תוצאת חיפוש

Animal Models of Psychiatric Diseases: Possibilities, Limitations, Examplesand Demonstration of Use

Haim Einat, RH Belmaker

Beer Sheva Mental Health Center, Faculty of Health Sciences, Ben Gurion University of the Negev, Beer Sheva, Israel

Animal models of psychopathology serve as a central tool for psychopharmacologists in their attempts to develop new, more efficient medications for psychiatric disorders, and in the efforts to explore the mechanisms of conventional and novel drugs. The development of efficient models for psychiatric diseases is complicated since the mechanisms of the disorders are not clear, major parts of the diagnosis depend on verbal communication with the patient and many of the symptoms are expressed mainly through the subjective experiences of the afflicted individual.

Inspite of these difficulties, effective models were developed for most psychiatric diseases. The development of such models is based on their validation in three different dimensions: face validity - behavioral similarities between the model and the disorder; construct validity - similarities between the mechanisms related to the model and a mechanistic theory of the disease; predictive validity - that the model response to the conventional medications that are effective in the disease and will not respond to drugs that are not effective in the disease.

The present paper presents three known models of depression; each induced in a different way and therefore represents a group of models:

*     Reserpine-induced hypoactivity - represents the group of pharmacologically induced models.

*     Forced swim test - represents the group of behaviorally induced models.

*     Flinders Sensitive Line - represents the group of genetically induced models.

The use of these models in an attempt to examine the range of action of a new potential antidepressant and its mechanisms of action is demonstrated with a recent set of experiments with inositol.

Jet Lag Causing or Exacerbating Psychiatric Disorders

Gregory Katz, Rimona Durst, Josef Zislin, Hilla Knobler, Haim Y. Knobler

Kfar Shaul Mental Health Center, Jerusalem (Affiliated with the Hebrew University-Hadassah Medical School, Jerusalem)

Desynchronization of circadian rhythmicity resulting from rapid travel through at least 4 time zones leads to symptoms of jet lag syndrome. The most commonly experienced symptoms in normal individuals are sleep disorders, difficulties with concentrating, irritability, mild depression, fatigue, and gastrointestinal disturbances.

There is strong evidence relating affective disorders to circadian rhythm abnormalities, such as occur in jet lag. Less convincing suggestions relate jet lag to psychosis. We presume, relying on the literature and our accumulated experience, that in predisposed individuals jet lag may play a role in triggering exacerbation of, or de novo affective disorders, as well as, though less convincing, schizophreniform psychosis or even schizophrenia. An illustrative case vignette exemplifies the possible relationship between jet lag following eastbound flight and psychotic manifestations.

Symptom Severity among Chronic Schizophrenics in Hospital and in the Community

Haim Y. Knobler, Dorit Ben Ami, Orna Intrator, Shlomit Katz, Daniela Moshe, Yaacov Lerner

Jerusalem Mental Health Center, Falk Institute of Psychiatric and Behavioral Studies, and Dept. of Statistics, Hebrew Universitry of Jeruselam

We compared severity of symptoms of chronic schizophrenics in a psychiatric hospital with those treated in its outpatient clinics.

The Positive and Negative Syndrome Scale and the Mini-Mental State examination were used to assess the schizophrenic symptoms and cognitperformance, respectively, of 25 chronic schizophrenic inpatients matched for gender, age and education with 25 chronic scoutpatients. The Global Assessment Scale and the Clinical Global Impression Scale were used to test global functioning. Assessment included psychiatric and medical history and treatment and demographic characteristics.

In-patients had significantly more positive, negative and general psychiatric symptoms. Their cognitive and general functioning were impaired. Most in-patients also had medical problems. Age of onset of schizophrenia among the in-patients was younger.

Results show a marked difference in severity of symptoms and level of functioning between chronic schizophrenic in-patients and out-patients. These differences should be considered in the planning of discharge of chronic in-patients from psychiatric hospitals into the community.

When are Menopausal Symptoms Psychiatric?

Helen Shoenfeld

Talbia Mental Health Center, Jerusalem

Nervousness, sleep disorders, mood instability and sexual dysfunction are frequent symptoms during menopause. It is commonly believed that they are due to the characteristic menopausal hormonal changes. However, they also commonly occur in psychiatric disorders unrelated to the menopause. The literature deals with the characteristic psychological aspects and studies have examined the ways in which menopausal phenomena are related to the hormonal background and its effect on the brain.

The clinical menopausal picture may be complicated by secondary psychiatric disease. Also, menopausal symptoms and symptoms of previous psychiatric disease may coexist. In addition, menopause may precipitate psychiatric disorders in women predisposed to them.

Accumulated personal myths and expectations related to the menopause are likely to affect the way in which a woman copes with it. Important factors in this connection include education, culture and certain life events. In all such cases precise evaluation of the etiology, with its intermingled gynecological and psychiatric factors is required. Such women should be treated by both a gynecologist and a psychiatrist.

We present 5 cases, 4 of which were sent to the menopause clinic and were then referred for psychiatric evaluation and treatment. The other case presented at a psychiatric clinic due to a first acute psychostate. Laboratory tests showed typical changes of menopause.
 

Clozapine in the Treatment of Schizophrenia

M. Mark, R. Magnezi, O. Luxenburg, M. Siebzehner, J. Shemer

Israel Center for Technology Assessment in Health Care, Sackler Faculty of Medicine, Tel Aviv University

Schizophrenia is associated with brain abnormalities and is typically evidenced by disorganized speech and behavior, delusions, and hallucinations; it usually requires extended hospitalization. Its incidence in the western world is estimated at 4-7 cases/10,000/year.

A method of shortening hospitalization and improving level of functioning is the use of unique medication, including clozapine, which has been in use in Israel for the past 6 years.

We report 327 patients who participated in a community rehabilitation program and were treated with clozapine. They were compared with 417 patients who corresponded to the guidelines of the Director of Mental Health Services for treatment with clozapine, but were not treated with it for reasons not defined in the guidelines.

The study included those 25-44 and 45-64 years of age and according to the division of the population of patients hospitalized in both government and private hospitals. The project demonstrates the savings from use of clozapine as opposed to the alternative of hospitalizing these patients. It also shows the complexity and difficulty in assimilating new technologies, in relation to the influence of social considerations and supplier/insurer accounting on the patterns of technological assimilation.

Neuropsychiatric Side Effects of Malarial Prophylaxis with Mefloquine

T. Minei-Rachmilewitz

Dept. of Psychiatry, Hadassah Hospital Ein Karem, Jerusalem

There has been an increased incidence of malaria among Europeans returning from Africa and Asia. The relatively new antimalarial mefloquine (Lariam) has become extremely popular due to its efficacy in treatinthe wide-spread chloroquine-resistant Plasmodium falciparum.

Mefloquine is used both for prophylaxis and treatment of malaria and is relatively well tolerated. However, since introduced in 1985, there have been over 100 reports of severe neurologic and psychiatric adverse effects associated with its use, including acute psychosis, affective disorders, acute confusional states and seizures.

We describe a 39-year-old woman who developed acute psychosis after being given mefloquine prophylaxis. Adverse effects occur more often after therapeutic rather than prophylactic use, and those with a history of seizures or psychiatric illness are at increased risk of developing these reactions. Physicians should be aware of these possible side effects and prescribe mefloquine only when indicated.

Depression Scale for Research in and Identification of Postpartum Depression

Saralee Glasser, Vita Barell

Health Services Research Unit, Ministry of Health, Sheba Medical Center, Tel Hashomer

Postpartum depression (PPD) is a relatively frequent and serious condition, with negative consequences for the mother, her infant, and the family. From research and clinical experience in many countries, it has been found that PPD can be identified early, and women at risk for developing PPD can be identified before delivery in the framework of primary health care service. The Edinburgh Postnatal Depression Scale (EPDS) has been found valid for this purpose, both in the original English version, and in translation to numerous languages. The Hebrew translation of the EPDS is presented, and it is recommended that Israeli researchers use the same translation to facilitate accumulation of knowledge regarding the epidemiology of PPD and intervention strategies in various Israeli population groups, and for comparison with data from other countries.

Oral Manifestations of Bulimia Nervosa

Doron Aframian, Alice Markitziu

Dept. of Oral Diagnosis, Medicine and Radiology, Hebrew University- Hadassah School of Dental Medicine, Jerusalem

Bulimia nervosa (BN) is an eating disorder frquently accompanied by changes of the hard and soft tissues of the oral cavity and of the salivary glands. Routine dental examination in a 25-year-old woman disclosed oral signs and symptoms characteristic of BN and she was referred for psychiatric evaluation. Oral evaluation of patients suspected of BN is recommended to prevent irreversible damage to the oral and perioral structures.

Quality Assurance in the Mental Health Department of the Israel Defense Forces

Mordechai Mark, Moshe Z. Abramowitz, Orna Intrator, Ehud Bodner, Rami Shklar, Haim Y. Knobler

Mental Health Department, Medical Corps, Israel Defence Forces

A review of quality assurance in the mental health department of the Israel Defence Forces allowed the examination of certain unique elements of quality control which pertain to the military. These include the psychiatric medical board, the computerized documentation of appointments and sessions with soldiers, the psychiatric hospitalization database, control systems implemented in the draft boards, peer-review boards and supervision, and a special officer in charge of handling outside consultations and queries. There were other components of quality assurance and control as well. These instruments are vital in a dynamic system constantly striving to improve clinical performance.

Future plans include the continued use and expansion of quality control boards, the inclusion of quality assurance in the curriculum of mental health officers, and the use of clinical guidelines in working with soldiers. All of this is in keeping with the principle of continuous quality improvement, with the aim of viewing the soldier in need of help as a client.

The Current Compulsory Hospitalization Order and Patients' Rights

Y. Bar-el, R. Durst, J Mazar, J. Rabinowitz, Y. Lerner, H.Y. Knobler

Office of Jerusalem District Psychiatrist; Jerusalem Mental Health Center, Kfar Shaul Hospital; Mental Health Services, Israel Ministry of Health; School of Social Work, Bar-Ilan University; and Falk Institute for Mental Health and Behavioral Sciences, Kfar Shaul (Affiliated with the Hebrew University - Hadassah Medical School)

Israel's "Treatment of Mentally Sick Persons Law" of 1955 was repealed and replaced by the "Treatment of Mental Patients Law" of 1991. Under the latter, the "Compulsory Hospitalization Order" (CHO) defines the new order based on accumulated experience with the old legislation, and on the philosophy that considers the CHO one of the most severely oppressive forms of deprivation of human liberty and rights. The new order sets limits and boundaries for CHO, guarding the rights of those unavoidably committed by force. According to the new law, the district psychiatrist decides upon and issues the order, while the tribunal (District Psychiatric Committee) considers appeals. The order is limited to 1 week, with an option for the district psychiatrist to prolong it on written request for up to 14 days. The tribunal can later prolong the order further.

The objective of this study was to review changes that have occurred following enforcement of the new law in the Jerusalem district. A comparison was made between CHO's issued the year before the new legislation took effect and the year after. The comparison included review of all CHO's and medical files of all patients hospitalized by coercion during 1990 and 1992. It was assumed that there would be a decline in rate and length of hospitalization of patients forced to be committed by the new law.

The main findings refuted this hypothesis. In 1992 there was an increase of 38% in the number of compulsory hospitalizations. This increase derived mainly from increased demands for CHO's from psychiatric emergency rooms. There was also an increase in patients hospitalized by order of the District Psychiatric Committee using its authority under section 10(C) of the law.

Conversely, length of compulsory hospitalization was shorter under the new law.

In light of these findings, it would seem that the new law has only partially fulfilled expectations of reform in individual rights. There is need for further evaluation and follow-up of the CHO in order to determine whether the "Treatment of Mental Patients Law" of 1991 has in fact fulfilled its objectives. Furthermore, it is necessary to determine means, medical or legal, that may possibly advance further the prospective of human rights while maintaining a suitable balance between civil liberties and clinical needs, of over-confinement versus under-treatment, which may lead to neglect or danger.

Comparison between Every-Day and Every-3-Days Fluoxetine in Young, Moderately Depressed Out-Patients

A. Shiber, H. Reuveni, A. Elhayany, I.Z. Ben-Zion

Psychiatric Dept., Psychiatric Division, Soroka Medical Center and Ben-Gurion University of the Negev, Beer Sheba; and Medical Division for Drug Utilization, Kupat Holim Klalit (Sick Fund)

Fluoxetine is now a well-known and often-used specific serotonin reuptake inhibitor (SSRI) and antidepressant. It has a very long active half- life, from 2-16 days. Our hypothesis was that sufficient therapeutic effectiveness would be achieved by prescribing the drug less frequently than once a day.

To establish whether there is a difference between fluoxetine given daily or every 3 days, we assigned 25 outpatients with mild to moderate, acute major depressions (DSM-IV) to receive fluoxetine (20 mg), either each day or every 3 days. The study was open-labelled, using for assessment the HAM-D, GHQ-28 side-effect checklist and clinical judgment questionnaires. Follow-up lasted 6 months.

Results indicated no differences in the clinical outcomes, except for slightly fewer side-effects in the study group. Although the open label design limits drawing definitive conclusions, our preliminary results provide more information, and support our hypothesis that low-dosage fluoxetine is beneficial. However, more comprehensive, double-blind studies are necessary to confirm our preliminary results.

Autonomic Dysregulation in Post-Traumatic Stress Disorder: Power Spectral Analysis of Heart Rate Variability

Hagit Cohen, Uri Loewenthal, Mike A. Matar, Hanoch Miodownik, Zeev Kaplan, Yair Cassuto, Moshe Kotler

Mental Health Center, Israel Ministry of Health; Anxiety and Stress Research Unit, Faculty of Health Sciences; Dept. of Life-Sciences, Ben-Gurion University of the Negev, Beer Sheba

Spectral analysis of heart rate variability (HRV) has been shown to be a reliable noninvasive test for quantitative assessment of cardiovascular autonomic regulatory response, providing a dynamic map of sympathetic and parasympathetic interaction. In a prior study exploring the state of hyperarousal that characterizes the post traumatic stress disorder (PTSD) syndrome, we presented standardized heart rate analyses in 9 patients at rest, which demonstrated clear-cut evidence of a baseline autonomic hyperarousal state.

To examine the dynamics of this hyperarousal state, standardized heart rate analysis was carried out in 9 PTSD patients, compared to a matched control group of 9 normal volunteers. 20-minute ECG recordings in response to a trauma-related cue, as opposed to the resting state, were analyzed. The patients were asked to recount the presumed triggering traumatic event, and the control subjects recounted a significant stressful negative life event.

Whereas the control subjects demonstrated significant autonomic responses to the stressogenic stimulus of recounting major stressful experiences, the patients demonstrated almost no autonomic response to the recounting of the triggering stressful event. The patients demonstrated a degree of autonomic dysregulation at rest comparable to that seen in the control subjects' reaction to the stress model.

The lack of response to the stress model applied in the study appears to imply that PTSD patients experience so great a degree of autonomic hyperactivation at rest, that they are unable to marshal a further stress response to the recounting of the triggering trauma, as compared to control subjects. A subsequent study of the effect of medication on these parameters showed that they are normalized by use of selective serotonin re-uptake inhibitors (SSRI's).

Neither the clinical implications of these findings, nor their physiological mechanisms are clear at present. We presume that they reflect a central effect, as the peripheral automatic effects of SSRI's are relatively negligible.

Feeding Disorders in Infancy: Feeding Interaction Concept in Diagnosis and Treatment

Miri Keren, Samuel Tyano

Community-based Mental Health Baby Clinic, Gehah Hospital and Sackler School of Medicine, Tel Aviv University

In infancy clinical manifestations of psychological distress are mainly somatic. Feeding disorders are one of the most common and nonspecific manifestations of different kinds of disturbed parent-child relationships. These disturbances may have their origins in the baby's constitution and physical status, in the parent's personality structure, or both, as has been conceptualized in the transactional model of normal and abnormal development. Among the daily interactions a baby has with parents, feeding has special inherent impact on the early parent-child relationship because of its psychological meanings. Therefore, feeding disorders, with or without failure to thrive, often reflect various disorders of infancy, still not well recognized in the medical community, such as regulatory disorders, attachment disorders, depression of infancy, disorders of separation-individuation, and post-traumatic eating disorder. 3 clinical cases are brought to increase awareness of psychological distress in the infant, and of feeding disorders as 1 of its manifestations. Each illustrates a different kind of feeding disorder in terms of etiology and pathogenesis. Through these cases we emphasize the need for a multidisciplinary, integrative approach in diagnosis and treatment. Our conceptual background is based both on the transactional model of development (infant and parental factors impact on each other) in a very dynamic paradigm, and on psychodynamic premises. Intrapsychic conflicts and past representations impact heavily on the parenting characteristics. We emphasize the psychological significance of disturbed feeding interactions, with or without failure to thrive.

Treating Mother and Baby in Conjoint Hospitalization in a Psychiatric Hospital

Shmuel Maizel, Vladislav Fainstein, Sarah K. Katzenelson

Dept. B, Eitanim Mental Health Center, Jerusalem

Since 1990 we have been admitting mothers with postpartum psychiatric morbidity together with their babies to our open psychiatric ward. The aim of conjoint hospitalization is to maintain and develop the bond between mother and baby while treating the mother's psychiatric disorder. The presence of the infant in the hospital allows both a thorough evaluation of the mothers' maternal ability and to use the infant as a facilitator of the mothers' recovery by engaging maternal functions. It prevents the infants from being placed in a foster home for the duration of the mothers' hospitalization. Readily available in Britain and Australia, such conjoint hospitalization is controversial and rarely available elsewhere. In the past 5 years we hospitalized 10 women with 11 babies (1 woman was hospitalized twice, after different births). All women had received psychiatric treatment prior to childbirth, but this was the first psychiatric hospitalization for 2 of them. Diagnoses (DSM-IIIR) were chronic paranoid schizophrenia (4), disorder (4), schizo-affective schizophrenia (1) and borderline disorder (1). 8 were suffering from active psychotic symptoms on admission. They were treated pharmacologically, received individual and group psychotherapy, and participated in all ward activities. Families were engaged in marital, family and/or individual therapy according to need. All participated in cognitive-behavior treatment tailored to individual need to build and enrich the mother-infant bond. All improved significantly and were able to function independently on discharge, but in 1 case adoption was recommended.

Folic Acid Deficiency in Chronically Hospitalized Mental Patients

Ivan Fuchs, Leonid Omansky, Yaakov Lerner

Eitanim Mental Health Center, Jerusalem (Affiliated with the Hebrew University-Hadassah Medical School)

Studies over the past 30 years have shown a relationship between folic acid deficiency and psychopathology. FA deficiency was observed more often in depressed and in psychotic patients, in alcoholics, in those suffering from organic mental disorders and in the psycho-geriatric population. In a chronic inpatient population of 120 patients, of the 106 in whom FA serum levels were examined, only 1 had a definitely subnormal level. An additional 16 had close to the lower limit of normal (2 ng/ml) and were considered borderline cases. FA-deficient and borderline patients were then compared to matched patients with normal FA levels on the MMSE and PANSS scales by blinded raters. Small differences were found between the 2 groups. The FA-deficient and borderline patients had more organic and psychotic symptoms, but the differences were not statistically significant.