Biomarkers for bipolar disorder: current insights

Figures & data

Table 1 Potential biomarkers for bipolar disorder

Potential markers	Findings	comparing patients with BD to non-psychiatric controls				Methods/instruments	Reference
		Mania	Euthymia	Depression	State not specified
Neuroimaging	Amygdala activity	↑	↑	↑		Functional MRI, positron emission tomography	For more information, please see Keener et al^Citation12
	Ventral striatal activity	↑	↑	↑
	Subcortical activity		↓
	Prefrontal activity		↓
	Subcortical limbic activity	↑		↑
	Dorsal cingulate activity		↓	↓
	Ventral prefrontal cortex activity	↓	↓
White matter integrity	Fraction anisotropy in forceps minor, anterior cingulate cortex, corpus collosum, hippocampal gyrus, thalamus and prefrontal cortex				↓	Diffusion tensor imaging	Versace et al;^Citation15 Brambilla et al;^Citation14 Vederine et al;^Citation23 McIntosh et al^Citation26
	Radial diffusivity in forceps minor				↑		Versace et al^Citation15
	Apparent diffusion coefficient in frontal, temporal, parietal, occipital lobes, subguenal regions				↑		Brambilla et al;^Citation14 Hong et al;^Citation24 Kafantaris et al^Citation25
Reward-related neural activation	Left lateral orbital frontal cortical activity (OFC; BA11/47)	↑	↑			Functional MRI E lectroencephalography Event-related potential	Nusslock et al;^Citation42 Bermpohl et al;^Citation43 Harmon-Jones et al;^Citation44 Mason et al^Citation45
Brain morphometry	Grey matter volume in frontal and subcortical regions				↓	Structural MRI	Savitz et al^Citation53
	Neuronal and glial cell density and number in prefrontal cortex and subguenal anterior cingulate circuits				↓	3D morphometric method Stereological rotate method	Ongur et al;^Citation61 Rajkowska et al^Citation62
Neurochemicals	Dopamine transporter levels				i	Western blot qRT-PCR PET imaging	Rao et al;^Citation74 Anand et al^Citation75
	Glutamate/glutamine ratio	↑	↑	↑		Proton MR spectroscopy	Yildiz-Yesiloglu and Ankerst;^Citation77 Frye et al;^Citation78 Ongur et al;^Citation79 Dager et al^Citation80
	VGLUTI (vesicular glutamate transporter 1) nectrin-G1 and -G2 levels				↑ ↑	qRT-PCR	Eastwood et al^Citation82 Eastwood et al^Citation82
Genes	CACNAIC, DTNA, FOXPI, GNG2, ITPR2, LSAMP, NPAS3, NCOA2, NTRK3, ODZ4, ANK3, NCAN				↑↓	Large-scale genome-wide association study (GWAS)	Psychiatric GWAS Consortium Bipolar Disorder Working Group;^Citation66 Nurnberger et al;^Citation87 Bhat et al;^Citation88 Soeiro-de-Souza et al;^Citation90 Ruberto et al;^Citation91 Cichon et al^Citation92
	NRGI, DISCI, BDNF, COMT, 5HTT, TPH2				↑↓	Direct candidate gene approach	Tiwary;^Citation93 Rotondo et al^Citation98
MicroRNAs	miR-504, miR-145, miR-145, miR-22, miR-l33b, miR-154, and miR-889 miR-454, miR-29a, miR-520c-3p, miR-l40-3p, miR-767-5p, miR-874, miR-32, and miR-573				↑	qRT-PCR	Kim et al;^Citation105 Geaghan and Cairns^Citation101
Oxidative stress	Lipid peroxidation				↑	Meta-analysis Correlation of serum measures with diffusion tensor imaging findings Immunohistochemistry	Brown et al;^Citation127 Versace et al;^Citation15 Wang et al^Citation121
	Protein oxidation and nitration				↑↓	Western blot Meta-analysis	Andreazza et al;^Citation122 Brown et al^Citation127
	DNA and RNA oxidation				↑↓	ELISA Immuno histochemistry	Machado-Vieira et al^Citation68Che et al^Citation123
Inflammation	IL-6, IL-Ιβ, and TNF-α				↑	ELISA	For more information please see Scola and Andreazza^Citation4
Neurotrophic factors	Brain-derived neurotrophic factor				↓	ELISA	For more information please see Scola and Andreazza^Citation4

Notes: (↑) increased, (↓) decreased, (↑↓) altered.

Abbreviations: qRT-PCR, quantitative real-time polymerase chain reaction; 3D, three-dimensional; IL, interleukin; TNF, tumor necrosis factor; ELISA, enzyme-linked immunosorbant assay; BD, bipolar disorder; MRI, magnetic resonance imaging.

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