Furlan2121. Furlan R, Melloni E, Finardi A, Vai B, Di Toro S, Aggio V, et al. Natural killer cells protect white matter integrity in bipolar disorder. Brain Behav Immun. 2019;81:410-21. |
Natural killer cells protect white matter integrity in bipolar disorder (Italy) |
BD: 30 HC: 36 |
DTI, fMRI |
NK cells |
↑ FA |
Yes |
|
|
|
|
CD56+,TNF-α+, IFN-g+, GMCSF+ |
↑ FA ↓ RD and MD |
|
Poletti2222. Poletti S, Myint AM, Schüetze G, Bollettini I, Mazza E, Grillitsch D, et al. Kynurenine pathway and white matter microstructure in bipolar disorder. Eur Arch Psychiatry Clin Neurosci. 2018;268:157-68. |
Kynurenine pathway and white matter microstructure in bipolar disorder (Italy) |
BD: 22 HC: 15 |
DTI |
Kyna |
↓ RD, MD |
Yes |
|
|
|
|
5-HIAA |
↑ AD, RD, and MD |
|
|
|
|
|
Trp, Kyn, 3-HK |
No association |
|
Benedetti2323. Benedetti F, Poletti S, Hoogenboezem TA, Mazza E, Ambrée O, Wit H, et al. Inflammatory cytokines influence measures of white matter integrity in bipolar disorder. J Affect Disord. 2016;202:1-9. |
Inflammatory cytokines influence measures of white matter integrity in bipolar disorder (Italy) |
BD: 31 HC: 0 |
DTI |
TNF-α, IL-8, IFN-g, IL-10 (cytokines), IGFBP-2 and PDGF-BB (growth factors) |
↓ FA ↑ MD and RD |
Yes |
|
|
|
|
IL-5, IL-6, IL-7, IL-8, MCP-1, CXCL10, PTX3, G-CSF, VCAM-1, ICAM-1, IL-1RA, IL-2RA, BDNF, S100B, SCF, EGF, VEGF |
No association |
|
Poletti2424. Poletti S, Melloni E, Aggio V, Colombo C, Valtorta F, Benedetti F, et al. Grey and white matter structure associates with the activation of the tryptophan to kynurenine pathway in bipolar disorder. J Affect Disord. 2019;259:404-12. |
Grey and white matter structure associates with the activation of the tryptophan to kynurenine pathway in bipolar disorder (Italy) |
BD: 72 HC: 36 |
DTI |
Kyn/Trp-ratio |
↓ FA (in depressed group) |
Yes |
|
|
|
|
Kyn |
↑ FA (in manic group) |
|
|
|
|
|
Trp |
No association |
|
Poletti2525. Poletti S, Aggio V, Bollettini I, Falini A, Colombo C, Benedetti F. SREBF-2 polymorphism influences white matter microstructure in bipolar disorder. Psychiatry Res Neuroimaging. 2016;257:39-46. |
SREBF-2 polymorphism influences white matter microstructure in bipolar disorder (Italy) |
BD: 93 HC: 0 |
DTI |
SREBF-2 A homozygotes |
↓ FA (compared to G carriers) ↑ RD (compared to G homozygotes) |
Yes |
|
|
|
|
SREBF-1 polymorphism |
No association |
|
Han2626. Han MR, Han KM, Kim A, Kang W, Kang Y, Kang J, et al. Whole-exome sequencing identifies variants associated with structural MRI markers in patients with bipolar disorders. J Affect Disord. 2019;249:159-68. |
Whole-exome sequencing identifies variants associated with structural MRI markers in patients with bipolar disorders (Korea) |
BD: 53 HC: 82 |
DTI and T1-weighted |
T allele homozygote of KMT2C rs4639425 |
↓ FA ↑ MD and RD |
Yes |
Bollettini2727. Bollettini I, Melloni EM, Aggio V, Poletti S, Lorenzi C, Pirovano A, et al. Clock genes associate with white matter integrity in depressed bipolar patients. Chronobiol Int. 2017;34:212-24. |
Clock genes associated with white matter integrity in depressed bipolar patients (Italy) |
BD: 140 HC: 0 |
DTI |
CLOCK rs1801260*C carriers |
↑ MD (compared to T/T homozygotes) |
Yes |
|
|
|
|
PER3-4/4 homozygotes |
↑ RD (compared to PER3-5/5 homozygotes) ↓ FA (compared to PER3-5/5 homozygotes) |
|
Papiol2828. Papiol S, Molina V, Desco M, Rosa A, Reig S, Sanz J, et al. Gray matter deficits in bipolar disorder are associated with genetic variability at interleukin-1 beta gene (2q13). Genes Brain Behav. 2008;7:796-801. |
Gray matter deficits in bipolar disorder are associated with genetic variability at interleukin-1 beta gene (2q13) (Spain) |
BD: 20 HC: 45 |
DTI |
IL-1 cluster genetic variability |
No association |
Yes |
Lotrich2929. Lotrich FE, Butters MA, Aizenstein H, Marron MM, Reynolds 3rd CF, Gildengers AG. The relationship between interleukin-1 receptor antagonist and cognitive function in older adults with bipolar disorder. Int J Geriatr Psychiatry. 2014;29:635-44. |
The relationship between interleukin-1 receptor antagonist and cognitive function in older adults with bipolar disorder (United States) |
BD: 21 HC: 26 |
DTI |
IL-1RA |
No association |
N/A |
Magioncalda3030. Magioncalda P, Martino M, Tardito S, Sterlini B, Conio B, Marozzi V, et al. White matter microstructure alterations correlate with terminally differentiated CD8+ effector T cell depletion in the peripheral blood in mania: Combined DTI and immunological investigation in the different phases of bipolar disorder. Brain Behav Immun. 2018;73:192-204. |
White matter microstructure alterations correlate with terminally differentiated CD8+ effector T cell depletion in the peripheral blood in mania: combined DTI and immunological investigation in the different phases of bipolar disorder (Italy) |
BD: 60 HC: 20 |
DTI |
CD8+ terminally differentiated effector memory and CD8+ IFN-g+ T cells |
↑ FA (in mania) ↓ RD (in mania) |
Yes |
|
|
|
|
CD4+ T cells and subpopulations CD8+ effector memory T cells |
No association |
|
Poletti3131. Poletti S, Wit H, Mazza E, Wijkhuijs AJM, Locatelli C, Aggio V, et al. Th17 cells correlate positively to the structural and functional integrity of the brain in bipolar depression and healthy controls. Brain Behav Immun. 2017;61:317-25. |
Th17 cells correlate positively to the structural and functional integrity of the brain in bipolar depression and healthy controls (Italy) |
BD: 25 HC: 21 |
DTI and fMRI |
CD4+CCR6+CXCR3CCR4+CCR10CD161+ (Th17) cells |
↑ FA |
Yes |
|
|
|
|
CD4+CD25+FoxP3 (Treg) cells |
↑ RD and MD |
|
|
|
|
|
Th1, Th2, Th22 cells |
No association |
|
Reckziegel3232. Reckziegel R, Rabelo-da-Ponte FD, Feiten JG, Remus IB, Goi PD, Vianna-Sulzbach MF, et al. Bipolar disorder: an association between body mass index and cingulate gyrus fractional anisotropy not mediated by systemic inflammation. Trends Psychiatry Psychother. 2022;44:e20200132. |
Bipolar disorder: an association of body mass index and cingulate gyrus fractional anisotropy not mediated by systemic inflammation (Brazil) |
BD: 35 HC: 66 |
DTI |
CRP |
No association |
Yes |
Mazza3333. Mazza E, Poletti S, Bollettini I, Locatelli C, Falini A, Colombo C, et al. Body mass index associates with white matter microstructure in bipolar depression. Bipolar Disord. 2017;19(2):116-127. |
Body mass index associates with white matter microstructure in bipolar depression (Italy) |
BD: 164 HC: 0 |
DTI |
Serum triglycerides |
↓ FA ↑ AD, RD, and MD |
Yes |
|
|
|
|
Serum glucose |
↓ FA ↑ RD and MD |
|
|
|
|
|
Serum cholesterol |
↓ FA |
|
Benedetti3434. Benedetti F, Poletti S, Locatelli C, Mazza E, Lorenzi C, Vitali A, et al. A Homer 1 gene variant influences brain structure and function, lithium effects on white matter, and antidepressant response in bipolar disorder: A multimodal genetic imaging study. Prog Neuropsychopharmacol Biol Psychiatry. 2018;81:88-95. |
Homer 1 gene variant influences brain structure and function, lithium effects on white matter, and antidepressant response in bipolar disorder: A multimodal genetic imaging study (Italy) |
BD: 199 HC: 0 |
Structural MRI of grey and WM, and 50 with BOLD functional MRI of emotional processing, and DTI |
Rs7713917 AA homozygotes |
↓ FA (compared to rs7713917*G carriers) |
Yes |
Versace1818. Versace A, Andreazza AC, Young LT, Fournier JC, Almeida JR, Stiffler RS, et al. Elevated serum measures of lipid peroxidation and abnormal prefrontal white matter in euthymic bipolar adults: toward peripheral biomarkers of bipolar disorder. Mol Psychiatry. 2014;19:200-8. |
Elevated serum measures of lipid peroxidation and abnormal prefrontal white matter in euthymic bipolar adults: toward peripheral biomarkers of bipolar disorder (United States + Canada) |
BD: 43 HC: 19 |
DTI |
LPH |
↓ FA ↑ RD |
Yes |
|
|
|
|
4-HNE |
No association |
|
Benedetti3535. Benedetti F, Bollettini I, Barberi I, Radaelli D, Poletti S, Locatelli C, et al. Lithium and GSK3-β promoter gene variants influence white matter microstructure in bipolar disorder. Neuropsychopharmacology. 2013;38:313-27. |
Lithium and GSK3-β Promoter Gene Variants Influence White Matter Microstructure in Bipolar Disorder (Italy) |
BD: 70 HC: 0 |
DTI |
GSK3 rs334558*C variant |
↑ AD and MD (compared to T/T homozygotes) |
Yes |
Benedetti3636. Benedetti F, Bollettini I, Poletti S, Locatelli C, Lorenzi C, Pirovano A, et al. White matter microstructure in bipolar disorder is influenced by the serotonin transporter gene polymorphism 5-HTTLPR. Genes Brain Behav. 2015;14:238-50. |
White matter microstructure in bipolar disorder is influenced by the serotonin transporter gene polymorphism 5-HTTLPR (Italy) |
BD: 140 HC: 0 |
DTI |
5-HTTLPR*s carriers |
↑ RD and MD (compared to l/l homozygotes) |
Yes |
Mazza3737. Mazza E, Calesella F, Paolini M, Pasquasio C, Poletti S, Lorenzi C, et al. Insulin resistance disrupts white matter microstructure and amplitude of functional spontaneous activity in bipolar disorder. Bipolar Disord. 2023;25:32-42. |
Insulin resistance disrupts white matter microstructure and amplitude of functional spontaneous activity in bipolar disorder (Italy) |
BD: 92 HC: 0 |
DTI and fMRI |
Insulin |
↓FA↑ RD and MD |
Yes |
|
|
|
|
Glucagon |
No association |
|
Aggio3838. Aggio V, Fabbella L, Finardi A, Mazza EB, Colombo C, Falini A, et al. Neurofilaments light: Possible biomarker of brain modifications in bipolar disorder. J Affect Disord. 2022;300:243-48. |
Neurofilaments light: Possible biomarker of brain modifications in bipolar disorder (Italy) |
BD: 45 HC: 29 |
DTI |
NfL |
↑ AD |
Yes |
Comai3939. Comai S, Melloni E, Lorenzi C, Bollettini I, Vai B, Zanardi R, et al. Selective association of cytokine levels and kynurenine/tryptophan ratio with alterations in white matter microstructure in bipolar but not in unipolar depression. Eur Neuropsychopharmacol. 2022;55:96-109. |
Selective association of cytokine levels and kynurenine/tryptophan ratio with alterations in white matter microstructure in bipolar but not in unipolar depression (Italy) |
MDD: 100BD: 66 |
DT-MRI |
IL-1β, Trp, Kyn, |
↓ FA |
Yes |
|
|
|
|
IL-1rα, IL-2, IL-4, IL-6, IL-8, IL-9, IL-10, IL-12, IL-13, IL-15, IL-17, IFN-γ , TNF-α, CCL2, CCL3, CCL4, CCL5, CCL11, C-X-C motif chemokine CXCL10, FGF, G-CSF, GM-CSF, PDGF-B, VEGF |
No association |
|
Poletti4040. Poletti S, Paolini M, Ernst J, Bollettini I, Melloni E, Vai B, et al. Long-term effect of childhood trauma: Role of inflammation and white matter in mood disorders. Brain Behav Immun Health. 2022;26:100529. |
Long-term effect of childhood trauma: Role of inflammation and white matter in mood disorders (Italy) |
MDD: 100BD: 100 |
DT-MRI |
IL-2, CCL3 |
↓ FA |
Yes |
|
|
|
|
IL-1β, IL-1rα, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12, IL-13, IL-15, IL-17, IFN-γ, TNF-α, CCL3, CCL4, CCL5, CCL11, CXCL10, FGF basic, G-CSF, GM-CSF, PDGF-B, VEGF |
No association |
|
Bond4141. Bond DJ, Andreazza AC, Torres IJ, Honer WG, Lam RW, Yatham LN. Association of total peripheral inflammation with lower frontal and temporal lobe volumes in early-stage bipolar disorder: A proof-of-concept study. J Affect Disord. 2022;319:229-34. |
Association of total peripheral inflammation with lower frontal and temporal lobe volumes in early-stage bipolar disorder: A proof-of-concept study (Canada) |
BD: 25 HC: 14 |
3T-MRI |
TNF-α, IFN-γ, MCP-1, IL-1α, IL-2, IL-6, IL-8, IL-4, IL-10 |
↓ WM |
Yes |
Jiang4242. Jiang X, Guo Y, Jia L, Zhu Y, Sun Q, Kong L, et al. Altered levels of plasma inflammatory cytokines and white matter integrity in bipolar disorder patients with suicide attempts. Front Psychiatry. 2022;13:861881. |
Altered levels of plasma inflammatory cytokines and white matter integrity in bipolar disorder patients with suicide attempts (China) |
BD: 38 HC: 26 |
DTI |
IL-1b, IL-6, TNF-α |
No association |
Yes |