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; percentage 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.

No evidence for a parent-of-origin effect detected in the pattern of inheritance of schizophrenia.

BACKGROUND: Schizophrenia is a complex genetic disorder with no clear pattern of inheritance. Epigenetic modification of genes may thus play a role in its transmission. METHODS: In our study, 439 families with at least two ill siblings with schizophrenia (208 with unilineal transmission) were examined for evidence of a parent-of-origin effect (e.g., evidence of parental imprinting on the familial transmission of schizophrenia). RESULTS: No significant difference in the prevalence of maternal compared with paternal transmission was found. In addition, affected male subjects did not differ from affected female subjects in the proportion of their offspring diagnosed with schizophrenia. CONCLUSIONS: Although the transmission of schizophrenia may be influenced by epigenetic events, our study fails to find evidence that one epigenetic mechanism, a parent-of-origin imprinting effect, determines whether an individual expresses the illness.

Lack of evidence for linkage to chromosomes 13 and 8 for schizophrenia and schizoaffective disorder.

A previous report [Blouin et al., 1998: Nat Genet 20:70-73] suggesting linkage to chromosomes 13q32 and 8p21 in families with schizophrenia led us to investigate these regions in a large set of 301 multiplex families with schizophrenia. Multipoint analyses failed to reveal evidence for linkage to any portion of chromosome 13, while only a weakly positive score was present on 8p using the identical marker reported in the earlier report. Failure to confirm the Blouin et al claims in a substantially larger cohort adds emphasis to the inconsistency of the findings concerning linkage in schizophrenia. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:235-239, 2000.

Failure to establish linkage on the X chromosome in 301 families with schizophrenia or schizoaffective disorder.

The hypothesis that a gene for susceptibility to psychosis (specifically in the X-Y homologous class) is located on the sex chromosomes has been proposed. Such a gene would account for the excess of sex chromosome anomalous males and females in populations of patients with psychosis, a tendency towards concordance by sex within families, and sex differences associated with psychosis and its underlying brain pathology. In earlier studies we observed small positive LOD scores in Xp11, and in a more recent and larger cohort of 178 sibling pairs, a peak multipoint nonparametric LOD score of 1. 55 at the locus DXS8032 in Xq21. The present study with a new set of markers extended the cohort to 301 ill sibling pairs and their parents. Despite the increase in sample size, the LOD score did not increase. A peak NPL of 1.55 was observed at the locus DXS1068 in proximal Xp, a region remote from the previous report. Separating families into those who were more likely to have X chromosome inheritance (maternal with no male to male transmission) did not yield stronger findings. In spite of the evidence that psychosis is related to a sex-dependent dimension of cerebral asymmetry, it is concluded that no consistent linkage of schizophrenia to the X chromosome can be demonstrated. In the context of the general failure of replication of linkage in psychosis, the possibility that the genetic predisposition to psychosis is contributed to by epigenetic modification rather than variations in the nucleotide sequence has to be considered.

Treatment and recovery rate in depression: a critical analysis.

The objective of this study was to evaluate the frequency and consequences of the presence of residual symptoms in patients treated for major depression. The literature specifically focused on recovery and residual symptomatology of depression was reviewed. Thirty per cent or more of treated patients present residual symptoms. These symptoms appear to be associated with a higher frequency and larger number of relapses and equally affect the outcome of depression in different age groups. They also seem to have a major impact on work and psychosocial functioning because of cognitive dysfunction and a reduction in social interaction affecting patients' quality of life. We found that there is scant literature on residual symptoms contrasting with the profuse reports on single or multiple antidepressant drug trials. Studies focusing on this important issue in the treatment of depression are needed.

New strategies for old problems: tardive dyskinesia (TD). Review and report on severe TD cases treated with clozapine, with 12, 8 and 5 years of video follow-up.

Tardive dyskinesia (TD) is the most feared and troublesome extrapyramidal side-effect of prolonged neuroleptic (NL) treatment. We present a review of TD. Its pathophysiology remains elusive, although extrapyramidal symptoms (EPS) increase the liability for TD. Nowadays, therefore, avoidance of all EPS remains the best preventive strategy, as it is not possible to predict which liable patients will develop TD, or of what type or severity. TD frequently includes dystonic features, and is more disabling when these dystonias are present. Clozapine (CLZ) has been reported to be effective in suppressing nearly 60% of TD syndromes, specially those with dystonic features. Based on the few reports in the literature on CLZ and TD by the early 1980s, we started to videotape the first severe TD patient treated with CLZ in 1984. We present the first three case reports of severe TD, with prominent disabling dystonic features, treated with CLZ and videotaped since pretreatment and then periodically for 12, 8 and 5 years of follow-up, respectively. The patients' current diagnosis, gender and age are: Case 1, DSM-IV Schizophrenia Residual Type, male, 39 years; Case 2, DSM-IV Polysubstance Related Disorder, Borderline Personality Disorder, female, 28 years; Case 3, DSM-IV Schizoaffective Disorder, male, 40 years. Two of them presented with a recurrence of TD because of CLZ interruption within the first 2 months of treatment, with no further breakthrough to date. The first two cases have complete remission of TD; the third case is still improving after 5 years of CLZ treatment, with only minor dystonic features persisting that constitute no impairment for work or daily routines at present. All patients, independent of their psychiatric primary diagnosis, have shown significant and progressive improvement in both motor and psychosocial aspects. None of them has been rehospitalized. Long-term treatment and follow-up is required to avoid TD recurrence and to assure full assessment of treatment effectiveness. Ideally, periodic video recording with standardized examination is advisable for long-term follow-up and outcome assessment. At present, CLZ could be regarded as the drug of choice for patients with TD, specially for those with disabling and or dystonic features and who require ongoing NL therapy. The use of novel antipsychotic agents for TD treatment and prevention, with their low EPS liability, is promising, but has yet to be tested.

Dorsomedial thalamotomy as a treatment for terminal anorexia: a report of two cases.

Anorexia nervosa has been considered a compulsive obsessive disorder (OCDS). We present a case report of two patients, male and female, suffering from an extremely severe, chronic and refractory anorectic syndrome. Both patients underwent bilateral stereotactic thalamotomy with involvement of the lamella medialis. Follow-up was 4 year and 2 year, respectively. Both patients have regained weight and improved significantly in terms of their obsessive-compulsive symptoms and in their quality of life. The results suggest that anorexia nervosa may be considered in the OCDS.

Actividad electrica amigdalino-piriforme registrada con tecnica estereotaxica. / Amygdala-pyriform electric activity registered with stereotaxic technic

Se presenta una serie de registros en area piriforme y nucleo amigdalino realizados en 26 pacientes sometidos a operacion estereotaxica por diferentes causas. El modo particular de actividad electrica espontanea detectada en esas regiones se supone relacionado con una funcion convergente de potenciales aferentes, sin connotacion patologica