Lack of cholinergic deficit in the neocortex in pick''s disease

1. 1. Choline acetyltransferase activity was decreased in the frontal cortex in Alzheimer's and Gerstmann-Straussler dementias but not in Pick's disease.

2. 2. Cortical somatostatin was only decreased in Alzheimer's dementia.

3. 3. Postsynaptic muscarinic binding sites appeared to be decreased in a subpopulation of Alzheimer's patients.

4. 4. Our data indicate that a loss of cholinergic innervation of the cortex is not common to all dementias.

Long term treatment with oxaprotiline in patients with major depression

1. 1) Four hundred thirty-seven patients with depressive illness were treated for up to 11 months with oxaprotiline (Ba-49802B)in a continuation study.

2. 2) Results of this study suggest that oxaprotiline continued to be effective in alleviating depressive symptoms.

3. 3) Additionally, evaluation of safety parameters failed to reveal any significant risk to patients who were treated with oxaprotiline over this extended period of time.

Fluoxetine in borderline personality disorder

1. 1. Twelve patients with borderline personality disorder and not suffering a major depression were treated with fluoxetine, a selective serotonin reuptake inhibitor, in an open label trial. All of the patients improved, and 75% were rated as much or very much improved.

2. 2. Treatment was generally very well tolerated, but careful dosage titration was important in some patients, especially to manage agitation.

3. 3. Improvement has been maintained with continued treatment throughout the follow-up period which ranged up to six months.

4. 4. Incidental findings suggest fluoxetine may also be of use in treating substance abuse, attention deficit hyperactivity disorder, late luteal phase dysphoria disorder, dysthymic and cyclothymic disorders, and seasonal pattern depression.

5. 5. These preliminary results support the hypothesis that borderline personality disorder may be related to a central scrotonergic deficit.

A preliminary study of serotonergic antidepressants in treatment of dysthymia

Rosenthal, Jesse et al. A Preliminary Study of Serotonergic Antidepressants in the Treatment of Dysthymia. Prog. Neuro-Psychopharmacol. & Biol. Psychiat. 1992, 16(6): 933–941.

1. 1. There is increasing evidence that antidepressants may alleviate symptoms of dysthymia, but few prior studies on selective serotonergic agents.

2. 2. Twenty patients meeting criteria for dysthymia, but not meeting criteria for major depression, received open label trials of a serotonergic antidepressant, either fluoxetine or trazodone.

3. 3. Seventeen (85%) completed three-month medication trials, and of these, twelve (70.6% of completers) responded to treatment. Seven (41.2% of completers) were still in remission on followup at five months.

4. 4. Both fluoxetine and trazodone were well tolerated in dysthymics, and showed similar short-term effectiveness in treating dysthymic symptoms.

Dexamethasone effects on numbers of cells in lymphocyte subpopulations: Changes associated with major depression and DST nonsuppression

1. 1. The authors studied the effects of administration of 1 mg of dexamethasone on the number of cells in discrete subpopulations of lymphocytes in major depressed and psychiatric control patients with depressive symptoms.

2. 2. Dexamethasone significantly decreased the total lymphocyte count and numbers of T and helper T lymphocytes in control patients.

3. 3. In contrast, dexamethasone failed to significantly decrease the numbers of cells in any of the subpopulations of lymphocytes studied in major depressed patients.

4. 4. Among major depressed patients both DST suppressors and nonsuppressors were insensitive to the suppressive effects of dexamethasone on lymphocyte numbers.

5. 5. However, in DST nonsuppressors, but not in DST suppressors, dexamethasone administration significantly the number of cytotoxic/suppressor T lymphocytes and natural killer cells.

6. 6. The authors conclude that insensitivity to the suppressive effects of dexamethasone on lymphocyte numbers is specific to major depression and is not associated with DST status. However, DST nonsuppression is associated with a facilitating effect of dexamethasone on the number of cells in some subpopulations of lymphocytes.

New concepts in benzodiazepine therapy: Rebound anxiety and new indications for the more potent benzodiazepines

1. 1. Abrupt withdrawal of benzodiazepine treatment in generalized anxiety patients was found to induce a rebound anxiety state in addition to minor physical symptoms.

2. 2. Controlled clinical trials suggest that the newer high potency benzodiazepines (alprazolam, clonazepam and bromazepam) have novel psychiatric indications and greater anxiolytic effect than the classical benzodiazepines.

3. 3. Alprazolam, a triazolobenzodiazepine, was superior to placebo in the treatment of panic disorder, for which medium or low potency benzodiazepines are generally inefficacious.

4. 4. Clonazepam, an anticonvulsant which increases 5HT synthesis, was more efficacious than lithium in reducing manic symptoms.

5. 5. Bromazepam, a new potent benzodiazepine, was superior to diazepam in the treatment of generalized anxiety disorder.

Increments in plasma homovanillic acid concentrations after neuroleptic discontinuation are associated with worsening of schizophrenic symptoms

Khan, René s., Farooq Amin, Peter Powchik, Peter Knott, Marvin Goldstein, Seth Apter, Ben Kerman, Stacey Jaff and Michael Davidson: Increments in Plasma Homovanillic Acid Concentrations after Neuroleptic Discontinuation are Associated with Worsening of Schizophrenic Symptoms. Prog. NeuroPsychopharmacol. & Biol. Psychiat. 1990, : 879–884.

1. 1. Thirty-two male schizophrenic patients participated in this study.

2. 2. Plasma concentrations of the dopamine metabolite, homovanillic acid (pHVA) were assessed once on neuroleptic medication and twice a week for a maximum of six weeks after its discontinuation.

3. 3. Psychiatric symptomatology was assessed once on neuroleptic medication and once a week for a maximum of six weeks after its discontinuation, using the brief psychiatric rating scale (BPRS).

4. 4. pHVA and total BPRS score increased significantly after discontinuation of neuroleptic as compared to baseline.

5. 5. The magnitude of pHVA and BPRS increments after discontinuation of neuroleptic correlated significantly.

6. 6. Results of this study suggest that worsening of schizophrenic symptoms after discontinuation of neuroleptic treatment is associated with increased pHVA concentrations.

Correlation of fluphenazine plasma levels versus clinical response in patients: A pilot study

1. 1. Five schizophrenic patients (diagnosed using Research Diagnostic Criteria) under treatment with intramuscular fluphenazine decanoate or oral fluphenazine dihydrochloride had serial plasma fluphenazine and plasma prolactin levels determined by a direct radioimmunoassay method.

2. 2. Clinical state was assessed utilizing the Global Assessment Scale and the Extrapyramidal Symptoms-Neurological Rating Scale.

3. 3. There was no correlation between clinical state and plasma fluphenazine or prolactin levels. All patients under treatment with the depot preparation remained clinically stable with serum fluphenazine levels between 1 and 3 ng/ml.

4. 4. In one patient, who received an intramuscular dose of fluphenazine decanoate, plasma levels were determined using direct radioimmunoassay, extraction followed by radioimmunoassay and gas liquid chromatography-mass spectrometry. There was good correlation between the three methods.

Neurotransmitter changes in early- and late-onset alzheimer-type dementia

Arai Heii., Yosuke Ichimiya, Kenji Kosaka, Takashi Noroji and Reiji Iizuka: Neurotransmitter Changes in Early- and Late-onset Alzheimer-type Dementia. Prog. Neuro-Psychophamacol. & Biol. Psychiat. 1992, 16(6):883–890.

1. 1. Neurotransmitter-related markers were examined in Alzheimer-type dementia (ATD) and studied whether or not there is biochemical difference between the early- and late-onset sub-groups.

2. 2. Postmortem brains were obtained from neuropathologically diagnosed ATD patients and control subjects with no clinico-neuropathological findings indicative of neuropsychiatric diseases.

3. 3. Neurochemical data in the early- and late-onset groups were compared to the age-matched younger and older control groups, respectively, and expressed as a percentage of the mean value in the respective controls.

4. 4. Choline acetyltransferase activity and concentrations of serotonin and noradrenaline were more severely depleted in the early-onset ATD group than in the late-onset ATD group.

5. 5. These findings indicative of heterogeneity of ATD patients were discussed from the pathogenetic and therapeutic viewpoints.

Determination of plasma haloperidol concentrations by radioreceptor assay in schizophrenia: Clinical utility

1. 1. Haloperidol concentrations were determined by radioreceptor assay (RRA) and prolactin concentrations were measured in 20 patients diagnosed as schizophrenia (DSM-III).

2. 2. The patients were treated with a fixed dose of haloperidol for 21 days.

3. 3. Our results suggest the existence of a curvilinear relationship, in the form of an inverted U, between stable haloperidol levels and clinical improvement assessed by total BPRS score.

4. 4. We also found a curvilinear relationship between the improvement observed in positive symptoms and state steady levels.

5. 5. No relationship was seen between improvement in negative symptoms and state steady levels.

6. 6. An interval of optimal haloperidol concentration was found: 8.1 ng/ml to 19.6 ng/ml.

7. 7. No relation was found between the dose of haloperidol administered and plasmatic concentration, nor between haloperidol and prolactin levels.

8. 8. Our findings suggest that haloperidol concentrations determined by RRA have clinical utility as predictors of response in schizophrenia.

Buspirone: An anxioselective alternative for the management of anxiety disorders

1. 1. Buspirone HCl (Buspar ) is a novel anxiolytic agent unrelated to the benzodiazepines or other psychotherapeutic agents.

2. 2. Animal studies support an anxioselective profile, relief of anxiety without sedation, muscle relaxation or anticonvulsant activity.

3. 3. Double-blind clinical studies show buspirone to be effective in the treatment of anxiety and anxiety in the presence of depression.

4. 4. The effects of buspirone on psychomotor function, physical dependence and abuse potential tests are similar to those seen with placebo treatments.

5. 5. Mechanism of action studies indicate activity in a variety of neuronal systems.

Regional glucose metabolism in schizophrenic patients before and during neuroleptic treatment

Wiesel, Frits-Axel: Regional glucose metabolism in schizophrenic patients before and during neuroleptic treatment. Prog. Neuro-Psychopharmacol. & Biol. Psychiat. 1992, 16(6): 871–881.

1. 1. Determination of regional glucose metabolism has been considered to be a tool to elucidate the mechanisms of action of neuroleptics.

2. 2. D₂-dopamine antagonists seem to increase glucose consumption in dopamine innervated areas.

3. 3. Studies in humans do not give results in complete accordance with animal findings.

4. 4. In patients neuroleptic compounds and dopamin agonists probably increase and decrease striatal metabolism respectively.

5. 5. Changes in metabolism, especially in the right hemisphere may be coupled with improvement of the patients.

6. 6. Future research must be based on protocols specially designed for the study of drug effects.

Treatment of alcohol organic mental disorder with piracetam

1. 1. The paper presents an investigation of the efficiency of piracetam in alcohol organic mental disorder.

2. 2. A double blind placebo controlled study design was used to compare two dosages of the substance (2 × 3g versus 2 × 12g).

3. 3. The cognitive functions of the patients, especially short term memory and concentration, were assessed on the days 0, 7, 14, 28 and 42 using various psychological instruments.

4. 4. An analysis of 39 patients showed an improvement of cognitive functions in all three groups.

5. 5. Patients receiving drug treatment showed earlier responses than patients receiving placebo; differences between the three investigational groups were not statistically significant.

6. 6. The results achieved make the effect of piracetam appear somewhat questionable.

CGP 11.952: An experimental benzodiazepine derivative. Effects on cognitive functioning in patients with epilepsy

1. 1. In two open studies using patients with intractable epilepsy, the effects of CGP 11.952, a triazolyl benzophenone, on cognitive functioning were assessed by means of a computerized neuropsychological battery.

2. 2. In the first study CGP 11.952 turned out to have a positive effect on information processing speed, perceptual sensitivity and precisaness of responses.

3. 3. Negative effects were found on reaction time.

4. 4. In the second study this latter effect was less clear.

5. 5. A striking result was the less negative effect on memory consolidation under influence of CGP 11.952 in comparison with other benzodiazepines.

Biogenic amine metabolites in delusional (psychotic) depression and melancholia subtypes of major depression

1. 1. The levels of the urinary main metabolites of norepinephrine 3-methoxy-4-hydroxyphenylglycol (MHPG), of dopamine homovanillic acid (HVA) and of serotonin 5-hydroxyindoleacetic acid (5-HIAA) were measured in 84 patients with major depressive disorder, 34 delusional and 50 nondelusional. Melancholia subtype was also defined (N=62).

2. 2. MHPG was significantly higher in the delusional depressed group (p=0.023). Female patients with delusional major depression also had significantly higher HVA excretion than female patients with non delusional major depression (p=0.036). 5-HIAA excretion was similar in the two patient subgroups.

3. 3. No significant differences in the three monoamine metabolites were found between the melancholic and nonmelancholic depressed patients.

Preclinical and clinical studies with cysteamine and pantethine related to the central nervous system

Vécsei, László and Erik Widerlöv: Preclinical and Clinical Studies with Cysteamine and Pantethine Related to the Central Nervous System. Prog. Neuro-Psychopharmacol. & Biol. Psychiat. 1990, : 835–862.

1. 1. Cysteamine is formed by degradation of coenzyme A (CoA) and causes somatostatin (SS), prolactin and noradrenaline depletion in the brain and peripheral tissues.

2. 2. Cysteamine influences several behavioral processes, like active and passive avoidance behavior, open-field activity, kindled seizures, pain perception and SS-induced barrel rotation.

3. 3. Cysteamine has several established (cystinosis, radioprotection, acetaminophen poisoning) and theoretical (Huntington's disease, prolactinsecreting adenomas) indications in clinical practice.

4. 4. Pantethine is a naturally occurring compound which is metabolized to cysteamine.

5. 5. Pantethine depletes SS, prolactin and noradrenaline with lower efficacy compared to that of cysteamine.

6. 6. Pantethine is well tolerated by patients and has been suggested to treatment of atherosclerosis. The other possible clinical indications (alcoholism, Parkinson's disease, instead of cysteamine) are discussed.

The association of tardive dyskinesia and pseudoparkinsonism

1. 1. A survey of 315 chronic inpatients for the presence of extrapyramidal side effects indicates that 58.7% of the patients had no evidence of extrapyramidal side effects, 28.6% had tardive dyskinesia (TD) alone, 8.9% had pseudoparkinsonism and 3.8% had a combination of both.

2. 2. Women seemed to exhibit more side effects.

3. 3. Aging was another factor associated with a higher risk for the appearance of extrapyramidal side effects.

4. 4. Affective disorder patients carried more risk than patients with schizophrenia.

5. 5. The low prevalence of the combined TD and pseudoparkinsonism may be related to several factors. The possible explanations are explored and discussed. These patients present a therapeutic dilemna.

Fever and leukocytosis: Physical manifestations of bipolar affective disorder?

1. 1. Fever and leukocytosis are occasionally observed in patients with psychiatric disorders. A thorough medical evaluation does not always reveal the origin of these abnormalities.

2. 2. We report the case histories of three patients with bipolar affective disorder and an abnormal DST who had fever and leukocytosis during the acute phase of their illness. No organic etiology could be found.

3. 3. All three patients responded to ECT with resolution of the depression, the fever, and the leukocytosis, and normalization of the DST.

4. 4. We propose that fever and leukocytosis may be rare physical manifestations of bipolar affective disorder, particularly in patients with abnormal DST.

Folic acid and psychopathology

1. 1. The incidence of folic acid deficiency is high in patients with various psychiatric disorders including depression, dementia and schizophrenia.

2. 2. In epileptics on anticonvulsants, folate deficiency often occurs because anticonvulsants inhibit folate absorption. In these patients folate deficiency is often associated with psychiatric symptoms.

3. 3. In medical patients psychiatric symptoms occur more frequently, and in psychiatric patients symptoms are more severe, in those with folate deficiency than in those with normal levels.

4. 4. Many open studies have demonstrated therapeutic effects of folate administration on psychiatric symptoms in folate deficient patients.

5. 5. Several placebo-controlled studies have not demonstrated therapeutic effects, possibly because the doses they used (15–20 mg/day) are known to be toxic and to cause mental symptoms.

6. 6. Two placebo-controlled studies have demonstrated beneficial effects of Folic acid administration, one in patients with a syndrome of psychiatric and neuropsychological changes associated with folate deficiency and the other in patients on long-term lithium therapy. In the latter study the dose was only 0.2 mg/day.

7. 7. Folic acid deficiency is known to lower brain S-adenosylmethionine and 5-hydroxy-tryptamine. S-Adenosylmethionine, which has antidepressant properties, raises brain 5-hydroxytryptamine. Thus, depression associated with folate deficiency is probably related to low brain 5HT.

8. 8. S-Adenosylmethionine is involved in many methylation reactions, including methylation of membrane phospholipids, which influences membrane properties. This may explain the wide variety of symptoms associated with folate deficiency.

9. 9. Because the costs and risks associated with low doses of folic acid (up to 0.5 mg/day) are small, folic acid should be given as an adjunct in the treatment of patients with unipolar or bipolar affective disorders and anorexia, epileptics on anticonvulsants, geriatric patients with mental symptoms and patients with gastrointestinal disorders who exhibit psychiatric symptoms.

10. 10. Although the majority of the patients listed above will probably not be helped by folic acid therapy, a significant minority are likely to have folate-responsive symptoms.

Can ECT-induced cognitive effects be altered pharmacologically?

Khan Arifulla, Mary Helen Mirolo, Hugh A. Mirolo and Sheree Miller: Can ECT-Induced Cognitive Effects be Altered Pharmacologically? Prog. Neuro-Psychopharmacol. & Biol. Psychiat. 1993, 17(6): 861–873.

1. 1. A systematic review of the literature revealed twelve clinical trials that evaluated nine different drugs, and used three different conceptual models to prevent, restore or treat ECT-induced cognitive deficits.

2. 2. This review indicated inconclusive results regarding clinical utility of any of the drugs.

3. 3. Major factors discussed include the complexities involved in the evaluation of ECT-induced cognitive deficits, and the techniques of evaluating changes in cognitive functions.

4. 4. Our conclusion is that future research should emphasize understanding the neural mechanisms related to ECT-induced cognitive deficits. We suggest several areas for future exploration.