The dexamethasone suppression test and unipolar/bipolar distinctions

In an attempt to validate several subtypes of affective disorders, 52 consecutive patients hospitalized at a clinical research center were comprehensively classified along several diagnostic and phenomenologic axes. Cortisol levels of each patient were evaluated at baseline and after the administration of 0.5 and 1.0 mg dexamethasone. None of the depressive subtypes responded significantly differently to the 1.0 mg dose. However, the bipolar subtype was associated with significantly different DST responses to the 0.5 mg dose. Patients with bipolar affective disorder, both manic and depressed, had higher postdexamethasone mean cortisol levels than all other groups. The results support the distinctiveness of the bipolar diagnosis.     

双相情感障碍抑郁相与单相抑郁发作临床分析

目的:对双相情感障碍抑郁相和单相抑郁发作进行临床分析。方法:对双相情感障碍抑郁相和单相抑郁发作患者各30例进行临床分析。结果:双相情感障碍抑郁相有如下特点:①发病年龄早;②女性多见;③具有“精力过盛”性人格;④一级亲属中有双相障碍的家族史;⑤症状多为非典型抑郁发作或伴有精神病性症状。结论:如首次抑郁发作的症状符合以上特点,则可能以后发展为双相情感障碍,应使用足量心境稳定剂,谨慎使用抗抑郁剂,以免转为躁狂发作。     

Glucocorticoids and relapse of major depression (dexamethasone/corticotropin-releasing hormone test in relation to relapse of major depression).

BACKGROUND: Knowledge of pathogenic mechanisms and predictors of relapse in major depressive disorder is still limited. Hypothalamic-pituitary-adrenocortical (HPA) axis dysregulation is thought to be related to the development and course of depression. METHODS: We investigated whether dexamethasone/corticotropin-releasing hormone (DEX/CRH) test parameters were related to the occurrence of relapse in 45 outpatients with clinically remitted major depression. The DEX/CRH test was administered before and after 8 weeks of antidepressant treatment. RESULTS: Posttreatment maximal adrenocorticotropic hormone (ACTH) and maximal cortisol levels, as well as delta ACTH and delta cortisol levels, were significantly higher (all p < .05) among patients who relapsed (n = 22) compared with patients in whom no relapse occurred (n = 23). Higher posttreatment maximal cortisol response on the DEX/CRH test was associated with shorter "relapse-free survival" (p = .05). CONCLUSIONS: In outpatients with clinically remitted major depression, higher posttreatment maximal cortisol levels on the DEX/CRH test were associated with relapse of major depression.     

The heritability of bipolar affective disorder and the genetic relationship to unipolar depression

BACKGROUND: Twin studies of bipolar affective disorder (BPD) have either been small or have not used explicit diagnostic criteria. There has been little use of genetic model fitting and no analyses to explore the etiological overlap with unipolar depression (UPD). METHODS: Sixty-seven twin pairs, 30 monozygotic and 37 dizygotic, in which the proband had BPD were ascertained, and lifetime diagnoses were made using DSM-IV criteria. Univariate models were applied to estimate the contribution of additive genetic and environmental effects. Bipolar data were then combined with those from 68 monozygotic and 109 dizygotic pairs in which the proband had UPD. Two models were explored: a classic 2-threshold approach, in which BPD and UPD occupy the same continuum of liability but differ in severity, and a correlated liability model of mania and depression. RESULTS: Heritability of BPD was estimated at 85% (95% confidence interval [CI], 0.73-0.93) using narrow concordance and 89% (95% CI, 0.61-1.0) using broad concordance, with no shared environmental effects detected. A 2-threshold model was an unsatisfactory fit. Fitting a correlated liability model revealed a genetic correlation of 0.65 (95% CI, 0.58-0.75) between mania and depression and a correlation of 0.59 (95% CI, 0.15-0.84) for nonfamilial environment. Approximately 71% of the genetic variance for mania was not shared with depression. CONCLUSIONS: As defined by the DSM-IV, BPD is highly heritable. There are substantial genetic and nonshared environmental correlations between mania and depression, but most of the genetic variance in liability to mania is specific to the manic syndrome.     

The thyrotropin-releasing hormone test in the diagnosis of unipolar depression

The establishment of criteria for a blunted thyroid-stimulating hormone (TSH) response to thyrotropin-releasing hormone (TRH) may prove useful in distinguishing patients with major unipolar depression from patients with nonmajor depressions and controls. To this end, we administered the TRH test to a group of depressed, euthyroid inpatients diagnosed by Research Diagnostic Criteria and 20 normal volunteer controls. The mean maximal TSH response (delta TSH) to infusion of 500 micrograms of TRH of 7.3 +/- SD 4.6 microIU/ml in the 105 patients with major depressive disorder, primary unipolar subtype was significantly lower than that of 13.4 +/- SD 4.4 in the 20 controls and 10.9 +/- SD 4.4 in the 40 patients with nonmajor depressions. The differences were not explainable by differences in baseline thyroid function, age, or sex. When a delta TSH less than or equal to 7.0 microIU/ml was used as a diagnostic test for unipolar depression, the sensitivity of the TRH test was 56%, the specificity 93%, and the predictive value 91%. These results suggest that the TRH test may be useful in confirming the diagnosis of major unipolar depression and hence identifying patients likely to respond to antidepressant medications or electroconvulsive therapy.     

From unipolar depression to bipolar illness: 29 who changed

We studied 29 patients who were admitted to a psychiatric hospital for depression, never had had a previous mania, and developed the mania in follow-up. When compared to patients who were stable unipolars, the potential bipolars had a history of more episodes prior to their onset of mania, more hospital admissions, more marked self-reproach and guilt; in follow-up, they had more hospitalizations.     

Types of depression more frequent in bipolar than in unipolar affective illness: results of the Polish DEP-BI study

BACKGROUND: The aim of the study was to assess the relative frequency of various kinds of depression in patients with bipolar and unipolar affective illness. The study was performed in the framework of the DEP-BI project aimed at assessing the prevalence of bipolar disorders among depressive outpatients treated by psychiatrists in Poland. METHODS: Eight-hundred and eighty patients (237 male, 643 female) participated in the study. The patients were classified into the following diagnostic categories: bipolar affective illness type I, type II, bipolar spectrum disorder and unipolar affective illness. The various kinds of depression in each group were assessed by means of a semistructured questionnaire added to the diagnostic interview. RESULTS: In the group of bipolar patients, a significantly higher frequency of psychotic depression in male compared to female patients was observed. Male bipolar patients compared with unipolar depressed ones had significantly more episodes of psychotic depression (odds ratio, OR, 4.29) and atypical depression (hypersomnia and hyperphagia; OR 2.82), and those with bipolar spectrum had more episodes of treatment-resistant depression (OR 2.56). Female bipolar patients compared with unipolar depressed ones had significantly more frequently an early onset of depression (before 25 years; OR 2.95) and postpartum depression (OR 2.48). On the other hand, the percentage of agitation, irritability, distractibility, thought racing and panic attacks during depression was not different in patients with bipolar and unipolar affective illness either in males or females. CONCLUSIONS: Some kinds of depression occur with a higher frequency in patients with bipolar compared to unipolar affective illness. The occurrence of a given type of depression may constitute an aid for the diagnosis of bipolar illness. The results of this study did not confirm the concept of bipolar mixed depression based on the presence of anxiety symptoms occurring during the depressive episode. The limitation of our study may be the lack of formal criteria or a structured interview to assess the symptoms occurring during depressive episodes.     

Rapid cycling in unipolar and bipolar affective disorders

To characterize the nature of rapid cycling affective disorders, the authors analyzed mood fluctuation patterns in 570 patients with affective disorders hospitalized in 1960, 1975, or 1985. Patients' records were rated for the frequency, duration, and complexity of distinct affective states. Very rapid mood fluctuations were absent among bipolar patients in 1960 but were evident in 1975 and 1985. In each year, bipolar patients displayed more frequent, complex, and mixed episodes than did unipolar patients. The results suggest that more frequent episodes occur among bipolar than unipolar patients and that very rapid switch processes have become more widespread for some bipolar patients.     

REM architecture changes in bipolar and unipolar depression.

The authors compared total night sleep measures and REM sleep architecture values for normal control subjects (N = 36), unipolar depressed patients (N = 36), and bipolar depressed patients (N = 22). The unipolar and bipolar patients had significantly greater fragmentation of REM periods than control subjects, and bipolar patients showed greater fragmentation of REM periods than unipolar patients. In both the unipolar and bipolar samples, the duration of successive REM periods was related to the total number of REM periods during sleep.     

A combined dexamethasone/corticotropin-releasing hormone test in patients with chronic PTSD--first preliminary results

BACKGROUND: Reports about alterations of hypothalamic-pituitary-adrenocortical (HPA) function in patients with chronic posttraumatic stress disorder (PTSD) are inconsistent and controversial. More refined laboratory tests and subgrouping of PTSD patients might help to decrease variance of findings. METHODS: 14 subjects with chronic PTSD and 14 healthy controls were examined between 13:00 and 17:00 using a modified combined dexamethasone/CRH test (0.5 mg dexamethasone at 23:00, 100 microg CRH at 15:00). Plasma adenocorticotropic hormone (ACTH), cortisol and blood pressure were measured every 15 min from 14:45 until 17:00. RESULTS: No significant differences between patients and controls were found in the analyses of ACTH and cortisol levels, but a significantly elevated systolic and diastolic blood pressure in PTSD. Severity of depressive symptoms had no influence. However, explorative analyses showed that patients with a history of childhood traumatization had significantly higher post-dexamethasone-ACTH levels and a significantly lower diastolic blood pressure in comparison to patients without early trauma. CONCLUSIONS: In this first pilot study in a typical clinical sample of patients with chronic PTSD we found effects of severe adverse events in childhood on HPA axis regulation. Maybe, childhood traumatization could influence HPA axis findings in PTSD. Further research is needed, especially dose-response studies with different doses of dexamethasone in dexamethasone/CRH tests in PTSD.     

Depressive symptoms in patients with unipolar and bipolar affective disorder.

The study of biologic differences in patients with affective illness is dependent in part on a clinical classification which separates depressed patients into subgroups of greater homogeneity. The unipolar-bipolar classification is one such system, and the use of this classification has been supported by clinical, biologic, genetic, and pharmacologic studies of affective disorder.¹ This paper is part of a series of studies to determine if patients with depression and hypomania (“bipolar II”) can be distinguished from patients with depression and severe mania (“bipolar I”) and patients with depression without hypomania (unipolar).^2–4 In this paper, symptoms of depression, as measured with the use of a modified Hamilton depression rating scale,⁵ a nurses' global rating scale, and self-administered adjective check list, will be examined in moderately to severely depressed patients who were admitted to a clinical metabolic research unit.     

单双相抑郁患者的情感气质特征及其与抗抑郁治疗反应的关系

目的探索单相抑郁、双相I型和双相II型抑郁患者情感气质特征的差异及其与抗抑郁治疗反应的关系。方法收集广州医科大学附属脑科医院和暨南大学第一附属医院的住院和门诊患者,包括332例单相抑郁患者、116例双相I型患者和152例双相II型患者,所有患者均处于重性抑郁发作期。在为期6周的半自然临床试验中,所有患者均接受抗抑郁药治疗,完成情感气质问卷中文版(TEMPS-A)和汉密尔顿抑郁量表17项版(HAMD-17)评定。比较治疗4、6周末不同气质类型为主导气质患者HAMD-17评分减分率。结果双相I型患者旺盛情感气质评分高于单相抑郁患者和双相II型患者[(9.91±4.53)分vs.(8.20±4.34)分vs.(8.53±4.14),F=6.562,P=0.002];而双相II型患者环性气质评分高于单相抑郁患者[(10.05±5.02)分vs.(7.47±5.22)分,F=12.89,P0.01]。治疗6周后,情感旺盛气质主导组HAMD-17评分减分率高于情感旺盛气质非主导组(F=6.44,P=0.011)。结论单双相抑郁患者的情感旺盛气质和环性气质的特征有所差异,旺盛情感气质可能可以作为处于重性抑郁发作期的情感障碍患者抗抑郁治疗反应的预测因子。     

Mortality in patients with primary unipolar depression, secondary unipolar depression, and bipolar affective disorder: a comparison with general population mortality

Mortality data are presented from a two to fourteen year follow-up of 705 primary unipolar depressives, 302 secondary unipolar depressives, and 586 patients with bipolar affective disorder (BAD) hospitalized at a tertiary care facility. Death ascertainment was made through a record-linkage process. Using sex- and age-standardized mortality ratios (SMRs), the mortality experience of the study population was compared with that of Iowa, the geographical area served by the admitting medical facility for this study group. Results show that risk for all-cause mortality was most pronounced during the first two years following hospital discharge, although secondary unipolar depressives continued to show a significant excess of deaths throughout the entire follow-up period. Deaths occurring from natural causes were significantly excessive only during the initial portion of the follow-up. Deaths from unnatural causes were significantly excessive throughout follow-up except for patients with bipolar affective disorder.     

Psychotic features in bipolar and unipolar depression

BACKGROUND: While some prior studies have found higher rates of psychotic depression in those with bipolar disorder or a bipolar relative, others have failed to confirm these observations. We examined the relationship of psychotic depression to polarity in several large familial samples of mood disorder. METHODS: A total of 4,724 subjects with major mood disorder in three family studies on the genetics of bipolar I disorder (BPI) or recurrent major depressive disorder (MDDR) were administered semi-structured interviews by clinicians. Determination of psychotic features was based on a report of hallucinations and/or delusions during the most severe depressive episode in the Schedule for Affective Disorders and Schizophrenia-Lifetime Version or the Diagnostic Interview for Genetic Studies interview. Rates of psychotic depression were calculated by diagnostic category and comparisons were made between diagnoses within and across studies using the generalized estimating equation. RESULTS: A diagnosis of BPI disorder was strongly predictive of psychotic features during depression compared to MDDR [odds ratio (OR) = 4.61, p < 0.0005]. Having bipolar II compared to MDDR was not predictive of psychosis (OR = 1.05, p = 0.260), nor was having a family history of BPI in MDDR subjects (OR = 1.20, p = 0.840). CONCLUSIONS: Psychotic features during a depressive episode increased the likelihood of a BPI diagnosis. Prospective studies are needed to confirm these findings. The potential genetic underpinnings of psychotic depression warrant further study.     

Psychomotor performance and monoamine function in bipolar and unipolar affective disorders.

BACKGROUND: Affective disorders are associated with prominent psychomotor abnormalities that may be related to changes in arousal or motivation due to altered catecholamine function. METHODS: We investigated relationships between performance on psychomotor tests of motor speed (reaction time and tapping speed) and visual tracking (trail making and dot placement) and catecholamine system function including cerebrospinal fluid (CSF) or urinary concentrations of catecholamines or their metabolites. Subjects were medicine-free inpatients with unipolar depression or with manic, depressive, or mixed episodes of bipolar disorder, and healthy controls matched by gender and stratified by age. RESULTS: Unipolar and bipolar depressed patients were impaired in motor speed, dexterity, and visual tracking, whereas manic and mixed patients did not differ from controls. Tapping speed correlated positively with CSF 3-methoxy-4-hydroxyphenylglycol in healthy controls and with CSF homovanillic acid in bipolar depressed subjects. Increased catecholamine function correlated with slowing in all other measures for patients with bipolar disorder. Relationships between catecholamines and psychomotor function were weaker in unipolar depressed subjects. Psychomotor function was related to severity of depression in bipolar, but not in unipolar, patients. CONCLUSIONS: These data suggest that catecholamine systems are associated with increased arousal and psychomotor impairment in patients with bipolar disorder. Similar behavioral changes have different neurotransmitter relationships in unipolar disorder.