Relationship between cortisol and serotonin metabolites and transporters in alcoholism [correction of alcolholism].
BACKGROUND
Stress hormone activation may induce clinical depression via an interference with central serotonergic neurotransmission. In alcoholics, a reduction in serotonin transporters was associated with clinical depression, and an activation of cortisol secretion is frequently found during detoxification. We assessed the interaction between stress hormone activation, serotonin transporters, monoamine metabolites in the cerebrospinal fluid (CSF), and mood states in male and female alcoholics and healthy control subjects.


METHODS
The availability of serotonin transporters was measured with [I-123]beta-CIT and SPECT in the raphe area of the brainstem in 31 alcoholics after four weeks of abstinence and in 25 age-matched healthy volunteers. Concentrations of plasma cortisol were measured on the day of the SPECT scan. Within one week after the SPECT scan, we assessed monoamine metabolites and corticotropin-releasing factor (CRF) in the CSF.


RESULTS
Clinical depression was associated with a reduction in serotonin transporter availability among male alcoholics. Among male alcoholics and healthy volunteers, CSF 5-HIAA and plasma cortisol concentrations were inversely correlated with the availability of raphe serotonin transporters and positively correlated with the severity of clinical depression. No significant correlations were observed between raphe serotonin transporters and HVA, MHPG and CRF concentrations in the CSF.


CONCLUSIONS
Our findings support the hypothesis of an interaction between reduced serotonin transporters, stress hormone activation and clinical depression. They confirm the hypothesis that serotonergic neurotransmission dysfunction in alcoholism is limited to male alcoholics. The observed interactions between high cortisol concentrations and reduced serotonin transporter availability warrant further studies in major depression and other neuropsychiatric diseases with implied cortisol activation and serotonergic dysfunction.
Heinz
A
A
Intramural Research Program, Clinical Brain Disorders Branch/NIMH, Bethesda, MD, USA. andreas.heinz@charite.de
Jones
D W
DW
Bissette
G
G
Hommer
D
D
Ragan
P
P
Knable
M
M
Wellek
S
S
Linnoila
M
M
Weinberger
D R
DR
D000328:Adult; D000339:Affect; D000437:Alcoholism / Q000097:blood / Q000134:cerebrospinal fluid / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism*; D016022:Case-Control Studies; D003346:Corticotropin-Releasing Hormone / Q000134:cerebrospinal fluid*; D003866:Depressive Disorder / Q000378:metabolism; D005260:Female; D006719:Homovanillic Acid / Q000134:cerebrospinal fluid; D006801:Humans; D006854:Hydrocortisone / Q000097:blood*; D006897:Hydroxyindoleacetic Acid / Q000134:cerebrospinal fluid; D007457:Iodine Radioisotopes; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D026901:Membrane Transport Proteins; D008734:Methoxyhydroxyphenylglycol / Q000134:cerebrospinal fluid; D008875:Middle Aged; D009419:Nerve Tissue Proteins; D011903:Raphe Nuclei / Q000378:metabolism*; D050486:Serotonin Plasma Membrane Transport Proteins; D013375:Substance Withdrawal Syndrome / Q000097:blood / Q000134:cerebrospinal fluid / Q000378:metabolism*; D015899:Tomography, Emission-Computed, Single-Photon
D002352:Carrier Proteins; D007457:Iodine Radioisotopes; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; D008734:Methoxyhydroxyphenylglycol; D006897:Hydroxyindoleacetic Acid; D003346:Corticotropin-Releasing Hormone; D006854:Hydrocortisone; D006719:Homovanillic Acid