TABLE 4.

Potential circulating blood‐brain barrier metabolites markers of stress and mood disorders

Marker	Disorder	Changes	Details/clinical symptoms	References
VCAM‐1 (Vascular cell adhesion molecule 1)	PTSD	↑		Sumner et al., (2018)
	MDD	↑/↓	Sex‐specific effects (↓♀, ↑ ♂)	Ramsey et al. (2016)
sVCAM‐1	BD	↑	First manic episode	Turan et al. (2014)
		↓	Acute and remission phases	Pantović‐Stefanović et al., (2018)
ICAM‐1 (Intercellular cell adhesion molecule 1)	PTSD	↑		Sumner et al., (2018)
		—		Jergović et al., (2015)
	MDD	↑		Lespérance et al. (2004) and Dimopoulos et al. (2006)
		↑	Pre‐treatment levels associated with treatment response	Chan et al., (2016)
sICAM‐1	PTSD	↑	Positive correlation with higher adversity and PTSD scores (UCLA PTSD scales)	Farr et al., (2015)
	MDD	↑	Late‐life depression	Van Agtmaal et al. (2017)
		↑	3‐days post antidepressant washout	Baghai et al. (2018)
	BD	↑	First manic episode	Turan et al. (2014)
		↑	Acute and remission phases	Pantović‐Stefanović et al., (2018)
		↑	Subthreshold hypomanic symptoms and depressive symptoms	Reininghaus et al., (2016)
Claudin‐5	BD	↑		Kılıç et al., (2020)
PAI‐1 (plasminogen activator inhibitor 1)	PTSD	↑	Positive correlation with symptoms of disease severity (re‐experiencing and arousal)	Farr et al., (2015)
	MDD	↑	No association with symptom severity (HAM‐D, HAM‐A) or disease duration	Eskandari et al., (2005)
			Linked to severity of symptoms (CES‐D)	Lahlou‐Laforet et al., (2006)
			♀, Increase linked to venlafaxine treatment response (HAM‐D)	Carboni et al., (2019)
		—	Linked to treatment response (HAM‐D, IDS)	Chan et al., (2016)
CCL11/eotaxin‐1	MDD	↑	Related to suicidal ideation	Simon et al. (2008) and Grassi‐Oliveira et al., (2012)
		—		Leighton et al. (2018)
	BD	—	Euthymic state	Brietzke, Kauer‐Sant’Anna, et al., (2009)
		↑	Euthymic patients, late‐stage only	Panizzutti et al. (2015)
MCP1/CCL2 (Monocyte chemoattractant protein 1)	PTSD	↑		Toft et al. (2018)
	MDD	↑		Piletz et al. (2009)
		—	Possibly related to metabolic effects	Bai et al. (2014)
MMP2 (Matrix metalloproteinase 2)	PTSD	↑		Brahmajothi and Abou‐Donia (2020)
	MDD	↓	Associated with response to ECT	Shibasaki et al. (2016) and Shibasaki et al. (2018)
		↑		Bobińska et al. (2016)
	BD	↓		Shibasaki et al. (2018)
MMP3	BD	↓		Haenisch et al. (2016)
MMP7	MDD	↑		Bobińska et al. (2016)
	BD	↑		Haenisch et al. (2016)
MMP9	PTSD	↑		Brahmajothi and Abou‐Donia (2020)
	MDD	↑	♀, associated with treatment response	Domenici et al. (2010), Bobińska et al. (2016), Shibasaki et al. (2018), and Carboni et al., (2019)
		—	Associated with severity of symptoms (depression, quality of life scores, and social function scores) ↓ in non‐relapsing patients after ECT	Yoshida et al. (2012) and Shibasaki et al. (2016)
	BD	↑		Haenisch et al. (2016)
		↑	Euthymic stage, correlated negatively with subthreshold hypomanic symptoms (YMRS), negative association with d2 Test of Attention	Reininghaus et al., (2016), Young et al., (1978)
S100β (S100 calcium binding protein B)	PTSD	—		(Brahmajothi & Abou‐Donia, 2020)
	MDD	↑	Associated with symptom severity and treatment response (HAM‐D)	Schroeter et al. (2002)
			In remission	Arolt et al. (2003), Dietrich et al. (2004), Hetzel et al. (2005), and Schroeter et al. (2008)
			No correlation with clinical severity of the patients (BDI‐II and HAM‐D)	Arora et al. (2019)
			♀, higher in remitting disorder	Yang et al. (2008) and Arora et al. (2019)
			High baseline levels associated with treatment response (HAM‐D)	Ambrée et al. (2015)
			Associated with treatment response (escitalopram) High baseline levels associated with smaller reductions in anhedonia (IDS‐C)	Jha et al. (2019)
			Associated with memory processes	Zhang et al. (2009)
		—	Remission, correlated with lower cognitive performance	Ottesen et al. (2020)
	BD	↑	Manic phase Manic and depressed phase	Machado‐Vieira et al. (2002) and Andreazza et al. (2007)
		—	↓ after treatment	Tsai and Huang (2017)
NSE (Neuron‐specific enolase)	BD	↓	Manic phase	Machado‐Vieira et al. (2007) and Wiener et al. (2013)
			Chronic patients, not first episode	Akcan et al. (2018)
		—	Manic phase	Tsai & Huang, (2017)

Abbreviations: BDI‐II, Beck Depression Inventory‐II; CES‐D, Center of Epidemiologic Studies Depression Scale; HAM‐A, Hamilton anxiety rating scale; HAM‐D, Hamilton depression rating scale; HC, healthy controls; IDS, Inventory of Depressive Symptoms; IDS‐C, 30‐item Inventory of Depressive Symptomatology Clinician‐Rated; YMRS, Young Mania Rating Scale.