Schizophrenia is a severe psychiatric disorder that causes a profound effect on society and the individual. Indeed, there can be no doubt that schizophrenia is a disease of the neurodevelopment of multifactorial origin. Many mechanisms can interact to produce psychotic manifestations, including genetic bases, viral diseases, immune dysfunctions, obstetric complications or environmental determinants that produce early stress factors.
More than 50% of patients usually have a intermittent course and about 20% tend to be chronic, unemployment is surprisingly high at 80–90%, and their life expectancy is reduced between 10 to 20 years. In England the cost per patient is around £7,000 – £40,000 each year. At present, the advances in the genome has opened a wide field for the understanding and progress as never before.
Genetic analysis of an Irish study in families of schizophrenics, which included 270 pedigrees, revealed that there is a significant association between disease and variations in the gene DTNBP1 (the gene for the protein of union dysbindin-1) The gene for dysbindin is located in the locus 6p24-21, a locus of susceptibility for schizophrenia as reported in several previous scientific work.
The dysbindin is a protein that makes up the so-called dystrophin complex which is located in the Postsynaptic Thickenings. This protein complex plays a crucial in the formation and maintenance of the neuromuscular synapse. The dysbindin also modifies the synaptic activity in the brain and modulates multiple receivers such as the GABA-A subtype of the hippocampus, the cerebral cortex and cerebellum. The potential role it would play this protein in synaptic transmission and its association with schizophrenia put it within the list of candidates of locus susceptible to the disease.
Antipsychotics are the first line medications and most commonly used for the treatment of the spectrum of schizophrenia and other psychotic disorders. In accordance with the heterogeneous nature of these disorders, clinical responses to antipsychotic drugs are highly variable. The treatments with antipsychotics of first and second generation produce small neurocognitive improvements in patients with chronic schizophrenia and first episode.
The cognitive responses to antipsychotic drugs show a marked individual variability and the base is unknown mechanics of this variability apparently unpredictable. In clinical practice can be seen as the antipsychotics improve notably positive symptoms, however show great uncertainty as to the negative symptoms of the disease. There is scarce biomarkers that can provide data on to predict the response to antipsychotics.
A team of researchers from Europe and the US analysed genetic data from 259 patients with chronic schizophrenia, all of whom were taking antipsychotics. This study was published in June in Nature Communications suggests that the protein dysbindin-1 may be a biomarker to identify which patients are more likely to show cognitive improvement in the antipsychotics.
The authors of the study found that the dysbindin-1 regulates the recycling of dopamine D2 receptors, the objectives of the antipsychotic drugs. A variant in the gene of the dysbindin-1 known as TAA results in the production of less protein dysbindin-1. Less dysbindin-1 means less recycling of dopamine receptors, which leads to an excess of dopamine signalling. This hyperactivity can affect thinking, and studies both in humans and mice have shown that the reduction of dysbindin-1 affects the cognitive flexibility, or the ability to easily change the thought of one as circumstances change.
The contribution of these researchers highlighted one of the mechanisms that could be used to identify a subset of patients with schizophrenia whose executive functions are likely to respond better to the antipsychotic drugs, based on the mechanisms of dysbindin-1.
Ultimately, these results could potentially apply to increase the effectiveness of antipsychotics, and reduce the duration of the empirical evidence often needed to select the medications or doses of appropriate antipsychotic drugs and could provide information on the failure of the antipsychotic drugs to improve the cognitive deficits in a large part of the population.
Dr Teraiza Mesa Rodriguez is a Psychiatrist in Venezuela. She sits on the board of the International Scientific Committee of Psiquiatria. She is also serves as a reviewer for the Journal of AIDS and HIV Research. Dr Mesa is an active member of the Venezuelan Society of Psychiatry and is also a member of the Venezuelan College of Psychopharmacology. You can connect with her on Twitter @Dra_TeraizaMesa