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Biomedical subjects

N M James

Publications and source records attributed to N M James.

At least 19 recordsLinked to original sources

On the perception of madness.

Since the beginning of recorded history, mental illness has been recognised as being primarily in the province of the healing profession. This view has continued, despite the fact that psychiatry left the mainstream of medicine with the development of asylums during the 19th century. With the advent of deinstitutionalization however, psychiatrists, particularly in Australia, have increasingly left public practice. As a result, the treatment of the severely and chronically mentally ill, especially those with behavioural disorder, has become neglected. It is argued that moves toward the mainstreaming of acute psychiatry to general hospitals offer a new opportunity for the profession to reassert itself in this essential but difficult area of psychiatric practice.

Australia↗

A specific laboratory test for the diagnosis of melancholia. Standardization, validation, and clinical utility.

Four hundred thirty-eight subjects underwent an overnight dexamethasone suppression test (DST) to standardize the test for the diagnosis of melancholia (endogenous depression). Abnormal plasma cortisol concentrations within 24 hours after dexamethasone administration occurred almost exclusively in melancholic patients. The best plasma cortisol criterion concentration, above which a DST result may be considered abnormal, was 5 microgram/dL. The optimal dose of dexamethasone was 1 rather than 2 mg. Two blood samples obtained at 4 and 11 PM after dexamethasone administration detected 98% of the abnormal test results. This version of the DST identified melancholic patients with a sensitivity of 67% and a specificity of 96%. Baseline nocturnal plasma cortisol concentrations were not useful. Abnormal DST results were found with similar frequency among outpatients and inpatients with melancholia; but they were not related to age, sex, recent use of psychotropic drugs, or severity of depressive symptoms. Extensive evidence validates this practical test for the diagnosis of melancholia.

Adolescent↗

Recent advances in the genetics of affective illness.

Variability in the classification of depressive illness greatly handicapped the work of geneticists prior to the application of the polarity concept. The past decade has however, seen a burgeoning of interest in this area, with researchers concentrating on bipolar illness, this being the most clearly defined entity. Findings of a lifetime morbidity risk for affective illness of 15-20% in the first degree relatives of bipolar patients has been usual. This compares with 10-15% for patients with unipolar illness. Transmission patterns indicative of known forms of Mendelian inheritance have not been consistently demonstrated. Genetic markers including colour blindness and HLA antigens have been pursued avidly but have yielded inconclusive results. Further progress seems unlikely unless more sub-groups are defined using biochemical and physiological markers.

Adoption↗

Diagnosis of endogenous depression. Comparison of clinical, research and neuroendocrine criteria.

Eighty-nine depressed outpatients were studied by clinical criteria, Research Diagnostic Criteria (RDC), and the dexamethasone suppression test (DST) of neuroendocrine regulation. A simple outpatient version of the DST, requiring only one blood sample, correctly identified 40% of patients diagnosed clinically as endogenous depression (ED), with a specificity of 98% and a diagnostic confidence of 95%. Differences in age, sex, or severity of symptoms between endogenous and non-endogenous depressives did not account for these results. By comparison, the diagnostic performance of the DST was weaker for the RDC categories Major Depressive Disorder (MDD) and primary MDD. These were less selective and more heterogeneous than the clinical category ED. The clinical diagnoses of ED were supported in 98% of cases by the RDC, but 22% of RDC endogenous MDD diagnoses were not supported by the clinical diagnoses. Abnormal DST results were found only in patients with both the clinical diagnosis of ED and the RDC diagnosis of endogenous MDD. Patients with definite endogenous MDD had a significantly higher frequency of abnormal DST results (42%) than those with probable endogenous MDD (14%), or those with other RDC diagnoses (3%). A significant association was found between positive DST results and a positive family history of depression. These results support other evidence for use of a positive DST result as an external validating criterion for ED. The category MDD contained all cases diagnosed clinically as ED, but was diluted by cases diagnosed clinically as non-endogenous depression who had no neuroendocrine disturbance. The results also confirmed that the endogenous/non-endogenous and primary/secondary classifications of depression are not identical. We conclude: (1) that the DST can be used in the differential diagnosis of depressed outpatients as well as inpatients; (2) that the RDC category primary MDD and the Washington University category primary depression are more heterogeneous and probably less valid than the clinical category ED; (3) that the RDC for endogenous MDD have only moderate validity; (4) that RDC diagnoses cannot substitute for careful clinical diagnoses in research studies; (5) that the best use of the RDC is to support clinical diagnoses, but not to generate diagnoses independently as a free-standing system; (6) that the concept of endogenous or endogenomorphic depression has validity and should be retained in research studies of depression.

Adult↗

Neuroendocrine dysfunction in genetic subtypes of primary unipolar depression.

Disinhibited activity of the hypothalamic-pituitary-adrenocortical (HPA) neuroendocrine system, characterized most specifically by abnormal responses to the dexamethasone suppression test (DST), is observed in 40-50% of patients with endogenous depression. The heterogeneity of endogenous depressives with respect to this neuroendocrine marker is so far unexplained. A recent report from Iowa suggested that genetic factors could account for this heterogeneity, since abnormal DST reponses were found with widely differing frequencies among primary unipolar depressives subtyped by the genetic criteria of Winokur. We studied 14 patients with primary endogenous delusional unipolar depression. Abnormal DST responses were found in 79% of the entire group, and with similar frequencies among each of the Winokur subtypes. In particular, five of six patients (83%) with depression spectrum disease had abnormal DST results. This contrasts with a frequency of 4% reported by the Iowa group. We conclude that disinhibited HPA activity does occur in depression spectrum disease when a delusional endogenous depression is present. Our results and those of the Iowa study could both be consistent with a threshold model of HPA activation. The high frequency of positive DST results in delusional endogenous depressives may be determined by disinhibited central pain mechanisms. Variations in this clinical dimension, combined with variations in threshold for HPA activation by pain mechanisms, could account for the heterogeneity of DST responses among endogenous depressives.

Delusions↗

Affective illness and HLA frequencies: no compelling association.

114 patients suffering from an endogenomorphic affective illness were typed for HLA antigens at the A and B loci, and the frequencies were compared with those of a control panel numbering 439 individuals. Using new analytical procedures, a large number of tests were conducted, but no convincing evidence for an association of HLA types with affective disorders was obtained. A reanalysis of the same data, where patients are classified according to Danish diagnostic criteria, yields a marginally significant association of the B locus alleles. The sample sizes for this latter analysis were small, the test criteria are undoubtedly inflated, and no compelling case can be made for a useful association.

Alleles↗

Normalization of dexamethasone suppression test: a laboratory index of recovery from endogenous depression.

Carroll et al. reported that an abnormal dexamethasone suppression test (DST) may identify approximately 50% of endogenous depressives and that normalization of the test occurs with clinical recovery. Brown et al. and Schlesser et al. have confirmed the diagnostic utility of the test. A preliminary study suggested that when the DST failed to normalize at discharge, patients were at high risk for early relapse. In this study, we compared ten unipolar or bipolar endogenous depressives who had an abnormal DST on admission and a normal DST at discharge, with four patients whose abnormal DST on admission failed to convert at discharge. On all measures, those whose DST fail to convert showed substantially less improvement. Patients whose DST fail to normalize may have incomplete resolution of their underlying depressive process. Despite clinical judgment that discharge may be appropriate these patients may require further active treatment. Use of the DST prior to discharge may help discriminate between patients whose remaining symptoms reflect situational or psychosocial problems and those with a continuing endogenomorphic process.

Adult↗

Early- and late-onset bipolar affective disorder. A genetic study.

A group of 46 bipolar probands was divided equally into those with early (before age 30) and later onset. The only significant difference found was a higher morbidity risk for the relatives of the early-onset group. Slater's model for a polygenic transmission was found compatible with this group, but insufficient data prevented its application in the older-onset group. In all other respects, however, no significant differences were found. Age of onset of illness may be unhelpful in elucidating the genetic basis of affective disorder. Further progress will depend on the development of more sensitive mathematical models and the finding of specific genetic markers.

Adult↗

Anorexia nervosa: a study of 44 strictly defined cases.

Forty-four patients with strictly defined anorexia nervosa were studied. They were found to come from the higher socio-economic levels and to be the early born of older parents. Their families were of average size, but females were over-represented. Premorbid obesity was uncommon, but over two-thirds had secondary depression. The treatment methods used until 1974 showed no great variation in success. Poor prognosis was most commonly linked to use of purgatives. A new treatment programme involving re-feeding to reach ideal weight and followed by psychotherapy shows encouraging results.

Adolescent↗

A double blind trial of nitrazepam and flurazepam as sedatives.

A double-blind cross-over trial was conducted using flurazepam and nitrazepam as sedatives in a group of a dozen psychiatric in-patients. The results show highly significant differences between placebo effects and the active drugs. The differences between the two drugs were not significant apart from the subjective estimate of time slept in which flurazepam was superior. As other studies have confirmed also their safety, relative lack of side effects and very low addictive potential it seems there is little to choose between them, except for the possibility that flurazepam may be preferred subjectively.

Adult↗

A genetic study of bipolar affective disorder.

A group of 46 bipolar probands and their first degree relatives were studied. A high rate of affective disorder (19.6 per cent) was found, including both unipolar (13.2 percent) and bipolar (6.4 per cent) types, with females predominating (3 : 1). The presence of four fatherson pairs suffering from affective disorder made the hypothesis of X-linked dominance untenable. Results compatible with polygenic inheritance were found, using both Slater's and Falconer's methods. There was no evidence for assortative mating or for increased total number of females (both well and ill) among first degree relatives. The probands and affectively ill first degree relatives who have died show an alarmingly high rate of suicide (46 per cent). Other forms of mental disorder, including alcoholism, were no more common than in the rest of the community.

Adult↗

A clinical trial of electrosleep therapy with a psychiatric inpatient sample.

The study assessed the effectiveness of electrosleep therapy in the treatment of depression, anxiety, and sleep difficulties in a small, heterogenous sample of psychiatric inpatients. A double-blind format was employed, one group receiving active treatment while the other received simulated treatment. The results showed active electrosleep to be no better than placebo in bettering quality of sleep or in lessening symptoms of depression or anxiety.

Adult↗