Towards a possible aetiology for depressions?

Abstract

Background: Since a genetic disposition for depression is probable, there ought to be biochemical changes. Increased peptide levels with relevant bioactivities have been found in urine in a previous investigation, which may be such changes.

Methods: Urine from patients with severe depression according to ICD 10 have been run on reversed phase High Performance Liquid Chromatography, and off line mass spectrometry was performed on some of these peptides.

Results: We find overlapping patterns of peptide peaks in severe depression, but with considerable individuality. Mass spectrometry shows that some of these peptides are probably of dietary origin, because their sequences are found only in certain dietary proteins. Opioids from casein and gliadin are typical examples.

Conclusion: Our data show that the disposition must be polygenetic because some peptide peaks with the same bioactivity are of different length in different patients, but with the same diagnosis. However, some of the peaks are common Peptide increase in urine is found when break down is deficient, and the data presented agree with reports on peptidase deficiencies in depression. Antidepressant drugs decrease the peptide level after about 3 weeks.

Figure 1

The top trace is a typical 215 nm normal elution pattern from a control on c-18 reverse phase column. (Vydac C-18 protein and peptide column, Vydac, Hesperia, Ca 250 × 4.5 mm) at 30 degrees C [11]. First morning urine equivalent to 250 nano-moles of creatinine was applied. The peaks after hippuric acid were integrated by the HPLC attached computer. The bottom trace is from a severely depressed female patient age 33 yr (Diagnosis: F: 33.3).

Figure 2

2a and 2b HPLC chromatogram from two depressed and hospitalized males with the same diagnosis (ICD 10: F33.3), and age (35 yr). Note the difference in pattern in spite of similar diagnosis, sex and age. The reproducibility of the points of elution running controls after each buffer renewal: For beta-casomorphine (bovine) 1–7: X ± SD = 62.18 ± 0.24 ml (n = 38); 95% Confidence interval = 62.10–62.26. For the beta-casomorphine like peak 1–5: 50.14 ± 0.19 (n = 38) and 95% Confidence interval = 50.08–50.20.

Figure 3

Gel filtration on P 2 gels 1.6 × 90 cm in 0.5 M acetic acid of 24 h complete urine of three patients suffering from depression. (ICD F33.3). The patients were on usual food supply but hospitalized. Whatman 3 MM paper filters was used to filter urine. Elution was monitored by measuring 5% aliquots by off line alkaline hydrolysis and ninhydrin colour developed as described [9], and with an equimolar absorption coefficient for peptides measured at 570 nm for each amino acid.

Figure 4

Serotonin uptake stimulation of the pure peptide. Concentration of peptide along the abcissa. Platelets were prepared as outlined in methods. -14 is 10 to the power of -14 M(10^-14 M). The typical hormetic dose response curve is shown.

Figure 5

Mass spectrometry of the peak from gel filtration with Kav = 0.61 characteristically partially overlapping with the peak with Kav = 0.66. The serotonin uptake stimulator is seen with mass +1 = 373.4 and a peptide with unknown function and mass +1 of 505.4(Y-P-E-P) which fits deamidated gliadinomoprhine tetrapeptide. Also casomorphine 3–6 with mass +1 = 417.6 is seen (F-P-G-P). A peptide with MW+1 = 489.3 (Expected = 489.5) that may be derived from kappa-casein has a probable structure of L-P-Y-P (casein κ 56–59). Several other peptides will be published separately when elucidated. The figure illustrates the heterogeneity of the gel filtration peaks and the amount of work needed to characterize the many eluted compounds.