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Biomedical subjects

I Hickie

Publications and source records attributed to I Hickie.

At least 37 records · Page 2Linked to original sources
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

The temporal stability and co-morbidity of prolonged fatigue: a longitudinal study in primary care.

BACKGROUND: Depression, anxiety and fatigue are among the most common symptoms presented in primary care. Whether such symptoms indicate discrete psychological syndromes or whether they result from a common vulnerability is not clear. This study examined longitudinally the patterns of co-morbidity between prolonged fatigue and other forms of psychological distress in patients attending general practitioners. METHODS: Adults attending primary care completed questionnaires designed to detect cases of prolonged fatigue and psychological distress at presentation and 12 months later. RESULTS: Of 652 patients, the prevalence rates of 'prolonged fatigue' alone, 'psychological distress' alone, 'prolonged fatigue + psychological distress' and 'no disorder' were 7%, 19%, 15% and 59% respectively at initial assessment. Of those patients with any prolonged fatigue syndrome initially, 58% still reported fatigue 12 months later (representing 13% of the total sample). Most importantly, the risk of developing prolonged fatigue was not increased in patients who initially had psychological distress (OR = 0.95; 95% CI 0.2-3.6), neither was the risk of developing psychological distress increased in patients who initially had prolonged fatigue (OR = 1.4; 95% CI 0.6-3.4). CONCLUSIONS: This study indicates that prolonged fatigue is a persistent diagnosis over time. The longitudinal patterns of co-morbidity with psychological distress do not support an aetiological model that proposes a common vulnerability factor for these disorders. Psychiatric classification systems may be better served by treating prolonged fatigue and psychological distress as independent disorders.

Adolescent↗
PubMed1999

Fatigue and psychiatric disorder: different or the same?

BACKGROUND: Fatigue and psychiatric symptoms are common in the community, but their association and outcome are sparsely studied. METHOD: A total of 1177 patients were recruited from UK primary care on attending their general practitioner. Fatigue and psychiatric disorder was measured at three time points with the 12-item General Health Questionnaire and the 11-item Fatigue Questionnaire. RESULTS: Total scores for fatigue and psychiatric disorder did not differ between the three time points and were closely correlated (r around 0.6). The association between non-co-morbid ('pure') fatigue and developing psychiatric disorder 6 months later was the same as that for being well and subsequent psychiatric disorder. Similarly, having non-co-morbid psychiatric disorder did not predict having fatigue any more than being well 6 months previously. Between 13 and 15% suffered from non-co-morbid fatigue at each time point and 2.5% suffered from fatigue at two time points 6 months apart. Less than 1% of patients suffered from non-co-morbid fatigue at all three time points. CONCLUSIONS: The data are consistent with the existence of 'pure' independent fatigue state. However, this state is unstable and the majority (about three-quarters) of patients become well or a case of psychiatric disorder over 6 months. A persistent, independent fatigue state lasting for 6 months can be identified in the primary-care setting, but it is uncommon of the order of 2.5%. Non-co-morbid (pure) fatigue did not predict subsequent psychiatric disorder.

Adolescent↗
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↗
PubMed1999

Prolonged fatigue, anxiety and depression: exploring relationships in a primary care sample.

OBJECTIVE: While prolonged fatigue states are frequently comorbid with other forms of distress, they are now the subject of independent aetiological and treatment research. The objective of this study was to use principal component analysis to clarify the relationships between proposed measures of prolonged fatigue and anxiety and depression in data obtained from patients attending primary care. METHOD: Self-report measures of prolonged fatigue and psychological distress (anxiety and depression) were administered to consecutive ambulatory care patients attending primary care. RESULTS: Data from 1593 subjects were obtained. A two-factor principal component solution (varimax rotation) demonstrated a clear separation between fatigue-related items (Cronbach's alpha = 0.81) as compared with those items describing anxiety and/or depression (Cronbach's alpha = 0.95). A four-factor solution produced similar results with two factors describing general psychological distress (contrasting anxiety and depression), with two other factors describing the profiles of mental and physical fatigue. CONCLUSIONS: The results lend weight to the argument that prolonged fatigue states can be measured independently of conventional notions of anxiety and depression in patients attending primary care. Epidemiological, aetiological and treatment research in psychiatry may need to focus greater attention on such prolonged fatigue states.

Adaptation, Psychological↗
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↗