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Biomedical subjects

I Hickie

Publications and source records attributed to I Hickie.

At least 19 recordsLinked to original sources
PubMed1999

Cognitive function in depression: a distinct pattern of frontal impairment in melancholia?

BACKGROUND: Although depressed patients demonstrate impaired performance on a range of neuropsychological tests, there is little research that examines either frontal cognitive deficits or possible differences in test performance between melancholic and non-melancholic subtypes. METHODS: Depressed subjects were administered a broad neuropsychological battery. In an overall analysis, 77 depressed subjects were compared with 28 controls. In a second set of analyses, the depressed sample was divided into melancholic and non-melancholic subsets according to DSM-III-R, the CORE system and the Newcastle scale. These depressed subsets were contrasted to controls and with each other using ANCOVA controlling for age, IQ, simple reaction time and Hamilton Depression scores where appropriate. RESULTS: The total depressed sample was impaired on most mnemonic tasks, simple reaction time and Trails B. Similar findings applied to DSM-III-R melancholic and non-melancholic subjects. When defined by the CORE and Newcastle (narrower definitions of melancholia), melancholic patients were additionally impaired on WCST (perseverative response) and (for Newcastle) digit symbol substitution. In contrast, the cognitive performance of the CORE and Newcastle-defined non-melancholic patients was largely unimpaired. CONCLUSIONS: Using narrower definitions of melancholia, i.e. CORE and (in particular) Newcastle, melancholic patients were impaired on mnemonic tasks and tasks of selective attention, and set-shifting while non-melancholic subjects were largely unimpaired in their cognitive performance. These differences may be due to impairment of specific neuroanatomical regions in narrowly defined melancholic patients, in particular the anterior cingulate.

Adult↗
PubMed1999

Complex genetic and environmental relationships between psychological distress, fatigue and immune functioning: a twin study.

BACKGROUND: Although there is considerable support for adverse relationships between states of psychological and somatic distress and immune response, there is little evidence in humans of the relative contribution of genetic and environmental factors. METHODS: This study utilized a twin methodology to examine the interplay between psychological distress, fatigue and immune function. We recorded a number of measures of distress, including conventional depression and anxiety as well as the somatic symptom of prolonged fatigue, and immune responsiveness (by delayed-type hypersensitivity skin response) in 124 normal adult twin pairs (79 monozygotic, 45 dizygotic). RESULTS: While there were strong genetic influences on the psychological distress and fatigue factors (only some of which are common to both), familial aggregation of immune responsiveness arose mainly from environmental factors shared by both members of a twin pair. Phenotypic correlations between psychological and immune measures were negligible, but multivariate genetic modelling revealed that these masked larger genetic and environmental correlations of opposite sign. Negative environmental effects of psychological distress and fatigue on immune responsiveness were countered by a positive genetic relationship between psychological distress and immune function. CONCLUSIONS: Our study suggests that current psychoneuroimmunological hypotheses in humans need to be modified to place increasing importance on the individual's genotype. In this cohort immune responsiveness varied in response to a complex interplay of genetic and environmental factors. Additionally, although psychological distress and fatigue had some shared genetic determinants, independent genetic and environmental risk factors for fatigue were also identified.

Adult↗
PubMed1999

Unique genetic and environmental determinants of prolonged fatigue: a twin study.

BACKGROUND: Prolonged fatigue syndromes have been proposed as prevalent and disabling forms of distress that occur independently of conventional notions of anxiety and depression. METHODS: To investigate the genetic and environmental antecedents of common forms of psychological and somatic distress, we measured fatigue, anxiety, depression and psychological distress in 1004 normal adult twin pairs (533 monozygotic (MZ), 471 dizygotic (DZ)) over 50 years of age. RESULTS: Familial aggregation of psychological distress, anxiety and fatigue appeared to be due largely to additive genetic factors (MZ:DZ ratios of 2.12-2.69). The phenotypic correlations between the psychological measures (distress, anxiety and depression) were moderate (0.67-0.79) and higher than that between fatigue and psychological distress (0.38). Multivariate genetic modelling revealed a common genetic factor contributing to the development of all the observed phenotypes (though most strongly for the psychological forms), a second independent genetic factor also influenced anxiety and depression and a third independent genetic factor made a major contribution to fatigue alone. In total, 44% (95% CI 25-60%) of the genetic variance for fatigue was not shared by the other forms of distress. Similarly, the environmental factor determining psychological distress made negligible contributions to fatigue, which was underpinned largely by its own independent environmental factor. CONCLUSION: This study supports the aetiological independence of prolonged fatigue and, therefore, argues strongly for its inclusion in classification systems in psychiatry.

Anxiety Disorders↗
PubMed1999

Nefazodone for patients with chronic fatigue syndrome.

OBJECTIVE: Patients with chronic fatigue syndrome (CFS) present with a variety of musculoskeletal, neurocognitive, sleep disturbance and mood symptoms. An open evaluation of the clinical utility of the novel antidepressant compound, nefazodone, was completed. METHOD: Ten patients with CFS presenting for assessment by a specialist psychiatrist were treated with nefazodone. Patients treated within this specialist service are also advised to engage in appropriate behavioural and sleep-wake cycle strategies to improve their level of functioning. RESULTS: Of the 10 patients, eight (80%) reported at least some improvement in the key symptom of fatigue, with four (40%) reporting moderate or marked symptom relief. Additionally, sleep disturbance and mood were both moderately or markedly improved in seven (70%) and eight (80%) of the patients, respectively. Five of the patients (50%) achieved at least a moderate improvement in overall functional outcome and were able to return to work or their previous level of role function. The mean dose of nefazodone was 370 mg/day (range = 200-800 mg), with a strong preference for nocturnal dosing. Seven of the patients had previously failed to respond to moclobemide, while seven had previously failed to respond to conventional antidepressant therapy. CONCLUSION: Nefazodone appears to be worthy of further systematic investigation in patients with CFS. Given its effects on sleep, mood and anxiety symptoms, it may have particular advantages in patients with this disorder.

Adult↗
PubMed1998

An akinetic-rigid syndrome, depression, and stereotypies in a young man.

A young man is presented who developed an akinetic-rigid syndrome shortly after a minor illness. Rituals and stereoptypies were prominent. At its most severe he was unable to feed himself. There was no response to L-dopa/cardopa treatment. A course of ECT was followed by a marked improvement in his condition. Attempts to stop ECT for more than a week have led to recurrence of his bradykinesia.

Adult↗
PubMed1998

Non-melancholic depression: the contribution of personality, anxiety and life events to subclassification.

BACKGROUND: We sought to develop a clinically useful subtyping system for the non-melancholic depressive disorders, and here we assess one weighted to central aetiological factors. METHODS: We studied 185 patients meeting DSM-III-R and/or clinical criteria for non-melancholic depression. Data were obtained by self-report, interview of patients and from corroborative witnesses. We developed a set of variables for class definition, assessing: (i) 'P', disordered personality as a vulnerability factor; (ii) 'A', meeting criteria for a lifetime anxiety disorder or positive on probe questions about trait anxiety characteristics, so assessing anxiety as a vulnerability factor; and (iii) 'L', psychiatrist and consensually-rated life event stress prior to depression onset. RESULTS: A latent class analysis generated a four-class solution for the P-A-L variables. Life event stressors had similar item probabilities across all four classes, and did not influence the four-class 'P-A' solution when deleted from the analysis, suggesting that life event stress may act more as a general provoking agent, rather than constituting any distinct 'reactive' or 'situational' depression class. Three classes generated clinically meaningful groupings, reflecting varying contributions of anxiety and disordered personality functioning, and with evidence of differential outcome over the following 12 months. CONCLUSIONS: We suggest that a refined aetiologically-weighted model may assist definition of the non-melancholic depressive disorders, and provide the logic for exploring the comparative utility of differing treatments to identified vulnerability-based classes.

Adult↗
PubMed1998

Qualitative and quantitative analyses of a 'lock and key' hypothesis of depression.

BACKGROUND: We examine a 'lock and key' ('L-K') hypothesis to depression which posits that early adverse experiences establish locks that are activated by keys mirroring the earlier adverse experience to induce depression. METHODS: Two-hundred and seventy clinically depressed patients were examined with open-ended and pre-coded interview questions to ascertain both early adverse experiences and precipitating life events. Qualitative and quantitative data analyses examined for any associations between developmental 'locks' and precipitating 'keys'. RESULTS: Qualitative assessment suggested 'L-K' links in almost one-third of the sample, and examples are provided. While quantitative analyses indicated significant associations between several identical 'lock' and 'key' constructs, evidence of specificity was rare. When individual 'locks' and 'keys' were consolidated into three higher-order constructs, variable models were suggested, including a non-specific link, a specific link and absence of any link. 'L-K' links appeared more likely in those with 'non-melancholic' (versus 'melancholic') depression, with the seemingly greater relevance to 'reactive' (versus 'neurotic') depression in the quantitative analyses inviting speculation that that 'disorder' may be more a reaction to a salient rather than a severe stressor. CONCLUSIONS: This exploratory study suggests that early adverse experiences may variably establish specific and non-specific patterns of vulnerability to having depression triggered by exposure to salient mirroring life event stressors.

Adjustment Disorders↗
PubMed1998

An aetiological model of non-melancholic depression: study design and validity of the measures.

OBJECTIVE: The aim of this paper is to describe an approach to sub-typing non-melancholic depression and to determine which raters from a variety of backgrounds provided the most valid information on study variables. METHOD: A sample of non-melancholic depressed patients is described. Multiple raters (i.e. patients, psychiatrists, referrers and corroborative witnesses) completed measures of the patient's trait anxiety levels, severity of recent life event stressors and personality functioning. RESULTS: The study and representative data are reported. Congruence between several measures employed indicated that psychiatrist rating of disordered personality was superior to corroborative witness report. Assessment of anxiety traits indicated reasonable agreement between referrers and corroborative witnesses but poor agreement between those ratings and interview-elicited ratings. There were also discrepancies in quantifying 'severity' of life event stress, with patients and their corroborative witnesses rating such events as more severe than either the interviewing psychiatrist or psychiatrists involved in consensus rating sessions. Importantly, the psychiatrists' capacity to quantify the relative contribution of disordered personality, anxiety and life-event stress to the particular depressive episode was supported. CONCLUSIONS: Results indicate some of the difficulties in operationalising determinants that may contribute to and sub-type the non-melancholic depressions, and demonstrate the advantages of using a range of rating strategies and raters. In this study, psychiatrist-generated judgements are clearly favoured, although the advantages of also assessing trait anxiety and life-event stress impact by self-report strategies are conceded. Some techniques for estimating the contribution of disordered personality function, anxiety and life-event stress are offered for both their research and their clinical utility.

Adjustment Disorders↗
PubMed1998

Outcomes focused service delivery: developing an academic-management partnership.

OBJECTIVE: Current mental health policies emphasise the need for services to be integrated and to develop outcomes-based evaluation systems. An overview of the challenges faced by service managers and clinical academics who develop the appropriate financial, personnel and academic infrastructure for these tasks is presented. METHOD: By drawing on experiences within the St George Service and references to other services, we propose a model for a successful partnership between the academic and management components of a district service. RESULTS: Major logistic impediments to the development of a partnership are identified, although the long-term scientific and service delivery benefits are highlighted. Key areas within both academic practice and managerial approaches requiring transformation are discussed. CONCLUSIONS: A successful long-term partnership between management and an academic department within a district service may provide the opportunity for rapid progress in population-based service evaluation and health outcomes research.

Community Mental Health Services↗
PubMed1998

Chronic fatigue syndrome: an immunological perspective.

OBJECTIVE: The aim of this study is to review research examining an immunological basis for chronic fatigue syndrome (CFS) and to discuss how a disturbance in immunity could produce central nervous system (CNS)-mediated symptoms. METHOD: Data relevant to the hypothesis that abnormal cytokine release plays a role in the pathogenesis of CFS are reviewed as well as recent evidence relating to potential mechanisms by which immune products may enter the brain and produce a disturbance in CNS processes. RESULTS: Examinations of cytokine levels in patients with CFS have produced inconclusive results. Recent evidence suggests that abnormal release of cytokines within the CNS may cause neural dysfunction by a variety of complex mechanisms. CONCLUSION: Neuropsychiatric symptoms in patients with CFS may be more closely related to disordered cytokine production by glial cells within the CNS than to circulating cytokines. This possibility is discussed in the context of unresolved issues in the pathogenesis of CFS.

Central Nervous System↗
PubMed1998

Neural network subtyping of depression.

OBJECTIVE: To examine the applicability of a neural network classification strategy to examine the independent contribution of psychomotor disturbance (PMD) and endogeneity symptoms to the DSM-III-R definition of melancholia. METHOD: We studied 407 depressed patients with the clinical dataset comprising 17 endogeneity symptoms and the 18-item CORE measure of behaviourally rated PMD. A multilayer perception neural network was used to fit non-linear models of varying complexity. A linear discriminant function analysis was also used to generate a model for comparison with the non-linear models. RESULTS: Models (linear and non-linear) using PMD items only and endogeneity symptoms only had similar rates of successful classification, while non-linear models combining both PMD and symptoms scores achieved the best classifications. CONCLUSIONS: Our current non-linear model was superior to a linear analysis, a finding which may have wider application to psychiatric classification. Our non-linear analysis of depressive subtypes supports the binary view that melancholic and non-melancholic depression are separate clinical disorders rather than different forms of the same entity. This study illustrates how non-linear modelling with neural networks is a potentially fruitful approach to the study of the diagnostic taxonomy of psychiatric disorders and to clinical decision-making.

Behavioral Symptoms↗
PubMed1997

Subcortical hyperintensities on magnetic resonance imaging in patients with severe depression--a longitudinal evaluation.

In a longitudinal evaluation of 37 patients with severe depression who had undergone brain magnetic resonance imaging (MRI) 6 months-2 years (mean 14.1 months) previously, the degree of residual dysfunction was predicted by the extent of subcortical white matter hyperintensities (WMHS, p < .01), longer time elapsed since the MRI scan (p < .05), older age (p < .05), and older age at onset of affective disorder (p < .05). Ten (27%) patients developed "probable" dementia syndromes of the vascular type, with such syndromes being predicted by WMHS (p < .01) and older age of onset of affective disorder (p < .05). Institutionalization of patients was predicted largely by the combination of chronic depression, progressive cognitive decline, and advanced age. The study supports the notion that a subgroup of patients with late-onset depressive disorders, without a family history of depression, and with risk factors to cerebrovascular disease, have extensive WMHS on MRI, and that such structural brain changes predispose to chronic depression and progressive cognitive decline.

Adult↗
PubMed1997

Intravenous immunoglobulin is ineffective in the treatment of patients with chronic fatigue syndrome.

PURPOSE: To determine whether the reported therapeutic benefit of intravenous immunoglobulin in patients with chronic fatigue syndrome (CFS) is dose dependent. PATIENTS AND METHODS: Ninety-nine adult patients, who fulfilled diagnostic criteria for CFS, participated in this double-blind, randomized, and placebo-controlled trial. Patients received intravenous infusions with either a placebo solution (1% albumin) or one of three doses of immunoglobulin (0.5, 1, or 2 g/kg) on a monthly basis for 3 months, followed by a treatment-free follow-up period of 3 months. Outcome was assessed by changes in a series of self-reported measures (quality-of-life visual analog scales, standardized diaries of daily activities, the profile of mood states questionnaire) and the Karnofsky performance scale. Cell-mediated immunity was evaluated by T-cell subset analysis and delayed-type hypersensitivity (DTH) skin testing. RESULTS: No dose of intravenous immunoglobulin was associated with a specific therapeutic benefit. Adverse reactions, typically constitutional symptoms, were reported by 70% to 80% of patients, with no relationship to immunoglobulin treatment. CONCLUSIONS: Intravenous immunoglobulin cannot be recommended as a therapy for the treatment of CFS. A better understanding of the pathophysiology of this disorder is needed before effective treatment can be developed.

Activities of Daily Living↗
PubMed1997

Increased rate of psychosis and psychomotor change in depression with age.

BACKGROUND: We examined the phenomenology of depression in younger (< 60 years old) versus older (> or = 60 years) subjects and, more specifically, the interaction between age and psychomotor disturbance associated with depression. METHOD: Two hundred and eighty-five patients with a DSM-III-R diagnosis of unipolar major depression referred to a mood disorders unit were assessed using the CORE rating scale, a sign-based system for defining melancholia. Subjects were also assessed using the Hamilton Rating Scale for Depression, Zung Depression Scale, Newcastle Endogenous Depression Inventory and the General Health Questionnaire. RESULTS: The total CORE score (and each of its subscales) was found to interact with age. Rates of psychotic and melancholic depression increased with age. Elderly depressives suffered more severe depression (higher HRSD scores), appetite loss and weight loss. Level of psychomotor disturbance and rates of psychosis did not differ between those elderly subjects with an early onset (before the age of 60 years) and those with a late onset (at or after 60 years) of depression. CONCLUSIONS: There appear to be robust phenomenological differences in depression between older and younger subjects. The association between age and psychomotor change may assist our understanding of the neurobiology of depression.

Adult↗
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↗