Yehuda Abarbanel Mental Health Center

There is increasing evidence for an association between the alteration of cytokine concentrations in blood and the pathophysiology of depressive disorders. Studies in humans have not investigated CSF cytokine concentrations and their relationship to depressive disorders. This study reports on the association of the CSF concentration of proinflammatory cytokines, IL-1beta, IL-6 and TNFalpha, and major depressive disorders. CSF samples were obtained from 13 hospitalized patients with acute unmedicated severe depression and were compared with 10 control subjects. Compared to the control group, the depressed patient group had higher CSF concentrations of IL-1beta, lower IL-6 and no change in TNFalpha. A positive correlation was found between serum IL-1beta and the severity of depression. These results indicate a unique profile for CSF proinflammatory cytokines in acute depression. These findings merit further investigation and if replicated may possibly offer immunological treatment options for depression.

INTRODUCTION: Behavioral and psychological symptoms of dementia (BPSD) are highly prevalent in Alzheimer's disease (AD) patients. They are a source of distress for the caregivers and one of the main reasons for nursing home placement, which is the major component of the cost of Alzheimer's disease. The aim of the present study was to assess the direct and indirect cost related to the care of BPSD within a prospective study examining the overall cost of AD in Israel. METHODS: Seventy-one community dwelling AD patients were interviewed. Interviews covered information about the number of caregivers' hours invested in caring for the patient and amount of expenditure such as in-house paid help and payments for day care. Effort devoted to BPSD was defined as the number of hours spent by primary and secondary caregivers in a typical week dealing with BPSD (managing aggression, pacing, attempts to leave the house under inappropriate circumstances, or comforting a hallucinating, depressed or anxious patient). RESULTS: The annual indirect cost for management of BPSD in an AD patient was approximately 2665 dollars -over 25% of the total annual indirect cost of care ($10 520). The annual direct cost of BPSD of an AD patient was approximately 1450 dollars -over 35% of the total annual direct cost of care (3900 dollars). CONCLUSIONS: Approximately 30% (4115 dollars) of the total annual cost of AD (14420 dollars) is invested in the direct management of BPSD. Given the importance of BPSD as one of the main components of the cost of AD, future cost studies should be designed to measure the cost of specific components of BPSD and verify which are the most costly aspects of the disease. Despite the considerable methodological difficulties in disentangling the costs of the specific symptoms of AD, cost effectiveness studies of different interventions should be conducted in order to determine the optimal intervention with relation to cost.

An operationalization of mental pain is presented in three studies. The first study describes the operationalization of mental pain and the factor structure of the items produced by a content analysis of self-reports yielding a scale with nine factors: the experience of irreversibility, loss of control, narcissistic wounds, emotional flooding, freezing, estrangement, confusion, social distancing, and emptiness. Study 2 tested the relationship between mental pain and depression and anxiety in a normal population. Study 3 focused on the relationship between mental pain and coping. Mental pain is conceptualized as a perception of negative changes in the self and its functions that are accompanied by negative feelings. It is suggested that it can be meaningfully applied to the study of different mental states, life conditions, and transitions in life.

OBJECTIVE: CSF levels of inositol have been reported to be lower than normal in depressed subjects. The authors administered inositol to depressed patients in a double-blind, controlled trial. METHOD: Under double-blind conditions, 12 g/day of inositol (N = 13) or placebo (N = 15) was administered to depressed patients for 4 weeks. RESULTS: The overall improvement in scores on the Hamilton Depression Rating Scale was significantly greater for inositol than for placebo at week 4. No changes were noted in hematology or in kidney or liver function. CONCLUSIONS: This may be the first use of the precursor strategy for a second messenger rather than a neurotransmitter in treating depression. Although inositol had a significant antidepressant effect in this study, replication is crucial.

Shneidman (1996) proposed that intense mental pain is related to suicide. Relatedly, Frankl (1963) argued that the loss of life's meaning is related to intense mental pain. The first goal of this research was to test Shneidman's proposition by comparing the mental pain of suicidal and nonsuicidal individuals. Meaning in life and optimism are the polar opposites of suicidality and hopelessness, and the examination of these variables in relation to mental pain was undertaken to provide a test of Frankl's proposition. In two studies, a relationship between a newly developed measure of mental pain--the Orbach & Mikulincer Mental Pain Scale, 2002 (OMMP; see also Orbach, Mikulincer, Sirota & Gilboa-Schechtman, 2002)--and suicidal behavior and life meaning were examined. Results confirmed both propositions. Implications for the study of mental pain and suicide are discussed.

A variety of psychiatric illnesses, including schizophrenia and bipolar disorder, have been reported in patients with microdeletion on chromosome 22q11-a region which includes the catechol-O-methyltransferase (COMT) gene. The variety of psychiatric manifestations in patients with the 22q11 microdeletion and the role of COMT in the degradation of catecholamine neurotransmitters may thus suggest a general involvement of the COMT gene in psychiatric diseases. We have previously reported on a significant association between a COMT haplotype and schizophrenia. In this study, we attempt to test for association between bipolar disorder and the polymorphisms implicated in schizophrenia. The association between COMT and bipolar disorder was tested by examining the allele and haplotype found to be associated with schizophrenia. A significant association between bipolar disorder and COMT polymorphisms was found. The estimated relative risk is greater in women, a result consistent with our previous findings in schizophrenia. We suggest that polymorphisms in the COMT gene may influence susceptibility to both diseases--and probably also a wider range of behavioral traits.

BACKGROUND: Child survivors of a catastrophic earthquake in Turkey were evaluated three and a half years after the event, and three years after a sub-group participated in a teacher-mediated intervention developed by the authors. The goal of this follow-up study was to determine the long-term effectiveness of the original intervention. METHODS: Subjects who participated in the intervention were compared with a control group of children similar in terms of demographics, risk and exposure. All children were evaluated in terms of posttraumatic, grief and dissociative symptomatology, as well as adaptive functioning (academic performance, social behavior and general conduct). RESULTS: The severity of post-traumatic, grief and dissociative symptoms of the two groups was comparable. Teachers blind to group assignment rated participating children significantly higher than the control group in terms of adaptive functioning. CONCLUSIONS: Early post-disaster intervention addressing children and their educational milieu provides children with significant symptomatic reduction, allowing the mobilization of adaptive coping, thereby enhancing their overall functioning as observed in school.

BACKGROUND: The incidence of cancer in patients with schizophrenia has been conversely reported to be higher, lower, or similar to that in the general population. The effects of lifestyle factors such as excess smoking, exposure to neuroleptic medications, and genetic factors that may influence the incidence of cancer in this group are not clear. The current study was performed to evaluate the frequency of cancer in a large cohort of patients with schizophrenia and to determine the standardized incidence ratios (SIRs) of any malignancy in this group. METHODS: Data regarding the design, setting, and participants of the current study were analyzed from a cohort of 3226 patients with schizophrenia who were enrolled in the computerized health registry of the Abarbanel Mental Health Center between 1993-2003. The mean age of the patients at the time of the diagnosis of cancer was 49 +/- 14.7 years, with the majority of patients (61%) being male. All patients with schizophrenia records in the database were combined with the records of the Israeli National Cancer Registry to identify pathologically confirmed cancer comorbidity. The cancer incidence rates among patients with schizophrenia were compared with the expected incidence in an age-matched and gender-matched general population sample for the same time interval. RESULTS: Among 1247 female patients with schizophrenia, 22 (1.8%) developed breast cancer and 68 (5.5%) developed cancers of any type. Fifty-two of the 1979 male schizophrenic patients (2.6%) developed cancer. The SIRs were 0.58 (95% confidence interval [95% CI], 0.48-0.69) with a P value of < 0.05 for all cancers in the cohort, and 0.60 (95% CI, 0.37-0.90) for female breast cancer. CONCLUSIONS: The results of the current study demonstrate a reduced risk of cancer in patients with schizophrenia. The mechanisms responsible for the lower risk need be investigated further.

BACKGROUND/AIMS: Large-scale population studies measuring rates and dynamics of cognitive decline in multiple sclerosis (MS) are lacking. In the current cross-sectional study we evaluated the patterns of cognitive impairment in MS patients with disease duration of up to 30 years. METHODS: 1,500 patients with MS were assessed by a computerized cognitive battery measuring verbal and non-verbal memory, executive function, visual spatial perception, verbal function, attention, information processing speed and motor skills. Cognitive impairment was defined as below one standard deviation (SD) and severe cognitive impairment as below 2SD for age and education matched healthy population norms. RESULTS: Cognitive performance in our cohort was poorer than healthy population norms. The most frequently impaired domains were information processing speed and executive function. MS patients with secondary-progressive disease course performed poorly compared with clinically isolated syndrome, relapsing-remitting and primary progressive MS patients. By the fifth year from disease onset, 20.9% of patients performed below the 1SD cutoff for impairment, p=0.005, and 6.0% performed below the 2SD cutoff for severe cognitive impairment, p=0.002. By 10 years from onset 29.3% and 9.0% of patients performed below the 1SD and 2SD cutoffs, respectively, p=0.0001. Regression modeling suggested that cognitive impairment may precede MS onset by 1.2 years. CONCLUSIONS: The rates of cognitive impairment in this large sample of MS patients were lower than previously reported and severe cognitive impairment was evident only in a relatively small group of patients. Cognitive impairment differed significantly from expected normal distribution only at five years from onset, suggesting the existence of a therapeutic window during which patients may benefit from interventions to maintain cognitive health.

BACKGROUND: Antipsychotics remain the mainstay of drug intervention in the management of schizophrenia. However, long-term treatment with antipsychotics is associated with a variety of movement disorders, the most disabling of which is tardive dyskinesia (TD), which occurs in up to 50% of patients hospitalized with chronic schizophrenia. The pathophysiology of TD is still unclear and no definite treatment exists. Both dopamine receptor supersensitivity and oxidative stress-induced neurotoxicity in the nigrostriatal system are apparently implicated. The pineal hormone melatonin is a potent antioxidant and attenuates dopaminergic activity in the striatum and dopamine release from the hypothalamus. Thus, it may have a beneficial effect for both the treatment and prevention of TD. METHODS: Using a double-blind, placebo-controlled, crossover study, we evaluated the efficacy of 10 mg/d of melatonin for 6 weeks in 22 patients with schizophrenia and TD. The primary outcome measure was the change from baseline in Abnormal Involuntary Movement Scale (AIMS) score. RESULTS: The decrease (mean +/- SD) in AIMS score was 2.45 +/- 1.92 for the melatonin and 0.77 +/- 1.11 for the placebo treatment groups (P<.001). No adverse events or side effects were noted. CONCLUSION: This is the first clinical evidence for efficacy of melatonin in the treatment of TD.

BACKGROUND: The relationship between self-stigma and self-esteem in patients with schizophrenia is receiving increased attention. However, studies to date have been limited to samples of persons under the age of 65. AIM: To examine the relationship between self-stigma and self-esteem in people with schizophrenia in both younger and older age groups. METHODS: Face-to-face interviews were completed with 86 inpatients with schizophrenia in a psychiatric hospital (mean age = 54, 55% female). Self-esteem was assessed using Rosenberg's Self Esteem Scale. Self-stigma was assessed using an adapted version of the Internalized Stigma of Mental Health (ISMI) scale. Information regarding socio-demographic characteristics and psychiatric history and symptomatology was collected. RESULTS: Self-stigma was moderate with only 20-33% of the participants reporting high levels of stigmatization. Older participants reported lower levels of self-stigma than younger participants. A relatively strong association between self-stigma and self-esteem was found. CONCLUSIONS: The findings point to the complexity of the association between self-stigma, self-esteem and age in people with schizophrenia. This study stresses the importance of clinicians taking the issue of self-stigma into consideration when treating young and old patients with schizophrenia.

BACKGROUND: Accumulating evidence indicates decreased melatonin levels in patients with schizophrenia. Insomnia, mainly difficulty in falling asleep at night, is commonly reported in this population. Association of insomnia with low or abnormal melatonin rhythms has been repeatedly documented. Melatonin is an endogenous sleep promoter in humans. We hypothesized that insomnia in patients with schizophrenia may be partially due to diminished melatonin output. In this study, we measured melatonin output in patients with chronic schizophrenia and assessed the effects of melatonin replacement on their sleep quality. METHOD: In a randomized, double-blind, cross-over, clinically based trial, 19 patients with DSM-IV schizophrenia who were treated with the normal treatment regimen were given melatonin (2 mg, controlled release) or placebo for 2 treatment periods of 3 weeks each with 1 week washout between treatment periods (7 weeks total). For measuring endogenous melatonin production, urine was collected from each patient every 3 hours between 9:00 p.m. and 9:00 a.m. Actigraphy was performed for 3 consecutive nights at the end of each period. Activity- and rest-derived sleep parameters were compared for the whole population with treatment arm as the intervening variable. A separate analysis was performed for patients subgrouped into high versus low sleep efficiency. RESULTS: All patients had low melatonin output. Melatonin replacement significantly improved rest-derived sleep efficiency compared with placebo (83.5% vs. 78.2%, p = .038) in this population. Improvement of sleep efficiency was significantly greater (p < .0014) in low-efficiency (80% vs. 67%) than high-efficiency sleepers (88% vs. 90%). In addition, during melatonin therapy, tendencies toward shortened sleep latency (by 40 minutes, p < .056) and increased sleep duration (by 45 minutes, p < .078) were observed in low- but not high-efficiency sleepers. CONCLUSION: Melatonin improves sleep efficiency in patients with schizophrenia whose sleep quality is low.

OBJECTIVE: Falls are an everyday risk for the elderly and their etiology is multifactorial. Because there are little data focusing on falls among elderly psychiatric inpatients, we aimed to retrospectively assess the characteristics of inpatients that had sustained a fall during hospitalization. METHODS: Over 4 years, all adverse-event reports of falls were reviewed. Inclusion criteria were age >65 years and intact cognition. The control group consisted of the previous and next admission of an elderly patient to the same ward. Anticholinergic score was calculated for each patient. RESULTS: Of 414 admissions of elderly patients, 34 (8.2%) patients had had a fall. The control group (n = 68) did not differ in mean age, distribution of diagnoses, or use of benzodiazepines, antidepressants, or antipsychotics. Two variables were significantly associated with falls: female gender (68% vs. 39%, p < .05) and anticholinergic burden score (ABS) (mean: 3.7 vs. 2.1, p < .05). CONCLUSIONS: Our results support reported findings of higher rates of falls among elderly women and suggest that ABS may be a risk factor for falls.

BACKGROUND: Negative attitudes towards patients with borderline personality disorder (BPD) may affect their treatment. We aimed to identify attitudes toward patients with BPD. METHODS: Clinicians in four psychiatric hospitals in Israel (n = 710; psychiatrists, psychologists, social workers and nurses) were approached and completed questionnaires on attitudes toward these patients. RESULTS: Nurses and psychiatrists reported encountering a higher number of patients with BPD during the last month, and exhibited more negative attitudes and less empathy toward these patients than the other two professions. The whole sample evaluated the decision to hospitalize such a patient as less justified than the decision to hospitalize a patient with Major Depressive Disorder. Negative attitudes were positively correlated with caring for greater numbers of patients with BPD in the past month and in the past 12 months. Nurses expressed the highest interest in studying short-term methods for treating patients with BPD and a lower percentage of psychiatrists expressed an interest in improving their professional skills in treating these patients. CONCLUSIONS: The findings show that nurses and psychiatrists differ from the other professions in their experience and attitudes toward patients with BPD. We conclude that nurses and psychiatrists may be the target of future studies on their attitudes toward provocative behavioral patterns (e.g., suicide attempts) characterizing these patients. We also recommend implementing workshops for improving staff attitudes toward patients with BPD.

INTRODUCTION: Multiple sclerosis (MS) is recognised as a central nervous system disease also affecting cognition. The rate of cognitive dysfunction in MS is in the range of 45-65% and adversely affect the quality of life. OBJECTIVE: To evaluate the effect of 1 year of treatment with interferon-beta-1b (IFNbeta-1b) on cognitive functions in patients suffering from relapsing-remitting MS. METHODS: A battery of cognitive tests was used to assess verbal learning, delayed recall, visual learning and recall, complex attention, concentration and verbal fluency at baseline and after 1 year of treatment with IFNbeta-1b. A group of 23 relapsing-remitting MS patients matched for neurological disability served as controls. RESULTS: Eighteen of 23 patients treated with IFNbeta-1b (74%) completed the study. In the IFNbeta-1b-treated group, complex attention, concentration as well as visual learning and recall improved significantly (p = 0.024, p = 0.006 and p = 0.005, respectively), while no deterioration was observed in the other dimensions. In the control group, complex attention, verbal fluency, as well as visual learning and recall deteriorated significantly (p = 0.02, p = 0.004 and p = 0.01, respectively), while no deterioration was observed in the other dimensions. CONCLUSION: Immunomodulating drugs that reduce the relapse rate and slow the disease progression also inhibit cognitive deterioration in patients with MS.

The sleep profiles of 13 children with attention-deficit/hyperactivity disorder (ADHD) who were treated with a fixed dose of methylphenidate for at least 1 month were compared with those of 16 healthy siblings. Sleep disturbances were assessed according to a structured sleep questionnaire, and the severity of ADHD was evaluated via the Conners Parents Teachers Rating Scale. The results indicated that significantly more children with ADHD demonstrated single or multiple sleep disturbances as well as higher rates of specific sleep disorders, such as initial and middle insomnia, compared with their siblings. No correlation was found between the severity of ADHD and disturbed sleep. Sleep duration and satisfaction with sleep were similar in the two groups. These findings raise important questions regarding the association between ADHD and disturbed sleep.

BACKGROUND: Tetrahydrocannabinol (THC) is a potential treatment for Alzheimer's disease (AD). OBJECTIVE: To measure efficacy and safety of medical cannabis oil (MCO) containing THC as an add-on to pharmacotherapy, in relieving behavioral and psychological symptoms of dementia (BPSD). METHODS: Eleven AD patients were recruited to an open label, 4 weeks, prospective trial. RESULTS: Ten patients completed the trial. Significant reduction in CGI severity score (6.5 to 5.7; p < 0.01) and NPI score were recorded (44.4 to 12.8; p < 0.01). NPI domains of significant decrease were: Delusions, agitation/aggression, irritability, apathy, sleep and caregiver distress. CONCLUSION: Adding MCO to AD patients' pharmacotherapy is safe and a promising treatment option.

We reviewed 36 reported psychiatric patients who were treated with a combination of electroconvulsive therapy (ECT) and clozapine. The indication of the ECT-clozapine treatment was resistance to classical antipsychotic agents, clozapine, or ECT alone. Sixty-seven percent of the patients benefited from the combined treatment. In most of the patients, the combined treatment was safe and well tolerated. Adverse reactions occurred in 16.6% of the patients and included prolonged ECT-induced seizures (one case), supraventricular (one case) and sinus tachycardia, and blood pressure elevation. It seems that combined ECT-clozapine treatment is effective and safe. This strategy may be a therapeutic option in treatment-resistant patients.

Tetrabenazine (TBZ) is a catecholamine depletor used for the treatment of a variety of movement disorders. The purpose of this study was to assess the efficacy of TBZ in a retrospective chart review in 3 tertiary care movement disorders centers over long-term treatment. Of 150 patients to whom TBZ was prescribed, 118 were followed up and assessed using the Clinical Global Impression of Change (CGIC), (-3 to +3), a composite grade from a patient and caregiver scale over variable periods. The patients had a variety of hyperkinetic movement disorders including dystonia (generalized and focal: axial, Meige syndrome, torticollis, blepharospasm, bruxism), Huntington disease (HD) or other choreas, tardive dyskinesia (TD) or akathisia, and Tourette syndrome. Mean patient age was 48.8 +/- 18.7 years; 48 were men (40.7%) with a mean disease duration of 93 months. The mean follow-up time was 22 months and the mean TBZ dose was 76.2 +/- 22.5 mg/d (median 75 mg, range 25-175 mg/d). The mean CGIC score was +1 (mild improvement). The group of patients who scored +3 on the CGIC (very good improvement) represented 18.6% (n = 22) of all patients. They had HD or other types of chorea 7.6% (n = 9), facial dystonia/dyskinesia (n = 7, 5.9%), 1 with TD, 2 with trunk dystonia, 2 with Tourette syndrome, and 1 with tardive akathisia. This group had the longest treatment duration and received a mean TBZ dose of 70.5 mg/d (median 75 mg/d) for a mean of 25.4 +/- 21.3 months. The report concludes that TBZ is a moderately effective treatment of a large variety of hyperkinetic movement disorders, with excellent effects in a subgroup with chorea and facial dystonia/dyskinesias.

The purpose of this study was to examine the sexual complaints and severity of sexual dysfunction in relapsing-remitting multiple sclerosis patients and to correlate them with psychological, neurological, and radiological variables. Frequency and characteristics of sexual disturbances were reported by 41 multiple sclerosis patients (32 females, 9 males; mean age 35.4 +/- 10.2 y). Clinical neurologic variables tested were disease duration, exacerbation rate, and disability; psychological variables tested were anxiety and depression. All patients underwent a brain magnetic resonance imaging (MRI) scan at the time of this study. The sexual dysfunction questionnaire included items based on the 3 phases of human sexual response: loss of libido, excitement (arousal difficulties, impotence, premature ejaculation), and anorgasmia. Five males (55.5%) and 16 females (50.0%) reported at least 1 sexual disturbance. The most frequent dysfunctions were loss of libido (26.8%) and arousal difficulties (19.5%). Females rated their difficulties as more severe. Sexual dysfunctions correlated with depression, (r = 0.68, P = 0.001). No correlation between MRI score and depression was found. Anorgasmia correlated with brain stem and pyramidal abnormalities (r = 0.56, P = 0.011; r = 0.56, P = 0.012, respectively). The total area of lesions (plaques) on the brain MRI scan also correlated with anorgasmia (r = 0.41, P = 0.02). Sexual dysfunctions in multiple sclerosis patients are frequent, are mild to moderate in severity, correlate with depression and in some cases central nervous system (CNS) demyelinating process, and thus may be related either to the psychological impact of this disease or to specific organic lesions in the brain.