Molecular biology in Schizophrenia

REF: PD 04
Principle investigator:
Amalia Lafuente / Miquel Bernardo
Contact details:



Research framework

The purpose of this programme of work is to develop translational research, between clinics, genetics and biological research, in the field of Schizophrenia to search for the molecular basis of the disease and improve pharmacological treatment.

Our preliminary results indicate that genetic polymorphisms favouring the presence of dopamine in the synapse may be risk factors for schizophrenia. Moreover, genetic polymorphisms that favour occupation of the dopamine receptor by antipsychotic drugs (AP) instead of occupation by dopamine are risk factors for extrapyramidal symptoms (EPS) induced by AP.

The most relevant publications that have shown different mechanisms associated with the risk of schizophrenia and also with extrapyramidalism-derived from antipsychotic treatment are:

  • Schizophrenia Research .90:115-122 (2007).
  • Pharmacogenomics J, 9, 404-410 (2009),
  • Am J Med Genet 153B 1052-59; 2010
  • Eur Neuropsychopharmacol 21; 294-99 (2010),
  • Pharmacogenomics 11(12):1725-31 (2010)
  • Pharmacogenomics J doi: 10.1038/tpj.2010.91 (2011)),
  • Eur Neuropschycopharmacol (accepted, 2012).

The most common techniques used are:
PCR, real time PCR (sequentiation); Arrays ; ELISA ; Cell culture ; Western Blot.

The added value of the group in this framework is detailed below:

  • Expertise in Bioinformatics
  • Multidisciplinar group combining clinical and basic research


Pharmacogenetics, genetics, schizophrenia, methylation, functional genomics

Main Challenges

The main challenge of this research is extending and improving previous results studying either:

  • linkage disequilibrium (LD) mapping in candidate genes,
  • copy number variations,
  • epigenetics: methylation of promoters (Illumina Golden Gate Methylation Panel Array), genomic methylation (ELISA Kit), genomic imprinting (bisulfite sequencing of H19/IGF2 locus), X chromosome inactivation (HUMARA test) and telomere methylation (bisulfite sequencing of telomer regions of chromosomes 2, 4 and 18).
  • Mitochondrial dynamics in response to dopamine and AP,
  • Identify new candidate genes through a translational strategy of convergent functional genomics, which integrates pharmacogenomic data (from animal models, cellular models and peripheral human tissues, cross-validated with genetic data from human association studies, post-mortem human tissues and biological function).

The candidate will work integrated in a research team. It is expected from him:

  • To contribute to the design and planning of experiments in relation to this project
  • To set up and run experiments in consultation with the Principal Investigator
  • To prepare progress reports on research

In addition he/she will prepare and present findings of research to the Principal Investigator and other members of the centre; perform some limited teaching and/or supervision of other members of staff and/or students, under the guidance of the Principal Investigator; record, analyse and write up the results of experiments and ensure that laboratory notebooks are kept fully up to date as a formal record of the research.

Team strategic objective in IDIBAPS

To study Schizophrenia from the neurobiological and therapeutic perspectives: The schizophrenia program focuses research on the first schizophrenic episodes and on resistant comorbid schizophrenia, through functional neuroimaging, neuropsychological tests , biological markers, genetics and pharmacogenetics.

The pharmacogenetics of antipsychotic drugs is studied to assess the efficacy and safety of these drugs on the basis of the individual genetic characteristics. Specifically we are analyzing the extrapyramidal effects. Genetic association studies are performed to find predictor polymorphisms or diseases markers.

(Read eligibility criteria)