[Follow-up of a 16-year-old adolescent with early-onset schizophrenia and catatonic symptoms]. / Suivi thérapeutique d'un adolescent de 16ans souffrant de schizophrénie précoce avec symptômes catatoniques.

INTRODUCTION: The aim of this paper is to underline the need of a systematic monitoring (1) of atypical antipsychotics and (2) of catatonic symptoms in child psychiatry. We present in this paper the clinical history of a 16-year-old adolescent inpatient needing a prescription of atypical antipsychotic drug. We present the most relevant results of our clinical monitoring over 7 months. CASE REPORT: A 16-year-old Caucasian male adolescent, by the name of Paul, was admitted in August 2009 to an Adolescent University Psychiatry Unit for an acute psychotic disorder. On admission, he presented paranoid delusion, auditory hallucinations and impulsive movements. The score on the Bush-Francis Catatonia Rating Scale (BFCRS) was 17 (the threshold score for the diagnosis of catatonic symptoms is 2). Laboratory tests showed the lack of blood toxic levels, creatine phosphokinase (CPK) level was 684 IU/L. Paul was treated with clonazepam (0.05 mg/kg/d). This particular day was considered to be day #1 of the clinical drug monitoring. Immediately after, regular follow-up of catatonic symptoms was performed. On day #15, the CPK level returned to normal with improvement of clinical catatonia but with still a score of 4 on the BFCRS scale. Auditory hallucinations and delusion persisted. Risperidone treatment was begun (1mg/d and 1.5mg/d after 24 hours), associated with oral clonazepam (0.05 mg/kg/d). On day #17, after 48 hours of improvement of delusion, the catatonic symptoms rapidly worsened. Risperidone was stopped; Paul was transferred to intensive care where he was treated with clonazepam IV (0.1mg/kg/d). The score on BFCRS scale was 20, Paul presented no fever and the CPK level was below 170 IU/L. The diagnosis was a relapse of the catatonic episode, which was caused by the administration of risperidone. On day #24, no improvement in the state of catatonia was obtained. The treatment was changed with the following combination of medicine: clonazepam (0.1mg/kg/d)-lorazepam (5mg/d)-carbamazepine (10mg/kg/d). With this combination, the state of catatonia improved quickly and on day #31, he was transferred to the adolescent psychiatry unit. However, delusion and hallucinations persisted; a treatment with olanzapine was started at 5mg/d and then progressively increased to 20mg/d for 10 days. On day #115, after 3 months with olanzapine, no improvement of the hallucinatory and delusional symptoms was observed; the diagnosis of early-onset refractory schizophrenia was established. The Therapeutic Drug Monitoring (TDM) confirmed the good compliance; clozapine was introduced and progressively increased up to 250 mg/d. On day #199, after 3 months under clozapine (250 mg/d), the speech was coherent and delusion was rare. During this period, no relapse of the catatonic state was observed. DISCUSSION: In this case, the BFCRS scale was sensitive to catatonic symptom diagnosis. CPK levels vary differently for each atypical antipsychotic and are not a specific complication indicator. In complex cases, the TDM seems useful when choosing atypical antipsychotics. CONCLUSION: The association of two benzodiazepines (clonazepam-lorazepam) with carbamazepin allowed the improvement of catatonic symptoms. Plasma levels of atypical antipsychotics helped the practitioner in deciding the type of care required: plasma levels confirmed the patient's treatment adherence and thus reinforced the choice of clozapine.

Associations between serum brain-derived neurotrophic factor levels and clinical phenotypes in schizophrenia patients.

This study investigated serum brain-derived neurotrophic factor (BDNF) protein levels in schizophrenia patients and healthy control subjects and schizophrenia patients with various clinical phenotypes. During a 1-year period, 126 schizophrenic patients and 96 healthy control subjects were recruited. Serum BDNF protein levels were measured using an ELISA Kit. Psychiatric diagnoses were made according to DSM-IV criteria. One-way analysis of variance (ANOVA) showed no significant differences in serum BDNF protein levels between schizophrenia and healthy normals. Additionally, no significant differences existed in BDNF levels between schizophrenia patients for the following variables: with/without a suicide attempt; antipsychotic drug use, family tendency and disease onset before and after 25 years old. However, patients with catatonic schizophrenia had lower serum BDNF protein levels than patients with paranoid or residual schizophrenia. These analytical results suggested that BDNF might play an important role in the clinical subtypes of schizophrenia, but it needed further investigation in future.

A prospective study of serum ghrelin levels in patients treated with clozapine.

We investigated serum ghrelin levels (SGL) in 12 patients with schizophrenia over a 10-week period after initiation of clozapine treatment. In contrast to increments of body mass indices (BMI, kg/m2) and serum leptin levels (SLL), no significant change in SGL was detected. Inverse correlations between delta SGL and delta SLL did not reach statistical significance. Linear mixed model analysis could not detect effects of age, sex, BMI, SLL and serum clozapine levels on SGL. Our results do not support a causal involvement of ghrelin in clozapine-related weight gain.

[Problem of side effects of leponex on blood (multicenter inter- national study)]. / K voprosu o pobochnom deistvii leponeksa na sostoianie krovi (mnogotsentrovoe mezhdunarodnoe issledovanie).

The authors provide the data on the dynamics of the hematological parameters during continuous leponex (clozapin) treatment of two group of patients treated in 1973-1989 at the All-Union Mental Health Research Center, USSR AMS (107 patients) and at 12 Research Centers of the USSR, CSFR, Bulgaria and Poland (642 patients). The mean duration of the treatment was 4.8 and 12.4 months respectively. Moderate leukopenia (3000-4000/ml) developed in 0.5 and 1.2% of all the analyses, the neutrophil/leukocyte ratio always remained within normal (50% and higher), whereas the neutrophil count did not drop below 1600/ml, i. e. it was not pathological. Despite the relatively long treatment no cases of granulocytopenia (or agranulocytosis) were recorded. It is shown that the side hematological effect is not related to the magnitude of the diurnal dose of leponex. Recommendations are given for wide use of leponex in medical practice under constant control of the blood status, with the use of the method of a slow and progressive augmentation of the daily dose.

Myelin basic protein antibodies in catatonic schizophrenia.

Myelin basic protein (MBP) antibodies were determined by solid-phase radioimmunoassay in the serum and cerebrospinal fluid of 10 patients with catatonia, 10 patients with other forms of schizophrenia, and 10 psychiatrically healthy controls. The mean counts per minute (cpm) value of serum anti-MBP antibody of the catatonia group was significantly higher than that of the patients with other forms of schizophrenic psychoses (p less than .05). No significant differences were observed among the cpm values of the CSF specimens from the three patient groups. The hypothesis of a central virus-induced immunologic aberration in catatonic schizophrenia is discussed.

Serum level monitoring of thiothixene in schizophrenia: acute single-dose levels at fixed doses.

After establishing a strong correlation between steady-state thiothixene levels and levels drawn 2.5 hours after a 20-mg test dose, the authors examined the correlation between clinical improvement and serum levels drawn 2.5 hours after a single 20-mg test dose of thiothixene. For 30 male schizophrenic inpatients, improvement on the Brief Psychiatric Rating Scale was significantly correlated with the single test-dose levels. Serum levels were also positively correlated with age, which may explain the tendency of elderly patients to require lower neuroleptic doses and to exhibit a higher incidence of side effects. The results suggest that acute single-dose levels may be useful in predicting clinical response to thiothixene.

The use of the dexamethasone suppression test in the differential diagnosis of catatonic stupor.

Catatonic stupor is a cluster of symptoms and not necessarily a disease entity. It may be seen not only in schizophrenia, but in major affective disorders, conversion disorders, organic brain syndromes, and atypical psychoses. The dexamethasone suppression test is a valuable tool in the diagnosis of major affective disorders, differentiating them from other types of psychopathology. In a twelve month retrospective study, five patients admitted to Psychiatric Institute of Atlanta were identified as meeting the criteria for catatonic schizophrenia. A dexamethasone suppression test was performed shortly after admission. Four of the five had patterns of inadequate suppression, indicative of a major affective disorder rather than a schizophrenic disorder. The dexamethasone suppression test is simple to administer, relatively painless, free from hazards, easy to interpret, readily available, and reliable. Not only can the dexamethasone suppression test be used in diagnosis, but also as a valuable aid in following the therapeutic progress in resolution of a major affective disorder.

Serotonin, folic acid, and uric acid metabolism in the diagnosis of neuropsychiatric disorders.

Metabolic compensation appears possible within the serotonergic, folate, purine system and it seems possible that clinical illness may result when the system can no longer compensate. For example, elevated serotonin, induced by stress accumulation of tryptophan, could be compensated by a lowered folate ratio, normalizing the beta-carboline index and preventing hallucinations. Conversely, deficient serotonin, induced by a psychological loss or transport deficit, could be compensated by raising the folate ratio, which would normalize the beta-carboline index and prevent further depression. Increased purine turnover would seemingly lower the folate ratio, compensating perhaps for hallucinatory activity or mania. Several genetic defects of enzymes or transport proteins could seemingly preclude normal compensations within the system.