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Integrated theory to unify status among schizophrenia and manic depressive illness.

Abstract
Tryptophan hydroxylase 1 is primarily expressed in the gastrointestinal tract, and has been associated with both schizophrenia and depression. Although decreased serotonin activity has been reported in both depression and mania, it is important to investigate the interaction between serotonin and other neurotransmitter systems. There are competitive relationships between branched-chain amino acids, and tryptophan and tyrosine that relate to physical activity, and between L-3,4-dihydroxyphenylalanine (L-DOPA) and 5-hydroxytryptophan (5-HTP), both highly dependent on intracellular tetrahydrobiopterin concentrations. Here, I propose a chaos theory for schizophrenia, mania, and depression using the competitive interaction between tryptophan and tyrosine with regard to the blood-brain barrier and coenzyme tetrahydrobiopterin. Mania may be due to the initial conditions of physical hyperactivity and hypofunctional 5-HTP-producing cells inducing increased dopamine. Depression may be due to the initial conditions of physical hypoactivity and hypofunctional 5-HTP-producing cells inducing decreased serotonin. Psychomotor excitation may be due to the initial conditions of physical hyperactivity and hyperfunctional 5-HTP-producing cells inducing increased serotonin and substantially increased dopamine. The hallucinatory-paranoid state may be due to the initial conditions of physical hypoactivity and hyperfunctional 5-HTP-producing cells inducing increased serotonin and dopamine.
AuthorsK Fukuda
JournalMedical hypotheses (Med Hypotheses) Vol. 85 Issue 4 Pg. 506-11 (Oct 2015) ISSN: 1532-2777 [Electronic] United States
PMID26141636 (Publication Type: Letter)
CopyrightCopyright © 2015 Elsevier Ltd. All rights reserved.
Chemical References
  • Antidepressive Agents, Tricyclic
  • Antipsychotic Agents
  • Neurotransmitter Agents
  • Biopterin
  • Serotonin
  • Tyrosine
  • Levodopa
  • 5-Hydroxytryptophan
  • sapropterin
  • Kynurenic Acid
  • Dopamine
Topics
  • 5-Hydroxytryptophan (metabolism)
  • Antidepressive Agents, Tricyclic (pharmacology)
  • Antipsychotic Agents (metabolism)
  • Biopterin (analogs & derivatives, metabolism)
  • Bipolar Disorder (drug therapy, metabolism, physiopathology)
  • Blood-Brain Barrier
  • Depression (metabolism, physiopathology)
  • Depression, Postpartum (metabolism)
  • Dopamine (metabolism)
  • Female
  • Hallucinations (physiopathology)
  • Humans
  • Kynurenic Acid (metabolism)
  • Levodopa (metabolism)
  • Male
  • Neuroleptic Malignant Syndrome (metabolism, physiopathology)
  • Neurotransmitter Agents (metabolism)
  • Paranoid Disorders (physiopathology)
  • Premenstrual Syndrome (metabolism)
  • Schizophrenia (drug therapy, metabolism, physiopathology)
  • Seasonal Affective Disorder (metabolism)
  • Serotonin (metabolism)
  • Serotonin Syndrome (metabolism)
  • Tyrosine (metabolism)

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