Lithium augmentation in antidepressant-resistant patients.
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Antidepressive Agents↗
Biomedical subjects
G M Goodwin
Publications and source records attributed to G M Goodwin.
The Edinburgh cohort of HIV-positive drug users: pattern of cognitive impairment in relation to progression of disease.
To examine the neuropsychiatric effects of infection with HIV, 220 drug users (27 HIV negative, 193 HIV positive) completed tests evaluating premorbid intelligence, memory, non-verbal performance, information processing speed, and mood. When these measures were compared cross-sectionally by the severity of HIV illness, symptomatic patients (in CDC stage IV) were impaired on Trails B, two-choice decision time, delayed recall of the Wechsler Logical Memory Test and most components of the Auditory Verbal Learning Test. These findings imply reduced capacity for concentration, speed of thought and memory. When 101 patients were retested a mean of 16 months after their initial assessment, performance on Trails A and B, Block Design and delayed recall of the Wechsler Logical Memory Test deteriorated more for patients at, or progressing within, CDC stage IV, than performance of patients at stage III. The results broadly correspond to the cross-sectional findings. However, there was a decline in all tests of memory function for the sample independent of clinical staging. This may be evidence of brain involvement before the appearance of other symptoms. Self-rated measures of mood did not change cross-sectionally, progressively, or interactively with time and stage of HIV illness, and cannot account for the changes in cognitive function observed. Change in drug use, similarly, does not account for the cognitive findings. Four (5%) of the retested subjects developed AIDS dementia complex, but most of the performance and memory impairments seen were subclinical despite the destructive neuropathology presumed to underlie intellectual decline in patients with HIV infection.(ABSTRACT TRUNCATED AT 250 WORDS)
AIDS Dementia Complex↗
Unilateral voluntary hand movement and regional cerebral uptake of technetium-99m-exametazime in human control subjects.
The study examines the sensitivity of a region of interest approach to detect functional changes in brain metabolism with SPECT and split-dose 99mTc-exametazime by replicating a simple hand movement experiment previously carried out with PET. Regional uptake of 99mTc-exametazime was determined in 12 healthy controls before and during a thumb-digit opposition task. Analysis of regional uptake was carried out blind to the hand used in the opposition task and showed a significant unilateral activation effect in a pericentral region of interest with opposite results in left- and right-handed activation. The maximum contralateral increase in tracer uptake was 16% before and 26% after correction for back diffusion. This is in good agreement with previous results employing absolute cerebral blood flow determination with PET and confirms the usefulness of 99mTc-exametazime SPECT for the examination of functional metabolic changes.
Aged↗
Regional cerebral blood flow and cognitive function in patients with chronic liver disease.
Subtle impairments of cognitive function may be an important cause of occupational and psychosocial morbidity in patients with chronic liver disease. Correlation of structural brain abnormalities with cognitive deficits has yielded inconsistent results. 10 patients with cirrhotic liver disease were compared with 10 age, education, and intelligence matched control subjects. Neuropsychological assessment revealed significant overall cognitive impairments in cirrhotic patients compared with controls (p = 0.02). Regional cerebral blood flow was measured by single photon emission computed tomography (SPET or SPECT) and showed increased uptake of radiotracer in the right and left posterior parts of the basal ganglia and right occipital lobe, together with reduced uptake in the right anterior cingulate region. The degree of cognitive impairment was directly correlated with functional abnormalities in the basal ganglia and limbic cortex (p less than 0.05). Our results suggest that impaired cognitive status may be associated with abnormalities of regional brain function in patients with chronic liver disease. Since these deficits are clinically inapparent, our findings have important implications for identification and management of patients with chronic liver disease.
Analysis of Variance↗
Intravenous L-tryptophan and regional cerebral blood flow.
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Adult↗
The effects of lithium discontinuation and the non-effect of oral inositol upon thyroid hormones and cortisol in patients with bipolar affective disorder.
Thyroid and adrenal function was assessed in euthymic bipolar patients, stable on prophylactic lithium for at least 1 year, before and after lithium discontinuation in a randomised double-blind placebo-controlled trial. All hormonal measurements were within the reference range, but a significant increase (P less than 0.001) in plasma thyroxine (T4) levels and a decrease (P less than 0.01) in TSH levels were observed 1 month after lithium withdrawal; cortisol concentrations showed a non-significant decrease in the same period. No relationship could be demonstrated between the magnitude of the change in hormone levels and the probability of relapse of manic symptoms. In the second part of this study, inositol was added for 11 days to the diets of bipolar patients being treated with prophylactic lithium and normal controls. No modification was shown in T4 and TSH in either group before or after inositol administration. Inositol did not alleviate other side-effects such as tremor and thirst in the patient group. This result suggests that short-term dietary inositol is not equivalent to lithium withdrawal and is of no value in reducing hormonal and other adverse effects of lithium prophylaxis.
Adult↗
Psychological, hormonal and biochemical changes following carbohydrate bingeing: a placebo controlled study in bulimia nervosa and matched controls.
The responses of thirteen patients with bulimia nervosa and sixteen controls matched for age and weight are described following the ingestion of a carbohydrate and a calorie-free placebo mixture in simulated binges. Psychological, hormonal and biochemical parameters were measured before and at 15 minute intervals for two hours after the simulated binge. At baseline, the bulimics were clearly more symptomatic than the controls. The control population showed a specific satiating effect of carbohydrate upon hunger ratings. Bulimic patients responded differently showing a blunting of the normal sensation of hunger and an enhanced rating for nausea. Prolactin, growth hormone (GH) and cortisol failed to show a carbohydrate-mediated stimulation in either population. The bulimic patients showed a different pattern of GH release, but this was independent of the challenge condition. Large neutral amino acid (LNAA) levels fell following carbohydrate ingestion, but produced an increase of up to 20% in the tryptophan: LNAA ratio in both bulimic patients and the control group. Thus, while this increase in tryptophan availability failed to provoke hormone release, the time course of the carbohydrate specific effect on the sensations of hunger and nausea is compatible with a mechanism based on increased tryptophan availability. The confusion of satiety with nausea may provide a useful focus for the future treatment of patients with bulimia nervosa.
Adult↗
The pattern of cerebral activity underlying verbal fluency shown by split-dose single photon emission tomography (SPET or SPECT) in normal volunteers.
Uptake of 99mTc-Exametazime, a marker of relative regional cerebral blood flow has been determined with Single Photon Emission Tomography (SPET or SPECT) in 20 healthy, elderly female subjects during neuropsychological challenge. Each subject was studied under basal conditions after injection of 125 MBq 99mTc-Exametazime. Without moving the head of the subject, they were scanned again after injection of 375 MBq 99mTc-Exametazime. The second injection was made in 10 subjects during a test of verbal fluency, usually regarded as a test of the integrity of function of the left frontal cortex. In the other 10 subjects the second injection was made during simple verbalization (counting). This method of splitting the normal full dose of 99mTc-Exametazime allows a novel comparison between basal and active conditions for different brain regions. Verbal fluency was associated with reduced uptake bilaterally in the region of the basal ganglia and in left temporal (peri-sylvian) cortex when compared with calcarine cortex, an unstimulated reference sensory area. By contrast, counting produced relative activation, greatest in frontal and parietal areas. Thus, a clinically relevant neuropsychological test can be characterized metabolically by a pattern of regional brain activity, whose localization cannot readily be predicted from classical studies of brain lesions. Reduction of regional uptake may suggest an important role for deactivation or inhibition of function in human cognition. The involvement of basal ganglia and temporal areas is of particular interest in relation to the investigation of functional psychiatric illness.
Aged↗
Inspection time, psychometric intelligence and clinical estimates of cognitive ability in pre-senile Alzheimer's disease and Korsakoff's psychosis.
Ten pre-senile Alzheimer's patients, 11 patients with Korsakoff's psychosis and 11 age- and pre-morbid intelligence-matched controls were given a test of Inspection Time, which estimates the efficiency of visual encoding or iconic memory. Alzheimer's patients had impaired Inspection Time while the Korsakoff group performed very similarly to the controls. Inspection Time performance correlated significantly with psychometric tests of cognitive ability and with clinical tests of cognitive ability (Mini Mental State Examination and Cambridge Mental Disorders of the Elderly Examination). The early stage of information processing measured by the Inspection Time procedure appears to be damaged by the Alzheimer's disease process, and to impose a rate-limiting effect on a wide variety of mental tests.
Alcohol Amnestic Disorder↗
Cerebral pharmacodynamics of physostigmine in Alzheimer's disease investigated using single-photon computerised tomography.
The effects of physostigmine on patterns of rCBF in patients with pre-senile Alzheimer's disease were studied using 99mTc-labelled HMPAO SPECT. Regional CBF increased in the left cortex relative to right, with the most significant effect in left frontal and higher frontal regions. Measures of regional brain function, such as SPECT, are an important complement to psychological test batteries in understanding the effects in brain of putative antidementia drugs. SPECT brain imaging could extend our understanding of the action of psychotropic drugs in other major psychiatric illnesses.
Aged↗
Lithium treatment and prophylaxis in unipolar depression: a meta-analysis.
Meta-analysis was used to establish the efficacy of lithium in acute treatment and prophylaxis of depressive illness from existing published clinical trials. Effect sizes were measured by the odds ratio using the Mantel-Haenszel method and the Pearson product-moment correlation coefficient. Some benefit from lithium, compared with other treatments, emerged from trials of acute treatment. Lithium was clearly superior to placebo in the acute treatment of bipolar depressed patients. In controlled studies of lithium prophylaxis over five months to three years, an impressive effect was found for lithium when compared with placebo. For uncontrolled studies there was a similar-sized effect, corresponding to an improvement in the rate of favourable outcome from 35% for placebo to 70% with lithium treatment. The comparison of lithium with other antidepressants in prophylaxis showed no conclusive advantage for lithium in unipolar illness. There is no reason to doubt the efficacy of lithium in the prophylaxis of unipolar depressive illness.
Antidepressive Agents↗
Lithium augmentation in antidepressant-resistant patients. A quantitative analysis.
A quantitative analysis was used to examine the efficacy of lithium augmentation in the acute treatment of depressed patients resistant to a standard trial of an antidepressant. Effect sizes were measured by the odds ratio using the Mantel-Haenszel method. Only controlled trials were included in order to minimise bias in method. A highly statistically significant effect for lithium augmentation was found, the pooled odds ratio being 0.146 and its 95% confidence interval 0.05-0.44 (i.e. the odds of remaining ill are reduced by between 56% and 95% with the use of lithium treatment). While these results support the case for lithium augmentation in treatment-resistant depression, there remains considerable uncertainty over the duration of treatment necessary to see and sustain the treatment response.
Antidepressive Agents↗
Studies on central nervous system serotonin receptors in mood disorders.
The evidence from studies of central nervous system serotonin (5-HT) receptors is reviewed and the role of these in the pathogenesis of mood disorders is discussed. Clinical evidence indicates that 5-HT function is abnormal in mood disorders. 5-HT precursors and selective inhibitors of 5-HT uptake are effective antidepressives and inhibition of 5-HT synthesis can block the action of antidepressives. Studies of 5-HT in experimental animals after chronic administration of antidepressive treatments suggest that intact 5-HT neurons are necessary for the action of these treatments. Multiple 5-HT receptor subtypes have recently been identified and the effects of chronic antidepressive treatment on some receptor subtypes function in experimental animals have been established. The increasing availability of powerful new in vivo imaging techniques like single photon emission tomography (SPET), and positron emission tomography (PET) may make possible a more direct examination of 5-HT receptor function in patients suffering from mood disorders.
Animals↗
Plasma concentrations of tryptophan and dieting.
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Amino Acids↗
Diurnal variation of plasma corticosterone in depression.
Hypersecretion of cortisol is associated with depression. Because corticosterone may show greater responsiveness than cortisol to exogenous ACTH in depression and it has behavioural effects in rodents, we determined whether depression is also associated with hypersecretion of corticosterone. Both cortisol and corticosterone were significantly elevated in depression, with greatest differences from control subjects during the afternoon and evening. The ratio of corticosterone/cortisol was constant and similar throughout the day in both depressed patients and controls. We conclude that there is no disproportionate endogenous hypersecretion of corticosterone in depression.
Adolescent↗
The efficacy of lithium in prophylaxis of unipolar depression Evidence from its discontinuation.
Forty unipolar patients satisfying DSM-III criteria for major depression who discontinued lithium therapy were retrospectively compared with 105 similar patients who continued the drug and served as a control group. The time to readmission from starting lithium was compared while both groups were still on lithium, and after discontinuation in one group and further continuation in the control group. The progressive increase in the probability of recurrence over two years was the greatest after discontinuation of lithium. For the patients who eventually discontinued lithium, the cumulative probability of recurrence in two years was 0.08 on lithium and 0.58 after stopping it. The probability of recurrence was unchanged over the duration of the study for patients who continued to take lithium. There was no evidence of a lithium withdrawal syndrome within three months of stopping the drug. The results support the view that the everyday clinical use of lithium as prophylaxis is beneficial in unipolar depression.
Bipolar Disorder↗
The Edinburgh cohort of HIV-positive drug users: auditory event-related potentials show progressive slowing in patients with Centers for Disease Control stage IV disease.
A two-tone auditory event-related potential (AEP) task was used to examine brain function in 206 HIV-positive individuals (infected by intravenous drug use) approximately 6-7 years after initial infection. Multiple regression analysis of AEP latency and amplitude components showed only small effects of past medical and psychiatric history, current symptoms and drug use on electrophysiological responses. HIV-positive patients had longer latency and reduced amplitude of the P300 (P3) component of the AEP compared with a normal control group, but were electrophysiologically similar to a matched control group of HIV-seronegative drug users. However, a lower P3 amplitude was seen in patients in Centers for Disease Control stage IV. One-year follow-up of 103 patients (50%) found significant lengthening of P3 latency in patients with stage IV disease but not in those with stage II or stage III disease. The results suggest that brain involvement in HIV infection can be detected electrophysiologically after the clinical diagnosis of stage IV disease.
Adult↗
The Edinburgh cohort of HIV-positive drug users: current intellectual function is impaired, but not due to early AIDS dementia complex.
Eighty people, all infected by HIV-contaminated drug injection equipment between 1983 and 1984, completed the National Adult Reading Test (NART) and selected revised Wechsler Adult Intelligence Scale (WAIS-R) subtests. Demographic variables (age, sex, years of education, and social class) were recorded as additional indices of premorbid functioning. Cross-sectional comparison of NART and WAIS-R scores showed that cognitive function was not more impaired with increasing severity of HIV illness, as defined by clinical staging. Nor were HIV-positive patients more impaired than a control group of seronegative drug users. Mean NART scores did not differ significantly from that predicted by a regression model, indicating that the NART can be reliably used to estimate premorbid intelligence for this population. However, current performance on WAIS-R subtests was below that expected from population models of cognitive function that combine measures of premorbid IQ and demographic factors, providing evidence of impaired intellectual function. Currently observed cognitive deficits are probably more due to drug use than to the insidious onset of AIDS dementia complex.
AIDS Dementia Complex↗