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Introduction: In recent years, several studies were conducted to explore the potential augmenting effect of oxytocin for the treatment of individuals with severe mental illness. Nonetheless, studies exploring its effects in routine inpatient settings using high-quality randomized controlled trials are scarce. The current study assessed the effect of oxytocin administration on treatment process and outcome among psychiatric inpatients, while employing a rigorous experimental methodology. Methods: A double-blind, placebo-controlled, randomized trial was conducted at a public psychiatric hospital in Israel. Patients (N = 87, 71.3% female participants) were administered intranasal oxytocin/placebo twice daily for 4 weeks, as add-on to usual care. Patients were assessed for severity of anxiety and depression symptoms and their working alliance with their therapist after each therapy session, and treatment outcome was assessed weekly. Multilevel modeling was performed to assess the linear change from pre- to post-treatment. Results: Patients receiving OT demonstrated significantly larger symptomatic improvements (B = −0.01, t [437] = −2.36, p = 0.01). Larger gains were also observed for depression (B = −0.14, p < 0.001 in the OT group, B = −0.06, p = 0.02 in the placebo group) and general distress (B = −0.57, p < 0.001 in the OT group, B = −0.29, p = 0.02 in the placebo group). No significant effect was observed for anxiety, the working alliance, or attachment. Discussion: Oxytocin has the potential to improve treatment outcome among inpatients. Nonetheless, additional controlled research is needed to further assess its effects on therapy process, as well as to account for therapeutic, pharmacological, and neuronal intervening factors.

The authors sought to assess the impact of a continuity-of-care model on quality-of-care measures among hospitalized patients with severe mental illness in Israel. A "continuity-of-care physician" provided psychiatric care to patients during hospitalization and outpatient care after discharge. In the year after the model's implementation, emergency department visits significantly decreased by 32% and rehospitalization rates of patients discharged within 30 and 90 days decreased by 40% and 29%, respectively. The yearly rate of compulsory admissions decreased from 35% to 25%, and the proportion of patients who entered rehabilitation significantly increased (from 9% to 13%). This model shows promise for improving quality of care of patients with severe mental illness admitted to acute psychiatric wards.

The response to placebo is robust in studies of various antidepressant treatments. The strong placebo response, combined with the absence of side-effects, has prompted suggestions to use the ethically sound open-label placebo (OLP) as a treatment for depression. The aim of the present study was to assess the efficacy of OLP as an adjunct to treatment as usual (TAU) in the setting of a randomized controlled trial for the treatment of unipolar depression.Thirty-eight patients (age: 50 ± 17.1; 73.7% females) were randomized to either eight-week OLP treatment (n = 18) or four weeks of TAU followed by four weeks of OLP (n = 20). Clinical and socio-demographic measures were assessed at baseline, after four weeks, and at the end of the trial. Response to treatment was determined using the QIDS SR-16.There was an overall decrease in depression levels over time, F(2,35) = 3.98, p = .028. A significant group x time interaction was found only among non-geriatric patients (65years) with an early onset of depression (50years), F(2,22) = 3.89, p = .036. Post-hoc tests indicated a significant decrease during the first four weeks, but only in the OLP group, t(11) = 2.29, p = .043.Small sample size and the use of a self-report questionnaire to assess depressive symptoms.Our findings support the possibility that OLP is an effective treatment for the relatively young population of depressed patients. Additional studies are warranted to explore the use of OLP in clinical practice.

BACKGROUND The concept of potential-to-experience is a major component in psychodynamic theory and assumed to be an important component of psychotherapeutic technique. However, as this assumption has never been empirically tested, the relationship between such interventions and treatment outcome is unclear. The aim of this pilot study is to explore the relationship between patient-therapist congruence of potential-to-experience engaged statements and the outcome of psychodynamic treatments. METHODS Transcripts of 90 sessions from good- and poor-outcome treatments (N = 18) were encoded using the MATRIX - a novel content analysis tool of psychodynamic psychotherapy. Based on fixed algorithms, this observer-coding system is designed to identify different types of clinical interventions, including those which focus on the potential-to-experience. Total number of MATRIX codes analysed was 11,125. We compared the total congruence/incongruence ratio of such statements in good and poor treatments. The importance of the congruence/incongruence ratio of the potential-to-experience statements was measured by applying general linear models to classify treatment outcome. RESULTS The congruence/incongruence ratio of the potential-to-experience engaged statements was significantly higher in good treatments. In the best model for classifying treatment outcome based on the congruence/incongruence ratios of several parameters, the congruence/incongruence ratio of the potential-to-experience engaged statements was the single most important predictor. DISCUSSION Maintaining the congruence of potential-to-experience engaged statements within the therapeutic session is associated with better clinical outcome. This provides an initial empirical indication to the importance of the potential-to-experience discourse in psychotherapy praxis. PRACTITIONER POINTS The concept of potential-to-experience is a major component in psychodynamic theory and assumed to be an important component of psychotherapeutic technique. The current results suggest that the ability of both patient and therapist to maintain the congruence of potential-to-experience statements within the session may improve clinical outcomes. These findings suggest a practical approach for a better management of the therapeutic process. Mainly, it recommends therapists to implement a very careful, active listening to potential-to-experience-related content throughout the session, while highlighting the patient's associations for their potential to become new modus operandi. Moreover, the current study presents an integrative, micro-level tool that enables the translation of complex theoretical concepts in psychotherapy into measurable constructs, aiming at the creation of a bridge between clinical theory and evidence-based practice.

Background Patient-reported outcome measures (PROMs) and patient-reported experience measures (PREMs) are increasingly recognized as important ways for patients to be more actively involved in their treatment and enhance shared decision-making. Objective The current study investigated the associations between PROMs, PREMs and various symptoms measures reported by clinicians and psychiatric patients. Method One hundred and twenty people admitted to a psychiatric hospital completed two PREMs, one PROM (the shortened version of the Manchester Short Assessment of Quality of Life scale) and Effects of Symptoms on Daily Functioning (the Sheehan Disability Scale), the Patient Clinical Global Impression and the Modified Colorado Symptom Index. Their psychiatrists rated them using the Global Assessment of Functioning scale, the Health of the Nation Outcome Scales and the Therapist Clinical Global Impression. Results There was a strong correlation between patient’s evaluation of their quality of life (PROM), experience of their care (PREM) and the overall severity of their condition and their progress. The pattern of correlation between patients’ and clinicians’ measures revealed a three-layer structure representing a continuum from inner experience to external presentation of experiences. Conclusion Together these findings help identify and emphasize various domains of subjective experiences and their relation to external ratings.

The potential of Oxytocin (OT) as a facilitator of psychotherapy has been previously acknowledged, nonetheless, randomized controlled trials thus far have not yielded conclusive results. One approach suggested to clarify empirical inconsistencies is to refine the study hypotheses and data collection process by utilizing an in-depth idiographic exploration of the investigated phenomena. In this case illustration we provide an in-depth analysis comparing two patients hospitalized in a closed psychiatric ward with depression and undergoing psychotherapy twice a week. These two patients were randomly allocated to receive either OT or placebo, twice a day for a period of 4 weeks. Both patients completed longitudinal assessments of process and outcome measures, and therapists' clinical notes were extracted and reviewed. Reliable clinical change was calculated for all outcome and process measures. The results indicated that the patient receiving OT showed significant improvement in interpersonal distress, as well as in anxiety and depression symptoms, while the placebo patient showed no significant change during the study period. Furthermore, while both patients showed no significant changes in the therapeutic alliance ratings, the therapist of the OT patient regularly reported positive changes in alliance in the medical notes, while no such report was observed in the placebo patient. These results suggest that changes produced by OT administration may be more noticeable by the therapist. Implications for future studies aimed at assessing the effect of OT on psychotherapy process and outcome are discussed.

Background Medication is a significant component of the cost of mental health care. Studies from different countries indicate that physicians are often not aware of medication costs, despite the impact of such knowledge on treatment plans. The purpose of this study was to examine Israeli psychiatrists’ knowledge regarding the cost of medication and rates of disability pension, and the impact of these factors on treatment decisions. Methods Cross-sectional study. A questionnaire was distributed by e-mail to psychiatry specialists and residents, including: (a) socio-demographic and professional information; (b) knowledge regarding rates of National Insurance disability pension and medications’ costs; (c) attitudes regarding relevance of knowledge of treatment costs. Correlations between socio-demographic variables and knowledge regarding treatment costs and attitudes were examined. Results Of the 175 psychiatrists who completed the questionnaire, 55% were men. The level of knowledge regarding cost of psychotropic medication and disability pension rates was low. Sixty-eight percent rated economic considerations as important or very important, yet 75% were informed of medication prices by their patients, and 57% by pharmaceutical companies. Doctors who worked in regions other than the center of the state were more aware of the economic aspects of treatment. Physicians who reported easy access to information regarding drug prices were less likely to err in estimating the price of medications. Conclusions Psychiatrists in Israel are not sufficiently informed of the costs of psychotropic medications, despite their awareness of the relevance of affordability to treatment compliance. Awareness of economic issues relating to treatment should be included in residency programs, and access to relevant information of medication cost and disability pensions should be more accessible to physicians both on national and local levels, by the government and health maintenance ogranizations (HMOs).

Objectives: Studies assessing the effect of the COVID-19 pandemic on psychiatric patients have mostly focused on cross-sectional evaluations of differences in levels of distress. In this study, we aimed to assess changes in distress and well-being following the COVID-19 pandemic outbreak as compared with pre-pandemic levels, as well as potential predictors of symptomatic deterioration, among psychiatric outpatients treated in a public mental health hospital in Israel.Methods: Patients evaluated for distress and well-being before the pandemic (n = 55) were re-evaluated at the end of the first lockdown in Israel.Results: Analyses revealed a significant decrease in the patients’ sense of personal growth. Increases in distress were significantly associated with fear of COVID-19 beyond patient characteristics.Conclusion: These results suggest that the pandemic has a short-term effect on patients’ well-being, and that fear of the pandemic is associated with elevations in distress.

Previous findings regarding European Holocaust survivors' suicide risk are conflicting. North African survivors' suicide risk was not previously studied. In this study, we aimed to determine suicide risk among European and North African Holocaust survivors. The study was based on the Israeli population census from 1972, followed until 2015 for suicide. European survivors were grouped into survivors of severe Nazi persecution (HS) and early HS. North African survivors were grouped into those from Algeria, Libya and Tunisia who were likely to have suffered more severe persecution (group 1) and those from Morocco who apparently suffered less persecution (group 2). Comparison groups were chosen according to similar ethnic origins who were not under Nazi control. Age standardized suicide rates, Standard Mortality Ratios (SMR) were calculated. Cox regression analysis was used to assess suicide risk. The age adjusted suicide rates (per 100,000) among Europeans were: HS 17.8 (95%CI 16.9-18.6), early HS 28.6 (95%CI 24.9-32.2), comparison group 20.3 (95%CI 18.5-22.1). Among North Africans: group 1, 6.9 (95%CI 5.6-8.2), group 2, 4.8 (95%CI 4.0-5.5), comparison group, 8.5 (95% CI 6.4-11.0). The SMRs with European comparisons were 0.88 (95%CI 0.84-0.92) for HS and 1.41 (95%CI 1.20-1.65) for early HS. SMRs with North African comparisons were 0.81 (95%CI 0.67-0.97) for group 1 and 0.57 (95%CI 0.48-0.66) for group 2. Cox regression models showed significantly higher suicide risk for European early HS vs comparisons (Hazard Ratio (HR) = 1.31, 95% CI 1.12-1.52), and lower risk for HS (0.89, 95%CI 0.80-0.98). North African group 2 had significantly lower HR (0.58, 95%CI 0.43-0.79). To conclude, higher resilience was found among European survivors of severe adversity, compared to those who suffered lesser persecution. No elevated risk was found among North African survivors.

Background: The proportion of persons with severe mental illness (SMI) who are parents has increased in recent decades. Children of parents with SMI are at increased risk for medical, behavioral, emotional, developmental, academic, and social problems. They also have an increased risk for injuries, accidents, and mortality, addictions, and various psychiatric disorders compared to children of parents with no such diagnoses. We aimed to examine the extent to which mental health professionals (MHPs) who treat adult patients with SMI in ambulatory settings are aware of these individuals’ functioning in three parenting domains: parental functioning, familial support system and children’s conditions. We also compared psychiatrists’ awareness with that of psychologists and social workers. Methods: In this retrospective practice-oriented study, we reviewed 80 clinical files of individuals diagnosed with schizophrenia, affective disorder or personality disorder treated in a mental health outpatient clinic, using the Awareness of Family’s Mental Health Checklist (AFMHC) developed for this study. Thus, awareness was determined on the basis of what was recorded in the patient file. Results: Almost half of the MHPs were unaware to their patients’ parental functioning as only 44% of files contained records relating to this issue. Awareness to other domains was even lower: 24% of files contained information on patient’s support system and 12% had information about their children’s mental and/or physical health. No statistically significant differences between psychiatrists and other MHPs were found with regards to awareness to the various domains. Positive correlations were found among MHP’s for awareness in the three domains. Conclusion: Lack of awareness among MHPs to their patients’ parental functioning is not specific to a certain profession and may be attributed to patients (e.g., reluctance to disclose relevant information) or to MHPs (e.g., lack of training). Awareness of family and parental functioning by MHPs working with persons with SMI should be part of a standard procedure, integrated into policy and training.

Highlights • The COVID-19 pandemic is expected to lead to broad psychological effects, which should be considered when performing studies assessing mental health. • Only a few studies have thus far have utilized validated scales to assess the influence of the pandemic on the population's mental health, partially due to the lack of knowledge regarding their psychometric properties. • The Fear of COVID-19 scale (FCV-19S) is a recently developed scale to assess different aspects of the fear of the pandemic. • When evaluating the psychometric properties of the scale in a large normative sample (n = 639) of participants in Israel, the scale showed good internal reliability and demonstrated association with stress, anxiety, and depression. • These results indicate that the scale can be utilized in studies assessing the effects of the pandemic on the population's mental health., Mental health clinicians worldwide have been expressing concerns regarding the broad psychological effects of the COVID-19 pandemic. Nonetheless, only a few studies have thus far evaluated the degree of fear of COVID-19, partially due to the lack of validated measures. In this study we evaluated the psychometric properties of the Hebrew version of the Fear of COVID-19 scale (FCV-19S), recently developed to assess different aspects of the fear of the pandemic, in a normative population of participants in Israel. Participants (n = 639) were asked to complete the FCV-19S scale, as well as to report anxiety, depression, and stress levels using validated scales. The results a unidimensional factor structure of the FCV-19S which explained 53.71% of the variance. When forcing a two-factor structure model, the analysis revealed two factors pertaining to emotional fear reactions and symptomatic expressions of fear. Gender, sociodemographic status, chronic illness, being in an at-risk group, and having a family member dying of COVID-19 were positively associated with fear of COVID-19. The measure was associated with anxiety, stress and depression. These results suggest that the FCV-19S has good psychometric properties, and can be utilized in studies assessing the effects of the pandemic on the population's mental health.

The MATRIX is a tool designed to analyze psychoanalytic sessions. It is composed of two axes: focus (patient, therapist, and dyad) and dimension (space, content, and order). The MATRIX was found to be a reliable tool, and valid for identifying the therapist's theoretical inclinations in psychoanalytic-oriented psychotherapy sessions. In the present study, we suggest that the MATRIX can identify different (Kleinian, Bionian, and relational) approaches to projective identification, thus providing therapists and supervisors an easy-to-use tool for monitoring, and better managing, projective identifications during psychoanalytically oriented psychotherapy.

Background Mental health clinicians have previously been reported to express reservations regarding the utility and accuracy of the psychiatric classification systems. In this study we aimed to examine clinicians’ experiences with instances of perceived inaccuracy of a schizophrenia diagnosis. Methods Mental health clinicians (N = 175) participated in an online survey assessing prevalence and perceived reasons for inaccuracies of a schizophrenia diagnosis. Respondents included psychiatric ward directors (13.1%), senior psychiatrists and psychologists (40.5%), and psychiatry and clinical psychology residents (36%). Results Fifty-three percent of respondents reported encountering instances where a schizophrenia diagnosis was assigned even though clinical presentation did not match diagnostic criteria. Seventy-three percent of senior psychiatrists in a position to determine a diagnosis declared assigning schizophrenia even when controversial among clinical staff, and 15% of them declared doing so frequently. The likelihood of frequently assigning a schizophrenia diagnosis even when clearly controversial was predicted by the perception that an inaccurate diagnosis is assigned due to the presence of negative symptoms (OR 2.20, 95% CI 1.04–4.66, p = 0.039) and due to patient-related factors, such as the need to facilitate rehabilitation (OR 1.77, 95% CI 1.07–2.90, p = 0.024). Conclusions Although a schizophrenia diagnosis is considered relatively stable and clear, our study indicates that, in clinical practice, the assignment of this diagnosis is frequently controversial. These controversies are associated with the perception that an inaccurate diagnosis is assigned due to diagnostic considerations, or due to the possibility that patients might benefit from such a diagnosis. Implications and limitations for psychiatric practice and discourse are discussed.

Objective: The present study aimed to examine the association between patient–therapist micro-level congruence/incongruence ratio and psychotherapeutic outcome. Method: Nine good- and nine poor-out...

Individual psychotherapy is an efficient tool and an integral part of psychiatric treatment. However, its status among psychiatrists in Israel has never been explored.To explore and map the attitudes of psychiatrists in Israel regarding psychotherapy and psychotherapy training during residency, with comparisons between residents vs. specialists, peripheral vs. central institutions and mental health vs. medical centers.We conducted a cross-sectional survey to examine the attitudes toward individual psychotherapy. The questionnaire was delivered via email and direct approach to psychiatrists in Israel.The survey was completed by 229 of 1,502 registered psychiatrists (15.3%). While 96% (n=218) had positive attitudes towards psychotherapy, 93.1% (n=215) thought psychotherapy was less available than pharmacotherapy. Psychiatrists from peripheral institutions prefer cognitive behavioral therapy, while psychiatrists from central institutions prefer dynamic psychotherapy. Psychiatrists from mental health centers use more dynamic psychotherapy compared to psychiatrists from medical centers. The number of dynamic psychotherapy treatments psychiatrists delivered during their residencies has been decreasing over time, meaning residents today deliver fewer dynamic psychotherapy treatments compared to the number of treatments specialists delivered during their residencies. Additionally, 97.4% (n=225) believed psychotherapy training should be included in the psychiatric residency and 87.3% thought that the training should be improved to a great extent.The survey demonstrates mixed but overall positive attitudes towards psychotherapy among psychiatrists in Israel. The findings should be taken into consideration by psychiatrists who design the residency program and by policy makers who are in charge of the mental health reform in Israel, or the psychotherapy usage and therapeutic potential may diminish, as has happened in other countries.

Objectives Latent inhibition (LI) refers to the retarding effects of inconsequential stimulus preexposure on subsequent conditioning to that stimulus, and reflects the organism’s capacity to ignore irrelevant stimuli. LI is disrupted in schizophrenia patients, due to faster learning of the association between the conditioned stimulus (CS) and an unconditioned stimulus (US). It was recently proposed that LI has an additional pole of abnormality indicated by LI persistence. Methods Two experiments were performed to test this hypothesis. Both experiments applied a new within-subject, visual recognition LI procedure in which the association between a cue (CS) and the target (US) is acquired. In Exp 1 the task was applied to healthy volunteers (n = 21). In Exp 2 chronic schizophrenia patients (n = 19) were compared to control subjects (n = 20). Results In Exp 1 the subjects showed LI in the initial trials of cue–target pairings, and an attenuation of the phenomenon at later trials. In Exp 2 control subjects showed a pattern of response comparable to the subjects of Exp 1, while the patients showed LI only on the later trials of the task. Conclusions This result suggests that patients with chronic schizophrenia showed LI persistence. The possible advantages of the new LI paradigm are discussed.

Forty-nine people suffering from schizophrenia performed an interactive bargaining task involving small monetary rewards, known in classical game theory as the Ultimatum Game. In this task, the subject, in the role of the Proposer, has to offer his or her (anonymous) counterpart, the Responder, a share of a given sum of money. If the Responder accepts the offer, then the sum is split accordingly between the two. Otherwise, if he or she decides to reject the offer, both receive nothing. The patients' strategic behavior in both roles was compared with that of healthy and clinical controls. It was hypothesized that cognitive deficits characterizing schizophrenia, together with difficulties in social judgment, would impair the patients' bargaining ability. We found that in general schizophrenic patients did not fully exploit their strategic power as Proposers. In contrast, as Responders, schizophrenic patients acted not significantly different from controls. Further investigation is needed to establish the links between cognitive and symptomatic mediators and strategic decision-making ability.

Learned irrelevance (LIrr) is a pre-exposure effect in which uncorrelated presentations of a conditioned stimulus (CS) and an unconditioned stimulus (US) retard subsequent CS-US association. LIrr is closely related to the phenomenon of latent inhibition (LI). LI refers to the retarding effects of inconsequential stimulus pre-exposure on subsequent conditioning to that stimulus, and is considered to reflect the organism's capacity to ignore irrelevant stimuli. LI is disrupted in schizophrenia patients, due to faster learning of the association between the preexposed CS and the US. A new within-subject target-recognition LIrr procedure was applied. The target was either cued by a priming signal or appeared at random, and priming signals were novel or preexposed cues. Schizophrenia patients were compared to age- and sex-matched control subjects. Normal subjects (n = 24) have shown robust LIrr, namely, faster cue-target associations of novel compared to preexposed cues. Schizophrenia patients at the early stages of their first episode (n = 7) showed LIrr disruption, namely, cue-target associations to preexposed cues were as fast as for novel cues. Chronic patients during an acute phase (n = 18) did not show LIrr as they failed to learn the cue-target association. In addition to the LIrr paradigm the same subjects were tested in a covert-orientation task. No differences were observed between the groups on this task. The possible advantages of the new LIrr paradigm are discussed.

Introduction Long-acting depot injections of antipsychotic medications are an important way to monitor treatment noncompliance in patients suffering from schizophrenia. Pain and discomfort at the injection site may result in patients' refusal of depot injections. The present study is a pilot study that attempts a systematic characterization of injection site pain. Method Thirty-four consecutive outpatients suffering from DSM-IV-defined schizophrenia or schizoaffective disorder and treated with depot antipsychotic medications were evaluated. The pain they suffered from the injections was quantified using a visual analog scale. This evaluation was made 5 minutes before the injection, 5 minutes after. 2 days after, 10 days after, and before the next injection. Patients were also administered a modified version of the Rating of Medication Influences scale that included a specific question on the possible relationship between injection-associated pain and future compliance to depot treatment. Results The depot injections cause pain, which is maximal immediately after the injection, declines substantially 2 days after, and disappears by the tenth day after the injection. A correlation exists between reported injection site pain and the effect it has on patients' attitude toward the depot injection as reported by the patients. Zuclopenthixol depot injection is more painful than other depot medications. Conclusion Depot injections are painful. The pain they inflict has a typical course, and medication type is among the factors that influence this pain. This pain might have an effect on patients' attitude toward depot injections and thus is of importance in the management of patients suffering from schizophrenia.

Objective Information on the indications, technique, and effectiveness of electroconvulsive therapy (ECT) in adolescent patients is scarce. The recommendations for the use of ECT in this age group are similar to those in adults. This study compares the experience with ECT in the two age groups in the same community psychiatric institution, which adheres to the accepted protocols for diagnosis and treatment. Method The files of 24 consecutive adolescent patients treated in an ECT unit located in the center of Israel in the years 1991–1995 were retrospectively examined, and the findings were compared with those in 33 adult patients who started their ECT course on the same day. The technique for applying ECT was essentially the same in the two age groups. Results ECT was equally effective for adolescents and adults (58% in each group achieved remission). The main difference was the diagnosis for which patients were referred: most of the adolescents were in the “psychotic spectrum,” whereas most of the adults were in the “affective spectrum.” Conclusions The findings support the current medical recommendations for the use of ECT in adolescents. Possible explanations for the differences in diagnosis between the two age groups are discussed.

The confusion technique is based upon statements that are meaningful in themselves but nonsensical in the context in which they are spoken. We describe a modification of this technique. Through unanticipated alterations in syntax, rhythm or content the patient's attention is diverted and then refocused on specific themes that are beneficial for induction or hypnotherapy. Due to its subtlety, this modification may be effective also in low-susceptible subjects. Copyright © 1999 British Society of Experimental and Clinical Hypnosis

Winnicott's transitional phase stands for the space where inner and outer realities are being connected and separated. It is through this unique phase that individuals progress from infantile autism to socialization. We suggest that hypnosis represents regression into the transitional phase. This may be of importance in designing therapy schemes that combine hypnosis and psychotherapy. Copyright © 1999 British Society of Experimental and Clinical Hypnosis

Experimental systemic lupus erythematosus (SLE) has been induced in mice by immunization with either a human anti-DNA mAb bearing a common idiotype (Id) designated 16/6 Id (antibody 1, Ab1) or with a murine anti-16/6 Id mAb (Ab2). In the present study a murine mAb (5G12-4, Ab3) that bears the 16/6 Id and binds to DNA was produced and was found to bind rabbit anti-16/6 Id sera and murine anti-16/6 Id mAb similarly to the human mAb 16/6 Id (Ab1). Moreover, mAb 5G12-4 was shown to share T cell epitopes with the human 16/6 Id mAb, since lymph node cells of mice immunized with the mAb 5G12-4 proliferated significantly to the human 16/6 mAb and vice versa. Following immunization of mice with the murine mAb bearing the 16/6 Id, antibodies to dsDNA, ssDNA, 16/6 Id, anti-16/6 Id, and to HeLa nuclear extract proteins were detected, similarly to those observed previously upon immunization with Ab1 or Ab2. Six months following the immunization, the mice exhibited leukopenia, increased erythrocyte sedimentation rates, and proteinuria. Examination of the kidneys of the mice disclosed immune complex deposits, thickening of the Bowman's capsule and glomerular necrosis. These results show the importance of the 16/6 Id network in the induction and progression of SLE in mice.

Previously we have shown the ability to induce experimental systemic lupus erythematosus (SLE) in naive mice with pathogenic antibodies carrying the 16 6 idiotype (Id) and with the T-cell line specific for the 16 6 Id. In the present study we established and characterized a series of T-cell clones that react against diverse autoantibodies carrying the 16 6 Id and show that they are capable of inducing a SLE-like disease in mice. The T-cell clones were generated from BALB c mice immunized with the human mAb anti-DNA antibody (SA-1) and the mouse monoclonal anti-tuberculous Ab ( TB 68 ), both carrying the 16 6 Id. The T-cell clones proliferated only in the presence of either human or mouse mAb carrying the 16 6 Id. All the T-cell clones were found to be of the helper type (L3T4) and were H-2 restricted in their function. The injection of the clones to BALB c mice resulted in serological findings (e.g., anti-DNA, anti-Sm), clinical manifestations (e.g., proteinuria, low white blood cell counts, increased erythrocyte sedimentation rate), and renal insult typical of SLE disease. Our data support the role attributed to pathogenic idiotypes in SLE on the one hand and that played by cellular immunity on the other. The mechanism by which Id-specific T-helper cells may induce SLE is currently not clear. The immunogenicity of the T-cell receptor ( anti- 16 6 ) and the cells themselves acting as effector/helper cells, thus leading to damage, may play a role in initiating a chain of events that ends in the production of a panoply of autoantibodies, some of which may also have a regulatory function.

The study was designed to determine whether manisfestations of autoimmunity are altered with age, using an experimental model in which systemic lupus erythematous (SLE) is induced in mice. Young (2-month-old), and aging (18-month-old) BALB/c female mice were immunized with a human monoclonal anti-DNA antibody that bears a common idiotype (16/6 ld). Control groups were either left untreated or were injected with human IgM (HIgM). Anti-16/6 Id levels were found to be significantly lower in the old mice than in the young. Similarly, anti-anti-16/6 Id (murine 16/6 Id + ) values were lower in the old. Mice injected with the 16/6 Id also produced various autoantibodies, including anti-dsDNA, anti-RNP, anti-Sm and anti-histones antibodies. The levels of these antibodies were lower in the old mice than in the young, yet the differences were not statistically significant. Levels of autoantibodies examined in control animals were either similar in both age groups (anti-RNP and histones) or lower in the old (anti-dsDNA and Sm). Four months after a booster injection of 16/6 Id, the young mice developed clinical manifestations of SLE, including proteinuria and leukopenia, which were seen, in milder form, in the aged mice. Immune complex depositions examined by immunohistology on kidney sections suggested similar differences based on the age of the animals. Our results suggest that aging might actually be associated with a decline in the capacity to produce autoimmune responses

We have previously reported the induction of experimental systematic lupus erythematosus (SLE) in mice by immunization with a human monoclonal antibody that expresses a common anti-DNA idiotype (16/6 Id). Following immunization, antibodies directed against various nuclear autoantigens could be detected in the sera of the mice. In the present study, we investigated the proliferative responses of lymph node cells to one particular autoantigen (DNA) following the induction of experimental SLE. Cells reactive with ssDNA could be detected following immunization of BALB/c mice with the 16/6 Id. The appearance of these DNA-reactive cells succeeded the appearance of 16/6 Id-specific cells. The activation of this subset of autoreactive cells could be achieved only by the immunization of the mice with the 16/6 Id, but not by their immunization with DNA, thus suggesting that the induction of experimental SLE is associated with the alteration of the low responsive potential of the mice to DNA.

General hospital staff is experienced in dealing with the death of a patient. However, aside from cases of sudden death among psychiatric inpatients, psychiatric medical staff faces such situations considerably less frequently. Many chronic psychiatric patients do not have a family or home, a situation which may become even more painful if the patient is dying of a physical illness. Coping with a terminally-ill oncology patient is a difficult task for the multidisciplinary staff and for fellow patients in chronic care psychiatric departments. The authors describe the slow deterioration of two psychiatric inpatients who were also diagnosed with advanced cancer, and present the dilemmas involved with continued treatment of terminal oncology patients in a psychiatric ward when the psychiatric status no longer warranted inpatient psychiatric care.

The La antigen is a highly conserved protein, originally defined by sera of patients with Sjögren's syndrome or systemic lupus erythematosus (SLE). In the present study, we have produced and characterized a monoclonal anti-la antibody derived from mice with experimental SLE. The induction of SLE in these mice was achieved by their immunization with a murine monoclonal anti-idiotypic antibody against a common idiotype (16/6 Id) found in SLE patients. The monoclonal anti-La antibody derived from these mice was found to be virtually identical to the anti-La antibodies found in human autoimmune sera. First, its binding to different nuclear extracts, as well as to protease-digested HeLa nuclear protein extracts, was found to be identical to that of human anti-La antibodies. Second, an inhibition study on blotted proteins demonstrated a very close relationship between the epitopes recognized by the murine monoclonal anti-La antibody and the human anti-La serum. Third, the monoclonal anti-La antibody was found by immunofluorescence to be directed against a nuclear antigen that gave a speckled pattern. Finally, the monoclonal anti-La antibody immunoprecipitated the La-associated small RNAs. This report provides evidence for the similarity of murine anti-La antibody produced in experimental SLE and human anti-La antibodies formed in autoimmunity.

SummaryWe examined the proliferative responses of T cells of patients with systemic lupus erythematosus (SLE). their first-degree relatives, and healthy donors, to a human monoclonal antibody that bears a common anti-DNA idiotype, 16/6 Id, and to a nurine, 16/6 Id-specific, monoclonal antibody. Both 16/6 Id+ and 16/6 Id-specific antibodies were previously shown to be involved in the induction of experimental SLE in mice. Here we show that T cells of fewer SLE patients, as compared with healthy donors, could proliferate to both antibodies. The difference between T cell responses of patients and controls to the 16/6 was found to be significant. The proliferative responses of T cells of first degree relatives of SLE patients to the anti-16/6 Id were found to be significantly lower compared with the responses detected in healthy donors and in SLE patients. The responses of T cells of SLE relatives to the 16/6 Id were also found to be lower than those of healthy donors, but this difference was not significant. The present study suggests a possible involvement of T cells, and specifically of idiotype and anti-idiotype specific T cells, in SLE.

We have previously demonstrated the pathogenicity of the common anti-DNA idiotype designated 16/6 Id. Immunization of naive mice with the 16/6 Id induced SLE-like disease characterized by serological (e.g. anti-dsDNA and anti-Sm auto-antibodies), clinical (increased ESR, leucopenia and proteinuria), and pathological (16/6 Id deposition in kidneys) parameters. To elucidate further the role of the 16/6 Id in SLE induction the following studies were carried out: BALB/c mice were immunized with SA-1, a human anti-DNA monoclonal antibody carrying the 16/6 Id; TB-68, a mouse monoclonal anti-tuberculosis (TB) glycolipid, which binds dsDNA and carries the 16/6 Id; TB-72, a mouse monoclonal anti-TB glycolipid that binds DNA and does not harbour the 16/6 Id; and 4B4, a human anti-Sm antibody that carries the 16/6 Id. SLE was induced in BALB/c mice only when immunized with SA-1, TB-68, and 4B4, namely antibodies with diverse binding capacities albeit having the 16/6 Id. Our studies further support previous evidence on the pathogenic role attributed to the 16/6 Id in SLE, and suggest that SLE is most probably an idiotype-induced disease.

There is a growing interest in gender differences of different psychiatric disorders, especially major depression. We sought a possible gender difference related to electroconvulsive therapy (ECT).This retrospective study compared 20 male and 23 female depressed adult patients treated by ECT. We compared their findings on gender differences to those of 12 female and 4 male bipolar patients and 11 male and 19 female schizophrenic patients, all treated in the same ECT setting.Depressed female patients underwent significantly fewer antidepressant drug trials than males before being referred to ECT (t41=2.09, P0.05). A similar gender difference was found in the treatment of patients suffering from schizophrenia: female patients underwent fewer pharmacological antipsychotic trials than males before being referred to ECT (t28=3.11, P0.01). ECT was significantly more effective in female patients than in male patients suffering from schizophrenia (U=38, P0.05).This is a retrospective pilot study whose results are based on subjective evaluations.The findings of this study may support a gender difference both in referral and in the outcome of ECT.there might be a need to consider lowering the number of pre-ECT drug trials for depressed males and to consider ECT as a viable therapeutic option for schizophrenic females.

It has been well established that patients with schizophrenia have impaired cognitive function on neuropsychological tasks related to memory. Previous studies also suggest serotonin's central role in memory. This double-blind crossover study aimed to explore the effect of Ondansetron, a selective serotonin 3 receptor (5-HT(3)) antagonist, on a variety of memory tasks in schizophrenic patients. Clozapine-treated schizophrenic patients in remission (N=21) were randomly treated with Ondansetron or placebo and then evaluated at three consecutive points. These evaluations included clinical measures (including Positive and Negative Syndrome Scale for Schizophrenia, Clinical Global Impression and Extrapyramidal Symptoms Rating Scale) and neuropsychological measures (including Digit Span, Paired Association, Rey-Osterich Complex Figure Test, Digit Symbol and the Rivermead Behavioral Memory Tests). Ondansetron, when compared with placebo, did not affect the above clinical measures and most of the neuropsychological tests. Short-term administration of Ondansetron, however, was associated with significantly improved visuo-spatial memory as measured by the Rey-Osterich Complex Figure Test. These preliminary results suggest Ondansetron's possible role in enhancement of memory function in schizophrenia.

In short-term studies, both in animals and in humans, fish oil seems to exert anti-inflammatory effects. However, these effects may vanish during long-term treatment. There is a possibility that in autoimmune diseases, supplementation of dietary n-3 fatty acids might lead to a decrease in the number of autoreactive T cells via apoptosis, as demonstrated in (NZBXNZW) F1 lupus mice [40]. Thus, the "fade away" effect might be due to regrowth of pathogenic autoreactive cells. In animal models of autoimmune diseases, diets high in n-3 fatty acids from fish oil increase survival and reduce disease severity in spontaneous autoantibody-mediated disease, while n-6 linoleic acid-rich diets appear to increase disease severity. The situation in human disease is probably more complex. Some of the discrepancy between studies can be attributed to methodologic problems. The effect of fish oil is dose, time and disease-dependent. Since the anti-inflammatory effects depend on the balance between n-3 and n-6 fatty acids, the relative proportion of EPA and DHA and possibly co-treatment with dietary vitamin E, the dose/effect ratio may vary between individuals. Furthermore, some animal studies demonstrating efficacy used very high doses that may be incompatible with human consumption. It seems that fish oil is only mildly effective in acute inflammation. In those chronic inflammatory disorders where it was found to be effective, several weeks are necessary to exhibit results. Yet, this mild anti-inflammatory effect, possibly through downregulation of pro-inflammatory cytokine production, leads to striking therapeutic improvement in critically ill patients. Fish oil supplementation seems advantageous especially in acute and chronic disorders where inappropriate activation of the immune system occurs. Fish oil has only a mild effect on active inflammation of diseases such as rheumatoid arthritis, SLE and Crohn's disease, but it could prevent relapse (in some of the studies). In diseases where the inflammation is mild, such as IgA nephropathy, fish oil may slow or even prevent disease progression. The above could explain the observation in some populations of a decreased incidence of inflammatory and autoimmune diseases [3], since the constant consumption of n-3 fatty acids could suppress any autoreactive (or hyper-reactive) T cells. However, if there is already an existing disease, increased consumption might not be beneficial over a long period. Therefore, the use of n-3 fatty acids can be recommended to the general healthy population, not only to prevent atherosclerosis but possibly also to reduce the risk of autoimmunity.

In the following study we have analyzed cytokine secretion of T-cells of suicidal and non-suicidal depressed patients and healthy controls. It was found that T-cells of suicidal depressed patients have Th1 characteristics, while T-cells of non-suicidal depressed patients have Th2 characteristics. Th1 environment is associated with most of autoimmune diseases. It is thus speculated that Th1 activation in suicidal depression may reflect a unique form of autoimmune suicide.

Experimental systemic lupus erythematosus (SLE) in mice can be induced by immunization either with a human monoclonal anti-DNA antibody bearing the 16/6 idiotype (16/6 Id) or with a mouse monoclonal anti-idiotypic antibody specific for the 16/6 Id. In the present report we investigated the pathogenic role of a monoclonal anti-La autoantibody in the induction and mediation of experimental SLE in mice. The monoclonal anti-La antibody was derived from a mouse in which experimental SLE was induced by immunization with the monoclonal anti-16/6 Id antibody. Following immunization with the anti-La antibody the mice produced antibodies to double-stranded DNA, single-stranded DNA, Sm, SS-A/Ro, SS-B/La, and ribonucleoprotein. Furthermore, even though the anti-La antibody does not express nor react with the 16/6 Id, the immunized mice produced high titers of anti-16/6 Id antibodies as well as 16/6 Id bearing antibodies. Four months following immunization the mice exhibited significant proteinuria, and kidney sections revealed immune complex deposits on the basement membrane of the glomeruli. These results suggest that anti-La autoantibodies are involved in the induction and mediation of SLE in mice.

Article de synthese sur les idiotypes des autoanticorps anti-DNA et leur role dans l'etablissement de l'autoimmunite qui peut conduire au developpement d'une maladie autoimmune

We have recently reported the induction of experimental systemic lupus erythematosus (SLE) in mice by a human anti-DNA monoclonal antibody (mAb) that bears a common idiotype, the 16/6 Id. In the present report we investigated the role of the idiotypic network in the induction of experimental SLE by using a murine anti-idiotypic mAb specific for the 16/6 Id. This anti-idiotypic mAb induced experimental SLE similarly to the 16/6 Id. Thus, following immunization, in addition to 16/6 Id+ antibodies, the mice produced antibodies to various nuclear antigens: single-stranded DNA, double-stranded DNA, poly(I), poly(G), Ro, La, Sm and ribonucleoproteins. Similarly to the 16/6 Id-immunized mice, the mice injected with the anti-16/6 Id mAb exhibited elevated erythrocyte sedimentation rate and leukopenia. The murine anti-16/6 Id mAb was found to be more effective than the 16/6 Id, in causing earlier onset of proteinuria and renal damage. These results suggest that the idiotypic network and particularly anti-idiotypic antibodies specific for anti-DNA common idiotypes found in SLE, play an important role in the induction of SLE in mice.

Systemic lupus erythematosus (SLE) has been induced in C3H.SW mice by their immunization with a human monoclonal anti-DNA antibody that bears a common idiotype-16/6 Id. Following immunization, high levels of murine anti-16/6 and anti-anti-16/6 antibodies were detected in the sera of the immunized mice. Elevated titers of autoantibodies reacting with ssDNA, dsDNA, poly(I), poly(G), RNP, Ro, and La were also observed. The serological findings were associated with significant proteinuria, leukopenia, and elevated erythrocyte sedimentation rate. Immune complex deposition in the glomerular mesangium and sclerosis of the glomeruli were demonstrated. To study whether or not anti-idiotypic antibodies are involved in the induction of the disease, a murine monoclonal antibody against the 16/6 Id was prepared and injected into C3H.SW mice. The anti-16/6 Id antibody induced experimental SLE similarly to the 16/6 Id with an accelerated kidney pathology. A study performed on different mouse strains indicated that the susceptibility to the induction of SLE by the 16/6 Id is strain dependent and directly correlates to their ability to produce anti-16/6 Id specific antibodies.