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Biomedical subjects

B J Carroll

Publications and source records attributed to B J Carroll.

At least 127 records · Page 7Linked to original sources

Problems with diagnostic criteria for depression.

Limitations of the three major psychiatric diagnostic systems are discussed, with particular reference to depression and its subtypes. The lack of demonstrated reliability and validity for standard diagnoses, and the use of these diagnoses as independent variables in clinical research, is criticized. Possible approaches to improving current classification methods include increased specificity and sensitivity of symptoms, differential weighting, and objective recording. Scientific validation procedures should be applied to the classification of depressions, including studies of natural history and course, specific antidepressant drug responses, and the use of laboratory markers such as the dexamethasone suppression test and sleep EEG parameters.

Antidepressive Agents↗

Dexamethasone suppression test for depression.

The DST is a practical laboratory test that can be used in outpatient or inpatient settings. The required laboratory technology is available at any hospital. No subjective, behavioral, or metabolic side-effects occur with the single-dose administration of dexamethasone, and the test is well tolerated by patients. The test is not affected by most of the usual psychotropic drugs, and no special dietary precautions are needed. The recommended procedure for inpatients yields good sensitivity (67%) and high specificity (96%). Like many laboratory tests, the DST will be most useful if there is a moderate probability that the disorder being considered (melancholia) is actually present (4). If the prevalence of melancholia in the population tested is at least 35%, then the predictive value (diagnostic confidence) of an abnormal test result will be at least 90%. If the prevalence is very low, however, then the predictive value also will be much lower. Thus, the DST is not suitable for screening unselected patients but should be used when the clinician thinks it might help to answer a specific diagnostic question. Several clinical applications of the DST are being developed, as outlined above. All of these proposed uses of the test need further study. As the test is used more widely, an important principle to remember will be that physicians treat patients, not laboratory results; the test results always should be interpreted in clinical context. Provided that the principles of application discussed above are observed, then the DST has real potential for aiding clinicians in the diagnosis and management of depressed patients. Given the known unreliability of clinical diagnoses, it will not be surprising to find that the laboratory test result causes clinicians at times to reevaluate their patients and to recognize treatable depressions that were previously overlooked.

Adolescent↗

Biological markers for endogenous depression in series and parallel.

Several authors have shown that endogenous depressed patients have biological abnormalities which exist to a lesser extent in nonendogenous depressives and in normals, and have suggested that these biological abnormalities may be used as markers to classify depressed patients as endogenous or nonendogenous. We have investigated several of these biological abnormalities, and have explored the diagnostic classifications based on individual markers and on two or more markers in combination. The evaluation of combinations of diagnostic tests requires different statistical techniques than does the evaluation of single tests, and we discuss two such techniques: stepwise multiple regression and contingency table analysis. We report here our results with the dexamethasone suppression test (DST), EEG studies of sleep, and the amphetamine-stimulated release of growth hormone separately and in combination. The amphetamine-stimulated release of growth hormone was not diagnostically useful.

Amphetamine↗

Dexamethasone suppression tests in antidepressant treatment of melancholia. The process of normalization and test-retest reproducibility.

Pilot studies suggest that changes in response to the dexamethasone suppression test (DST) in melancholic patients receiving antidepressants might represent a laboratory marker of clinical progress. We performed weekly DSTs in 31 hospitalized patients with major depressive disorder, primary and endogenous subtypes, during drug-free and subsequent treatment periods. Most nonsuppressors had progressive normalization of DST responses in conjunction with clinical improvement, DST normalization usually preceded or coincided with good clinical response, and failure to normalize was often associated with poorer clinical outcome. Occasional patients with baseline dexamethasone suppression become nonsuppressive after withdrawal from medication, but the DST has no apparent value as a serial marker in patients with well-documented normal DST findings. Our results extend the construct validity of the DST as a state-related marker in nonsuppressors and suggest future clinical applications.

Adult↗

Separation of subtypes of depression using discriminant analysis. Separation of bipolar endogenous depression from nonendogenous ("Neurotic") depression.

We derived a discriminant function separating patients with bipolar endogenous depression ("melancholia") from patients with nonendogenous ("neurotic") depression, and showed that the difference between the groups was not one of overall severity of illness alone. The discriminant function (DF) included 5 clinical items. We reduced the DF to a discriminant index (DI) with integral item weights, and trichotomized the DI scores into two definite classifications and an intermediate, uncertain classification. We cross-validated this DI in a separate group of patients, and found no decrease in the accuracy of classification on cross-validation. Thirty-three of 41 (80%) of the patients in the cross-validation group were classified by the DI; 26 of 33 (79%) correctly. We also validated the DI classification against an external, biological marker, the dexamethasone suppression test (DST). The DI predicted the DST result with the same accuracy as the clinical diagnoses did, supporting the validity of the DI.

Adult↗

Inferential statistical methods for strengthening the interpretation of laboratory test results.

Laboratory test results for the diagnosis of psychiatric illness usually are reported descriptively despite the ready availability of appropriate inferential statistics. A test's sensitivity, specificity, and diagnostic confidence are conditional probabilities. Confidence intervals may be calculated for these probabilities in any given study. Statistical tests for comparing the results of several studies use techniques for planned and posterior comparisons applied to contingency tables. These established statistical methods aid in the interpretation of laboratory test findings.

Depressive Disorder↗

Escape from dexamethasone suppression: possible role of an impaired inhibitory opioid mechanism.

Several lines of evidence indicate that the activity of the hypothalamus-pituitary-adrenal (HPA) axis in depression is disinhibited. Escape from dexamethasone suppression, although not limited to is more frequent in patients with endogenous depression compared to normals or patients with other psychiatric diagnoses. Norepinephrine, serotonin and acetylcholine have been implicated in the pathophysiology of this neuroendocrine abnormality. Morphine, 5 mg intravenously, suppressed cortisol secretion in healthy volunteers (n = 4) and the majority of 32 psychiatric inpatients. However, patients with endogenous depression and abnormal dexamethasone suppression test results show early resumption (escape) of cortisol secretion following the initial suppression induced by morphine. It is concluded that the pathophysiology of this neuroendocrine abnormality is not limited to classical neurotransmitter-HPA axis interaction but that it also involves opioid inhibitory mechanisms.

Depressive Disorder↗

Depressive pseudodementia: a suggested diagnostic profile.

Severe cognitive and memory impairments often occur during episodes of depression, making it difficult to differentiate true dementia from depressive pseudodementia. The dexamethasone suppression test (DST) and the computerized tomography of the brain (CT scan) may aid in this problem. Eleven patients were assessed with the Hamilton Depression Rating Scale (HDRS), a Dementia Scale (DS), the overnight DST, and CT scans. Clinicians and raters were blind to DST results. All patients initially had high DS scores. These changed in most patients following antidepressant treatments. This study suggests a profile for the diagnosis of pseudodementia. Patients with cognitive impairment, dysphoric mood, abnormal response to the DST, and normal CT scan tend to have depressive pseudodementia. Patients with the first three features but with an abnormal CT scan likely have depression and structural brain pathology. Both groups respond to antidepressant treatments, although the latter continued to have some cognitive dysfunction during euthymia. A third group, the "true" dementia patients, may have abnormal CT scans and a normal DST response but larger samples are needed for confirmation.

Aged↗

Use of the Children's Depression Rating Scale in an inpatient psychiatric population.

The Children's Depression Rating Scale is a useful and reliable instrument for measuring the severity of depression in children. The scale was initially used in a pediatric liaison population. This study reports its use in consecutive admissions to a child inpatient unit. Systematic evaluations of the children resulted in many diagnoses of depression which were missed by the clinical staff. Two relatively inexperienced raters did nearly as well as two raters who originated the scale, suggesting that the CDRS may have practical utility in many settings.

Child↗

Detailed analysis of estrous-related changes in wheel running and self-stimulation.

Previous studies have demonstrated that a number of behaviors change their probability of occurrence during the estrous cycle. Wheel running is known to show estrous-related changes while reports upon intracranial reinforcement (self-stimulation, ICS) have been equivocal. The present studies examined both behaviors to further resolve the underlying behavioral determinants of these estrous effects. Data for wheel running and intracranial self-stimulation behaviors of adult female Holtzman rats were collected nightly on a minute by minute basis across the estrous cycle. It was found that: (a) both behaviors showed significant estrous-related changes in frequency; (b) the two behaviors occurred in discontinuous episodes (bursts) during the dark phase of the diurnal cycle; and (c) of three burst parameters (number/session, average length, rate of response), number proved the best predictor of estrous-related behavioral change. Burst number may reflect an important motivational parameter underlying estrous-related changes in behavior.

Animals↗

Clinical applications of the dexamethasone suppression test for endogenous depression.

The dexamethasone suppression test (DST) was developed from the neuroendocrine research strategy to provide indirect information about the integrity of the limbic system in patients with endogenous depression (ED). Abnormal test results occur in close temporal relationship to clinical episodes of ED, but not during the intervals between episodes. The neuroendocrine disinhibition revealed by the test is not a trait marker of individuals predisposed to develop ED. A standardized DST procedure has been established and can be applied in outpatient or inpatient routine clinical practice, with good sensitivity (50-65%) and high specificity (96%). The conditional probability principles of interpreting the test results are discussed and the effect of prevalence on the predictive value of the test results is emphasized. The DST should not be used as a screening test for all psychiatric patients but should be reserved for cases where clinical indications for its use are present. These indications include diagnostic confirmation of ED, monitoring the response to treatment, prediction of relapse or new episodes, and possibly prediction of suicide risk in patients with ED. The test may be especially useful in the diagnostic assessment of patients with difficult or confusing presentations of ED such as catatonia, depressive pseudodementia, depression in adolescents or children, "masked" depression, depression complicated by a personality disorder, and schizoaffective depression.

Aging↗

The kinetics of solubilization of single component non-polar oils by a non-ionic surfactant.

The kinetics of solubilization of two non-polar oils (hexadecane and 2,6,10,15,19,23 hexamethyl tetracosane) by a pure non-ionic surfactant (n-dodecyl hexaethylene glycol ether) have been investigated using a recently developed technique. A linear dependence of rate upon surfactant concentration above the cmc and a rapid increase in rate at temperatures close to the cloud point were observed. A previously developed theoretical description of the process has been expanded to account for the observation that the rates for the oils in given systems are not in the exact ratio of the equilibrium capacities of the system for the respective oils. If the effects of changes in aggregation number and shape of the micelle/solubilizate complex are considered, the absolute values of the measured and theoretical rates are in good agreement. Furthermore, the activation energies are nearly equal for the two solubilizates, a result which is in accord with theory. The micelle relaxation time tau 2 is practically independent of surfactant concentration.

Chemistry, Pharmaceutical↗

Application of biological markers in depression secondary to thyrotoxicosis.

Biological markers of affective disorders have not been studied intensively in patients with secondary depression. An elderly woman with severe delusional depression secondary to thyrotoxicosis was monitored with weekly dexamethasone suppression tests (DSTs) and three sleep electroencephalography (EEG) evaluations. She received treatment only for her thyrotoxicosis, but her depression resolved completely. The serial DSTs were normal throughout her depression, consistent with the specificity of this test for primary endogenous depression. The sleep EEG erroneously suggested a diagnosis of primary depression but effectively monitored clinical improvement. Biological markers may have applicability in evaluating and monitoring patients with secondary depression.

Aged↗