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Biomedical subjects

P K Bridges

Publications and source records attributed to P K Bridges.

At least 19 recordsLinked to original sources

Effect of psychotropic drugs on excitatory amino acids in patients undergoing psychosurgery for depression.

Samples of ventricular CSF were taken from 52 consecutive patients admitted for psychosurgery for intractable depression. Concentrations of asparagine, aspartate, glutamine, glutamic acid, and serine were determined. Glutamate and aspartate concentrations, implicated in excitotoxic brain damage, were not affected by various types of psychotropic drug treatment. Serine, a modulator of glutamate responses, was significantly elevated in samples from subjects receiving antidepressants. These subjects responded poorly to the operation. Psychotropic drugs are unlikely to be neurotoxic. Nevertheless, antidepressants may influence excitatory neurotransmission.

Adult

Tyramine conjugation test distinguishes unipolar from bipolar depressed patients and controls.

Tyramine sulphate conjugation following oral tyramine administration (the tyramine test) has previously been found to distinguish endogenous unipolar from neurotic depression and appears to be a trait marker. In this study, the test was used in 24 unipolar depressed patients compared with similar sized matched groups of bipolar depressed patients and normal controls. Most of the depressed patients in each group showed endogenous features. The study found that whereas tyramine sulphate conjugation was significantly impaired in unipolar patients, values in the bipolars were similar to those of controls. These results provide further evidence for the biological difference between unipolar and bipolar depression.

Administration, Oral

Neuropsychological correlates of stereotactic subcaudate tractotomy. A prospective study.

Stereotactic subcaudate tractotomy is a surgical procedure performed for the alleviation of intractable affective disorders. It involves the destruction of bifrontal pathways located beneath and in front of the head of the caudate nucleus. We report the first prospective study of the neuropsychological correlates of this operation in 23 patients. Tests of general intelligence, speed and attention, as well as a wide range of focal cognitive tests, including tasks which have been reported in the literature to be sensitive to frontal lobe dysfunction, were administered 1 wk before the operation, 2 wks after the operation and approximately 6 mths after the operation. The results indicated that this operation does not cause any significant, long-term adverse, cognitive deficits. In the post-operative assessment, however, patients show a significant deterioration in their performance on recognition memory tests and a large proportion of them present with a marked tendency to confabulate on recall tasks. In addition, their performance on some of the tasks which are considered to be sensitive to frontal lobe dysfunction is found to be significantly impaired. These deficits are interpreted to reflect frontal lobe dysfunction due to widespread post-operative oedema rather than damage to the subcaudate pathways. The potential for research on these transient effects of the operation for the advancement of our understanding of frontal lobe functions is discussed.

Adult

Altered magnetic resonance white-matter T1 values in patients with affective disorder.

The MRI T1 proton relaxation values were assessed in 14 patients with bipolar affective disorder and 10 with a unipolar disorder and a matched normal control group. The T1 values in the frontal white matter of patients significantly exceeded those of the controls. This difference was accounted for by an increase in T1 values in the frontal white matter of unipolar patients: the values for bipolar patients alone did not differ from those for controls. These preliminary findings support a hypothesis of frontal lobe dysfunction mediating pathological changes in mood.

Adult

Brain amino acid concentrations and Ca2+-dependent release in intractable depression assessed antemortem.

The concentrations of 3 putative neurotransmitters (glutamate, aspartate and gamma-aminobutyrate), 4 related amino acids and 5 non-transmitter-related amino acids have been measured in neurosurgical samples (frontal cortex) from patients with intractable depression and controls. In addition, the glutamate receptor agonist 2-amino-4-sulpho-butanoic acid (homocysteic acid) has been identified in human brain and measured in these samples. There were no changes in the concentrations of amino acids in depressed patients compared to control with the exception of aspartic and homocysteic acids which were elevated in a sub-group of patients with depression compared to control. The Ca2+-dependent release (K+-stimulated) of putative neurotransmitters has been demonstrated for the first time from brain tissue of depressed patients. Glutamate release was unaltered from the control value. Aspartate values showed unexplained variability but it's release and that of gamma-aminobutyrate were elevated in some depressed subjects. These results do not support the hypothesis of reduced amino acid function in depressive illness.

Aged

Relationship between plasma adrenocorticotrophic hormone and cortisol concentrations in chronic alcoholic patients with depression.

In 20 hospitalized male chronic alcoholic patients, plasma adrenocorticotrophic hormone (ACTH) levels were estimated by radioimmunoassay and cortisol levels by the competitive protein binding (CPB) method with radioactive selenium-75 on admission and during abstinence along with rating of the degree of depression immediately after the acute phase of the ethanol withdrawal syndrome was over. Duration of drinking ranged from 5 to 25 years and average daily ethanol intake was between 100 and 150 g. Plasma ACTH levels were found to be raised in drinking chronic alcoholics. There was a positive and statistically significant correlation between depression ratings and plasma ACTH concentrations (r = + 0.379; P less than 0.05). In chronic alcoholism the negative feedback mechanism seems to be disturbed between plasma ACTH and cortisol levels which are not normalised after 1 week of total abstinence. Chronic ethanol ingestion might have a direct stimulatory effect on the adrenal cortex leading to dysregulation of the hypothalamo-pituitary-adrenocortical axis.

Adrenocorticotropic Hormone

Mianserin and trazodone for cardiac patients with depression.

In a placebo controlled double-blind cross-over study, the cardiovascular and antidepressant effects of three weeks' treatment with mianserin (30-80 mg daily) and trazodone (150-400 mg daily) were studied in depressed patients who had co-existant cardiac disease. In 14 of the 16 patients, no haemodynamic deterioration occurred with either drug. Two patients withdrew from the study. One with coronary artery disease, whose concomitant medication included a calcium-antagonist and a beta-adrenoceptor blocker and who developed severe postural hypotension after his first dose of trazodone while the other had an increased frequency of transient cerebral ischaemic attacks with both mianserin and trazodone, but not with placebo. Mianserin and trazodone are comparable for both antidepressant efficacy and paucity of cardiovascular effects. Although unwanted effects were generally mild, the incidence of dizziness was greater in those patients receiving trazodone. Caution is advised, however, when prescribing either drug to patients with transient cerebral ischaemic attacks or those with coronary artery disease receiving medication.

Adult

Amino acid levels in depression: a preliminary investigation.

Plasma, cerebrospinal fluid and brain tissue amino acid levels were measured in 14 patients with affective illness and generally confirm previous findings. There was no correlation between these values and age, sex, family history and levels of anxiety. GABA levels measured in cortex tissue were negatively correlated with depressive mood (P less than 0.05), supporting a possible involvement of GABA in depressive illness.

Adult

The dexamethasone suppression test in chronic alcoholics with and without depression and its relationship to their hepatic status.

Fifty consecutively admitted male alcoholics (mean age = 42.8 +/- 8.5 years) were selected. This study shows objectively that 31/50 chronic alcoholics (62%) were found to be severely depressed (Hamilton Depression Rating Scale (HRS) greater than 22); 12/50 (24%) moderately depressed (HRS = 16-22); and 7/50 (14%) were not depressed (HRS less than 15). According to dexamethasone suppression test (DST) results, 8 out of 50 patients showed escape from suppression with 2 mg dexamethasone while 42/50 showed normal suppression. Depression in alcoholics may be of neurotic type or it may be ethanol-induced reactive depression. Raised cortisol levels and abnormal DST response showed a definite tendency towards normalisation after total abstinence accompanied by clinical improvement of depressive symptomatology. The DST showed improvement on improvement of mood and sleep in these patients during total abstinence. An abnormal DST response in chronic alcoholics seems to be state-related and not trait-dependent; it seems to be a non-specific test for depression in alcoholics. Hepatic status was affected equally in both suppressors and non-suppressors of DST. It is therefore suggested that abnormal DST in alcoholics may be due to the abnormality of the hypothalamo-pituitary-adrenocortical (HPA) axis and not due to abnormal hepatic function or histological status.

Adult

Resistant bipolar affective disorder treated by stereotactic subcaudate tractotomy.

The results of stereotactic subcaudate tractotomy in nine patients with resistant bipolar affective disorder are presented in the form of a single case study with a summary of the other eight cases. Follow-up studies at 2-4 years showed substantial improvement in five patients and amelioration of symptoms in a further four patients, with a tendency for a greater improvement in the manic than in the depressive episodes. These preliminary results suggest that there is a place for this operation in the management of severe bipolar affective disorders which are not responding to any other treatment, although decisive recovery occurs less often than with unipolar depression.

Bipolar Disorder

Psychosurgery in Britain now.

Between 1979 and 1986 the number of psychosurgical operations carried out in Britain fell from 70 to 15 procedures annually. There are a number of possible reasons for this change of which increased experience with new regimes of psychotropic medication is perhaps the most important. The new Mental Health Act (1983) which brought psychosurgery under the direct jurisdiction of the law was followed by a sudden reduction in the number of patients treated but referals are now increasing. In current psychiatric practice, classification relies largely on description of syndromes, each characterised by a set of core symptoms. Schizophrenia and affective psychoses (endogenous depression, mania and obsessional illness of late onset) are characterised by disturbances of mood, thinking and perception often so profound as to impair the patient's contact with reality. In contrast, neuroses produce symptoms which are quantitatively, rather than qualitatively different from normal experience and psychosurgery has no place in their treatment. Following the introduction of phenothiazines in the early 1950's schizophrenia ceased to be an indication for psychosurgery. For a small group of severely disabled and distressed people suffering from endogenous depressive and obsessional illnesses, when other treatments have failed or ceased to be effective, psychosurgery remains an appropriate treatment. Just over half the patients treated at the Geoffrey Knight Unit are relieved to the extent that they are either free of symptoms or such symptoms that remain do not significantly impair social function. Following operation recovery is slow and progressive and a programme of rehabilitation is usually necessary. Personality which is often severely damaged by the effects of long illness returns towards normal. Neuropsychiatric evaluation has consistently failed to demonstrate adverse cognitive effects. Evaluation and selection of patients for operation should be done by a psychiatrist and neurosurgeon working in partnership. Stereotactic techniques have made it possible to produce precisely located lesions of consistent size, virtually eliminating side effects and reducing the epileptic risk to between two and three percent. The Mental Health Act, contrary to early expectations, has allowed that psychosurgery retains a place in the treatment of a small highly selected group of patients.

Humans

The stalemate position.

The psychosurgical operation of stereotactic subcaudate tractotomy can be a highly effective treatment for chronic and intractable affective disorders. We have lately given increasing attention to cases where the depressed mood appears to lift although there is little improvement in social function. In these cases there has been a failure of rehabilitation and the complexities of this process post-operatively are discussed. In addition, relatives report in some 10% of cases "personality changes" after the operation which are not perceived in this way by an independent medical assessor and these observations seem to depend upon relatives mis-interpreting the resumption of pre-morbid personality function after long illnesses as undesirable side-effects. Case histories illustrating the problems are described. Treatment and rehabilitation strategies are outlined.

Depressive Disorder