Differences in blood pregnenolone and dehydroepiandrosterone levels between schizophrenia patients and healthy subjects.

BACKGROUND AND OBJECTIVE: Contradictory and confusing reports on serum dehydroepiandrosterone (DHEA) levels in schizophrenia led us to compare the serum concentration of its precursor, pregnenolone (PREG), between medicated schizophrenia patients and healthy subjects. The neurosteroid levels were monitored for two months and the relationship of these neurosteroids with schizophrenic symptomatology, emotional distress, and anxiety was examined. METHOD: We determined blood levels of PREG, and DHEA in 15 schizophrenia patients and 12 healthy controls at four time points: at the start of the study, after 2, 4 and 8 weeks. Analysis of covariance and canonical correlations across four time points were applied. RESULTS: Controlling for age, serum concentrations of PREG were lower, while the DHEA level and the molar ratio values of DHEA/PREG were higher in schizophrenia patients compared to healthy controls. Both levels of PREG and DHEA and their molar ratio did not change significantly during the study's period either among schizophrenia patients or healthy controls. The blood levels of PREG appear to be associated with trait-anxiety scores in the schizophrenia patients, while associations of clinical symptoms with two neurosteroids did not reach a significant level when the confounding effect of emotional distress, and anxiety scores was controlled. CONCLUSION: Low serum pregnenolone concentrations in schizophrenia appear to be associated with trait-anxiety scores independent of symptoms. Further research into the role of pregnenolone in schizophrenia is warranted.     

Effects of rapid volume expansion on the right filling pressures after prosthetic valve surgery.

The effects of rapid intravascular volume expansion were studied in 12 patients, 4 to 14 years after single prosthetic heart valve replacement. The data observed showed a statistically significant mean difference before and after volume expansion of right atrial mean pressure and right ventricular end diastolic and pulmonary capillary pressures. However, right atrial and pulmonary capillary pressures equilibration was not detected. The right atrial pressure form showed abnormal variations during inspiration. Dip and plateau right ventricular diastolic pressure configuration was recorded in 6 patients after expansion, was absent in 2 and questionable in 4. A deep Y descent with an M-shaped right atrial pressure form was recorded in all 12 patients. The explanation for these phenomena is unclear. Thus, in the absence of pressure equilibration and clinical evidence of constriction, the abnormalities recorded during rapid volume expansion should be cautiously interpreted.     

True conversive hallucinations

A case of true conversive hallucinations in a 19-year-old female soldier is described. This phenomenon is rare and should be distinguished from psychotic or dissociative states.     

Antinuclear autoantibodies in chronic schizophrenia

We determined the presence of antinuclear autoantibodies (ANA), antinative DNA and histone-reactive ANA in 3 groups of chronic schizophrenic patients (n= 85): haloperidol-treated patients (for at least 3 months) (n= 35), drug-free for at least 3 months (n= 35) and neuroleptic-naive patients (n= 15). The autoantibody titers were compared with those of healthy controls (n= 37). A significantly higher frequency of positive ANA was found among chronic schizophrenic patients (～20%) as compared with the controls (～5 %), irrespective of drug treatment, sex and age. No antinative ANA autoantibodies or histone reactive ANA were detected in either schizophrenic patients or controls. Further studies are needed to isolate and characterize in ANA-positive schizophrenic patients 1 a putative specific ANA profile.     

Decreased platelet vesicular monoamine transporter density in habitual smokers.

The brain vesicular monoamine transporter (VMAT2) is part of the re-uptake mechanism which regulates monoaminergic neurotransmission. We demonstrated previously a high degree of similarity between the pharmacodynamic characteristics of platelet and brain VMAT2. Nicotine induced increase of dopamine and serotonin neurotransmission in limbic structures may alter the expression of VMAT2 in brains of smokers. In this study we measured the VMAT2 pharmacodynamic characteristics using high-affinity [3H]dihydrotetrabenazine (TBZOH) binding to platelets of smokers (n=15) compared to sex and age matched healthy nonsmokers controls (n=14). A significant decrease (17%, P=0.02) in VMAT2 density (Bmax) was observed in platelets of smokers compared to nonsmokers. There was no significant difference in the affinity of [3H]TBZOH to its platelet binding site and the VMAT2 density did not correlate with the heaviness of smoking. The decreased density of the VMAT2 in the platelets of smokers may reflect nicotine induced desensitization of VMAT2, a phenomenon that may be relevant to the addictive properties of nicotine.     

CAG repeat polymorphism within the KCNN3 gene is a significant contributor to susceptibility to anorexia nervosa: a case-control study of female patients and several ethnic groups in the Israeli Jewish population.

The human small-conductance Ca(2+)-activated potassium channel gene KCNN3 has been involved in mechanisms underlying neuronal function and plasticity. A multiallelic CAG repeat polymorphism within the KCNN3 has been associated with schizophrenia and bipolar disorder. We have previously reported in a family-based study that longer CAG repeats are preferentially transmitted to patients with anorexia nervosa (AN). The present study extends the analysis of KCNN3 allele distribution to a larger series of AN female patients and control groups, incorporating information on ethnicity and co-morbidities associated with AN. The data analysis is presented while considering separately the two alleles of each individual, namely a minor (shorter) and a major (longer) allele. This study has found that the KCNN3 allele distribution in the general Israeli population does not differ significantly in at least four Jewish ethnic groups of Ashkenazi, North African, Iraqi, and Yemenite origin. These have been used as control groups in a matched case-control analysis that has demonstrated a significant over-representation of KCNN3 alleles with longer CAG repeats among AN patients (P < 0.001 for the major allele and P = 0.035 for allele sum). Under dichotomization, a significantly higher prevalence of the L allele (>19 repeats) has been observed among AN patients (P < 0.001). While considering AN and co-morbid phenotypes, a tendency towards longer (L) alleles has been observed in the subset of patients with obsessive-compulsive disorder (OCD) co-morbidity. These findings further implicate KCNN3 as a significant contributor to predisposition to AN.     

Electroconvulsive therapy in adolescent and adult psychiatric inpatients--a retrospective chart design

BACKGROUND: The knowledge available on electroconvulsive therapy (ECT) in adolescents is largely anecdotal, or based on findings from adults. The aim of the present study is to compare the use of ECT in adolescent and adult inpatients. METHODS: We retrospectively analyzed the files of all 36 adolescent (between the ages of 13 and 19) and 57 randomly selected adult inpatients (above the age of 20) treated with ECT in a university-affiliated mental heath center in Israel between 1991 and 1997. RESULTS: Sixty one percent of the adolescents improved by the end of treatment, and 53% were not hospitalized in the subsequent year. The respective percentages among adults were 83% and 49%. Whereas most adults were treated with ECT because of schizophrenic disorders, almost half of the adolescents received ECT for affective disorders. Significantly more adolescents were treated with ECT because of acute life-endangering conditions (catatonia or severe suicidal risk). No significant adverse effects were found in both groups. LIMITATIONS: Our study is based on a retrospective chart review. The adolescent and adult groups are different in psychiatric morbidity, diagnosis and outcome, have not been assessed in a blind manner, and we have not used standardized psychometric batteries for the evaluation of ECT-related memory disturbances. CONCLUSIONS: ECT may be an effective, well-tolerated and safe procedure in both adult and adolescent inpatients.     

Involvement of tumor necrosis factor alpha and interleukin-1beta in enhancement of pentylenetetrazole-induced seizures caused by Shigella dysenteriae

Neurologic manifestations, mainly convulsions, are the most frequent extraintestinal complications of shigellosis. We used an animal model to study the roles of tumor necrosis factor alpha (TNF-alpha) and interleukin-1 beta (IL-1beta) in Shigella-related seizures. Administration of Shigella dysenteriae 60R sonicate enhanced the sensitivity of mice to the proconvulsant pentylenetetrazole (PTZ) within 7 h. This was indicated by a significantly higher mean convulsion score and an increased number of mice responding with clonic-tonic seizures in the Shigella-pretreated group. Preinjection of mice with anti-murine TNF-alpha (anti-mTNF-alpha) or anti-murine IL-1beta (anti-mIL-1beta) 30 min prior to administration of Shigella sonicate abolished their enhanced response to PTZ at 7 h. Mean convulsion scores were reduced by anti-mTNF-alpha from 1.2 to 0.8 (P = 0.017) and by anti-mIL-1beta from 1.3 to 0.7 (P = 0.008). Preinjection of anti-mTNF-alpha also reduced the percentage of mice responding with clonic-tonic seizures, from 48 to 29% (P = 0.002), and preinjection of anti-mIL-1beta reduced it from 53 to 21% (P = 0. 012). Neutralization of TNF-alpha or IL-1beta did not protect the mice from death due to S. dysenteriae 60R. These findings indicate that TNF-alpha and IL-1beta play a role in the very early sensitization of the central nervous system to convulsive activity after S. dysenteriae administration. Similar mechanisms may trigger neurologic disturbances in other infectious diseases.     

Impact of Treatment for Childhood Obesity on Parental Risk Factors for Cardiovascular Disease

Background. Family-based approaches using the parents as agents of change to treat childhood obesity are superior to programs targeting only children in achieving weight reduction and have a lower dropout rate.Objective. The aim of this study was to compare the impact of two behavioral approaches (parents only vs children only) for the treatment of childhood obesity on parental weight, eating, and activity habits as well as cardiovascular risk factors.Design. A randomized 1-year clinical intervention study was performed.Methods. Sixty obese children (≥20% over ideal weight for age, height, and sex), ages 6–11 years, were randomly allocated to the experimental (parents as sole agents of change) or conventional groups (children as sole agents of change). Fourteen (1-h-long) support/educational sessions were conducted by a clinical dietitian for the parents in the experimental group and 30 sessions for children in the conventional group. Anthropometric and biochemical measurements were determined at the start and end of the program.Results. The experimental approach, when compared to the conventional intervention, was found to be superior in the reduction of fathers overweight (P < 0.05). The former approach resulted also in improved profile of risk factors for cardiovascular disease in both parents. These changes could be ascribed to a greater improvement in eating and activity behaviors observed in parents belonging to the experimental intervention group who participated in a family-based intervention to treat their children's obesity.Conclusions. Treatment of childhood obesity targeting the parents as the sole agent of change, which is more effective for the treatment of childhood obesity when compared to a children-oriented program, may in addition award parents with the benefit of changing their own eating and activity patterns, thus making this program ideal for treatment of obesity in children and their overweight parents.     

Clozapine in elderly psychiatric patients: tolerability, safety, and efficacy.

Psychotic disorders in the elderly are frequent, of multiple etiologies, and little researched. With the advent of "atypical" neuroleptics, their role in treating elderly psychiatric patients needs to be investigated. Clozapine is widely used; however, its use is common in the elderly whose psychosis is a feature of neurological morbidity (Parkinson's disease, dementia, etc.), making it difficult to ascertain the safety, tolerability, and efficacy in psychiatric disorders in late life. The aim of the present review is to evaluate clozapine's effect in elderly psychiatric patients with no neurological comorbidity. A computerized literature search (MedLine 1966 to 1997) revealed 133 patients fulfilling said criteria. Fifteen patients had side effects and/or adverse events during treatment; nine of these were receiving a dosage greater than 100 mg clozapine daily. In 19 patients, treatment was discontinued, three due to noncompliance and 16 due to side effects. In seven patients, leukopenia/agranulocytosis was reported. The majority of side effects (27 of 34) and treatment discontinuations were within the first 90 days of treatment. Although efficacy is difficult to compare across studies because of differing methods of evaluation, the great majority of patients showed moderate to marked improvement of psychotic features. The reported effectiveness in patients able to continue treatment for extended periods is significant. Thus, clozapine at a relatively low mean dose (134 mg daily) seems to be safe, tolerated, and effective in elderly psychiatric patients. Agranulocytosis is more frequent than in younger adults and should be monitored carefully.