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Biomedical subjects

M P Austin

Publications and source records attributed to M P Austin.

16 recordsLinked to original sources
PubMed1995

Subcortical hyperintensities on magnetic resonance imaging: clinical correlates and prognostic significance in patients with severe depression.

In 39 hospital inpatients with severe primary depressive disorders, we evaluated the relationships between subcortical hyperintensities on magnetic resonance imaging (MRI) and clinical features, neuropsychological impairment and response to standard therapies. Both white matter and gray nuclei lesions were associated with older age and the absence of a family history of affective disorder. White matter hyperintensities were also associated with onset of first affective episode after the age of 50 years and impaired psychomotor speed. Most importantly, the severity of white matter hyperintensities predicted a poorer response to treatment (r = -0.44, p < .01). Negative correlations of the same order were detected in those (n = 20) who received electroconvulsive therapy (r = -0.42, p = .06) and those (n = 19) who received pharmacotherapy alone (r = -.49, p < .05). This study provides preliminary evidence supporting the clinical and prognostic significance of extensive white matter hyperintensities in patients with severe depression.

Activities of Daily Living↗
PubMed1995

Sub-typing depression, I. Is psychomotor disturbance necessary and sufficient to the definition of melancholia?

Melancholia is most commonly distinguished from non-melancholic depression by the presence of psychomotor disturbance (PMD) and a set of 'endogeneity' symptoms. We examine the capacity of an operationalized clinician-rated measure of PMD (the CORE system) to predict diagnostic assignment to 'melancholic/endogenous' classes by the DSM-III-R and Newcastle systems. Examining a pre-established CORE cut-off score (> or = 8) against independent diagnostic assignment, PMD was present in 51% of those assigned as melancholic by DSM-III-R, and 85% of those assigned as endogenous by the Newcastle system, quantifying the extent to which it is 'necessary' to the two definitions of 'melancholia'. Additionally, multivariate analyses established that the addition of a refined set of historically suggested endogeneity symptoms added only slightly to overall discrimination of melancholic and non-melancholic depressives. While only few endogeneity symptoms independent of psychomotor disturbance were suggested, their specific relevance varied against system definition of melancholia (appetite/weight loss and terminal insomnia being identified for DSM-III-R; anhedonia for Newcastle; and diurnal variation in mood and energy for both systems). Results allow consideration of the relative importance of two domains (psychomotor disturbance and 'endogeneity' symptoms) to clinical definition of melancholia, and have the potential to assist both classification and pursuit of neurobiological determinants. We interpret findings as suggesting a 'core and mantle' model for conceptualizing the clinical features of melancholia, with psychomotor disturbance as the core and with independent endogeneity symptoms as only a thin mantle.

Adult↗
PubMed1995

Sub-typing depression, II. Clinical distinction of psychotic depression and non-psychotic melancholia.

We have attempted to clarify clinical differentiating features of psychotic depression. Forty-six depressed subjects meeting DSM-III-R criteria for major depression with psychotic features were compared with (i) DSM-defined melancholic, (ii) Newcastle-defined endogenous, and (iii) a residual DSM-defined major depressive episode group. Additionally, a 'bottom up' latent class analysis (LCA) suggested a larger sample of 82 'psychotic depressive' subjects, and multivariate analyses contrasted these subjects with both LCA-identified melancholic and all residual depressed subjects. Analyses suggested that, in addition to two features with absolute specificity (delusions and hallucinations), both the DSM-defined and LCA-defined 'psychotic depressive' subjects were significantly more likely to demonstrate marked psychomotor disturbance, to report two morbid cognitions (feeling sinful and guilty; feeling deserving of punishment), as well as be more likely to report constipation, terminal insomnia, appetite/weight loss and (variable across the defined 'psychotic depressive' groups) loss of interest and pleasure. The study identifies a wider set of potentially discriminating clinical variables than previous studies, as well as both indicating the existence and assisting identification of 'true' psychotic depression in the absence of formal psychotic features being acknowledged or elicited.

Adult↗
PubMed1995

A clinical perspective on SPECT.

The potential clinical utility of SPECT (Single Photon Emission Computed Tomography) brain imaging to clarifying certain diagnostic dilemmas faced by clinical psychiatrists is considered generally and is illustrated by several case vignettes. Three case histories consider dementia vs depressive pseudodementia, two the possibility of a cerebral vasculitis in patients with auto-immune conditions, and two whether the patient had a "type" of depression likely to benefit from a course of ECT. Published studies reviewing the utility of SPECT in dementia, depression, depressive "pseudodementia" and cerebral lupus are considered. It is suggested that SPECT is an important investigatory technique providing additional information that may assist some diagnostic decisions, while its utility in assisting other clinical decisions awaits clarification.

Adult↗
PubMed1994

Uptake of 99mTc-exametazime shown by single photon emission computerized tomography in obsessive-compulsive disorder compared with major depression and normal controls.

Twelve patients with obsessive-compulsive disorder (OCD) were investigated at rest using single photon emission computerized tomography with 99mTc-exametazime. The uptake of 99mTc-exametazime was expressed relative to calcarine/occipital cortex. Patients were matched for drug treatment with 12 patients with a major depressive episode and the patient groups were compared with a control group. Significant bilateral decreases in tracer uptake were confined to basal ganglia in the OCD group. There was a paradoxical positive correlation between anxiety ratings and tracer uptake to basal ganglia in the OCD group. The findings confirm that the functional topography of OCD implicates altered function in the basal ganglia.

Adult↗
PubMed1994

Treatment resistant depression in an Australian context. I: The utility of the term and approaches to management.

The concept of "treatment resistant depression" (TRD) has generally been defined in terms of failure to respond to a standard course of somatic therapy with little reference to diagnostic sub-types or relevant psychosocial factors. In this paper we examine problems with the use of the term "treatment resistant depression" and then outline an approach to TRD employed in an Australian mood disorders unit. After discussing the need for a biopsychosocial assessment, multimodal management strategies for melancholic and non-melancholic TRD patients are described.

Affective Disorders, Psychotic↗
PubMed1993

State changes in brain activity shown by the uptake of 99mTc-exametazime with single photon emission tomography in major depression before and after treatment.

Twenty-eight patients with a major depressive episode previously investigated at rest using Single Photon Emission Tomography (SPET or SPECT) with 99mTc-exametazime, were followed up at an interval of 9-28 months with the same investigation after full recovery. All patients were unipolar and were rated on the Newcastle scale and with the 17-item Hamilton scale. The uptake of 99mTc-Exametazime was expressed relative to calcarine/occipital cortex. Sixteen patients were scanned when optimally matched for drug treatment (4) or on both occasions drug free (12). The other 12 patients were fully recovered but could not be matched for drug status; these patients showed significantly more retardation, diurnal mood variation and guilt at presentation. Significant bilateral increases in tracer uptake were confined to basal ganglia and inferior anterior cingulate cortex in the matched group, where there were additional increases in thalamus and posterior cingulate cortex on the right side. There were no statistically discernible changes in the neocortex in the matched sample. The unmatched sample yielded inconclusive evidence of increased tracer uptake in left temporal cortex. The findings give a potential focus to the neuropharmacological analysis of depressive illness because the topography of the state change in brain function implicates dopamine function.

Adult↗
PubMed1993

The elevation of plasma beta-endorphin levels in major depression.

Day-time plasma beta-endorphin/beta-lipotrophic hormone (beta-ENDO/beta-LPH), ACTH and cortisol have been determined in 26 patients with major depression and 25 controls. beta-ENDO/beta-LPH and cortisol were significantly elevated in patients, while ACTH was not. Cortisol levels were significantly negatively correlated with age in controls as were beta-ENDO/beta-LPH and ACTH. In patients, by contrast, cortisol levels were positively, albeit not significantly, related to age. Peptide levels were not related to age in the patient group. Instead, beta-ENDO/beta-LPH was negatively correlated with clinical ratings of symptom severity in patients and positively associated with an acute psychosocial precipitant. The findings cast further light on beta-ENDO/beta-LPH as a measure of hypothalamic-pituitary over activity in depressive illness. A negative association with symptom severity suggests that beta-ENDO/beta-LPH responses are, like those of ACTH, down-regulated in the course of depressive illness.

Adrenocorticotropic Hormone↗
PubMed1993

A single photon emission computerised tomography study of regional brain function in elderly patients with major depression and with Alzheimer-type dementia.

The uptake, at rest, of 99mTc-exametazime into different brain regions was compared using SPECT for 20 elderly subjects with major depressive disorder, 20 with Alzheimer-type dementia, and 30 age-matched normal volunteers. Uptake was referred to calcarine-occipital cortex as a reference sensory area. Cross-sectional differences between the three groups were highly statistically significant, but reflected primarily the reductions in cortical uptake in the Alzheimer group. A detailed comparison of depressed patients and controls identified decrements in anterior cingulate, temporal and frontal cortex and in caudate and thalamus in men only. These decrements were correlated with impairment of performance on a trail-making task, but were also associated with continuing treatment with antidepressants or benzodiazepines. However, most depressed patients had quantitatively normal scans for posterior parietal association cortex, and this suggests that SPECT may find a limited role in the differential diagnosis of depression and dementia. The reduced brain function in some depressed patients may parallel the findings from studies of brain structure in elderly depressives; there was between good outcome at 6-18 months and increased tracer uptake in subcortical areas.

Age of Onset↗
PubMed1992

Single photon emission tomography with 99mTc-exametazime in major depression and the pattern of brain activity underlying the psychotic/neurotic continuum.

Forty patients with a major depressive episode were investigated at rest using Single Photon Emission Tomography (SPET or SPECT) with 99mTc-exametazime, an intravenous ligand taken into brain in proportion to regional cerebral blood flow, thereby providing an estimate of regional metabolism. All patients were unipolar and were rated on the Newcastle scale and with the 17-item Hamilton scale. They also completed a range of neuropsychological tests. They were compared with 20 control subjects matched for age, gender, premorbid intelligence and education. The uptake of 99mTc-exametazime was expressed for a range of anatomically defined regions of interest relative to calcarine/occipital cortex. The depressed group showed reduced uptake in the majority of cortical and sub-cortical regions examined, most significantly in temporal, inferior frontal and parietal areas. Unexpectedly, there was a strong positive association between uptake and scores on the Newcastle scale, especially in cingulate areas and frontal cortex. After removing the variance attributable to the Newcastle ratings, however, there emerged the expected negative association between Hamilton scores and anterior tracer uptake. The associations between neuropsychological impairment and regional brain uptake of tracer in part reflected the pattern seen with the Newcastle scale: for example, impairment of memory function correlated with higher uptake into posterior cingulate areas. We propose that depressive illness may be characterised by two processes. One leads to an overall reduction in anterior neocortical function, perhaps related to symptom severity. The other mechanism is manifest as relatively increased function, most notably within cingulate and frontal areas of the cerebral cortex in association with psychotic symptoms. The findings offer new understanding of the brain states underlying depressive illness and a potential focus to subsequent neuropharmacological analysis.

Adult↗
PubMed1992

Cognitive function in major depression.

Forty patients with a major depressive episode were divided into equal endogenous and neurotic sub-groups using the Newcastle scale. They were all rated on the 17-item Hamilton scale and with a variety of neuropsychological tests. They were compared with 20 age- and education-matched control subjects. Both endogenous and neurotic groups had impaired memory function on the auditory verbal learning test; recall and recognition were equally impaired suggesting that effort was not a major determinant of performance. The endogenous group was more impaired on digit symbol substitution and the Trail making test (A and B). Impairment was correlated with symptom scores on the Hamilton and Newcastle scales, even after allowing for the effect of age. It is concluded that the conventional distinction between organic and functional impairment breaks down in severe depressive illness. The implications of this for clinical neuropsychological testing and the anatomy of the brain dysfunction in depressive illness are discussed.

Adult↗
PubMed1992

Puerperal affective psychosis: is there a case for lithium prophylaxis?

It is well known that women with a history of manic-depressive or puerperal affective psychosis are at particularly high risk of relapse in the puerperium. This paper describes the use of lithium given during or after pregnancy to women with a history of bipolar illness or puerperal affective psychosis. The rate of puerperal relapse in these subjects was compared with that in a similar group of women not on lithium. The significantly better outcome of the treatment group highlights the need for a prospective controlled trial looking at the effectiveness of lithium in minimising puerperal bipolar relapse.

Adult↗
PubMed1991

Lithium augmentation in antidepressant-resistant patients. A quantitative analysis.

A quantitative analysis was used to examine the efficacy of lithium augmentation in the acute treatment of depressed patients resistant to a standard trial of an antidepressant. Effect sizes were measured by the odds ratio using the Mantel-Haenszel method. Only controlled trials were included in order to minimise bias in method. A highly statistically significant effect for lithium augmentation was found, the pooled odds ratio being 0.146 and its 95% confidence interval 0.05-0.44 (i.e. the odds of remaining ill are reduced by between 56% and 95% with the use of lithium treatment). While these results support the case for lithium augmentation in treatment-resistant depression, there remains considerable uncertainty over the duration of treatment necessary to see and sustain the treatment response.

Antidepressive Agents↗