Molecular basis and treatment of psychiatric and stress related disorders
Stress related (acute stress reaction, posttraumatic stress disorder) and eating disorders, addictions (alcoholism), aggressive/suicidal behavior, and attention deficit hyperactivity disorder are frequent multifactorial and polygenic psychiatric disorders that induce a great suffering in patients and their families, and carry financial burden to the whole society. Molecular basis of these disorders involves the changes in neurotransmitter (primarily serotonin - 5-HT, noradrenalin, dopamine) and neuroendocrine systems, and functional gene polymorphisms controlling the activity of the corresponding proteins.
The aims of the study are to determine biological (5-HT and monoamine oxidase - MAO in platelets, dopamine-beta-hydroxylase - DBH, catechol-o-methyltransferase (COMT), cortisol) and genetic (MAO-A, MAO-B, DBH, COMT, brain-derived neurotrophic factor, transporters and receptors for 5-HT, dopamine and noradrenalin) markers involved in development and treatment, and to explore the relation between these biomarkers and suicidal/aggressive behavior, or response to treatment, in psychiatric, stress-related, behavioural, comorbid cognitive disorders and addictions.
The hypothesis is that biomarkers are altered in these disorders, and might help to improve diagnostic procedures, differentiate between the type of illness, predict a treatment response, or suicidal/aggressive behavior, or detect the subjects who will develop a disorder after a trauma exposure.
We expect that the results will enhance the knowledge of the development and treatment, explain the multiple interactions between biological systems and genes, in psychiatric and stress related disorders, and improve the understanding of their biological and genetic origin.
Biological markers in the blood of the patients and healthy controls will be determined by the fluorimetric, photometric, and chemoluminiscent, and gene polymorphisms by molecular genetic (PCR, real time-PCR and RFLP) methods. Diagnoses will be done using Structured clinical interview (DSM-IV criteria) and clinical rating scales. The results will be verified if biomarkers, determined “blindly”, i.e. without knowing the diagnoses, confirm the subtype of disease, certain behavior, or therapeutic response.
The importance of this study is in its clinical application: biomarkers might predict the treatment response, the subtype of disorder, development of the illness after exposure to a psychotrauma, or detect suicidal or aggressive behavior.