Age-associated alterations in corpus callosum white matter integrity in bipolar disorder assessed using probabilistic tractography.

OBJECTIVES: Atypical age-associated changes in white matter integrity may play a role in the neurobiology of bipolar disorder, but no studies have examined the major white matter tracts using nonlinear statistical modeling across a wide age range in this disorder. The goal of this study was to identify possible deviations in the typical pattern of age-associated changes in white matter integrity in patients with bipolar disorder across the age range of 9-62 years. METHODS: Diffusion tensor imaging was performed in 57 (20 male and 37 female) patients with a diagnosis of bipolar disorder and 57 (20 male and 37 female) age- and sex-matched healthy volunteers. Mean diffusivity and fractional anisotropy were computed for the genu and splenium of the corpus callosum, two projection tracts, and five association tracts using probabilistic tractography. RESULTS: Overall, patients had lower fractional anisotropy and higher mean diffusivity compared to healthy volunteers across all tracts (while controlling for the effects of age and age(2) ). In addition, there were greater age-associated increases in mean diffusivity in patients compared to healthy volunteers within the genu and splenium of the corpus callosum beginning in the second and third decades of life. CONCLUSIONS: Our findings provide evidence for alterations in the typical pattern of white matter development in patients with bipolar disorder compared to healthy volunteers. Changes in white matter development within the corpus callosum may lead to altered inter-hemispheric communication that is considered integral to the neurobiology of the disorder.

Prevalence and correlates of antipsychotic polypharmacy in children and adolescents receiving antipsychotic treatment.

Antipsychotic polypharmacy (APP), which is common in adults with psychotic disorders, is of unproven efficacy and raises safety concerns. Although youth are increasingly prescribed antipsychotics, little is known about APP in this population. We performed a systematic PubMed search (last update 26 January 2013) of studies reporting the prevalence of APP in antipsychotic-treated youth. Summary statistics and statistical tests were calculated at the study level and not weighted by sample size. Fifteen studies (n = 58 041, range 68-23 183) reported on APP in youth [mean age = 13.4 ± 1.7 yr, 67.1 ± 10.2% male, 77.9 ± 27.4% treated with second-generation antipsychotics (SGAs)]. Data collected in these studies covered 1993-2008. The most common diagnoses were attention-deficit hyperactivity disorder (ADHD; 39.9 ± 23.5%) and conduct disorder/oppositional defiant disorder (CD/ODD; 33.6 ± 24.8). In studies including predominantly children (mean age = <13 yr, N = 5), the most common diagnosis were ADHD (50.6 ± 25.4%) and CD/ODD (39.5 ± 27.5%); while in studies with predominantly adolescents (mean age = ⩾13 yr, N = 7) the most common diagnoses were schizophrenia-spectrum disorders (28.6 ± 23.8%), anxiety disorders (26.9 ± 14.9%) and bipolar-spectrum disorders (26.6 ± 7.0%), followed closely by CD/ODD (25.8 ± 17.7). The prevalence of APP among antipsychotic-treated youth was 9.6 ± 7.2% (5.9 ± 4.5% in child studies, 12.0 ± 7.9% in adolescent studies, p = 0.15). Higher prevalence of APP was correlated with a bipolar disorder or schizophrenia diagnosis (p = 0.019) and APP involving SGA+SGA combinations (p = 0.0027). No correlation was found with APP definition [⩾1 d (N = 10) vs. >30-⩾90 d (N = 5), p = 0.88]. Despite lacking safety and efficacy data, APP in youth is not uncommon, even in samples predominantly consisting of non-psychotic patients. The duration, clinical motivations and effectiveness of this practice require further study.

Clozapine-Induced Myocarditis: A Case Report of an Adolescent Boy with Intellectual Disability.

Background. Although known for its efficacy in treatment-resistant schizophrenia, the usage of clozapine has been limited due to concerns over potential adverse effects. Myocarditis, one potential fatal complication, can develop at any point during treatment but has been most commonly observed 2-3 weeks after clozapine initiation. Objective. A case of acute clozapine-induced myocarditis is described, highlighting the history, onset, and treatment course of presentation. There is a need to raise awareness of this potential complication, especially in the pediatric population. Results. 17-year-old Puerto Rican boy, with history of schizophrenia, disorganized type (treatment resistant), and intellectual disability, developed myocarditis on the thirteenth day following clozapine commencement. Initial presenting symptoms included tachycardia, lethargy, and vague gastrointestinal distress. Patient fully recovered after supportive medical care and clozapine discontinuation. Conclusions. Myocarditis is a known potential complication of clozapine initiation; however, due to its limited usage in the pediatric population, reported cases are limited. There is a need to establish evidence-based monitoring guidelines for clozapine usage, particularly in the pediatric population where the presentation may be atypical and clinical suspicion may be overlooked.