Plasma metabolomic patterns in patients with exhaustion disorder

Figures & data

Table

Diagnostic criteria for Exhaustion Disorder
A	Physical and mental symptoms of exhaustion with minimum two weeks duration. The symptoms have developed in response to one or more identifiable stressors which have been present for at least 6 months.
B	Markedly reduced mental energy, which is manifested by reduced initiative, lack of endurance, or increased time needed for recovery after mental efforts.
C	At least four of the following symptoms have been present most of the day, nearly every day, during the same 2-week period:
	1	Persistent complaints of impaired memory.
	2	Markedly reduced capacity to tolerate demands or to work under time pressure.
	3	Emotional instability or irritability.
	4	Insomnia or hypersomnia.
	5	Persistent complaints of physical weakness or fatigue.
	6	Physical symptoms such as muscular pain, chest pain, palpitations, gastrointestinal problems, vertigo or increased sensitivity to sounds.
D	The symptoms cause clinically significant distress or impairment in social, occupational or other important areas of functioning.
E	The symptoms are not due to the direct physiological effects of a substance (such as a drug of abuse or a medication) or a general medical condition (e.g., hypothyroidism, diabetes, infectious disease).
F	If criteria for major depressive disorder, dysthymic disorder or generalized anxiety disorder are met, Exhaustion Disorder is set as a comorbid condition

Table 1. Descriptives.

	Clinical burnout	Healthy controls
	N = 20	N = 21	p value^a
Women/men (n)	10 / 10	12 / 9	.758
Age, mean (SD)	41 (6)	37 (4)	.032
BMI, mean (SD)	24.6 (2.9)	22.8 (2.2)	.030
WHR, mean (SD)	0.87 (0.07)	0.85 (0.06)	.240
Burnout score, median (range)	4.4 (2.0-6.2)	2.0 (1.1-2.6)	<.001

^a Sex, was tested by chi-square test, burnout score by Mann–Whitney U-test, and age, BMI and WHR by t-test.

Figure 1. Principal component analysis (PCA) plots for the fasting and the postprandial condition. Grey circles are ED patients and the black circles controls.

Figure 2. Loadings scatter plot visualizing the metabolite distribution in fasting. Healthy control subjects to the left (negative values) and ED patients to the right (positive values).

Figure 3. Metabolites identified by gas chromatography mass spectrometry (GC-MS) analysis. Metabolites of importance according to OPLS-DA analysis (Variable of Importance (VIP) > 1) are marked with arrows indicating higher (?) or lower (?) abundance in ED patients. A = fasting, B = nonfasting.

Table 2. OPLS metabolic compounds of importance for the fasting model.

Metabolite	Loadings value	VIP
CYSTEINE	−0.17	1.57
HEXADECANOIC ACID	0.19	1.54
OCTADECENOIC ACID	0.19	1.54
TRYPTOPHAN	−0.15	1.48
RI 1675 M/z 243	−0.15	1.45
OCTADECADIENOIC ACID	0.17	1.43
GLYCINE	−0.17	1.42
RI 1450 M/z 170	−0.12	1.36
GLUTAMINE	−0.11	1.36
ARABITOL	−0.13	1.35
XYLITOL	−0.13	1.35
PHENYLALANINE	−0.11	1.34
LYSINE	0.15	1.27
DODECANOIC ACID	0.16	1.25
1,5-ANHYDRO-D-GLUCITOL	−0.13	1.23
METHIONINE	−0.10	1.20
INOSITOL, scyllo	−0.10	1.20
RIBITOL	−0.09	1.18
RI 2163 M/z 202	−0.12	1.15
CITRULLINE	−0.09	1.14
PYROGLUTAMIC ACID	−0.11	1.13
4-HYDROXYPHENYLACETIC ACID	−0.14	1.11
GAMMA-TOCOPHEROL	−0.13	1.09
CITRIC ACID	−0.11	1.07
ASPARAGINE	−0.06	1.07
ACONITIC ACID	−0.11	1.07
SERINE	−0.10	1.02
GLUCONIC ACID	−0.11	1.01

Figure 4. Loadings scatter plot visualizing the metabolite distribution in nonfasting. Healthy control subjects to the left (negative values) and ED patients to the right (positive values).

Table 3. OPLS metabolic compounds of importance for the nonfasting model.

Metabolite	Loadings value	VIP
LYSINE	0.23	1.89
ADENOSINE-5-MONOPHOSPHATE	−0.20	1.72
GLYCINE	−0.18	1.50
URIC ACID	0.18	1.50
INOSITOL, scyllo	0.13	1.45
RI 2171 M/z 290 1 M/z523	−0.17	1.43
CITRULLINE	0.15	1.41
GLUCONIC ACID	−0.15	1.40
MALIC ACID	−0.15	1.34
VALINE	0.12	1.33
SERINE	−0.13	1.33
3-HYDROXYBUTYRIC ACID	0.15	1.30
LACTULOSE	−0.11	1.27
GLUTAMINE	−0.08	1.25
RIBITOL	0.08	1.19
OCTADECANOIC ACID	0.13	1.16
RI 1349 M/z 203 1 M/z293	0.14	1.15
ALPHA-TOCOPHEROL	0.10	1.12
PHENYLALANINE	0.04	1.10
RI 1450 M/z 170 1 M/z244	0.04	1.10
PYROGLUTAMIC ACID	0.08	1.09
ARABITOL	0.05	1.06
XYLITOL	0.05	1.06
CYSTEINE	0.08	1.06
TRYPTOPHAN	0.01	1.06
THREONINE	0.05	1.04
OCTADECENOIC ACID	0.11	1.03
TARTARIC ACID	−0.12	1.03
ASPARAGINE	0.06	1.03