Revisiting the Dexamethasone Suppression Test in unipolar major depression: an exploratory study

Background

Important methodological questions still exist concerning the Dexamethasone Suppression Test (DST), including the possibility of a better way of interpreting it. The aim of the present study was to explore the feasibility of an alternative way of interpreting DST results.

Methods

A total of 50 patients with major depression aged 41.0 ± 11.4 years old participated in the study. Past and present suicide attempts were recorded. Psychometric assessment included the Hamilton Depression Rating Scale (HDRS), the Hamilton Anxiety Scale (HAS), the Newcastle Depression Diagnostic Scale (NDDS), the Diagnostic Melancholia Scale (DMS) and the General Assessment of Functioning (GAF) scale. The 1 mg DST protocol was used. Analysis methods included the chi square test and analysis of covariance (ANCOVA) with Fisher least significant difference (LSD) as post hoc tests.

Results

In all, 34 patients (68%) were suppressors, 16 (32%) were non-suppressors and 14 patients had cortisol values above 5 μg/dl at baseline. Baseline cortisol level did not influence the classical DST interpretation. A total of 18 patients (36%) showed an increase of their cortisol levels after dexamethasone administration and 32 patients (64%) showed a decrease. Reducers had less melancholic features, similar levels of depression, better sleep and less suicidal thoughts in comparison to increasers. No relationship of DST to suicidality was found.

Discussion

The present study explored the pattern of cortisol response to dexamethasone suppression and suggested an alternative way of coding and interpreting the DST on the basis of whether the cortisol levels remain stable or increase vs decrease after the administration of cortisol. The results put forward a complex way of understanding the relationship of the DST results with clinical symptoms.     

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

Background  

Reports 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.     

Thyroid function in clinical subtypes of major depression: an exploratory study

Background  

Unipolar depression might be characterized by a 'low-thyroid function syndrome'. To our knowledge, this is the first study which explores the possible relationship of DSM-IV depressive subtypes and the medium term outcome, with thyroid function.     

Thyroid function in clinical subtypes of major depression: an exploratory study

Background

Concentrations of monoamine metabolites in human cerebrospinal fluid (CSF) have been used extensively as indirect estimates of monoamine turnover in the brain. CSF monoamine metabolite concentrations are partly determined by genetic influences.

Methods

We investigated possible relationships between DNA polymorphisms in the serotonin 2C receptor (HTR2C), the serotonin 3A receptor (HTR3A), the dopamine D₄ receptor (DRD4), and the dopamine β-hydroxylase (DBH) genes and CSF concentrations of 5-hydroxyindolacetic acid (5-HIAA), homovanillic acid (HVA), and 3-methoxy-4-hydroxyphenylglycol (MHPG) in healthy volunteers (n = 90).

Results

The HTR3A 178 C/T variant was associated with 5-HIAA levels (p = 0.02). The DBH-1021 heterozygote genotype was associated with 5-HIAA (p = 0.0005) and HVA (p = 0.009) concentrations. Neither the HTR2C Cys23Ser variant, nor the DRD4 -521 C/T variant were significantly associated with any of the monoamine metabolites.

Conclusions

The present results suggest that the HTR3A and DBH genes may participate in the regulation of dopamine and serotonin turnover rates in the central nervous system.     

Life events and clinical subtypes of major depression: a cross-sectional study

The present study aimed to investigate the relationship between stressful life events and depression. Ninety major depressive patients, aged 36.57 +/- 12.02 years, and 121 matched controls, aged 27.11 +/- 10.59 years, took part in the study. The life change units (LCU) according to Rahe et al. were used for the quantification of life events. The results suggested that males reported significantly more life events than females. Atypical males differed from all other gender-by-type groups, while no other differences emerged. LCU correlated with melancholic indices but did not correlate with anxiety or functioning. The results suggest that subgroups of depressive patients are characterized by the presence of stressful life events. Male atypical patients reported the highest load of life events. The question that arises is whether this finding is valid or whether these patients (who have higher personality psychopathology and interpersonal rejection sensitivity) tend to over-report life events.     

Causal relationship between stressful life events and the onset of major depression.

OBJECTIVE: Stressful life events are associated with the onset of episodes of major depression. However, exposure to stressful life events is influenced by genetic factors, and these factors are correlated with those that predispose to major depression. The aim of this study was to clarify the degree to which stressful life events cause major depression. METHOD: The authors assessed the occurrence of 15 classes of stressful life events and the onset of DSM-III-R major depression over a 1-year period in female twins ascertained from a population-based registry. The sample contained 24,648 person-months and 316 onsets of major depression. Stressful life events were individually rated on contextual threat and dependence (the degree to which the stressful life event could have resulted from the respondent's behavior). The nature of the relationship between stressful life events and major depression was tested by 1) discrete-time survival analysis examining the relationship between dependence and the depressogenic effect of stressful life events and 2) a co-twin control analysis. RESULTS: While independent stressful life events were significantly associated with onsets of depression, when level of threat was controlled, the association was significantly stronger for dependent events. The odds ratio for onset of major depression in the month of a stressful life event was 5.64 in all subjects, 4.52 within dizygotic pairs, and 3.58 within monozygotic pairs. CONCLUSIONS: Stressful life events have a substantial causal relationship with the onset of episodes of major depression. However, about one-third of the association between stressful life events and onsets of depression is noncausal, since individuals predisposed to major depression select themselves into high-risk environments.     

DSM-III personality disorders among patients with major depression, anxiety disorders, and mixed conditions

Of 298 mainly nonpsychotic psychiatric outpatients between 19 and 59 years of age, a group of patients having either pure major depression, major depression in combination with anxiety disorders, or pure anxiety disorders was extracted. The anxiety disorders were further differentiated in panic and nonpanic anxiety disorders. The groups were compared as to differences in frequency of personality disorders assessed by means of the Structured Interview for DSM-III Personality Disorders. The mixed major depression/anxiety disorder group appeared to be the most deviant with more severe personality disorders such as paranoid and borderline in addition to avoidant and dependent personality disorder. The differentiation between panic and nonpanic anxiety showed that it was patients with nonpanic anxiety features in addition to major depression who had this higher frequency of personality disorders. These findings imply that it is important to distinguish between major depression cases with and without anxiety disorders both in forthcoming research and in clinical practice.     

The interrelationship of neuroticism, sex, and stressful life events in the prediction of episodes of major depression

OBJECTIVE: Three potent risk factors for major depression are female sex, the personality trait of neuroticism, and adversity resulting from exposure to stressful life events. Little is known about how they interrelate in the etiology of depressive illness. METHOD: In over 7,500 individual twins from a population-based sample, the authors used a Cox proportional hazard model to predict onsets of episodes of DSM-III-R major depression in the year before the latest interviews on the basis of previously assessed neuroticism, sex, and adversity during the past year; adversity was operationalized as the long-term contextual threat scored from 15 life event categories. RESULTS: In the best-fit Cox model for prediction of depressive onsets, neuroticism, female sex, and greater adversity all strongly increased risk for major depression. An interaction was seen between neuroticism and adversity such that individuals with high neuroticism were at greater overall risk for major depression and were more sensitive to the depressogenic effects of adversity. An interaction was also seen between adversity and sex, as the excess risk for major depression in women was confined to individuals with low stress exposure. CONCLUSIONS: Psychosocial adversity interacts both with neuroticism and with sex in the etiology of major depression. The impact of neuroticism on illness risk is greater at high than at low levels of adversity, while the effect of sex on probability of onset is the opposite--greater at low than at high levels of stress. Complete etiologic models for major depression should incorporate interactions between risk factor classes.     

Genetic risk, number of previous depressive episodes, and stressful life events in predicting onset of major depression

OBJECTIVE: The association between stressful life events and the onset of major depression decreases as the number of previous depressive episodes increases. How do genetic risk factors for major depression impact on this "kindling" phenomenon? In particular, do those at high genetic risk exhibit an increase in the speed of kindling, or are they "prekindled"? METHOD: Using discrete-time survival analysis, the authors examined the interaction between genetic risk, number of previous depressive episodes, and life event exposure in the prediction of episodes of major depression in female-female twin pairs from a population-based registry. The twins were interviewed four times over a 9-year period, producing 92,521 person-months of exposure. RESULTS: The decline in the association between stressful life events and risk for major depression as the number of previous depressive episodes increased was strongest in those at low genetic risk and was weak to absent in those at high genetic risk. In the absence of previous depressive episodes, those at high genetic risk frequently experienced depressive episodes without major environmental stressors. CONCLUSIONS: Genetic risk factors for depression produce a "prekindling" effect rather than increase the speed of kindling. The "kindled" state, wherein depressive episodes occur with little provocation, may be reached by two pathways: many previous depressive episodes, perhaps driven by multiple adversities, and high genetic risk.     

Prospective study on suicidal ideation among Japanese undergraduate students: correlation with stressful life events, depression, and depressogenic cognitive patterns

The present study examines the effects of stressful life events, depression, and depressogenic cognitive patterns on suicidal ideation in 500 Japanese undergraduate students. The above factors were assessed at baseline (T1) and two weeks later (T3). At T1, structural equation modeling confirmed that (1) cognitive patterns and depression, but not stressful life events, influence suicidal ideation, and (2) cognitive patterns also influence suicidal ideation through depression. These findings were confirmed in a longitudinal analysis. The results suggest that the effects of stressful life events on suicidal ideation are indirect and are mediated by depressogenic cognitive styles and depressed mood.     

Dexamethasone suppression test findings in subjects with personality disorders: associations with posttraumatic stress disorder and major depression

OBJECTIVE: Previous studies using the 1.0-mg dexamethasone suppression test (DST) in subjects with personality disorders have produced mixed results. However, these studies focused on major depression and did not consider the possible effects of the comorbidity of posttraumatic stress disorder (PTSD). PTSD has been shown to be associated with increased cortisol suppression. To investigate the effect of PTSD, the authors conducted a 0.5-mg DST, which is more sensitive than the 1.0-mg DST for detection of increased cortisol suppression, in a group of subjects with personality disorders. METHOD: Subjects with personality disorders (N=52) ingested 0.5 mg of dexamethasone. Pre- and postfasting blood samples were drawn for measurement of cortisol levels. A three-way analysis of covariance was used to test for the main effects of major depression, PTSD, and gender on percent cortisol suppression, with plasma dexamethasone concentration as a covariate. Secondary analyses assessed for main and interaction effects of age at which trauma(s) occurred and a diagnosis of borderline personality disorder. RESULTS: Neither major depression nor gender had a significant effect on percent cortisol suppression. Subjects with PTSD had significantly higher percent cortisol suppression than subjects with major depression. Age at which trauma(s) occurred and a borderline personality disorder diagnosis had no significant main or interaction effects on cortisol suppression. CONCLUSIONS: A high level of cortisol suppression was associated with PTSD in subjects with personality disorder. This finding is similar to published findings for PTSD subjects without personality disorders. Major depression, gender, age when trauma(s) occurred, and a diagnosis of borderline personality disorder did not have significant main or interaction effects on cortisol suppression.     

Consequences of comorbid personality disorders in major depression

To describe consequences of the presence of a comorbid personality disorder (PD) in inpatients with a major depressive disorder (MDD) on variables connected to course and outcome of the unipolar affective illness, 117 inpatients with a major depressive episode were assessed at various times during inpatient treatment. Trait markers (including personality and PDs) were obtained toward the end of the treatment, when acute psychopathology had largely remitted. Fifty-one percent of all patients fulfilled the criteria for a DSM-III-R PD, 15% met the criteria for two or more PDs, and 18% fulfilled the criteria for at least one cluster A or B PD. Except for age of onset, number of suicide attempts and quality of life all other outcome and course variables were unrelated to the presence or absence of a comorbid PD. In this sample, one comorbid PD in patients with MDD was of limited relevance to the course of the affective illness, especially if it was a cluster C PD. Two or more comorbid PDs in patients with unipolar depression tended to reduce quality of life and have an earlier age of onset. Patients with cluster A or B PD and MDD had attempted suicide more often than patients with a cluster C PD and MDD. Although comorbid cluster C PDs were seen in all age groups of patients with an MDD, cluster A or B PDs and the presence of more than one PD were mainly seen in younger patients with an MDD.     

Personality and personality disorders among patients with major depression in combination with dysthymic or cyclothymic disorders

Personality traits and personality disorders in 298 consecutive outpatients with pure major depression, major depression with dysthymic or cyclothymic disorder, pure dysthymic or cyclothymic disorder and other disorders were investigated. Patients with dysthymic or cyclothymic disorders alone or in combination with major depression showed more self-doubt, insecurity, sensitivity, compliance, rigidity and emotional instability. They were more schizoid, schizotypal, borderline and avoidant according to MCMI and had a higher prevalence of DSM-III Axis II diagnoses, and more borderline, avoidant, and passive-aggressive personality disorders, as measured by SIDP. All in all, dramatic and anxious clusters of personality disorders were more frequent among patients with dysthymic-cyclothymic disorders in addition to major depression than among patients with major depression only. The findings elucidated the close connection between the more chronic affective disorders and the personality disorders, irrespective of any concomitant diagnosis of major depression.     

Associations between major life events, traumatic incidents, and depression among Buffalo police officers

Police officers are considered to be a highly stressed population due to the nature of the work they perform. Repeated exposures to work stress and stressful life events can affect one's psychological and physiological well-being. The objective of this study was to determine whether negative life events and traumatic police incidents are associated with depression in police officers. One hundred randomly selected urban officers completed a series of self-report measures as part of a cross-sectional pilot study. Using four negative life event categories (none, low, medium, and high) a J-shaped pattern was observed with mean depression scores (+/- SD) of 9.26 (+/- 7.41), 6.21 (+/- 5.94), 8.17 (+/- 7.42), and 14.64 (+/- 8.04), respectively (test for linear trend p = 0.0186). Adjustment for age (p = 0.0209), then age, gender and ethnicity together (p = 0.0184) did not alter this pattern appreciably. No association between traumatic police incidents and depression was observed. Results indicate that exposure to multiple negative life events is significantly associated with elevated depression scores among this sample. Police agencies should consider developing psychological assistance efforts to help affected officers cope with these events and deal with depression.     

A comparison of life events between suicidal adolescents with major depression and borderline personality disorder

The current study compared the correlations of different types of stressful life events (SLE) between suicidal adolescents with major depressive disorder (MDD) and suicidal adolescents with borderline personality disorder (BPD). Both groups were referred following an attempted suicide. Twenty adolescents with MDD and 20 adolescents with BPD who were consecutively referred to an outpatient clinic following a suicide attempt were evaluated. A community control group of adolescents with no lifetime history of suicidal behavior was also assessed. The following measurements were employed: the Suicide Risk Scale (SRS) Beck Depression Inventory (BDI), the Life Events Checklist (LEC), and the Childhood Sexual Abuse Questionnaire (CSEQ). Both groups of suicidal subjects reported more SLE in general and more physical abuse than community controls in the 12 months before the suicide attempt. The MDD adolescents had more lifetime death-related SLE than the BPD and control groups, while the BPD adolescents reported more lifetime sex abuse-related SLE than the other two groups. Thus, suicidal behavior in general may be related to the amount of SLE. However, different disease-specific life events may precipitate suicide attempts in adolescents with MDD and BPD.     

Resilience,stressful life events,and depressive symptomatology among older Chinese adults

Objective: The association between exposure to stressful life events (SLEs) and late-life depression is well-documented. However, the role of resilience as a buffer against the adverse mental health effects of SLEs in late life has not been convincingly demonstrated. In this paper, the moderating effect of resilience in the relationship between SLEs and depressive symptomatology in older Chinese adults is investigated.

Method: A population sample of 385 community-dwelling older Chinese adults aged ≥60 years responded to questionnaires on resilience (Connor–Davidson resilience scale), depressive symptomatology (Geriatric Depression Scale, GDS-15) and SLEs.

Results: Increased numbers of SLEs (β = 0.343, p < .001) and lower levels of resilience (β = –0.137, p < 0.001) were significantly associated with higher levels of depressive symptomatology. There was a significant interaction of resilience and number of SLEs on depressive symptomatology (p = 0.003). The sense of personal competence and optimism was the principal underlying resilience dimension moderating the relationship for both the young–old (aged 60–69) and the old–old (aged 70 and above).

Conclusion: The finding of significant interaction supported the role of resilience in moderating the adverse effect of SLEs in terms of depressive symptoms among older Chinese adults.