Audiologic and psychological profile of Greek patients with tinnitus--preliminary findings.

Tinnitus is a common complaint among people who suffer from auditory disorders. Altering the patients' response to tinnitus and the development of coping techniques are the most important goals of the therapeutic or suppression methods. This is the first study in the Greek population to investigate the personality characteristics and coping techniques of tinnitus patients. We have studied the relation between the subjective assessment of tinnitus intensity with factors such as sex, age, duration of symptom, and degree of hearing loss. We have also studied the possible relation between the patients' personality characteristics on their attitude towards tinnitus. The participants were 80 tinnitus sufferers, men and women, between 18 and 65 years of age. The personality characteristics were assessed with the Minnesota Multiphasic Personality Inventory (MMPI). The mean MMPI scores in both men and women were within the normal range. The duration of symptoms did not prove to be an important factor for the patients' subjective assessment of the tinnitus intensity. Most patients showed "effective" coping style, were well adjusted to tinnitus, and had no significant interference in their everyday functioning. The above are discussed in the context of the influence of geographical, climatological, economic, social, and cultural factors that influence psychological functioning.

Gabaergic mechanisms and anxiety: an overview and a new neurophysiological model.

GABA is one of the principal inhibitory neurotransmitters in the mammalian brain and an ever increasing wealth of information suggests that GABAergic mechanisms have a special role in the neurophysiology of anxiety. All of the most commonly used antianxiety drugs (the benzodiazepines, the barbiturates, ethanol) selectively enhance only GABA-mediated synaptic transmission. Furthermore, the relative affinities of pharmacologically active benzodiazepines for the benzodiazepine receptor correlate well with their ability to antagonize GABA-modulin (the endogenous inhibitor of GABA receptors) in vitro, as well as with their ability to potentiate GABA-mediated electrically evoked cortical inhibition in vivo. Finally, it is of interest for the neurophysiology of anxiety that repetitive stimulation of the recurrent inhibitory GABAergic pathway in the rat hippocampus leads to a remarkable reduction of the effectiveness of GABA; this elimination of GABAergic "inhibition" is counteracted by antianxiety drugs. On the basis of the above a neurophysiological model of anxiety is proposed.

High doses of diazepam improve neuroleptic-resistant chronic schizophrenic patients.

According to the two currently most popular biological hypotheses, schizophrenic symptoms result from a hyperactivity in dopaminergic neurotransmission or from a hypoactivity in GABAergic neurotransmission. Since diazepam is known to reduce dopamine release and to potentiate GABA, the possible beneficial effects of diazepam were tested in ten hospitalized chronic schizophrenic patients who were resistant to standard neuroleptic treatment. High doses of diazepam, up to 200 mg/day initially, but smaller maintenance doses (less than 55 mg/day diazepam in eight of the ten patients) were added to the previous neuroleptic medication of these patients. The diazepam dose was adjusted daily to avoid oversedation. The effects of diazepam treatment on the mental status were assessed weekly for 12 weeks by the Brief Psychiatric Rating Scale (BPRS), the physician's Clinical Global Impressions Scale (CGI), and the Psychotic Inpatient Profile Scale (PIP). For additional documentation, videotapes of mental status interviews were obtained at baseline and during diazepam treatment. These videotapes were rated blind by an independent psychiatrist. The addition of diazepam produced a marked improvement in three, a moderate improvement in four, a mild improvement in one and no change in two of the ten patients. Four of the ten patients were so much improved that they were discharged from the hospital. No side effects were noted, except for one patient who became confused and disoriented on 160mg diazepam/day.(ABSTRACT TRUNCATED AT 250 WORDS)

Cholecystokinin appears to have antipsychotic properties.

1. According to a currently popular biological hypothesis schizophrenic symptoms are caused by a hyperactivity in dopaminergic neurotransmission. Since cholecystokinin (CCK) is a neuromodulator of dopaminergic neurotransmission, the effects of CCK (0.3 microgram/kg; given in a single dose intravenously) were studied in six chronic paranoid schizophrenic patients. 2. Following 3 baseline assessments on separate days, the effects of CCK treatment were assessed immediately after the injection, daily for one week and weekly thereafter for 5 weeks by the Brief Psychiatric Rating Scale (BPRS) and by the Schizophrenia Subscale of the Present State Examination (SS-PSE). 3. One way analysis of variance revealed statistically significant changes in all BPRS factors as well as in the nuclear syndrome and in the total score of the SS-PSE. Dunnett's tests revealed that the time at which the changes from baseline became statistically significant was as follows: anxiety-depression factor of the BPRS, immediately after the injection; anergia factor of the BPRS, by day 2; thought disturbance factor of the BPRS, immediately after; activation factor of the BPRS, immediately after; hostile-suspiciousness factor of the BPRS, by day 1; total BPRS score, immediately after; nuclear syndrome of the SS-PSE, by day 1; and total score of the SS-PSE, by day 1. 4. It is concluded that further controlled studies of the antipsychotic properties of CCK are warranted.

Diazepam in high doses is effective in schizophrenia.

1. Diazepam in high doses, up to 400 mg per day, was administered to paranoid schizophrenic patients in a double-blind placebo-controlled study. 2. The effects of treatment were assessed by the following: the Brief Psychiatric Rating Scale (BPRS); the Clinical Global Impressions Scale (CGI); the Schizophrenia Subscale of the Present State Examination (SS-PSE); the Simpson-Angus Rating Scale (SARS) for extrapyramidal symptoms; the Nurses' Observation Scale for Inpatient Evaluation (NOSIE); and a 90 item Self-Assessment Questionnaire (SCL-90). 3. Within a few hours to a few days from the onset of diazepam treatment both positive (such as auditory hallucinations and persecutory delusions) and negative (such as emotional withdrawal and blunted affect) schizophrenic symptoms were dramatically eliminated in 5 out of the 6 patients.

Benzodiazepine and gaba receptors are functionally related: further electrophysiological evidence in vivo.

1. The effects of five benzodiazepines (Ro 21-3981, flurazepam, chlordiazepoxide, medazepam and clozapine) on GABA-mediated electrically-evoked cortical inhibition were tested. 2. These five drugs were chosen because their solubility in water allows their microiontophoresis and because their relative affinities for the benzodiazepine receptor in rat brain membranes have been measured. 3. When tested with equal iontophoretic doses in 11 different neurons, the degree of potentiation of electrically evoked cortical inhibition produced by these benzodiazepines correlated significantly (r = -0.60704; p less than 0.01; phi = 33) with the logarithm of the Ki values of these drugs for inhibiting specific 3H-diazepam binding to rat brain membranes. 4. When tested with iontophoretic doses which were directly proportional to their Ki values for inhibiting 3H-diazepam binding to rat brain membranes, these benzodiazepines produced very similar potentiations of electrically evoked cortical inhibition.

Sexual behavior of the male schizophrenic: the impact of illness and medications.

The literature concerning the impact of (a) the schizophrenic illness and (b) the neuroleptic drugs (which are the most commonly employed medications for this disorder) on male sexual behavior is critically reviewed in the light of what is currently known about the interaction of both the schizophrenic illness and the neuroleptic drugs with hormones and neurotransmitters known to play a role in male sexual behavior. The effect of the schizophrenic illness on male sexual behavior is unclear, but there are some indications that chronic, severe schizophrenia may exert detrimental effects on many aspects of male sexual behavior. As for neuroleptic drugs, a wealth of evidence suggests that they have many detrimental effects on male sexual behavior. Nevertheless, since the introduction of these drugs, the reproductive rates of male schizophrenics have increased. The multiplicity of factors involved in the sexual behavior of the schizophrenic patient is emphasized. It is concluded that the sexual behavior of the male schizophrenic provides an important forum for studying the interaction between psychological, sociological and biochemical-pharmacological factors which determine sexual behavior.

Ethanol specifically potentiates GABA-mediated neurotransmission in feline cerebral cortex.

Ethanol (ethyl alcohol) potentiates the inhibition of cortical neurons by gamma-aminobutyric acid. This effect is specific, since ethanol does not potentiate inhibiton by glycine, serotonin, or dopamine. These results have implications for alcoholism because (i) gamma-aminobutyric acid mediates anxiolytic mechanisms, and (ii) anxiety is implicated in the etiology of alcoholism.

Benzodiazepines in schizophrenia: a need for reassessment.

The controlled clinical studies that have attempted to evaluate the usefulness of benzodiazepines in the treatment of schizophrenic patients are reviewed. It is concluded that the doses used were probably too small and inadequate to induce an ameliorating effect. Benzodiazepines may be promising candidates for antipsychotic drugs since, by facilitating CABAergic neurotransmission, they diminish dopaminergic neurotransmission.

Effects of microiontophoretically applied flurazepam on responses of cerebral cortical neurones to putative neurotransmitters.

Utilizing standard microiontophoretic techniques and recording extracellularly in cats, we studied the effects of flurazepam, a water-soluble benzodiazepine, on the spike activity of single cerebral neurones and its interactions with several excitatory and inhibitory putative neurotransmitters. Large iontophoretic doses (5--30 nA, 0.1 M solution) of flurazepam induced a depression of spike amplitude. Smaller doses (less than 5 nA, 0.1 M solution or 20--50 nA, 20 mM in 0.16 M NaCl) reduced the excitation produced by glutamate, aspartate, and homocysteate, but antagonism of acetylcholine-evoked excitations required large flurazepam doses (up to 30 nA, 0.1 M solution). Even lower doses of flurazepam (less than 10 nA, 20 mM in 0.16 M NaCl) enhanced the inhibitory effect of gamma-aminobutyric acid (GABA) but antagonized that of 5-hydroxytryptamine, and had no effect on dopamine-induced inhibition of firing. Hence, only GABA-evoked inhibitions were significantly potentiated by flurazepam. These results demonstrate the multiple possible interactions between a benzodiazepine and different putative neurotransmitters in the mammalian cerebral cortex.

Factors related to tardive dyskinesia.

The authors found a 31% incidence of tardive dyskinesia among 261 schizophrenic outpatients treated with neuroleptics. Multiple linear logistic regression analysis revealed a higher incidence of tardive dyskinesia among elderly patients, those with longer records of hospitalization, those for whom neuroleptic medication had little therapeutic effect, and those treated with fluphenazine. Patients manifesting tardive dyskinesia tended to have fewer parkinsonian symptoms than those without the disorder, especially when tremors and akathisia were excluded from consideration. Multiple linear regression analysis indicated that brain-damaged patients and male patients were more susceptible to severe forms of the disorder, even though these factors were not implicated in its initial appearance.

A presynaptic component of the action of iontophoretically applied flurazepam on feline cortical neurones.

The effect of iontophoretically applied flurazepam on the spike activity of pericruciate cortical neurones of the cat was studied. Flurazepam increased cortical inhibition produced either by local electrical stimulation (which is known to release gamma-aminobutyric acid (GABA) or by iontophoretically applied GABA. Following intravenous treatment with thiosemicarbazide (a GABA-synthesis inhibitor), flurazepam still augmented the action of GABA but was much less effective on electrically evoked cortical inhibition. These findings suggest that part of the action of flurazepam on inhibitory cortical transmission might be at the presynaptic level.

Butaclamol in the treatment of schizophrenia. A standard-controlled clinical trial.

A 16-week, standard-controlled, double-blind study was conducted to compare the efficacy of butaclamol with that of fluphenazine in the treatment of 24 newly admitted schizophrenic patients. Statistically significant improvement occurred in the entire population in the total scores of the BPRS and PAS; in the activation, anergia, thought disturbance and hostile/suspiciousness factor scores of the BPRS; and in the scores of 9 of the 12 factors of the PAS. There were no statistically significant differences between the scores of the two treatment groups on the total or factor scores of either scale during the course of the clinical trial. The most frequently occurring adverse effects in the butaclamol group were rigidity, akathisia and excitement/agitation. The most frequently occurring adverse effects in the fluphenazine group were insomnia, decreased motor activity and tremor. It is concluded that butaclamol exerts potent neuroleptic effects on schizophrenic patients.

WIN 27,147-2 in the treatment of depression. An uncontrolled clinical study.

An uncontrolled clinical study with WIN 27,147-2 was conducted with 10 hospitalized depressed psychiatric patients. There was statistically significant improvement in the total scores of the HAM-D, BPRS and Zung; in the scores of all the factors of the HAM-D and Zung; in the scores of the anxiety/depression and activation factors of the BPRS, and in the scores of 6 of the 18 items of the BPRS. Judged by clinical global impression, 9 of the 10 patients were very much improved and 1 patient much improved. The most frequently occurring adverse effects were dry mouth, sweating, drowsiness and insomnia.