Serum 3-Hydroxybutyrate in Patients with Psychogenic Somatoform Symptoms May Be a Predictor of the Effectiveness of Sertraline and Venlafaxine

Figures & data

Table 1 Comparison of Clinical Characteristics Between Normal-3HB Group and High-3HB Group

	Total	Normal-3HB Group	High-3HB Group
	n = 132	n = 92	n = 40
Age ± SD	57.2 ± 18.6	58.7 ± 17.4	53.7 ± 21.0
Female (%)	88 (66.7%)	62 (67.4%)	26 (65.0%)
BMI ± SD	23.8 ± 3.7	23.7 ± 3.8	24.1 ± 4.3
No. of smoker patients (%)	24 (18.2%)	16 (17.4%)	8 (20.0%)
Blood tests
Albumin ± SD (g/dL)	4.21 ± 0.33	4.19 ± 0.30	4.24 ± 0.39
Creatinine ± SD (mg/dL)	0.71 ± 0.15	0.72 ± 0.14	0.71 ± 0.16
HbA1c ± SD (%)	5.46 ± 0.33	5.48 ± 0.34	5.42 ± 0.30
Psychological tests
CES-D ± SD	22.2 ± 13.8	21.4 ± 13.8	24.1 ± 13.8
STAI-state ± SD	49.7 ± 11.4	49.5 ± 12.1	50.3 ± 9.7
STAI-trait ± SD	51.9 ± 11.3	50.9 ± 11.5	53.9 ± 10.8
Current use of benzodiazepines (%)	44 (33.3%)	32 (34.8%)	12 (13.0%)
Psychological complaints and episodes
Fatigue (%)	60 (45.5%)	39 (42.4%)	21 (52.5%)
Dizziness or vertigo (%)	33 (25.0%)	19 (20.7%)	14 (35.0%)
Headache (%)	46 (34.8%)	24 (26.1%)	22 (55.0%)**
Non-headache pain (%)	45 (34.1%)	25 (27.2%)	20 (50.0%)*
Numbness (%)	24 (18.2%)	18 (19.6%)	6 (15.0%)
Nausea (%)	23 (17.4%)	17 (18.5%)	6 (15.0%)
Chest tightness (%)	24 (18.2%)	18 (19.6%)	6 (15.0%)
Palpitation (%)	26 (19.7%)	18 (19.6%)	8 (20.0%)
Chronic cough or globus syndrome (%)	28 (21.2%)	20 (21.7%)	8 (20.0%)
Breathlessness (%)	8 (6.1%)	6 (6.5%)	2 (5.0%)
Psychological complaints and episodes
Anorexia (%)	36 (27.3%)	22 (23.9%)	14 (35.0%)
Insominia (%)	87 (65.9%)	63 (68.5%)	24 (60.0%)
Diminished motivation (%)	85 (64.4%)	57 (62.0%)	28 (70.0%)
Suicidal ideation (%)	26 (19.7%)	8 (8.7%)	18 (45.0%)***
Psychiatric diagnosis^#(ultimately)
Mood disorder (%)	48 (36.4%)	32 (34.8%)	16 (40.0%)
<Major depression (%)>	29 (22.0%)	18 (19.6%)	11 (27.5%)
Anxiety disorder (%)	21 (15.9%)	16 (17.4%)	5 (12.5%)
Somatoform disorder (%)	79 (59.8%)	54 (58.7%)	25 (62.5%)
Treatment-effective patients (%)	83 (62.9%)	46 (50.0%)	37 (92.5%)***

Note: *Significance compared with normal-3HB group (*p<0.05, **p<0.01, ***p<0.001). ^#Diagnosis is overlapped in some patients.

Table 2 Comparison of Characteristics Between Treatment Non-Effective Group and Effective Group

n= 132	Non-Effective Group	Effective Group
	n = 49	n = 83
Age ± SD	58.5 ± 19.1	56.4 ± 18.4
Female (%)	34 (69.4%)	54 (65.1%)
BMI ± SD	24.2 ± 3.8	23.6 ± 3.6
No. of smoker patients (%)	6 (12.2%)	18 (21.7%)
Blood tests
Albumin ± SD (g/dL)	4.26 ± 0.33	4.18 ± 0.33
Creatinine ± SD (mg/dL)	0.71 ± 0.12	0.71 ± 0.16
HbA1c ± SD (%)	5.47 ± 0.30	5.46 ± 0.34
3HB ± SD (μmol/L) before treatment (%)	49.0 ± 46.8	81.0 ± 62.0 ***
No. of patients with high-3HB^# before treatment (%)	3 (6.1%)	37 (44.6%) ***
Psychological tests
CES-D ± SD	19.6 ± 12.4	23.7 ± 14.4
STAI-state ± SD	48.8 ± 12.9	50.3 ± 10.5
STAI-trait ± SD	50.8 ± 11.5	52.5 ± 11.3
Current use of benzodiazepines (%)	17 (34.7%)	27 (32.5%)
Physical complaints and episodes
Fatigue (%)	18 (36.7%)	42 (50.6%)
Dizziness or vertigo (%)	12 (24.5%)	21 (25.3%)
Headache (%)	11 (22.5%)	34 (41.1%)*
Non-headache pain (%)	12 (25.0%)	33 (40.1%)
Numbness (%)	11 (22.5%)	13 (15.7%)
Nausea (%)	9 (18.4%)	14 (16.9%)
Chest tightness (%)	11 (22.5%)	13 (15.7%)
Palpitation (%)	11 (22.5%)	15 (18.1%)
Chronic cough or globus syndrome (%)	12 (25.0%)	16 (19.3%)
Breathlessness (%)	3 (6.1%)	5 (6.0%)
Psychological complaints and episodes
Anorexia (%)	13 (26.5%)	23 (27.7%)
Insominia (%)	33 (67.4%)	54 (65.1%)
Diminished motivation (%)	28 (57.1%)	57 (68.7%)
Suicidal ideation (%)	2 (4.1%)	24 (29.0%) ***
The ultimate psychiatric diagnosis ^$
Mood disorder (%)	12 (24.5%)	36 (43.4%) *
<Major depression (%)>	7 (15.3%)	23 (27.7%)
Anxiety disorder (%)	8 (16.3%)	13 (15.7%)
Somatoform disorder (%)	36 (73.5%)	43 (51.8%)*

Notes: *Significance compared with non-effective group (*p<0.05, ***p<0.001). ^#High-3HB: ≥80 μmol/L. ^$Diagnosis is overlapped in some patients.

Table 3 Multiple Logistic Regression Analysis of the Factors Associated with Elevation of 3HB

n=132	Regression Model
Independent Valuables	Odds Ratio	p
Age	0.99 (0.97–1.02)	0.627
Gender (Female=1, Male=0)	1.18 (0.42–3.34)	0.753
BMI	1.06 (0.93–1.21)	0.397
Smoking	0.89 (0.26–3.10)	0.859
CES-D	0.99 (0.93–1.04)	0.615
STAI-state	0.95 (0.88–1.02)	0.144
STAI-trait	1.04 (0.97–1.12)	0.257
Current use of benzodiazepines	0.71 (0.23–2.23)	0.558
Fatigue	1.32 (0.45–3.87)	0.619
Dizziness or vertigo	1.03 (0.29–3.57)	0.967
Headache	2.64 (0.80–8.72)	0.112
Non-headache pain	1.83 (0.52–6.37)	0.345
Numbness	0.55 (0.13–2.38)	0.426
Nausea	0.49 (0.12–2.04)	0.324
Chest tightness	0.87 (0.22–3.41)	0.847
Palpitation	1.91 (0.50–7.33)	0.347
Chronic cough or globus syndrome	1.85 (0.52–6.63)	0.346
Breathlessness	0.77 (0.09–6.88)	0.814
Anorexia	1.97 (0.63–6.14)	0.240
Insomnia	0.40 (0.11–1.41)	0.154
Diminished motivation	1.45 (0.42–4.94)	0.556
Suicidal ideation	10.2 (2.46–42.2)	0.001**
Predictive accuracy (%)	80.3
−2 Log likelihood	121.8

Note: 95% confidence intervals are included in parentheses. **p<0.01.

Table 4 Hierarchical Multiple Logistic Regression Analysis of the Factors Associated with Effectiveness of Sertraline or Venlafaxine

n=132	Model 1		Model 2
Independent Valuables	Odds Ratio	p	Odds Ratio	p
Age	1.01 (0.98–1.03)	0.548	1.01 (0.99–1.04)	0.337
Gender (Female=1, Male=0)	0.98 (0.38–2.51)	0.969	1.02 (0.37–2.80)	0.977
BMI	0.96 (0.85–1.08)	0.465	0.94 (0.83–1.07)	0.361
Smoking	1.76 (0.57–5.45)	0.325	1.98 (0.60–6.51)	0.261
CES-D	1.02 (0.97–1.07)	0.404	1.02 (0.97–1.07)	0.366
STAI-state	1.00 (0.94–1.06)	0.931	1.02 (0.95–1.08)	0.610
STAI-trait	0.98 (0.92–1.04)	0.535	0.96 (0.90–1.03)	0.251
Current use of benzodiazepines	0.86 (0.33–2.20)	0.749	0.93 (0.34–2.55)	0.886
Fatigue	1.81 (0.66–4.97)	0.253	2.01 (0.66–6.16)	0.221
Dizziness or vertigo	0.66 (0.21–2.06)	0.471	0.67 (0.20–2.25)	0.514
Headache	1.73 (0.57–5.25)	0.335	1.40 (0.43–4.57)	0.582
Non-headache pain	1.86 (0.56–6.12)	0.310	1.64 (0.46–5.83)	0.445
Numbness	0.44 (0.13–1.55)	0.203	0.51 (0.13–2.05)	0.346
Nausea	0.64 (0.19–2.09)	0.457	0.79 (0.22–2.78)	0.709
Chest tightness	0.67 (0.22–2.07)	0.489	0.71 (0.21–2.37)	0.574
Palpitation	1.19 (0.39–3.69)	0.758	1.03 (0.30–3.51)	0.962
Chronic cough or globus syndrome	1.02 (0.32–3.28)	0.976	0.97 (0.25–3.80)	0.967
Breathlessness	1.40 (0.24–8.23)	0.710	1.64 (0.24–11.2)	0.616
Anorexia	0.78 (0.28–2.14)	0.628	0.60 (0.20–1.79)	0.357
Insomnia	0.68 (0.24–1.95)	0.473	0.86 (0.26–2.81)	0.801
Diminished motivation	1.02 (0.37–2.85)	0.965	0.88 (0.28–2.75)	0.822
Suicidal ideation	6.91 (1.31–36.4)	0.022*	3.30 (0.54–20.2)	0.197
High-3HB (≥80 μmol/L)			10.0 (2.49–40.3)	0.001**
Predictive accuracy (%)	72.0		74.2
−2 Log likelihood	151.8		134.7
p value for Δ-2 Log likelihood change	<0.001***

Notes: 95% confidence intervals are included in parentheses. *p<0.05, **p<0.01, ***p<0.001.

Figure 1 Levels of 3HB before and after treatment with sertraline or venlafaxine in the non-effective group and effective group.