Tryptophan as an evolutionarily conserved signal to brain serotonin: molecular evidence and psychiatric implications.
The role of serotonin (5-HT) in psychopathology has been investigated for decades. Among others, symptoms of depression, panic, aggression and suicidality have been associated with serotonergic dysfunction. Here we summarize the evidence that low brain 5-HT signals a metabolic imbalance that is evolutionarily conserved and not specific for any specific psychiatric diagnosis. The synthesis and neuronal release of brain 5-HT depends on the concentration of free tryptophan in blood and brain because the affinity constant of neuronal tryptophan hydroxylase is in that concentration range. This relationship is evolutionarily conserved. Degradation of tryptophan, resulting in lower blood levels and impaired cerebral production and release of serotonin, is enhanced by inter alia inflammation, pregnancy and stress in all species investigated, including humans. Consequently, tryptophan may not only serve as a nutrient, but also as a bona fide signalling amino acid. Humans suffering from inflammatory and other somatic diseases accompanied by low tryptophan levels, exhibit disturbed social behaviour, increased irritability and lack of impulse control, rather than depression. Under particular circumstances, such behaviour may have survival value. Drugs that increase brain levels of serotonin may therefore be useful in a variety of psychiatric disorders and symptoms associated with low availability of tryptophan.
Russo
Sascha
S
Department of Psychiatry, University Medical Centre Groningen, 9700 RB Groningen, The Netherlands.
Kema
Ido P
IP
Bosker
Fokko
F
Haavik
Jan
J
Korf
Jakob
J
D000374:Aggression / Q000523:psychology; D000818:Animals; D005075:Biological Evolution; D001921:Brain / Q000503:physiopathology*; D003866:Depressive Disorder / Q000235:genetics / Q000503:physiopathology; D007174:Disruptive, Impulse Control, and Conduct Disorders / Q000235:genetics / Q000503:physiopathology; D005260:Female; D006801:Humans; D007508:Irritable Mood / Q000502:physiology; D001523:Mental Disorders / Q000235:genetics / Q000503:physiopathology*; D010802:Phylogeny; D011110:Polymorphism, Genetic / Q000235:genetics; D011247:Pregnancy; D011599:Psychopathology; D011985:Receptors, Serotonin / Q000235:genetics / Q000502:physiology; D012701:Serotonin / Q000502:physiology*; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*; D012919:Social Behavior; D013045:Species Specificity; D014364:Tryptophan / Q000097:blood* / Q000172:deficiency / Q000235:genetics; D014365:Tryptophan Hydroxylase / Q000235:genetics
D011985:Receptors, Serotonin; D050486:Serotonin Plasma Membrane Transport Proteins; D012701:Serotonin; D014364:Tryptophan; C497467:TPH1 protein, human; C494784:TPH2 protein, human; D014365:Tryptophan Hydroxylase