Molecular genetic studies of ADHD: 1991 to 2004 Bobb, Aaron J.; Castellanos, F. Xavier; Addington, Anjene M. ...
American journal of medical genetics. Part B, Neuropsychiatric genetics,
5 September 2006, Letnik:
141B, Številka:
6
Journal Article
Objective: Clozapine is a unique atypical antipsychotic with superior efficacy in treatment-resistant schizophrenia. Plasma concentration of clozapine and its major metabolite N-desmethylclozapine ...(NDMC) as well as the ratio of NDMC to clozapine have been reported to be predictors of clozapine response. Here we evaluate these as well as other measures in an effort to find predictors of response to clozapine in our early-onset treatment-refractory population. Method: Fifty-four children and adolescents participated in double-blind (n = 22) or open-label (n = 32) clozapine trials. Clinical evaluations took place at baseline, week 6 on clozapine, and at 2- to 6-year follow-up. The data were analyzed in relation to demographics, age at onset, IQ, clozapine dose, and plasma concentrations of prolactin, clozapine, NDMC, and NDMC/clozapine ratio. Stepwise regression and correlation analyses were performed to find predictors of treatment response. Results: Clinical improvement after 6 weeks of clozapine treatment, as measured by the percentage of improvement on the Brief Psychiatric Rating Scale and the Scale for the Assessment of Positive Symptoms, was strongly associated with the NDMC/clozapine ratio at the 6-week time point (Pearson correlation coefficient: r = 0.41; p less than 0.01 for Brief Psychiatric Rating Scale and r = 0.43; p less than 0.01 for Scale for the Assessment of Positive Symptoms). Although the rate of side effects was higher than that typically found in the adult population, it did not appear to be related to clozapine dose, clozapine or NDMC plasma concentrations, or NDMC/clozapine ratio. Outcome at long-term follow-up, as measured by Children's Global Assessment Scale, was associated with lesser illness severity at baseline and with greater improvement during the initial 6 weeks of clozapine treatment. Conclusions: The NDMC/clozapine ratio may be a valuable predictor of response to clozapine and may suggest new approaches to clozapine treatment. (Contains 5 tables.)
Objective: Weight gain is a serious side effect of atypical antipsychotics, especially in childhood. In this study, the authors examined six weight gain-related hormones in patients with ...childhood-onset schizophrenia (COS) after 6 weeks of clozapine treatment. Method: Fasting serum samples for 24 patients with COS and 21 matched healthy controls (HC) were obtained. Levels of leptin, insulin, adiponectin, amylin, reline, and tumor necrosis factor alpha were measured and compared between the groups. For 23 patients with COS, hormonal levels were measured at background and week 6 of clozapine treatment. Change in body mass index was correlated with levels of clozapine and changes in hormonal levels and clinical ratings. Results: At baseline, COS did not differ significantly from HC on any hormonal measure. Clozapine treatment was associated with significant (7.9% + or - 8.5%) increase in mean body mass index. Only leptin levels increased significantly from baseline to week 6 on clozapine (p = .003). Body mass index increase was significantly correlated with decrease in reline and adiponectin and was positively correlated with clinical improvement. Conclusions: This is the first study of weight gain-related hormones in children on clozapine. Hormonal changes are correlated with weight gain. How effectiveness of clozapine is linked to weight gain remains uncertain.
Opinion statement
Millions of Americans develop cannabis use disorder, which requires treatment to prevent numerous associated adverse outcomes. There are several evidence-based behavioral ...interventions, including motivational interviewing, motivational enhancement therapy, cognitive behavioral therapy, contingency management, and multidimensional family therapy, all with moderate effectiveness. None of the behavioral interventions are clearly superior to any of the others, whether in combination or alone. Thus, individual patient and therapist factors, such as patient preference and therapist expertise, should determine which is used. Currently, there are no FDA-approved medications for treatment of cannabis use disorder. Some pharmacologic agents have shown promise in early studies, most notably n-acetylcysteine and gabapentin, but none have been replicated. Given that gabapentin and buspirone have been widely used in psychiatric populations and have relatively few side effects, either could be considered as an augmenting agent to behavioral interventions, but neither should be continued for more than 12 weeks unless there is clear evidence of reduction in use. Evidence suggests venlafaxine and naltrexone are not effective in reducing use.
Pre-, peri-, and postnatal obstetric complications (OC) are reported to be more frequent in adult patients with schizophrenia and have been linked to both greater severity and to “earlier” age of ...onset (before either age 18 or 22) in studies of adult patients. We hypothesized that by extrapolation, patients with childhood-onset schizophrenia (COS), with very early onset and very severe illness, would have had more numerous or more salient OC compared with their healthy siblings.
We compared the obstetric records of 60 COS children and 48 healthy siblings using the Columbia Obstetrics Complication Scale, a comprehensive measurement scale consisting of 37 variables having included a separate scale for fetal hypoxia.
Patients with COS did not have a higher incidence of OC than the healthy sibling control group with the exception of increased incidence of maternal vomiting.
Obstetric complications, with the possible exception of maternal vomiting, are unlikely to play a major role in the etiopathogenesis of childhood-onset schizophrenia.
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