Genetic and biochemical markers of serotonergic and catecholaminergic systems in neuropsychiatric disorders

Literature data suggest that the interaction between internal (neurohumoral, genetic) and external (environmental) factors has an important role in the etiopathogenesis of complex and polygenetic neuropsychiatric disorders. Postmortem or neuroimaging brain studies and the investigations of peripheral biochemical markers (platelet serotonin /5-HT/ concentration, platelet monoamine oxidase type B /(MAO-B/ activity and plasma dopamine-beta hydroxylase /DBH/ activity) showed a dysfunction of the serotonergic and catecholaminergic systems in neuropsychiatric disorders like Alzheimer’ s disease (AD), posttraumatic stress disorder (PTSD) and alcoholism. These central and peripheral neurobiological changes could be related to the modification of genes encoding for proteins involved in the serotonergic and catecholaminergic neurotransmission. Clinical diagnoses of AD, PTSD and alcohol dependency were made using structured clinical interview according to the DSM- IV criteria. The control subjects were Croatian healthy subjects with no personal or familiar history of neuropsychiatric disorders. The values of peripheral biochemical variables platelet 5-HT concentration, platelet MAO-B activity and plasma DBH activity were compared with the genetic variants of genes coding for 5-HT transporter (5-HTTLPR ; genetic locus 17q11.1, OMIM *182138), MAO-B (genetic locus Xp11.23, OMIM *309850) and DBH (locus 9q34, OMIM *609312). Other relevant candidate genes, i.e. serotonergic receptors type 1B (5-HT-1B ; genetic locus 6q13, OMIM*182131) and type 2A (5-HT-2A ; genetic locus 13q14 – q21, OMIM *182135), as well as catechol-O- methyltransferase (COMT ; genetic locus 22q11.2, OMIM *116790) were also analyzed in patients and healthy controls. The biochemical markers were determined using the spectrofluorometric and spectrophotometric methods, and the genetic variants using standard methods of molecular genetics. Similar genotype and allele frequencies of candidate genes polymorphisms were found in healthy controls and patients with AD, PTSD and alcoholism. There was no relationship between the smoking status, plasma DBH activity and polymorphisms within DBH gene. The smoking status was associated with platelet MAO-B activity, but not with genetic variants of MAO-B. The results suggest that the genotype-controlled measurement of plasma DBH activity might be used as a potential biological marker in AD and PTSD. The lack of association was found between gene variants of MAO-B and platelet MAO-B activity and between 5-HTTLPR and platelet 5-HT concentrations in healthy controls. The identification of biochemical markers and genetic variations, associated with the serotonergic and catecholaminergic systems, represents a promising approach for the recognition of individuals vulnerable to development of particular neuropsychiatric disorder, as well as for detection of susceptibility gene(s), whose protein product(s) could be crucial to the occurrence of the disease.