Association of human hippocampal neurochemistry, serotonin transporter genetic variation, and anxiety.
The impact of the serotonin transporter (5-HTT) gene-linked polymorphic region (5-HTTLPR) on anxiety-related behavior and related cerebral activation has facilitated the understanding of neurobiological mechanisms of anxiety. However, the influence of the 5-HTTLPR genotype on hippocampal neuronal development and neurochemistry, which is relevant to anxiety behavior, has not been investigated. In 38 healthy subjects, absolute concentrations of N-acetylaspartate (NAA) were measured as a main surrogate parameter for hippocampal neurochemistry on a 3-T scanner. A significantly lower hippocampal NAA concentration in s allele carriers was observed as compared to l/l genotype. Other metabolites (choline, creatine + phosphocreatine, glutamate) were unaffected by genotype. The hippocampal NAA concentration was negatively correlated with trait anxiety scores (STAI). Metabolites measured in the anterior cingulate cortex (reference region) were not associated with genotype. The results are in accordance with the recently reported relationship between hippocampal neuronal development and anxiety behavior in adult animals and show an association between human limbic neurochemistry and genetically driven serotonergic neurotransmission relevant to anxiety.
Gallinat
Jürgen
J
Clinic for Psychiatry and Psychotherapy, Charité University Medicine, Berlin, Germany. juergen.gallinat@charite.de
Ströhle
Andreas
A
Lang
Undine E
UE
Bajbouj
Malek
M
Kalus
Peter
P
Montag
Christiane
C
Seifert
Frank
F
Wernicke
Catrin
C
Rommelspacher
Hans
H
Rinneberg
Herbert
H
Schubert
Florian
F
D000483:Alleles; D001007:Anxiety / Q000235:genetics* / Q000378:metabolism* / Q000523:psychology; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000378:metabolism; D015415:Biomarkers; D004247:DNA / Q000235:genetics; D005838:Genotype; D006179:Gyrus Cinguli / Q000378:metabolism / Q000502:physiology; D006624:Hippocampus / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008562:Membrane Glycoproteins / Q000235:genetics*; D026901:Membrane Transport Proteins / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics*; D011569:Psychiatric Status Rating Scales; D050486:Serotonin Plasma Membrane Transport Proteins; D013569:Synapses / Q000502:physiology
D015415:Biomarkers; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; D001224:Aspartic Acid; D004247:DNA; C000179:N-acetylaspartate