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Biomedical subjects

M W Carney

Publications and source records attributed to M W Carney.

At least 19 recordsLinked to original sources
PubMed2000

Homocysteine, folate, methylation, and monoamine metabolism in depression.

OBJECTIVES: Previous studies suggest that folate deficiency may occur in up to one third of patients with severe depression, and that treatment with the vitamin may enhance recovery of the mental state. There are, however, difficulties in interpreting serum and red cell folate assays in some patients, and it has been suggested that total plasma homocysteine is a more sensitive measure of functional folate (and vitamin B12) deficiency. Other studies suggest a link between folate deficiency and impaired metabolism of serotonin, dopamine, and noradrenaline (norepinephrine), which have been implicated in mood disorders. A study of homocysteine, folate, and monoamine metabolism has, therefore, been undertaken in patients with severe depression. METHODS: In 46 inpatients with severe DSM III depression, blood counts, serum and red cell folate, serum vitamin B12, total plasma homocysteine, and, in 28 patients, CSF folate, S-adenosylmethionine, and the monoamine neurotransmitter metabolites 5HIAA, HVA, and MHPG were examined. Two control groups comprised 18 healthy volunteers and 20 patients with neurological disorders, the second group undergoing CSF examination for diagnostic purposes. RESULTS: Twenty four depressed patients (52%) had raised total plasma homocysteine. Depressed patients with raised total plasma homocysteine had significant lowering of serum, red cell, and CSF folate, CSF S-adenosylmethionine and all three CSF monoamine metabolites. Total plasma homocysteine was significantly negatively correlated with red cell folate in depressed patients, but not controls. CONCLUSIONS: Utilising total plasma homocysteine as a sensitive measure of functional folate deficiency, a biological subgroup of depression with folate deficiency, impaired methylation, and monoamine neurotransmitter metabolism has been identified. Detection of this subgroup, which will not be achieved by routine blood counts, is important in view of the potential benefit of vitamin replacement.

Adult↗
PubMed1992

Folate deficiency, biopterin and monoamine metabolism in depression.

Seven (21%) of 34 patients with a severe DSM-III diagnosis of major depression had red-cell folate levels below 150 ng/ml. This subgroup with folate deficiency had significantly lower CSF 5-hydroxyindoleacetic acid (5HIAA) compared to neurological controls. For all depressed patients red-cell folate was significantly correlated with CSF 5HIAA and homovanillic acid (HVA). CSF tetrahydrobiopterin (BH4) was significantly correlated with CSF 5HIAA and HVA and red-cell folate. Our observations provide further evidence of the links between folate, biopterin and monoamine metabolism in depression.

Adult↗
PubMed1990

Enhancement of recovery from psychiatric illness by methylfolate.

41 (33%) of 123 patients with acute psychiatric disorders (DSM III diagnosis of major depression or schizophrenia) had borderline or definite folate deficiency (red-cell folate below 200 micrograms/l) and took part in a double-blind, placebo-controlled trial of methylfolate, 15 mg daily, for 6 months in addition to standard psychotropic treatment. Among both depressed and schizophrenic patients methylfolate significantly improved clinical and social recovery. The differences in outcome scores between methylfolate and placebo groups became greater with time. These findings add to the evidence implicating disturbances of methylation in the nervous system in the biology of some forms of mental illness.

Adult↗
PubMed1990

Red cell folate concentrations in psychiatric patients.

Red cell folate and vitamin B12 estimations were performed on 243 successively admitted in-patients at a District General Hospital Psychiatric Unit and 42 out-patients (29 attending a lithium clinic). Patients were classified into five diagnostic groups. The mean ages of the manic and schizophrenic patients were lower than of the depressed or euthymic patients but age was not correlated with red cell folate or serum B12 levels in any group. There were 89 (31%) patients with red cell folate below 200 ng/ml and 35 (12%) with concentrations below 150 ng/ml. Significantly more of these low-folate patients were in-patients than out-patients. The mean red cell folate in the depressed patients was significantly lower than in the euthymic, manic and schizophrenic groups. Alcoholics had a similar mean red cell folate to depressed patients which was not quite significantly lower than the other groups. The mean serum B12 level in the alcoholics was, however, significantly raised. There were no significant differences in red cell folate or serum B12 between lithium-treated and untreated euthymic patients. The highest proportions of values below 200 ng/ml and 150 ng/ml were found in depressed and alcoholic patients. Endogenous depressives had the highest percentage of values below 150 ng/ml (folate-deficient) of all psychiatric groups and alcoholic patients. The significance of these findings is discussed.

Adolescent↗
PubMed1990

Cerebrospinal fluid S-adenosylmethionine in depression and dementia: effects of treatment with parenteral and oral S-adenosylmethionine.

Cerebrospinal fluid (CSF) S-adenosylmethionine (SAM) levels were significantly lower in severely depressed patients than in a neurological control group. The administration of SAM either intravenously or orally is associated with a significant rise of CSF SAM, indicating that it crosses the blood-brain barrier in humans. These observations provide a rational basis for the antidepressant effect of SAM, which has been confirmed in several countries. CSF SAM levels were low in a group of patients with Alzheimer's dementia suggesting a possible disturbance of methylation in such patients and the need for trials of SAM treatment.

Administration, Oral↗
PubMed1989

The switch mechanism and the bipolar/unipolar dichotomy.

During open trials of intravenous and oral S-adenosyl methionine (SAM) and a placebo-controlled trial of intravenous SAM in 29 patients, 25 patients had SAM and four had placebo (27 courses of SAM, two of the patients receiving two trials a piece). Nine of 11 bipolar patients (all SAM-treated) switched into elevated mood state (hypomania, mania and euphoria) and two did not respond. Six endogenous unipolar patients improved and five did not. No non-endogenous patient or placebo patient responded for more than 14 days. No unipolar patient switched into elated mood. In eleven (38%) trials and nine (33%) patients there was a switch from depression to elation. Biochemical data from the cerebrospinal fluid of eight patients suggested that the role of the dopaminergic system should be further explored.

Administration, Oral↗
PubMed1988

Diethylpropion and psychosis.

Five female patients who developed psychosis while taking diethylpropion hydrochloride are described, four with paranoid psychosis and one with manic psychosis. In all but one patient, these drugs were medically prescribed. Although relatively few cases of psychosis and psychosis-like illness were reported to the Committee for Safety of Medicines from 1963 until 1986, further cases may be anticipated. Patients on the drug should be carefully supervised and it should not be prescribed to those with personality disorder, previous evidence of amphetamine, alcohol, or other drug abuse, or those with a history of psychiatric breakdown.

Adult↗
PubMed1988

Benzodiazepine abuse and management of anxiety in the community.

Medication is largely inappropriate in the management of anxiety, and benzodiazepines are not apparently effective in the minor affective disorders commonly seen in general practice (Catalan and Gath, 1985). Enough has been said to indicate that other measures are likely to be more helpful and to reduce the tendency to prescribe benzodiazepines. The taking of these drugs threatens to become epidemic and while medical agencies are by no means the only sources, sensible prescribing will go--and may already have gone, as the DHSS (1986) figures suggest--some way toward limiting consumption of these drugs. The DHSS needs to record more specific data relating to benzodiazepine use and abuse. Comparative trials of benzodiazepines and alternative non-benzodiazepine methods of anxiety management need to be set up as matter of urgency. The (no doubt) false impression that the pharmaceutical industry is dragging its feet in planning and sponsoring such trials should be speedily dispelled. Benzodiazepine prescribing, if it increases, may well in itself become a major danger to public health.

Anti-Anxiety Agents↗
PubMed1987

S-adenosylmethionine and affective disorder.

Several open and double-blind studies suggest that SAMe may have an anti-depressant effect, and further studies are indicated. SAMe may exert a beneficial effect selectively on endogenous rather than neurotic depression. SAMe crosses the blood-brain barrier. SAMe is involved in several central enzyme pathways relating to transmethylation and folate and monoamine metabolism as well as in membrane function and neuro-transmission. The neuropharmacology of SAMe's effect on mood and the switch mechanism has yet to be fully explored. The actions of SAMe on the dopaminergic system are as yet unclear. SAMe is a physiologic substance that is non-toxic and relatively free of severe side effects (with the exception of mania, which may be a manifestation of the basic mood disorder.

Antidepressive Agents↗
PubMed1987

Prediction of outcome in depressive illness by the Newcastle Diagnosis Scale. Its relationship with the unipolar/bipolar and DSM-III systems.

The Newcastle scores of a group of 64 and subsample of 52 severely depressed inpatients were not normally distributed. Evidence for discontinuity in these distributions was adduced from the contrast in outcome between the endogenous and neurotic patients thus defined, the endogenous consistently doing better than the neurotic group. The unipolar/bipolar system failed to predict different results for endogenous and neurotic patients unless unipolar was subdivided into endogenous and neurotic subgroups. The DSM-III criteria for major depression and melancholia failed to identify subgroups of differing prognoses.

Depressive Disorder↗