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Biomedical subjects

I Hickie

Publications and source records attributed to I Hickie.

At least 55 records · Page 3Linked to original sources
PubMed1997

Cognitive deficits in patients suffering from chronic fatigue syndrome, acute infective illness or depression.

BACKGROUND: Patients with chronic fatigue syndrome (CFS) report neuro-psychological symptoms as a characteristic feature. We sought to assess cognitive performance in patients with CFS, and compare cognitive performance and subjective workload experience of these patients with that of two disease comparison groups (non-melancholic depression and acute infection) and healthy controls. METHOD: A computerized performance battery employed to assess cognitive functioning included tests of continuous attention, response speed, performance accuracy and memory. Severity of mood disturbance and subjective fatigue were assessed by questionnaire. RESULTS: All patient groups demonstrated increased errors and slower reaction times, and gave higher workload ratings than healthy controls. Patients with CFS and non-melancholic depression had more severe deficits than patients with acute infection. All patient groups reported more severe mood disturbance and fatigue than healthy controls, but patients with CFS and those with acute infection reported less severe mood disturbance than patients with depression. CONCLUSIONS: As all patients demonstrated similar deficits in attention and response speed, it is possible that common pathophysiological processes are involved. The differences in severity of mood disturbance, however, suggest that the pathophysiological processes in patients with CFS and acute infection are not simply secondary to depressed mood.

Acute Disease↗
PubMed1997

Erotomania associated with temporal lobe abnormalities following radiotherapy.

OBJECTIVE: The aetiology of primary erotomania is usually discussed in terms of psychological disturbance in the patient. A case associated with demonstrable left temporal lobe abnormalities is described. CLINICAL PICTURE: An elderly female patient presented with the delusion of being loved by a physician who had treated her previously. She had received radiotherapy to her left periorbital area in childhood. Structural and functional neuroimaging revealed medial temporal lobe damage. TREATMENT AND OUTCOME: She was treated with haloperidol with moderate improvement in her distress. CONCLUSIONS: This case illustrates the contribution of both cerebral injury and psychosocial factors in the eventual development of this unusual psychiatric syndrome.

Aged↗
PubMed1997

Molecular biology and the major psychoses.

OBJECTIVE: To highlight the potential role of molecular biological studies in examining the expression of genes of interest in brain tissue to elucidate the pathophysiological basis of the major psychoses. METHOD: To review the principles underlying the available techniques for expression studies. RESULTS: Detection of messenger RNA by in situ hybridisation and quantitation by Northern analysis are powerful tools to detect abnormalities in gene expression in brain tissue. CONCLUSION: The availability of simple techniques to examine the expression of RNA and protein products of individual genes, including examination at the level of individual cells, offers a clear opportunity to define the molecular basis of the major psychoses.

Brain↗
PubMed1997

Utilising molecular biological and histopathological techniques to study the dopaminergic system in patients with melancholia.

OBJECTIVE: To describe the rationale for investigating the dopaminergic system in patients with melancholia by applying molecular biological (notably, in situ hybridisation) and histopathological techniques in postmortem brain tissue. METHOD: Relevant advances in the functional neuroanatomy of frontostriatal circuits, as well as insights from clinical neuroimaging studies in primary and secondary depressive disorders, are presented. These are integrated with developments in the pharmacological and molecular characteristics of dopamine receptor subtypes and recognition of their selective anatomical distribution. RESULTS: Converging data from the basic and clinical neurosciences suggest that the pathophysiology of depressive disorders characterised by psychomotor phenomena, such as melancholia, may involve dysregulation of dopaminergic mechanisms within complex frontostriatal circuits. CONCLUSIONS: The key feature of in situ hybridisation is its capacity to test for variations in the functional components of designated biochemical systems within highly specific anatomical regions. We utilise this approach, in combination with relevant histopathological techniques, to test the structural and functional integrity of the dopaminergic system within key fronto-striatal circuits in patients who had exhibited psychomotor phenomena. The same approach can also be used to study the integrity of other relevant biochemical systems, such as the serotoninergic and noradrenergic systems, in patients with other mood disorders.

Brain Mapping↗
PubMed1996

Depressive psychomotor disturbance, cortisol, and dexamethasone.

We examine the dexamethasone suppression test as a biological correlate of melancholia as defined by the CORE system, a scale for rating objective signs of psychomotor disturbance. Postdexamethasone cortisol concentrations and rates of nonsuppression were higher in CORE, Newcastle, and DSM-III-R defined melancholic groups. These differences, however, were no longer significant after partialling out the combined effects of age, dexamethasone, and basal cortisol concentrations. There was a significant correlation between the CORE (but not the Newcastle) scale and 8:00 AM postdexamethasone cortisol levels, which persisted after partialling out those same three covariates. Dexamethasone concentrations themselves were lower in CORE- and Newcastle-defined melancholics, though these were no longer significant after covarying for cortisol concentrations. Dexamethasone levels were also significantly inversely correlated with CORE and Newcastle scales. A significant correlation between CORE (but not Newcastle) scores and dexamethasone levels at 4:00 PM persisted after partialling out the effects of age and cortisol. These findings indicate an intriguing relationship between the CORE system as a dimensional construct for rating psychomotor disturbance, and both postdexamethasone cortisol and dexamethasone concentrations.

Age Factors↗
PubMed1996

Comparative validity of two measures of psychomotor function in patients with severe depression.

Psychomotor function is a key construct in depressed patients and two measures have been developed for systematic rating. Parker and colleagues utilise an observer-rated scale (CORE) while the scale (DRRS) developed by Widlöcher assesses motor and ideational aspects. Association between the scales and their relative capacity to predict ECT response were investigated in a sample of 81 depressed patients. Both predicted ECT response. While the CORE scale rates a wider variety of phenomena (including non-interactiveness and agitation) and does not rely on the subject's capacity to report aspects of their cognitive function, the study supports the predictive and comparitive validity of both scales.

Adult↗
PubMed1996

Prediction of ECT response: validation of a refined sign-based (CORE) system for defining melancholia.

BACKGROUND: The clinical validity of melancholia has been argued on the basis of its capacity to predict response to electroconvulsive therapy (ECT). We have argued that a sign-based (CORE) rating system of psychomotor disturbance can identify patients with melancholia. Therefore, the clinical validity of the CORE system was tested here in terms of its capacity to predict response to ECT. METHOD: The response of 81 patients with primary affective disorders to an individualised course of ECT was investigated. CORE scores and other clinical predictors were evaluated in terms of their capacity to predict effect size changes in symptoms and disability. RESULTS: CORE scores predicted ECT response, as did the presence of psychotic features. The combination of marked psychomotor change (high CORE scores) and psychotic features predicted the best response to ECT. CONCLUSION: This study supports the clinical validity of the CORE system for diagnosing melancholia.

Aged↗
PubMed1996

If the referral fits: bridging the gap between patient and referrer requirements in a tertiary referral unit.

OBJECTIVE: We examined the reasons for which doctors refer and patients request referral to our tertiary Mood Disorders Unit (MDU), focussing on congruence and 'fit', and the potential for more efficient use of referral resources. METHOD: A postal survey of patients (n = 265 or 83% responders) and referrers (n = 156 or 94% responders) sought views regarding referral and service components. Ratings from 156 matched referrer-patient dyads were compared. RESULTS: Overall, referrers and patients were satisfied with the MDU. There was disparity between what referrers sought and what patients thought were the reasons for referral, and different perceptions of the value of interventions and the amount of improvement. Congruent matched referrer-patient judgements of patient outcome were more likely to correspond with objective clinician ratings than discordant ratings. Satisfaction with MDU contact or intervention was not necessarily linked to improvement; better management of chronic depression was also valued. Referrer and patient responses to open-ended questions highlighted beneficial ingredients of referral. CONCLUSIONS: There was considerable lack of fit between referrers' and patients' experience of the referral. Better communication between referrer and patients can clarify the purpose of referral and possibly lead to increased compliance with medical regimens.

Adolescent↗
PubMed1996

Clinical and subclinical hypothyroidism in patients with chronic and treatment-resistant depression.

OBJECTIVE: To investigate the relationship between hypothyroidism and treatment-resistant depression (TRD). METHOD: A retrospective case audit of 93 inpatients of a specialist Mood Disorders Unit. Patients referred with TRD were sub-classified into 'adequate' or 'inadequate' prior treatment groups on the basis of pre-established criteria, and compared with a 'non-TRD' control sample. Grades I (clinical) and II (subclinical) hypothyroidism were determined by review of relevant thyroid indices. RESULTS: Patients had chronic depressive disorders (sub-group means of 57.5-82.2 weeks of illness). Of those patients referred with TRD, 22% (10/46) had evidence of clinical or subclinical hypothyroidism compared with 2% (1/47) of the non-TRD patients (p < 0.01). A gradient in the rates of grade I hypothyroidism was observed with the adequately-treated TRD patients having the highest rate (13%), the inadequately-treated TRD patients having an intermediate rate (7%), and the non-TRD patients having the lowest rate (2%). Consistent with this view, the inadequately-treated TRD group had the highest rate of grade II hypothyroidism (p = 0.01) and tended to have higher thyroid stimulating hormone (TSH) values (p = 0.06). Differences in the rates of hypothyroidism could not be accounted for by differences in age or prior exposure to lithium and/or carbamazepine. Duration of the depressive episode was negatively correlated with both the free thyroxine indices (r = -0.25, P < 0.05) and TSH levels (r = -0.32, p < 0.01). CONCLUSIONS: This study suggests that relative hypothyroidism may play a role in the development of some treatment-resistant depressive disorders.

Adult↗
PubMed1996

Is there a postinfection fatigue syndrome?

Prolonged fatigue syndromes are common in general practice. Most of these syndromes are secondary to other common medical or psychological disorders. It appears, however, that some specific infectious illnesses are associated with prolonged recovery. Theories as to the mechanisms for such post infection fatigue syndromes include a range of immunological, psychological and neurobiological processes. Current evidence suggests disruption of fundamental central nervous system mechanisms, such as the sleep-wake cycle and the hypothalamic-pituitary-adrenal axis, may underpin the clinical features of this disorder. Treatment should focus on the provision of continuous medical care, physical rehabilitation and adjunctive psychological therapies.

Fatigue↗
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

Delayed-type hypersensitivity skin testing: normal values in the Australian population.

In our human psychoimmunological studies we have utilized a standardized assessment kit, the cell-mediated immunity (CMI) Multitest system, for determining delayed-type hypersensitivity (DTH) skin responses to a panel of ubiquitous antigens. Although the kit had been assessed in large populations of healthy controls in the U.S.A. and Europe, few data were available with regard to normative values in the Australian population. There are cogent reasons to suspect that results for the test will vary depending on geographical location, age cohort, compliance with specific immunization schedules and rates of natural exposure to certain diseases in differing populations. Most of our patient cohorts have a preponderance of female subjects and most standardization had been conducted in males. We tested medically and psychologically healthy males (n = 66) and females (n = 53). The percentage of positive responses to individual antigens was similar to other Australian studies but lower than that reported internationally. The mean number of positive responses was 3.7 for men and 2.8 for women, while the mean induration diameter was 17.5 mm for men and 12.2 mm for women. Three per cent of men and 5.6% of women were anergic (no positive responses), while a further 10.6% of men and 9.4% of women fell into the "hypoergic" category. These results, and those from other studies, indicate that the pattern of response to the CMI Multitest differs in healthy Australians. Therefore, researchers need to exercise caution when selecting patient and control samples (controlling for exposure factors), applying the test, reporting results (i.e. including all relevant parameters-with an emphasis on dimensional rather than categorical scores) and when designating subjects as having "impaired" responses.

Adolescent↗
PubMed1995

Are cytokines associated with neuropsychiatric syndromes in humans?

Traditional aetiological models in neuropsychiatry have placed little emphasis on the abnormal behavioural responses (decreased psychomotor activity, anorexia, weight loss, decreased social exploration and sexual behaviour, impaired cognitive function and increased somnolence) that are common to both psychiatric syndromes, notably depression, and the illness behaviour of sick animals. In recent years, the possible role of cytokines, as mediators of not only the immunological and metabolic responses to infection and inflammation but also a co-ordinated behavioural response, has been described. Further, a range of possible mechanisms for these effects has been postulated, notably involving corticotropin releasing factor (CRF) and prostaglandins of the E series (PgE) with the central nervous system (CNS). Here we outline a series of human clinical conditions where neuropsychiatric syndromes co-occur with a host response to infection or inflammation. These may be characterized by cytokine production (e.g. acute, recurrent and chronic viral illness, systemic autoimmune diseases and chronic fatigue syndrome). Other clinical situations characterized by exposure to or in vivo production of cytokines (e.g. treatment of chronic infections and malignancies, progression and/or recurrence of malignancies) are also discussed. We postulate that the stereotyped behavioural repertoire observed is mediated by cytokine-dependent mechanisms within the CNS. Systematic studies of the behavioural responses of such patient groups are suggested, noting specifically correlations between the time course and severity of immune and neuroendocrine and behavioural responses and dose-response effects.

Animals↗
PubMed1995

Biochemical correlates of in vivo cell-mediated immune dysfunction in patients with depression: a preliminary report.

We have previously demonstrated that at least 50% of patients with melancholia have impaired cell-mediated immunity (CMI) as assessed by delayed-type hypersensitivity (DTH) skin responses to a standardized battery of antigens. Hypercortisolaemia and increased circulating catecholamines both occur in patients with severe depressive disorders and each has been proposed as a possible mediator of observed immune abnormalities in patients with mood disorders. As part of a larger study, we collected 24 h urine samples from 28 patients with major depression and measured concentrations of urinary free cortisol (UFC), the noradrenaline metabolite dihydroxyphenylglycol (DHPG), adrenaline, and the dopamine metabolite DOPAC. CMI multitest skin testing revealed a reduced or absent response in 54% of subjects. Those with reduced DTH skin responses demonstrated increased urinary adrenaline (P < 0.02), with trends toward increased UFC (P = 0.052) and increased DHPG (P = 0.06). These differences could not be attributed to differences in age or depression severity. Correlational analyses demonstrated inverse associations between the extent of DTH responsiveness and 24 h levels of urinary adrenaline and DHPG, with similar trends evident for UFC and DOPAC. These results suggest that both circulating catecholamines and cortisol may play roles in the reduction of CMI in patients with severe depression.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1995

Cell-mediated immune function and the outcome of chronic fatigue syndrome.

This study examined the importance of cell-mediated immunity in determining the long-term outcome of patients diagnosed with chronic fatigue syndrome (CSF). A total of 103 patients (74%) of 139 previously enrolled in one of two treatment trials conducted within a university hospital referral center was reviewed a mean of 3.2 yr after trial entry. Ongoing symptom severity, levels of disability and immunological function were assessed at follow-up. The relationship between immunological function at trial entry and measures of outcome was also evaluated. Sixty-five patients (63%) had improved, while only 6 (6%) reported no current symptoms. Thirty-one subjects (30%) were unable to perform any form of work and 26 (25%) were on a disability benefit directly attributable to CFS. Cell-mediated immune function, as measured at trial entry or follow-up, did not appear to affect outcome. Whilst improvement occurred in the majority of patients with CFS, a substantial proportion (37%) remained functionally impaired. Impairment of cell-mediated immunological function measured during the course of the illness may not be an important factor in determining long-term outcome.

Adult↗
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↗