Hanan Munitz

Velocardiofacial manifestations and microdeletions in schizophrenic inpatients

Velocardiofacial syndrome (VCFS) is associated with an increased frequency of schizophrenia and other types of psychiatric morbidity. In this study, we tried to identify a subgroup of schizophrenic patients with deletions in the VCFS region of the long arm of chromosome 22. For that purpose, we screened the records of two major general hospitals for patients with abnormalities characteristic of VCFS, such as cardiac anomalies and cleft palate, and cross-checked the data with the register of psychiatric hospitalizations in four psychiatric hospitals. Of the 24 patients that qualified, only seven patients could be studied. An additional eight schizophrenic inpatients were ascertained clinically, based on a working VCFS Clinical Scale. FISH studies and molecular analyses, using polymorphic markers from the VCFS region, documented hemizygosity of 22q11 in three out of 15 patients (20.0%). Increased awareness of psychiatrists to signs of VCFS among patients with psychiatric illnesses is encouraged, in order to direct molecular studies effectively. In order to cut down the cost of testing, we suggest screening suspected patients with a single marker, such as D22S941, and to study further only those who have a single electrophoretic band.

Clinical characteristics of schizophrenia associated with velo-cardio-facial syndrome

Velo-cardio-facial syndrome (VCFS) is caused by a microdeletion in the long arm of chromosome 22 and is associated with an increased frequency of schizophrenia and bipolar mood disorder. The purpose of this study was to investigate the genetic, physical, developmental and psychiatric features of schizophrenic patients with VCFS microdeletion. It describes the clinical findings in four schizophrenic inpatients with the characteristic chromosomal deletion. The four patients displayed delayed motor development, language deficits, learning disabilities, mental retardation, early age of onset, chronic and disabling course of illness and poor response to classical neuroleptic drugs and electroconvulsive therapy. Two patients benefited from treatment with clozapine. We suggest that schizophrenic patients with a history of delayed motor development, early onset of the disorder, history of learning disability, mental retardation, congenital cardiac anomalies and/or hypernasal speech should be screened for the velo-cardio-facial syndrome deletion. The implications of this study for psychiatric phenotype, nosology, disease mechanism, and possible new treatments in the future are discussed.

Cyproheptadine versus propranolol for the treatment of acute neuroleptic-induced akathisia: a comparative double-blind study.

The purpose of this study was to investigate the efficacy of cyproheptadine, an antiserotonergic agent, in the treatment of neuroleptic-induced akathisia (NIA), as compared with propranolol, the current gold standard. In a double-blind trial, 30 patients with schizophrenia and NIA received either cyproheptadine 16 mg/day (N = 18) or propranolol 80 mg/day (N = 12) for 4 days, followed by 3 days without any anti-NIA treatment. The Barnes Akahisia Scale, Simpson-Angus Extrapyramidal Effects Rating Scale, and Brief Psychiatric Rating Scale were used to assess the severity of NIA, parkinsonism, and psychosis, respectively. In both groups, the severity of NIA decreased significantly over time (cyproheptadine, −46%; propranolol, −42%), with no significant intergroup difference. The NIA symptoms worsened significantly when cyproheptadine and propranolol were discontinued. We conclude that cyproheptadine 16 mg/day is as effective as propranolol for the treatment of acute NIA. The antiakathisic effect of cyproheptadine may be mostly attributable to its serotonin antagonistic activity.

Abnormal thermoregulation in drug-free male schizophrenia patients

Schizophrenia patients may develop various thermoregulatory disturbances. We hypothesized that a standardized exercise-heat tolerance test [two 50-min bouts of walking a motor-driven treadmill at 40 degrees C (relative humidity=40%)] would reveal abnormal thermoregulation in drug-free schizophrenia patients. Six drug-free schizophrenia outpatients and seven healthy comparison subjects participated in this study. The schizophrenia patients exhibited significantly higher baseline and exertion-related rectal temperature. The relevance of these findings to the pathophysiology of schizophrenia-related thermoregulatory disorders is as yet unclear.

Suicide by related kidney donors following the recipients' death

Two cases of suicide by related kidney donors following graft rejection and the death of the recipients are reported. It is concluded that psychiatric screening of the donor before transplantation is necessary in order to obtain information about past psychopathology, ambivalence involved in donating the kidney, psychological style, characteristic defenses and behavioral repertoire used to cope with anxiety and disappointed life circumstances. The data are necessary to assess the donors capability of accepting a possible failure of the transplantation procedure. A psychiatric evaluation after transplantation is indicated following graft rejection and death of the recipient to assess the development of depression and suicidal potential of the related donor.

Serotonin uptake by blood platelets of acute schizophrenic patients.

Active uptake of serotonin by blood platelets of acute schizophrenic patients has been compared to that of a control group. Preliminary results presented in this article indicate that the uptake of the schizophrenic patients was about 40% lower than that of controls. Patients were followed over a period of 5 weeks with no significant change in uptake.

Active uptake of serotonin by blood platelets of schizophrenic patients.

Platelets have become a popular model for the monoaminergic neurons and especially for studies of serotonin uptake and metabolism [1,2]. Considering that human platelets can be obtained very easily, studies were directed towards comparing storage, metabalism and uptake of serotonin in various ~eurolo~c~ and mental illnesses [3,4]. Differences have been reported in serotonin levels and MAO activity between schizophrenics and healthy people [S

Poor neuroleptic response in acutely exacerbated schizophrenic patients

1. This led to the hypothesis that the pharmacodynamics of blood platelet serotonin is abnormal in certain conditions characterized by disturbed brain functions. If platelet serotonin is a reflection of malfunction ofindolalkylamine metabolism, such platelet abnormalities may reflect changes that have occurred in scrotonin-containing neurons in the central nervous system. We have shown [7] that the active uptake of serotonin in schizophrenic patients in acute state is much lower (35%) than that of control group. We would like to report here b~ochemic~ and ph~rmacolo~c~ properties related to this si~i~can~y lower uptake. These b~ochemic~ parameters may give some indication of the serotonin carrier condition in the platelet membrane,

The effectiveness of olanzapine in treatment-refractory schizophrenia when patients are nonresponsive to or unable to tolerate clozapine

Poor neuroleptic response is a major unresolved clinical problem. Precise data concerning the frequency of poor neuroleptic response are not available. The implementation of treatment modalities that are specifically recommended for non‐responders (such as clozapine) increases the desirability of such data. This study evaluated the proportion of acutely exacerbated schizophrenics who remained unimproved by consecutive administration of haloperidol, chlorpromazine and perphenazine, in randomly determined order. The overall improvement rate was 95%. The frequency of good responses to the first, second and third drug were 67%, 55%, and 67% respectively. Differences in receptor affinity profile might explain the added beneficial effect of a second or third drug.

High serum creatinine kinase level: possible risk factor for neuroleptic malignant syndrome.

OBJECTIVE This multicenter, open-label study was designed to assess the efficacy and tolerability of olanzapine in patients with chronic schizophrenia who are resistant to therapy with classic neuroleptic agents and are either not responsive to or unable to tolerate clozapine. METHODS Patients received olanzapine orally once daily for 18 weeks at doses ranging from 5 to 25 mg. The primary efficacy measure was change in the total score on the Positive and Negative Syndrome Scale (PANSS) from baseline to end point. Secondary efficacy measures were the total score on the Brief Psychiatric Rating Scale (BPRS); the PANSS positive, negative, general psychopathology, and mood subscores; and the Clinical Global Impression improvement score. Also recorded were spontaneously reported adverse events; extrapyramidal symptoms (assessed by the Abnormal Involuntary Movement Scale, Simpson-Angus Scale, and Barnes Akathisia Scale); vital signs; and clinical laboratory test results. RESULTS Forty-eight patients were treated with olanzapine; of these, 45 were assessable over the full 18-week study period. Total scores on the PANSS and BPRS were reduced from baseline by an average of 17.7 (14.2%) and 9.8 points (20.2%), respectively. Eighteen patients (40.0%) experienced a treatment response, defined as a reduction in PANSS total score of > or = 20%. A total of 25 patients (55.6%) achieved a similar reduction in BPRS total score. Significant reductions were seen in both the positive and negative symptom scores on the PANSS (P < 0.001). Olanzapine was well tolerated, with minimal treatment-emergent adverse events or clinically relevant changes in vital signs or clinical laboratory test results. No clinically significant blood dyscrasias were observed in olanzapine-treated patients, including those who had discontinued clozapine because of treatment-associated leukopenia or neutropenia. CONCLUSION The results of this study suggest that olanzapine may be of benefit in patients who are refractory to or unable to tolerate clozapine.