Roberto Mester

Elevated levels of serum interleukin-1β in combat-related posttraumatic stress disorder

Levels of serum interleukin-1 beta (IL-1 beta) and soluble interleukin-2 receptor (sIL-2R) were assessed in 19 male patients with combat-related posttraumatic stress disorder (PTSD) in comparison to 19 age- and sex-matched healthy volunteers. Serum IL-1 beta levels (but not sIL-2R) were significantly higher (p < .001) in the PTSD patients than in the controls. IL-1 beta levels did not correlate with cortisol levels, severity of PTSD, anxiety, depressive symptoms, or alexithymia score; however, they did correlate significantly (r = .54, p < .005) with the duration of PTSD symptoms. It is possible that desensitization of the hypothalamic-pituitary-adrenal axis in chronic PTSD patients counteracts the stimulatory effect of IL-1 beta on cortisol secretion.

Increased serotonin 5-HT2 receptor binding on blood platelets of suicidal men.

In search of a physiological marker of depression and suicidal behavior, serotonin receptors of the 5-HT2 type were studied on platelet membranes from 19 control and 22 suicidal subjects. All were young, drug — and medication free men (18–21-years-old). 5-HT2 receptor binding was assayed using tritiated ketanserine at two concentrations. Receptor binding in the suicidal subjects was significantly higher than controls at both concentrations, the mean difference being around 50%. A similar difference between patients with major depressive disorder and matched controls has been observed previously. These findings support the use of 5-HT2 receptors on platelets as a research and diagnostic tool in depression and suicide.

Circulatory levels of catecholamines, serotonin and lipids in attention deficit hyperactivity disorder.

Attention deficit hyperactivity disorder (ADHD) may be associated with a dysregulation of the catecholaminergic and serotonergic systems. Furthermore, ADHD is frequently complicated by aggressive impulsive behaviour, which is suggested to be related to low serum cholesterol levels. We examined the relationship between blood serotonin, norepinephrine, dopa and lipid levels and the degree of hyperactivity, impulsiveness, lack of concentration, and aggressiveness in boys with ADHD of low and high severity as determined by a specially designed formulated scale based on the DSM‐IV criteria for ADHD. No differences were noted between the groups in any of the peripheral biological parameters except blood serotonin, for which a tendency (P =0.08) towards lower levels was observed in the children with more severe disorder. We conclude that children with severe ADHD may have a different serotonin turnover compared to children with mild ADHD. These results may have implications for our understanding of the pathogenesis of ADHD, at least the more severe type.

Combined electroconvulsive-clozapine therapy.

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.

Analysis of neurosteroid levels in attention deficit hyperactivity disorder

Neurosteroids are important neuroactive substrates with demonstrated involvement in several neurophysiological and disease processes. Attention deficit hyperactivity disorder (ADHD) has been associated with dysregulation of the catecholaminergic and serotonergic systems, however its relationship to irregularities or changes in neurosteroid levels remains unknown. We examined the relationship between blood levels of dehydroepiandrosterone (DHEA), its principal precursor pregnenolone and its principal metabolite dehydroepiandrosterone sulphate (DHEAS) in 29 young male subjects aged 7-15 years with DSM-IV criteria of ADHD. Subjects were evaluated by a specially designed scale, following which patients were divided into two groups according to severity of symptomatology. Results indicated significant inverse correlations between clinical symptomatology and levels of DHEA and pregnenolone in the total group. These inverse correlations were particularly evident in the less severe group of subjects. Levels of DHEA and DHEAS were inversely correlated with the hyperactivity subscale. Furthermore, using median blood levels as a cut-off indicator, higher blood levels of DHEA and DHEAS were associated with fewer ADHD symptoms, in particular hyperactivity symptomatology. Our findings suggest a possible protective effect of various neurosteroids on the expression of ADHD symptomatology.

Reduction of Aggressiveness and Impulsiveness during Clozapine Treatment in Chronic Neuroleptic-Resistant Schizophrenic Patients

Aggressive and impulsive behavior is frequently observed in schizophrenic patients. Previous studies suggest that impulsive aggression may be the most common behavioral correlate of central serotonergic system dysfunction. This study was aimed to determine if clozapine, an atypical antipsychotic agent with potent serotonergic antagonistic properties, can reduce impulsiveness and aggression in neuroleptic-resistant chronic schizophrenic patients. Fourteen neuroleptic-resistant chronic schizophrenic patients were treated with clozapine and prospectively evaluated for aggressiveness and impulsiveness for 18 weeks. Clozapine treatment induced a marked decrease in impulsiveness (32% on the Impulsivity Scale; p < 0.0001) and aggressiveness (98% on the Overt Aggression Scale; p < 0.0001). We conclude that clozapine treatment may be effective in reducing psychotic symptoms as well as in controlling aggressive and impulsive behavior in neuroleptic-resistant chronic schizophrenic patients.

Clozapine Treatment in Very Early Onset Schizophrenia

Very early onset schizophrenic patients only partially benefit from conventional antipsychotic treatment and are at increased risk for developing tardive dyskinesia (TD). Clozapine, which lacks extrapyramidal side effects including TD, has been proved effective for adult schizophrenic patients who are resistant to other neuroleptics. Clozapine, therefore, may offer an alternative treatment for these patients. The authors report four successful trials of clozapine in children aged 10 to 12 years old with schizophrenia, the youngest group reported on to date, who were unresponsive to conventional neuroleptic treatment.

The impact of clozapine treatment on serum lipids in chronic schizophrenic patients

The aim of this retrospective study is to determine whether lipid levels rise in neuroleptic-resistant chronic schizophrenic patients during clozapine treatment and if this rise is correlated with a decrease in aggressive and suicidal behavior. Seventy neuroleptic-resistant schizophrenic patients treated with clozapine for at least 6 months were compared with 30 chronic schizophrenic patients treated with classic antipsychotic agents for the same length of time. Data on serum levels of cholesterol and triglycerides and on aggressive and suicidal behavior, as measured by the Overt Aggression Scale (OAS), were collected in both groups before treatment and 6 months later. A significant reduction in aggressive and suicidal behavior was noted in the clozapine-treated group but not in the classical antipsychotic-treated group. Clozapine treatment was associated with an elevation in serum triglyceride level, whereas classic antipsychotic treatment was associated with an increase in serum cholesterol level. We conclude that serum cholesterol level does not play a role in the clozapine-induced attenuation in aggressive and suicidal behavior in neuroleptic-resistant schizophrenic patients, though the accompanying elevation in triglycerides may be relevant to a behavioral effect.

Olanzapine treatment in chronic drug-resistant childhood-onset schizophrenia: an open-label study.

The use of typical antipsychotics is limited in children with schizophrenia, owing to the high rate of response failure and early appearance of extrapyramidal syndromes as well as tardive and withdrawal dyskinesia. The aim of the present study was to examine the effectiveness of the atypical antipsychotic olanzapine in the treatment of childhood-onset schizophrenia. The study sample included nine children hospitalized for schizophrenia who had proven refractory to treatment with at least two antipsychotic drugs. Olanzapine was administered after a 2-week washout period in gradually increasing doses to a maximum of 5 mg/day on day 5 and 10 mg/day in week 3; six patients received up to 20 mg/day as of week 5. The duration of the study was 12 weeks. Patient psychiatric status was measured with three scales at onset of therapy and thereafter once weekly. Patients also underwent regular blood, laboratory, and liver function tests, and we also monitored their blood pressure and weight and performed electrocardiography and electroencephalography. A reduction in all psychopathology scores was obtained at 12 weeks from baseline. All extrapyramidal symptoms of previous medications resolved, and there were no new incidents. Side effects were mild. There were no adverse changes in blood chemistry, hematological tests, or electrocardiography parameters, but the treatment was associated with a significant weight gain (6.10 +/- 3.25 kg). At 1-year follow-up, the improvement in psychiatric symptoms was sustained in eight children. We conclude that olanzapine may have potential as a first-line drug in the treatment of drug-resistant childhood-onset schizophrenia. Large-scale, double-blind, placebo-controlled comparative studies are needed to clarify the role of the various atypical antipsychotics in both treatment-resistant and treatment-naïve populations with psychotic symptoms/disorders.

Trihexyphenidyl treatment of clozapine-induced hypersalivation.

The objective of this study was to investigate the efficacy of the anticholinergic agent trihexyphenidyl in the treatment of cluzapine-induced hypersalivation. Fourteen chronic schizophrenic patients who exhibited nocturnal hypersalivation during clozapine treatment were coadministered trihexvphenidyl (5–15 mg/day, at bedtime) for 15 days. Salivation was assessed by a single-item 5-point scale. A reduction of 44% in the reported nocturnal hypersalivation was observed after trihexyhenidyl treatment. These results indicate that at least some; chronic schizophrenic patients with clozapine-induced nocturnal hypersalivation may benefit from anticholinergic treatment.