Sexual dysfunction in patients with schizophrenia treated with conventional antipsychotics or risperidone

Hong Liu-Seifert1, Bruce J Kinon1, Christopher J Tennant2, Jennifer Sniadecki1, Jan Volavka31Lilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN, USA; 2CJT Biomedical Consulting, South Lake Tahoe, CA, USA; 3New York University, New York, NY, USAObjective: To better understand sexual dysfunction in patients with schizophrenia and its associations with prolactin and reproductive hormones.Methods: This was a secondary analysis of an open-label, one-day study (N = 402). The primary objective of the study was to assess the prevalence of hyperprolactinemia in patients with schizophrenia who had been treated with conventional antipsychotics or risperidone. Other atypical antipsychotics available at the time of the study were not included due to a more favorable prolactin profile.Results: The majority of patients (59% of females and 60% of males) reported impairment of sexual function. In postmenopausal females, risk of impaired sexual interest was increased by 31% for every 10 ng/ml increase in prolactin (p = 0.035). In males, lower testosterone was associated with higher prolactin (p < 0.001) and with orgasmic (p = 0.004) and ejaculatory dysfunction (p = 0.028).Conclusion: These findings suggest that hyperprolactinemia may be associated with sexual dysfunction. They also provide more information on the relationships between prolactin, reproductive hormones, and sexual dysfunction. Sexual dysfunction is an understudied yet important consideration in the treatment of schizophrenia. More attention is warranted in this area as it may provide opportunities for improved quality of life and adherence to treatment for patients.Keywords: sexual dysfunction, schizophrenia, hyperprolactinemia, antipsychotics, risperidon

Semantic inference using chemogenomics data for drug discovery

<p>Abstract</p> <p>Background</p> <p>Semantic Web Technology (SWT) makes it possible to integrate and search the large volume of life science datasets in the public domain, as demonstrated by well-known linked data projects such as LODD, Bio2RDF, and Chem2Bio2RDF. Integration of these sets creates large networks of information. We have previously described a tool called WENDI for aggregating information pertaining to new chemical compounds, effectively creating evidence paths relating the compounds to genes, diseases and so on. In this paper we examine the utility of automatically inferring new compound-disease associations (and thus new links in the network) based on semantically marked-up versions of these evidence paths, rule-sets and inference engines.</p> <p>Results</p> <p>Through the implementation of a semantic inference algorithm, rule set, Semantic Web methods (RDF, OWL and SPARQL) and new interfaces, we have created a new tool called Chemogenomic Explorer that uses networks of ontologically annotated RDF statements along with deductive reasoning tools to infer new associations between the query structure and genes and diseases from WENDI results. The tool then permits interactive clustering and filtering of these evidence paths.</p> <p>Conclusions</p> <p>We present a new aggregate approach to inferring links between chemical compounds and diseases using semantic inference. This approach allows multiple evidence paths between compounds and diseases to be identified using a rule-set and semantically annotated data, and for these evidence paths to be clustered to show overall evidence linking the compound to a disease. We believe this is a powerful approach, because it allows compound-disease relationships to be ranked by the amount of evidence supporting them.</p

Violent behaviour in early psychosis patients: Can we identify clinical risk profiles?

The objective of this study is to explore, within a sample of early psychosis patients (EPP), if subgroups regarding rate of violent behaviour (VB) against others can be identified on the basis of dynamic risk factors (treatment modifiable characteristics). In a sample of 265 EPP, treated at the Treatment and Early Intervention in Psychosis Program in Lausanne, we conducted a latent-class analysis on the basis of the main dynamic VB risk factors (substance use disorder [SUD], positive symptoms, insight, and impulsivity). VB were restricted to "serious violence" and were assessed through patients self-report, interview with relatives or forensic services and with a standardized instrument. The analysis confirmed the heterogeneity of the sample regarding rate of VB. Patients could be stratified within 4 subgroups, 3 of which were at increased risk of VB. The two groups with the highest rates of VB displayed specific clinical profiles. The first one was characterized by high levels of impulsivity, hostility, positive symptoms and SUD, and the second, by low level of insight and low social functioning. These patterns suggest that significant difficulties in social interaction may contribute to the emergence of aggressive reactions against others. Identification of EPP at increased risk of VB seems possible on the basis of dynamic risk factors. If confirmed prospectively, this could pave the way to the development of preventive strategies and specific interventions

Aggression and Quantitative MRI Measures of Caudate in Patients With Chronic Schizophrenia or Schizoaffective Disorder

Caudate dysfunction is implicated in schizophrenia. However, little is known about the relationship between aggression and caudate volumes. Forty-nine patients received magnetic resonance imaging scanning in a double-blind treatment study in which aggression was measured. Caudate volumes were computed using a semiautomated method. The authors measured aggression with the Overt Aggression Scale and the Positive and Negative Syndrome Scale. Larger caudate volumes were associated with greater levels of aggression. The relationship between aggression and caudate volumes may be related to the iatrogenic effects of long-term treatment with typical anti-psychotic agents or to a direct effect of schizophrenic processes on the caudate

Schizophrenia and Violence: Systematic Review and Meta-Analysis

Seena Fazel and colleagues investigate the association between schizophrenia and other psychoses and violence and violent offending, and show that the increased risk appears to be partly mediated by substance abuse comorbidity

Quantitative MRI measures of orbitofrontal cortex in patients with chronic schizophrenia or schizoaffective disorder

The relationship between orbitofrontal cortex (OFC) volumes and functional domains in treatment-resistant patients with schizophrenia or schizoaffective disorder is poorly undestood. OFC dysfunction is implicated in several of the behaviors that are abnormal in schizophrenia. However, little is known about the relationship between these behaviors and OFC volumes. Forty-nine (49) patients received magnetic resonance imaging scanning as part of a double-blind treatment study in which psychiatric symptomatology, neuropsychological function, and aggression were measured. OFC volumes were manually traced on anatomical images. Psychiatric symptomatology was measured with the Positive and Negative Syndrome Scale (PANSS). Aggression was measured with the Overt Aggression Scale (OAS) and with the PANSS. Neuropsychological function was assessed using a comprehensive test battery. Larger right OFC volumes were associated with poorer neuropsychological function. Larger left OFC gray matter volumes and larger OFC white matter volumes bilaterally were associated with greater levels of aggression. These findings are discussed in the context of potential iatrogenic effects

Systematic meta-analyses and field synopsis of genetic association studies of violence and aggression

A large number of candidate gene studies for aggression and violence have been conducted. Successful identification of associations between genetic markers and aggression would contribute to understanding the neurobiology of antisocial behavior and potentially provide useful tools for risk prediction and therapeutic targets for high-risk groups of patients and offenders. We systematically reviewed the literature and assessed the evidence on genetic association studies of aggression and related outcomes in order to provide a field synopsis. We searched PubMed and Huge Navigator databases and sought additional data through reviewing reference lists and correspondence with investigators. Genetic association studies were included if outcome data on aggression or violent behavior either as a binary outcome or as a quantitative trait were provided. From 1331 potentially relevant investigations, 185 studies constituting 277 independent associations on 31 genes fulfilled the predetermined selection criteria. Data from variants investigated in three or more samples were combined in meta-analyses and potential sources of heterogeneity were investigated using subgroup analyses. In the primary analyses, which used relaxed inclusion criteria, we found no association between any polymorphism analyzed and aggression at the 5% level of significance. Subgroup analyses, including by severity of outcome, age group, characteristics of the sample and ethnicity, did not demonstrate any consistent findings. Current evidence does not support the use of such genes to predict dangerousness or as markers for therapeutic interventions

Packages of Care for Schizophrenia in Low- and Middle-Income Countries

In the third in a series of six articles on packages of care for mental disorders in low- and middle-income countries, Jair Mari and colleagues discuss the treatment of schizophrenia

EEG Biofeedback as a Treatment for Substance Use Disorders: Review, Rating of Efficacy, and Recommendations for Further Research

Electroencephalographic (EEG) biofeedback has been employed in substance use disorder (SUD) over the last three decades. The SUD is a complex series of disorders with frequent comorbidities and EEG abnormalities of several types. EEG biofeedback has been employed in conjunction with other therapies and may be useful in enhancing certain outcomes of therapy. Based on published clinical studies and employing efficacy criteria adapted by the Association for Applied Psychophysiology and Biofeedback and the International Society for Neurofeedback and Research, alpha theta training—either alone for alcoholism or in combination with beta training for stimulant and mixed substance abuse and combined with residential treatment programs, is probably efficacious. Considerations of further research design taking these factors into account are discussed and descriptions of contemporary research are given