Glial reactivity after antipsychotic treatment. An experimental study in rats and its implications for psychiatry.

INTRODUCTION: The importance of the glial cells in the function of the nervous system and in its pathology has been the object of multiple studies in the last years. Specifically, their role in the action of the antipsychotics is debated. Our study has analyzed glial reactivity in rats treated with antipsychotics. METHODOLOGY: In a first ultrastructural study of the arcuate nucleus of the hypothalamus, the animals were treated with chlorpromazine for 40 days, and were sacrificed at the end of the treatment, after 20 days of rest without treatment. In another series of studies, with the light microscope and immunohistochemistry we evaluated the immunoreactivity of the glial fibrillary acidic protein (GFAP) in six regions of the central nervous system of rats treated with typical and atypical antipsychotics. RESULTS: With the electron microscope, the animals treated with chlorpromazine showed a significant reduction of the axosomatic synapses on the neurons of the hypothalamic arcuate nucleus and an increase of glial presence, as noted by the greater amount of astrocyte processes. The mentioned modifications were reversible, tending to normalize in a group of animals sacrificed 20 days after completion of the treatment. In the immunohistochemical study, the glial reaction was important in the territory of the nucleus accumbens with all the antipsychotics, moderate in the cingulate cortex, although only with atypical antipsychotics, and scarcely significant in the rest of the regions. CONCLUSIONS: Our results confirm that the glial cells are targets of the antipsychotic action, and this will allow us to better understand the action of these drugs and the role of the glial cells in the normal function of the nervous system and in the mental disease.

Reactividad glial tras el tratamiemto con antipsicóticos. Estudio experimental en ratas e implicaciones para la psiquiatría / Glial reactivity after antipsychotic treatment. An experimental study in rats and its implications for psychiatry

Introducción. La importancia de las células gliales en la función del sistema nervioso y en su patología ha sido objeto de múltiples estudios en los últimos años. Concretamente se debate su papel en la acción de los antipsicóticos. Nuestro estudio analiza la reactividad glial en ratas tratadas con antipsicóticos. Metodología. En un primer estudio ultraestructural del núcleo arcuato del hipotálamo, los animales fueron tratados con clorpromacina durante 40 días, sacrificándose al final del tratamiento y tras 20 días de descanso. En otra serie de estudios, con el microscopio de luz y con técnicas inmunohistoquímicas valoramos la reacción a la proteína glial fibrilar ácida (GFAP) en seis regiones del sistema nervioso central de ratas tratadas con antipsicóticos típicos y atípicos. Resultados. Con el microscopio electrónico, las ratas tratadas mostraron una reducción significativa de las sinapsis axosomáticas sobre las neuronas del núcleo arcuato del hipotálamo, así como un incremento de la presencia glial evidenciable por la mayor cantidad de laminillas de astrocitos. Las modificaciones mencionadas son reversibles, tendiendo a normalizarse en los animales sacrificados a los 20 días de finalizado el tratamiento. En el estudio inmunohistoquímico la reacción astrocitaria fue muy importante en el territorio del núcleo accumbens con todos los antipsicóticos, moderada en la corteza cingular, aunque sólo con los atípicos, y discreta en el resto de las regiones. Conclusiones. Nuestros resultados confirman que las células gliales son diana de los antipsicóticos, lo que ha de contribuir a entender mejor la acción de estos fármacos y el papel de las células gliales en el normal funcionamiento del sistema nervioso y en la enfermedad mental (AU)

Introduction. The importance of the glial cells in the function of the nervous system and in its pathology has been the object of multiple studies in the last years. Specifically, their role in the action of the antipsychoticsis debated. Our study has analyzed glial reactivity in rats treated with antipsychotics. Methodology. In a first ultrastructural study of the arcuate nucleus of the hypothalamus, the animals were treated with chlorpromazine for 40 days, and were sacrificed at the end of the treatment, after 20 days of rest without treatment. In another series of studies, with the light microscope and immunohistochemistry we evaluated the immunoreactivity of the glial fibrillary acidic protein (GFAP) in six regions of the central nervous system ofrats treated with typical and atypical antipsychotics. Results. With the electron microscope, the animals treated with chlorpromazine showed a significant reduction of the axosomatic synapses on the neurons of the hypothalamic arcuate nucleus and an increase of glial presence, as noted by the greater amount of astrocyte processes. The mentioned modifications were reversible, tending to normalize in a group of animals sacrificed 20 days after completion of the treatment. In the immunohistochemical study, the glial reaction was important in the territory of the nucleus accumbens with all the antipsychotics, moderate in the cingulate cortex, although only with atypical antipsychotics, and scarcely significant in the rest of the regions. Conclusions. Our results confirm that the glial cells are targets of the antipsychotic action, and this will allow us to better understand the action of these drugs and the role of the glial cells in the normal function of the nervous system and in the mental disease (AU)

López Ibor frente a Freud y precursor de la moderna nosología psiquiátrica / López Ibor versus Freud and forerunner of modern psychiatric nosology

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Consideraciones sobre el mecanismo de acción de los antidepresivos / Considerations on the mechanism actino of antidepressant agent

Los autores, después de un breve estudio de las vicisitudes que experimentan los antidepresivos desde que se ingieren por vía oral o parenteral en el organismo y de la utilidad de medir los niveles plasmáticos, se ocupan de las más recientes investigaciones sobre el mecanismo de acción de los mismos, superando las posiciones simplistas de sus relaciones con los neurotransmisores y los receptores sinápticos. Se señalan las diferencias conocidas entre los diversos antidepresivos, comparando las situaciones de las sinapsis en estado eutímico y depresivo sin tratamiento con las que se producen con los distintos antidepresivos. La conclusión más importante es que el mecanismo íntimo de acción de los antidepresivos todavía es poco conocido, siendo fundamental su intervención en la cascada de acontecimientos postsinápticos que llevan por transducción la señal hasta el genoma, planteando una nueva comprensión entre factores genéticos y ambientales en la depresión.. (AU)

[Clinical and epidemiological study of depression and aggressiveness in a rural population center]. / Estudio clínico y epidemiológico de las depresiones y la agresividad en un núcleo de población rural.

In a rural community of the province of Salamanca we studied the magnitude and distribution of depression and aggressiveness in a psychopathological study, following a previously established protocol of methods that includes the Hamilton Scale of Psychiatric Evaluation, the EPI Personality Questionnaire, Instrument I for the measurement of aggressiveness of Ledesma et al., and Pöldinger's Evaluation Scale for the risk of suicide (for suicidal tendency?). Forty-three depressive patients were found, forming 7.46% of the whole population studied (6.29% of the male population and 8.75% of the female one). We also studied the characteristics profiles of the depressive patients, the relationship with being firstborn and the psychiatric history and suicide cases in direct family members, establishing comparisons with a control group of non-depressive subjects.

[An MMPI subscale for assessment alexithymia in duodenal ulcer patients]. / Una subescala del M.M.P.I. para la medida de la alexitimia en pacientes con E.U.D.

We measured the alexithymia by the Kleiger-Kinsman scale in 36 patients with D.U.D. We employed 34 patients with irritables Bowel Syndrome and 30 patients with chronic organic pathologia as control groups. Our results show two possible conclusions: 1) The absence alexithymia's specificity in our ulcerous patients and/or the incapacity of this M.M.P.I.'s subescale to discriminate this feature in the psichosomatic diseases.

[The personality of wives of alcoholic patients]. / Estudio de la personalidad en las esposas de pacientes alcohólicos.

This work is a study of the personality of the wives of alcoholic patients composed by means of a structures interview, the MMPI personality questionnaire and the Instrument I used to evaluate aggressivity. Among the discoveries made, we must emphasize that 20% of the wives knew of their partner's excessive alcohol consumption before marriage, while married, 75% were victims of some kind of violent incident, 43% had personal psychopathological backgrounds, 15% were "repeaters wives" "those who had alcoholic parents). In the MMPI test, these women represent a significantly high profile, in which the scales Hs, D and Hy are the highest, amongst which their most outstanding personality traits include passivity, dependency and insecurity. Furthermore, those wives whose husbands have had relapses, represent a higher Pd scale than the other group. The Instrument I used to evaluate aggressivity also emphasizes this passive-aggressive tendency in the wives.

[Duodenal ulcer disease. A controlled study of aggressiveness and other personality factors]. / La enfermedad ulcerosa duodenal. Un estudio controlado de la agresividad y otros factores de la personalidad.

We study the aggressivity level and its direction in the context of personality, in 36 patients with DUD (23 males and 13 females). We employed 30 patients with chronic disease (15 men with COPD and 15 female with arthrosis) as control groups, in addition to the normal population. The purpose of this investigation is to determinate if suffering or chronicity could determinate psychopathological findings similar to those described in the literature about patients with DUD. The results point out that we can not consider a specific ulcerous personality, but a psychophysiological reaction or psychopathological alterations resulting from a somatic disease, on the other hand the autoaggressivity factor pulsion-inhibition, is the most reliable variable when compared with control groups (p less than 0.05-0.01).

[Measurement of aggressiveness and its direction in patients with duodenal ulcer. A double-control study]. / La medida de la agresividad y su dirección en pacientes con ulcus duodenal. Un estudio de doble control.

We measure aggressivity in 36 patients with DUD (duodenal ulcer disease). We use two control groups as sample: normal population and other group of chronic organic pathologies. The results denote that the autoaggression-inhibition factor is the best discriminate variable to our group of duodenal ulcer patients of both sexes.

[Psychopathologic aspects of cancer in gynecology. Cancer of the breast]. / Aspectos psicopatológicos del cáncer en ginecología: cáncer de mama.

We study 31 female patients diagnosed and treated with the usual method for breast cancer. We use the clinical report and psychobiography, Instrument I to measure the aggressivity and M.M.P.I. The most significant results are: slowness in the first examination, influence of psychosomatic life events and spontaneous signs during the interviews, increase of autoaggressivity, and raising of the neurotic triad, dependence and introversion. It is clear from this statement the general conclusion of this patients having a want of contact so that their psychological signs don't develop into psychopathological.

[Personality and aggressiveness in cancer patients]. / Estudio de la personalidad y de la agresividad en pacientes cancerosos.

The authors studied the Personality and Aggressiveness of fifty-three cancer patients by using MMPI and the Instrument I for the Aggressiveness Measurements. The common characteristics in all of then were that they suffered solid tumors, were submitted to hospital treatments and had an absence of psychiatric illness in their personal history. Among the results that stand out most is the sensations of change that the patients experience due to their own illness, the hospitalization and the treatments which they undergo. There exists on increase of self-aggressiveness or a decrease of hetero-aggressiveness which predominates the scales of depression and social introversion, with a decrease of inner strength. In any case, the neuroticism and the dependence are increased and there are decreases in the scales of psychopathic deviation and domination. The four psychosis is staying normal, the hysteria is decreased in men and the hypochondria is increased in women. The defence mechanism that predominates are the denial and the avoidance reaction.

[Aggressiveness and the teaching function]. / Agresividad y función docente.

The authors study aggression with the "Instrument I to measure aggression of Ledesma Jimeno, Rodrigues Isidoro and Izquierdo de la Torre" in a sample of teachers (N = 48) made up of 15 university professors and 33 non-university professors (primary school, secondary school and professional training). The teacher sample is compared with a control sample of 479 men. The group of non-university professors showed more self-aggression and less aggression toward others than the control sample and university sample did. Both groups of teachers showed high levels of "technical intelligence". The aggression of the university professors was very similar to the control group and showed special peculiarities giving high values of intrapsychic incoherence that made their conduct more unforeseeable, with higher creative dispositions and a higher risk to their mental health than the other two groups studied.

[Psychosomatics and cancer]. / Psicosomática y cáncer.

The cancerous patient who suffers a coinciding psychiatric illness shows, according to the M.M.P.I., signs of a depressive personality with marked introversion and dependence. The aggressivity test shows that self-aggressiveness coincides with inhibition and lethargy tone. An accumulation of stress factors and events stand out in patients with depression (72%), which do not appear in those patients diagnosed as having neuroses and schizophrenia. There is a need for psychiatric attention which contributes to treating the patient interdepartmentally; thus relieving both the moral and physical pain which these patients suffer.

[Relationship between psychiatric emergencies and meteorologic factors]. / Relaciones entre las urgencias Psiquiátricas y los factores meteorológicos.

Man's environment, natural as well as artificial, may exert a pathogenic influence on man's life, according to which we could divide the population in meteorosensitive (about 60%) and non meteorosensitive. Psychic patients and patients who suffer from certain organic diseases are those ones who more frequently behave as meteorosensitive. We accept this as starting point of our work. In our paper we analysed statistically the relation among different cosmo-meteorologic factors in the incidence of psychiatric emergencies during two years separated by five years and the probable existence of seasonal rhythms in the different studied diagnostic categories. As well as partial results for every diagnostic category we elaborate as final conclusion that these relations have a multifactorial character, that is to say, there are several factors that interact to unchain certain pathology in meteorosensitive people. We emphasize the existence of seasonal cycles in certain psychiatric syndromes. These conclusions are seen specially in personality disorders, suicide attempts, anxiety crisis and disorders, drug addictions and psycho-organic diseases.

Simulation of plasma bentazepam levels in multiple dosage regimens from parameters established by non-linear regression and bayesian estimation.

In the present study, a simulation was made of the time-course of the plasma levels of bentazepam, administered orally at a dose of 25 mg with dosage intervals of 8, 12 and 24 h over 5 days of treatment. The pharmacokinetic parameters corresponding to a single-compartment model were calculated in a previous study with 10 patients who received the drug in a multiple dosage regimen, using all the data relating to plasma levels even though they corresponded to different administrations, by non-linear regression employing programs based on homoscedastic, heteroscedastic and bayesian estimation methods. The mean values of the kinetic parameters obtained previously and used in the present study were as follows: for the absorption constant, mean values of 2.33, 2.18 and 2.75 h-1 were used; for the elimination constant, the values used were 0.10, 0.09 and 0.22 h-1 and for the apparent distribution volume, the values used were 1.89, 2.89 and 0.80 l/kg, with each of the above-mentioned calculation programs, respectively. The highest value for the maximum concentration at steady state proved to be 313.2 ng/ml for a dosage interval of 8 h according to the parameters established with the program using homoscedastic estimation. In the same case (homoscedastic estimation) the highest value of the minimum at steady state was 168.7 ng/ml. By contrast, the lowest value of the maximum value at steady state--129.3 ng/ml--was obtained with a dosage interval of 24 h using the parameters of the heteroscedastic estimation method, while the lowest value of the corresponding minimum was also observed for an interval of 24 h but using the parameters of the bayesian estimation; this was 2.8 ng/ml.

Parametrization by non-linear regression and bayesian estimation of bentazepam in a multiple dosage regimen in humans.

The plasma levels of bentazepam were determined by an HPLC technique in a total of 10 patients receiving the drug orally in pill form who were on a dosage regimen with the drug administered every 8, 12 or 24 h. Blood samples were taken three times following the administration of the first and last dose and at times, immediately after the administration of intermediate doses. The parameters corresponding to a one-compartment kinetic model were calculated in each patient by using all the data on plasma levels still corresponding to different administrations by non-linear regression and applying programs with homoscedastic, heteroscedastic and bayesian estimation. The absorption constant had mean values of 2.33, 2.18 and 2.75 h-1. The elimination constant proved to be equal to 0.10, 0.09 and 0.22 h-1 while for the apparent distribution volume mean values of 1.89, 2.89 and 0.80 l/kg were found with each of the estimation programs employed, respectively. The values found for each of the kinetic parameters and with each of the programs were subjected to the non-parametric Kruskal-Wallis test with a view to detecting the presence or absence of statistically significant differences. The discrimination of the program that yielded the best fit was performed by linear regression between the values found for the plasma calculations and those calculated theoretically at the same time with each of the programs.