title: Does serotonin deficit mediate susceptibility to ADHD?
abstract: The onset of attention-deficit-hyperactivity-disorder (ADHD) in childhood is characterized by developmentally inappropriate levels of hyperactivity, impulsivity and inattention. A chronic deficit of serotonin (5-HT) at the synapse may trigger symptoms of ADHD. This review focuses on neuro-anatomical, experimental and clinical pharmacological evidence, as well as the genetic underpinnings of serotoninergic involvement in the etiology of ADHD. Neuro-anatomical investigations suggest that serotonin through the orbitofrontal-striatal circuitry may regulate behavioral domains of hyperactivity and impulsivity in ADHD. Studies from animal models of ADHD indicate intimate interplay between 5-HT and dopaminergic neurotransmission. Selective serotonin re-uptake inhibitors, as also non-stimulant drugs acting on the 5-HT system are, however, clinically effective. They impart less severe side effects in patients with no risk of addiction. Oral administration of l-tryptophan, the amino acid precursor of 5-HT, significantly alleviates ADHD symptoms. Given the multifactorial nature of ADHD, candidate gene and genome-wide association studies have suggested that serotoninergic gene variants are associated with increased risk of ADHD with each locus individually exerting a modest effect on overall risk.
authors: Department of Genetics, University of Calcutta, 35, Ballygunge Circular Road, Kolkata 700019, India.
authors: Emili
authors: E
authors: Banerjee
authors: Department of Genetics, University of Calcutta, 35, Ballygunge Circular Road, Kolkata 700019, India. Electronic address: knandago2007@gmail.com.
authors: Krishnadas
authors: K
authors: Nandagopal
mesh_terms: D000293:Adolescent; D000818:Animals; D000831:Animals, Newborn; D001289:Attention Deficit Disorder with Hyperactivity / Q000188:drug therapy / Q000235:genetics* / Q000503:physiopathology; D000697:Central Nervous System Stimulants / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D003342:Corpus Striatum / Q000503:physiopathology; D004195:Disease Models, Animal; D004298:Dopamine / Q000502:physiology; D059647:Gene-Environment Interaction; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D007266:Inhibition, Psychological; D018345:Mice, Knockout; D020412:Multifactorial Inheritance; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000502:physiology; D050479:Neurotransmitter Transport Proteins / Q000172:deficiency / Q000235:genetics; D016627:Oxidopamine / Q000633:toxicity; D017397:Prefrontal Cortex / Q000187:drug effects / Q000503:physiopathology; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D044302:Receptor, Serotonin, 5-HT1B / Q000172:deficiency; D012701:Serotonin / Q000172:deficiency* / Q000502:physiology; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D014364:Tryptophan / Q000172:deficiency / Q000627:therapeutic use
chemical_list: D000697:Central Nervous System Stimulants; D004298:Dopamine; D009419:Nerve Tissue Proteins; D050479:Neurotransmitter Transport Proteins; D016627:Oxidopamine; D044302:Receptor, Serotonin, 5-HT1B; D012701:Serotonin; D017367:Selective Serotonin Reuptake Inhibitors; D014364:Tryptophan
keywords: ADHD; Animal model; Clinical pharmacology; Genetics; Neuroanatomy; Serotonin