Abstract
BackgroundAttention deficit hyperactivity disorder (ADHD) is an etiologically complex childhood onset neurobehavioral disorder characterized by age-inappropriate inattention, hyperactivity, and impulsivity. Symptom severity varies widely and boys are diagnosed more frequently than girls. ADHD probands were reported to have abnormal transmissions of dopamine, serotonin, and/or noradrenaline. Monoamine oxidase A (MAOA) and B (MAOB), mitochondrial outer membrane bound two isoenzymes, mediate degradation of these neurotransmitters and thus regulating their circulating levels. Case-control analyses in different populations, including Indians, suggested involvement of MAOA and MAOB genes in the etiology of ADHD. Due to high heritability rate of ADHD, we tested familial transmission of MAOA and MAOB variants to ADHD probands in 190 nuclear families having ADHD probands from Indo-Caucasoid ethnicity.MethodsSubjects were recruited following the Diagnostic and Statistical Manual of Mental Disorders-4th edition (DSM-IV). Appropriate scales were used for measuring the behavioral traits in probands. Genotyping was performed through PCR-based amplification of target sites followed by DNA-sequencing and/or gel-electrophoresis. Data obtained were analyzed by family based statistical methods.ResultsOut of 58 variants present in the analyzed sites only 15 were found to be polymorphic (30 bp-uVNTR, rs5906883, rs1465107, rs1465108, rs5905809, rs5906957, rs6323, rs1137070 from MAOA and rs4824562, rs56220155, rs2283728, rs2283727, rs3027441, rs6324, rs3027440 from MAOB). Statistically significant maternal transmission of alleles to male probands was observed for MAOA rs5905809 ‘G’ (p = 0.04), rs5906957 ‘A’ (p = 0.04), rs6323 ‘G’ (p = 0.0001) and MAOB rs56220155 ‘A’ (p = 0.002), rs2283728 ‘C’ (p = 0.0008), rs2283727 ‘C’ (p = 0.0008), rs3027441 ‘T’ (p = 0.003), rs6324 ‘C’ (p = 0.003), rs3027440 ‘T’ (p = 0.0002). Significantly preferential maternal transmissions of different haplotype combinations to male probands were also noticed (p < 0.05), while female probands did not reveal such transmission bias. Behavioral traits of male probands exhibited significant association with gene variants. Age of the mother at pregnancy also revealed association with risk variants of male probands.ConclusionsIt may be inferred that the MAOA and MAOB variants may contribute to the etiology of ADHD in the Indo-Caucasoid population and could be responsible for higher occurrence of ADHD in the boys.
Highlights
Attention deficit hyperactivity disorder (ADHD) is an etiologically complex childhood onset neurobehavioral disorder characterized by age-inappropriate inattention, hyperactivity, and impulsivity
Diagnosis was performed by child psychiatrist and clinical psychologist following the Diagnostic and Statistical Manual of Mental Disorders-4th edition (DSM-IV) criteria [50]. 74.74% of the recruited ADHD probands were of the combined subtype, while inattentive and hyperactive-impulsive subtypes were of 13.68% and 11.58% respectively
Limitations of the study The major limitation of the present study was the sample size and further in depth analysis on a large cohort of samples belonging to different ethnic groups would help in validation of the present observation. It may be inferred from the data obtained that both Monoamine oxidase A (MAOA) and Monoamine oxidase B (MAOB) gene variants could be considered as risk factors for ADHD in the Indo-Caucasoid population from eastern India
Summary
Attention deficit hyperactivity disorder (ADHD) is an etiologically complex childhood onset neurobehavioral disorder characterized by age-inappropriate inattention, hyperactivity, and impulsivity. Attention deficit hyperactivity disorder (ADHD) is an etiologically complex neurobehavioral disorder, diagnosed mostly during early childhood [1]. Candidate genes involved in the regulation of dopamine, serotonin, and noradrenalin were widely studied in ADHD subjects since behavioral traits are regulated by these neurotransmitters [13, 15, 17, 18] and both dopaminergic [15, 19,20,21] and serotonergic [22] transmissions revealed significant impact on behavioral as well as cognitive features
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