers (HV) and 19 mixed HD/HV exhibiting dexamethasone suppression test (DST) non-suppression to 73 mixed HD/HV DST controls. The genome-wide methylation pattern was measured in whole blood from 94 subjects using the Illumina Infinium Methylation EPIC BeadChip and preprocessed according to specialized protocols suitable for epigenetic age estimation. The online DNAm Age Calculator (https://dnamage.genetics.ucla.edu/) was implemented to retrieve various EA predictors, which were compared between the in-silico generated subgroups. ResultsQuality control analyses indicated strong correlations between the EA measure DNA methylation GrimAge (DNAm GrimAge – the EA clock most reliably associated with mortality risk) and chronological age in all sub-groups. The study was adequately powered to detect differences of 2.5 and 3.0 years in DNAm GrimAge minus age in relation to both HD and HPA-axis dysregulation, respectively. Baseline DNAm GrimAge exceeded chronological age by 2.8 years on average across all samples. No EA acceleration marker was associated with HD or DST suppression status (p > 0.05). ConclusionEA acceleration markers shown to be strongly predictive of physiological dysregulation and mortality-risk, are not related to HD or DST non-suppression status (measured after 0.5 mg dexamethasone). The independency of HPA-axis dysregulation to EA acceleration does not support the biological relevance of this dosage-regimen when applied to patients with HD. These findings do not support the notion of accelerated cellular senescence in HD. Studies stratifying DST non-suppressors according to established dosage-regimens in somatic settings are needed to fully elucidate the putative contribution of HPA-axis dysregulation to EA.

HPA axis dysregulation is associated with differential methylation of CpG-sites in related genes

DNA methylation shifts in Hypothalamic–pituitary–adrenal (HPA) axis related genes is reported in psychiatric disorders including hypersexual disorder. This study, comprising 20 dexamethasone suppression test (DST) non-suppressors and 73 controls, examined the association between the HPA axis dysregulation, shifts in DNA methylation of HPA axis related genes and importantly, gene expression. Individuals with cortisol level ≥ 138 nmol/l, after the low dose (0.5 mg) dexamethasone suppression test (DST) were classified as non-suppressors. Genome-wide methylation pattern, measured in whole blood using the EPIC BeadChip, investigated CpG sites located within 2000 bp of the transcriptional start site of key HPA axis genes, i.e.: CRH, CRHBP, CRHR-1, CRHR-2, FKBP5 and NR3C1. Regression models including DNA methylation M-values and the binary outcome (DST non-suppression status) were performed. Gene transcripts with an abundance of differentially methylated CpG sites were identified with binomial tests. Pearson correlations and robust linear regressions were performed between CpG methylation and gene expression in two independent cohorts. Six of 76 CpG sites were significantly hypermethylated in DST non-suppressors (nominal P < 0.05), associated with genes CRH, CRHR1, CRHR2, FKBP5 and NR3C1. NR3C1 transcript AJ877169 showed statistically significant abundance of probes differentially methylated by DST non-suppression status and correlated with DST cortisol levels. Further, methylation levels of cg07733851 and cg27122725 were positively correlated with gene expression levels of the NR3C1 gene. Methylation levels of cg08636224 (FKBP5) correlated with baseline cortisol and gene expression. Our findings revealed that DNA methylation shifts are involved in the altered mechanism of the HPA axis suggesting that new epigenetic targets should be considered behind psychiatric disorders.

Are the thyroid and adrenal system alterations linked in depression?

BackgroundDisturbances in the hypothalamic-pituitary-thyroid (HPT) and hypothalamic-pituitary-adrenal (HPA) axes have been frequently found in major depression. Given that glucocorticoids may inhibit thyrotropin (TSH) and thyrotropin-releasing hormone (TRH) secretion, it has been hypothesized that hypercortisolemia could lead to HPT axis abnormalities. So far, data on interactions between the HPA and HPT axes in depression remain inconclusive. MethodsIn order to investigate this issue, we examined circadian rhythms of serum TSH and cortisol (sampled at 4 -hly intervals throughout a 24 -h span), TSH responses to 0800 h and 2300 h protirelin (TRH) tests and cortisol response to dexamethasone suppression test (DST) in 145 unmedicated inpatients meeting DSM-IV criteria for major depressive disorder (MDDs) and 25 healthy hospitalized control subjects (HCs). ResultsThe secretion of TSH and cortisol exhibited a significant circadian rhythm both in HCs and MDDs. However, compared to HCs, MDDs showed: 1) reduced TSH mesor and amplitude values; 2) blunted 2300 h-ΔTSH and ΔΔTSH values (i.e. differences between 2300 h and 0800 h TRH-TSH responses); and 3) increased cortisol mesor and post-DST cortisol values. DST nonsuppresssors (n = 40, 27 %) showed higher cortisol mesor than DST suppressors (n = 105, 73 %). There was no difference between DST suppressors and nonsuppressors in their TSH circadian parameters and TRH-TSH responses. In addition, cortisol values (circadian and post-DST) were not related to TRH test responses. ConclusionOur results do not confirm a key role for hypercortisolemia in the HPT axis dysregulation in depression.

Hypothalamic–pituitary–adrenal axis hyperactivity is associated with decreased brain-derived neurotrophic factor in female suicide attempters

Introduction: Both decreased levels of brain-derived neurotrophic factor (BDNF) and hypothalamic–pituitary–adrenal (HPA) axis dysregulation may be involved in the pathophysiology of suicidal behaviour, as well as cognitive symptoms of depression. Pre-clinical and clinical studies have shown interactions between HPA-axis activity and BDNF, but this has not been studied in a clinical cohort of suicidal subjects. The purpose of this study was, therefore, to investigate associations between HPA-axis activity and BDNF in suicide attempters. Furthermore, this study examined the relationship between the HPA-axis, BDNF, and cognitive symptoms in suicidal patients. Since previous data indicate gender-related differences in BDNF and the HPA axis, males and females were examined separately.Method: Seventy-five recent suicide attempters (n = 41 females; n = 34 males) were enrolled in the study. The Dexamethasone Suppression Test (DST) was performed and BDNF in plasma were analysed. Patients were evaluated with the Comprehensive Psychopathological Rating Scale (CPRS) from which items ‘Concentration difficulties’ and ‘Failing memory’ were extracted.Results: Only among females, DST non-suppressors had significantly lower BDNF compared to DST suppressors (p = 0.022), and there was a significant correlation between post-DST serum cortisol at 8 a.m. and BDNF (rs = −0.437, p = 0.003). Concentration difficulties correlated significantly with post-DST cortisol in all patients (rs = 0.256, p = 0.035), in females (rs = 0.396, p = 0.015), and with BDNF in females (rs = −0.372, p = 0.020).Conclusion: The findings suggest an inverse relationship between the HPA-axis and BDNF in female suicide attempters. Moreover, concentration difficulties may be associated with low BDNF and DST non-suppression in female suicide attempters.

Increased left ventricular mass in hypercortisolemic depressed patients: A hypothesis based on a case series

BackgroundHypercortisolemia in depressed patients is known to be related to changes in body composition, especially increased ectopic fat and lowered bone mineral density. Both hypercortisolemia in patients with Cushing’s disease and depression in patients undergoing treatment with hemodialysis have been shown to be associated with increased left ventricular mass. HypothesisIncreased activity of the hypothalamus–pituitary–adrenal (HPA) system in depressed patients is related to high left ventricular mass. Empirical dataTo corroborate our hypothesis, we measured left ventricular mass in 5 depressed patients with clear evidence for HPA system activation (nonsuppression in dexamethasone suppression test [DST]; increased 24h cortisol excretion) and 27 healthy controls. We found increased left ventricular mass in hypercortisolemic depressed patients compared to healthy controls (343±97 vs. 176±57 gr; p=0.007). ConclusionsDepression is known to be related to an increased risk of cardial morbidity and mortality, although the risk architecture is not completely understood. We hypothesize that hypercortisolemic depression is associated with increased left ventricular mass, which is known to be a strong predictor for cardial mortality. Thus, a potential effect of activated stress-responsive systems on heart morphology may contribute to depressed patients’ increased cardiovascular risk.

Cortisol responses on the dexamethasone suppression test among women with Bulimia-spectrum eating disorders: Associations with clinical symptoms

Evidence associates Bulimia Nervosa (BN) with altered functioning of the hypothalamic-pituitary-adrenal (HPA) axis, but the clinical implications of such alterations need to be better understood. We contrasted cortisol responses to the dexamethasone suppression test (DST) in bulimic and non-eating disordered women and examined relationships among DST cortisol responses, eating symptoms and co-morbid disturbances. Sixty women with Bulimia Spectrum (BS) Disorders (either BN or normal weight Eating Disorder NOS with regular binge eating or purging) and 54 non-eating disordered women of similar age and body mass index participated in a 0.5 mg DST, and completed interviews and questionnaires assessing eating symptoms and co-morbid psychopathology. Compared with the normal-eater group, the BS women demonstrated significantly less DST suppression. Among BS women, DST non-suppression was associated with more severe depression, anxiety and eating preoccupations. Our findings show BS women to show less DST suppression compared to normal eater women, and results link extent of non-suppression, in BS individuals, to severity of depression, anxiety and eating preoccupations.

Childhood traumata, Dexamethasone Suppression Test and psychiatric symptoms: a trans-diagnostic approach

Childhood traumatic events and functional abnormalities of the hypothalamus-pituitary-adrenal (HPA) axis have been widely reported in psychiatric patients, although neither is specific for any diagnosis. Among the limited number of studies that have evaluated these topics, none has adopted a trans-diagnostic approach. The aim of the present research is to explore the relationship between childhood stressors, HPA axis function and psychiatric symptoms, independent of the diagnosis. A total of 93 moderate to severely ill psychiatric out-patients of Florence and Pisa University Psychiatric Units and 33 healthy control subjects were recruited. The assessment consisted of salivary cortisol pre- and post-low dose (0.5 mg) Dexamethasone, early and recent life events, 121 psychiatric symptoms independent of diagnosis, SCID, BPRS. In total, 33.5% of patients were Dexamethasone Suppression Test (DST) non-suppressors, compared with 6.1% of controls (p=0.001). Among patients, non-suppression was associated with particular symptoms (i.e. depressive and psychotic), but not to any specific diagnosis. Early stressful life events were significantly associated with higher salivary cortisol levels, with DST non-suppression and with approximately the same subset of symptoms. A recent stressful event seemed to be associated to the HPA response only in those subjects who were exposed to early traumata. Our report suggests a relationship between life stress, HPA axis and psychopathology. A cluster of specific psychiatric symptoms seems to be stress related. Moreover, it seems that an abnormal HPA response is possibly triggered by an excessive pressure in vulnerable individuals.

Does the Dexamethasone Suppression Test Reliably Discriminate Between Psychotic and Nonpsychotic Major Depression?

Previous research has shown that psychotic major depression (PMD) is often associated with higher rates of nonsuppression on the dexamethasone suppression test (DST) compared with nonpsychotic major depression (NMD), suggesting the potential importance of cortisol hypersecretion in the psychotic subtype of the disorder. However, these patient groups also are known to differ from one another on a variety of other clinical variables, and there are numerous factors independent of diagnostic status known to affect the DST. Thus, we investigated possible confounds that could help account for the apparent DST abnormalities in PMD sometimes reported in past research. Hospitalized patients with PMD (n = 11) and NMD (n = 58) were compared on the DST and other clinical variables. As expected, PMD patients showed significantly higher rates of DST nonsuppression (55% vs. 24%; p = 0.04). However, PMD patients also had significantly higher levels of anxiety severity (p = 0.01). The higher rates of nonsuppression in the PMD group were attenuated when these patients were compared with a subsample of NMD patients matched on anxiety severity (55% vs. 55%). Implications for future research on biological markers of PMD are discussed.

FC04-05 Attempted suicide and HPA axis dysregulation as suicide predictors in elderly mood disorder inpatients

Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis function is associated with suicidal behaviour and age-associated alterations in HPA axis functioning may render elderly individuals more susceptible to HPA dysregulation related to mood disorders. Research on the role HPA axis function in suicidal behaviour in elderly mood disorder patients is sparse.The study sample consisted of 99 depressed elderly inpatients 65 years of age or older admitted to the department of Psychiatry at the Karolinska University Hospital between 1980 and 2000. 24 % of patients had attempted suicide just before admission. The hypothesis was that elderly mood disorder inpatients who fail to suppress cortisol in the dexamethasone suppression test (DST) are at higher risk of suicide.During a mean follow-up time of 17 years (range 6-25.5 years), six suicides were identified from the death certificates. The DST non-suppression distinguished between suicides and survivors in elderly depressed inpatients and the suicide attempt at the index episode was a strong predictor for suicide. Additionally, the DST non-suppression showed higher specificity and predictive value in the suicide attempter group. Due to age associated alterations in HPA axis functioning, the optimal cut-off for DST non-suppression in suicide prediction may be higher in elderly mood disorder inpatients.

CSF 5-HIAA and DST non-suppression — Orthogonal biologic risk factors for suicide in male mood disorder inpatients

Two biomarkers of suicide risk; non-suppression in the dexamethasone suppression test (DST) and low 5-hydroxyindoleacetic acid (5-HIAA) in the cerebrospinal fluid (CSF) have been reported to be predictors of suicide in mood disorders. The interrelation of the two systems seems to be different in suicide attempters compared with depressed inpatients who have not made a suicide attempt, indicating that the two biomarkers may be seen as independent. This investigation examined the interrelation of low CSF 5-HIAA and DST non-suppression in suicide victims with mood disorder. Fifty-eight mood disorder inpatients not receiving any treatment with antidepressants underwent lumbar puncture and the DST. Plasma cortisol levels at 8:00 a.m., 4:00 p.m. and 11:00 p.m. were analysed in relation to CSF 5-HIAA. All patients were followed up for causes of death and suicides were verified with death certificates. During follow-up (mean 21 years), 11 (19%) patients had committed suicide. In male suicide victims ( n = 6), the serum cortisol level at 4:00 p.m. showed a significant positive correlation with CSF 5-HIAA. Low CSF 5-HIAA predicted all early suicides (within 1 year), whereas all males who committed suicide after 1 year were DST non-suppressors. In female suicide victims ( n = 5), the post-DST serum cortisol did not correlate with CSF 5-HIAA. Low CSF 5-HIAA and DST non-suppression are orthogonal biologic risk factors for suicide in male mood disorder inpatients. CSF 5-HIAA is associated with short-term suicide risk; dysregulation of the hypothalamic-pituitary-adrenal axis seems to be a long-term suicide predictor.

HPA axis hyperactivity and cardiovascular mortality in mood disorder inpatients

Depression is associated with an increased risk of cardiovascular disease (CVD), coronary heart disease (CHD) and cardiac death. Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis function is frequent in major depression and hypercortisolemia may be a mediating factor in these relationships. The aim of this study was to assess HPA axis function measured with the dexamethasone suppression test (DST) in relation to CVD and CHD mortality in a cohort of 382 inpatients with mood disorder admitted to the department of Psychiatry at the Karolinska University Hospital between 1980 and 2000. Death certificates ascertained that 75 patients had died of cardiovascular disease and 30 patients of CHD during the mean follow-up of 18 years. DST non-suppression and higher baseline serum cortisol predicted CVD death. In male inpatients with mood disorder, the DST non-suppressor status was significantly associated with CVD death but not with CHD death. In depressed female inpatients the DST non-suppression was not associated with cardiovascular mortality. Baseline serum cortisol and post-dexamethasone serum cortisol levels at 4:00 p.m. showed a trend to be higher in female CVD/CHD victims. Effect of aging on HPA axis functioning was shown in male CHD deaths. HPA axis dysregulation may be a mediating factor between depression and increased risk of cardiovascular death in male mood disorder inpatients indicating that HPA-axis hyperactivity is a long term risk factor for cardiovascular mortality.

HPA axis hyperactivity and attempted suicide in young adult mood disorder inpatients

Background Hyperactivity of the Hypothalamic–Pituitary–Adrenal (HPA) axis is a consistent finding in Major Depressive Disorder (MDD) and most prospective studies of HPA-axis function have found that non-suppressors in the dexamethasone suppression test (DST) are more likely to commit suicide during follow-up. The results of studies on HPA-axis function and attempted suicide are less consistent. Suicide attempts are more common among young people than the elderly, whereas suicide is more common among the elderly. The impact of age related changes in HPA-axis system activity in relation to suicidal behaviour across the lifecycle may be of importance. Methods The aim of the present study was to investigate the DST results in 36 young adult (30 years or younger) inpatients with mood disorder, with ( n = 18) and without suicide attempt at the index episode. Results The DST non-suppressor rate was 25% among young mood disorder inpatients. DST non-suppression was associated with suicide attempt and post-dexamethasone serum cortisol at 11:00 p.m. was significantly higher in suicide attempters compared to non-attempters. The DST non-suppressor rate was 39% in young adult suicide attempters compared with 11% in non-attempters. Conclusions The results add to previous evidence in support of the role of HPA axis hyperactivity and suicidal behaviour. The present findings motivate to include HPA axis measures in the assessment of depression in young adults.

HPA axis hyperactivity as suicide predictor in elderly mood disorder inpatients

Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis function is associated with suicidal behaviour and age-associated alterations in HPA axis functioning may render elderly individuals more susceptible to HPA dysregulation related to mood disorders. Research on HPA axis function in suicide prediction in elderly mood disorder patients is sparse. The study sample consisted of 99 depressed elderly inpatients 65 years of age or older admitted to the department of Psychiatry at the Karolinska University Hospital between 1980 and 2000. The hypothesis was that elderly mood disorder inpatients who fail to suppress cortisol in the dexamethasone suppression test (DST) are at higher risk of suicide. The DST non-suppression distinguished between suicides and survivors in elderly depressed inpatients and the suicide attempt at the index episode was a strong predictor for suicide. Additionally, the DST non-suppression showed higher specificity and predictive value in the suicide attempter group. Due to age-associated alterations in HPA axis functioning, the optimal cut-off for DST non-suppression in suicide prediction may be higher in elderly mood disorder inpatients. These data demonstrate the importance of attempted suicide and DST non-suppression as predictors of suicide risk in late-life depression and suggest the use for neuroendocrine testing of HPA axis functioning as a complementary tool in suicide prevention.

Season of birth, clinical manifestations and Dexamethasone Suppression Test in unipolar major depression

BackgroundReports in the literature suggest that the season of birth might constitute a risk factor for the development of a major psychiatric disorder, possibly because of the effect environmental factors have during the second trimester of gestation. The aim of the current paper was to study the possible relationship of the season of birth and current clinical symptoms in unipolar major depression.MethodsThe study sample included 45 DSM-IV major depressive patients and 90 matched controls. The SCAN v. 2.0, Hamilton Depression Rating Scale (HDRS) and Hamilton Anxiety Scale (HAS) were used to assess symptomatology, and the 1 mg Dexamethasone Suppression Test (DST) was used to subcategorize patients.ResultsDepressed patients as a whole did not show differences in birth season from controls. However, those patients born during the spring manifested higher HDRS while those born during the summer manifested the lowest HAS scores. DST non-suppressors were almost exclusively (90%) likely to be born during autumn and winter. No effect from the season of birth was found concerning the current severity of suicidal ideation or attempts.DiscussionThe current study is the first in this area of research using modern and rigid diagnostic methodology and a biological marker (DST) to categorize patients. Its disadvantages are the lack of data concerning DST in controls and a relatively small size of patient sample. The results confirm the effect of seasonality of birth on patients suffering from specific types of depression.

CSF 5-HIAA and DST non-suppression -independent biomarkers in suicide attempters?

Background Two major biomarkers of suicidal behaviour; low 5-hydroxyindoleacetic acid (5-HIAA) in the cerebrospinal fluid (CSF) and non-suppression in the dexamethasone suppression test (DST) have evidence for predictive power for suicide in mood disorders. Previous suicide attempt is the most robust clinical risk factor. Purpose of study To study the interrelationship of suicide risk factors: low CSF 5-HIAA and the DST non-suppression in mood disorder patients with and without an index suicide attempt. Methods Fifty-eight hospitalised mood disorder patients (twenty-five with an index suicide attempt), who were not receiving any treatment with antidepressants, underwent lumbar puncture and DST. Plasma cortisol levels were determined from blood samples drawn the following day at 8:00 a.m., 4:00 p.m. and 11:00 p.m. and analysed in relation to CSF 5-HIAA. Results In the sample as a whole, the serum cortisol level at 4:00 p.m. showed a significant positive correlation to CSF 5-HIAA ( r = 0.3, p < 0.02). In the patients with an index suicide attempt, the serum cortisol at 4.00 p.m. correlated positively with CSF 5-HIAA ( r = 0.65, p < 0.0006), but not in the non-attempters (NS). Conclusion The positive correlation means that low CSF 5-HIAA and DST non-suppression are relatively independent biomarkers of suicide risk in suicide attempters. The interrelation of the two systems seems to be different in suicide attempters compared to depressed inpatients without suicide attempt.

Neopterin levels and dexamethasone suppression test in obsessive–compulsive disorder

Neopterin, a biopterin precursor that is released by macrophages, is an important immunological marker in psychiatric disorders. It has been reported that glucocorticoids may cause suppression of cell-mediated immunity and consequently result in decreased neopterin levels. In the present study, we evaluated whether dexamethasone suppression test (DST) and neopterin findings were associated with pure obsessive–compulsive disorder (OCD) patients (OCD-D group) and the concomitant OCD and depression (OCD+D group). The sample comprised 44 patients with OCD (27 with OCD-D and 17 with OCD+D) and 30 control subjects. There was significantly higher DST nonsuppression in the OCD+D group than in the OCD-D group. With regard to mean neopterin levels, there was no significant difference between the OCD-D group and the control group, but there was a statistically significant difference between the OCD+D group and the control group. The OCD+D group had significantly lower neopterin levels than the 20 OCD-D group. We suggest that this distinction may reflect the fact that glucocorticoids can lead to suppression of cell-mediated immunity and consequently can result in decreased neopterin levels. In conclusion, our results suggest that not the OCD-D group had normal neopterin levels and DST results, and also that OCD may be a heterogeneous subtype characterized by some biological indicators or anxiety and affective disorders.

DST non-suppression predicts suicide after attempted suicide

Most prospective studies of HPA axis have found that non-suppressors in the dexamethasone suppression test (DST) are more likely to commit suicide during the follow-up. Attempted suicide is a strong clinical predictor of suicide. The aim of this study was to assess the predictive value of DST for suicide in a group of depressed inpatients with and without an index suicide attempt. Historical cohort of 382 psychiatric inpatients with mood disorder admitted to the department of Psychiatry at the Karolinska University Hospital between 1980 and 2000 were submitted to the DST and followed up for causes of death. During the follow-up (mean 18 years), 36 suicides (9.4%) occurred, 20 of these were non-suppressors and 16 were suppressors. There was no statistically significant difference in suicide risk between the suppressors and non-suppressors for the sample as a whole. An index suicide attempt predicted suicide. In suicide attempters with mood disorder, the non-suppressor status was significantly associated with suicide indicating that HPA axis hyperactivity is a risk factor for suicide in this group. The dexamethasone suppression test may be a useful predictor within this population.

Hormonal differences between psychotic and non-psychotic melancholic depression

BackgroundThe dexamethasone suppression test (DST) is the main hormonal disturbance in psychotic depression compared to non-psychotic depression. However, although there have been many studies of individual hormonal axes in depression, few multi-axial studies have been reported. This study aims to examine hormonal differences between these groups of patients through three functional hormonal tests: DST, thyroid stimulating hormone response to thyroid releasing hormone (TSH–TRF) and growth hormone response to growth hormone releasing factor (GH–GRF). MethodsForty inpatients meeting DSM-III-R criteria for major depressive episode with melancholia (21 non-psychotic and 19 psychotic) were studied. Dexamethasone suppression test, TSH–TRF and GH–GRF tests were undertaken for all patients. ResultsIn the whole melancholic sample, 80.0% showed disturbances in at least one hormonal axis, 40.0% in two axes and 5.0% in all three axes. Basal and post-dexamethasone cortisol levels were significantly higher in psychotic than in non-psychotic patients. An association between post-dexamethasone cortisol and blunted GH–GRF response was demonstrated in those with psychotic depression. In the whole sample, GH blunting was found in 62.5% of patients, DST non-suppression in 37.5% and TSH blunting in 25.0% (no differences were found between psychotic and non-psychotic patients). LimitationsSample was restricted to melancholia and unknown factors may influence hormonal responses to stress. ConclusionsHormonal disturbances in depression are more evident when studying several axes, being the HPA and the GH axes the most prominents. Psychotic depression showed more HPA disturbance than non-psychotic depression. Influence of the HPA on the GH axis is discussed.

Are Dexamethasone Suppression Test Nonsuppression and Thyroid Dysfunction Related to a Family History of Dementia in Patients with Major Depression? An Exploratory Study

Recent data suggest that the low thyroid function syndrome in depression is nonspecific. They also suggest that depression may constitute a risk factor for the development of dementia, especially in atypical patients who have high rates of hypothalamo-pituitary-adrenal axis disorders. This study aimed to search for correlations among Dexamethasone Suppression Test (DST) cortisol levels, thyroid indices, and family history of dementia in patients with depression. A sample of 30 patients, aged 21 to 60 years and suffering from major depression according to DSM-IV criteria, took part in the study. Three had a family history of dementia in first-degree relatives. We measured their serum levels of free T3, free T4, thyroid-stimulating hormone, thyroid binding inhibitory immunoglobulines, thyroglobulin antibodies, and thyroid microsomal antibodies (TMAs). We applied the 1-mg DST to all patients. The statistical analysis included 1-way multivariate analysis of covariance using t tests as the post hoc tests. Significantly higher levels of TMAs were found in patients with a family history of dementia, compared with those who did not have this family history. The results of this study suggest that a more pronounced autoimmune process may characterize depression patients with a family history of dementia.