. 2015 Feb 2;9:18. doi: 10.3389/fnhum.2015.00018

Table 1.

Summary of included studies.

	Type of study and setting	Sample size at follow-up	Depression diagnosis criteria	*Source of Biomarker (Serum/Plasma/whole blood), Biomarkers Assessed (and type of biomarker) implies statistically significant (p-value < 0.05)**	Treatment offered	Follow-up duration	Outcomes studied
Alvarez et al., 1999; France	Cohort; psychiatry inpatients	N = 8	MADRS ≥ 20	Serum 5 plasma fluoxetine (Neurotransmitter metabolism)	Fluoxetine 20 mg	28 days	Treatment response defined as 50% reduction in MADRS scores from baseline
				Plasma norfluoxetine (Neurotransmitter metabolism)
				Plasma fluoxetine plus norfluoxetine (Neurotransmitter metabolism)
				Plasma 5 HT (Neurotransmitter metabolism)
				Serum 5HT (Neurotransmitter metabolism)
Arolt et al., 2003; Germany	Case-control; psychiatry inpatients	N = 25 (MDD), N = 25 (healthy controls)	Composite International	Plasma S100 B protein* (Neurotrophic)	Different groups of anti-depressants	28 days	Treatment Response defined as 50% reduction in HDRS from baseline
Arolt et al., 2003; Germany	Case-control; psychiatry inpatients	N = 25 (MDD), N = 25 (healthy controls)	Diagnostic Interview for DSM-IV criteria for MDD	Plasma S100 B protein* (Neurotrophic)	Different groups of anti-depressants	28 days
Baldwin et al., 2006; UK	Case-control; Community	N = 28 (MDD), N = 35 (healthy controls)	SCID for MDD	HDL cholesterol* (Metabolic)	Not specified	3.1 years	Poor outcome of depression based on author described criteria assessed by SCID
				LDL cholesterol (Metabolic)
				BMI (Metabolic)
				ESR (Inflammatory)
				Pre-prandial glucose (Metabolic)
				Source: Serum/Plasma/Whole blood was not specified
Baune et al., 2012; Australia	Cohort; community	N = 73	GDS ≥ 6	Serum IL1β (Inflammatory)	Not specified	23.39 months (average)	Remission of depression symptoms defined as GDS <6
				Serum IL6 (Inflammatory)
				Serum IL8 * (Inflammatory)
				Serum IL10 (Inflammatory)
				Serum IL 12p70 * (Inflammatory)
				sVCAM-1 (Inflammatory)
				Serum PAI-1 (Inflammatory)
				SAA (Inflammatory)
				Serum TNF-α (Inflammatory)
				Serum CRP (Inflammatory)
Duval et al., 1996; France	Cohort study; psychiatry Inpatients	N = 30	Unstructured interview for DSM-IV for MDD	Plasma TSH (Neuroendocrine)	1.Amitriptyline (n = 13)	1 month	1. Remission of depression symptoms defined as HDRS<8
				Plasma Free T3 (Neuroendocrine)	2.Fluoxetine (n = 9)		2. “Partial Response” (treatment response) defined as HDRS 8–15
				Plasma Free T4 (Neuroendocrine)	3.Toloxatone (n = 8)
				Plasma TSH response to Protirelin stimulation* *(for outcomes 1 and 2)* (Neuroendocrine)
				Plasma Free T3 response to Protirelin stimulation (Neuroendocrine)
				Plasma Free T4 response to Protirelin stimulation (Neuroendocrine)
Jang et al., 2008; South Korea	Case-control; Psychiatry Outpatients	N = 59 (MDD), N = 34 (healthy controls)	SCID for MDD	Serum S100B protein * (Neurotrophic)	Different groups of anti-depressants	6 weeks	Treatment response defined as 50% reduction in HDRS from baseline
Johnston et al., 1999; UK	Cohort; Psychiatry Outpatients and Inpatients	N = 34	SCID for MDD	Plasma Norepinephrine* (Neuroendocrine)	Not specified	8 years (average)	Poor Outcome defined by Depression Outcome Scale and Lee and Murray criteria
Johnston et al., 1999; UK	Cohort; Psychiatry Outpatients and Inpatients	N = 34	SCID for MDD	Plasma Cortisol (Neuroendocrine)	Not specified	8 years (average)
Jokinen and Nordstrom, 2009; Sweeden	Cohort; Psychiatry Inpatients	N = 346	DSM- IV criteria for all mood disorders, diagnostic method unspecified	Plasma Cortisol* (for outcomes 1 and 2) (Neuroendocrine)	Not specified	18 years (average)	1. Death due to natural causes
Jokinen and Nordstrom, 2009; Sweeden	Cohort; Psychiatry Inpatients	N = 346		Plasma Dexamethasone non-suppression* (for outcomes 1 and 2) (Neuroendocrine)	Not specified	18 years (average)	2. Cardiovascular deaths
Kin et al., 1997; Multi-center	RCT with 3 arms; not specified	N = 70 randomized into 3 arms	HDRS ≥ 18	Plasma dexamethasone non-suppression* (only in Nortriptyline arm) (Neuroendocrine)	3 arms: 1. Nortriptyline 75 mg	7 weeks	Treatment Response defined as 50% reduction in HDRS from baseline
					2.Moclobemide 400 mg
					3. Placebo
Ladwig et al., 2005; Germany	Cohort; Community	N = 975 (only males)	von Zerssen affective symptom check list with a score ≥11	Serum Highly sensitive CRP high risk group > 3 mg/ml* (Inflammatory)	Not specified	7.7 years (average)	1. Myocardial Infarction 2. Sudden cardiac death
Lanquillon et al., 2000; Germany	Cohort; Psychiatry inpatients	N = 24	SCID for MDD	Whole blood Lymphocyte count (Inflammatory)	Amitriptyline in increasing dose	6 weeks	Treatment Response defined as 50% reduction in HDRS and MADRS from baseline
				Whole blood Monocyte count (Inflammatory)
				Whole blood Ratio lymphocyte/monocyte* (Inflammatory)
				Whole blood CRP (Inflammatory)
				Whole blood ESR (Inflammatory)
				Whole blood IL-6 * (Inflammatory)
				Whole blood TNF-alpha (Inflammatory)
Perez et al., 1998; Spain	Cohort; Psychiatry Inpatients	N = 83	HDRS ≥ 17	Plasma 5HIAA (Neurotransmitter)	Different groups of anti-depressants	6 weeks	Treatment Response defined as 50% reduction in HDRS from baseline
				Plasma Total Tryptophan (Neurotransmitter)
				Plasma 5 HT (Neurotransmitter)
				Platelet 5 HT with high concentration 800 ng/10⁹ platelets* (stronger relationship in SSRI sub-group) (Neurotransmitter)
Raison et al., 2013; US	RCT with 2 arms; Community	N = 60 randomized into two arms	Treatment resistance Depression diagnosed using Massachusetts	Plasma Highly sensitive CRP high risk group > 5 mg/ml (Inflammatory)	2 arms: 1.Infliximab infusions × 3 2. Placebo	12 weeks	1. Treatment Response defined as 50% reduction in HDRS from baseline
Raison et al., 2013; US	RCT with 2 arms; Community	N = 60 randomized into two arms	General Hospital Staging method for treatment resistance ≥ 2		2 arms: 1.Infliximab infusions × 3 2. Placebo	12 weeks	2. Remission of depression symptoms defined as HDRS<8
Ribeiro et al., 1993; US	Meta-analysis with 3 different research questions (RQ1-3)	RQ-1	Heterogeneous, including different symptoms scores and interview techniques	Dexamethasone non-suppression* (for RQ2 only) Source: Serum/Plasma/Whole blood was not specified for the included studies	Various	Not specified	1. (RQ1) “Treatment Response”
Ribeiro et al., 1993; US	Meta-analysis with 3 different research questions (RQ1-3)	N = 1273			Various	Not specified	1. (RQ1) “Treatment Response”
		RQ-2	Heterogeneous, including different symptoms scores and interview techniques		Various	1–7 weeks	1. (RQ1) “Treatment Response”
		N = 412			Various	1–7 weeks	1. (RQ1) “Treatment Response”
		RQ-3	Heterogeneous, including different symptoms scores and interview techniques		Various	1–60 months	3. Long term outcome of depression based on predefined author criteria
		N = 411			Various	1–60 months

MADRS, Montgomery Asperg Depression Rating Scale; 5HT, 5 Hydroxytryptamine; HDRS, Hamilton Depression Rating Scale; DSM-IV, Diagnostic and Statistical Manual IV; MDD, Major Depressive Disorder; SCID, Structured Diagnostic Interview for DSM-IV; HDL, High Density Lipoprotein; LDL, Low Density Lipoprotein; ESR, Erythrocyte Sedimentation Rate; BMI, Body Mass Index; GDS, Geriatric Depression Scale; IL, Interleukin; sVCAM-1, Serum Vascular Cell AdhesionMolecule -1; PAI-1, Plasminogen Activator Inhibitor-1; SAA, Serum Amyloid A; TNF-α, Tumor, Necrotic Factor-alpha; CRP, C Reactive Protein; TSH, Thyroid Stimulating Hormone; RCT, Randomized Controlled Trial; 5-HIAA, 5-Hydroxyindoleacetic acid, RQ, Research Question.