Abstract
Objective: Schizophrenia, bipolar affective disorder, major depression and dementia in Alzheimer's disease have a strong genetic and neurobiological background. The aim of this review is to briefly sum up recent knowledge on genetics and epigenetics of these serious mental disorders in order to educate professionals in the field of biological psychiatry and stimulate further research.
Results: Cardinal new knowledge on the genetics of serious mental disorders was recently brought by whole-genome association studies. Dozens of single nucleotide DNA polymorphisms significantly associated with schizophrenia were detected.
These genetic variants are related to the development of brain structures, their interconnection, neural communication, immune reaction and regulation of DNA expression. As of the bipolar affective disorder, significant genes especially apply to neural connectivity, neuroplasticity and neural transmission, in particular calcium signalling.
In the etiology of major depression, genes influencing serotonin signalling, neurotrophic substances, the hypothalamus-pituitary-adrenalin axis or immunity are of import. However, external stressful stimuli are also substantial.
In the familial form of dementia in Alzheimer's disease, the genes participating in the betaamyloid synthesis are of importance. As for the sporadic dementia in Alzheimer's disease, the Apolipoprotein E gene involved in the beta-amyloid formation is definitely relevant.
At the same time, several genes linked to immunity or DNA expression regulation are also substantial. The results of the most frequently published epigenetic studies accentuate the significance of DNA methylation, histone modifications and mikroRNAs, when all these factors influence gene expression and subsequently protein synthesis.
Unfortunately, epigenetic studies were so far not able to bring consistent results, and epigenetic research of serious mental disorders is more at its beginning than at its end. Conclusion: It becomes apparent that genetic and epigenetic etiology of serious mental disorders is very complex and comprise a whole range of different mechanisms.
Whole-genome association studies were a big contribution in our discovery of genetic etiology, but pathogenesis still remains unclear. Epigenetic research partly moved our recognition ahead, but its results are still far from consistency.
The interesting fact is that some epi/genetic findings overlap between individual mental disorders, e.g. between schizophrenia and bipolar disorder. It is legitimate to anticipate that new neurobiological examination methods and statistical assessment methods will elucidate the issues of epi/genetics of serious mental disorders in the future.