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Biomedical subjects

I N Ferrier

Publications and source records attributed to I N Ferrier.

At least 37 records · Page 2Linked to original sources
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↗
PubMed1998

Gastrointestinal absorption of aluminium and citrate in man.

Aluminium (Al) is an abundant terrestrial element, but toxic to tissues, including brain. The body is largely protected because systemic Al absorption is very low and in normal individuals almost all absorbed Al is excreted from the body. However gastrointestinal (Gl) absorption is enhanced by organic acids, including citrate. Aluminium and citrate Gl absorption was measured in three healthy males, aged 40-46. After overnight fast, subjects drank a 100 ml fruit drink containing 280 mg Al and 3.2 g citrate (104 and 167 mM, respectively). Al was measured in timed blood and urine samples by GFAAS and serum citrate by enzymatic assay. Blood Al peaked by an increase of 13 +/- 2.1 micrograms/l after 87 +/- 19 min then fell slowly over 24 h. Plasma citrate peaked after 32 min, returning to baseline by 90 min. Al was excreted at a constant rate for the first 24 h, 0.4% of the dose being excreted in urine by this time. It is unlikely that Al is absorbed as Al citrate because the blood citrate peak preceded the Al peak by 45-60 min.

Administration, Oral↗
PubMed1998

Mood and neuropsychological function in depression: the role of corticosteroids and serotonin.

BACKGROUND: Depressed patients show deficits on neuropsychological tests. However, the basis of these impairments and their relationship with mood disturbance remains unclear. METHODS: This paper reviews the literature regarding the relationship between mood disturbance and neuropsychological impairment in depression and the evidence for serotonergic and hypothalamic-pituitary-adrenal (HPA) axis involvement in these two domains. RESULTS: Mood disturbance and neuropsychological impairment both occur in depression, but have no clear relationship in time or degree. Impairment of post-synaptic 5-HT1A receptor function may result in the symptom of low mood in depression. Depressed patients demonstrate abnormalities in the functional control of the HPA axis with a resultant hypercortisolaemia, which may impair neuropsychological function. These processes may be related given the extensive interactions between the serotonergic system and the HPA axis. CONCLUSIONS: We argue that there is a neurobiological cause of impaired neuropsychological function in depression. The complex relationship between neuropsychological function and mood may be a result of interactions between the serotonergic system and the HPA axis, particularly in the hippocampus with involvement of serotonergic 5-HT1A and glucocorticoid receptors. A primary dysfunction in these receptors will produce a lowering of mood and neuropsychological impairment respectively. Either dysfunction will result in a secondary impairment of the alternate system. Thus, the effective and psychological changes of depressive illness are likely to have complex relationships in time and severity to one another and the illness as a whole may result from a range of primary aetio-pathologies.

Adrenal Cortex Hormones↗
PubMed1998

Superoxide, neuroleptics and the ubiquinone and cytochrome b5 reductases in brain and lymphocytes from normals and schizophrenic patients.

The effects of the neuroleptic flupenthixol on the expression of the genes coding for the mitochondrial ubiquinone and cytochrome b5 reductases have been studied because of the importance of these enzymes in energy metabolism, oxidative stress and also because similar but oppositely directed changes have been previously observed in the cerebral cortex from schizophrenics. The neuroleptic flupenthixol reduces the expression in rats of the gene coding for NADH-cytochrome b5 reductase as measured by in situ hybridisation and its enzymic manifestation. Flupenthixol also reduces the enzymic activity of the mitochondrial NADH-ubiquinone reductase, and it has been previously shown that mRNA from the mitochondrially coded parts of the enzyme are reduced by the drug. Both the cis- and therapeutically less active trans-flupenthixol were found to produce these changes in rats. Post-mortem brain tissue from schizophrenics who have received neuroleptic medication have reduced levels of both reductases as measured enzymically, Lymphocyte samples from schizophrenics also have reduced levels of both reductases compared with normals. The superoxide anion O2- is the principle agent of oxidative stress and both the cytochrome b5 and the ubiquinone reductase enzymes were semi-purified from sheep liver and shown to produce appreciable amounts of superoxide. Superoxide production is reduced in brain homogenates from rats treated with flupenthixol. Its production is also reduced in brain tissue and lymphocytes from schizophrenics receiving neuroleptic medication. We conclude that neuroleptic medication reduces the expression of both the ubiquinone and cytochrome b5 reductase and among the effects of this reduction is a decrease in the production of neurotoxic superoxide.

Adult↗
PubMed1998

Lamotrigine and gabapentin. Alternative in the treatment of bipolar disorder.

The anticonvulsants carbamazepine and sodium valproate have efficacy in hypomania, bipolar depression and in the prophylaxis of bipolar disorder. This paper reviews published evidence on the effects of the new anticonvulsants gabapentin and lamotrigine in bipolar disorder. The conclusion is that there is good evidence from open studies to indicate that randomised double-blind trials of these compounds should be carried out. The pharmacology of these anticonvulsants is reviewed and putative predictors of good response identified.

Acetates↗
PubMed1997

Gastrointestinal absorption of aluminum is increased in Down's syndrome.

Individuals with Down's Syndrome (DS) develop the neuropathological features of senile dementia of the Alzheimer's type (SDAT) by early middle age. Because of recent evidence that gastrointestinal (GI) aluminum (Al) absorption is increased in patients with SDAT, and that Al may contribute to associated neuropathological changes, we have investigated the GI uptake of Al in patients with DS by two methods. The first measured the absorption of 27Al at concentrations associated with antacid use, in the presence of citrate, using atomic absorption spectrometry. There was no difference between basal blood concentrations of 27Al in 15 DS subjects (36-46 years) and 15 age-matched controls. The mean increase in 27Al blood concentrations 60 minutes after the dose of Al was four times greater in the DS group than in controls (p < 0.001). The second measured GI absorption of 26Al under normal dietary conditions using accelerator mass spectrometry. With 26Al the mean Al absorption in DS subjects (n = 5) exceeded that of controls (n = 4) by a factor of 6 (p < 0.02). Although the mechanisms of enhanced absorption are unknown, the data indicate that similar abnormalities in the GI handling of Al occur in both SDAT and DS suggesting that it may be advisable to minimize dietary exposure to Al in subjects at risk of developing Alzheimer-type pathology.

Adult↗
PubMed1997

D2 dopamine receptor gene (DRD2) Taq1 A polymorphism: reduced dopamine D2 receptor binding in the human striatum associated with the A1 allele.

The relationship between a dopamine D2 receptor genetic polymorphism at the Taq1 A locus and the level of D2 receptor binding was investigated in normal, middle aged to elderly subjects with no psychiatric or neurological disorders. D2 receptor binding was measured by autoradiography in the caudate, putamen and nucleus accumbens, using the specific D2 receptor ligand [3H]-raclopride. In a sample of 44 individuals, only one was homozygous for the A1 allele, 25 were homozygous for A2 and 18 were heterozygotes. The presence of one or two A1 alleles was associated with reduced D2 receptor binding in all areas of the striatum, reaching statistical significance in the ventral caudate and putamen (p = 0.01 and p = 0.044, respectively). This reduction was more marked in males than females, particularly in the putamen. A genetic predisposition to lower D2 receptor expression may increase susceptibility to neuroleptic medication or clinical symptoms that are associated with diseases involving dopaminergic pathology.

Aged↗
PubMed1995

The relationship between premorbid neuroticism, cognitive dysfunction and persistence of depression: a 1-year follow-up.

In a previous report of patients with unipolar major depressive disorder, we found that deficits in autobiographical memory predicted depression levels over a 7-month interval. This follow-up examined predictors of recovery as defined by a period of 8 weeks with no or minimal symptoms of depression and examined the extra predictor variable, neuroticism. In a sample of 21 patients, episode duration was significantly correlated with high levels of premorbid neuroticism, dysfunctional attitudes and overgeneral autobiographical memories produced in response to emotionally negative cue words. When severity of depression was partialled out, high N score was significantly but independently correlated with each of these cognitive variables. The implication of these attitudinal and information processing biases were explored.

Adult↗
PubMed1995

A study of altered gene expression in frontal cortex from schizophrenic patients using differential screening.

In order to examine the molecular basis of schizophrenia we have employed a sequential differential hybridisation protocol to isolate mRNAs whose abundances are altered in schizophrenic compared to normal frontal cortex. Five cDNAs present at abnormal levels in the schizophrenic brain have been isolated by this method. The sequences were identified on the basis of homologies in the EMBL and Genbank databases. All the sequences encode mitochondrial transcripts; one encodes part of the 12s rRNA, three encode parts of the 16s rRNA region of the mitochondrial genome whilst the fourth encodes part of the amino acid sequence of cytochrome oxidase sub-unit II. It was established that mitochondrial sequences were not over-represented in the library and that this could therefore not account for the isolation of five mitochondrial transcripts by this procedure. Increased levels of cytochrome oxidase mRNA were detected in a further set of extracts from the frontal cortex of eight schizophrenic patients and five controls. The amount of mt-DNA was measured in these samples but there was no difference between schizophrenic and control. These results indicate a possible abnormality of mitochondrial function in the schizophrenic frontal cortex.

Adult↗
PubMed1994

An evaluation of the predictive validity and inter-rater reliability of clinical diagnostic criteria for senile dementia of Lewy body type.

Several recent autopsy studies suggest that senile dementia of Lewy body type (SDLT) may be the second most common neuropathologic cause of dementia in the elderly, accounting for 7 to 30% of all cases. Operational criteria for the antemortem clinical diagnosis of SDLT have already been proposed by our group. The performance of these is now examined by randomizing the case notes from a new series of SDLT, Alzheimer, and multi-infarct dementia patients for psychiatric assessment by four raters of varying clinical experience and blind to pathologic diagnosis. Using the SDLT criteria, the two most experienced raters agreed in 94% of cases (kappa = 0.87), with the least experienced rater agreeing in 78% (kappa = 0.50). Diagnostic specificity for SDLT was uniformly high (90.0 to 97.0%), with a mean sensitivity of detection of 74%, and was greater by the experienced (90.0%) than the least experienced (55%) clinician. The antemortem identification of SDLT patients can therefore be achieved with a high degree of diagnostic specificity using such operationalized criteria, although there remains a minority of patients who present with either "typical" Alzheimer-type symptoms or with paranoid or delusional symptoms in the absence of substantial cognitive impairment. Sensitivity to neuroleptics may be a useful diagnostic pointer in these patients.

Aged↗
PubMed1993

Effect of silicon on gastrointestinal absorption of aluminium.

The reported geographical association between Alzheimer's disease and levels of aluminium (Al) in water supplies may reflect the inverse relation between Al and silicon (Si) concentrations in water, and the potential for Si to reduce the bioavailability of the metal. We tested this hypothesis using isotopic 26Al tracer administered orally to five healthy volunteers in the presence and absence of Si. Dissolved Si, at a concentration found in some water supplies (100 mumol/L), reduced the peak plasma 26Al concentration to 15% of the value obtained in the absence of Si. The results indicate that dissolved Si is an important factor in limiting the absorption of dietary Al.

Administration, Oral↗
PubMed1993

Monoaminergic activities in Lewy body dementia: relation to hallucinosis and extrapyramidal features.

Serotonergic (5-HT) and dopaminergic activities have been examined in Lewy Body Dementia (LBD) and compared with Parkinson's disease (PD) and Alzheimer's disease (AD). In the neocortex the LBD subgroup experiencing hallucinations was distinguished from the other categories by an increase in the 5HIAA:5HT ratio measured in frontal cortex and by the serotonergic (5-HIAA or 5-HIAA:5-HT): cholinergic (choline acetyltransferase) ratio in frontal and temporal cortex. In the neostriatum (caudate nucleus), loss of dopamine and increased HVA:dopamine ratio correlated with the reduction in substantia nigra neurons in LBD but not PD, despite the greater loss of neurones and dopamine and the higher dopamine turnover ratio in PD. LBD patients experiencing severe Parkinsonism as a result of neuroleptic treatment tended to have lower neuron counts, in combination with higher turnover ratios, than the remainder. Qualitative differences between LBD and PD included decreased cortical 5-HT turnover in PD compared with the increase in LBD. There were no significant changes in any parameter in AD, with the exception of a reduction in temporal cortex 5HIAA. The results suggest that although the neurochemical pathology of LBD and PD involves similar systems, the nature of the derangements differs sufficiently between the diseases to account for differences in symptomatology.

Aged↗
PubMed1993

Patterns of treatment resistance in bipolar affective disorder.

The mean index episode length in 19 consecutive admissions with treatment-resistant bipolar affective disorder was 21.7 months. Four patterns of resistance were identified: rapid cycling (37%), other forms of cycling (32%), chronic depression (26%) and mixed states (6%). Female gender was significantly associated with rapid cycling. Other risk factors for treatment-resistant bipolar disorder, including a high prevalence of family history of affective disorder (72%) and electroencephalographic abnormalities (54% of recordings), were not confined to the rapid cycling group.

Adult↗
PubMed1993

Autobiographical memory in depression: state or trait marker?

Two cognitive measures were used to assess 22 patients who met DSM-III-R criteria for major depressive disorder: the Autobiographical Memory (AM) test and the Dysfunctional Attitude Scale. They were followed up over seven months. Measurement of dysfunctional attitudes did not predict outcome at seven months. Overgeneral recall on the AM test at initial assessment, especially for emotionally positive memories, was highly correlated with failure to recover from depression and accounted for 33% of the variance in HRSD score at follow-up. Overgeneral recall of emotional memories did not change during follow-up. It is suggested that overgenerality is a trait marker indicating vulnerability to persistent depression.

Adult↗