Are reprogrammed cells a useful tool for studying dopamine dysfunction in psychotic disorders? A review of the current evidence.
Since 2006, reprogrammed cells have increasingly been used as a biomedical research technique in addition to neuro-psychiatric methods. These rapidly evolving techniques allow for the generation of neuronal sub-populations, and have sparked interest not only in monogenetic neuro-psychiatric diseases, but also in poly-genetic and poly-aetiological disorders such as schizophrenia (SCZ) and bipolar disorder (BPD). This review provides a summary of 19 publications on reprogrammed adult somatic cells derived from patients with SCZ, and five publications using this technique in patients with BPD. As both disorders are complex and heterogeneous, there is a plurality of hypotheses to be tested in vitro. In SCZ, data on alterations of dopaminergic transmission in vitro are sparse, despite the great explanatory power of the so-called DA hypothesis of SCZ. Some findings correspond to perturbations of cell energy metabolism, and observations in reprogrammed cells suggest neuro-developmental alterations. Some studies also report on the efficacy of medicinal compounds to revert alterations observed in cellular models. However, due to the paucity of replication studies, no comprehensive conclusions can be drawn from studies using reprogrammed cells at the present time. In the future, findings from cell culture methods need to be integrated with clinical, epidemiological, pharmacological and imaging data in order to generate a more comprehensive picture of SCZ and BPD.
Department of Psychiatry and Psychotherapy, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria.
Ulrich
U
Sauerzopf
Institute of Science and Technology Austria, Klosterneuburg, Austria.
Roberto
R
Sacco
Institute of Science and Technology Austria, Klosterneuburg, Austria.
Gaia
G
Novarino
Institute of Pharmacology, Medical University of Vienna, Vienna, Austria.
Marco
M
Niello
Department of Psychiatry and Psychotherapy, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria.
Ana
A
Weidenauer
Department of Psychiatry and Psychotherapy, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria.
Nicole
N
Praschak-Rieder
Institute of Pharmacology, Medical University of Vienna, Vienna, Austria.
Harald
H
Sitte
Department of Psychiatry and Psychotherapy, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria.
Matthäus
M
Willeit
D000818:Animals; D001714:Bipolar Disorder / Q000235:genetics / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D020022:Genetic Predisposition to Disease; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D011618:Psychotic Disorders / Q000235:genetics / Q000378:metabolism*; D012559:Schizophrenia / Q000235:genetics / Q000378:metabolism*
D004298:Dopamine
bipolar disorder; dopamine; induced neuron; induced pluripotent stem cell; neuronal progenitor cell; schizophrenia
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