Antipsychotic treatment in schizophrenia: the role of computerized neuropsychological assessment.

The present study analyzes the role of neurocognitive assessment instruments in the detection of the contribution of antipsychotic treatment to cognitive functioning. Recently, a panel of experts suggested six main domains (working memory; attention/vigilance; verbal/visual learning and memory; reasoning and problem solving; speed of processing) implicated in schizophrenia-related cognitive deficits, which serve as a theoretical base for creation of real-time computerized neurocognitive batteries. The high sensitivity of computerized neuropsychological testing is based on their ability to adopt the reaction time (RT) paradigm for the assessment of brain function in a real-time regime. This testing is highly relevant for the monitoring of the cognitive effects of antipsychotics. Computerized assessment assists in the identification of state- and trait-related cognitive impairments. The optimal real-time computerized neurocognitive battery should composite balance between broad and narrow coverage of cognitive domains relevant to the beneficial effects of antipsychotics and will enable better planning of treatment and rehabilitation programs.

The role of real-time computerized neuropsychological examination in forensic psychiatry practice.

Neuropsychological examination (NPE) is an important tool for evaluation of cognitive functioning in clinical and forensic situations. In forensic practice, NPE usually focuses on competency to stand trial, the mental state at the time of the offense, risk for future violence and malingering/aggravation issues. Real-time computerized NPE shows more accurate results than traditional pen-and-paper tests and provides quantitative data in a relatively standard format. It permits detection of any manipulation by the examinee in "real time." Therefore, it makes it possible not only to analyze the final results, but also to monitor closely the sequence of single acts of the assessment procedure. Thus, the computerized NPE attenuates possible examinee-related manipulations, which may distort the test results. The real-time NPE report of these elementary behavioral parameters can be used in the courts as acceptable evidence under cross-examination. This method leaves less room for bias; however, a cautious interpretation is always essential since the computerized data do not transform subjective methods into objective ones. Establishing a standard testing procedure and further utilization of real-time computerized tools could improve significantly the quality of NPE in forensic psychiatric practice.

Sulpiride augmentation of olanzapine in the management of treatment-resistant chronic schizophrenia: evidence for improvement of mood symptomatology.

Several recent studies, albeit limited in sample number, design and generalizability, have suggested that augmentation of atypical antipsychotic medication (such as clozapine and olanzapine) with sulpiride, a substituted benzamide antipsychotic medication, may play a role in the management of treatment-resistant psychotic conditions. The objective of this study was to investigate any change in clinical symptomatology or side-effect profile in treatment-resistant schizophrenia patients receiving sulpiride in addition to olanzapine. Seventeen patients with treatment-resistant chronic schizophrenia, who were receiving olanzapine monotherapy for at least 6 months before study commencement, were randomized in a 1:1 fashion to receive either adjunctive treatment with sulpiride (study group) or to continue their pre-study treatment with olanzapine with no medication augmentation (control group), each for a period of 8 weeks. Changes in measures of positive and negative symptoms, anxiety, depression and extrapyramidal symptoms were assessed at baseline and at 8 weeks. Study observations indicated no significant differences in the changes in positive or negative symptomatology between patients receiving a combined regimen of olanzapine with sulpiride (600 mg/ day) augmentation and controls. However, a significantly greater improvement of depressive symptomatology (P < 0.05; as assessed by the Hamilton Scale for Depression) was noted in the sulpiride augmentation group. These data indicate improvement in depressive symptomatology with sulpiride augmentation of olanzapine in treatment-resistant chronic schizophrenia patients.

The significance of the nitric oxide in electro-convulsive therapy: a proposed neurophysiological mechanism.

Electroconvulsive therapy (ECT) is used to treat patients with major depressive disorder, manic episodes and other serious mental disorders. Virtually every neurotransmitter system is affected in ECT. The significance of the nitric oxide (NO), which has an established role as a neurotransmitter, neuromodulator, and an intraneuronal second messenger, in ECT is still not clear. We described the involvement of NO in long-term potentiation, the N-methyl-D-aspartic acid (NMDA) receptor activity, regulation of cerebral blood flow, and the hypothalamic-pituitary axis and propose that this involvement is critical in ECT's efficiency, treatment refractoriness, and neuropsychological sequelae by its influences on these systems. Nitric oxide's significant role in other pathophysiological mechanisms has led to current therapeutic protocols and may be applicable in this setting.

Variability of color choice in the Lüscher Color Test--sex differences.

In this preliminary investigation of variability of responses on the Lüscher Color Test, subjects were 567 volunteers administered the test twice with a 10-min. interval between them. Two hypotheses were tested: (a) that variability of responses attests to the personality of the respondent (tested by the relations of variability and MMPI scale scores), and (b) variability of responses is based on learning the test's content. As such, men's scores should be more variable than women's. Analysis showed that variability was not correlated with scores for personality on the MMPI scales. Men's scores are more variable than women's, but only until age 45.

Suicidal behavior of adolescent girls: profile and meaning.

In the last two decades the incidence of adolescent suicides has been very high (though it has been on the decrease in the U.S.A. over the last four years), giving rise to a multitude of empirical and theoretical studies. The extensive knowledge that has accumulated regarding adolescent suicidal behavior has led to a more differentiated attitude. Many studies try to clarify specific needs, motivations and the conceptualization of death and suicide in various adolescent subgroups (minorities, females, homosexuals), thereby enabling more specific and exact methods of evaluation, prevention and intervention. Adolescent girls' suicidal behavior is different in many aspects from boys' suicidal behavior: Girls mortality rate from suicide is a 3-5 times lower rate than boys, but their attempted suicide rate is four to hundreds time higher. Girls suicide mainly by drugs and their suicide is mainly in reaction to interpersonal difficulties. Their motivation is often a cry for help. The comorbidity of suicide and depression is much higher for adolescent girls than boys. These differences generate a different understanding and separate treatment strategies. Two theoretical approaches that may explain the profile which characterizes suicidal girls will be presented. One has a psychological developmental context, and the other a social cultural context. Implications for specific prevention measures include legal action on pack sizes of analgesics, compulsory registration of attempted suicide and more gender specific treatment and prevention programs.

[Compulsory treatment of nondelinquent drug-alcohol abusers in Israel: the present situation and feasible solutions].

The number of persons affected by alcoholism and/or substance abuse is constantly increasing in Israel as well the number of those suffering from severe addictions. The Israel Law for the Treatment of the Mentally Ill, 1991, does not allow the compulsory treatment of nondelinquent alcoholics and/or drug abusers who refuse treatment and who are not in a psychotic condition which includes severe and immediate danger to themselves or others. This paper analyzes and discusses the possibilities of assisting this group of patients within the framework of the present Israel legislation, other than the Law for the Treatment of the Mentally Ill of 1991, as well as focusing on modifications of this law that would be necessary to facilitate the implementation of urgent therapeutic interventions.

Can Minnesota Multiphasic Personality Inventory-2 predict response to selective serotonin reuptake inhibitors in depressed outpatients?

There is growing evidence that individual differences among patients with major depressive disorder (MDD) on psychological and demographic measures may predict the therapeutic response to selective serotonin reuptake inhibitors (SSRIs). In this retrospective chart review, 108 outpatients with current major depressive episodes were treated with citalopram, paroxetine, or fluvoxamine. The Hamilton Depression Rating Scale and the Minnesota Multiphasic Personality Inventory-2 were administered before and after 8 weeks of SSRIs treatment. Clinical response was defined as a 50% or greater decrease in the 17-item Hamilton Depression Rating Scale total score (final visit minus baseline). This naturalistic short-term follow-up outcome study demonstrates that among depressive outpatients who responded to an 8-week trial, 57.4% achieved a good response to SSRIs. Statistical analysis showed that SSRI treatment may be 3.03 times more advantageous for MDD outpatients who are younger than 39 years. The patients with an elevated score of above 66T on the Social Introversion Minnesota Multiphasic Personality Inventory-2 scale are approximately 0.37 times as likely to be SSRI responders as are patients with a Social Introversion score less than 66T. Thus, it seems that in MDD outpatient age is the strongest predictor of response to SSRIs.

Stroop performance in major depression: selective attention impairment or psychomotor slowness?

BACKGROUND: Numerous neuropsychological studies reported impaired Stroop performance in major depressive disorder (MDD) patients. METHODS: The present study attempted to identify possible neuropsychological mechanisms involved in this impairment in untreated MDD outpatients (n=75) as compared to healthy subjects (n=83). Inspection Time, Finger Tapping, Simple and Choice Reaction Time were considered as measures of perceptual, motor, psychomotor speed, and response selection, respectively. RESULTS: MDD patients performed significantly slower than healthy controls in the neutral and the congruent conditions, but not in the incongruent ones. In order to identify predictors of Stroop performance, linear hierarchical regressions analyses were performed. Age, motor and psychomotor speed were predictors of response time and accuracy on Stroop performance. Significant correlations between response time and the number of errors in all three Stroop conditions were found in MDD patients, while such a correlation was obtained in the healthy controls only in the incongruent condition. LIMITATIONS: Although education was included as a covariate in our analyses, suggesting that the observed effects could not be ascribed to education differences, further testing with education-matched samples is warranted. CONCLUSIONS: Our study shows that the Stroop task performance is affected by both aging and MDD. Impairment in the Stroop performance can be predicted by psychomotor slowness and by vigilance level in MDD outpatients, but not by impairment of selective attention per se.

The association between length of post-kidney transplant hospitalization and long-term graft and recipient survival.

BACKGROUND: There has been a general trend towards shortened length of post-kidney transplant hospitalization (LOH). The decision regarding patients's discharge from the hospital theoretically may be based on several factors, including, but not limited to, patient well being, insurance status, family situation and other, mostly socio-economic factors, as opposed to hard medical evidence. However, the appropriate LOH in kidney transplant recipients is not well studied regarding long-term outcomes. METHODS: This study retrospectively analysed the association between LOH and graft and recipient survival based on United States Renal Data System dataset. In total, 100,762 patients who underwent transplant during 1995-2002 were included. Kaplan-Meier survival analysis and Cox models were applied to the whole patient cohort and on sub-groups stratified by the presence of delayed graft function, patient comorbidity index and donor type (deceased or living). RESULTS: In recipient survival, both short (<4 d) and long (>5 d) LOH showed a significant adverse effect (p < 0.01) on survival times. In the analysis of graft survival, long LOH (>or=2 wk) also showed significant adverse effects (p < 0.001) on survival times. However, short LOH (<4 d) did not reach statistical significance, although it was still associated with adverse effects on graft survival. These observations were consistent across the whole patient cohort and sub-groups stratified by the presence of delayed graft function, patient comorbidity index and donor type. CONCLUSION: Clinical considerations should be used to make the decision regarding appropriate time of post-kidney transplant recipient discharge. Based on this study, shorter than four d post-kidney transplant hospitalization may potentially be harmful to long-term graft and recipient survival.

Safety and efficacy of long-term low-dose clozapine aftercare treatment in a patient with learning difficulties who suffered from neuroleptic malignant syndrome.

INTRODUCTION: Antipsychotic medication continues to be an essential component in the treatment of schizophrenia. Neuroleptic malignant syndrome (NMS) is one of the most serious complications of neuroleptic treatment and the optimal therapeutic aftercare regimen for patients is unclear. Also, it is not clear if low-dose neuroleptic maintenance in such patients is safe and efficient enough over time. METHOD: We present a case of a 56-year-old woman suffering from schizoaffective disorder, who was successfully treated with a low dosage of clozapine for 6.5 years following a NMS episode. RESULT: To the best of our knowledge this is the first report of such a long-term beneficial use of low-dose clozapine in a patient who previously underwent such a serious complication. CONCLUSION: Large-scale studies are needed to substantiate this observation. (Int J Psych Clin Pract 2002; 6: 121-123).

Sildenafil citrate for the sexual dysfunction in antidepressant-treated male patients with posttraumatic stress disorder. A preliminary pilot open-label study.

BACKGROUND: Previous studies have suggested that posttraumatic stress disorder (PTSD) may be associated with pervasive sexual dysfunction. Sildenafil citrate was established as a highly effective and well-tolerated oral agent for the treatment of sexual dysfunction of various etiologies. There are no studies that have examined the efficacy of oral sildenafil in PTSD patients with sexual dysfunction. OBJECTIVE: The current study evaluated the impact of sildenafil added to an ongoing antidepressive treatment in male PTSD patients. METHODS: Ten consecutive male PTSD patients who complained of sexual dysfunction were enrolled in an open-label 4-week fixed-dose study of sildenafil citrate 50 mg/day p.r.n. Patients were evaluated at baseline and after treatment with the Clinician-Administered PTSD Scale (CAPS); sexual function assessments were performed using the International Index of Erectile Function. RESULTS: All patients completed the study and statistically significant improvement was observed in all evaluated domains of sexual functioning: erectile function (53.5%), orgasmic function (40.3%), sexual desire (53%), intercourse satisfaction (82%) and overall satisfaction (57.4%). Oral sildenafil treatment appeared to be well tolerated and no single patient stopped the treatment. Improvements in various CAPS subscales were also obtained; however, there was no significant correlation between improvement in sexual functioning and the changes in CAPS subscale scores. CONCLUSION: Sildenafil seems to be an efficacious, safe and well-tolerated treatment of sexual dysfunction in antidepressant-treated male PTSD patients.

Granulocytopenia associated with neuroleptic therapy in a patient with benign familial leukopenia.

Benign familial leukopenia (BFL) has been reported in several ethnic groups, including Ethiopians of Jewish origin. To date, there are no reported cases of patients with BFL developing granulocytopenia following administration of neuroleptics. We report a case of a young Ethiopian Jew suffering from schizophrenia, who exhibited premorbid benign reduced white blood cells (WBC) count and developed leukopenia and neutropenia following exposure to typical (zuclopentixol, perphenazine, haloperidol) antipsychotics and the atypical antipsychotic risperidone. The diagnosis of BFL was established and tissue typing of the patient was determined. To the best of our knowledge, this is the first report of leukopenia with neutropenia in an ethnically susceptible (due to BFL) schizophrenia patient following exposure to typical and atypical antipsychotics. HLA typing of this patient was distinct from that reported in patients susceptible to clozapine-induced agranulocytosis. Further extensive investigations including HLA typing in a larger cohort of schizophrenic patients is needed in order to define the association between HLA haplotypes and neuroleptic-induced hematological reactions and to identify the potentially vulnerable individuals.

A highly significant association between a COMT haplotype and schizophrenia.

Several lines of evidence have placed the catechol-O-methyltransferase (COMT) gene in the limelight as a candidate gene for schizophrenia. One of these is its biochemical function in metabolism of catecholamine neurotransmitters; another is the microdeletion, on chromosome 22q11, that includes the COMT gene and causes velocardiofacial syndrome, a syndrome associated with a high rate of psychosis, particularly schizophrenia. The interest in the COMT gene as a candidate risk factor for schizophrenia has led to numerous linkage and association analyses. These, however, have failed to produce any conclusive result. Here we report an efficient approach to gene discovery. The approach consists of (i) a large sample size-to our knowledge, the present study is the largest case-control study performed to date in schizophrenia; (ii) the use of Ashkenazi Jews, a well defined homogeneous population; and (iii) a stepwise procedure in which several single nucleotide polymorphisms (SNPs) are scanned in DNA pools, followed by individual genotyping and haplotype analysis of the relevant SNPs. We found a highly significant association between schizophrenia and a COMT haplotype (P=9.5x10-8). The approach presented can be widely implemented for the genetic dissection of other common diseases.

COMT: a common susceptibility gene in bipolar disorder and schizophrenia.

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.