DST in depression is unaffected by altering the clock time of its administration

Circadian oscillators in major depressive illness may be phase advanced by several hours. We attempted to determine whether phase advance of the oscillator responsible for hypothalamic-pituitary-adrenal (HPA) function in depressives might influence the outcome of the overnight dexamethasone suppression test (DST). Six major depressives underwent DST with dexamethasone doses administered in a randomized fashion at 1900h and 2300h on separate evenings. Twenty-four hour cortisol secretory patterns basally and postdexamethasone were obtained for each subject. Postdexamethasone cortisol responses were similar for both the 1900h and 2300h dosage schedules in suppressors, nonsuppressors, and an early escape responder. We conclude that failure of the HPA axis to suppress normally with DST in major depressive illness is a primary feature of neuroendocrine regulatory mechanisms rather than secondary to a posited phase advance of the related circadian oscillator.     

A clinical study of reactive psychosis

Manifest psychopathology, life events, family history and personality traits were studied in a group of 22 patients diagnosed to have reactive psychosis. Individually matched healthy controls were also assessed for life events. The patient group had significantly higher weighted stress scores than the controls. Compared with Scandinavian patients, the study patients had more delusions, hallucinations and emotional syndrome.     

Dexamethasone suppresion test (DST) and plasma dexamethasone levels in depressed patients

The dexamethasone suppression test (DST) was evaluated in newly hospitalized patients with a DSM-III diagnosis of major depression. Patients with other psychiatric disorders and a normal control group were also studied. Plasma dexamethasone levels were obtained in all patients, and the relationship between plasma cortisol and plasma dexamethasone was examined. Rates of non-suppression in patients with major depression (39%) were not significantly different from those in patients with minor depression (25%), mania (38%), or other psychiatric illnesses (17%). The ranges of dexamethasone levels at 8 a.m. and 4 p.m. were similar between patient groups and controls. However, there was a significant difference in dexamethasone levels between suppressors and nonsuppressors, irrespective of diagnosis, which could not be explained by differences in weight or plasma dexamethasone half-life. Inappropriately high dexamethasone levels were found in some patients with a 1 mg test, a problem that critically affects the sensitivity of the test procedure.     

Ventricular dilatation and brain atrophy of normal elderly individuals and patients with Alzheimer-type dementia: A retrospective longitudinal computed tomographic study of autopsy cases

A retrospective longitudinal study of autopsy cases was performed in order to investigate the time course of ventricular dilatation and brain atrophy in normal individuals and patients with Alzheimer-type dementia (ATD) subjects over 70 years of age. The brains of eight non-demented individuals with no neurological or psychiatric illness (normal subjects, aged between 73 and 91 years), and the brains of seven ATD subjects (aged 68–96 years) were studied. The clinical records, including computed tomographic (CT) films, and autopsy findings were examined to eliminate subjects with conditions other than ATD. The rate of ventricular dilatation and brain atrophy was determined by volumetric measurement using serial CT films. Alzheimer-type dementia was diagnosed on the basis of clinical findings, the presence of laminar cortical degeneration of the medial temporal cortex, and the density of senile plaques and neurofibrillary tangles. Ventricular dilatation was not detected in the normal subjects but was detected in the ATD patients during the follow-up period. Brain atrophy was detected in both groups of subjects. However, the mean rate of brain atrophy of the ATD subjects was four times greater than that in the normal subjects. In addition, brain atrophy was accompanied by ventricular dilatation in all of the ATD patients, but was not evident in six of the eight normal subjects. Thus, the rate of ventricular dilatation was correlated with that of brain atrophy in the ATD patients, but not in the normal subjects. These results show that after 70 years of age: (i) the ventricular dilatation in normal subjects probably does not progress; (ii) brain atrophy in most normal subjects may continue; and (iii) rapidly progressive brain atrophy with ventricular dilatation is probably a common characteristic of ATD patients.     

Provocative endocrine testing in recovered depressives

Twenty-eight patients underwent a series of provocative endocrine tests an average of one year after their last admission for depression. Hypersecretion of cortisol, early escape of cortisol from dexamethasone suppression, diminished growth hormone response to insulin-induced hypoglycemia and altered thyrotropin response to thyrotropin-releasing hormone reported in acute primary depression were not observed after recovery. There were no differences in these measures after recovery between previous suppressors and nonsuppressors to dexamethasone. The cortisol response to insulin-induced hypoglycemia was less than expected in 6 of 16 recovered patients tested. There were significant differences in post-dexamethasone urinary free cortisol and in basal and early post-insulin serum cortisol levels between patients who had been suppressors and those who had been nonsuppressors to dexamethasone during acute depression. Further studies need to be done to substantiate these findings. These data indicate that hormone responses in recovered depressives are largely normal, suggesting that abnormalities during depression are "state" related phenomena.     

Mortality in the elderly— A 3-year follow-up of an elderly community sample

A simple random sample of 334 persons aged 75+ years living in their own homes was initially examined in 1984/1985 and reexamined by the same physician 3 years later. The assessment included measures of mental and physical health, social integration, functional capacity, use of drugs and use of tobacco and alcohol. Mortality was recorded in the following 3 years. The mortality rate was increased among demented and depressed elderly and persons suffering from stroke or cancer. Increased mortality was also seen among subjects with hearing impairment, poor mobility and poor social integration, and in users of neuroleptics, digitalis and tobacco. A stepwise logistic regression analysis identified dementia, cancer, male sex and hearing impairments as explanatory variables for death. The study concludes that several factors may predict mortality in the elderly, especially in persons of 75 years and over. When compared with other studies, the most consistent predictors of death in elderly persons are dementia, depression and poor social integration.     

Effect of interrupted sleep patterns and partial sleep deprivation on DST and mood in psychiatric house officers

To gain further insight into clinical associations seen in depression, the authors investigated the effect of interrupted night-time sleep on the HPA axis and mood in 20 psychiatric house officers taking overnight call. Specific interest was in whether multiple awakenings could induce a positive DST. No statistically significant association emerged between number of nocturnal awakenings, number of hours of sleep deprivation or temporal occurrence of sleep deprivation and cortisol, DST or mood. The results suggest that cortisol and DST changes are not likely to be causally linked to, or epiphenomenon of disrupted sleep. The implications of these findings for major depression are discussed.     

The effect of weight loss and inappropriate plasma dexamethasone levels on the DST

Recent studies from different research groups have raised fundamental questions about the postulated specificity of the dexamethasone suppression test (DST) for endogenous depression. Findings in 116 psychiatric inpatients and 24 semi-starved healthy volunteers underline the importance of weight loss as a factor affecting DST results. A study of 160 DSTs in 93 psychiatric inpatients further revealed a significant negative correlation of plasma cortisol and plasma dexamethasone levels 10 hours after oral administration of 1 mg of dexamethasone. These results suggest a decisive effect of the pharmacokinetics of dexamethasone, at least on the 1-mg DST.     

Mean 14.00-17.00 h plasma cortisol concentration and its relationship to the 1 mg-dexamethasone suppression response in depressives and controls

Three-hour cortisol-profiles and cortisol responses to a 1 mg dose of dexamethasone were recorded in 31 depressed patients and nine controls. The data indicate that the likelihood of detecting non-suppressible cortisol concentrations after dexamethasone is significantly increased in depressed patients with a hypersecretion of cortisol. However, a considerable subsample of normosecretors shows abnormal DST results. Conversely, hypersecretion is often associated with dexamethasone suppression. In this study a 1 mg-DST did not reflect the adrenocortical activity with ultimate accuracy. Therefore any attempts which correlate psychopathological or biological data with pituitary-adrenal activity and use a DST-result as measure are criticizable . Data derived from volunteers illustrate that medical factors such as weight-loss, steroid-containing contraceptives and sleep deprivation can make a pituitary-adrenal activity test ambiguous.     

Total plasma 3-methoxy-4-hydroxyphenylglycol (MHPG) in alzheimer patients. Comparison with depressives and normal controls

Plasma levels of total 3-methoxy-4-hydroxyphenylglycol (MHPG) were found to be significantly higher in patients with Alzheimer's disease (N = 20) than in age- and sex-matched normal controls and dexamethasone-resistant melancholic patients. Contrary to previous studies, the highest levels were not found in the most severely demented patients and this increase was not related to the duration of the illness. Although the significance of these findings remains unclear, they suggest that determination of total plasma MHPG may be useful in the differential diagnosis of Alzheimer's disease and depressive disorder.     

Theory of mind in individuals with Alzheimer-type dementia

Abstract

Background: Theory of Mind (ToM) ability allows attribution of mental states to oneself and others. Recent studies suggest that impairment of ToM may be a partial cause of social-communication impairment in adults with right hemisphere disorder, frontal lobe damage, and the frontal variant of frontotemporal dementia. Initial evidence has also been presented for a ToM impairment in individuals with Alzheimer's disease (AD), but extant investigations have inadequately controlled for other cognitive impairments.

Aims: The purpose of this study was to determine whether individuals with AD exhibit a ToM impairment that is distinguishable from cognitive and executive function deficits, and to investigate whether memory support affects their ToM performance.

Methods & Procedures: Ten participants with mild to moderate AD completed first‐order and second-order false belief tasks with and without memory support, and their performances on ToM testing were compared to those of elderly controls. All ToM testing was controlled with memory, comprehension, and general inferencing questions. AD participants completed neuropsychological testing to concurrently assess general cognitive functioning, memory, and executive functioning. Independent and paired t‐tests compared experimental and control group ToM performances. Correlations assessed relations between ToM and neurocognitive test performances.

Outcomes & Results: Results indicated that, in the absence of memory support, AD participants did not exhibit a specific ToM difficulty as compared to control participants. However, significant group differences for specific ToM impairment that appeared to be separable from comprehension, memory, and general inferencing difficulties emerged during ToM testing when memory support was provided. Correlations between ToM performance and neurocognitive test performances were not significant; however, four of the eight AD participants who exhibited specific, ToM difficulty also had difficulty with executive function testing.

Conclusions: These results indicate that individuals with mild to moderate AD may possess an underlying, mild, specific ToM impairment, which becomes apparent during supported memory testing. Such mild ToM impairment in moderate AD individuals must be further investigated, and possible contributions of executive function impairments to apparent ToM difficulty further explored before the current results can be confidently generalised to a larger AD population.     

Symptoms and subtypes of depression among adolescents distinguished by the dexamethasone suppression test: A preliminary report

Twenty-three adolescents hospitalized on an inpatient psychiatric unit underwent a dexamethasone suppression test (DST) and were diagnosed as having major depressive disorder by interviewers blind to the DST results. These patients were divided into four categories according to whether they had major depressive disorders, endogenous (MDDe) or nonendogenous (MDD), and whether they were nonsuppressors (+) or suppressors (-) in response to the DST, i.e., MDDe (+) MDDe (-), MDD (+), or MDD (-). Psychomotor features significantly differentiated the MDDe group from the MDD group. Among symptoms this further differentiated the MDDe (+) from the MDD (-) group. The primary subtype of depression occurred significantly more frequently among the MDDe group than the MDD group. The primary subtype also occurred more frequently among the MDDe (+) group than the MDD (-) group, whereas the MDD (-) group had a greater frequency of secondary depression.     

The dexamethasone suppression test in demented outpatients with and without depression

The dexamethasone suppression test (DST) was given to 33 elderly, male outpatients, previously diagnosed by DSM-III criteria as having dementia. Fifteen of these patients also had signs and symptoms of depression and, except for the presence of organic mental syndrome, would have met DSM-III criteria for major depressive episode. Of these 15 depressed, demented patients, 40% had abnormal DST results. None of the 18 patients who had dementia alone had abnormal DSTs. Our data suggest that in elderly, demented outpatients, an abnormal DST may be associated with concomitant depression.     

Plasma ACTH levels in depression before and after recovery: relationship to the dexamethasone suppression test

Sixteen patients with major depressive disorder who were nonsuppressors on the dexamethasone suppression test (DST) on hospital admission were studied for plasma levels of adrenocorticotropic hormone (ACTH). Eight patients reverted to normal suppression with clinical recovery, while eight remained nonsuppressors. There was a significant reduction of ACTH levels in those who normalized on their DST, while ACTH levels remained high in the group that continued to be nonsuppressors. The results favored the hypothesis that dexamethasone nonsuppression in depression is mediated by high ACTH levels.     

Cerebrospinal fluid acetylcholine and choline in vascular dementia of Binswanger and multiple small infarct types as compared with Alzheimer-type dementia

Summary The acetylcholine (ACh) and choline (Ch) concentrations in the cerebrospinal fluid were investigated in patients with vascular dementia of the Binswanger type (VDBT) or multiple small infarct type (MSID) as compared with patients with Alzheimer-type dementia (ATD). The ACh concentration in patients with ATD was found to be significantly lower than in controls (73%, p < 0.0001), and showed a significant positive correlation with dementia scale scores (r_s=0.63, p < 0.03). The Ch concentration in the CSF of ATD patients was approximately the same as in controls. In VDBT/MSID patients, the ACh concentration was significantly lower than in controls (p < 0.001), also showing a significant positive correlation with dementia scale scores (r_s=0.62, p < 0.02), but was significantly higher than in ATD patients (p < 0.001). Moreover, the Ch concentration in VDBT/MSID patients was significantly higher than in controls (p < 0.001) or ATD patients (p < 0.001). These results suggest that simultaneous determination of ACh and Ch concentrations in CSF may be useful for differentiating VDBT/MSID from ATD and that increasing the ACh level using cholinergic agents may be a beneficial therapeutic strategy for the treatment of ATD as well as VDBT/MSIT, and is worthy of further investigation.     

Occurrence of high concentrations of postdexamethasone cortisol in elderly psychiatric inpatients

The authors retrospectively studied 161 psychiatric inpatients who had received a dexamethasone suppression test (DST). The majority of the patients were over 60 years old, female, and had concurrent chronic medical illnesses. Age was significantly correlated with log-transformed postdexamethasone cortisol concentrations in the 118 nondemented patients with major depression. Four p.m. cortisol concentrations greater than 15 micrograms/dl occurred in 15 patients. All were over 60 years old; all but one had major depressive disorder (MDD); and five had dementia plus MDD. In the same population, a 5 micrograms/dl criterion did not distinguish MDD from non-MDD patients. The results support the existence of a clinically relevant age effect on the DST in patients with MDD. Elderly depressed patients with markedly elevated cortisol concentrations occur frequently, and warrant further clinical and pathophysiological study.     

Platelet MAO activity in clinical subtypes of depression and DST suppression

Platelet MAO activity was measured in 75 hospitalized depressed patients and in 31 healthy subjects. Plasmas post dexamethasone cortisol levels were examined in 73 patients. Results indicate that higher platelet MAO activity does not occur in all, but only in male major depressed patients. No relationship between changes of MAO activity and specific clinical subtypes was found. Platelet MAO activity is not different between DST suppressors and DST non suppressors. The authors suggest that platelet MAO activity may be related to non specific factors such as sex, age, but not to diagnosis of depression.     

The Relationship Between DST Results and Suicidal Behavior

The authors assessed the relationship between dexamethasone suppression test (DST) results and suicidalideations and behavior. Four-hundred-twenty-three mood disorder patients admitted to a tertiary caremedical center were administered the DST from 1978 to 1981. The patients were subsequently followed upto determine death status using a record-linkage method. More than 44% had abnormal cortisolsuppression (nonsuppressors) at the index admission. Suppressors and nonsuppressors did not differsignificantly with respect to frequency of suicidal ideations or completed suicides. Suppressors weresignificantly more likely than nonsuppressors to have a history of suicide attempts or to have a suicideattempt following hospital discharge. Using logistic regression, and controlling for several important variables including diagnosis, maximum postdexamethasone cortisol was not significantly associated withsuicide, suicidal ideation, or suicide attempts. We conclude that an abnormal DST is not useful as apredictor of suicidal behavior.     

Are depression and denutrition good predictors of dexamethasone suppression test (DST) in anorexia nervosa?

This study was conducted to investigate the corticotropic axis in anorexia nervosa. In 93 female inpatients who met DSM-III-R criteria for anorexia nervosa, subsample (n = 64) with DSM-III criteria was also considered. Using stepwise regression analysis, this study examined the relationship between independent variables ie, age, body mass index, scores on depression scales and postdexamethasone serum cortisol, considered as a dependent variable. In patients who met DSM-III criteria, 16.7% of the variance of serum cortisol can be explained. The main predictors are depressive retardation, emaciation and age. Using stepwise logistic regression the main categorical predictors of the test suppression vs non suppression are of the same nature. The condition of realisation of DST are discussed.