bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of Spleen-Cell-Conditioned Medium on [3H]-Choline Uptake by Retinal Cells in vitro Is Mediated by IL-2
Authors: Sholl-Franco Alfred , Marques Patrícia M.B. , Paes-de-Carvalho Roberto , de Araujo Elizabeth G.
Published: April 2003

Cytokines are essential molecules throughout the development of the nervous system and also play an important role during the adult life span. In the present work, we analyzed in vitro the effect of spleen-cell-conditioned medium (SCM) on the survival and [3H]-choline uptake of neonatal rat retinal cells. SCM induced an increase in neuronal survival, glial cell proliferation and neurite outgrowth, as evaluated by biochemical and morphological criteria. These effects were time dependent; after 120 h, SCM induced a 6-fold increase in the total protein level. The effect of SCM was blocked both by the inhibition of protein tyrosine kinase activity (10 μM genistein) and by the inhibition of cell division (20 μM fluorodeoxyuridine). SCM also increased the uptake of [3H]-choline by retinal cells. The effect was time dependent. The maximum effect was obtained after 48 h and was maintained at a high level until 120 h. Treatment by 10 μM genistein and 15 μM bis(2-aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid (BAPTA-AM) (an intracellular calcium chelator) completely blocked this effect. However, 20 μM fluorodeoxyuridine did not abolish it. Conditioned medium obtained from glial cells stimulated with SCM (S-GCM) induced an effect on [3H]-choline uptake earlier than that promoted by SCM. Anti-interleukin-2 (IL-2) antibodies blocked the effect of both SCM and S-GCM on [3H]-choline uptake after 48 and 72 h. IL-2 (50 U/ml) elicited the same effect as that observed when the cells were maintained in the presence of SCM. Taken together, our results suggest that IL-2 plays an important role in controlling the survival and differentiation of retinal cells in vitro.
Modulation of IL-18 Production in the Adrenal Cortex following Acute ACTH or Chronic Corticosterone Treatment
Authors: Conti Bruno , Sugama Shuei , Kim Yoonseong , Tinti Cristina , Kim Hocheol , Baker Harriet , Volpe Bruce , Attardi Barbara , Joh Tong
Published: April 2003

Interleukin (IL)-18 is a proinflammatory cytokine and a stimulator of cell-mediated immune responses. We have previously reported that acute stress stimulates the production of IL-18 mRNA in the glucocorticoid (GC)-producing cells of the adrenal cortex. In order to investigate the mechanisms governing the expression of IL-18 in the adrenal cortex, the effects of acute ACTH or chronic corticosterone treatment on the levels of IL-18 mRNA and protein were examined by in situ hybridization and Northern and Western blot assays. Adult male Sprague-Dawley rats received a subcutaneous injection of ACTH or subcutaneous implantation of slow-release corticosterone pellets followed by an injection of saline or ACTH. After 4 h, ACTH induced a 4-fold increase in IL-18 mRNA levels and elevated the content of pro-IL-18 peptide. Six days of chronic corticosterone treatment did not alter the basal levels of IL-18 mRNA and reduced those of pro-IL-18. Finally, ACTH treatment of animals under the corticosterone regimen induced a 2-fold increase in IL-18 mRNA and elevated the levels of the pro-IL-18 protein. The levels of the precursor, p45, and the active subunit p10 peptides of the IL-18-processing enzyme, IL-1β-converting enzyme (ICE), showed no substantial differences in all the conditions tested. IL-1β was not detected under these experimental conditions. These data demonstrate that the production of IL-18 in the adrenal cortex is stimulated by ACTH treatment and is not inhibited by the direct action of corticosterone. In contrast to the anti-inflammatory action of GCs, IL-18 may have an immunostimulatory role during acute stress.
Interleukin-2: Structural and Biological Relatedness to Opioid Peptides
Authors: Jiang Chun-Lei , Xu Di , Lu Chang-Lin , Wang Yuan-Xia , You Zhen-Dong , Liu Xin-Yuan
Published: April 2003

Interleukin (IL)-2 is not only an immunoregulatory factor, but also an analgesic molecule. There are distinct domains of immune and analgesic functions in the IL-2 molecule. The analgesic domain is located around the 45th Tyr residue of human IL-2 in tertiary structure. Antiopioid (β-endorphin, Leu-enkephalin, Met-enkephalin and dynorphin A1–13) sera partially neutralized the analgesic activity of IL-2. Monoclonal antibody against the IL-2 receptor α subunit (Tac) could not block the analgesic activity of IL-2. There existed cross-reactivity between IL-2 and antiopioid sera by indirect ELISA. These studies show strong structural and biological similarities between IL-2 and opioid peptides. The tertiary structure around the 45th residue of IL-2 composes the analgesic domain that is similar to that of endogenous opioids. These results are consistent with the hypothesis that multiple domains of cytokines serve as the structural bases for the immunoregulatory and neuroregulatory effects of cytokines.
Peripheral Effects of Methionine-Enkephalin on Inflammatory Reactions and Behavior in the Rat
Authors: Vujić-Redžić Vesna , Dimitrijević Mirjana , Stanojević Stanislava , Kovačević-Jovanović Vesna , Miletić Tatjana , Radulović Jelena
Published: April 2003

Methionine-enkephalin (Met-Enk) induces notable alterations in immune and central nervous system functions. The present study was conducted in order to compare peripheral and central effects of Met-Enk on nonspecific immunity, open field behavior and pain perception in the rat. The results showed that 0.2 mg/kg of Met-Enk given intraperitoneally (i.p.) increased concanavalin A (Con-A)-induced paw edema and enhanced basal and phorbol myristate acetate (PMA)-stimulated H2O2 production of peritoneal macrophages. Met-Enk-induced immunopotentiation was antagonized by anti-Met-Enk antibodies (anti-Met-Enk-Ig) and quaternary naltrexone (qNtx). Met-Enk injected i.p. produced an increase of horizontal and vertical locomotor activity in the open field that was reversed by i.p. administration of anti-Met-Enk-Ig and qNtx. The dose of 0.2 mg/kg of Met-Enk applied i.p. did not affect the number of writhes in the test of analgesia. Intracerebroventricular (i.c.v.) injection of Met-Enk, given in a dose that was previously shown to be immunostimulatory, enhanced only basal H2O2 production of peritoneal macrophages, and anti-Met-Enk-Ig antagonized this effect. Besides, i.c.v. treatment with anti-Met-Enk-Ig increased and decreased H2O2 production of peritoneal macrophages under basal and stimulated conditions, respectively. Met-Enk and anti-Met-Enk-Ig injected i.c.v. did not influence activity in the open field and pain sensitivity. Thus, the i.c.v. dose of Met-Enk that was sufficient to modulate immune functions did not influence behavior. It may be concluded that Met-Enk modulated nonspecific immune responses and open field behavior by peripheral mechanisms.
Electrical Sources of P300 Event-Related Brain Potentials Revealed by Low Resolution Electromagnetic Tomography
Authors: Anderer Peter , Saletu Bernd , Semlitsch Heribert V. , Pascual-Marqui Roberto D.
Published: April 2003

In a double-blind, placebo-controlled study the effects of Actovegin® on frontal and parietal electrical P300 sources revealed by low resolution electromagnetic tomography (LORETA) were studied in age-associated memory impairment (AAMI) patients. Actovegin is a protein-free metabolically active hemoderivative improving oxygen and glucose utilization. Each patient had, in randomized order, a treatment of 2 weeks with 250 ml 20% Actovegin and 250 ml placebo daily. Auditory ERPs were recorded before and 5 h after drug administration on day 1 (acute effect) and on day 15 (subacute and superimposed effect). Compared to age- and sex-matched normal controls, AAMI patients showed a trend towards P300 latency prolongation and a significantly reduced P300 global field power (GFP). Maximal LORETA source strength did not differ from controls. After Actovegin parietal P300 scalp amplitudes increased, while frontal and temporal amplitudes decreased as compared to placebo. This increase in hilliness, measured by the GFP, was significant. Moreover, the parietal P300 source strength increased after acute, subacute and superimposed infusion of Actovegin as compared to placebo. This may reflect improved availability of cognitive processing resources in the parietal cortex, an area that on the one hand plays an important role in fundamental aspects of attention and on the other hand has been found to be functionally impaired in dementia.
Analysis of Quantitative EEG with Artificial Neural Networks and Discriminant Analysis – A Methodological Comparison
Authors: Winterer G. , Ziller M. , Klöppel B. , Heinz A. , Schmidt L.G. , Herrmann W.M.
Published: April 2003

Artificial neural networks (ANN) are widely used to solve problems of differentiating between groups. However, serious comparisons of this method with the traditional procedure for such tasks (discriminant analysis) are rare. Discussing the results of both methods with the example of highly topical data, we try to demonstrate advantages and drawbacks of both methods. For this purpose, quantitative EEGs of 78 alcoholics were investigated in order to determine whether it is possible to predict relapse of these patients at the beginning of treatment. ANN software is available in Kassel (Institute for Computer Sciences and Mathematics).
Nitric Oxide, Free Radicals and Polyamines May Have a Role in the Membrane Pathology of Schizophrenia
Authors: Das I. , Ramchand C.N. , Gliddon A. , Hirsch S.R.
Published: April 2003

Studies on skin fibroblasts in culture derived from schizophrenic and control subjects showed that polyamines are increased, nitrate levels are reduced and thiobarbituric acid reacting substances did not alter in cultured cells from schizophrenic patients compared to control subjects. Results seem to indicate some alteration in membrane functions in schizophrenia, which is susceptible to neuroleptic treatment. Significantly increased levels of polyamines in drug-treated schizophrenic cells indicates a possible role of polyamines in the activation of proposed hypofunctional NMDA subtype of glutamate receptor systems in schizophrenia.
Thyroid Parameters during Therapy with Zotepine in Delusional Depression
Authors: König Frank , Hauger Barbara , Barg Thomas , Wolfersdorf Manfred
Published: April 2003

There are only few data on the effects of atpyical neuroleptics on thyroid function. In an open pilot study of 12 inpatients with delusional depression, thyroid hormone levels and TRH-TSH test were determined during neuroleptic treatment with zotepine. No significant changes in triiodothyronine (T3), thyroxine (T4) and delta-TSH levels were found in this observation period (28 days).
Platelet 5-HT and Plasma Cortisol Concentrations after Dexamethasone Suppression Test in Patients with Different Time Course of Schizophrenia
Authors: Jakovljević Miro , Mück-Šeler Dorotea , Pivac Nela , Crnčević Željka
Published: April 2003

Platelet 5-HT and plasma cortisol concentrations were determined in 59 schizophrenic patients with different time course of illness before and after dexamethasone suppression test (DST). An abnormal DST (nonsuppression) was observed in 51% of patients. In these patients basal cortisol and platelet 5-HT concentrations were higher than in patients with normal DST. After DST, plasma cortisol levels were higher in nonsuppressors with intermittent and intermittent-chronic time course, whereas platelet 5-HT concentrations were increased in nonsuppressors with intermittent-chronic time course. The results suggest that schizophrenic patients have dysregulated hypothalamic-pituitary-adrenal axis as shown by a high rate of DST nonsuppression, and that nonsuppressors showed hypercortisolemia and hyperserotonemia independent of the time course of schizophrenia. No significant association between DST and time course of the illness was found.
Amperozide Influences Feeding Independently of 5-HT2A Receptor Antagonism
Authors: Price Ingrid V. , Gorzalka Boris B. , White Sarah J. , Arkinstall Kim H.
Published: April 2003

Amperozide has been biochemically classified as a selective 5-HT2A (serotonin type 2A) receptor antagonist. However, research on the behavioral effects of amperozide suggests the possibility of other mechanisms. The present study in the male rat is an investigation of the effect of amperozide on feeding, a behavior which can be inhibited by 5-HT2A agonists such as 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI). Experiments revealed that amperozide acted to inhibit feeding behavior both when administered alone and when administered in combination with DOI. These results are inconsistent with 5-HT2A receptor antagonism by amperozide. Further experiments suggested that amperozide may be acting via α2-adrenergic or 5-HT1A receptors to inhibit feeding. These studies imply that amperozide’s selective 5-HT2A antagonistic activity is behaviorally specific.
Effects of Pemoline on Spontaneous and Event-Related Electrical Activity of the Brain
Authors: Wright N.A. , Belyavin A.J. , Birch C.L. , Pascoe P.A.
Published: April 2003

The effect of pemoline on the electrical activity of the brain (electroencephalogram, EEG) was studied in relation to time since sleep and time of day in 6 healthy subjects carrying out periods of work lasting 18 h. Power of the spontaneous EEG increased with time since sleep and amplitude of the P3 event-related response decreased. The changes may be interpreted as the reduction in alertness with time awake. In contrast, pemoline decreased power of the spontaneous EEG and increased the amplitude the P3 response, effects that are consistent with improved alertness. The changes in brain activity were paralleled by effects on performance, in terms of percentage of correct responses and reaction time. Performance decreased with time awake, and was improved by pemoline compared with placebo. The drug counteracted the adverse effects of time since sleep, with the beneficial effect of the drug persisting over the 18-hour period of work. The findings emphasise that spontaneous and event-related activity of the EEG may be used both to complement measures of performance in the laboratory and to assess behaviour in occupational situations where performance testing is impractical.
Predictors of Lithium Treatment Responsiveness in Bipolar Patients
Authors: Kusalic Maria , Engelsmann Frank
Published: April 2003

Twenty-nine bipolar patients were assessed before the start of lithium therapy to study the prognostic criteria of long-term response to therapy. Assessment included clinical and demographic data and laboratory tests administered before and 2–5 days after initiation of therapy. The tests included calcium and magnesium serum levels, and thyroid hormonal status. Patients were followed up for 2 years. None of the single variables predicted the response to lithium therapy, but a combination of clinical and demographic variables, used in a discriminant function analysis, correctly identified 78.9% of responders. Multiple regression analysis predicted 46.2% of the outcome. The strongest univariate predictors were mood quality, illness duration, and substance abuse.
Increased Plasma Vasopressin and Atrial Natriuretic Peptide in Chronic Schizophrenic Patients during Abdominal Surgery
Authors: Kudoh Akira , Kudo Mihoko , Ishihara Hironori , Matsuki Akitomo
Published: April 2003

Chronic schizophrenic patients are reported to develop imbalanced water homeostasis by the pathological secretion of vasopressin and aldosterone. We measured plasma vasopressin, aldosterone and atrial natriuretic peptide in schizophrenic patients to elucidate the role of these hormones during a perioperative period. Eighteen schizophrenic patients with chronic antipsychotic drugs over 10 years and 22 as a control group who underwent elective lower abdominal surgery were the subjects of this study. In the schizophrenic patients, plasma aldosterone secretion was significantly inhibited, while plasma vasopressin and atrial natriuretic peptide were significantly increased during surgery. A good relationship (r = 0.69, p < 0.01) between plasma atrial natriuretic peptide and plasma osmolality was obtained 60 min after skin incision, but not before the induction of anesthesia. The findings suggest that chronic schizophrenic patients may develop an abnormal secretion of vasopressin, aldosterone and atrial natriuretic peptide during anesthesia.
Immunological Dysfunction in Schizophrenia: A Systematic Approach
Authors: Rothermundt Matthias , Arolt Volker , Weitzsch Christine , Eckhoff Dörte , Kirchner Holger
Published: April 2003

Background: In the present study, immunological alterations were investigated as one possible factor contributing towards the pathogenesis of schizophrenia. Specifically cellular changes, deviating cytokine production and interfering variables were studied in order to improve our understanding of how these factors interact. Method: 44 acutely ill schizophrenics were compared with matched healthy controls. Cell numbers were determined by flow cytometry and cytokine production by whole blood assay and ELISA. A criss-cross technique was employed for the assessment of interfering serum factors. Results: Cell counts for leukocytes, lymphocytes, pan T cells, activated T cells and the absolute B cell count of the schizophrenic patients were all within normal limits. The absolute and relative monocyte counts, the number of IL-2 receptor carrying T cells and the relative B cell count were slightly elevated. IL-2 and IFN-γ production were increased while IL-10 production, the sIL-2R and cortisol levels remained unchanged. No interfering serum factors were detected. Conclusion: The deficient production of TH-1 cytokines in schizophrenia is not due either to a changed number of immunocompetent cells or to a counterregulation of the TH-2 cytokine IL-10. Serum factors in in vitro testing are not responsible for the deficient cytokine production.
Cardiovascular Autonomic Reactivity in Schizophrenics under Neuroleptic Treatment: A Potential Predictor of Short-Term Outcome?
Authors: Agelink M.W. , Malessa R. , Kamcili E. , Zeit T. , Lemmer W. , Bertling R. , Klieser E.
Published: April 2003

In schizophrenics cardiovascular autonomic reactivity (CAR) can be used as an indicator of autonomic arousal. Using a standardized autonomic test battery (modified according to Ewing and Clarke) we prospectively compared the CAR between 46 actually ill schizophrenics (diagnosis according to DSM-III-R) treated with either haloperidol (n = 26) or clozapine (n = 20) and 30 well-matched healthy volunteers. Multivariate analysis demonstrated a significant effect of neuroleptic medication (haloperidol vs. clozapine) on heart rate and diastolic blood pressure under resting conditions as well as on the heart rate variance (30:15 ratio, deep-breathing, Valsalva) and blood pressure tests (sustained handgrip, Schellong). In addition a positive treatment response (using predefined outcome criteria of the Brief Psychiatric Rating Scale) was independently associated with lower resting heart rates and less impaired 30:15 ratios under neuroleptic medication. Our data indicate that clozapine treatment was associated with a substantial impairment of CAR, which can be explained by the drug’s anticholinergic properties in combination with an increase in norepinephrine outflow. The greater heart rate variability in responders might be due to an early neuroleptic-induced decrease of sympathetic activity in the autonomic nervous system, which may precede clinical improvement. Our findings are discussed in relation to neuroleptic-induced changes in plasma catecholamine levels suggested to be useful biological markers in predicting treatment outcome.
Effects of Thyrotropin-Releasing Hormone on the Sleep EEG and Nocturnal Hormone Secretion in Male Volunteers
Authors: Hemmeter U. , Rothe B. , Guldner J. , Holsboer F. , Steiger A.
Published: April 2003

Various peptides including corticotropin-releasing hormone (CRH) exert selective effects on sleep structure and noctural secretions of cortisol and growth hormone (GH). In animal studies analeptic effects and sleep disturbances after thyrotropin-releasing hormone (TRH) administration have been observed; studies of endocrine function in depressed patients suggest a pathological activity of CRH and TRH as compared with that in healthy volunteers. As the role of TRH in the regulation of the sleep endocrine pattern in humans has not yet been clarified, we performed a study to examine the effects of pulsatile administration of TRH on the sleep EEG pattern and the nocturnal secretions of cortisol and GH in 7 healthy male subjects. The sleep EEG was recorded from 23.00 to 07.00 h, and blood samples were collected every 20 min from 20.00 to 07.00 h for the analysis of GH and cortisol concentrations during intravenous administration of placebo or 4 × 50 µg TRH at 22.00, 23.00, 24.00, and 01.00 h. In contrast to the well-known effects of CRH on the sleep endocrine pattern, TRH exerts only a weak effect on the sleep EEG which is reflected in a slight decrease in sleep efficiency associated with a trend to wakefulness during the night. Furthermore, after TRH administration, the cortisol rise appeared earlier, and a nonsignificant tendency to an increased secretion of cortisol during the first half of the night was found. The GH secretion did not differ significantly after application of TRH or placebo. The activating, albeit weak, effect of TRH on the sleep EEG and nocturnal cortisol secretion in healthy volunteers confirms and adds to the results previously observed in animals. On the basis of these findings, we surmise that TRH may contribute to the disturbed sleep continuity seen in depressed patients, probably acting as a cofactor of CRH in a synergistic manner.
Effects of Nicotine in a Bimodal Attention Task
Authors: Lindgren M. , Stenberg G. , Rosén I.
Published: April 2003

Fifteen male users of oral snuff participated in an experiment where we used an auditory-visual vigilance task to study nicotine effects on P300 and response parameters. Quantitative EEG was also studied. Fifteen male nonusers served as controls. We found some decrease of response times and a tendency towards improved signal detection. P300 parameters were not affected in this study. Quantitative EEG analysis indicated an expected increase of arousal, as the activity within the alpha band shifted towards higher frequencies.
Correlation of qEEG with PET in Schizophrenia
Authors: Alper Kenneth , Günther Wilfred , Prichep Leslie S. , John E. Roy , Brodie Jonathan
Published: April 2003

PET relative metabolism was correlated with quantitative EEG in 9 schizophrenic patients. The PET metabolic regions of interest were the frontal lobes, thalamus and basal ganglia, and right and left temporal lobes. Significant positive correlations were seen for the frontal lobes and delta EEG power, and alpha power with subcortical metabolism. The physiologic plausibility of those correlations is discussed with reference to the possible effect of neuroleptic medication.
Differences in Whole Blood Serotonin Levels Based on a Typology of Parasuicide
Authors: Rilke Olaf , Safar Christian , Israel Matthias , Barth Thomas , Felber Werner , Jochen Oehler J.
Published: April 2003

Suicidal behavior has to be considered as a multifactorial phenomenon, which can be analyzed in a classifying-phenomenological manner. We have examined the relation of parasuicide typology to whole blood concentrations of serotonin, HVA, and tryptophan in 58 patients classified into 4 groups of parasuicide typology compared to 22 nonsuicidal depressed patients and 20 healthy subjects. Suicidal patients classified as impetuous, desperate and ambivalent types had significantly reduced whole blood 5-HT levels in comparison with the appealing type as well as nonsuicidal subjects. No differences were detected in the HVA content, but whole blood tryptophan concentrations were significantly reduced in impetuous suicidal patients and depressed patients compared to healthy subjects. This study provides evidence for reduced whole blood serotonin content based on different types of parasuicide.
The Cholinergic Basis of the Smoking-Induced EEG Activation Profile
Authors: Knott Verner J. , Harr Anne , Ilivitsky Vadim , Mahoney Colleen
Published: April 2003

Acute quantitative electroencephalographic effects of cigarette smoking were examined in 15 smokers within a repeated-measures design which assessed changes in power-spectral estimates following acute pre-treatment with placebo, a dose (20 mg) of mecamylamine, a dose (0.6 mg) of scopolamine and a combined dose of mecamylamine and scopolamine. Compared to sham smoking, the smoking of a single cigarette following placebo pre-treatment reduced absolute and relative power in slow (delta, theta) frequency bands, increased absolute and relative power in alpha and beta frequency bands and accelerated mean frequency. These smoking-induced power changes in slow- and fast-frequency bands were differentially affected by the separate and combined actions of the cholinergic antagonists with treatments involving mecamylamine tending to abolish smoking-induced slow-frequency absolute power reductions and fast-frequency relative power increments. Self-ratings of smoking-induced increases in alertness were altered by mecamylamine and combined treatments while sensory aspects of cigarette smoking were only altered with combined mecamylamine and scopolamine pre-treatment. The results are discussed with respect to brain-behaviour relationships and mechanisms maintaining the smoking habit.
Modulation of Calcium and Potassium Currents by Lamotrigine
Authors: Grunze Heinz , von Wegerer Jörg , Greene Robert , Walden Jörg
Published: April 2003

Actions of the new antiepileptic drug lamotrigine (LTG) were characterized using extracellular and whole cell patch clamp recordings from rat CA1 and CA3 pyramidal cells in vitro. The results suggest that LTG, beside its previously described effect on the fast sodium inward current, also modulates – presumably voltage-gated – calcium currents and the transient potassium outward current ID. These may be effective mechanisms to inhibit pathological excitation in epilepsy and may be of potential benefit in treating underlying cellular disturbances in bipolar disorder.
New Antiepileptic Drugs and Psychopathology
Authors: Trimble Michael
Published: April 2003

The literature on the effects of anticonvulsant drugs on behaviour is reviewed, with particular attention to the new agents. Positive psychotropic effects, and negative influences on behaviour are noted. The latter include depression and psychoses. The drugs most involved seem to be those with GABAergic properties, and the role of forced normalisation is discussed.
Lamotrigine and Gabapentin
Authors: Ferrier I.N.
Published: April 2003

The anticonvulsants carbamazepine and sodium valproate have efficacy in hypomania, bipolar depression and in the prophylaxis of bipolar disorder. This paper reviews published evidence on the effects of the new anticonvulsants gabapentin and lamotrigine in bipolar disorder. The conclusion is that there is good evidence from open studies to indicate that randomised double-blind trials of these compounds should be carried out. The pharmacology of these anticonvulsants is reviewed and putative predictors of good response identified.
Renal Impairment as a Possible Side Effect of Gabapentin
Authors: Grunze Heinz , Dittert Sebastian , Bungert Martina , Erfurth Andreas
Published: April 2003

A bipolar I manic patient was treated successfully by adding gabapentin to perazine and clonazepam. Also initially tolerated well, an increase of creatinine after several weeks of GP (2000 mg) was observed which was reversible after discontinuation of GP. It is suggested that the possibility of renal dysfunction should be kept in mind with the usage of gabapentin.
Female Genital Disorder as Adverse Symptom of Lamotrigine Treatment
Authors: Erfurth Andreas , Amann Benedikt , Grunze Heinz
Published: April 2003

The new anticonvulsant, lamotrigine, is becoming an important tool in the treatment of bipolar disorder, including bipolar depression. Its efficacy in bipolar depression might be linked to its inhibition of serotonin uptake. We present the case of a female schizoaffective patient successfully treated with 400 mg of lamotrigine developing considerable genital disorder, a side effect well known from the treatment with selective serotonin reuptake inhibitors (SSRIs). We suggest that female genital disorder induced by high doses of lamotrigine is a serotoninergic side effect.
Regional Cerebral Blood Flow in Schizophrenia Using Stable Xenon-Enhanced Computed Tomography
Authors: Mori Kazuhiko , Teramoto Katsuya , Nagao Masatsugu , Horiguchi Jun , Yamawaki Shigeto
Published: April 2003

To investigate the regional cerebral blood flow (rCBF) and the factors affecting the rCBF in schizophrenia, we measured the rCBF using stable xenon-enhanced computed tomography in 118 schizophrenic patients and 21 healthy subjects. A multiple regression analysis was applied to assess the potential affecting factors, i.e. age, gender, duration of illness, dose of antipsychotics and usage of antiparkinsonism and antianxiety drugs. The rCBF of the schizophrenic patients was significantly lower than that of the healthy subjects in all regions except for the occipital region. The rCBF was decreased with increasing age in both groups to the same extent. The dosage of antipsychotic drugs taken had a significant regression relationship with the rCBF in the bilateral thalamus.
Apolipoprotein E Genotype and Schizophrenia
Authors: Chen Jen-Yeu , Hong Chen-Jee , Chiu Hsien-Jane , Lin Chih-Yuan , Bai Ya-Mei , Song Hsiu-Li , Lai Hao-Che , Tsai Shih-Jen
Published: April 2003

Schizophrenic disorders are complex genetic disorders and may involve multiple genes of small effect. The presence of apolipoprotein E (apoE) is associated with several neuropsychiatric disorders. Previous studies on apoE genotype distribution in schizophrenia have reported conflicting findings. We studied the genotype frequencies in a large group of schizophrenic patients. The genotype distribution was significantly different between the schizophrenic patients and the control subjects. Persons who were σ3 carriers have an increased risk of schizophrenia. This result suggests that apoE isoforms may play a functional role in the pathogenesis of schizophrenic disorders. Some possible mechanisms regarding the effect of apoE on the development of schizophrenia are discussed.
Lithium and Haloperidol Treatments Differently Affect the Mononuclear Leukocyte Gαs Protein Levels in Bipolar Affective Disorder
Authors: Karege Félicien , Golaz Jean , Schwald Michèle , Malafosse Alain
Published: April 2003

Despite numerous suggestions of the involvement of GTP-binding proteins in the mechanisms of action of psychoactive drugs in bipolar affective disorder, few studies have been conducted during the drug treatment of patients. The aim of the present study was to investigate the effects of a mood stabilizer and an antipsychotic drug on Gαs proteins. Patients with bipolar affective disorder under lithium treatment with or without haloperidol were assessed with respect to their mononuclear leukocyte (MNL) Gαs subunit protein. Gαs-45 protein subunit levels were analyzed by the Western immunoblot method. The subjects consisted of a group of 20 patients, all diagnosed as euthymic bipolars, and a comparison group of 15 drug-free healthy subjects. Results showed that Gαs levels were significantly decreased in the bipolar patients (BP) compared to drug-free healthy subjects (Mann-Whitney U test, p < 0.002). The drug effect was evaluated by a factorial analysis of variance and showed significant differences between groups (Kruskal-Wallis H test, p < 0.02). Lithium-treated patients displayed the most decreased Gαs levels (normalized mean values 53.2 ± 31 vs. 122 ± 45% for BP and controls, respectively, p < 0.001), while no change was observed in Gαs levels of haloperidol-treated patients compared to controls (mean values: 124.9 ± 37%; NS). The data indicate that lithium and haloperidol affect the mechanism of Gαs protein signal transduction differently, consistent with previous animal studies.
Impairment of the Correlation between Urinary Contents of Alpha-1-Microglobulin and Ulinastatin Is Induced by Intracerebroventricularly Administered Interleukin-6 in Mice
Authors: Kaku Koichi , Shikimi Tadahiro , Inagaki Takuji , Ishino Hiroshi , Okunishi Hideki , Takaori Shuji
Published: April 2003

We have found previously that the correlation between urinary contents of alpha-1-microglobulin (α1M) and ulinastatin (UT) depends on the type of neuropsychiatric disease. Since interleukin (IL)-1β and IL-6 are closely involved in pathophysiological aspects of various neuropsychiatric diseases, effects of intracerebroventricularly (i.c.v.) administered IL-1β and IL-6 on the correlation between urinary contents of these two glycoproteins were examined in mice, a species in which α1M and UT and also the correlation between the urinary contents thereof are expressed similarly to humans. Indices (volume, contents of creatinine, α1M and UT, and α1M/UT ratio) in urine collected after i.c.v. administrations of 2 and 20 ng of either IL-1β or IL-6 were not statistically different from those of the vehicle-treated (control) groups. Neither IL-1β (2 and 20 ng) nor the lower dose of IL-6 (2 ng) affected the positive correlation between urinary contents of α1M and UT. However, a higher dose of IL-6 (20 ng) nullified the positive correlation for 2 days after administration. Recovery to a positive correlation was thereafter displayed. These findings suggest that central IL-6 plays an important role in correlating urinary contents of α1M and UT without affecting the renal functions.
No Changes in Paired Viral Antibody Titers during the Course of Acute Schizophrenia
Authors: Fukuda Rimmei , Sasaki Tsukasa , Kunugi Hiroshi , Nanko Shinichiro
Published: April 2003

Although there have been many studies surveying the prevalence of specific viral antibodies in a large cohort of patients with schizophrenia, changes in antibody levels during the course of acute illness have not been fully investigated. We conducted a preliminary study investigating levels of antibodies to 5 herpesviruses (herpes simplex virus type 1, cytomegalovirus, Epstein-Barr virus, varicella-zoster virus and human herpesvirus type 6) and 6 other viruses (measles, rubella, mumps, influenza A and B and Japanese encephalitis viruses) in paired sera of 8 patients with acute onset or exacerbation of schizophrenia. Assay for specific immunoglobulin M (IgM) antibody was also performed for herpesviruses and mumps. Neither any relevant change in antibody levels nor appearance of specific IgM antibody was observed for any of the viruses in any of the patients investigated. It is unlikely that the active infection or reactivation of these viruses has direct causal relationship to schizophrenia in these patients.
Smoking History and Aging-Associated Cognitive Decline:An Event-Related Brain Potential Study
Authors: Knott Verner J. , Harr Anne , Mahoney Colleen
Published: April 2003

Although cigarette smoking has been associated with reduced risk for dementia of the Alzheimer type, relatively little is known about the central impact of a lengthy smoking history, particularly with respect to the cognitive effects, on the normal aging brain. Given that elderly adults have been reported to exhibit poor short-term memory in conditions requiring divided attention, this study utilized behavioral performance and event-related potential (ERP) measures to compare groups (n = 10/group) of young (18–39 years) and elderly (64–81 years) adult smokers and nonsmokers during a continuous visual word recognition task carried out alone and concurrently with an auditory (oddball) tone discrimination task. Young and elderly adult smokers had average smoking histories of 9.3 and 52.0 years, respectively. Significant aging (young > elderly adults) and task (single-task > dual-task) effects were observed for performance accuracy and speed measures as well as for N400/P600 ERP waveform components elicited by ‘old/new’ word recognition and P300 ERP indices elicited by auditory target detection. The effects of smoking history were limited to the P600 component, which showed faster latencies in elderly smokers than elderly nonsmokers and young nonsmokers. Young smokers exhibited longer latencies than young nonsmokers. The results were discussed in relation to normal and pathological cognition in the elderly.
Potentiation of Antidepressants with Lithium or Carbamazepine in Treatment-Resistant Depression
Authors: Rybakowski Janusz K. , Suwalska Aleksandra , Chłopocka-Woźniak Maria
Published: April 2003

Fifty-nine patients with treatment-resistant depression were randomly allocated an addition of either lithium (Li; 31 patients) or carbamazepine (CBZ; 28 patients) to ongoing antidepressant treatment. The therapeutic efficacy of both strategies, assessed after 28 days, was not significantly different. In the Li group, clinical improvement significantly correlated with decrease in thyroxine concentration. Also, a decrease in cortisol level in Li responders and an increase in nonresponders was observed, suggesting a regulatory effect of Li on the hypothalamic-pituitary-adrenal axis activity. CBZ responders had lower baseline severity of depression than CBZ nonresponders and clinical improvement significantly correlated with increase in erythrocyte ATPase activity in the CBZ group.
The Influence of Clozapine and Typical Neuroleptics on Information Processing ofthe Central Nervous System under Clinical Conditions in Schizophrenic Disorders: Implications for Fitness to Drive
Authors: Grabe H.J. , Wolf T. , Grätz S. , Laux G.
Published: April 2003

The present study investigates the psychomotor performance of schizophrenic inpatients receiving neuroleptic medication and comedication according to their clinical demands in regard to their fitness to drive. The hypothesis was tested that even under polydrug medication, the clozapine-treated patients (n = 10) would have a superior performance compared to the patients taking classical neuroleptics (n = 18). The data were collected by technical equipment (Act and React Testsystem) measuring reaction time, vigilance, visual perception and stress tolerance. The patients’ driving ability turned out to be equally impaired in both treatment groups; 11% of the patients passed all tests without major impairment; 32% of the patients showed some impairments that required individual evaluation of their driving ability; 57% were considered to be severely impaired and driving could not be recommended. Except for one test, no significant group differences in psychomotor reaction performance were obtained. These results are discussed concerning limitations and consequences.
The Human Serotonin Receptor Gene (HTR2) MspI Polymorphism in Japanese Schizophrenic and Alcoholic Patients
Authors: Yoshihara E. , Nakamura K. , Itoh M. , Ameno K. , Takeuchi Y. , Ijiri I. , Iwahashi K.
Published: April 2003

Epidemiological and genetic studies of alcoholism and schizophrenia have been performed, and in this study, the human serotonin receptor (HTR2) polymorphism was examined in 75 alcoholics and 31 schizophrenic patients. We found that there might not be a significant difference between these psychiatric disease patients and controls in the frequency of the C1/C2 HTR2 gene (MspI polymorphism). The results suggest that the human HTR2 MspI polymorphism might not be associated with a risk factor for developing alcohol dependence or susceptibility to schizophrenia. It is possible that there may be a racial difference in the frequency of the C1/C2 gene between Japanese and Caucasians. Further studies are required to determine whether or not the novel serotonin receptor polymorphism reflects the pathogenesis of alcoholism or schizophrenia.
Policosanol, Reaction Time and Event-Related Potentials
Authors: Fontani Giuliano , Maffei Domenico , Lodi Leda
Published: April 2003

The aim of the present study was to compare the results of a 1-week, double-blind placebo-controlled trial investigating the effects of isopolicosanol and octacosanol on reactivity and related brain activity. In particular, reaction time (RT) and event-related potentials such as contingent negative variations (CNV) and P300 (P3) have been studied. Thirty sedentary healthy students were tested before and after treatment (3.6 mg/die for 7 days) with orally administered tablets of placebo (group A), isopolicosanol (B) and octacosanol (C). RT were studied according to three procedures: simple RT (SRT), go/no-go RT (GRT) and choice RT (CRT). Results show that before treatment, there were no significant differences between groups A, B and C. After treatment, the RT of group A was unchanged, while the RT of groups B and C were reduced. In group B, in the SRT test, the reduction of RT was accompanied by electrical data exhibiting increased amplitudes of CNV and shorter latencies of P3. These results show that the main effect on reactivity and event-related potentials can be ascribed to policosanol and is mainly evident in the SRT test.
Is MDMA (‘Ecstasy’) Neurotoxic in Humans? An Overview of Evidence and of Methodological Problems in Research
Authors: Curran H. Valerie
Published: April 2003

Evidence from research with a range of animal species, from rodents to non-human primates, has shown that MDMA (±3,4-methylenedioxymethamphetamine) is neurotoxic. This article explores the evidence that MDMA may be neurotoxic in humans by briefly overviewing three types of research: (1) neurobiological, (2) psychological/somatic and (3) psychiatric. The first type of evidence derives from neuropharmacological and neuroendocrine studies, the second type focuses on psychological function and somatic symptoms in MDMA users, and the third involves studies of psychiatric cases in people who have taken MDMA. Evidence from these types of studies is indirect and differs in the degree to which any causative links are implied between observed effects, MDMA use and human neurotoxicity. These issues are critically discussed within the context of the wide-ranging methodological problems in human research with MDMA.
Alterations of Continuous MEG Measures during Mental Activities
Authors: Fell Jürgen , Röschke Joachim , Grözinger Michael , Hinrichs Hermann , Heinze Hans-Jochen
Published: April 2003

In a pilot study, we investigated the topography of 11 continuous MEG measures for the eyes-opened and eyes-closed condition together with three simple mental tasks (mental arithmetic, visual imagery, word generation). One-minute recordings for each condition from 16 right-handed subjects were analyzed. The electrophysiological measures consisted of 6 spectral band measures together with spectral edge frequency and spectral entropy, plus the time-domain-based entropy of amplitudes (ENA) and the nonlinear measures correlation dimension D2 and Lyapunov exponent L1. In summary, our results indicate a pronounced task-dependent difference between the anterior and the posterior region, but no lateralization effects. Although the nonlinear measures ranged in the middle field with respect to the number of significant contrasts, they were the only ones to be partially successful in discriminating the mental tasks from each other. The most efficient measure turned out to be the ENA. Under mental activation the ENA was larger than in both no task conditions (eyes opened and eyes closed). This finding reflects lower variations of the maximum amplitude during performance of mental tasks than during no task states.
Effects of Antidepressants on γ-Aminobutyric Acid- and N-Methyl-D-Aspartate-Induced Intracellular Ca2+ Concentration Increases in Primary Cultured Rat Cortical Neurons
Authors: Takebayashi Minoru , Kagaya Ariyuki , Inagaki Masatoshi , Kozuru Tosiro , Jitsuiki Hiroaki , Kurata Kenichi , Okamoto Yasumasa , Yamawaki Shigeto
Published: April 2003

We investigated the effects of antidepressants on the intracellular Ca2+ concentration ([Ca2+]i) increases induced by γ-aminobutyric acid (GABA) or N-methyl-D-aspartate (NMDA) in primary cultured rat cortical neurons using fluorescence imaging. Acute treatment with imipramine inhibited GABA- and NMDA-induced increases in [Ca2+]i in a concentration-dependent manner. Doses of 30 μM clomipramine, desipramine, amoxapine and maprotiline also inhibited both the GABA- and NMDA-induced [Ca2+]i increases significantly. Both inhibitory effects of the five major antidepressants on the GABA- or the NMDA-induced [Ca2+]i increases were well-correlated. Imipramine could inhibit significantly high-K+-induced [Ca2+]i increases. Our previous study has already shown that the GABA-induced [Ca2+]i increase involves a similar pathway to high-K+-induced Ca2+ influx. In conclusion, imipramine and several other antidepressants have acute inhibitory effects on the GABA-, NMDA- and high-K+-induced [Ca2+]i increases, suggesting that these inhibitory effects are not related to specific receptors. One possibility is that these effects may be commonly mediated via part of the high-K+-induced [Ca2+]i pathway.
Tissue-Specific Regulation of the Peripheral Benzodiazepine Receptor by Antidepressants and Lithium
Authors: Leschiner Svetlana , Weizman Ronit , Shoukrun Rami , Veenman Leo , Gavish Moshe
Published: April 2003

Peripheral benzodiazepine receptors (PBR) have been identified in peripheral organs as well as in brain glial cells. PBR differ from central benzodiazepine receptors (CBR) in their lack of coupling to the γ-aminobutyric acid receptors and the chloride ion channels. We investigated the effect of 21 days administration, followed by 7 days withdrawal, of fluvoxamine (10 mg/kg), desipramine (10 mg/kg) and lithium carbonate (25 mg/kg) on PBR and CBR binding characteristics in male Sprague-Dawley rats. All three agents significantly increased PBR density in the testes and adrenals. All tested drugs induced a significant decrease in PBR density in the kidney and liver. After withdrawal, PBR density remained decreased in the liver in all three groups and in the kidneys of the desipramine- and lithium-treated animals. In the cerebral cortex, CBR density increased in response to all three agents, whereas PBR density decreased significantly in response to desipramine and lithium carbonate. Chronic treatment with fluvoxamine, desipramine and lithium carbonate is apparently associated with a modulation in PBR expression in the testes, adrenals, kidneys, liver and brain, and in CBR expression in brain. The relevance of these tissue-selective alterations to the antidepressive and/or anxiolytic effects of these agents, or their adverse effects, still needs to be determined.
Adult Levels of Testosterone Alter Catecholamine Innervation in an Animal Model of Attention-Deficit Hyperactivity Disorder
Authors: King Jean A. , Kelly Terri-Ann N. , Delville Yvon
Published: April 2003

The spontaneously hypertensive rat (SHR) has been used as an animal model of attention-deficit hyperactivity disorder (ADHD). This disorder, which is most prevalent in males during childhood, persists in adulthood more frequently in females. Since other work has shown that neonatal testosterone levels may be a contributing factor in the expression of ADHD-like behavior, the present study was designed to determine whether androgen levels also altered the neurobiology of adult SHRs compared to Wistar (WKY) controls. Males castrated on postnatal day 45 were implanted with testosterone, and the density of tyrosine-hydroxylase-immunoreactive (TH-ir) fibers (an indicator of catecholamine innervation) in the frontal cortex was compared between animals. The data show that testosterone-treated SHRs were associated with higher levels of TH immunoreactivity in the frontal cortex and hippocampus than WKY rats. These results may explain why high circulating levels of testosterone during adulthood do not support an increase in ADHD-like behavior in both the animal model and human males.