Baseline HDRS scores were as follows: drug-free remitted group (M = .89, SD = 1.16), healthy control group (M = .79, SD = .86), and paroxetine-treated remitted group (M = 3.32, SD = 3.00).
Depletion related side effects were similar in frequency and severity to those observed in previous reports. Six subjects (25%) complained of nausea, two of them (8%) experienced vomiting. In all cases nausea and vomiting resolved prior to lumbar puncture. Two of the subjects complained of headaches after the lumbar puncture. In one of the cases, the headache was mild and resolved promptly. In the other case, due to the severity and persistence or recurrence of the headache after 24 hours the subject required treatment with a blood patch, a procedure in which a small amount of the patient's blood is injected through a standard lumbar puncture procedure in order to correct the presumed leakage of CSF from the sampling site. This headache occurred following the sham condition and resolved without further complications. We were unable to obtain a CSF sample in one female subject during one of the test sessions. One female healthy control did not return for her second test session, and did not state her reason for discontinuation. All available data was analyzed.
During TRP depletion TRP levels decreased by an average of 89.1 % (range 79 to 94%) (t = 22.95, df = 20, p< 0.01), ΣLNAA levels increased by an average of 303% (range 157% to 479%) (t = −10.17, df = 20, p< 0.01), and TRP/ΣLNAA decreased by an average of 96.1% (range 90% to 99%; t = 15.91, df = 20, p< 0.01). During sham condition TRP levels increased by an average of 90.5 % (range −17% to +338%) (t = −7.64, df = 23, p< 0.01), ΣLNAA levels increased by an average of 269% (range 78% to 686%) (t = −7.57, df = 23, p< 0.01), and TRP/ΣLNAA decreased by an average of 25.31% (range +38 to −74%; t = 5.27, df = 23, p< 0.01). ΣLNAA level changes were very similar during TRP depletion and sham condition (difference of 13.6%, t = −.77, df = 20, p= 0.45). [See for plasma levels].
Plasma Amino Acid Levels During TRP Depletion and Sham Condition
Mean CSF 5-HIAA concentration was significantly lower following active TRP depletion (values represent mean ± standard deviation) (6.34 ± 3.18 ng/ml) than following sham condition (8.36 ± 3.68 ng/ml), representing a mean 24.16% difference between conditions (t = −5.1, df = 20, p <0.01) [See ]. CSF TRP was significantly lower during TRP depletion (80.2 ± 47.29 ng/ml) than during sham condition (490.69 ± 174.85 ng/ml), representing a 73.66% difference between conditions (t = −13.51, df = 20, p <0.01) [See ]. CSF NPY was 4.23% higher during TRP depletion (54.39 ± 9.6 pmol/L) than during sham testing (52.18 ± 7.54 pmol/L) (t = 1.747, df = 19, p <0.10). There were no significant differences in CSF neurochemical findings between subject-groups, and there were no differences between TRP depletion and sham tests in CSF HVA, MHPG, and CRH (see ).
CSF 5-HIAA Concentrations at Nine Hours Following Active and Sham Tryptophan Depletion Protocol
CSF TRP Concentrations at Nine Hours Following Active and Sham Tryptophan Depletion Protocol
CSF Neurochemicals During TRP Depletion and Sham Condition
Relationship of Plasma amino acids and CSF neurochemicals
A number of significant correlations between plasma TRP, ΣLNAA levels, TRP/ΣLNAA and CSF neurochemicals were observed. Of note, during TRP depletion, CSF TRP levels were more highly correlated with plasma ΣLNAA levels and TRP/ΣLNAA than with plasma TRP levels. TRP/ ΣLNAA correlated significantly with CSF TRP levels during sham condition. Additionally, CSF 5-HIAA correlated strongly with CSF HVA during both test conditions. (Pertinent findings are reported in ).
Selected Correlations Between Biochemical Parameters During TRP Depletion and Sham Condition
ANOVA of HDRS scores did not show statistical significant main effects of time (F = 1.66, df = 3, p >0.1), condition (F = 0.05, df = 1, p > 0.1), or any significant interaction effects. Similarly, HAMA and SC scores showed no significant main or interaction effects. There were no sex differences in CSF TRP and CSF5-HIAA for any of the groups.
Relationship of HDRS and CSF TRP
During TRP depletion, Pearson's correlation of maximum HDRS score and CSF TRP had a trend of significance in subjects in remission from depression (R = −.45, N = 17, p =.07); but not in healthy controls (R = −.01, N = 5, p =.98).