Apomorphine, haloperidol and the average evoked potentials in normal human volunteers.
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Biomedical subjects
Publications and source records attributed to R M Post.
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The hypotensive drug clonidine, which stimulates central alpha-adrenergic receptors, was administered to psychiatric patients in a preliminary double-blind study. Two schizophrenic patients became more agitated and aggressive during the trial. The drug showed some antidepressant effects in three of five depressed patients. Clonidine withdrawal appeared to potentiate symptoms in a manic patient. Drug treatment reduced blood pressure and rapid eye movement sleep. Interpretation of behavioral effects of clonidine is limited by uncertainty about the balance of its pre- and postsynaptic effects.
In addition to familiar themes of depressive thought content, the authors describe changes in the form of language and thinking in depression which reflect serious disturbances in ego functioning. These disturbances are associated with an inability to express and experience a wide range of affects. The authors suggest that paradoxically, this painful state of affective inaccessibility, rather than an excess of depressive feeling, may be a major component of severe and/or prolonged depression. The evolution of this phase of affective blockade may have important theoretical and clinical treatment implications.
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The effects of a single night of total sleep deprivation were observed in 16 primary depressed patients. Responders to treatment were rated as significantly more depressed and revealed a more "depressed" EEG sleep pattern prior to sleep deprivation than did nonresponders. Following sleep deprivation, patients who improved experienced a rebound in REM sleep during the second night of recovery sleep.
DDAVP (1-desamino-8-d-arginine vasopressin), a synthetic analogue of vasopressin with prolonged half-life and high antidiuretic and low pressor activity, was given in a double-blind placebo-controlled trial to four patients with major affective illness. Three of four patients showed highly significant and consistent improvements in tests designed to measure the formation, encoding, and organisation of long-term trace events in memory. Two patients also showed a significant but less consistent amelioration of other depressive symptoms during DDAVP treatment. These findings implicate central vasopressin function in the processing of information and possibly other aspects of affective illness.
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The effect of long-term lithium carbonate treatment on parameters of immediate, short-, and long-term memory was examined in a group of bipolar affectively ill patients. The lithium treatment group recalled significantly fewer words across trials on a verbal learning task than a group of bipolar affectively ill patients receiving no medication. The ability to consistently recall material for which prior learning had been demonstrated was also decreased and accounted for most of the variance in total number of words recalled. Possible mechanisms of effect are discussed.
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1. Current research strategies in the pharmacotherapy of the affective disorders are reviewed in an attempt to highlight major trends and areas of particular promise. 2. There has been some progress toward the identification of biologically defined subgroups by assessing amine metabolites in urine or cerebrospinal fluid which may lead to a more rational choice of therapies for depressed patients. 3. The use of drugs with receptor agonist properties may help define biological substrates altered in affective illness and lead to new approaches to treatment, such as utilization of low doses of receptor agonists which may preferentially stimulate presynaptic receptors. 4. Study of time-dependent and adaptive changes in receptor sensitivity may also add an important perspective in conceptualizing the cyclic process in manic-depressive illness and its treatment.
Researchers have found that state-dependent learning is associated with the administration of a wide variety of drugs. Recent data suggest that similar phenomena may occur secondary to endogenous changes in neuroregulatory substances. The authors point out that awareness of such changes in cognitive processing strategies and abilities should help to further our understanding of the phenomenology of psychiatric states and should generate psychotherapeutic techniques designed to maximize the transfer of information across psychiatric states.
Small but statistically significant increases in serum total calcium and serum inorganic phosphorus concided with repeated onsets of psychotic agitation or mania in nine psychotic in-patients experiencing rapid cycles of illness. These increases were not accompanied by changes in magnesium or other constituents, which might suggest non-specific haemoconcentration. Similar increases in calcium or phosphorus were not present in patients without the same cycles of psychotic illness. The observed increases could neither be simulated nor altered by stress or activity, and it remains unclear whether they might be accounted for by dietary changes, sleep disruption, circadian phase shifts or by endocrine alterations.
The authors attempt to integrate several psychoanalytical and more recent neurobiological concepts regarding the development of the organism and emergence of psychopathology. They highlight the rough temporal correspondence of neurodevelopmental myelination cycles with stages of psychosocial development. They discuss concepts of critical periods and unique times of vulnerability to psychosocial insult and recurrence of critical stresses, gleaned from a multidisciplinary point of view, in relation to the occurrence of psychic aberrations. They suggest that it may be fruitful to explore further psychological constructs such as fixation and regression, as well as unconscious mental processes, in relation to their biochemical, physiological, and anatomical representations in the brain.
Gamma-Aminobutyric acid (GABA) has been implicated in the neurochemistry of epilepsy. Lumbar cerebrospinal fluid (CSF) GABA concentrations determined using an ion-exchange fluorometric assay reflect brain GABA content. The mean lumbar CSF GABA concentration among 21 medicated patients with intractable seizures was significantly lower (p less than 0.001) than that of 20 unmedicated normal volunteers. Patients with generalized tonic-clonic (grand mal) and complex partial (psychomotor) seizures had significantly lower (p less than 0.05) CSF GABA concentrations than those with simple partial (focal sensory/motor) seizures. Although lumbar CSF GABA levels in our seizure patients did not significantly correlate with serum concentrations of phenytoin, phenobarbital, or primidone, additional study of medication-free epileptic patients may be required to evaluate the possibility of anticonvulsant-drug-induced CSF GABA alterations.
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In a study of electrolytes in lumbar cerebrospinal fluid (csf) from psychiatric patients, the authors found a positive correlation between calcium concentration and symptom severity in hospitalized depressed patients. CSF calcium levels tended to decrease as patients improved. In four rapidly cycling patients, CSF calcium was higher during depression than during mania. Mean CSF calcium for the depressed patients as a group was not significantly different from neurological controls or other psychiatric patients. Symptom remission from acute psychosis in schizophrenic patients was accompanied by a significant increase in CSF calcium concentration. These findings are discussed in relationship to calcium-induced alterations in neuronal and physiological excitability.