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Neurocognitive deficits are associated with chronic schizophrenia and aging. We investigated whether elderly chronic schizophrenia inpatients who also suffer from posttraumatic stress disorder (PTSD) have more severe cognitive impairment than elderly schizophrenia inpatients that do not. Fourteen schizophrenia inpatients that are Holocaust survivors and suffer from PTSD (survivor group) were compared with schizophrenia inpatients not exposed to the holocaust and without PTSD (comparison group) using neurocognitive assessments and psychiatric evaluation instruments. The survivors performed significantly worse on measures of processing speed and visual scanning, recognition memory, and general mental status, than the comparison group. Though nonsignificantly, the comparison group revealed better performance on tests that measured visuospatial perception, visuospatial planning and strategies, organizational and constructional skills. The survivor group displayed a greater severity of antipsychotic-induced side effects that were not associated with differences in cognitive performance. Comorbid PTSD may contribute to the severity of neurocognitive impairment in elderly chronic schizophrenia patients.

Angiotensin converting enzyme (ACE) is a candidate gene for psychiatric disorders. We examined the frequency of a functional insertion/deletion (I/D) polymorphism in the 16th intron of the ACE gene (located on chromosome 17q23) in groups of patients with schizophrenia (n = 104 and 113), major depression (n = 55), and bipolar disorder (n = 87) compared to healthy control subjects (n = 87). There was no evidence for allelic or genotypic association of the polymorphism with any of the disorders or with tardive dyskinesia (TD) in patients with schizophrenia. In a sample of nuclear families (n = 61) made up of one or more patients with schizophrenia recruited with their parents, there was no evidence for biased transmission of ACE I/D alleles. Particularly in the case of schizophrenia, these findings do not support an association of the ACE I/D polymorphism with the phenotypes examined. © 2002 Wiley-Liss, Inc.

Rationale: Tardive dyskinesia (TD) is a long-term adverse effect of dopamine receptor blockers. The dopamine D3 receptor gene (DRD3) ser9gly polymorphism has been previously associated with susceptibility to TD. Serotonin receptor antagonism has been proposed as a common mechanism contributing to the low extrapyramidal effects profile of atypical antipsychotic drugs. Objectives: To examine the association of a functional polymorphism in the 5-HT2C receptor gene (HT2CR) with TD and the joint contribution of HT2CR and DRD3 to susceptibility. Methods: Case control association analysis of allele and genotype frequencies among schizophrenia patients with (n=55) and without TD (n=60), matched for antipsychotic drug exposure and other relevant variables, and normal control subjects (n=97). Parametric analyses of the contribution of 5-HT2Cser and DRD3gly alleles to dyskinesia scores. Results: We found a significant excess of 5-HT2Cser alleles in schizophrenia patients with TD (27.2%) compared to patients without TD (14.6%) and normal controls (14.2%; χ2=6.4, df 2, P=0.03) which was due to the female patients (χ2=8.6, df 2, P=0.01). Among the female TD patients there was an excess of cys-ser and ser-ser genotypes (χ2=11.9, df 4, P=0.02). Analysis of covariance (ANCOVA), controlling for age at first antipsychotic treatment, revealed a significant effect of 5-HT2C genotype on orofacial dyskinesia (OFD) scores (F=3.47, df 2, P=.03). In a stepwise multiple regression analysis, 5-HT2C and DRD3 genotype (5-HT2Cser and DRD3gly allele carriage) respectively contributed 4.2% and 4.7% to the variance in OFD scores. Conclusions: These findings support a small but significant contribution of the HT2CR and DRD3 to susceptibility to TD, which is additive in nature.

In compliance with public health measures initiated by the Israel Ministry of Health following an outbreak of influenza, amantadine was administered to all patients in the psychogeriatric department of Lev Hasharon Mental Health Center to reduce transmission and illness severity in this susceptible population.To evaluate the potential beneficial effects of amantadine on elderly hospitalized patients with persistent schizophrenia.We conducted a retrospective case review of the treatment effects of amantadine on the mental, cognitive and clinical states of elderly chronic schizophrenic patients who received concomitant amantadine treatment and were routinely evaluated with the Positive and Negative Syndrome Scale, the Mini Mental State Examination, and Sandoz Clinical Assessment Geriatric Scale.No significant differences before and after amantadine treatment were noted.Amantadine did not influence the mental, cognitive and clinical states of elderly schizophrenia patients and thus can be considered as an anti-influenza preventive measure for this population, when indicated.

Leukopenia and agranulocytosis are well reported and dangerous haematological side-effects associated with the use of typical and atypical antipsychotics. These potentially life-threatening phenomena have led to treatment discontinuation and the consequent reemergence of psychiatric symptoms. We report three cases of patients who developed leukopenia during olanzapine treatment. In each case, the leukopenia was dose-dependent. Reduction in the dose of olanzapine was followed by normalization of the white blood count which allowed continuation of the medication. These cases suggest the possibility that, in some patients, leukopenia or agranulocytosis during olanzapine treatment might be dose-related. Thus, olanzapine dose reduction may permit treatment continuation where this is clinically indicated. In our cases, haematological side-effects were satisfactorily controlled by dose reduction without allowing the reemergence of psychiatric symptoms. This clinical management may offer an alternative to treatment suspension. A careful monitoring of the white blood count is obviously recommended. Olanzapine may be considered a potential and safer treatment for a this specific group of patients.

In 1996, mobile polls were introduced in Israel, enabling physically and emotionally ill inpatients to vote. We surveyed the rate of participation of inpatients at Lev-Hasharon Mental Health Center in parliamentary elections, their feelings regarding voting, and the nature of their vote, compared with the general population. One hundred eighteen of 306 (38.6%) patients voted compared with 63.8% of the general population. Forty-nine more patients (16%) wanted to vote but were unable to for technical reasons. More patients voted in the open than the closed wards (Χ 2 = 14.5; df= 1; p =.001). Most patients reported positive subjective feelings, a sense of responsibility (39%), belonging to the general community (28%), and pride (22%) after voting. Psychiatric inpatients voted similarly to the general population, though their percentage of voters was significantly lower. This discrepancy can be accounted for by lack of concern and ineligibility due to lack of identification documents that may reflect fundamental illness-related problems.

Many Holocaust survivors who have both psychotic disorders and residual symptoms of posttraumatic stress disorder (PTSD) remain chronically hospitalized in psychiatric institutions. This study investigated the clinical benefits of a therapeutic process facilitating a detailed videotaped account of traumatic experience (testimony method) in elderly long-term hospitalized Holocaust survivors.Twenty-four schizophrenia patients (mean age=72.2 years) who were chronically hospitalized in Israeli state psychiatric hospitals underwent assessment by blind rating with a battery of psychiatric rating scales before and 4 months after extensive videotaped interview. The rating scales included the Positive and Negative Syndrome Scale; Clinical Global Impression (CGI); Mini-Mental State Examination (MMSE); Clinician-Administered PTSD Scale, Form 2; and Structured Interview for Disorders of Extreme Stress. Full pre- and postinterview data were available for 21 patients.Thirty-eight percent of the patients met the criteria for PTSD at the first interview, compared with only 19% at the second interview. The patients had significant reductions in functional impairment and in the severity and intensity of all posttraumatic symptom clusters (intrusion, avoidance, hyperarousal); the avoidance cluster showed the most reduction. Eleven subjects had an improvement of 30% or more in total posttraumatic severity score. No differences in Positive and Negative Syndrome Scale, MMSE, Structured Interview for Disorders of Extreme Stress, and CGI total scores were noted postinterview or between the two preinterview evaluation batteries in the comparison group. Female patients had a higher prevalence of PTSD symptoms. Total Clinician-Administered PTSD Scale, Form 2, scores and total Positive and Negative Syndrome Scale scores were inversely correlated both at baseline and at follow-up.Study observations suggest clinical benefits of the testimony method in the alleviation of many posttraumatic symptoms, but not psychosis, in a cohort of psychiatrically ill Holocaust survivors, despite an interval of as many as 60 years since the traumatic events. The findings have implications for care and rehabilitation of patients many years after acute traumatic events.

Psychiatric patients' coping capacity with various life situations is limited due to their mental illness. This difficulty is even more pronounced when dealing with severe physical conditions such as kidney failure, the need for dialysis and kidney transplant. In the past, similar to patients who suffered from additional physical conditions, patients with major psychiatric disorders, long-term psychotic illness such as schizophrenia, were not considered candidates for dialysis treatment. Although these attitudes have changed, there is still concern that psychiatric patients would find it difficult to cooperate with the long-term treatment required following kidney transplant, and that lack of careful adherence to medication regimens could lead to rejection of the implant. This article describes five mentally ill individuals who suffer from terminal kidney failure, and illustrates the dilemma associated with dialysis and kidney transplant in psychiatric patients. Close cooperation between the psychiatric staff and the nephrology team can lead to the hoped for outcomes.

This is the first study of a possible molecular genetic basis for schizophrenia with obsessive-compulsive disorder (OCD). We performed a case–control association study of the catechol- O -methyltransferase (COMT) Val 158 Met polymorphism in schizophrenia–OCD patients, OCD and healthy controls. One hundred and thirteen schizophrenia–OCD patients, 79 OCD patients and 171 control subjects were genotyped for the Val 158 Met polymorphism in the COMT gene. There was no significant difference in allele and genotype distribution of the COMT gene between schizophrenia–OCD patients and healthy controls. The low-activity Met allele and Met/Met genotype were more frequent in OCD men than in schizophrenia–OCD and control individuals. This difference, however, was not statistically significant following correction for multiple comparisons. These results do not support the hypothesis that the COMT Val 158 Met gene polymorphism is associated with liability to schizophrenia–OCD.

Schizophrenia is a severely limiting chronic illness. The disease is characterized by periods of psychoses, remission, and sometimes even recovery. Effective pharmacotherapy for schizophrenia began with the development of antipsychotic neuroleptics in the 1950's, followed by the second generation of antipsychotic agents developed in the 1990's. Across time, treatment with some of these preparations revealed extrapyramidal and other side effects, including metabolic phenomenon, such as: an increase in the incidence of diabetes, and weight gain. When choosing the appropriate medication from among the second generation of antipsychotic agents, the following aspects should be considered; cost, efficacy, unique advantages, employment rehabilitation, relapse and metabolic side effects. Therapeutic algorithms and recommended guidelines are helpful when planning treatment strategies. Information regarding prior beneficial treatments, cost, and the patient's quality of life should be considered. Today, when patients' rights, economic and legal aspects are emphasized, the physician must take into account multiple factors when choosing the most appropriate treatment for the patient.

One unique characteristic of lysergic acid diethylamide (LSD) and LSD-like substances is the recurrence of some of the symptoms which appeared during the intoxication after the immediate effect of the hallucinogen has worn off. This recurring syndrome, mainly visual, has not been clearly understood, appreciated or distinguished from other clinical entities by clinicians. The terms Flashback and Hallucinogen Persisting Perception Disorder (HPPD) are used interchangeably in the professional literature. Flashback is a usually short-term, non-distressing, spontaneous, recurrent, reversible and benign condition accompanied by a pleasant affect. In contrast, HPPD is a generally long-term, distressing, spontaneous, recurrent, pervasive, either slowly reversible or irreversible, non-benign condition accompanied by an unpleasant dysphoric affect. Flashback and HPPD appear to be part of a vast and broad spectrum of non-psychopathological and psychopathological states reported by hallucinogen users. Pharmacological agents such as clonidine, perphenazine and clonazepan have been shown to ameliorate this syndrome in some of the individuals seeking treatment.

The serotonin transporter gene (SLC6A4), which plays a key role in the serotonergic pathway in the brain, is a candidate for mediating genetic susceptibility to various psychiatric disorders. There are two predominant alleles in the polymorphic promotor region [5-HT transporter gene-linked polymorphic region (5-HTTLPR)] of this gene: a long and a short allele with 16 and 14 repeat units, respectively. The short allele has lower activity and is associated with several psychiatric disorders and personality traits. We identified and sequenced a novel allele with 13 repeat units, 23 base pairs shorter than the common short allele. This unique allele was detected in a schizophrenic patient of Jewish Libyan origin. The patient exhibited extreme aggressive behavior and committed suicide after several attempts. The novel short allele was not detected in 172 healthy control subjects and 361 patients with various mental disorders. The presence of a very short unique allele in a severely aggressive schizophrenic patient may reflect a specific effect on the particular phenotype, although it is unlikely that this allele has a major contribution to susceptibility to schizophrenia. The role of the allele in serotonin transport and possible association with disease phenotype should be further investigated.

Three outpatients who fulfilled full DSM-IV diagnostic criteria for premenstrual dysphoric disorder (PDD) were successfully treated with intermittent (luteal phase) nefazodone. They received the medication at low doses of up to 100 mg/day (50 mg b.i.d.), for 2 weeks through the luteal phase of the menstrual cycle only. All the patients reported a marked symptomatic improvement, including full remission of their emotional symptoms, and two achieved in addition full remission of their somatic symptoms. Side-effects reported during the treatment were mild. The use of luteal phase nefazodone seems to be a promising treatment strategy for the management of PDD. It offers advantages over daily dosing throughout the menstrual cycle, such as reduced incidence and severity of side-effects, and avoids the stigma that may accompany the continuous use of psychopharmacological treatment, with the advantage that compliance may be improved.

Two cases are reported of patients who developed agranulocytosis after treatment with typical and atypical antipsychotics. The patients were successfully treated with olanzapine. We suggest the consideration of olanzapine as a safer treatment in patients who require immediate continuation of antipsychotic medication and have a prior history of classic and atypical neuroleptic-induced agranulocytosis.