A three-component-system hypothesis of psychosis. Impairment of binocular depth inversion as an indicator of a functional dysequilibrium.
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Attention↗
Biomedical subjects
H M Emrich
Publications and source records attributed to H M Emrich.
Suppression of preoptic GABA release caused by push-pull-perfusion with sodium valproate.
The in vivo-effects of various concentrations of the anticonvulsant drug sodium valproate--within and above the therapeutic range for humans (40-100 micrograms/ml)--on the release of gamma-aminobutyric acid (GABA) were studied perfusing the preoptic area of unanaesthetized, freely moving ovarectomized rats through push-pull-cannulae at a flow rate of 20 microliters/min with a fraction period of 5 and 15 min, respectively. Local treatment with 40, 80, 100, and 200 micrograms valproate/ml perfusion medium induced a highly significant decrease in preoptic GABA release. After return to valproate-free medium this effect was reversible. A rapid onset and termination of the valproate effect within 5 min could be observed. Going higher with valproate concentrations the suppressive effect became less and at supratherapeutic valproate levels of 1600 micrograms/ml CSF an increase in GABA release could be observed in 4 out of 8 animals. This does response relationship points to a biphasic effect of valproate on the available amount of GABA in the synaptic cleft, which may be produced by at least two different dose-dependent mechanisms of action. The present results indicate that the action of therapeutic concentrations of valproate involves an alteration of GABAergic transmission different from increasing synaptic GABA release. Nevertheless, the data suggest that valproate action, at least at the level of the preoptic area, involves an enhancement of GABAergic transmission causing--via a negative feedback mechanism--the observed suppression of GABA release into the synaptic cleft.
Animals↗
Current and historical concepts of opiate treatment in psychiatric disorders.
In recent years psychiatric research has rediscovered the theoretical and clinical importance of opiates, especially for the understanding of depressive disorders. However, opiate treatment is not a new therapeutic concept in psychiatry. The use of opium for "melancholia" and "mania" may be traced to ancient classical medicine. After Paracelsus and Sydenham, the psychiatry of the German Romantic Era widely discussed therapeutic opium use with the Engelken family going on to develop a structured opium treatment of depression in the first half of the nineteenth century. Although the underlying scientific problems of psychiatric opium therapy were never solved, it gained an outstanding position as a practical treatment for over 100 years.
Depressive Disorder↗
The seeking and liking potentials of alprazolam.
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Adult↗
[Development of a systems theory of productive psychoses].
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Hallucinations↗
Diurnal variation of mood and the cortisol rhythm in depression and normal states of mind.
A large scale chronobiological investigation was undertaken in 20 drug-free psychiatric inpatients displaying RDC major depression (endogenous subtype) in comparison to 10 healthy control subjects and 10 of the patients after clinical recovery. A series of measurements was taken 6 times a day and, in 8 of a total of 14 variables, also once a night over a period of 10 to 14 days. The following variables were assessed: mood (three different scales), performance (two tests), motor activity (three measures), salivary flow, urinary excretion of water, sodium, potassium, and free cortisol (UFC), and rectal temperature. A phase chart of the acrophases of the 8 variables with measurements taken during day and night revealed two clusters in the depressives and three in the non-depressed subjects. In the depressives, the acrophases of the mood scales clustered around the time of awakening in the morning, together with the acrophase of UFC, whereas all other acrophases clustered in the afternoon. In the non-depressed subjects, however, the mood scales reached their circadian maxima in the middle of the night around the time when sleep was interrupted to take measurements. All other acrophases corresponded roughly with those found in the depressives. The coincidence of the time course of depressed mood and cortisol excretion in the patients was interpreted as reflecting a temporal relationship between diurnal mood swings in depression and the cortisol rhythm. This interpretation was supported by the significant correlation between the acrophases of the two respective rhythms in patients showing a significant diurnal variation in mood. The mood curves of non-depressed subjects seemed unrelated to the cortisol rhythm. Probably, they mirror diurnal fluctuations of vigilance rather than fluctuations of mood. According to the literature, this rhythm is temporally related to the rhythm of melatonin secretion.
Adult↗
Regional cerebral glucose metabolism in anorexia nervosa measured by positron emission tomography.
Regional cerebral glucose metabolism was measured in five female anorectic patients, during the anorectic state and after weight gain, using the fluorodeoxyglucose method and positron emission tomography. In addition, these results were compared with those of 15 young male normals. During the anorectic state, significant caudate hypermetabolism was found bilaterally, unlike the finding in repeat measurements or in male normals. In some other brain structures (temporal cortex, lentiform nucleus, thalamus, and brainstem), significant hypermetabolism was also found during the anorectic state, but these results were not concordant for both sides and in both comparisons. There was no difference between patients after improvement and young male normals.
Adolescent↗
Carbamazepine as an adjunct of antipsychotic therapy.
The effect of low-dose haloperidol combined with the anticonvulsant carbamazepine was investigated in a 5-week placebo-controlled, double-blind study in acute schizophrenic patients. Weekly ratings showed a clinically pronounced and statistically significant improvement in both the carbamazepine and placebo groups. However, the patients on carbamazepine needed less neuroleptic and anticholinergic medication and experienced fewer side effects compared to the patients on placebo. Moreover, patients in the carbamazepine group showed a clear deterioration after discontinuation of carbamazepine (but maintenance of neuroleptic medication), while the placebo group did not change after discontinuation of placebo. Concomitant treatment with carbamazepine in psychotic patients may help to reduce neuroleptic dosages and unwanted side effects.
Adjuvants, Pharmaceutic↗
Characterization of benzodiazepine withdrawal in high- and low-dose dependent psychiatric inpatients.
Fourteen patients with high- (n = 7) and low-dose (n = 7) benzodiazepine (BDZ) dependency presented predominantly with anxious and depressive neurotic symptoms which caused long-term BDZ medication. Their BDZ dependency was characterized by giving preference to the abuse of benzodiazepines with long elimination half-life. Significant enlargement of CSF spaces was only found in high-dose dependent patients. Withdrawal after long-term BDZ medication revealed no differences between high- and low-dose BDZ dependency with respect to onset of withdrawal reaction and the correlation between onset of withdrawal and peak fall of BDZ serum level. The peak of withdrawal was reached 3-4 days later in high-dose BDZ dependent patients compared with those with a low-dose dependency. The peak withdrawal in high-dose dependent patients appeared when the serum BDZ metabolite nordiazepam dropped significantly. No such concomitant appearance of peak withdrawal and drop of serum nordiazepam level could be found in low-dose dependent patients. Specificity and intensity of BDZ withdrawal symptoms were the same for those dependent upon high doses of BDZs and those dependent upon low doses, but a protracted withdrawal was only observed in low-dose BDZ-dependent patients. During the withdrawal period psychopathometric measurements consistently revealed parallel changes in the scores for physical withdrawal symptoms, anxiety and depression. It is not clear whether anxiety and depression are "typical" BDZ withdrawal reactions or represent a "reactivated" state of the psychopathological disturbance which lead to the BDZ dependency. Possible implications for the therapeutical management of BDZ-dependent patients are discussed.
Adult↗
Serotonin reuptake inhibition vs. norepinephrine reuptake inhibition: a double-blind differential-therapeutic study with fluvoxamine and oxaprotiline in endogenous and neurotic depressives.
The antidepressive properties of the specific serotonin reuptake inhibitor fluvoxamine and the specific norepinephrine reuptake inhibitor oxaprotiline were investigated in a sequential design with the aim of evaluating the hypothesis that two distinct biochemical subtypes of depression exist. Responders were treated for 7 weeks with the compound to which they had responded. After 1 placebo week, the nonresponders were switched to the alternative compound. An evaluation of the data obtained during the 3-week treatment periods from 24 patients (37 trials) with major depression revealed a highly significant reduction of Hamilton Scores with both compounds, oxaprotiline and fluvoxamine. If the patients with major depression are subdivided into two groups, endogenous depressives and neurotic depressives, there is no significant difference between the therapeutic improvements (both compounds) achieved in the two groups. The data shows that only about 20% of the nonresponders on one compound responded to the alternative drug, whereas 90% of responders (within 3 weeks) were still responders after 7 weeks. The data are at variance with the concept of two distinct biochemical subtypes of depression (serotonergic vs. norepinephrinergic). Dexamethasone suppression tests, performed in 23 patients, gave no prognostic hint as to whether the patients reacted well to drug therapy or not.
Adult↗
Antipsychotic effect of buprenorphine in schizophrenia.
The antipsychotic potency of the partial opiate agonist buprenorphine was evaluated in 10 neuroleptic-free schizophrenic patients suffering from frequent hallucinations, delusions, and severe formal thought disorders. Buprenorphine had a pronounced antipsychotic effect, which lasted about 4 hours, in patients with schizophreniform disorders (N = 4) and paranoid schizophrenia (N = 3).
Adult↗
Psychotomimesis mediated by kappa opiate receptors.
The kappa opioid agonists are analgesics that seem to be free of undesired morphine-like effects. Their dysphoric actions observed with the kappa agonist cyclazocine are thought to be mediated by an action at sigma-phencyclidine receptors. The benzomorphan kappa agonist MR 2033 is inactive at sigma-phencyclidine receptors. In male subjects, the opiate-active (-)-isomer, but not the (+)-isomer, elicited dose-dependent dysphoric and psychotomimetic effects that were antagonized by naloxone. Thus, kappa opiate receptors seem to mediate psychotomimetic effects. In view of the euphorigenic properties of mu agonists, our results imply the existence of opposed opioid systems affecting emotional and perceptual experiences.
Adult↗
Use of calcium antagonists in mania.
The organic calcium antagonist verapamil in doses of 320-480 mg/day reduced manic symptomatology in seven of eight patients manifesting a manic or schizomanic syndrome in a placebo-controlled, double-blind study. The delayed onset of antimanic effects parallels the action of lithium in acute mania. Common pharmacological profiles of lithium, certain anticonvulsants, and neuroleptics with regard to calcium dependent processes are discussed.
Bipolar Disorder↗
Dopamine and the action of opiates: a reevaluation of the dopamine hypothesis of schizophrenia. With special consideration of the role of endogenous opioids in the pathogenesis of schizophrenia.
It is suggested that the antipsychotic efficacy of opioids in patients suffering from schizophrenia may result from an interaction of opioids with the dopaminergic system. The modulatory effect of opioids on dopaminergic functions has already been demonstrated in basic experiments: Anatomical and biochemical data reveal an interaction between opioid receptors and dopamine (DA) actions on dopaminergic nerve terminals, cell bodies, and afferent nerve endings. Endogenous enkephalin levels correlate well with the endogenous dopamine content in various brain areas. Systemic or iontophoretic administration of morphine alters the spontaneous activity of ventral tegmental dopaminergic neurons. Morphine and enkephalin effectively enhance pituitary prolactin release, whereas dopamine inhibits it. Opioid agonists effectively alter DA release, DA reuptake, and DA metabolism in the striatum and substantia nigra. In reverse, chronic neuroleptic treatment enhances the synthesis and release of pituitary beta-endorphin. Opioids affect contralateral rotation elicited by dopamine agonists in animals with unilateral lesions of the nigrostriatal pathway. Phencyclidine, a psychotropic drug that shares certain pharmacological characteristics with the putative sigma-opioid receptor ligand SKF 10,047, indirectly mimics the effects of dopamine agonists on prolactin release, release of acetylcholine, etc. It is suggested that an imbalance of opiate-DA interaction might be involved in the pathogenesis of schizophrenia. Consequently, clinical studies on the effects of opioids on psychotic symptoms should also examine opioid influence on dopaminergic functions in these patients.
Brain↗
Circadian rhythms in endogenous depression.
A comprehensive study of circadian rhythms was carried out in 16 drug-free patients with endogenous depression, 10 of whom were reinvestigated after clinical remission, and 10 healthy controls. No free-running periods were observed in body temperature, urinary excretion of potassium and free cortisol, or any other variable. Moreover, there was little, if any, indication of phase-advance. The circadian variation of several variables was reduced during depression, e.g., motor activity, body temperature, and (less markedly) urinary potassium, but not cortisol. The circadian worsening of mood tended to occur around the time of awakening during depression, i.e., several hours later than after remission or in normal controls. In patients with circadian variation of self-rated mood, the acrophase of this variable correlated significantly with that of urinary free cortisol. This indicates an entrainment of the disease process to the circadian rhythm of cortisol secretion, probably via circadian variations of neurotransmitters in the hypothalamus. The other circadian phenomena observed in depression can adequately be explained by masking effects (negative or positive) of psychopathological symptoms (e.g., early morning awakening) on overt circadian rhythms.
Adult↗
Lithium effects on ophthalmological-electrophysiological parameters in young healthy volunteers.
The effects of lithium on the visual system in man have been tested. Ten healthy volunteers followed a 10-day lithium regimen. Lithium plasma levels in the range of 0.6-0.8 mmol/l were obtained. Clinically used ophthalmological-electrophysiological tests were performed. Most of the tests showed no significant change during the lithium treatment. The lithium regimen resulted in a strong reduction of the slow phase. Also the "Arden-ratio", measured by electrooculogram (EOG), was influenced by lithium. The "Arden-ratio" reflects the corneo-fundal potential in retinal illumination and dark adaptation and is influenced by the state of adaptation. All the demonstrated effects were fully reversible at the end of lithium administration. Possible mechanisms of the action of lithium are discussed (for example Ca2+-fluxes, c-AMP, cGMP). These lithium-induced effects on the visual system in man may give some hint of the individual responsiveness to lithium.
Adult↗
Action of the benzodiazepine antagonist Ro 15-1788 in humans after sleep withdrawal.
Subsequent to one night of sleep withdrawal the specific benzodiazepine antagonist Ro 15-1788 was infused to 5 healthy volunteers using a double-blind placebo-controlled cross-over design. Using several standardized psychological tests (viso-motor tracking task, complex choice reaction time, trail making test, visual attention and concentration), no performance-improving effects of Ro 15-1788 could be demonstrated. The results are discussed regarding the possible existence of endogenous benzodiazepine ligands.
Adult↗
The effect of neuroleptic treatment and of high dosage diazepam therapy on beta-endorphin immunoreactivity in plasma of schizophrenic patients.
In 14 schizophrenic patients, treated with neuroleptic drugs, and in 7 patients, treated with high-dosage diazepam, beta-endorphin-like immunoreactivity in plasma has been measured by use of a highly sensitive and relatively specific radioimmunoassay. Neuroleptic treatment induced a significant increase of beta-endorphin-like immunoreactivity (beta-ELI). The pharmacological and clinical implications of this finding are discussed. High-dosage diazepam treatment induces a slight reduction of plasma beta-ELI, a finding which is attributed to antistress effect of diazepam.
Adolescent↗