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Table 1 Summary of characteristics of the included studies

From: Correlations between multimodal neuroimaging and peripheral inflammation in different subtypes and mood states of bipolar disorder: a systematic review

References

BD type

Mood state

Sample size BD/HC

Age (years) BD/HC

Male% BD/HC

Inflammation factors

MRI modality

Outcomes

Benedetti et al. (2016a, b)

I

Depressed

26

47.59

26.9%

SCF

rs-fMRI

Increased stem cell factor levels positively correlated with greater gray matter volume in frontal and parietal cortices and neural responses of ACC and medial PFC

NA*

NA

NA

BDNF

sMRI

Benedetti et al. (2016a, b)

I

Depressed

31

48.0

32.0%

TNF-α

DTI

The TNF-α, IFN-γ, IL-8, and IL-10 shared the same associations with lower fractional anisotropy and higher mean diffusivity in the anterior part of brain

NA

NA

NA

IFN-γ

Poletti et al. (2017)

I

Depressed

25

47.44

32.0%

Th17 cells

ts-fMRI

The frequency of circulating T regulatory cells correlated to lower neuronal responses in the right dorsolateral PFC and higher radial and mean diffusivity

21

27.61

34.8%

DTI

Poletti et al. (2019)

I

Depressed

26

47.96

35.0%

CCL4

rs-fMRI

CCL4 and ICAM1 negatively correlated with cortical thickness in the inferior temporal gyrus; TNF-α positively associated with cortical thickness in the ACC

23

27.50

34.8%

TNF-α

sMRI

Chung et al. (2013)

I

Euthymic

17

31.3

41.2%

hs-CRP

sMRI

Elevation of serum hs-CRP levels associated with reduced volume of the orbitofrontal cortex

NA

NA

NA

Tsai et al. (2019)

I

Euthymic

32

61.2

37.5%

sIL-2R

sMRI

The bilateral hippocampal volumes were inverse to the sIL-2R level; the total gray matter volume was inverse to sTNF-R1 and IL-1β

NA

NA

NA

sTNF-R1

Mohite et al. (2021)

I

Euthymic

21

33.90

33.3%

INF-γ

sMRI

The lower right medial orbitofrontal volume negatively correlated with INF-γ levels; the smaller left posterior cingulate cortex positively correlated with IL-10

22

33.91

40.9%

IL-10

Barzman et al. (2014)

I

NA

15

15.0

33.3%

TNF-related gene

ts-fMRI

Expression of TNF-related genes correlated with activation of the amygdala, subgenual ACC, orbitofrontal cortex and thalamus in the affective task

NA

NA

NA

Lesh et al. (2018)

I

NA

16

21.4

75.0%

IL-1β, IL-2

sMRI

Whole brain white matter percentage showed an inverse trend with IL-1β

53

19.5

64.0%

Chen et al. (2020a)

I

NA

22

28.1

18.2%

TNF-R1

sMRI

The elevated TNF-R1 levels and lower Wisconsin card sorting test performance were positively correlated with smaller gray matter volume in the medial PFC

22

27.4

18.1%

sIL-6R

Furlan et al. (2019)

I

Depressed, manic

30

44.23

30.0%

Natural killer

ts-fMRI

The levels of NK cell positively correlated with fractional anisotropy

36

41.75

33.3%

cells

DTI

Quidé et al. (2021)

I

Depressed, manic, euthymic, mixed

52

36.43

32.7%

CRP, IL-6

sMRI

Increased systemic inflammation correlated with increased covariation in the striatum and cerebellum

59

36.27

44.9%

Chen et al. (2020a)

II

Depressed

41

26.71

43.9%

IL-6

rs-fMRI

The FC between the right posterior insula and left postcentral gyrus was decreased and negatively correlated with the IL-6 level

68

31.27

48.5%

TNF-α

Tang et al. (2021)

II

Depressed

42

26.95

45.2%

IL-6

rs-fMRI

The decreased FC of the right postcentral gyrus was inversely correlated with higher IL-8 levels

69

31.48

47.8%

IL-8

King et al. (2019)

II

Euthymic

15

22–57

NA

CRP

MRS

There was no significant difference in neuroimaging or inflammatory markers between BD and HC groups

13

22–57

NA

IL-6

Savitz et al. (2015)

I, II

Depressed

63

38.8

19.0%

Kynurenic acid

sMRI

The kynurenic acid/3-hydroxy-kynurenine was positively associated with hippocampal and amygdala volume

48

32.6

40.0%

Mansur et al. (2020)

I, II

Depressed

55

44.85

20.0%

TNF-α

sMRI

The decreased TNF-α levels were related to increased whole-brain cortical thickness in the infliximab BD group

NA

NA

NA

Lotrich et al. (2014)

I, II

Euthymic

21

64.8

38.1%

IL-1RA

DTI

Higher IL-1RA levels inversely correlated with cognitive function even when co-varying for either IL-6 or brain-derived neurotrophic factor

25

65.5

46.1%

IL-6

Tu et al. (2017)

I, II

Euthymic

75

42.67

36.0%

sIL-6R

rs-fMRI

Increased sIL-6R correlated with the thinner right middle temporal gyrus cortex

NA

NA

NA

sMRI

Emiroglu et al. (2015)

NA

Euthymic

30

16.37

40.0%

NGF

sMRI

The right hippocampal volume negatively correlated with the duration of the disorder and medication, which positively correlated with the nerve growth factor

23

16.30

52.1%

BDNF

Tseng et al. (2021)

NA

Euthymic

25

36.48

36.0%

hs-CRP

rs-fMRI

Enhanced FC between the right dorsal caudal putamen and ventrolateral PFC was correlated with higher hs-CRP levels and lower continuous performance tests

43

31.05

48.8%

Hoseth et al. (2016)

I, II, NA

NA

117

32.0

39.3%

sTNF-R1

sMRI

Levels of sTNF-R1 were negatively associated with memory learning; hippocampal volume positively correlated with delayed free recall

236

35.0

44.1%

Shonibare et al. (2020)

I, II, NA

NA

38

17.5

39.0%

IL-1β genetic variation

sMRI

T-carriers with BD had more significant surface areas in the dorsolateral PFC and lateral occipital cortex

32

16.4

41.0%

Strenn et al. (2021)

I, II, NA

NA

188

38.0

39.4%

IL-1β gene

sMRI

The T allele at rs16944 and the C allele at rs1143627 were associated with increased volumes of the left putamen and hippocampus

54

40.0

40.7%

Jiang et al. (2022)

I, II, NA

Depressed, manic, euthymic

38

26.46

47.4%

IL-1β

DTI

Fractional anisotropy decreased in the body and genu of the corpus callosum; no significant correlation between inflammation and white matter integrity

26

28.23

38.5%

TNF-α

Poletti et al. (2020)

I, II

Depressed, manic, euthymic

63

46.81

27.0%

IL-9

MRS

IL-9 positively predicted glutamate, IL-1β positively predicted Myo-inositol, and CCL5 positively predicted N-acetyl aspartate concentrations

49

33.70

57.1%

CCL5

Gong et al. (2022)

I, II

Depressed euthymic

51

27.84

47.1%

TNF-α

rs-fMRI

The higher TNF-α level negatively correlated with decreased FC between the right medial amygdala and bilateral medial frontal cortex

69

31.48

47.8%

IL-1β

Chen et al. (2019)

NA

Depressed, manic, euthymic

23

41.96

21.7%

IL-6

sMRI

Proinflammatory cytokines, especially IL-6, were related to the decreased gray matter volume in the frontal, temporal, and cingulate cortex

NA

NA

NA

TNF-R1

Bai et al. (2020)

NA

Depressed, manic, euthymic

72

39.5

37.5%

sIL-6R

sMRI

The reduced gray matter volume in 12 brain regions negatively correlated with sIL-6R and sTNF-R1 levels

NA

NA

NA

sTNF-R1

Bond et al. (2020)

NA

Depressed, manic, euthymic

51

22.9

47.1%

Epidermal growth factor

sMRI

More mood episodes in the past predicted lower mean log(e)-transformed epidermal growth factor and smaller bilateral temporal lobe volumes

22

25.0

40.9%

Bond et al. (2022)

NA

Depressed, manic, euthymic

25

23.0

40.0%

Total inflammation

sMRI

The elevated total inflammation level predicted lower white matter volume in the left frontal lobe and bilateral temporal lobes

14

24.0

28.6%

Besga et al. (2017)

NA

NA

24

 > 50

NA

IL-1β

DTI

Late-onset BD showed increased IL-1β, IL-6 and fractional anisotropy than Alzheimer’s subjects; IL-6 level positively correlated with white matter integrity

19

NA

NA

IL-6

Comai et al. (2022)

NA

NA

66

47.58

33.3%

Kynurenine tryptophan

DTI

Higher kynurenine/tryptophan ratio and IL-1β correlated with lower fractional anisotropy in the inferior fronto-occipital fasciculus

NA

NA

NA

Papiol et al. (2008)

NA

NA

20

43.3

50.0%

IL-1β gene (2q13)

sMRI

A polymorphism (rs16944) of the IL-1β gene correlated with whole brain and left dorsolateral PFC gray matter deficits

43

29.4

55.8%

  1. BD, bipolar disorder; MRI, magnetic resonance imaging; sMRI, structural MRI; DTI, diffusion tensor imaging; ts-fMRI, task state functional MRI; rs-fMRI, rest state functional MRI; MRS, magnetic resonance spectroscopy; IL, interleukin; sIL-R, soluble IL-receptor; IL-1RA, IL-1 receptor antagonist; hs-CRP, high-sensitivity C-reactive protein; TNF, tumor necrosis factor; TNF-R1, TNF-receptor 1; IFN, interferon; CCL, C–C chemokine ligand; ICAM1, intercellular adhesion molecule; FC, functional connectivity; ACC, anterior cingulate; PFC, prefrontal cortex
  2. *NA: not applicable