*2.1.1 Healthy volunteers*

The sample sizes and ages of participants are as follows. Old men (n = 25; age, 60.8 ± 9.9) and old women (n = 39; age, 67.4 ± 7.5) and young men (n = 49; age, 20.7 ± 1.5) and young women (n = 47; age, 21.2 ± 0.7). Characteristics of these people are described in **Table 1**.


**135**

detection.

**Table 1**.

*Studies on Tryptophan Metabolites in Patients of Major Monopolar Depression*

Outpatients of depression were recruited in this study. Fasting blood samples were taken early in the morning. Their severity of depression was checked by clinical global impression—severity scale (CGI-S), SRS, and

Sample numbers are 55 (male, 15; female, 40; average age, 45.4 ± 11.9). The number of MDD is 38 and BD is 17. Further characteristics of patients are

rpm/min at 4°C). Ethylenediaminetetraacetic acid (EDTA) was used as an

*2.1.3 The simultaneous measurements of TRP metabolites in plasma*

improvement of the assay method is described here.

lites of TRP including melatonin in clinical sample.

*2.1.3.1 Reagents and instrumentation*

Aldrich (St. Louis, MO, USA).

Hamilton depression rating scale (HDRS). The history of prescriptions of drugs such as antidepressants, anxiolytics, mood stabilizers, and other drugs were

Plasma factors were measured after plasma was separated from blood (3000

An ultrahigh-speed liquid chromatography/spectrometry was used for the assay.

The simultaneous analytical method developed can be adapted to major metabo-

The analytical targets of developed method are major metabolites, such as tryptophan (TRP), L-5-hydroxytryptophan (5-HTP), serotonin (5-HT), kynurenine (KYN), 5-hydroxy-tryptophol, tryptophol, 5-hydroxyindoleacetic acid (5-HIAA), indole-3-acetic acid, anthranilic acid (AA), kynurenic acid (KYNA), quinaldic acid, indole-3-butyric acid, 3-hydroxykynurenine (3-HKYN), 3-hydroxyanthranilic acid (3-HAA), xanthurenic acid (XA), melatonin, and quinolinic acid (QA). Each compound was purchased from major chemical regent manufacturers, such as FUJIFILM Wako chemical (Osaka, Japan) and Sigma-

Metabolite analysis was performed by a liquid chromatograph tandem mass spectrometer, the LCMS-8060 quadrupole mass spectrometer combined with Nexera X2 liquid chromatograph system (Shimadzu Corporation, Kyoto, Japan). The targets are separated by reversed-phase chromatography using C18 analytical column, L-Columns ODS2 (2.1 mm × 150 mm, CERI, Tokyo, Japan) with a gradient elution. Mobile phases were 0.1% formic acid solution and acetonitrile with the gradient elution by 5% concentration of acetonitrile in 3 min and then 5–95% in 6 min, followed by 5% in 3 min at a total flow rate of 0.4 mL/ min. The temperature of the column was 40°C. Electrospray ionization (ESI) was used as mostly positive ionization with multi-reaction monitoring (MRM)

Flow rate of the neutralizer and the drying gas were 2 L/min and 10 mL/min, respectively. Temperature of desolvation line (heated capitally tube) was 250°C. ESI interface was used at 400°C with 10 L/min of heating gas flow. Each MRM transition was optimized using each standard solution. Optimized results were shown in

Although detailed methodology was described elsewhere [5–9], the important

*DOI: http://dx.doi.org/10.5772/intechopen.91967*

*2.1.2 Patients*

asked.

described below.

anticoagulant.

**Table 1.**

*Background of healthy participants.*

*Studies on Tryptophan Metabolites in Patients of Major Monopolar Depression DOI: http://dx.doi.org/10.5772/intechopen.91967*

### *2.1.2 Patients*

*Melatonin - The Hormone of Darkness and Its Therapeutic Potential and Perspectives*

interventions.

analysis [4].

depressive patients.

MS) [9–12].

**2. Results**

*2.1.1 Healthy volunteers*

described in **Table 1**.

so we do not discuss these roles in detail.

**and patients of major depression**

levels of TRP metabolites in patients of depression.

of major monopolar depression and healthy volunteers.

Major depressive disorder is one of the most common psychiatric disorders which is burdensome and costly worldwide in adults. Although pharmacological and non-pharmacological treatments are available, because of inadequate resources, antidepressants are used more frequently than psychological

By using a meta-analysis, all antidepressants were shown more efficacious than

Serotonin (5-HT) has been indicated to be involved in etiology of depression [5]. The roles of various metabolites of kynurenine (KYN) pathway are reviewed [6],

As to relationships between serotonin levels and depression, we analyzed plasma

Although the concentration of 5-HT has been considered to be low in depressive patients [7], 5-HT concentration in the brains of suicide victims were not low [8]. Therefore, it is not known if 5-HT concentration is decreased in the brains of

We have recently succeeded in simultaneous measurements of TRP metabolites in plasma using an ultrahigh-speed liquid chromatography/mass spectrometry (LC/

We now report age and gender differences of various TRP metabolites in patients

**2.1 Comparison of plasma levels of TRP metabolites between healthy people** 

The sample sizes and ages of participants are as follows. Old men (n = 25; age, 60.8 ± 9.9) and old women (n = 39; age, 67.4 ± 7.5) and young men (n = 49; age, 20.7 ± 1.5) and young women (n = 47; age, 21.2 ± 0.7). Characteristics of these people are

placebo in adults with major depressive disorder. Smaller differences between active drugs were found when placebo-controlled trials were included in the

**134**

**Table 1.**

*Background of healthy participants.*

Outpatients of depression were recruited in this study. Fasting blood samples were taken early in the morning. Their severity of depression was checked by clinical global impression—severity scale (CGI-S), SRS, and Hamilton depression rating scale (HDRS). The history of prescriptions of drugs such as antidepressants, anxiolytics, mood stabilizers, and other drugs were asked.

Sample numbers are 55 (male, 15; female, 40; average age, 45.4 ± 11.9). The number of MDD is 38 and BD is 17. Further characteristics of patients are described below.

Plasma factors were measured after plasma was separated from blood (3000 rpm/min at 4°C). Ethylenediaminetetraacetic acid (EDTA) was used as an anticoagulant.
