Jorge Ospina

Olanzapine as alternative therapy for patients with haloperidol-induced extrapyramidal symptoms: results of a multicenter, collaborative trial in Latin America.

Conventional antipsychotic agents can induce extrapyramidal symptoms (EPS) that may be alleviated by switching patients to novel agents such as olanzapine. Patients with schizophrenia and related disorders (ICD-10) who were taking haloperidol (N = 94; mean dose = 12.7 mg/day) and had EPS (Simpson-Angus Scale [SAS] > 3) were directly switched to 6 weeks of open-label olanzapine treatment (mean dose = 11.4 mg/day). There were significant mean improvements (p <0.001 for all measurements) from baseline to endpoint on the SAS (−9.69 ± 5.33; percentage change, 87.2%), the Barnes Akathisia Scale (−1.00 ± 1.19; percentage change, 82.5%), and the Abnormal Involuntary Movement Scale (−1.48 ± 2.89; percentage change, 81.1%), and anticholinergic use decreased from 47.9% to 12.8% (mean baseline to endpoint change: −1.52 ± 1.91-mg equivalents of benztropine;p < 0.001). Significant mean baseline to endpoint improvements (p < 0.001 for all measurements) were observed on the Positive and Negative Syndrome Scale (PANSS; −25.28 ± 18.67; percentage change, 30.3%), the PANSS-extracted Brief Psychiatric Rating Scale (0–6 scale, −13.41 ± 10.16; percent-age change, 54.4%), and the Clinical Global Impressions Severity scale (−1.16 ± 1.19; percentage change, 26.4%). Spontaneously reported treatment-emergent adverse events with a greater than 5% incidence were somnolence (16.0%), increased appetite (14.9%), weight gain (11.7%), headache (8.5%), anxiety (7.4%), dizziness (6.4%), and insomnia (5.3%). Criteria for a successful switch were met by 90.5% of patients. Psychotic symptom exacerbation was experienced by 30.9% of patients at any time during the study and by 11.7% of patients at endpoint. Results suggest that a direct switch to olanzapine is a therapeutic option when patients with haloperidol-induced EPS are unable to tolerate a more gradual switch.

Transmission distortion of BDNF variants to bipolar disorder type I patients from a south american population isolate

Recent reports have implicated polymorphisms in the brain derived neurotrophic factor (BDNF) gene region in the etiology of several psychiatric phenotypes, including bipolar disorder. Significant disease association has been reported for the G allele at SNP rs6265, which encodes for Valine at position 66 of BDNF (Val66Met), an apparently functional variant of this key BDNF. Here we examined a sample of 224 bipolar type I patients and available parents (comprising a total of 212 nuclear families) ascertained in a South American population isolate (Antioquia, Colombia). We tested for transmission distortion to bipolar patients of alleles at the rs6265 polymorphism and at a microsatellite marker 1.3 kb away from this SNP. Significant excess transmission of the rs6265 G allele to cases was observed (χ2 = 10.77, d.f. = 1, P = 0.001). Two‐locus haplotype analysis showed a significant global transmission distortion (χ2 = 16.059, d.f. = 7, P = 0.025) with an excess transmission of a haplotype comprising the rs6265 G allele and microsatellite allele 227. These results are consistent with previous studies pointing to a role for BDNF in susceptibility to mood disorders.

A narrow and highly significant linkage signal for severe bipolar disorder in the chromosome 5q33 region in Latin American pedigrees.

We previously reported linkage of bipolar disorder to 5q33‐q34 in families from two closely related population isolates, the Central Valley of Costa Rica (CVCR) and Antioquia, Colombia (CO). Here we present follow up results from fine‐scale mapping in large CVCR and CO families segregating severe bipolar disorder, BP‐I, and in 343 population trios/duos from CVCR and CO. Employing densely spaced SNPs to fine map the prior linkage peak region increases linkage evidence and clarifies the position of the putative BP‐I locus. We performed two‐point linkage analysis with 1134 SNPs in an approximately 9 Mb region between markers D5S410 and D5S422. Combining pedigrees from CVCR and CO yields a LOD score of 4.9 at SNP rs10035961. Two other SNPs (rs7721142 and rs1422795) within the same 94 kb region also displayed LOD scores greater than 4. This linkage peak coincides with our prior microsatellite results and suggests a narrowed BP‐I susceptibility regions in these families. To investigate if the locus implicated in the familial form of BP‐I also contributes to disease risk in the population, we followed up the family results with association analysis in duo and trio samples, obtaining signals within 2 Mb of the peak linkage signal in the pedigrees; rs12523547 and rs267015 (P = 0.00004 and 0.00016, respectively) in the CO sample and rs244960 in the CVCR sample and the combined sample, with P = 0.00032 and 0.00016, respectively. It remains unclear whether these association results reflect the same locus contributing to BP susceptibility within the extended pedigrees.