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.

Reduced P3 amplitudes are associated with both a family history of alcoholism and antisocial personality disorder

1. 1. Previous research has demonstrated that the amplitude of the P3 component of the event-related electroencephalographic potential (ERP) is influenced by the presence/absence of a family history of alcoholism (FHA). The present study extended this line of research by examining the P3 effects of both FHA and antisocial personality disorder (ASP) in a 2 × 2 factorial design.

2. 2. The task required subjects to judge the orientation of an infrequently-occurring outline drawing, representing an aerial view of a human head.

3. 3. Analyses of P3 amplitudes elicited by this drawing revealed reductions attributable to the effects of both FHA and ASP, but not their interaction. These effects were most apparent at frontal electrode sites. Analyses of P3 latency revealed no consistent pattern of findings. However, the interval between P3 and manual reaction time was shorter in the ASP+ group relative to the ASP- group.

Membrane glycoconjugates as potential mediators of alcohol effects

1. 1. Membrane glycoconjugates include glycoproteins and glycolipids that have many important functions in a wide variety of tissues, especially brain.

2. 2. Alcohol's ability to fluidize and swell plasma membranes could be expected to alter the orientation and conformation of the embedded glycoconjugates.

3. 3. Both kinds of glycoconjugates can contain terminal moieties of sialic acid, which has been shown to be decreased by single doses of alcohol. Chronic exposure to alcohol may have no effect on sialic acid, except in very young animals.

4. 4. Glycolipids containing sialic acid (gangliosides) are also decreased by acute doses of alcohol, but chronic alcohol has little effect. Thus, gangliosides may have a role in the development and expression of tolerance.

5. 5. Glycoproteins containing sialic acid may also be involved in alcohol action, but there has been less research in this area.

6. 6. Alcohol-induced disruptions in membrane glycoconjugates could affect the important cellular functions that glycoconjugates have, and thus research on alcohol effects on glycoconjugates could lead to important discoveries of diagnostic and therapeutic value for alcohol abuse and alcoholism.

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.

Simple reaction time event-related potentials: Effects of alcohol and diazepam

1. 1. Acute effects of alcohol and diazepam on reaction time (RT) and event-related potential (ERP) measures were examined in 108 healthy male volunteers.

2. 2. The subjects engaged in a simple RT task at two levels of stimulus intensity during baseline and treatment sessions.

3. 3. Lower stimulus intensity produced increased RTs, increased ERP peak latencies, and suppression of peak amplitudes.

4. 4. Moderate and high doses of alcohol, and high doses of diazepam produced increased RTs. Alcohol suppressed P100 and N100 amplitudes, while diazepam suppressed P100 amplitudes only. P100 amplitudes were correlated to RTs under baseline and treatment conditions.

5. 5. These results were taken as evidence for impaired stimulus detection during alcohol and diazepam intoxication, with both drugs influencing sensory-perceptual processes and alcohol alone influencing the degree of attentiveness.

Biological markers of depression: Who multi-center studies and future perspective

Tsukasa Koyama and Itaru Yamashita: Biological Markers of Depression; WHO Multi-Center Studies and Future Perspective. Prog. Neuro-Psychopharmacol. & Biol. Psychiat. 1992, 16(6): 791–796.

1. 1. Dexamethasone suppresion test (DST), imipramine platelet binding and sleep EEG in depressed patients were studied by the network of WHO Collaborating Centers.

2. 2. DST and sleep EEG indicated abnormalities characteristic to depression, but imipramine platelet binding failed to show difference between depressed and normal subjects.

3. 3. 20 papers related to markers of depression were presented at the 17th Congress of CINP, Kyoto, 1990.

4. 4. They were introduced under 5 headings: 1) DST and its modifications, 2) serotonergic functions, 3) platelet studies, 4) ocular potentials and melatonin, and 5) brain imaging. There are reviewed here.

GABA-Transaminase in brain and blood platelets: Basic and clinical aspects

1. 1. Several lines of evidence suggest that the major inhibitory neuro-transmitter, gamma-aminobutyric acid (GABA) is involved, both directly and indirectly, in the pathogensis of certain neurological and psychiatric disorders.

2. 2. The main enzyme responsible for GABA catabolism is gamma-aminobutyrate aminotransferase (GABA-T). Inhibition of this enzyme produces a considerable elevation of brain GABA concentrations, and such elevation has been correlated with many pharmacological effects.

3. 3. There seems to be that, as is discussed below, GABA-T activity in the brain and/or blood platelets is related to some neuro-psychiatric disorders such as alcoholism, epilepsy and Alzheimer's disease.

4. 4. GABA-T has been identified in the blood platelets with similar characteristics to those of brain GABA-T. In this way, studies on GABA-T activity in neuro-psychiatric disorders could be performed to understand, diagnosis and treat GABA-related disorders of the central nervous system (CNS).

Multidimensional behavioral effects of marijuana

Kelly Thomas H., Richard W. Foltin, Cleeve S. Emurian and Marian W. Fischman: Multidimensional Behavioral Effects of Marijuana. Prog. Neuro-Psychopharmacol. & Biol. Psychiat. 1990, : 885–902.

1. 1. Five groups of three healthy adult male volunteers (n = 15), all reporting occasional, controlled marijuana use, gave written consent and participated in residential studies lasting 6 to 15 days.

2. 2. Subjects smoked marijuana cigarettes (0 1.3 2.3 or 2.7% THC, w/w) at 0945, 1330, 1700 and 2030 every day, and each subject received both active and placebo marijuana cigarettes in 2–5 consecutive day phases, with placebo and active doses presented in an alternating fashion.

3. 3. In comparison with placebo, active marijuana produced a variety of effects on measures of human behavior, including in food consumption and errors on psychomotor tasks, in bouts of tobacco-cigarette smoking and verbal interactions and in rates of task performance, time spent under social conditions or social cooperation.

4. 4. Dimensions of human behavior were differentially sensitive to the effects of smoked marijuana.

5. 5. The simultaneous measurement of multiple dimensions of human behavior is a useful procedure for determining dose potency following marijuana administration.

Relationship of cognitive ability to the developmental course of antisocial behavior in substance-dependent patients

1. The present study examined cognitive differences among three groups of abstinent substance-dependent patients and a control group of non-drug users. The patient groups were defined according to their DSM III-R substance dependence diagnosis(es): heroin, cocaine, or dual alcohol and cocaine dependence.

2. In the initial analysis, which compared the four subject groups on scores from the Shipley Institute of Living Scale, no significant differences were found. However, the groups did vary on the number of Antisocial Personality Disorder (ASPD) behaviors.

3. Another set of analyses was conducted to examine the relationship between ASPD and SILS scores. Analyses of the effects of ASPD (+/−) across all of the patients revealed lower SILS scores in the ASPD-positive group. Additional analyses examined the developmental course of the ASPD effect by contrasting 1) patient groups characterized by childhood Conduct Disorder (CD) combined with adult ASPD vs. 2) childhood CD which did not continue into adulthood as ASPD vs. 3) adults who did not report childhood CD but who met other ASPD behavioral criteria as adults, vs. 4) subjects who had neither childhood CD nor adult ASPD.

4. In this analysis, it was found that patients who met diagnostic criteria for childhood Conduct Disorder, but whose antisocial behaviors resolved after age 15, had equivalent SILS scores to those patients with no childhood CD or adult ASPD. A decrement in SILS scores was only found in those patients whose antisocial behaviors persisted into adulthood.

5. ASPD adults who did not report childhood CD behaviors had normal SILS scores compared to Controls.

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.

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.

Electroconvulsive therapy and plasma prostaglandin E2 metabolite in major depressive disorder

1. 1. Animal experiments show that PGE₂ affects the release of ACTH and corticosteroids. In depressed subjects, plasma concentrations of the same hormones are increased immediately following ECT. Consequently we explored passible effects of ECT on PGE₂.

2. 2. The major plasma PGE₂ metabolite (PGEM), ACTH, and cortisol were determined by RIA.

3. 3. PGEM did not change with time alone and anesthesia without ECT also did not have a consistent effect. PGEM was significantly elevated at all post ECT sampling times. The maximum increase, about fifty percent, was attained at 15 and 30 minutes. Similar changes were observed following ECT-I and ECT-VI.

4. 4. Positive correlations between PGEM, ACTH and cortisol were obtained.

5. 5. The results demonstrate that following ECT stimulus there is a robust increase in circulating PGEM. The increased release of PGE₂ may, in part, account for the elevated plasma ACTH and cortisol.

Glycosaminoglycan polysulfate (ateroid) in old-age dementias: effects upon depressive symptomatology in geriatric patients

1. 1. Glycosaminoglycan polysulfate is a mixture of sulfo-muco-polysaccharides with hypolipidemic activity. A number of clinical studies have indicated that it is effective in improving psychopathology in patients with cardiac and/or cerebral disease associated with arteriosclerosis.

2. 2. A multicenter clinical trial was performed to compare the effects of two different dosages of glycosaminoglycan polysulfate upon depressive symptomatology in patients with multi-infarct dementia and primary degenerative dementia.

3. 3. A total of 39 patients were treated in an 18-week clinical trial which followed a singleblind parallel design.

4. 4. Results indicated that patients with both diagnoses improved significantly in depressive symptomatology over the course of treatment, with particular improvement noted in cognitive disturbance. Drug dosage was not a significant determinant of treatment response for either diagnostic group.

An experimental antidepressant increases rem sleep

1. 1. An experimental antidepressant was studied through sleep laboratory recordings, psychoendocrinological tests and clinical measurements in terms of its efficacy, side effects and effects on sleep.

2. 2. The design included a four-week drug administration period, proceeded and followed by a one week placebo period.

3. 3. In the presence of antidepressant efficacy, the drug did not disturb sleep induction and maintainance.

4. 4. The only effect on sleep stages was an increase of REM sleep during the short-term drug administration period which is contrary to the REM supressant effect of most antidepressants.

5. 5. This finding suggests that REM supression and antidepressant efficacy are not necessarily related.

6. 6. Further, given that the only known action of the drug is its inhibitory effect on GABA-ergic transmission, one can speculate that GABA mechanisms may be involved in REM sleep modulation.

Serotonergic function in cocaine addicts: prolactin responses to sequential D,L-fenfluramine challenges.

BACKGROUND: Preclinical studies have shown that cocaine produces alterations in serotonergic function but our knowledge of the serotonergic alterations due to cocaine abuse in humans is still fragmentary. We therefore assessed the central serotonergic responsivity of cocaine addicts and control subjects by neuroendocrine challenges with the serotonin releaser and reuptake inhibitor D,L-fenfluramine (FEN). METHODS: Plasma prolactin levels following a 60 mg oral dose of FEN and placebo were studied in 25 hospitalized male cocaine addicts and 13 healthy male subjects. Control subjects underwent one set of FEN/placebo challenges and cocaine addicts two sets of challenges, during the first and third weeks following cocaine discontinuation. Patients were divided into two subgroups as a function of presence (FH+) and absence (FH-) of a paternal history of substance abuse. The following comparisons were made: 1) Control subjects versus entire patient group and versus patient subgroups; 2) entire patient group and patient subgroups responses to first versus second challenges; 3) FH+ versus FH- patients' early responses and FH+ versus FH- patients' late responses. RESULTS: The prolactin responses to FEN increased significantly in the entire patient group as time following cocaine discontinuation increased. The FH+ patients had significantly blunted early responses by comparison with FH- patients and control subjects. There was a more pronounced rebound of the responses of FH+ patients by comparison with those of FH- patients. As a result, comparisons of the late responses of FH+ and FH- patients and of FH+ patients and control subjects became nonsignificant. CONCLUSIONS: Cocaine use appears to have an effect on the serotonergic mechanisms mediating prolactin release in humans. In the present study, this effect was more pronounced in a subgroup of patients with a paternal history of alcoholism or drug abuse. The greater blunting of the prolactin response observed within days of cocaine discontinuation followed by a greater rebound of this response 2 weeks later could indicate an increased vulnerability to the disruptive effects of cocaine in these patients.     

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.

Escape from dexamethasone suppression: Possible role of an impaired inhibitory opioid mechanism

1. 1. Several lines of evidence indicate that the activity of the hypothalamus-pituitary-adrenal (HPA) axis in depression is disinhibited.

2. 2. Escape from dexamethasone suppression, although not limited to is more frequent in patients with endogenous depression compared to normals or patients with other psychiatric diagnoses.

3. 3. Norepinephrine, serotonin and acetylcholine have been implicated in the pathophysiology of this neuroendocrine abnormality.

4. 4. Morphine, 5 mg intravenously, suppressed Cortisol secretion in healthy volunteers (n = 4) and the majority of 32 psychiatric inpatients.

5. 5. However, patients with endogenous depression abnormal dexamethasone suppression test results show early resumption (escape) of cortisol secretion following the initial suppression induced by morphine.

6. 6. It is concluded that the pathophysiology of this neuroendocrine abnormality is not limited to classical neurotransmitter-HPA axis interaction but that it also involves opioid inhibitory mechanisms.

Neurotransmitter functions in depression

The understanding and management of depression has now progressed beyond the limitations imposed by clinical examination. Biochemical and pharmacological studies based on the biogenic amine hypothesis have investigated neurotransmitter mechanisms to varying degrees.

1. Subgroups of depressions may be identified and treated based on MHPG execution.

2. HVA correlates more with activity than with mood.

3. CSF-5HIAA may be helpful in categorising some depressions.

4. Acetylcholine has some effect on mood most probably through indirect action on other neurotransmitters.

5. GABA is still not adequately investigated.

6. Desensitization of presynaptic adrenergic autoreceptors may explain some of the mechanisms of antidepressant action of drugs.

7. Decreased post-synaptic adrenergic activity is a common effect of most antidepressants and of ECT.

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.

Time course of physostigmine effects on neuroendocrine responding at varying environmental temperatures

1. 1. Hypothermia was found to be related to both the dose of physostigmine and the environmental temperature.

2. 2. Plasma corticosterone levels were elevated above controls regardless of dose of physostigmine or environmental temperature.

3. 3. Plasma free fatty acid levels appeared to be inversely related to physostigmine-induced hypothermia.

4. 4. A hyperglycemic response was observed under all experimental conditions at 0.5 hours and 1.0 hour post injection.

5. 5. Significant inhibition of brain acetylcholinesterase was observed, whereas, plasma and erythrocyte acetylcholinesterase activity was inconsistent.