engleski

Molecular markers of behavioral and emotional disorders

Introduction: Behavioral and emotional disorders are highly prevalent and heterogeneous common disorders in children and adolescents that include attention- deficit/hyperactivity disorder (ADHD), adjustment disorders, anxiety disorders, obsessive/compulsive disorder (OCD), posttraumatic stress disorder, conduct disorder, oppositional defiant disorder, depression and others. These disorders are frequently associated with the negative outcomes in adulthood, substance abuse and dependence, early pregnancy, persistent health problems, increased aggression, impulsivity, hyperactivity, inattention, obsessions, compulsions, anxiety, suicidality, delinquency, and criminality. These disorders are multifactorial and heterogeneous, with a complex etiology and strong genetic component. No single deficit is sufficient to explain all clinical cases of these disorders. Various child-specific, environmental, demographic, psychosocial, psychiatric, cognitive, developmental and genetic factors, with the stress exposure or adverse early life experiences, and a complicated interplay of these factors, contribute to the development and maintenance of these disorders and antisocial, violent and suicidal behaviors. The neurobiological basis of these disorders is not clear, but it is assumed to involve particular gene mutations and altered functions of the main neurotransmitter (dopamine, norepinephrine, serotonin /5-HT/) and neuroendocrine (hypothalamic-pituitary-adrenal axis) systems. Materials and Methods: Platelet markers, monoamine oxidase (MAO-B) and 5-HT, and polymorphisms of the genes for catechol-o- methyl-transferase (COMT) and brain derived neurotrophic factor (BDNF) were determined in male and female children with depression, OCD, ADHD, and phobias. Children were further subdivided according to the gender and suicidal behavior. Clinical diagnoses and suicidal behavior were assessed according to the DSM-IV criteria, different clinical scales and the psychiatric interview. Results: Significant differences were found in platelet 5-HT concentration between healthy boys and girls, but not among suicidal and non-suicidal children. Significant differences in the frequency of the Val66Met BDNF genotypes between suicidal, non-suicidal and healthy groups were detected. The distribution of the Val158/108Met COMT variants, and platelet MAO-B activity, did not differ significantly between the studied groups. Discussion: Our results did not support the hypothesis that reduced platelet 5-HT concentration or lower platelet MAO-B activity or Val158/108Met COMT variants present the risk factors for suicidal behavior in children. The significant contribution of the Met/Val genotype of the Val66Met BDNF to the observed significance suggested that Val66Met BDNF might present a risk factor for suicidal behavior. This result should be confirmed on the larger sample. Since the clinical features of behavioral and emotional disorders are heterogeneous and complex, further research of the risk factors for suicidal behavior is important to identify and properly treat children and adolescents prone to suicidal behavior, in order to prevent suicidal behavior, suicidal attempts and completed suicides.

Platelet MAO-B ; platelet 5-HT ; polymorphisms ; COMT ; BDNF ; children ; depression ; OCD ; ADHD ; phobias ; suicidal behavior

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