Correlated changes in symptoms and neurotransmitter indices during maintenance treatment with clozapine or conventional neuroleptics in adolescents and young adults with schizophrenia.

A study of 40 young patients (age 14-22 years) with DSM-III-R schizophrenia (without substance abuse) was conducted following a mean of 3.4 years of neuroleptic treatment. After failing on conventional agents in clinical trials lasting a mean of 2 years, 20 patients were prospectively maintained on open-label clozapine (mean 324 mg daily), and another 20 patients continued on typical neuroleptics (mean 465 mg chlorpromazine-equivalents daily). Patients were then sampled for biochemical measures and assessed for psychopathology (Brief Psychiatric Rating Scale, Scales for the Assessment of Positive/ Negative Symptoms) on six occasions at consecutive 6-week intervals-during maintenance treatment on clozapine or conventional neuroleptics. There were 22-fold interindividual differences in clozapine levels and also high intraindividual differences over time. Maintenance dosage was linearly related to plasma levels of clozapine and its metabolites. Prolactin levels were elevated with typical neuroleptics but not clozapine. Blood levels of serotonin, methoxyhydroxyphenylglycol (MHPG), norepinephrine, and epinephrine (but not dopamine) were significantly higher in clozapine-treated patients than in conventionally treated patients. Higher serotonin levels were associated with significantly fewer negative symptoms, whereas higher MHPG levels were correlated with less depression. These findings suggest involvement of norepinephrine and serotonin in the pathophysiology of schizophrenia (with depression associated with lower MHPG levels and negative symptoms associated with lower serotonin levels) and in the therapeutic actions of clozapine. Speculatively, a treatment strategy of targeting specific neurotransmitter systems might be based on the presence of specific symptoms in adolescents and young adults with schizophrenia.

Childhood-onset schizophrenia: history of the concept and recent studies.

Schizophrenic disorders in childhood are rare: 0.1-1 percent of all schizophrenic disorders manifest themselves before age 10, and 4 percent before age 15. There is, however, a remarkable increase in schizophrenia during adolescence. Age and developmental stage also influence symptoms, course, and outcome. The evidence for a male preponderance in the very early-onset group (< 14) does not apply for adolescents over age 14. The presence of positive and negative precursor symptoms can be demonstrated in child and adolescent schizophrenia before the first clinical manifestation leading to inpatient treatment. With regard to pharmacologic treatment, atypical neuroleptics such as clozapine can be used successfully. As to outcome, schizophrenic psychoses with early manifestation have a poor prognosis. The patients' premorbid personality also seems to be of great importance: A poor prognosis can be found in patients who were cognitively impaired, shy, introverted, and withdrawn before the beginning of their psychotic state.