Gene expression biomarkers of response to citalopram treatment in major depressive disorder

There is significant variability in antidepressant treatment outcome, with ∼30–40% of patients with major depressive disorder (MDD) not presenting with adequate response even following several trials. To identify potential biomarkers of response, we investigated peripheral gene expression patterns of response to antidepressant treatment in MDD. We did this using Affymetrix HG-U133 Plus2 microarrays in blood samples, from untreated individuals with MDD (N=63) ascertained at a community outpatient clinic, pre and post 8-week treatment with citalopram, and used a regression model to assess the impact of gene expression differences on antidepressant response. We carried out technical validation of significant probesets by quantitative reverse transcriptase PCR and conducted central nervous system follow-up of the most significant result in post-mortem brain samples from 15 subjects who died during a current MDD episode and 11 sudden-death controls. A total of 32 probesets were differentially expressed according to response to citalopram treatment following false discovery rate correction. Interferon regulatory factor 7 (IRF7) was the most significant differentially expressed gene and its expression was upregulated by citalopram treatment in individuals who responded to treatment. We found these results to be concordant with our observation of decreased expression of IRF7 in the prefrontal cortex of MDDs with negative toxicological evidence for antidepressant treatment at the time of death. These findings point to IRF7 as a gene of interest in studies investigating genomic factors associated with antidepressant response

A retrospective comparison of cognitive performance in individuals with advanced Parkinson’s disease in Hong Kong and Canada

202303 bckwAccepted ManuscriptOthersMitacs Globalink; PolyU Student Attachment ProgrammePublishe

Genética do transtorno bipolar Genetics of bipolar disorder

O Transtorno bipolar (TB) possui alta prevalência na população mundial e causa perdas significativas na vida dos portadores. É uma doença cuja herança genética se caracteriza por mecanismos complexos de transmissão envolvendo múltiplos genes. Na tentativa de identificar genes de vulnerabilidade para o TB, várias estratégias de investigação genética têm sido utilizadas. Estudos de ligação apontam diversas regiões cromossômicas potencialmente associadas ao TB, cujos marcadores ou genes podem ser candidatos para os estudos de associação. Genes associados aos sistemas monoaminérgicos e vias de sinalização intracelulares são candidatos para investigação da etiologia genética do TB. Novas técnicas de mapeamento de expressão gênica em tecidos especializados apontam para novos genes cujas mutações possam ser responsáveis pelo aparecimento da doença. Em virtude da complexidade do modo de transmissão do TB e de sua heterogeneidade fenotípica, muitas dificuldades são encontradas na determinação desses genes de vulnerabilidade. Até o momento, há apenas resultados preliminares identificando alguns genes associados à vulnerabilidade para desenvolver o TB. Entretanto, a compreensão crescente dos mecanismos epigenéticos de controle da expressão gênica e a abordagem dimensional dos transtornos mentais podem colaborar nas investigações futuras em genética psiquiátrica.<br>Bipolar disorder (BD) is a worldwide highly prevalent mental disease. This disorder has a genetic inheritance characterized by complex transmission mechanisms involving multiple genes. Many investigation strategies have been put forward in order to identify BD susceptibility genes. Linkage studies reveal markers and candidate genes for the association studies. Monoaminergic system genes and intracellular signaling pathway genes are also important candidates to be investigated in the etiology of this disorder. Recent techniques of gene expression mapping suggest novel genes whose mutations may be responsible for BD. Due to the complexity of the transmission pattern for BD and its phenotypic heterogeneity many difficulties have emerged to exactly define bipolar susceptibility genes. There is currently only preliminary results of genes associated with BD. However, the increasing understanding of gene expression regulation by epigenetic mechanisms and the dimensional approach to mental disorders can give directions for further research in psychiatric genetics