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Biomedical subjects

I N Ferrier

Publications and source records attributed to I N Ferrier.

At least 19 recordsLinked to original sources
PubMed2002

Hypothalamic-pituitary-adrenal axis function in patients with chronic depression.

BACKGROUND: Hypothalamic-pituitary-adrenal (HPA) axis function in patients with chronic depression has previously been shown to be normal when measured using the dexamethasone suppression test (DST). We examined patients with chronic depression using the sensitive dexamethasone/corticotropin releasing hormone (dex/CRH) test and the dexamethasone suppression test (DST) to establish whether HPA axis abnormalities are present in this group. We also compared the sensitivity of the two tests and compared the results with previous studies in depression that have not specifically selected chronic patients. METHOD: Twenty-nine patients with the chronic subtype of major depressive disorder and 28 matched controls underwent examination of HPA axis function. RESULTS: Neither the cortisol response to the DST or the dex/CRH test differed significantly between the patient and control groups. There was a trend in favour of more patients than controls having an abnormal response to the dex/CRH test (P = 0.052). Neither the patients with an abnormally enhanced response, nor the magnitude of response could be predicted by any illness or demographic variable. CONCLUSION: The HPA axis is not overtly abnormal in chronic depression. This contrasts with previous findings in acute depression and bipolar disorder and may suggest that the HPA axis abnormalities present in acute depression resolve, but are not accompanied by symptom resolution. Alternatively, a subgroup of depressives with less HPA dysfunction may progress to chronicity. This has implications for treatment and prognosis. The dex/CRH is a more sensitive test of HPA axis function than the DST in patients with chronic depression.

Adult↗
PubMed2002

Thioridazine and sudden unexplained death in psychiatric in-patients.

BACKGROUND: Sudden death has been linked to antipsychotic therapy, but the relative risk associated with specific drugs is unknown. AIMS: To assess the risk of sudden unexplained death associated with antipsychotic drug therapy and its relation to drug dose and individual agents. METHOD: A case-control study of psychiatric in-patients dying suddenly in five hospitals in the north-east of England and surviving controls matched for age, gender and mental disorder. Logistic regression analysis was used to identify significant risk factors, and odds ratios were calculated. RESULTS: Sixty-nine case-control clusters were identified. Probable sudden unexplained death was significantly associated with hypertension, ischaemic heart disease and current treatment with thioridazine (adjusted odds ratio=5.3, 95% CI 1.7-16.2, P=0.004). There was no significant association with other individual antipsychotic drugs. CONCLUSIONS: Thioridazine alone was associated with sudden unexplained death, the likely mechanism being drug-induced arrhythmia.

Adolescent↗
PubMed2001

Electrophysiological and cognitive function in young euthymic patients with bipolar affective disorder.

OBJECTIVES: EEG abnormalities and neurocognitive deficits have been reported in patients with bipolar affective disorder. The aim of this study was to ascertain whether brain function remains impaired in young bipolar patients who have become euthymic in response to treatment. METHODS: Brain function was assessed by quantitative electroencephalographic (EEG) power-spectral mapping and by a battery of neuropsychological tests. The subjects were 29 euthymic bipolar patients aged 18-40 years and 26 healthy volunteers of similar age, IQ and socioeconomic status. RESULTS: Grand means of spectral power of the resting EEG showed significantly (from p < 0.01 to p < 0.0001) greater power in all wave bands (delta, theta, alpha and beta) in patients compared with controls. The most marked increases were in right temporal theta and left occipital beta power (with eyes open) encompassing brain areas concerned in visuospatial processing. Neurocognitive performance was significantly impaired in the patients compared with controls in a range of visuospatial tasks. CONCLUSIONS: The findings show significant disturbance of EEG activity and deficits in visuospatial processing in young bipolar patients despite clinical euthymia. The abnormalities were not related to age of onset or duration of illness and do not appear to be attributable to medication. The cognitive impairments were associated with the number of previous affective episodes.

Adolescent↗
PubMed2001

Raised levels of plasma interleukin-1beta in major and postviral depression.

OBJECTIVE: Interleukin-1beta (IL-1beta) is released as part of the acute phase immune response and can directly stimulate the release of corticotrophin-releasing hormone and thus induce hypothalamic pituitary adrenal axis hyperactivity. Major depression has been shown to be accompanied by both an acute phase immune response, including raised IL-1beta production and hypothalamic pituitary adrenal axis hyperactivity. In this study the possible role of IL-1beta in major depression and postviral depression was investigated. METHOD: Plasma IL-1beta levels were measured in four groups; patients suffering from postviral depression (n= 17), patients with major depression (n = 20), subjects who were postviral and euthymic (n= 12) and normal controls (n = 20). RESULTS: IL-1beta serum concentrations were significantly elevated in both groups of depressed patients compared to controls. The serum concentrations of IL-1beta were higher in the postviral group than in the major depression group; this difference was not significant. CONCLUSION: These data confirm previous suggestions of elevated IL-1beta levels in major depression and postviral depression. IL-1beta is known to induce depressive symptoms as well as sickness behaviour and may contribute to the hypothalamic pituitary adrenal axis hyperactivity found in mood disorders.

Major Depressive Disorder↗
PubMed2001

Developments in mood stabilisers.

Bipolar affective disorder is a life-long condition with profound effects on sufferers' social and occupational life. Despite efficacy in clinical trials and in some groups of patients, lithium's effectiveness in clinical practice is hampered by its side effect profile and limited concordance. Alternative and adjunctive treatments to lithium in bipolar disorder have been sought and the anticonvulsants carbamazepine and valproate show promise. Despite these advances, treatment resistance persists. Lamotrigine, a new anticonvulsant, is increasingly used in treatment-resistant cases under specialist supervision. Further pharmacological and non-pharmacological strategies for bipolar prophylaxis are currently under investigation. These developments are the focus of this review.

Anticonvulsants↗
PubMed2001

A neuropathological study of vascular factors in late-life depression.

OBJECTIVES: Depression is a common psychiatric disorder in late life and it may be associated with vascular disease processes. Although there are clinical and neuroimaging studies lending support to such a "vascular depression" hypothesis there have been no neuropathological studies to directly test this. Postmortem tissue was investigated to determine whether late life depression was associated with atheromatous change in large and medium vessels and microvascular disease in the brain. METHODS: Postmortem tissue was obtained from 20 patients with a history of at least one episode of DSM-IV major depression and 20 control subjects. Standard procedures were carried out to analyze and quantify Alzheimer type pathology (plaques, tangles, Braak staging) and cortical Lewy bodies. Coronary arteries, cerebral vessels, and aorta were rated for atheromatous disease on a 0-3 scale and the four neocortical areas were rated for microvascular disease. RESULTS: The two groups showed no significant differences in age, sex, or postmortem delay. There was a significant increase in atheromatous disease in the depressed group (p=0.023). No differences were found for microvascular disease, either in the brain generally or locally in the frontal lobes. No subject had any significant Alzheimer type or Lewy body pathology. CONCLUSIONS: Neuropathological evidence was found for an excess of atheromatous disease, related to the aortic and cerebral vessels, in late life depression. However, there was no evidence of an increase in microvascular disease. The findings broadly support the vascular depression hypothesis.

Aged↗
PubMed2001

White matter lesions and season of birth of patients with bipolar affective disorder.

OBJECTIVE: It is established that patients with bipolar disorder have an excess of births in winter or early spring. The authors investigated a link between season of birth and white matter lesions with magnetic resonance imaging (MRI). METHOD: T(2)-weighted and proton density MRI scans were examined for 79 patients with bipolar disorder (DSM-IV) for the presence of deep subcortical and periventricular white matter lesions. The birth seasons of patients with white matter lesions were compared with those of the general population. RESULTS: Thirteen subjects exhibited deep subcortical white matter lesions, of whom nine (69.2%) were born in the winter months (January to March). Seven of these patients remained symptomatic, despite adequate treatment for more than 2 years. CONCLUSIONS: Birth season, illness outcome, and deep subcortical white matter lesions appear to be closely linked. Deep subcortical white matter lesions may be a marker of a toxic or infective insult in utero.

Adult↗
PubMed2001

Cerebral white matter lesions in bipolar affective disorder: relationship to outcome.

BACKGROUND: Twenty per cent of patients with bipolar affective disorder suffer an illness that responds inadequately to treatment and has a poor outcome. Many patients, but not all, with bipolar disorder show white matter abnormalities on T(2)-weighted magnetic resonance imaging (MRI). AIMS: To explore the hypothesis that white matter abnormalities on MRI are seen more frequently in subjects whose illness has a poor outcome compared with those with a good outcome or controls. METHOD: Two groups of age- and gender-matched patients with bipolar disorder (14 with a good outcome and 15 with a poor outcome) and 15 controls, aged 20-65 years, were studied. Axial T(2)-weighted MRI scans were examined for the presence and severity of white matter abnormalities. RESULTS: Significantly more poor outcome group members had deep subcortical punctate, but not periventricular, white matter hyperintensities than the good outcome group (P:=0.035) or controls (P:=0.003) and these abnormalities were of greater severity (P:=0.030 and P:<0.014, respectively). CONCLUSIONS: Subcortical white matter lesions are associated with poor outcome bipolar disorder.

Adult↗
PubMed2001

Characterizing the ideal antidepressant therapy to achieve remission.

A paradigm shift in the management of depression has transpired in recent years with the modification of treatment goals toward remission, an outcome that transcends response. Pharmacotherapy, psychotherapy, electroconvulsive therapy, and combination therapies are treatment modalities available to the clinician for facilitating remission in depressed patients. For patients with moderate-to-severe depression, pharmacotherapy, either alone or in combination with other therapeutic approaches, is the treatment of choice. Antidepressants have heterogeneous effects on neurotransmitter systems that are manifested in different levels of selectivity and potency, influencing the drugs' safety profile through their potential for inducing drug-drug interactions. In terms of the pharmacokinetic-pharmacodynamic characteristics of antidepressants, a positive dose-response relationship has been shown to enhance the achievement of full remission because it allows the clinician to maximize drug dosage to optimize efficacy. Evidence from several studies indicates that treatment strategies that involve combined serotonergic and noradrenergic mechanisms result in pharmacologic synergism that leads to an enhanced antidepressant effect. This article identifies key characteristics of antidepressants that have been associated with greater efficacy.

Antidepressive Agents↗
PubMed2000

QTc-interval abnormalities and psychotropic drug therapy in psychiatric patients.

BACKGROUND: Sudden unexplained death in psychiatric patients may be due to drug-induced arrhythmia, of which lengthening of the rate-corrected QT interval (QTc) on the electrocardiogram is a predictive marker. We estimated the point prevalence of QTc lengthening in psychiatric patients and the effects of various psychotropic drugs. METHODS: Electrocardiograms were obtained from 101 healthy reference individuals and 495 psychiatric patients in various inpatient and community settings and were analysed with a previously validated digitiser technique. Patients with and without QTc lengthening, QTc dispersion, and T-wave abnormality were compared by logistic regression to calculate odds ratios for predictive variables. FINDINGS: Abnormal QTc was defined from the healthy reference group as more than 456 ms and was present in 8% (40 of 495) of patients. Age over 65 years (odds ratio 3.0 [95% CI 1.1-8.3]), use of tricyclic antidepressants (4.4 [1.6-12.1]), thioridazine (5.4 [2.0-13.7]), and droperidol (6.7 [1.8-24.8]) were robust predictors of QTc lengthening, as was antipsychotic dose (high dose 5.3 [1.2-24.4]; very high dose 8.2 [1.5-43.6]). Abnormal QT dispersion or T-wave abnormalities were not significantly associated with antipsychotic treatment, but were associated with lithium therapy. INTERPRETATION: Antipsychotic drugs cause QTc lengthening in a dose-related manner. Risks are substantially higher for thioridazine and droperidol. These drugs may therefore confer an increased risk of drug-induced arrhythmia.

Adolescent↗
PubMed2000

Cognitive vulnerability in patients with bipolar disorder.

BACKGROUND: No study has simultaneously explored key components of Beck's model of cognitive vulnerability to depression in people with bipolar disorders. METHODS: We compared 41 euthymic bipolar patients with 20 healthy control subjects. All subjects were assessed on the Hamilton Rating Scale for Depression, the Autobiographical Memory Test and the Mean Ends Problem-Solving procedure and also completed the Beck Depression Inventory, the Dysfunctional Attitude Scale, the Sociotropy Autonomy Scale and the Rosenberg Self-Esteem Questionnaire. RESULTS: In comparison to control subjects, patients with bipolar disorder demonstrated significantly higher levels of dysfunctional attitudes (particularly perfectionism and need for approval) and sociotropy, significantly greater over-general recall on an autobiographical memory test and significantly less ability to generate solutions to social problem-solving tasks. These between group differences remained significant when age, intelligence, latency to respond to autobiographical memory test cue words, and subjective mood ratings were included as co-variates in the statistical analysis. Within the patient group, cognitive dysfunction was significantly correlated with level of morbidity (as measured by number of previous illness episodes). CONCLUSIONS: This study suggests that cognitive vulnerability in patients with bipolar disorder is similar to that described in unipolar disorders. It is not clear whether this dysfunction is a cause or an effect of repeated episodes of bipolar disorder. However, the findings may have implications for clinical treatment as well as suggesting a number of important new avenues of research into psychological models of affective disorder.

Adult↗
PubMed2000

Distribution of amyloid beta 42 in relation to the cerebral microvasculature in an elderly cohort with Alzheimer's disease.

Amyloid beta (A beta) deposits and neurofibrillary pathology are characteristic features of Alzheimer's disease (AD). The association of A beta with cerebral vessels is an intriguing feature of AD. While some degree of cerebral A beta angiopathy involving the leptomeninges and intraparenchymal vessels occurs in almost all cases of AD, the proportion of microvessels within a neocortical region containing deposits of A beta peptide is not known. In this study, we examined a cohort of clinically and pathologically evaluated AD cases to assess the percentage of cerebral microvessels in the temporal cortex and parahippocampal gyrus associated with the predominant, A beta 42 form of the peptide. We also assessed whether the distribution and burden of amyloid was related to apolipoprotein E (APOE) genotype. Using double immunostaining methods, we surprisingly found that at least 40% of the microvessels in the two brain regions contained A beta 42 deposits. There was no correlation of such localization with APOE genotype, however, epsilon 4 homozygotes revealed a greater burden of A beta 40. These observations suggest that high proportions of cortical microvessels are associated with A beta 42, which may affect microvascular function.

Aged↗
PubMed2000

Elevation in late-life depression of intercellular adhesion molecule-1 expression in the dorsolateral prefrontal cortex.

OBJECTIVE: Late-life depression may be associated with vascular disease. The authors investigated this association by determining whether intercellular adhesion molecule-1 (ICAM-1), a marker of ischemia-induced inflammation, is elevated in the dorsolateral prefrontal cortex in depression. METHOD: The authors studied postmortem tissue from 20 depressed subjects and a matched comparison group of 20 nondepressed subjects. They used immunocytochemistry to stain ICAM-1 in blood vessels on sections of the dorsolateral prefrontal cortex and occipital cortex and quantitative true color image analysis to measure the proportion of vessels expressing ICAM-1. RESULTS: ICAM-1 was significantly higher in both the gray and white matter of the depressed subjects' dorsolateral prefrontal cortex than the comparison subjects' dorsolateral prefrontal cortex. The difference between these groups was much smaller in the gray and white matter of the occipital cortex. CONCLUSIONS: These findings support the vascular depression hypothesis, which has important implications for the understanding and management of late-life depression.

Age Factors↗
PubMed1999

Neuropsychological function in euthymic patients with bipolar disorder.

BACKGROUND: The assumption that patients with bipolar disorder make a full inter-episode recovery has been challenged by limited evidence that suggests that neuropsychological dysfunction in bipolar disorder may persist beyond episodes of illness. AIMS: To test the hypothesis that patients with euthymic bipolar disorder show neuropsychological impairment. METHOD: A battery of neuropsychological tests (assessed attention, working memory, learning and executive function) was administered to three matched groups of subjects: good-outcome patients with bipolar disorder (n = 21); poor-outcome patients with bipolar disorder (n = 20); controls (n = 20). All patients were clinically euthymic, although some had low levels of depressive symptoms. RESULTS: Patients performed worse than controls on a number of neuropsychological tests. When age, premorbid IQ and depressive symptoms were controlled for, the results indicated impairment of executive function. CONCLUSIONS: These findings provide good evidence for the existence of neuropsychological impairment in patients with euthymic bipolar disorder, although the possible effect of medication should not be overlooked. This may be of clinical relevance and raises questions about the course and outcome of the illness.

Adult↗
PubMed1999

Treatment of major depression: is improvement enough?

The goals of antidepressant treatment are to induce remission and prevent relapse or recurrence. While response is the standard criterion applied to comparisons of antidepressant drugs indicating an improvement from baseline, the more stringent criterion of remission is more relevant to clinical practice because it indicates that the patient is asymptomatic (i.e., "well"). Patients may enter into a remission or partial remission, which is characterized by the presence of residual symptoms and an increased risk of relapse, impairment, and suicide. Studies with many antidepressants demonstrate response rates of 50% to 60% but remission rates of only 20% to 30%. Venlafaxine is an antidepressant that is characterized as a serotonin-norepinephrine reuptake inhibitor (SNRI). Using the criterion of remission, placebo-controlled and comparative trials demonstrate a higher remission rate with venlafaxine than with other antidepressants, thus improving the proportion of patients who are "well." Selection of optimal antidepressant therapy should consider drugs that have the greatest potential to induce remission.

Antidepressive Agents↗
PubMed1998

Structural and functional abnormalities in elderly patients clinically recovered from early- and late-onset depression.

BACKGROUND: Structural and functional brain changes have been described in elderly patients with unipolar affective disorder. Changes appear to be more marked in patients with late-onset depression, but the reversibility of such changes after clinical recovery is not known. METHODS: Magnetic resonance imaging, electroencephalography (EEG), and cognitive tests were performed in 23 elderly patients (mean age 66.5 years) clinically recovered from major depression. Twelve had late-onset depression (first episode over 55 years of age); 11 had early onset (first episode before 50 years). EEG and cognitive testing were also performed on 15 control subjects. RESULTS: Patients with late-onset depression had larger third and lateral ventricles, increased ventricular-brain ratio, and greater frequency and severity of subcortical white matter lesions than those with early onset. There was no difference between early- and late-onset patients in EEG and cognitive measures, but compared with controls patients showed significant changes in EEG evoked potentials and increased slow-wave activity, slowed reaction times, and global impairments in cognitive function. CONCLUSIONS: These results suggest that structural changes are greater in patients with late-onset depression, and that EEG and cognitive impairments persist after recovery, regardless of age of onset of depression, and are independent of structural changes.

Age of Onset↗