Chromatin Remodeling in Schizophrenia and Bipolar Disorder
Psychiatry is a field which remains limited by the lack of reliable, objective criteria such as blood tests or imaging investigations that can accurately characterize illness and guide treatment. The authors of this article describe an approach which may prove useful, firstly in diagnosis and secondly in selecting patients that are likely to respond to a particular drug therapy, thus minimising the process of medication trial and error. They focussed on epigenetic modification of histone residues which has previously been proposed as a cause of schizophrenia and bipolar disorder. What makes this paper intriguing is that the researchers ran parallel in vitro and in vivo trials in an effort to make their results directly relevant to clinical practice.
In the clinical part of the trial, 11 patients with schizophrenia and 7 with bipolar disorder were given 4 weeks of treatment with VPA - a drug commonly used in bipolar disorder and one which has been shown to inhibit HDAC (histone deacetylase). Blood was taken before and after the treatment period with results indicating that the participants with schizophrenia started with lower levels of H3K9, K14ac (acetylated histone 3) and showed a lesser increase through the study period when compared to the bipolar group. GAD67 (a gene shown to have reduced activity in schizophrenia) mRNA levels increased in 10 of the participants with the serum VPA level rather than initial diagnosis being the strongest predictor of change. These and other results led the researchers to make a number of conclusions : 1/ the chromatin is more restrictive in schizophrenia patients and responds less well to HDAC inhibition; 2/ VPA can influence GAD67 gene expression, probably via the alteration of chromatin; 3/ This experimental model could be used to assess the epigenetic regulation of other genes in a research or clinical scenario; and 4/ There may be a therapeutic use for drugs such as VPA which ‘soften’ the chromatin and may improve the subsequent efficacy of other psychotropic medications.
Potentially, this could revolutionise psychiatric practice as patients could be individually assessed at a chromatin level with the results guiding treatment and helping to reduce the burden of disease.
Joshua Betts
s3308412
In the clinical part of the trial, 11 patients with schizophrenia and 7 with bipolar disorder were given 4 weeks of treatment with VPA - a drug commonly used in bipolar disorder and one which has been shown to inhibit HDAC (histone deacetylase). Blood was taken before and after the treatment period with results indicating that the participants with schizophrenia started with lower levels of H3K9, K14ac (acetylated histone 3) and showed a lesser increase through the study period when compared to the bipolar group. GAD67 (a gene shown to have reduced activity in schizophrenia) mRNA levels increased in 10 of the participants with the serum VPA level rather than initial diagnosis being the strongest predictor of change. These and other results led the researchers to make a number of conclusions : 1/ the chromatin is more restrictive in schizophrenia patients and responds less well to HDAC inhibition; 2/ VPA can influence GAD67 gene expression, probably via the alteration of chromatin; 3/ This experimental model could be used to assess the epigenetic regulation of other genes in a research or clinical scenario; and 4/ There may be a therapeutic use for drugs such as VPA which ‘soften’ the chromatin and may improve the subsequent efficacy of other psychotropic medications.
Potentially, this could revolutionise psychiatric practice as patients could be individually assessed at a chromatin level with the results guiding treatment and helping to reduce the burden of disease.
Joshua Betts
s3308412
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